The Cambridge World History of Human Disease

The Cambridge World History of Human Disease
Cambridge Histories Online © Cambridge University Press, 2008

Board of Editors
Arthur C. Aufderheide Stanley Engerman William McNeill

Department of Pathology Department of Economics Department of History
University of Minnesota University of Rochester University of Chicago
Duluth, Minnesota Rochester, New York Chicago, Illinois
Thomas G. Benedek Robert Fogel Ronald Numbers
Veterans Administration Medical Center for Population Economics Department of the History of
Center University of Chicago Medicine
Pittsburgh, Pennsylvania Chicago, Illinois University of Wisconsin
W. F. Bynum Madison, Wisconsin
The Wellcome Institute for the Roger K. French
K. David Patterson
History of Medicine The Wellcome Institute for the
Department of History
London, England History of Medicine
University of North Carolina
London, England
Ann G. Carmichael Charlotte, North Carolina
Department of History Nancy E. Gallagher James C. Riley
Indiana University Department of History Department of History
Bloomington, Indiana University of California Indiana University
Santa Barbara, California Bloomington, Indiana
James Cassedy
History of Medicine Division Jerome Handler Guenter B. Risse
National Library of Medicine Department of Anthropology Department of the History and
Bethesda, Maryland Southern Illinois University Philosophy of the Health Sciences
Donald B. Cooper Carbondale, Illinois University of California
Department of History San Francisco, California
The Ohio State University D. A. Henderson
School of Hygiene and Public Health Charles Rosenberg
Columbus, Ohio Department of the History and
The Johns Hopkins University
Alfred W. Crosby Baltimore, Maryland Philosophy of Science
Department of American Studies University of Pennsylvania
University of Texas Arthur Kleinman Philadelphia, Pennsylvania
Austin, Texas Department of Anthropology
Todd L. Savitt
Harvard University
Philip Curtin Humanities Program — School of
Cambridge, Massachusetts
Department of History Medicine
The Johns Hopkins University Stephen J. Kunitz East Carolina University
Baltimore, Maryland Department of Preventive Medicine Greenville, North Carolina
Wilbur G. Downs University of Rochester Medical R. Ted Steinbock
The Yale Medical School Center Department of Radiology
New Haven, Connecticut Rochester, New York Baptist Hospital East
Louisville, Kentucky
John Duffy Judith Ladinsky
University of Maryland Department of Preventive Medicine Paul U. Unschuld
Baltimore, Maryland, and University of Wisconsin Medical Institut fur Geschichte der Medizin
Tulane University Medical School School Ludwig-Maximilians-Universitat
New Orleans, Louisiana Madison, Wisconsin Munich, Germany

The Cambridge World History
of Human Disease
Editor
KENNETH F. KIPLE
Executive Editor
Rachael Rockwell Graham
Associate Editors
David Frey
Brian T. Higgins
Kerry Stewart
H. Micheal Tarver
Thomas W. Wilson
Brent Zerger
Assistant Editors
Alicia Browne
Roger Hall
Paul Henggeler
Bruce O. Solheim
Dalila de Sousa
CAMBRIDGE
UNIVERSITY PRESS

PUBLISHED BY THE PRESS SYNDICATE OF THE UNIVERSITY OF CAMBRIDGE
The Pitt Building, Trumpington Street, Cambridge, United Kingdom
CAMBRIDGE UNIVERSITY PRESS

The Edinburgh Building, Cambridge CB2 2RU, UK http: //www.cup.cam.ac.uk
40 West 20th Street, New York, NY 10011-4211, USA http: //www.cup.org
10 Stamford Road, Oakleigh, Melbourne 3166, Australia
© Cambridge University Press 1993
This book is in copyright. Subject to statutory exception and

to the provisions of relevant collective licensing agreements,
no reproduction of any part may take place without
the written permission of Cambridge University Press.
First published 1993
Reprinted 1994 (thrice), 1995, 1999
Printed in the United States of America
Typeset in Century Schoolbook
A catalogue record for this book is available from the British Library
Library of Congress Cataloguing-in-Publication Data is available
ISBN 0-521-33286-9 hardback

In Memory of
Michael Dols
Wilbur Downs
Lu Gwei-Djen
R. H. Kampmeier
Edward H. Kass
John L. Kemink
Jerry Stannard
and
Miguel M. Ornelas

Contents
List of tables, figures, and maps page xn 111.2. Immunology 126

List of contributors xvii Pauline M. H. Mazumdar
Preface xxi 111.3. Nutritional Chemistry 140
Acknowledgments xxiii Kenneth J. Carpenter
111.4. Diseases of Infancy and Early
Introduction Childhood 147
I. Medicine and Disease: An Overview Elizabeth Lomax
1.1. History of Western Medicine from 111.5. Famine and Disease 157
Hippocrates to Germ Theory 11 Robert Dirks
Guenter B. Risse 111.6. A History of Chiropractic 164
1.2. History of Chinese Medicine 20 Steven C. Martin
Paul U. Unschuld 111.7. Concepts of Addiction: The U.S.
1.3. Islamic and Indian Medicine 27 Experience ' 170
Nancy E. Gallagher David F. Musto
1.4. Disease, Human Migration, and 111.8. Tobaccosis 176
History 35 R. T. Ravenholt
David E. Stannard 111.9. Occupational Diseases 187
Gerald Markowitz and
II. Changing Concepts of Health David Rosner
and Disease III. 10. History of Public Health and
II. 1. Concepts of Disease in the West 45 Sanitation in the West before
Robert P. Hudson 1700 192
11.2. Concepts of Disease in East Asia 52 Ann G. Carmichael
Shigehisa Kuriyama III. 11. History of Public Health and
11.3. Concepts of Mental Illness in the Sanitation in the West since 1700 200
West 59 John Duffy
Jack D. Pressman
11.4. Sexual Deviance as a Disease 85 IV. Measuring Health
Vern L. Bullough IV.l. Early Mortality Data: Sources and
11.5. Concepts of Heart-Related Difficulties of Interpretation 209
Diseases 91 F. Landis MacKellar
Joel D. Howell FV.2. Maternal Mortality: Definition and
H.6. Concepts of Cancer 102 Secular Trends in England and
Thomas G. Benedek and Wales, 1850-1970 214
Kenneth F. Kiple Irvine Loudon
IV.3. Infant Mortality 224
III. Medical Specialties and Disease Edward G. Stockwell
Prevention IV.4. Measuring Morbidity and
m.l. Genetic Disease 113 Mortality 230
Eric J. Devor James C. Riley

Vlll Contents
rv.5. Stature and Health 238 VI.8. Diseases of the Premodern Period
John Komlos in Korea 392
Lois N. Magner
V. The History of Human Disease VI.9. Diseases of the Modern Period in
in the World Outside Asia Korea 400
V.I. Diseases in the Pre-Roman World 247
Lois N. Magner
Donald J. Ortner and VI.10. Diseases of Antiquity in South
Gretchen Theobald Asia 408
V.2. Diseases of Western Antiquity 262
Ranes C. Chakravorty
Jerry Stannard VI.ll. Diseases of the Premodern Period
V.3. Diseases of the Middle Ages 270
in South Asia 413
Ynez Viole O'Neill Mohammed Said
V.4. Diseases of the Renaissance and VI. 12. Diseases of the Modern Period in
Early Modern Europe 279
South Asia 418
Ann G. Carmichael David Arnold
V.5. Diseases and the European VI. 13. Diseases of Antiquity and the
Mortality Decline, 1700-1900 287
Premodern Period in Southeast
Stephen J. Kunitz Asia 425
V.6. Diseases of Sub-Saharan Africa to Scott Bamber
1860 293
VI. 14. Diseases and Disease Ecology of
Kenneth F. Kiple the Modern Period in Southeast
V.7. Diseases of Sub-Saharan Africa Asia 440
since 1860 298
Keith W. Taylor
Maryinez Lyons
V.8. Diseases of the Pre-Columbian VII. The Geography of Human Disease
Americas 305
VII. 1. Disease Ecologies of Sub-Saharan
Jane E. Buikstra Africa 447
V.9. Diseases of the Americas, K. David Patterson
1492-1700 317
VII.2. Disease Ecologies of the Middle
Ann Ramenofsky East and North Africa 453
V.10. Diseases and Mortality in the LaVerne Kuhnke
Americas since 1700 328 VII.3. Disease Ecologies of South Asia 463
Stephen J. Kunitz Surinder M. Bhardwaj
V.ll. Diseases of the Islamic World 334 VII.4. Disease Ecologies of East Asia 476
Michael W. Dols Ann Bowman Jannetta
VI. The History of Human Disease VII.5. Disease Ecologies of Australia and
in Asia Oceania 482
VI. 1. Diseases of Antiauitv in China 345 Leslie B. Marshall
Lu Gwei-Djen and Joseph VII.6. Disease Ecologies of the Caribbean 497
Needham Kenneth K. Kiple
VI.2. Diseases of the Premodern Period VII.7. Disease Ecologies of Europe 504
in China 354 Stephen R. Ell
Angela Ki Che Leung VII.8. Disease Ecologies of North
VI.3. Diseases of the Modern Period in America 519
China 362 Frank C. Innes
Thomas L. Hall and VII.9. Disease Ecologies of South
Victor W. Sidel America 535
VIA. Diseases of Antiquity in Japan 373 Mary C. Karasch
Shoji Tatsukawa
VI.5. Diseases of the Premodern Period VIII. Major Human Diseases Past
in Japan 376 and Present
W. Wayne Farris VIII.l. Acquired Immune Deficiency
VI.6. Diseases of the Early Modern Syndrome (AIDS) 547
Period in Japan 385 Allan M. Brandt
Ann Bowman Jannetta VIII.2. African Trypanosomiasis
VI.7. Diseases of Antiquity in Korea 389 (Sleeping Sickness) 552
Lois N. Magner Maryinez Lyons

Contents IX
VIII.3. Ainhum 561 VIII.29. Clonorchiasis 654

Donald B. Cooper K. David Patterson
VIII.4. Alzheimer's Disease 561 VIII.30. Croup 654
Joseph A. Kwentus James D. Cherry
VIII.5. Amebic Dysentery 568 VIII.31. Cystic Fibrosis 657
K. David Patterson Thomas G. Benedek
VIII.6. Anemia 571 VIII.32. Cytomegalovirus Infection 659
Alfred Jay Bollet and R. H. Kampmeier
Audrey K. Brown VIII.33. Dengue 660
VIII. 7. Anorexia Nervosa 577 James McSherry
Heather Munro Prescott VIII.34. Diabetes 665
VIII.8 Anthrax 582 Leslie Sue Lieberman
Lise Wilkinson VIII.35. Diarrheal Diseases
VIII.9. Apoplexy and Stroke 584 (Acute) 676
Jacques Poirier and Herbert L. DuPont
Christian Derouesne VIII.36. Diphtheria 680
VIII. 10. Arboviruses 587 Ann G. Carmichael
Wilbur G. Downs VIII.37. Down Syndrome 683
VIII. 11. Arena viruses 595 Christine E. Cronk
Wilbur G. Downs VIII.38. Dracunculiasis 687
VIII. 12. Arthritis (Rheumatoid) 599 Donald R. Hopkins
Howard Duncan and VIII.39. Dropsy 689
James C. C. Leisen J. Worth Estes
VIII. 13. Ascariasis 603 VIII.40. Dysentery 696
K. David Patterson K. David Patterson
VIII. 14. Bacillary Dysentery 604 VIII.41. Dyspepsia 696
K. David Patterson James Whorton
VIII. 15. Beriberi 606 VIII.42. Ebola Virus Disease 699
Melinda S. Meade Wilbur G. Downs
VIII.16. Black Death 612 VIII.43. Echinococcosis (Hydatidosis) 703
Katharine Park K. David Patterson
VIII.17. Black and Brown Lung VIII.44. Eclampsia 704
Disease 616 Sally McMillen
Daniel M. Fox VIII.45. Emphysema 706
VIII. 18. Bleeding Disorders 618 Ronald J. Knudson
Oscar D. Ratnoff VIII.46. Encephalitis Lethargica 708
VIII. 19. Botulism 623 R. T. Ravenholt
William H. Barker VIII.47. Enterobiasis 712
VIII.20. Brucellosis 625 K. David Patterson
Lise Wilkinson VIII.48. Epilepsy 713
VIII.21. Bubonic Plague 628 Jerrold E. Levy
Ann G. Carmichael VIII.49 Ergotism 718
VIII.22. Carrion's Disease 631 John S. Holier, Jr.
Oscar Urteaga-Balldn VIII.50. Erysipelas 720
VIII.23. Catarrh 635 Ann G. Carmichael
Roger K. French VIII.51. Fascioliasis 721
VIII.24. Cestode Infections 636 K. David Patterson
K. David Patterson VIII.52. Fasciolopsiasis 722
VIII.25. Chagas' Disease 636 K. David Patterson
Marvin J. Allison VIII.53. Favism 722
Vffl.26. Chlorosis 638 Peter J. Brown
Robert P. Hudson VIII.54. Filariasis 724
VIII.27. Cholera 642 Todd L. Savitt
Reinhard S. Speck VIII.55. Fungus Infections (Mycoses) 730
VIII.28. Cirrhosis 649 Geoffrey C. Ainsworth
Thomas S. N. Chen and VIII.56. Fungus Poisoning 736
Peter S. Y. Chen Geoffrey C. Ainsworth

Contents
Vffl.57. Gallstones (Cholelithiasis) 738 VIII.83. Lupus Erythematosus 848

R. Ted Steinbock Thomas G. Benedek
VIII.58. Gangrene 741 vni.84. Lyme Borreliosis (Lyme Disease) 852
Diane Quintal and Robert D. Leff
Robert Jackson vni.85. Malaria 855
VIII.59. Giardiasis 745 Frederick L. Dunn
K. David Patterson vm.86. Marburg Virus Disease 862
VIII.60. Glomerulonephritis (Bright's Wilbur G. Downs
Disease) 746 VIII.87. Mastoiditis 865
Donald M. Larson John L. Kemink, John K. Niparko,
VIII.61. Goiter 750 and Steven A. Telian
Clark T. Sawin VIII.88. Measles 871
VIII.62. Gonorrhea 756 Robert J. Kim-Farley
Richard B. Rothenberg VIII.89. Meningitis 875
VIII.63. Gout 763 K. David Patterson
Thomas G. Benedek VIII.90. Milk Sickness (Tremetol
VIII.64. Herpes Simplex 773 Poisoning) 880
R. H. Kampmeier Thomas E. Cone, Jr.
VIII.65. Herpesviruses 779 VIII.91. Multiple Sclerosis 883
R. H. Kampmeier W. I. McDonald
VIII.66. Histoplasmosis 779 VIII.92. Mumps 887
Scott F. Davies Robert J. Kim-Farley
VIII.67. Hookworm Disease 784 VIII.93. Muscular Dystrophy 890
John Ettling Thomas G. Benedek
VIII.68. Huntington's Disease VIII.94. Myasthenia Gravis 891
(Chorea) 788 Bernard M. Patten
Eric J. Devor VIII.95. Nematode Infections 895
VIII.69. Hypertension 789 K. David Patterson
Thomas W. Wilson and VIII.96. Onchocerciasis 895
Clarence E. Grim K. David Patterson
VIII.70. Infectious Hepatitis 794 VIII.97. Ophthalmia (Conjunctivitis and
Francis L. Black Trachoma) 897
VIII.71. Infectious Mononucleosis 799 Mary C. Karasch
R. H. Kampmeier VIII.98. Osteoarthritis 906
VIII.72. Inflammatory Bowel Disease 800 Charles W. Denko
Joseph B. Kirsner VIII.99. Osteoporosis 909
VIII.73. Influenza 807 R. Ted Steinbock
Alfred W. Crosby VIII. 100. Paget's Disease of Bone 911
VIII.74. Japanese B Encephalitis 811 Roy D. Altman
Edward H. Kass VIII. 101. Paragonimiasis 914
VIII.75. Lactose Intolerance and K. David Patterson
Malabsorption 813 VIII. 102. Parkinson's Disease 914
Norman Kretchmer Bernard M. Patten
VIH.76. Lassa Fever 817 VIII. 103. Pellagra 918
Wilbur G. Downs Elizabeth W. Etheridge
VIII.77. Lead Poisoning 820 VIII. 104. Periodontal Disease (Pyorrhea) 924
Arthur C. Aufderheide Jeffrey Levin
VIII.78. Legionnaires' Disease 827 VIII. 105. Pica 927
David W. Fraser Brian T. Higgins
vni.79. Leishmaniasis 832 VIII. 106. Pinta 932
Marvin J. Allison Don R. Brothwell
VIII.80. Leprosy 834 VIII. 107. Plague of Athens 934
Ann G. Carmichael Ann G. Carmichael
VHI.81. Leptospirosis 840 VIII. 108. Pneumocystis Pneumonia
Otto R. Gsell (Interstitial Plasma Cell
vni.82. Leukemia 843 Pneumonia, Pneumocystosis) 937
Gordon J. Filler K. David Patterson

Contents XI
VIII. 109. Pneumonia 938 VIII. 135. Syphilis, Nonvenereal 1033

Jacalyn Duffin Kenneth F. Kiple
VIII. 110. Poliomyelitis 942 VIII.136. Tapeworm 1035
H. V. Wyatt K. David Patterson
VIII.111. Protein-Energy Malnutrition 950 VIII. 137. Tay-Sachs Disease 1036
James L. Newman Bradford Towne
VIII. 112. Protozoan Infections 955 VIII. 138. Tetanus 1043
K. David Patterson Robert J. T. Joy
VIII. 113. Puerperal Fever 955 VIII. 139. Tetanus, Neonatal 1046
K. Codell Carter Sally McMillen
VIII. 114. Q Fever 957 VIII. 140. Tetany 1049
S. R. Palmer Kenneth F. Kiple
VIII. 115. Rabies 962 VIII. 141. Toxoplasmosis 1051
K. David Patterson K. David Patterson
VIII. 116. Relapsing Fever 967 VIII. 142. Trematode Infections 1052
Anne Hardy K. David Patterson
VIII. 117. Rheumatic Fever and VIII. 143. Trench Fever 1052
Rheumatic Heart Disease 970 Victoria A. Harden
Thomas G. Benedek VIII. 144. The Treponematoses 1053
VIII. 118. Rickets and Osteomalacia 978 Kenneth F. Kiple
R. Ted Steinbock VIII. 145. Trichinosis 1055
VIII.119. Rickettsial Diseases 981 Donald E. Gilbertson
Victoria A. Harden VIII. 146. Trichuriasis 1058
VIII. 120. Rocky Mountain Spotted Fever K. David Patterson
and the Spotted Fever Group VIII. 147. Tuberculosis 1059
Diseases 982 William D. Johnston
Victoria A. Harden VIII. 148. Tularemia 1068
VIII. 121. Rubella 986 Patrick D. Home
Robert J. Kim-Farley VIII. 149. Typhoid Fever 1071
VIII.122. St. Anthony's Fire 989 Charles W. LeBaron and
Ann G. Carmichael David N. Taylor
VIII.123. Scarlet Fever 990 VIII. 150. Typhomalarial Fever 1077
Anne Hardy Dale Smith
VIII. 124. Schistosomiasis 992 VIII.151. Typhus, Epidemic 1080
John Farley Victoria A. Harden
VIII. 125. Scrofula (Scrophula) 998 VIII. 152. Typhus, Murine 1085
Roger K. French Victoria A. Harden
VIII. 126. Scurvy 1000 VIII. 153. Typhus, Scrub (Tsutsugamushi) 1086
Roger K. French Victoria A. Harden
VIII. 127. Sickle-Cell Anemia 1006 VIII. 154. Urolithiasis (Renal and Urinary
Georges C. Benjamin Bladder Stone Disease) 1088
VIII. 128. Smallpox 1008 R. Ted Steinbock
Alfred W. Crosby VIII. 155. Varicella Zoster 1092
VIII. 129. Streptococcal Diseases 1014 R. H. Kampmeier
Peter C. English VIII. 156. Whooping Cough 1094
VIII. 130. Strongyloidiasis 1016 Anne Hardy
K. David Patterson VIII. 157. Yaws 1096
VIII.131. Sudden Infant Death Syndrome 1017 Don R. Brothwell
Todd L. Savitt VIII. 158. Yellow Fever 1100
VIII. 132. Sudden Unexplained Death Donald B. Cooper
Syndrome (Asian) 1020 and Kenneth F. Kiple
Neal R. Holtan
VIII. 133. Sweating Sickness 1023 Indexes 1109
Name Index 1111
Ann G. Carmichael 1138
VIII.134. Syphilis 1025 Subject Index
Jon Arrizabalaga

Tables, Figures, and Maps
Tables IV.4.1. Abridged life table for Sweden,

11.6.1. Ten most common invasive neo- 1751-90 232
plasms, and estimated new cases V.8.1. Healed fracture frequencies for
as percentage of all new cases in North American prehistoric
the United States, 1990 page 104 remains 308
11.6.2. Deaths due to cancer as V.9.1. Diseases suggested to have been
percentage of all deaths introduced to the Americas 322
according to sex and age group, V.9.2. Viral, bacterial, and protozoal
United States, 1986 104 agents introduced to the
11.6.3. Most common cancers as causes of Americas 324
death from cancer, according to VI.3.1. Leading causes of death, selected
sex and age group, United States, cities and counties of Shanghai,
1986 104 1957 and 1984 363
11.6.4. Five-year survival rates by race VI.3.2. Leading provincial causes of
in two time periods from principal death in China, 1985 364
malignant neoplasms in the VI.3.3. Communicable diseases in China,
United States 105 1985 365
111.8.1. U.S. tobacco production and VII.8.1. Incidents of serious contamination
consumption, 1900-88 180 in U.S. work sites and residential
111.8.2. Per capita adult consumption of areas 531
cigarettes, by country, 1985 181 VIII.10.1. 512 recognized arboviruses listed
111.8.3. Percentage of U.S. adults who by family and subcategories, with
smoked regularly, 1945-85 182 totals 588
111.8.4. Deaths and mortality rates among VIII. 10.2. Size, morphology, structure, and
smoking U.S. veterans, 1980 183 composition of selected virus
HI.8.5. Estimated number of deaths families or genera that contain
caused by cigarette smoking in arboviruses 590
the United States, 1980 184 VIII. 10.3. Twenty-nine selected arbo-
IV.2.1. Birthrates and maternal deaths i viruses important in
in England and Wales, 1851- causing human and/or animal
1980 214 diseases, with data on vectors,
IV.3.1. Infant mortality rates for income hosts, and geographic
areas in metropolitan Ohio, distributions 591
1979-81 227 VIII.11.1. History and natural occurrence of
IV.3.2. Infant mortality rates by broad arenaviruses 596
cause-of-death group for income VIII.19.1. Types of Clostridium botulinum,
areas in metropolitan Ohio, susceptible species, and sites of
1979-81 228 outbreaks 623

Tables, Figures, and Maps xm
VIIL19.2. Reports of botulism from (children > 4 years, and
various countries in recent adults) 815
years 624 VIII.75.2. Distribution of the adult
VHI.28.1. Etiology and incidence of lactase phenotypes in human
cirrhosis 650 populations 815
VIII.30.1. Classification of crouplike vm.76.i. Lassa fever outbreaks: West
illnesses 654 Africa, 1969-88 818
VIII.34.1. Causes and suspected causes vm.8i.i Serologic classification of
of, and risk factors for, leptospires 841
diabetes 668 VIII.81.2. Symptoms occurring in
VIII.34.2. Prevalence of diagnosed diabetes leptospiroses 842
in representative populations, VIII.85.1. Malaria in 1984 857
1960-85 671 VIII.86.1. Serologic studies of Marburg
VIII.34.3. Diabetes mortality trends by virus in humans and other
country and geographic area, primates 863
1970-2 and 1976-83 (rates per VIII. 110.1 Comparison of paralysis of
100,000 population) 672 lower limbs in temperate and
VIII.35.1. Commonly identified etiologic developing countries 946
agents in diarrheal disease 678 VIII.117.1 Age distribution of admissions
VIII.35.2. Etiologic agents of diarrhea, for acute rheumatic fever 972
characteristically identified in VIII. 117.2 Cases of rheumatic fever per
special settings 678 1,000 admissions, various
VIII.36.1. Diphtheria mortality rate per hospitals 973
100,000 population 683 VIII.117.3 Signs of acute rheumatic fever
VIII.42.1. Ebola serosurveys 700 worldwide 975
VIII.46.1. Time interval from encephalitis VIII. 134.1 Etiology, epidemiology, and
to parkinsonism to death in six clinical manifestations of the
patients 711 human treponematoses 1026
VIII.58.1. Causes of gangrene 742 VIII.154.1 Major features differentiating
VIII.63.1. Occurrence of nephrolithiasis bladder and renal stone
with gout 765 disease 1089
VIII.63.2. Prevalence of hyperuricemia 768 VIII. 154.2 Paleopathological specimens
VIII.63.3. Prevalence of gout in relation of renal and bladder stones 1091
to serum uric acid content in
men 769 Figures
VIII.63.4. Serum uric acid in two II.5.1. Rate of coronary heart disease
American Indian tribes 769 per 100,000 people in the
VIII.63.5. Serum uric acid in South United States 96
African black and white II.5.2. Annual change in mortality
populations 771 from ischemic cardiac disease,
VIII.69.1. Prevalence of hypertension in 1968-77 96
20- to 59-year-olds, by region, in III.l.l. Mixed model of liability for
ascending order by prevalence: complex human disease 114
52 populations, INTERSALT m.i.2. A representation of metabolic
Study, 1988 790 pathways involving the amino
VIIL69.2. Relationship between blood acid tyrosine 119
pressure and mortality: ni.i.3. The original two-dimensional
Northwestern Mutual Life chromatographic spreads of
Insurance Company, 1907-14 793 normal and sickle-cell
VHI.69.3. "Normal" and "unacceptable" hemoglobins 121
systolic blood pressures by HI.1.4. G-banded chromosome spread
age: Northwestern Mutual of a man with Down
Life Insurance Company, syndrome and ideogram of
1914 793 human chromosome 21 123
VIII.75.1. Lactose absorption and ffl.5.1. Relation of social cooperation
malabsorption correlated with to ecological stress in a social
degree of Indian blood action system 159

XIV Tables, Figures, and Maps
HI.8.1. Annual consumption of VI.3.1. Mortality rates for the urban

cigarettes by U.S. adults, population of Shanghai, 1949-
1900-88 179 83 363
III.8.2. Cigarette consumption and VIII.2.1. Glossina palpalis 552
tobaccosis mortality in the VIII.2.2. Glossina morsitans 552
United States, 1900-87 184 VIII.20.1 Graphs illustrating the dramatic
III.8.3. The price of pleasure: deaths reduction in the incidence of
from addictive substances and brucellosis in the British garrison
AIDS in the United States, in Malta from 1905 to 1907,
1980s 185 following the ban on the use of
IV.2.1. Birthrates and maternal goat's milk 627
mortality rates for England and VIII.22.1 Bartonella bacilliformis within
Wales, 1851-1980 215 red blood cells stained by Giemsa
IV.2.2. Maternal mortality rates for and Romanovsky stains 632
England and Wales, 1851-1980 215 VIII.22.2 Verrucose eruptions: miliary
IV.2.3. Maternal mortality rates in form, diffuse and generalized;
different countries, 1880-1950 216 nodular form, two intradermic
IV.2.4. Maternal mortality rates in nodules; and mular form 633
Scotland, England, Wales, and VIII.22.3 Intracellular reproduction cycle of
Sweden, 1870-1950 217 the Bartonella bacilliformis in the
IV.2.5. Maternal mortality rates in cytoplasm of a histiocytic bone
England, Wales, and the United marrow cell and the endothelial
States, 1910-50 219 cells of a lymph node 633
IV.4.1. Survival curves 231 VIII.22.4 Erythrophagocytosis of
IV.4.2. Mortality risk for medieval parasitized erythrocytes in
Hungary, England (1871-80), and peripheral blood and spleen 634
the United States (1979-81) 234 VIII.25.1 Megaesophagus from a case of
IV.4.3. Morbidity rates for nineteenth- possible Chagas' disease from the
century Britain 235 Tarapaca Valley in northern
IV.4.4. Mortality schedules for Sweden, Chile (c. third century A.D.) 638
1816-40 and 1979-83 236 VIII.46.1 Encephalitis lethargica,
V.I.I. Probable unhealed ax wound in influenza-pneumonia, other
an adult male skull, 1100-655 pneumonia/bronchitis deaths in
B.C. 249 Seattle-King County,
V.1.2. Partial antemortem destruction of Washington, 1918-26 709
the fourth lumbar vertebral body VIII.60.1 Urine-secreting structure
from the skeleton of a young (nephron) 746
adult, 3100 B.C. 251 VIII.60.2 Normal glomerulus 746
V.I.3. Chronic inflammation of the left VIII.60.3 Acute glomerulonephritis 747
tibia and fibula in an adult VIII.62.1 Gonorrhea incidence in selected
woman, Early Bronze Age 252 countries, 1940-83 758
V.1.4. Dental caries in an adult male, VIII.62.2 Gonorrhea rates in men and
Early Bronze Age 255 women, aged 20-4, United States,
V.I.5. Benign tumor in the area of 1956-85 759
fusion between the pubic and iliac VIII.62.3 Gonorrhea: age-specific rates for
bones of an adult woman, c. 1990 men and women, United States,
B.C. 257 1985 759
V.1.6. Malignant tumor of the proximal VIII.62.4 Distribution of gonorrhea in
left humerus of a Celtic warrior, Denver, Colorado, 1974-6 761
800-600 B.C. 257 VIII.62.5 Occurrence of gonorrhea in
V.8.1. Model time line for prehistoric Buffalo, New York, 1975-80;
eastern North America 306 distribution of core and adjacent
V.8.2. Model time line for prehistoric tracts 762
Peru and Chile 307 VIII.62.6 Penicillinase-producing Neisseria
V.8.3. Different methods of trepanation 307 gonorrhea (PPNG) as a
VI. 1.1. Oracle-bone and bronze terms percentage of total gonorrhea, by
specifying disease entities 346 zip code analysis in Miami,

Tables, Figures, and Maps xv
Florida, March 1985 to countries, compared with
February 1986 762 Miami, Florida, United
VTII.64.1. Percentage distribution of States, 1948-9 949
antibodies to HSV-1, HSV-2, vm.122.1. Woodcut of St. Anthony by
and intermediate form (types Johannes Wechtlin 990
1 and 2) in 239 patients of Vm.134.1. Two hypotheses as to the
various age groups 774 possible evolution of the
VIII.64.2. Number of consultations, all organisms responsible for
five office visits, and first of human treponematoses 1027
five visits for genital herpes, VIII. 134.2. Infectious diseases considered
United States, 1966-83 774 as a dynamic triangular
VIII.64.3. Schematic graph of the interaction among host,
clinical course of primary parasite, and environment 1029
genital herpes 776
VIII.77.1. World lead production during Maps
past 5,500 years 822 IV.2.1. Differences in maternal
VIII.79.1. The uta form of leishmaniasis 833 mortality rates in England
VIII.81.1. Leptospires on dark field 840 and Wales, 1924-33 218
VIII.81.2. Phases and relevant IV.2.2. Differences in maternal
diagnostic procedures of mortality rates in the United
leptospiroses 841 States, 1938-40 219
VIII.100.1 Severe Paget's disease of the VII.3.1. General endemicity of cholera,
bone in a 66-year-old male 912 malaria, and "kangri burn"
VIII.102.1. Scheme illustrating the cancer 466
mechanism of MPTP toxicity VII.3.2. Malaria: annual parasite
at nigral dopamine neurons in index (API), per 1,000
primates 916 population, for selected years 469
VIII. 110.1. Cases of paralytic VII.3.3. Leprosy: prevalence rate
poliomyelitis in Malta, 1920- percentage, 1974-5 471
64 943 VII.3.4. General distribution of
VIII.110.2. Case-fatality rates for filariasis and goiter 472
poliomyelitis based on records VII.8.1. Diffusion of smallpox among
from England and Wales, native Americans, 1928 524
1947-50 (average of male and VII.8.2. Diffusion of smallpox among
female rates; 28 notified native Americans, 1983 525
cases); Denmark, 1947-50 (28 VII.8.3. Malarial disease deaths per
paralytic cases); France, 1952 1,000 population, 1870 527
(average of male and female VII.8.4. "Consumption" deaths per
rates; 28 notified cases); 1,000 population, 1870 528
Sweden 1935-44 (28 VII.8.5. Leprosy area of New
confirmed paralytic cases); Brunswick, predominantly in
Eskimos, Chesterfield Inlet the nineteenth century 529
(14 cases); Cutter vacinees (27 VIII.2.1. Distribution of African
cases); West Virginia, (18 sleeping sickness (palpalis
cases); Malta, 1942-3 (service group) 553
cases, 20-30 years of age, VIII.2.2. Distribution of African
number of cases not specified); sleeping sickness (morsitans
Sweden, 1911-13 (5 cases) 944 group) 553
VIII.110.3. Numbers of publications VIII.38.1. Areas in which dracunculiasis
about polio by year, 1890 to is reported or probably exists 687
1986; the Current Vni.80.1. Estimated endemicity of
Bibliography of Poliomyelitis, leprosy in the world, 1983 835
Index Medicus, and the VHI.120.1. Epidemiological map of Rocky
Bibliography of Infantile Mountain spotted fever in
Paralysis 947 Bitterroot Valley, Montana,
VIII.110.4. Age of onset of cases of 1902 983
poliomyelitis in developing VIII. 124.1. Distribution of Schistosoma

XVI Tables, Figures, and Maps
haematobium in Africa and VIII.151.1. Outline map of the world (c
the Middle East 993 World War II), showing the
VIII. 124.2. Distribution of Schistosoma approximate geographic
mansoni in Africa and the distribution of epidemic
Middle East 993 (exanthematic) louse-borne
VIII. 124.3. Distribution of Schistosoma typhus, murine (endemic)
mansoni in the Western flea-borne typhus, and Brill's
Hemisphere 994 disease 1082
VIII. 124.4. Distribution of Schistosoma VTII.153.1. Known geographic
japonicum and Schistosoma distribution of mite (scrub)
mekongi 994 typhus in Asia, July 1948 1086

Contributors
Geoffrey C. Ainsworth Georges C. Benjamin Kenneth J. Carpenter

Commonwealth Mycological Institute Department of Human Services University of California
Kew, England Washington, D.C. Berkeley, California
Marvin J. Allison Surinder M. Bhardwaj K. Codell Carter

Medical College of Virginia Kent State University Brigham Young University
Richmond, Virginia Kent, Ohio Provo, Utah
Francis L. Black Ranes C. Chakravorty
Roy D. Altman
Yale University School of Medicine Veterans Medical Hospital
University of Miami School of
New Haven, Connecticut Salem, Virginia
Medicine
Miami, Florida Alfred Jay Bollett Peter S. Y. Chen
Yale University University of Massachusetts Medical
David Arnold New Haven, Connecticut School
School of Oriental and African Worcester, Massachusetts
Studies Allan M. Brandt
London, England Department of Social Medicine Thomas S. N. Chen
University of North Carolina New Jersey Medical School
Jon Arrizabalaga Chapel Hill, North Carolina Newark, New Jersey
Consejo Superior de Investigaciones
Don R. Brothwell James D. Cherry
Cientificas
University of London UCLA School of Medicine
Barcelona, Spain
London, England Los Angeles, California
Arthur C. Aufderheide Audrey K. Brown Thomas E. Cone, Jr.
University of Minnesota SUNY Health Science Center The Children's Hospital
Duluth, Minnesota Brooklyn, New York Boston, Massachusetts
Scott Bamber Peter J. Brown Donald B. Cooper
The Australian National University Emory University The Ohio State University
The Research School of Pacific Atlanta, Georgia Columbus, Ohio
Studies
Jane E. Buikstra Christine E. Cronk
Canberra, Australia
University of Chicago Southern Illinois University
William H. Barker Chicago, Illinois Carbondale, Illinois
University of Rochester Vern L. Bullough Alfred W. Crosby
Rochester, New York State University College University of Texas
Buffalo, New York Austin, Texas
Thomas G. Benedek
Veterans Administration Medical Ann G. Carmichael Scott F. Davies
Center Indiana University Hennepin County Medical Center
Pittsburgh, Pennsylvania Bloomington, Indiana Minneapolis, Minnesota

XV111 Contributors
Charles W. Denko Elizabeth W. Etheridge Anne Hardy
Case Western Reserve University Longwood College The Wellcome Institute for the
Hospitals Farmville, Virginia History of Medicine
Cleveland, Ohio John Ettling London, England
Christian Derouesn6 University of Houston Brian T. Higgins
Centre Hospitalier Houston, Texas Toledo University
Universitaire Henri Mondor John Farley Toledo, Ohio
Creteil, France Dalhousie University Neal R. Holtan
Eric J. Devor Halifax, Nova Scotia, Canada St. Paul-Ramsey Medical
University of Iowa Wayne W. Farris Center
Iowa City, Iowa University of Tennessee St. Paul, Minnesota
Knoxville, Tennessee Donald R. Hopkins
Robert Dirks
Illinois State University Daniel M. Fox The Carter Presidential Center
Normal, Illinois State University of New York Atlanta, Georgia
Stony Brook, New York Patrick D. Home
Michael W. Dols
David W. Fraser York County Hospital
The Wellcome Institute for the
Swarthmore College Newmarket, Ontario, Canada
History of Medicine
University of Oxford Swarthmore, Pennsylvania Joel D. Howell
Oxford, England Roger K. French University of Michigan Medical
The Wellcome Institute for the Center
Wilbur G. Downs Ann Arbor, Michigan
History of Medicine
The Yale Medical School
London, England Robert P. Hudson
New Haven, Connecticut
Nancy E. Gallagher University of Kansas
Jacalyn Duffin University of California Kansas City, Kansas
Queen's University Santa Barbara, California
Kingston, Ontario, Canada Frank C. Innes
Donald E. Gilbertson University of Windsor
John Duffy James Ford Bell Museum of Natural Windsor, Ontario, Canada
University of Maryland History
Baltimore, Maryland, and Robert Jackson
Minneapolis, Minnesota
Tulane University Medical School University of Ottawa
New Orleans, Louisiana Clarence E. Grim Ottawa, Ontario, Canada
Hypertension Research Center
C. R. Drew University of Medicine Ann Bowman Jannetta
Howard Duncan
Henry Ford Hospital and Science University of Pittsburgh
Detroit, Michigan Los Angeles, California Pittsburgh, Pennsylvania
Otto R. Gsell William D. Johnston
Fredrick L. Dunn
University of Basel Wesleyan University
University of California
Lenzerheide, Switzerland Middletown, Connecticut
San Francisco, California
Lu Gwei-Djen Robert J. T. Joy
Herbert L. DuPont Uniformed Services University for
University of Texas Health Sciences The Needham Research Institute
Cambridge, England the Health Sciences
Center Bethesda, Maryland
Houston, Texas Thomas L. Hall
University of California R. H. Kampmeier
Stephen R. Ell San Francisco, California Vanderbilt University School of
University of Utah Medical Center Medicine
Salt Lake City, Utah John S. Haller, Jr. Nashville, Tennessee
University of Colorado
Peter C. English Denver, Colorado Mary C. Karasch
Duke University Medical Center Oakland University
Durham, North Carolina Victoria A. Harden
Rochester Hills, Michigan
NIH Historical Office and
J. Worth Estes Dewitt Stetten, Jr., Museum of Edward H. Kass
Boston University School of Medicine Natural Research Channing Laboratory
Boston, Massachusetts Bethesda, Maryland Boston, Massachusetts

Contributors xix
John L. Kemink Jeffrey Levin David F. Musto
University of Michigan Medical Phipps and Levin Dentistry Yale University School of Medicine
Center Bowling Green, Ohio New Haven, Connecticut
Ann Arbor, Michigan Jerrold E. Levy Joseph Needham
Robert J. Kim-Farley University of Arizona The Needham Research Institute
World Health Organization Ex- Tuscon, Arizona Cambridge, England
panded Program on Immunization Leslie Sue Lieberman
Commugny, Switzerland James L. Newman
University of Florida
Syracuse University
Kenneth F. Kiple Gainesville, Florida
Syracuse, New York
Bowling Green State University Elizabeth Lomax
Bowling Green, Ohio University of California John K. Niparko
Los Angeles, California University of Michigan Medical
Joseph B. Kirsner
Center
University of Chicago Medical Irvine Loudon
Center Ann Arbor, Michigan
Green College
Chicago, Illinois Oxford, England Ynez Viole O'Neill
Ronald J. Knudson University of California
Maryinez Lyons
University of Arizona School of Los Angeles, California
University of London
Medicine London, England Donald J. Ortner
Tucson, Arizona
W. I. McDonald National Museum of Natural History
John Komlos Institute for Neurology Smithsonian Institution
University of Pittsburgh The National Hospital Washington, D.C.
Pittsburgh, Pennsylvania London, England S. R. Palmer
Norman Kretchmer F. Landis MacKellar Centre for Communicable Disease
University of California Unit6 de Planification de la Surveillance
Berkeley, California Population London, England
La Verne Kuhnke Lome, Togo
Katharine Park
Northeastern University Sally McMillen Wellesley College
Boston, Massachusetts Davidson College Wellesley, Massachusetts
Stephen J. Kunitz Davidson, North Carolina
Bernard M. Patten
University of Rochester Medical James McSherry Baylor College of Medicine
Center Queen's University Houston, Texas
Rochester, New York Kingston, Ontario, Canada
Joseph A. Kwentus K. David Patterson
Lois N. Magner
The Dartmouth Hospital University of North Carolina
Purdue University
Dayton, Ohio Charlotte, North Carolina
West Lafayette, Indiana
Donald M. Larson Gerald Markowitz Gordon J. Piller
University of Minnesota John Jay College of Criminal Justice Leukaemia Research Fund
Duluth, Minnesota City University of New York London, England
Charles W. LeBaron New York, New York
Jacques Poirier
Centers for Disease Control Leslie B. Marshall Centre Hospitalier
Atlanta, Georgia University of Iowa Universitaire Henri Mondor
Iowa City, Iowa Creteil, France
Robert D. Leff
University of Minnesota Steven C. Martin Heather Munro Prescott
Duluth, Minnesota Albert Einstein School of Medicine Cornell University
James C. C. Leisen Bronx, New York Ithaca, New York
Henry Ford Hospital Pauline M. H. Mazumdar
Jack D. Pressman
Detroit, Michigan University of Toronto
Institute for Health, Health Care
Toronto, Canada
Angela Ki Che Leung Policy, Aging Research
Sun Yat-Sen Institute for Social Melinda S. Meade Rutgers-Princeton Program in
Sciences and Philosophy University of North Carolina Mental Health Research
Nankang, Taiwan, Republic of China Chapel Hill, North Carolina New Brunswick, New Jersey

XX Contributors
Diane Quintal Shigehisa Kuriyama Steven A. Telian
University of Ottawa Emory University University of Michigan Medical
Ottawa, Ontario, Canada Atlanta, Georgia Center
Victor W. Sidel Ann Arbor, Michigan
Ann Ramenofsky
University of New Mexico Montefiore Medical Center/Albert
Gretchen Theobald
Albuquerque, New Mexico Einstein College of Medicine
Smithsonian Institution
Bronx, New York
Oscar D. Ratnoff Washington, D.C.
University Hospitals of Cleveland Dale Smith
Cleveland, Ohio Uniformed Services University of Bradford Towne
Health Sciences Southwest Foundation for Biomedical
R. T. Ravenholt Bethesda, Maryland Research
World Health Surveys Incorporated San Antonio, Texas
Seattle, Washington Reinhard S. Speck
University of California
James C. Riley Paul U. Unschuld
San Francisco, California
Indiana University Institut fur Geschichte der Medizin
Bloomington, Indiana David E. Stannard Ludwig-Maximilians-Universitat
University of Hawaii Munich, Germany
Guenter B. Risse Honolulu, Hawaii
University of California Oscar Urteaga-Ball6n
Jerry Stannard
San Francisco, California University of San Marcos
University of Kansas
Lima, Peru
David Rosner Lawrence, Kansas
Bernard Baruch College and R. Ted Steinbock James Whorton
Mt. Sinai School of Medicine Baptist Hospital East University of Washington
New York, New York Louisville, Kentucky Seattle, Washington
Richard B. Rothenberg Edward G. Stockwell
Centers for Disease Control Lise Wilkinson
Bowling Green State University
Atlanta, Georgia University of London
Bowling Green, Ohio
London, England
Mohammed Said Shoji Tatsukawa
Hamdard Foundation Kitasato University Thomas W. Wilson
Karachi, Pakistan Kanagawa-Ken, Japan Charles R. Drew University of
Todd L. Savitt Medicine and Science
David N. Taylor
Martin Luther King, Jr., General
East Carolina University School of Walter Reed Army Institute of
Medicine Hospital
Research
Greenville, North Carolina Los Angeles, California
Washington, D.C.
Clark T. Sawin Keith W. Taylor H. V. Wyatt
Veterans Administration Cornell University University of Leeds
Boston, Massachusetts Ithaca, New York Leeds, Yorkshire, England

Preface
Over the past few decades or so, scholars and the knows or thinks it knows about disease and history
public alike have been made increasingly aware of as an artifact for generations to come.
the role pathogens have played in shaping the his- One of the most striking features of world health
tory of humankind - an awareness now underscored today that scholars of those generations (as well as
by Quincentenary literature and exhibitions, which our own) will doubtless struggle to explain is the
depict disease as a potent ally of the Spanish explor- widely varying differences in infant, child, and adult
ers and conquerors of the Americas. Certainly the mortality rates from region to region (as well as
swath that disease cut into the ranks of the Indians, within regions) and the causes that generate those
and the chain of events the thinning of those ranks rates. In those less developed areas that embrace the
set in motion, constitute a vivid example of the im- majority of the world's population, the diseases that
portance of epidemiology in the unfolding of the his- winnow human ranks remain, for the most part, the
torical process - a process that quickly spilled over very killers that brought death to distant ancestors.
from the Western Hemisphere to influence pro- In the world's more developed portions, however,
foundly events in Africa, Europe, and ultimately the new maladies of old age, such as heart diseases,
entire globe. cancer, and Alzheimer's disease, have supplanted
Yet this example, however compelling, can be as communicable and deficiency diseases as the great-
misleading as it is instructive when it creates the est outlets of human life.
impression that the forces unleashed by pathogens Such differences confront us with political, eco-
in the Americas were products of circumstances that nomic, social, and certainly moral questions-
render them discrete. In fact, as the pages that fol- questions that make the study of health in the less
low demonstrate, pathogens have wielded (and are developed world a very pressing matter indeed. For
wielding) a similar dramatic and decided power over this reason we have endeavored to bring the epide-
the history of all peoples everywhere throughout the miological history of that world right up to the pres-
whole of humankind's stay on the planet. ent. Yet because of a certain "sameness" in the his-
To make such a demonstration in substantial de- tory of disease of the developed countries we felt no
tail and from many different angles is one of the such obligation, but rather permitted these regional
major purposes of this work. Another is to provide a treatments to "trail off" and let topical entries such
place to start for others who wish to elaborate a as "Alzheimer's Disease," "Concepts of Cancer,"
biological dimension for their own research. A final "Concepts of Heart-Related Diseases," and the like
purpose is to encapsulate what this generation continue the story into the twentieth century.

Acknowledgments
This work is the fruit of the Cambridge History and Fund. These monies were absolutely crucial in the
Geography of Human Disease Project that was early stages of the project both to launch it and to
launched in late 1985. During the six years or so it instill in us some confidence that others besides our-
took to complete, we have accumulated a consider- selves thought the effort important. A grant from
able amount of indebtedness. That incurred by indi- the Earhart Foundation in 1987 helped to keep the
vidual authors is acknowledged in their essays. It is project moving, and in 1988 the generosity of the
my pleasure, however, to acknowledge the indebted- National Endowment for the Humanities (Tools Divi-
ness of the project as a whole to many splendid sion) made available the necessary funds to see it
individuals and institutions. through to completion in late 1990.1 am enormously
Funding for the project was provided as needed by grateful to all of these very fine organizations.
various offices on the Bowling Green State Univer- The project was born of discussions with Frank
sity campus from beginning to end. Louis Katzner, Smith, our editor at Cambridge University Press,
Dean of the Graduate School, and Gary Hess, Chair and Frank has been extraordinarily supportive of
of the History Department, made certain that the the effort from the very first. That support, however,
project was always staffed by at least one graduate was much more than just encouragement from the
assistant, and often two, on a year-round basis. The sidelines. Frank was involved with the project's con-
History Department also purchased computer equip- ceptualization; he helped to assemble the Board of
ment for the project including an optical scanner, Editors, and, on more than one occasion, found au-
made an office available for the staff, and provided thorities to write essays that I had become convinced
secretarial service. Indeed, I shudder to think at would go unwritten. To say that without his support
what stage the effort would still be without Connie this project would have never been realized is
Willis, Judy Gilbert, and Phyllis Wulff, who per- merely to state the obvious.
formed a myriad of tasks including the typing of I would also like to acknowledge the considerable
hundreds of letters and retyping of dozens of essays. effort on our behalf made by copy editors Rosalind
In addition, Christopher Dunn, Director of Re- Corman and Mary Racine who, under the direction
search Services, helped us struggle with fundraising of Sophia Prybylski, were not at all intimidated by
problems and made "seed money" available, the four thousand or so manuscript pages of the
whereas the Faculty Research Committee provided a project. Rather they scrutinized each and every
salary and travel funds during two of the summers page, frequently calling us to task, and forcing upon
spent on the project. Finally, Eloise Clark, Vice Presi- us that last round of writing, checking, and double
dent for Academic Affairs, gave us the resources checking that is so important but so painful. On the
needed to meet our payrolls on two critical occasions. other hand, there are those who saved us a great
Seed money from outside the university was deal of pain, and I am most grateful to some very
awarded to the project in 1986 by Cambridge Univer- gifted as well as good-hearted scholars who helped
sity Press, the Hoffman-La Roche Corporation, us with the intricacies of accenting, spelling, even
Pfizer Pharmaceuticals, and the Milbank Memorial rendering languages we had absolutely no compe-

XXIV Acknowledgments
tence in. These are board members Nancy Gallagher Tom Benedek, Jim Cassedy, Arthur Kleinman,
and Paul Unschuld; Oliver Phillips of the University Steve Kunitz, Ron Numbers, Dave Patterson, and
of Kansas; and Bowling Green colleagues Ed Chen, Paul Unschuld, were called upon with sufficient fre-
Larry Daly, Fujiya Kawashima, and Kriemhild quency to provoke a bit of "testiness." But the collec-
Conee Ornelas. tive performance of the entire board constituted a
Three generations of graduate students at Bowl- remarkable display of the highest possible standards
ing Green have labored on the project, some for con- of scholarship, right to the end when Ann Carmi-
siderable periods of time, checking sources, entering chael, Nancy Gallagher, Ron Numbers, and Guenter
essays into our computer equipment, preparing in- Risse more or less cheerfully helped in reading the
dexes, and performing countless other chores, includ- Name Index. In some cases revisions called for by
ing tutoring the rest of us on increasingly complex our board members were not made, or were only
computer hardware and software. I thank them all. partially made. Negotiations with individual au-
If these individuals were with us for a year or more, thors account for some of these differences, disagree-
we have listed them as the associate editors they, in ment in the reports of board members account for
fact, were. Others who were with us for only a semes- more, and, on occasion, editorial decisions in our
ter appear as assistant editors, but these distinctions office were the reason. This is all by way of saying
are in no way intended to indicate reflections on the that despite the board members' incredible amounts
quality of the effort they gave us. of selfless input, only the authors and I bear final
Rachael R. Graham has been the only permanent responsibility for the essays in this volume.
staff member to work on the project, and, as Execu- This work is, of course, first and foremost the
tive Editor, it is she who has provided the continuity product of those who wrote it, and my admiration
that kept the project from sliding into the abyss of for, and gratitude to, our 160 or so authors is bound-
chaos on numerous occasions. She also imposed sty- less. Surely, as experts in their fields with countless
listic continuity on it by reading, with marvelously other things besides this project to worry about,
critical eyes, each of our some 200 entries countless many of them must have felt sorely put upon by our
times, researching many of them, and working with (occasional) seemingly endless demands on their
the authors to completely rewrite a few. In addition, time. Doubtless this was very often the case for those
she corresponded regularly with our authors, and contributors in faraway countries, when we encoun-
even as I write these words is readying a new cap- tered both technical and linguistic problems of com-
tion listing of tables, graphs, charts, and so forth, munication as drafts, revisions, advice, criticism,
while at the same time helping me with the latest and corrections traveled uncertainly back and forth
versions of both of the indexes. It is impossible to via telephone, faxlines, and the mail services. Yet
express adequately my gratitude for all of her consid- even if we tried the patience of many, the complaints
erable effort and for her unfailing, and contagious, have been few, and I thank all of the authors for the
enthusiasm that accompanied it. But I shall try any- tremendous effort that their work represents and
way with a simple "Thank you, Rachael." I also the wisdom it contains.
thank her husband, James Q. Graham, Jr., for all of One of the great pleasures of any new project is that
his labors on our behalf in acquiring and setting up it generally brings new friends, and this one brought
our various pieces of computer equipment. Finally I them by the score. But a project of this magnitude is
thank him for the considerable patience he exercised also likely to bring sadness, and so it did as seven of
during years of hearing about the project from both our authors died while the work was still in progress.
of us and for the very good advice he provided on The loss of Michael Dols, Wilbur Downs (a board
many occasions, just to prove he was still listening. member as well), Lu Gwei-Djen, R. H. Kampmeier,
I am immensely grateful as well for all of the Edward H. Kass, John L. Kemink, and Jerry Stan-
splendid advice given, and critical reviewing done, nard was a heavy one for medicine and for its history.
by the board members, some of whom, like Philip During the course of the project, I also lost one of
Curtin and Ann Carmichael, helped to initiate the the best friends any person could hope for, when
project. The board members recommended most of Miguel M. Ornelas, Director of Affirmative Action
the authors for the project, in many cases wrote and Handicapped Services at Bowling Green State
essays themselves, and read essays in their areas of University, passed away. And it is to his memory,
expertise for scientific and historical accuracy. Be- and to the memory of our seven colleagues on the
cause of the nature of that expertise, some, such as project, that I dedicate this book.

Introduction
Between 1860 and 1864, August Hirsch published his minology and concepts, daunting indeed. We do not,
monumental Handbuch der historisch-geographi- however, ignore the needs of specialists in the many
schen Pathologie in two volumes. In 1881 he finished fields our work encompasses. Most of the following
an introduction to an updated edition, which Charles essays have been written by specialists, and all have
Creighton translated from German into English. been refereed by one or more of our board members,
This opus, published by the New Sydenham Society who are also specialists.
in three volumes, appeared during the years 1883 to
1886 and was entitled Handbook ofGeographical and Parts I Through VIII
Historical Pathology. The Handbook represented a Part I of the work presents the major historical roots
Herculean effort to detail the distribution of diseases and branches of medical thought from ancient times
of historical and geographic interest in time and in to the twentieth century, and introduces the reader
place. to the interplay of human migration, epidemiology,
Our work represents a similar undertaking, but and immunology. Some may be interested to learn
with a major difference. In the second half of the that despite popular notions about the antiquity of
nineteenth century, the dawn of germ theory, it was Chinese medicine, it actually trailed behind medi-
still possible (as Hirsch proved) for an individual cine in the West as a systematic discipline.
working alone to produce a compilation of this sort. Part II deals with concepts of disease in the East
Today even the contemplation of such an attempt and in the West, as well as with concepts of complex
boggles the mind. The Cambridge World History of physical and mental ailments, the emphasis being
Human Disease project was launched in 1985 as a on how those concepts have changed over time. As
collective effort of some 160 social and medical scien- medicine has become more a science and less an art,
tists to provide at the close of this century something it has helped to tame yesterday's plagues, which
of what the Hirsch volumes provided at the end of capriciously brought sudden death so frequently to
the preceding century. We hope that, like the Hirsch so many. As a result, many now have the question-
volumes, our own effort will aid future students of able privilege of living long enough to develop can-
health and disease in grasping our present-day uncer or heart-related illnesses, which have sup-
derstanding of diseases in their historical, spatial, planted infectious disease and malnutrition in the
and social dimensions. developed world as the most important causes of
Another important purpose of the project is to death. Increasing life expectancy has also contrib-
make available an understandable and accessible uted to the growth of that branch of medicine that
history of disease to social scientists and humanists deals with disorders of the mind and that, as Vern
in their many varieties. As historians, geographers, Bullough points out, has tended over time to appro-
anthropologists, and other researchers have become priate for itself the right to decide what is deviant in
increasingly aware of the importance of adding a sexual as well as other matters.
biological dimension to their work, they have found Some chapters in Part III deal with the inheritance
the usual medical tomes, with their unfamiliar ter- of disease. Certainly one can inherit genetic diseases

Introduction
just as one can inherit disease immunities. Some the Renaissance onward, increasing urbanization
disease immunities are acquired, but even these can created more and larger breeding grounds for dis-
be viewed as a heritage of the disease environment of ease in Europe. In addition, the expanded travel of
one's birth. Children "inherit" what might be consid- Europeans into the larger world - travel fraught
ered special illnesses because of their age, and the with pathogenic peril - introduced them to still
heritage of human-modified environments has fre- more diseases. All of this seems to have stimulated a
quently been famine, illnesses of malnutrition, and compulsiveness in the West to give names to ill-
illnesses triggered by occupation. In addition, the nesses, which was not shared by medical practitio-
"heritage" of habits can often produce illness, as is ners elsewhere.
made clear in the essays on substance abuse and Part VIII discusses the history and geography of
tobaccosis (along with those on cirrhosis and emphy- the most notable diseases of humankind in alphabeti-
sema in Part VIII). The remaining chapters of Part cal order, from AIDS through yellow fever. Most
III deal with efforts outside mainstream medicine to essays are divided by the subheadings definition,
prevent and control disease; these include public distribution and incidence or prevalence, epidemi-
health projects and the rise of chiropractic - a sys- ology, etiology, clinical manifestations and pathology,
tem of alternative medicine. and history and geography. However, because of the
Part IV is essentially demographic. It focuses on variable nature of illnesses, some essays are orga-
measuring the health of various groups by nutri- nized in a way that is more suitable to the topic
tional status, by morbidity, and especially by mortal- under discussion.
ity. An extremely important contribution of this sec- In Part VIII readers will encounter some disease
tion derives from the methodological questions that entities discussed under archaic names, because
are raised. they occur with some frequency in historical works.
The following three parts provide regional histo- In certain cases we know what disease entity or
ries of disease around the globe from prehistory to entities they were intended to describe. The term
the present. Part V concentrates on Europe, the Mid- catarrh, for example, was used in the past (and occa-
dle East, Africa, and most of the Americas, whereas sionally is still used) to label a variety of conditions
Part VI is devoted to Asia. We have employed two that produced an inflamation of the mucous mem-
types of historical division in these sections- branes of the head and throat. In other instances,
Western idiosyncratic divisions in Part V and the such as chlorosis, which was proabably often ane-
more straightforward (and convenient) divisions of mia, we kept the name because it specifically signi-
"ancient," "premodern," and "modern" for Asia in fies a "disease" recognized in the past as one that
Part VI. Part VII completes the regional treatment struck mostly young women. However, in the case of
by presenting a larger picture of changing disease other ephemeral diseases such as sweating sickness,
ecologies. In addition to encapsulating the more de- typhomalarial fever, and the plague of Athens, we
tailed discussions of Europe, the Americas, Africa, had no choice but to use the archaic terms because to
and Asia that appear in Parts V and VI, this section this day we can only guess what they were.
deals with two more geographic areas —the Carib- Most of these ailments are found in Hirsch under
bean and Australia/Oceania. Because of their diver- their now archaic names. He did not, of course, dis-
sity and relatively small populations, they were cuss AIDS or other newly discovered, extremely
omitted from the history sections. deadly infections such as Ebola virus disease, Lassa
Collectively, the essays in Parts V through VII fever, or Legionnaires' disease, or illnesses such as
reveal how much more is known about the history of Alzheimer's disease that were not recognized as spe-
disease in Europe and the Americas than in the rest cific clinical entities when Hirsch wrote. Others,
of the world. There are a number of reasons for this, however, like poliomyelitis are treated in his work
but three stand out. One is that anthropologists and under a different name (in this case, epidemic
other investigators of diseases that afflicted our dis- cerebrospinal meningitis). Indeed, what is striking
tant ancestors have been considerably more active about a comparison of the illnesses discussed in our
in the West than elsewhere. The second is that West- volume and those dealt with by Hirsch is how few
ern medical observers have historically been more diseases have disappeared and how few new ones
empirically oriented than their philosophically in- have arisen to take their places in the century that
clined counterparts elsewhere. The third reason is divides the two efforts. Perhaps most striking of all,
that Western observers have had greater opportuni- however, is the change in emphasis. When Hirsch
ties to observe a greater variety of illnesses. From wrote, the world was still ignorant of the causes of

Introduction
epidemic diseases. Today, it is the chronic diseases ally held to have been free of epidemic diseases as
such as cancer, Alzheimer's disease, and heart- well as of many other illnesses now regarded as
related ailments about which we are most ignorant. "diseases of civilization." In fact, there is some agree-
ment that the cradle of many epidemic viral ail-
ments, such as smallpox, was ancient South Asia,
Indexes, Overlap, and Illustrative
which was among the first regions to develop civiliza-
Materials tions large enough to support these ailments. From
By means of two detailed indexes we have attempted there the diseases traveled east to China and then
to make the information in this work as useful, and accompanied Buddhist missionaries to Korea and
accessible, as possible. The larger, general index pro- Japan.
vides many cross-references and historical syn- Much evidence suggests that the West was rela-
onyms for diseases. The second index lists proper tively free of eruptive fevers such as smallpox, mea-
names and supplies the dates and a brief biographi- sles, and rubella until the first millennium A.D.,
cal sketch of all historical figures in medicine men-
when they finally settled in. These fevers are not
tioned by more than one author. Thus, it is possible mentioned in Greek texts, and as Stephen Ell points
to consult an entry on, say, the perception of disease out in his study of the disease ecologies of Europe,
in Asia during the eighth century (Parts I and II); to the military fortunes of the Romans and their ene-
turn to another entry on the impact of smallpox and mies do not seem to have been influenced by the
other epidemic diseases in eighth-century Japan kinds of diseases that decimated later European
(Part VI); to read another entry that discusses small- armies - or at least this influence was not felt until
pox as a disease entity and provides its history; to very late in the Empire's decline. But at that time,
discover something about Edward Jenner in the in-
the eruptive ailments had apparently taken root, as
dex of names; and then, using the general index, to is indicated by a change in Roman strategy and by
trace the course of smallpox over time and around the fate of wave after wave of invaders who enjoyed
the globe. initial success only to go finally into sharp decline.
The fact that this is possible means that there is It is now clear that leprosy was a serious health
some overlap. Yet from the outset it was decided that problem for Europeans during much of the Middle
each essay should stand on its own. Thus, some repe- Ages. Excavations of leper cemeteries leave no doubt
tition was not only inevitable but even desirable. that those interred were suffering from that disease
Indeed, given the variety of methods and approaches and not something else such as yaws, as earlier
employed by the contributors, what might be writers have argued. The reason or reasons for the
thought to be duplication is often scrutiny of a ques- disappearance of leprosy remain subject to dispute.
tion with different lenses. Still, much overlap has Some researchers believe that it had to do with the
been avoided because of the different approaches. rise of tuberculosis - a disease that provides some
Medical scientists tend to emphasize subjects that immunity to leprosy; others argue that the plague
social scientists do not, and among the latter, anthro- killed so many lepers that the disease itself died out.
pologists, demographers, economists, geographers,
and historians all manage to disagree (not always As for the plague, a great number of the questions
cheerfully) about what is important. The various regarding its course in Europe remain unanswered.
disciplines have also dictated an uneven deployment It is generally accepted that it originated in the
of illustrative materials. Geographers use maps; de- Himalayan borderlands between India and China
mographers, charts and graphs; anthropologists, dia- and that the plague of Justinian (542-3), which
grams; whereas historians all too often believe that reached Europe by 547, was in fact bubonic plague.
their words are descriptive enough. But why it disappeared from Europe for some 800
years remains a mystery. Plague certainly seems to
have been active in China during this period. The
Overview circumstances of its reappearance are also obscure.
Despite the diversity, some consensus can be gleaned Our authors note that it may have reached the West
from the essays, and the epidemiological overview from the Middle East. But the most likely explana-
presented here is an attempt to highlight some new tion is that a plague epidemic began in China in
findings and old answers as well as the many peren- 1331, found its way to the Crimea by 1346, and then
nial questions that remain unanswered. diffused over Europe. Yet how this disease could
Hunter-gatherers and early agriculturalists of the linger on for centuries, very possibly without a
Old World, although hardly disease free, are gener- sylvatic focus and with little evidence of widespread

Introduction
rat mortality, has not been explained. Nor have the tion caused by the death of adults who normally
circumstances of the eventual disappearance of provided food and care for the young and the old.
plague from western Europe in the late seventeenth Malaria is blamed for having depopulated much of
and early eighteenth centuries been determined. Ex- the interior of Brazil, which brings us to still other
planations ranging from a mutation of the bacillus Old World ailments, and to Africa.
to the rise of strong governments able to regulate If it is generally conceded that Asia was the cradle
trade (and, often by accident, disease) continue to be of many of the illnesses so far discussed (i.e., dis-
advanced. eases that probably reached humankind via domesti-
Among scholars of diseases in the Americas, there cated animals), there is no doubt that Africa was the
is a noticeable tendency to accept the notion that cradle of another group of illnesses - those of wild
much larger Indian populations developed in isola- animals and thus diseases that in many instances
tion from the rest of the world than has previously antedated the human species. These African dis-
been believed. Indeed, even the now nearly empty eases include some malarial types and other proto-
Amazon basin was teeming with them. Like the Old zoal infections, such as African trypanosomiasis,
World hunter-gatherers, these people were not dis- which first infected our primate predecessors, as
ease free. Intestinal parasites, a form of tuberculosis well as viral infections such as yellow fever and
that may have become extinct, encephalitis, and dengue.
hepatitis tormented them along with some kind or Malaria, of course, has plagued India and China
kinds of treponemal infection, and in certain locales, for millennia. But Africans and those of African
such uniquely American ailments as Carrion's dis- descent living elsewhere around the globe are al-
ease and Chagas' disease were present. But despite most completely refractive to vivax malaria. This
the fact that some populations were dense enough to suggests that they have had the longest experience
host them, neither the Old World epidemic diseases, with what is generally believed to be the most an-
nor malaria or yellow fever, infected the native cient of the malarial types to affect humans. Indeed,
Americans. If the Indians lacked pathogens to kill because black Africans are so refractory to vivax
them, they seem to have made up for it by violence, malaria, the disease has disappeared from almost
because burial sites often reveal that trauma was an all of sub-Sahara Africa. By contrast, falciparum
important cause of death. malaria, which is the most deadly of the malarial
European diseases changed this state of affairs - types, is also the newest; it too seems to have an
abruptly in the case of Caribbean Indians, some- African origin (or at least to have plagued Africans
what more slowly in the Inca and Aztec empires, and the longest), because Africans have by far the great-
substantially more slowly among other groups in est variety and highest frequencies of genetic de-
Brazil and North America. But it is generally con- fenses against it.
ceded that, despite locale, about 90 percent of the Nonetheless, falciparum malaria spread out across
population eventually died out before demographic the Sahara desert to take up residence around the
recovery began. Ann Ramenofsky has pinned down Mediterranean and to become a serious threat in
at least 13 diseases that arrived in the Americas classical times, whereas vivax malaria had diffused
with the Europeans and Africans during the first much earlier over much of the globe. Vivax malaria
two centuries after the discovery of the American doubtless reached the New World in the blood of early
continent: viral diseases including influenza, mea- Spanish conquistadors, and falciparum malaria in
sles, mumps, rubella, smallpox, and yellow fever; the blood of the first slaves to be imported, if not
bacterial ailments embracing pneumonia, scarlet fe- before. Yellow fever, by contrast, was confined to Af-
ver, pertussis, anthrax, and bubonic plague; typhus, rica until the slave trade brought it to the Americas
whose causative microorganism stands midway bein the mid-seventeenth century. It seems to have be-
tween a virus and bacteria; and one protozoal gun tormenting European cities only in the eigh-
infection — malaria. There is general agreement teenth century, and never became established in Asia
that, outside of Brazil, smallpox was the most devas- despite a plethora of suitable vectors, as well as mon-
tating disease, though there is puzzlement as to how key and human hosts. One possible explanation for
a relatively benign disease suddenly became deadly the latter is that Asia supports so many other group B
in Europe as well as the Americas in the sixteenth arborviruses that there has been no room for another.
century. But all authors concerned with the matter In any event, such was not the case in the Ameri-
point out the devastating impact of disease after cas. Both malaria and yellow fever joined in the
disease sweeping over a people and the social disloca- slaughter of Indians; in the Caribbean this African

Introduction
wave of disease, coming hard on the heels of the Meanwhile, from the 1770s onward, the natives of
European wave, almost obliterated them. But Afri- Australia and Oceania were subjected with increas-
can diseases also killed whites, while sparing blacks, ing ferocity to the same trial by disease that had
who seemed immune to both. These differences in begun almost two centuries earlier in the Americas.
susceptibility suggested to the Europeans that nei- And according to David Stannard, the results were
ther Indians nor whites could survive hard labor in similar, at least in Hawaii, where he places the popu-
warmer regions of the hemisphere. This brought lation decline at 90 percent and blames smallpox, as
about an accelerated slave trade and, of course, an well as other epidemic illnesses and venereal dis-
accelerated flow of African pathogens to the New ease, for both increased mortality and reduced fertil-
World. Indeed, much oftropical and subtropical Amer- ity. Elsewhere the process was often more gradual
ica became more an extension of the African disease and is unfortunately still ongoing in some places,
environment than of the European, until late in the such as Brazil and Colombia.
nineteenth century. Even smallpox arrived from Afri- As the world's cities grew in importance, so did
can, as opposed to European, reservoirs. tuberculosis, in both Asia and the West. Our authors
Whether the Indians gave syphilis to the rest of leave no doubt about the relationship between urban-
the world is a question taken up by a number of ization and tuberculosis. Yet the disease began reced-
authors in this work. The biological anthropologists ing while urbanization was still accelerating and
report that the treponemal lesions found in the bones long before medicine had acquired its therapeutic
of pre-Columbian Indians are probably not those of "magic bullet." This leaves still another unresolved
syphilis (as previously thought), or at least not of medical mystery, although it would seem that the
syphilis as we know it today. Moreover, the ability of explanation lies somewhere within the parameters
Indians to resist the disease, which has been taken of improving nutrition and the development of resis-
by some as proof of its pre-Columbian presence in tance to the illness.
the Americas, can be explained to some extent by Crowded nineteenth-century cities with poor sani-
the prevalence of pinta and perhaps nonvenereal tation and impure water supplies were natural tar-
syphilis - both milder forms of treponemal disease gets for another of the plagues from India - Asiatic
that nonetheless would have provided some cross- cholera. In his essay, Reinhold Speck demonstrates
immunity. Also, our authors take into account the the role of the British army in unwittingly unleash-
opinion of European physicians who claimed that ing the disease. He traces each of the pandemics,
the syphilis they saw at the beginning of the six- straightens out the problem of dating one of them,
teenth century was simply a more virulent form of and shows how cholera did much to emphasize the
an old disease they had always treated. In view of importance of public health and sanitation programs.
these circumstances it is tempting to speculate that The end of the 1800s brought an understanding of
two treponemal infections, one from the Old World the role of vectors in a number of diseases, including
and the other from the New World, somehow fused to malaria and yellow fever, and this along with an
become the disease that ravaged Europe for more increase in the production of quinine permitted the
than a century before becoming more benign. Europeans finally to venture beyond the coasts into
Somewhere around the beginning of the eigh- the interior of Africa. Tropical medicine became an
teenth century, Europe's population began to in- integral part of colonizing efforts, although as both
crease and, despitefitsand starts, has continued to do Maryinez Lyons and K. David Patterson make clear,
so. How much of this growth can be credited to im- the initial aim was not so much to help those colo-
proved nutrition, the abatement of disease, increas- nized as it was to preserve the health of the coloniz-
ing fertility and decreasing infant and child mortal- ers. Moreover, in modifying environments to suit
ity, medical intervention, the growth of nation-states themselves, the latter inadvertently facilitated the
and improved public health, and changes in human spread of such illnesses as African trypanosomiasis,
attitudes and behavior has long been a subject of onchocerciasis, schistosomiasis, and leishmaniasis.
considerable debate. Stephen Kunitz believes that all The twentieth century dawned with the principles
are important factors and that no single one provides of germ theory still being digested by the world's
a full explanation. Nonetheless, he, along with other medical community. As our authors on Asia and
authors considering the problem in Asia, does stress Africa indicate, Western medicine has (perhaps fortu-
the importance of the growth of cities in which dis- nately) not always supplanted local medicine but
eases could become endemic and thus transformed rather has often coexisted with it. Nonetheless, the
into childhood ailments. effectiveness of Western medicine in combating

Introduction
trauma and illnesses such as rabies, cholera, ty- Unfortunately, other diseases of the young con-
phoid, gangrene, puerperal fever, and yaws was tinue to be prevalent, especially in the developing
quickly recognized. world, where protein-energy malnutrition, respira-
Yet Western medicine was completely over- tory infections, dysenteries, and helminthic and pro-
whelmed as influenza became the next great plague tozoal parasites, separately and working in concert,
to sweep the earth just as World War I was winding kill or retard the development of millions each year.
down. As Alfred Crosby emphasizes, although the As our specialists make clear, much headway must
case mortality rate for the disease is low, the disease be made in that world against other potentially crip-
killed upward of 30 million across the globe, making pling ailments such as yaws, leprosy, and ophthal-
it perhaps the "greatest single demographic shock mia. Some malarial strains have become drug resis-
that the human species has ever received." Nor did tant, and continued dengue epidemics, carried by
the dying cease after the pandemic was over: As R. T. the same vectors that spread yellow fever, raise the
Ravenholt reveals in his essay on encephalitis lethar- very real possibility of yellow fever making a come-
gica, this illness was a peculiar sequela to the so- back in the Western Hemisphere, as it seems to be
called Spanish flu. doing in parts of Africa.
After the influenza epidemic, the developed world In the developed world, chronic diseases such as
enjoyed perhaps its first extended respite from epi- cancer, heart-related illnesses, and Alzheimer's dis-
demic disease since classical times. Medical science ease have supplanted infectious diseases as the im-
made great strides in understanding and control- portant killers, and increasingly the role of genes in
ling infectious illnesses. Because of the emphasis on the production of these diseases has come under scru-
germ theory, however, the etiologies of nutritional tiny. In addition, medicine has concentrated on un-
ailments remained elusive for a time, but eventu- derstanding the genetic basis for such diseases as
ally those of beriberi, pellagra, rickets, and scurvy cystic fibrosis, Down syndrome, epilepsy, favism,
were unraveled and the role of vitamins discovered. hemophilia, Huntington's disease, leukemia, multi-
In the tropical and subtropical worlds, Rockefeller ple sclerosis, muscular dystrophy, Parkinson's dis-
programs were launched to rid these regions of ease, sickle cell anemia, and Tay-Sachs disease.
long-standing illnesses, and if hookworm disease Some of these, such as sickle-cell anemia, favism,
and yellow fever were not eradicated as had been and possibly Tay-Sachs disease, are an unfortunate
confidently expected, at least much was learned result of the body's evolutionary attempt to protect
about their control. itself against other diseases.
Rickettsial diseases have always been trouble- As this research has gone forward, it has become
some for armies. Typhus has been credited with de- clear that many other disease conditions, such as
feating Napoleon in Russia, and during World War I lactose intolerance and diabetes, are strongly influ-
the disease killed some 2 million to 3 million soldiers enced by heredity. Leslie Sue Lieberman argues that
and civilians. But in World War II and its aftermath, in the latter instance a "thrifty gene" left over from
important advances were made in combating rickett- the feast and famine days of our hunter-gatherer
sial diseases. In addition, new drugs were developed ancestors may be at work. Genes also play a vital
against malaria. role in selecting cancer and heart disease victims or
As the authors writing on the ailments of infants even gout patients, although in these cases genetic
and children make evident, the young have histori- predisposition can often be modified by behavioral
cally suffered most from epidemic and endemic dis- changes - and to that extent these illnesses can be
eases. But in the past several decades this has been viewed as human made. No wonder, then, that there
changed by the development of antibiotics and by has been a recent upsurge of concern about the air
accelerated worldwide programs of vaccination. In we breathe and the food and other substances we
fact, as Alfred Crosby points out, in his essay on take into our bodies.
smallpox, one of these programs led by the World It may well be that environmental factors are
Health Organization appears to have ended the ca- bringing us back face to face with epidemic illnesses.
reer of that disease, which killed so many for so long. For example, as more and more individuals are enter-
Poliomyelitis, which briefly loomed as another of the ing our shrinking rain forests, new and deadly vi-
world's great plagues, was also brought under con- ruses are being released into the rest of the world. In
trol by similar programs, although as H. V. Wyatt fact, AIDS, which almost certainly originated in non-
reminds us, such efforts are not without some risk human primates, has become a plague of such propor-
and the disease lingers in many parts of the world. tions that it may eventually be ranked along with

Introduction
the Black Death, smallpox, cholera, and influenza as mans have created their own disease ecologies and
among the most disastrous epidemic scourges of hu- their own diseases by the ways they live and the
mankind. In addition, as Wilbur Downs shows, other ways they manipulate their environments. As we
extraordinarily lethal viruses such as Ebola, Mar- approach the twenty-first century, we have finally
burg, and Lassa also lurk in these rain forests and begun to acquire that understanding. Whether at
pose a serious threat to us all. the same time we have acquired a sufficient appre-
When Hirsch wrote in the preceding century, few ciation of what we have done is another matter.
understood and appreciated the extent to which hu- Kenneth F. Kiple

PARTI
Medicine and Disease:
An Overview

I.I. Western Medicine from Hippocrates to Germ Theory 11
liver, was hot and moist, and was prone to overflow
I.I during the spring. Not only were humors the mate-
History of Western Medicine rial and dynamic components of the body, but their
ever-imperfect and labile mixture was responsible
from Hippocrates to Germ for a person's psychological makeup, or "tempera-
Theory ment," as well as for deficiencies in bodily constitu-
tion that created susceptibilities to disease.
Illness thus occurred when the humoral balance
Greece and Rome was upset either by a lack of proper nourishment or
Before the fifth century B.C., ancient Greece had by the imperfect production, circulation, and elimi-
physician-seers (iatromantis) who combined magical nation of the humors. The physician's goal was to
procedures and drug treatments, and wound healers restore a healthy balance through the use of diet,
deft at caring for battlefield trauma. Another group rest, or exercise and a limited number of drugs, all
of practitioners were engaged in medical dietetics, a capable of aiding the natural healing powers be-
tradition that developed primarily in response to the lieved to exist in every human being.
needs of athletes. Ultimately, it encompassed not This somewhat conservative approach of merely
only questions regarding exercise, bathing, and re- assisting nature and above all not harming the sick
laxation, but the regulation of food and drink for all characterized the method of Hippocratic physicians.
citizens. All of these traditions eventually merged It was congruent with the rather tenuous social posi-
around 500 B.C. into a techne iatriche, or healing tion of the early Greek healer, often an itinerant
science, that sought to define its own intellectual craftsman entirely dependent on his personal reputa-
approach and methodology. For this purpose, the tion because the country lacked an educational and
new medicine adopted a theoretical framework capa- licensing system for medical professionals. Given
ble of explaining the phenomena of health and ill- the elementary state of medical knowledge as re-
ness. The new techne was also heavily dependent on flected in the absence of properly identified disease
clinical observations from which careful inferences entities, the demands made of Hippocratic healers
and generalizations were derived. were simple prognostications — will the patient live
The foremost representative of classical Greek or die? - and ideally some amelioration of symptoms
medicine was Hippocrates, a prominent practitioner by complementing the healing forces. Unfettered by
and teacher who came to personify the ideal Western religious barriers, although coexisting with a reli-
physician. Within a century of his death in 370 B.C., gious healing system based on the cult of Asclepius
several unknown disciples wrote nearly 60 treatises, (the god of medicine), the techne iatriche prospered
come clinical and some theoretical, on medical sub- within the flexible tenets of humoralism, a cultural
jects differing widely in content and style. This col- system that was widely shared by healers and their
lection of writings, which comprised a comprehen- patients and that allowed for the gradual inclusion
sive and rational healing system usually known as of new clinical observations.
"Hippocratic" medicine, emphasized the individual After the death of Alexander the Great in 323 B.C.
patient. Its practitioners focused exclusively on and the partial dismembering of his empire, Egypt
physical factors related to health and disease, includ- flourished under the rule of the Ptolemies. Alexan-
ing the immediate environment. Indeed, among the dria, the chief cultural and commercial center, be-
most famous works of the Hippocratic corpus was came famous for its library and museum, attracting
the treatise Airs, Waters, and Places, an early manuscripts and scholars from the entire Hellenistic
primer on environmental medicine. Another was world. In addition to collecting medical literature,
Epidemics, a day-to-day account of certain patients, scholars such as Herophilus of Chalcedon and
and a third was Regimen, a prescription of diet and Erasistratus of Cos carried out systematic human
life-style conducive to health. dissections, identifying structures of the circulatory
For the ancient Greeks, health was a state of bal- and nervous systems, the eye, and the female repro-
ance among four bodily humors: blood, phlegm, yel- ductive organs.
low bile, and black bile. Each had a specific bodily Given the limitations of contemporary medical
source, a pair of fundamental qualities, and a par- knowledge, as the Hippocratic healing profession be-
ticular season in which it could be produced in ex- gan to compete for upper-class patronage serious de-
cess. The blood, for example, was elaborated in the bates ensued about the value of medical theory and

12 I. Medicine and Disease: An Overview
bedside expertise. Two "sects," the Dogmatists and Faced with a growing population and adverse eco-
Empiricists, first became involved in this dispute. nomic conditions, the early Christian church created
The former, led by Praxagoras of Cos, emphasized the a number of philanthropic institutions. The provi-
need for theoretical knowledge in medicine, espe- sion of shelter and food for the poor and for strangers
cially to establish plausible explanations for the was extended to several forms of health care in
phenomena of health and disease. The Empiricists, houses called xenones (hostels) and more specifically
under the guidance of Herophilus, revolted against nosokomeia (places for the sick). Among the first was
excessive speculation and expressed skepticism an inn built by Bishop Basil around 375 in Caesarea,
about the value of medical theory, placing instead which was apparently staffed by nurses and physi-
greater emphasis on bedside experience. Two centu- cians. Two decades later similar institutions opened
ries later, a third group of Greek physicians residing their doors in Constantinople, and thereafter such
in Rome — the Methodists — espoused a simplistic hospitals proliferated in other major commercial cit-
view of bodily functioning and restricted their treaties of the Byzantine Empire.
ments to bathing, diet, massage, and a few drugs. In western Europe, monks played an important
In Rome, healing was essentially a popular skill role in Christian healing as well as in the collection
practiced by heads of families, slaves, and foreign- and preservation of medical manuscripts. Whereas
ers. A lack of regulations and low social status con- Augustinian monks lived a life of isolation and
tributed to a general mistrust of physicians. An ex- prayer, the followers of Benedict created working
ception, however, was the respect accorded to Galen communities that cared for their sick brethren as
of Pergamon of the second century, a well-educated well as visitors and transients. Monasteries such as
follower of Hippocratic medicine who managed to the cloister of Monte Cassino, founded in 529, and
overcome the schisms of sectarianism. A prolific the cathedral schools after the year 800 became
writer who authored hundreds of treatises, Galen heirs to fragments of classical medical knowledge.
also carried out anatomic dissections and physiologi- Many Benedictine monasteries - such as St. Gall (c.
cal experiments on animals. He successfully inte- 820) - continued both a hospitale pauperum for pil-
grated his extensive clinical experience, which he grims and an infirmarium for sick monks and nov-
acquired mainly as a surgeon to performing gladia- ices. Monasteries were constructed along important
tors, into his basic theoretical knowledge, providing roads or in surviving Roman towns, notably in south-
medicine with a comprehensive system destined to ern France and Italy. Sick care was dispensed as part
survive for nearly 1,500 years. of the traditional Christian good works. By contrast,
medical treatment under the supervision of physi-
Early Christian Era, East and West cians remained sporadic.
After the collapse of the Roman Empire, Western
medicine experienced a period of retrenchment and Islam
decline. Healing became an important act of Chris- Before the seventh century, Islamic healing con-
tian charity, a divine gift freely provided within the sisted merely of a collection of popular health rules,
framework of the new church and not restricted to or hadiths, known as "Muhammad's medicine" for
professional physicians. Given this religious orienta- use by devout Muslims living on the Arabic penin-
tion, Christians healed through the confession of sula. In accordance with basic religious and philo-
sins, prayer, the laying on of hands, exorcisms, and sophical ideas, this system was holistic, emphasizing
miracles, occasionally performed by saints or church both body and soul. However, as the Islamic Empire
fathers. gradually expanded, a comprehensive body of Greco-
In Byzantium, the Christian magical-religious Roman medical doctrine was adopted together with
healing flourished side by side with the earlier ra- an extensive Persian and Hindu drug lore.
tional Greco-Roman medicine in spite of frequent The collection, preservation, and eventual trans-
tensions, especially because physicians often ex- mission of classical medical knowledge went on for
acted exorbitant payments for their services. Sev- several centuries. Even before the Arab conquest of
eral of them, including Oribasius of the fourth cen- 636, Nestorian Christians in Jundishapur, Persia,
tury, Aetius of Amida and Alexander of Tralles of had played a prominent role in safeguarding Greek
the sixth century, and Paul of Aegina of the seventh learning by translating many Greek works into the
century, compiled and preserved ancient medical Syriac language. Later, under Islamic rule, these
knowledge and with their writings made Galen the Nestorian physicians wielded great influence over
central medical authority for the next 500 years. the early caliphs, conducting searches for additional

Greek manuscripts in the Middle East and directing designed to enforce law and order according to the
a massive translation program of scientific texts mandates of the Koran gradually extended its juris-
from Syriac into Arabic. diction over multiple healing activities. Physicians,
Islam's political supremacy and commercial net- surgeons, bonesetters, and pharmacists were exam-
works made possible the collection of medicinal ined by the caliph's chief physician or an appointed
plants from the Mediterranean basin, Persia, and inspector before receiving permission to practice. Un-
India. The eleventh-century author Abu al-Biruni questionably, such official efforts to establish ethical
composed a treatise on pharmacy in which he listed and practical standards for medical conduct and ac-
about 720 drugs. In addition, Islamic alchemy fur- tion were important steps in the professionalization
nished a number of metallic compounds for the treat- of medicine.
ment of disease. Such expansions in materia medica
and the compounding of remedies led to the estab- Middle Ages
lishment of a separate craft of pharmacy. After the twelfth century, medieval medical knowl-
In medical theory, authors writing in Arabic edge in the Occident ceased to be based solely on a
merely followed and further systematized classical number of scattered Greek and Latin manuscripts
humoralism. Whereas al-Razi, or Rhazes, of the carefully collected and preserved for centuries in
ninth and early tenth centuries contributed a num- monasteries and schools. A rapidly growing number
ber of original clinical works such as his treatise on of classical medical texts, including the Canon of
smallpox and measles, the Canon of Medicine com- Avicenna and clinical treatises of Rhazes, were trans-
posed in the early eleventh century by the Persian lated from Arabic to Latin. Nonetheless, the theory
physician Ibn Sina, or Avicenna, became the leading of four humors and qualities remained the basis for
medical encyclopedia and was widely used until the explaining health and disease. It was supplemented
seventeenth century. Finally, Moses Maimonides, a by the notion that an essential or "radical" moisture
Jewish physician and prolific author, wrote on clini- was needed to ensure proper mental and physical
cal subjects and medical ethics. functioning. Based on the natural wetness of bodily
Islam significantly influenced hospital develop- tissues, this element played an important role in
ment, creating secular institutions devoted to the explaining disease, senility, and death.
care of the sick. The first bimaristan - a Persian The inclusion of medicine in early university stud-
term meaning "house for the sick" - was established ies had momentous consequences. Teachers devised
in Baghdad before the year 803 by Ibn Barmak, the formal curricula and identified a specific body of
famous wazir of Harun al-Rashid. It was based on medical knowledge to be mastered by students. For
Byzantine models transmitted to Jundishapur. Un- the first time, physicians could acquire an academic
like previous and contemporary Christian institu- degree in the field of medicine, thus laying claim to
tions devoted to medical care, bimaristans were pri- greater competency and legitimacy. Among the first
vate hospitals symbolizing royal prestige, wealth, schools to offer medical studies was in Salerno,
and charity. Their selected inmates came from all around 985, but the real growth in medical educa-
sectors of the population and included mentally dis- tion occurred in the thirteenth century with the
turbed individuals. Operated by a director together founding of three major university centers: Montpel-
with a medical staff, pharmacist, and servants, lier and Paris in France, Bologna in Italy. Because a
bimaristans offered comprehensive medical care and medieval medical education stressed theory, rheto-
educational opportunities for students serving ap- ric, and philosophical speculation, graduates ac-
prenticeships. In fact, the hospitals had their own quired an unprecedented degree of prestige and sta-
libraries, which contained copies of medical texts tus. In contrast, the practical aspects of healing
translated from the Greek and Syriac. lacked intellectual standing, and surgery was there-
In addition to providing clinical training, medical fore excluded from university studies. Graduates, in
education became more formalized. Small private turn, created select medical organizations - often un-
schools offered a flexible curriculum of lectures and der royal patronage - and worked hard to achieve a
discussions, generally under the direction of famous monopoly on practice.
physicians. In recognition of these cultural appren- Teaching centers became focal points for medical
ticeships, the state issued licenses for practicing investigations. Human dissection, for example, be-
medicine to students who had successfully completed gan at the University of Bologna toward the end of
a course of theoretical and clinical studies. The tradi- the thirteenth century, prompted by forensic as well
tional Islamic hisbah system of codes and regulations as medical considerations: Both lawyers and practi-

tioners were interested in ascertaining the causes of derstood. For example, the early-sixteenth-century
death from foul play or epidemic disease. In 1316, a findings of Andreas Vesalius of Padua, based on me-
Bolognese professor, Mondino de Luzzi, wrote the ticulous and systematic dissections that established
first modern treatise on anatomy. This specific inter- the foundations of modern anatomy in the West,
est was continued at other universities, including contradicted Galen's descriptions. In fact, Vesalius
those of Padua, Florence, and Pisa. All works on demonstrated that Galen's findings were based on
anatomy were designed to illustrate the descriptions animal dissections - especially of the barbary ape -
of Galen, still the absolute authority on the subject. instead of human dissections.
In response to repeated and deadly plague Another sixteenth-century attack on classical
epidemics - the first pandemic struck Europe be- medicine came from a Swiss practitioner, Philippus
tween 1348 and 1350 - northern Italian city-states von Hohenheim, better known by his adopted name,
instituted a series of public health measures designed Paracelsus. His goal was to investigate nature di-
to protect the healthy elite from the ravages of the rectly and thereby discover the hidden correspon-
disease. Because poisonous miasma was blamed for dences between the cosmos and human beings. Dur-
the humoral imbalance that caused susceptibility to ing his many travels, Paracelsus acquired a detailed
plague, authorities isolated ships whose crews and knowledge of occupational diseases. For example, he
cargoes were suspected of carrying miasma. The observed the ailments contracted by European min-
isolation - or so-called quarantenaria — necessary to ers, an unprecedented pathology without adequate
neutralize the offending particles lasted for 40 days. classical antecedents. On the basis of his alchemical
Venice and Ragusa were among the first cities to education and clinical experience, Paracelsus formu-
implement such measures, the former in 1348, the lated a new theory of medicine based on the notion
latter in 1377. Burial regulations, the control of wa- that the body functioned chemically under the direc-
ter supplies, the cleansing or burning of contami- tion of an internal "archeus," or alchemist, responsi-
nated possessions - all inaugurated a comprehensive ble for maintaining the proper balances and mix-
sanitary program widely adopted by other European tures. Consequently, cures could be achieved only
cities in ensuing centuries. through the administration of chemically prepared
The emergence during the twelfth century of lay remedies. Paracelsus strongly advocated the use of
communities in which the principal focus of charita- mercury in the treatment of syphilis, a potentially
ble work was care of the sick can be seen as a re- toxic therapy widely accepted by his contemporaries.
sponse to Europe's growing burden of disease. The Equally important were the innovations in surgi-
Knights of St. John, the Teutonic Knights, and the cal technique and management of gunshot wounds
Augustinian Brotherhood played key roles in this by the sixteenth-century French surgeon Ambroise
evolution. Hospital foundations, sponsored by the Pare\ On the basis of new anatomic knowledge and
rulers of newly created kingdoms or local bishops, clinical observations, Pare questioned a series of tra-
provided the poor, elderly, unemployed, and sick ditional assumptions concerning the treatment of
with spiritual and physical care in the form of diet injured soldiers, including venesection, cauteriza-
and nursing. The rising prevalence of leprosy after tion, and the use of boiling oil. Pare's publications,
1200 forced the establishment of nearly 20,000 shel- written in the vernacular, profoundly influenced the
ters to separate these stigmatized sufferers from the surgical craft of his day, replacing ancient methods
general population. With the onset of plague after with procedures based on empirical knowledge.
1348, local authorities set up quarantine stations
and pesthouses aimed at isolating those suspected of Seventeenth Century
harboring the disease. The classical assumptions of humoralism that had
explained human functioning in health and disease
Renaissance for nearly two millennia in the Western world were
With the revival of classical Greek learning, or hu- severely challenged in the seventeenth century. Dur-
manism, during the Renaissance, Western medicine ing this century, the body came to be viewed as
was profoundly influenced by the replacement of something like a machine governed by physical prin-
corrupt and incomplete texts with new Latin transla- ciples. This view was expressed by the philosopher
tions of the original Greek. However, tensions devel- Rene Descartes in a treatise published posthu-
oped between the old learning and contemporary mously in 1662. Cartesian man had a dual nature: a
insights into the phenomena of health and disease, physical body ruled by universal laws of matter and
some of which had been previously ignored or misun- motion, and an immaterial soul or mind - a pure

thinking entity - located in the pineal body of the sician, urged his colleagues to ignore the conflicting
brain. The body was conceived of as a vast hydraulic theoretical views, proposing instead the careful
network of hollow pipes, moving blood and nervous study of individual diseases at the bedside. Syden-
fluid in the circulatory and nervous systems under ham's goal was the establishment of complete clini-
the influence of the mind. cal descriptions of particular diseases, their subse-
Descartes's mechanical theory spawned a mechani- quent classification, and the development of specific
cal school of human physiology located primarily in remedies for each identified ailment.
northern Italy,- where Galileo Galilei, the great
physicist, had already established a science of me- Eighteenth Century
chanics. Following in Galileo's footsteps, a mathema- In the occidental world, the Enlightenment created
tician, Giovanni A. Borelli, analyzed the phenome- an optimistic outlook concerning the role and bene-
non of muscular contraction and a physician, fits of medicine. Most contemporary thinkers be-
Sanctorius of Padua, studied metabolic combustion lieved that health was a natural state to be attained
and insensible perspiration. and preserved. Society had to be made aware of
In England, William Harvey's experimental dis- medical possibilities through the employment of pro-
covery of the blood circulation, announced in 1628, fessionals who could deal expertly with all health-
contributed to the mechanical view of living organ- related problems. Governments increasingly sought
isms while discrediting Galen's fanciful hypothesis to develop social policies that included the physical
of a humor ebb andflow.The heart was now viewed well-being of the public. A new medical elite took
as a pump, its chambers closing tightly with the help charge and began to play a more prominent role in
of valves. Blood was impelled into an intricate sys- European society.
tem of vessels according to the laws of hydrodynam- Among the requirements of national power per-
ics and traveled in a close circle through the arterial, ceived by European authorities was a healthy and
venous, and capillary systems. expanding population. Greater emphasis was placed
Not only did Harvey'sfindingssupport a mechanis- on environmental health, infant and maternal wel-
tic view of the human organism, but his approach to fare, military and naval hygiene, as well as mass
the theory - which included dissections, animal ex- treatment of the poorer sectors in newly erected
periments, and mathematical reasoning - demon- hospitals and dispensaries. Absolutist governments
strated the potential usefulness of scientific research established systems of "medical police." These orga-
in resolving physiological questions. On the basis of nizations were responsible for establishing and im-
the ideas of Pierre Gassendi, a seventeenth-century plementing programs, such as that designed by the
French philosopher, regarding the corpuscular na- German physician Johann P. Frank, to monitor and
ture of matter, various British investigators working enforce public and private health regulations from
in concert studied the phenomenon of respiration. By cradle to grave. In Britain, private philanthropy
the 1670s, Robert Boyle, Robert Hooke, Richard substituted for governmental action in matters of
Lower, and John Mayow had concluded that certain health. Although frequently Utopian in its goals,
air particles entering the lungs and mixing with arte- the medical police movement created greater aware-
rial blood were essential for all vital functions. At the ness of the social and economic factors conducive to
same time, chemical fermentation studies by Jean disease. In turn, physicians and reformers were suc-
Baptiste van Helmont and Francois de la Boe ex- cessful in establishing charitable institutions for
plained the nature of digestion. Microscopic studies, care of the sick, including mothers and children.
carried out by Anton van Leeuwenhoeck in Holland Needy ambulatory patients were seen in dispensa-
using a single-lens instrument with a magnification ries and polyclinics. Although often crowded and a
of about 300 diameters, remained unequivocal. source of contagion, such establishments provided
Although corpuscular dynamics replaced tradi- shelter, food, and a modest medical regimen de-
tional humors and their qualities in the explanation signed to manage illness.
of human physiology, clinical medicine failed to bene- Efforts to control smallpox focused on a practice
fit from the new medical theories. Practitioners popular in the Orient: smallpox variolation. The vi-
treating the sick could not readily apply these views rus, taken from pustules of an active case, was inocu-
to the therapeutic tasks at hand, preferring instead lated in healthy individuals on the assumption that
to prescribe their traditional cures by adhering to this transfer would attenuate the agent and produce
obsolete ideas of humoral corruption and displace- only a mild case of the disease in exchange for perma-
ment. Thomas Sydenham, a prominent English phy- nent immunity. In England the procedure was pio-

neered in 1721, but it remained controversial be- tems remained highly subjective and dependent on
cause of its potential for causing full-fledged, often the clinical experience of the nosologist who pro-
fatal cases of smallpox and thus triggering unex- duced them. Greater accuracy and uniformity were
pected epidemics. After the 1760s, however, simpli- achieved as bedside experiences were linked to struc-
fied and safer inoculation methods found popular tural changes observed at postmortem dissections,
acceptance, and these were replaced in the 1790s by an approach pioneered by the Italian physician Gio-
cowpox vaccination, introduced by Edward Jenner. vanni B. Morgagni but not fully implemented until
On the theoretical front, the eighteenth century decades later in France.
became the age of medical systems in the Western
world. It was clear that a synthesis of the isolated Nineteenth Century
physical and chemical discoveries of the preceding
century into a comprehensive system would be neces- French Clinical School
sary to provide a rationale for and guidance to clini- Modern Western medicine emerged in France at the
cal activities. Spurred by success in the physical Paris Medical School during the first half of the nine-
sciences, especially Newton's formulation of the laws teenth century. After the French Revolution, political
of gravity, physicians set out to establish principles developments and a new philosophical outlook radi-
governing the phenomena of health and disease. cally changed the theoretical and institutional bases
Such efforts were as old as medicine itself. However, of medicine. Given the population explosion and ur-
new models of anatomy and physiology based on banization, hospitals became the key locations for
Vesalius's dissections and Harvey's experiments, cou- medical advances. Housing thousands of poor pa-
pled with chemical and microscopic findings, de- tients, the Parisian hospitals offered unique opportu-
manded placement into an updated scaffolding. nities for the observation of a large number of sick
Most eighteenth-century systematists tended to individuals.
be prominent academics. As teachers and famous The French medical revolution was ushered in by
practitioners, they zealously promoted and defended an important change in approach. Arguing that it
their creations, fueling bitter controversies within was not necessary to discover the ultimate causes of
the medical profession. System building conferred health and disease, early leaders of the Paris Medi-
status and a mantle of intellectual respectability cal School, such as Pierre J. Cabanis and Philippe
conducive to patient patronage and separation from Pinel, postulated that physicians could perceive the
quacks. Among those who adhered to mechanical effects of disease and apprehend the relationships
concepts in explaining clinical events were the between the disease and the patient, accessible to
Dutch professor Herman Boerhaave of Leyden and observation only at the bedside. Thus, only the incon-
the German Friedrich Hoffmann of Halle. By con- testable truths of sensory perception had validity in
trast, a colleague of Hoffmann, Georg Stahl, tried to any attempt to understand health and disease.
remedy the apparent inadequacies of iatromecha- These phenomena were too complex and variable to
nism by postulating the existence of a vital princi- be placed into the straitjacket of a specific medical
ple, a soul or "anima," capable of harmoniously di- theory. Stress was to be placed on practical problem
recting all mechanical activities in the body and solving, with sense impressions providing the only
thus ensuring organic unity. Two subsequent sys- reliable data.
tems elaborated by the Scottish physicians William This skeptical empiricism gave rise to a new
Cullen and John Brown assumed that a properly method: "analysis." Disease was composed of many
balanced and stimulated nervous system played a symptoms and signs, and these confusing combina-
pivotal role in the maintenance of human health. tions appeared sequentially at the sickbed. The most
Efforts to classify diseases were intensified. important task was to record the regular order of
Nosology, the systematic division of disease entities, such manifestations, correlate them with physical
prospered side by side with similar taxonomic efforts signs, and thus recognize simple patterns. Eventu-
directed at plants and animals. Physicians such as ally, practitioners would be able to discern specific
Carl von Linne (Linnaeus), Boissier de Sauvages, disease entities and finally classify them. Pinel
and Cullen established complex classification sys- urged physicians to walk the hospital wards fre-
tems designed to bring order to the myriad symptom quently, notebook in hand, recording the hourly and
complexes found at the bedside as well as to provide daily progression of illness. The goal was better diag-
guidelines for treatment. Unfortunately, these sys- nosis and prognosis based on clinical events.

Emphasis on the physician's powers of observation later. Further answers had to be sought in the labora-
increased the importance of physical diagnosis and tory, not just at the sickbed.
expanded the techniques employed in eliciting physi-
cal signs of illness. Until this time, practitioners had German Scientific Medicine
relied almost entirely on their patients' accounts to Before the eclipse of the Paris Medical School, Ger-
reach a diagnosis. Although the clinical history re- man medicine began to emerge from its earlier,
mained important, French physicians began to ap- speculative period, frequently labeled "romantic."
ply new methods starting with Jean N. Corvisart's From 1800 to 1825 physicians in the politically di-
direct percussion in 1808, the employment of a vided German states made a serious attempt to es-
stethoscope by Rene T. H. Laennec in 1816, and tablish a "science" of medicine using criteria from
indirect percussion of the body with a plessimeter the critical philosophy of Immanuel Kant. But their
designed by Pierre A. Piorry in 1826. These proce- efforts were doomed given the elementary state of
dures were, of course, also based on the premise that knowledge of what we consider to be the "basic"
certain organs in the patient's diseased body suf- medical sciences: anatomy, physiology, biochemistry,
fered a number of structural changes. pathology, and pharmacology.
Thus, another fundamental development of the By the 1830s, however, the foundations had been
Paris Medical School was pathological anatomy, the laid for less ambitious but more fruitful investiga-
study of localized changes in bodily organs accom- tions into the phenomena of health and disease. The
plished through systematic postmortem examina- 1834 Prussian-German Customs Union and exten-
tions of the thousands of patients who died in hospi- sive railroad network brought a measure of eco-
tals. Correlating clinical symptoms and signs with nomic prosperity to the German states, enabling
specific organic lesions enabled practitioners to rede- them to support the reform of their autonomous uni-
fine particular disease entities and understand the versity system. Armed with an ideology of pure re-
underlying structural defects. Such clinicopatho- search and lack of concern for immediate practical
logical correspondences expanded medicine's knowl- results, German physicians went to work in aca-
edge of diseases, their effects, and natural evolution. demic laboratories and dissecting halls. The empha-
As a corollary, French physicians became more inter- sis on and prestige accorded to the pursuit of intellec-
ested in improving their diagnostic rather than their tual activities was eagerly supported by the highest
therapeutical skills. authorities, who perceived such scientific enter-
Another tool, the "numerical method," was intro- prises as enhancing national prestige.
duced in 1828 by Pierre C. A. Louis to compare Studies in physiology, microscopic anatomy, em-
clinicalfindingsand identify through medical statis- bryology, as well as comparative and pathological
tics general disease characteristics as well as the anatomy flourished. One of the key figures promot-
efficacy of traditional therapies. Although this ap- ing these studies was Johannes Mueller, a physiolo-
proach initially raised a storm of protest among prac- gist searching for the ultimate truths of life behind
titioners who felt that statistical calculations tended empirical data. Although his philosophical goals re-
to obscure the significance of individual clinical mained elusive, Mueller had trained a whole genera-
variations, the method launched a new era of clini- tion of outstanding German scientists by the time of
cal investigation, replacing intuitive and impression- his death in 1858. They included Theodor Schwann,
istic decision making at the bedside. proponent of the cell theory; Emil DuBois Reymond,
By the mid-nineteenth century, however, the and Hermann von Helmholtz, famous for their dis-
French school lost its undeniable leadership in West- coveries in nerve electrophysiology and the physics
ern medical practice. Although tremendously fruit- of vision; Jakob Henle, the founder of histology; and
ful, the clinical approach based on bedside observa- Rudolf Virchow, the founder of cellular pathology.
tions and postmortem findings had its limitations. Indeed, these men rejected a general philosophical
Consciously ignored were questions concerning the framework and adopted a purely reductionist view-
causes of disease and the nature of biological events point, attempting to explain all biological phenom-
surrounding the phenomena of health and disease. ena as merely following the laws of physics and
What had been a realistic approach in an era of chemistry.
speculative chemistry and physiology, imperfect mi- Germany's university system played a central
croscopes, and nonexistent pharmacological knowl- role in the development of scientific medicine in
edge around 1800 became an anachronism 50 years the West after 1840. Unlike the near monopoly of

French academic studies in one city, Paris, there impressive and promised further breakthroughs. At
were more than 20 institutions of higher learning the same time, greater technological assistance and
scattered throughout the German states, each self- diagnostic complexity shifted medical care to hospi-
governing and intensely competitive. Since degree tals and clinics, significantly raising costs. But the
requirements included the submission of disserta- actual practice of medicine remained unaffected.
tions based on original research, the stage was set Although the fledgling pharmaceutical industry be-
for a spectacular increase in scientific activity once gan to purify a number of traditional remedies and
the universities had established prestigious profes- develop a few new drugs, therapeutics lagged.
sorships and built adequate laboratory facilities. Translating scientific understanding into convinc-
Medical research became a respectable career, made ing practical results had to await the development
possible by the proliferation of fellowships and assis- of vaccines, sera, and antisepsis based on a knowl-
tantships. Successful individuals were rewarded edge of bacteriology.
with academic posts and further facilities, leading to
a dramatic rise in scientific professionalization and Germ Theory
specialization. Since the time of Hippocrates, Western practitioners
Even in clinical disciplines German academics had blamed factors in the atmosphere for the appear-
with proper research experience edged out outstand- ance of infectious disease. A "miasma" composed of
ing practitioners. A whole generation of physicians malodorous and poisonous particles generated by the
who had trained abroad — especially in Paris - decomposition of organic matter was implicated in a
returned with a knowledge of physical diagnosis and broad array of fevers, including plague, malaria, and
pathological anatomy. A new bedside approach com- yellow fever. Speculations about the nature of these
bined the French methods with German chemical miasmatic specks waxed and waned, from Girolamo
and microscopic examinations based on a growing Fracastoro's seminaria, or "seeds of disease," in 1546,
understanding of human physiology and physio- to microscopic "worms," or multiplying ferments,
pathology. Although the first key step of disease de- zymes, proposed by William Fair in 1842. However,
scription and identification had taken place in Pari- physicians remained generally skeptical of theories
sian hospitals, German physician-scientists sought that implicated microscopic substances in the genesis
to understand the mechanisms that caused pathologi- of complex disease entities. Moreover, their rudimen-
cal changes. Here the laboratory became important tary microscopes only added to the confusion by re-
for biochemical analyses, microscopic observations, vealing myriad objects.
and animal experiments. Given the clinical behavior of the most common
The quest for greater diagnostic precision was nineteenth-century diseases such as typhus, cholera,
aided by the design of new tools for visualizing dis- typhoid, and yellow fever, most physicians accepted
ease. In 1851, Helmholtz described the ophthalmo- the notion that they were not directly contagious
scope, an instrument capable of directly exposing and could occur only because of specific environmen-
eye disorders and testing visual acuity. The success- tal conditions. This anticontagionist posture was
ful assembly of a laryngoscope by Johann N. strongly reinforced by political and economic groups
Czermak in 1857 permitted inspection of the throat, that sought to avoid the imposition of costly quaran-
especially the larynx and vocal cords. Visualization tines. But others argued that certain contagious dis-
of the esophagus was accomplished in 1868 by Adolf eases, such as smallpox, measles, and syphilis, were
Kussmaul with an esophagoscope, and the bladder indeed transmitted by living parasites.
came to be observed with the help of the cystoscope, In the 1840s, chemists, including Justus von
invented by Max Nitze in 1877. Finally, in 1895, Liebig, proposed that both contagion and miasma
Wilhelm C. Roentgen, a physicist, discovered the were actually "ferments," consisting of self-repro-
rays that carry his name. Henceforth, X-ray photo- ducing particles of a chemical nature spontaneously
graphs andfluoroscopesbecame common features in generated during the decomposition of organic mat-
clinical diagnosis, especially that of chest diseases. ter. At about the same time, Henle, a German anato-
German advances in the basic medical sciences mist, suggested that such particles were actually
and clinical diagnosis were not matched at the alive and behaved like parasites after invading the
therapeutic level. In fact, a better understanding of human organism. He believed that the causes of
disease processes often led to skepticism - even infectious disease could be found by a careful search
nihilism - regarding possible cures. To be sure, the for these parasites, believed to be members of the
conceptual advances in understanding disease were plant kingdom. The proof for this causal relation-

ship between disease and parasites was contained technical methods for cultivating and studying bacte-
in Henle's three "postulates": constant presence of ria, Pasteur and his collaborators turned their efforts
the parasite in the sick, its isolation from foreign toward determining the actual mechanisms of bacte-
admixtures, and reproduction of the particular dis- rial infection and host resistance. By 1900 not only
ease in other animals through the transmission of were physicians able to diagnose the presence of spe-
an isolated parasite. cific microorganisms in the human body and hence
Thanks to the work of Louis Pasteur, a French diagnose an infectious disease, but they possessed
chemist, fermentation and putrefaction were shown some knowledge concerning natural and acquired im-
to be indeed mediated by living microorganisms. In munity. In several instances, the latter could be suc-
1857 Pasteur claimed that the yeast responsible for cessfully induced, a belated triumph of modern labo-
lactic fermentation was such a microorganism. In ratory medicine.
the early 1860s, Pasteur disposed of the doctrine of GuenterB. Risse
spontaneous generation, proving through a series of
clever experiments that only by exposure to tainted Bibliography
air would processes of fermentation and putrefaction Ackerknecht, Erwin H. 1967. Medicine at the Paris Hospi-
take place. Microbial life could not exist in any or- tal, 1794-1848. Baltimore.
ganic medium that had been sterilized and subse- 1982. A short history of medicine. Baltimore.
quently protected from outside contamination. Ben David, E. G. J. 1960. Scientific productivity and aca-
With the existence of microscopic germs and some demic organization in 19th century medicine. Scien-
tific Sociological Review 25: 828-43.
of their actions firmly established, researchers such
Bullough, Vern. 1966. The development of medicine as a
as Pasteur and the German physician Robert Koch profession. Basel.
began to study specific diseases. In 1876 Koch pub- Cipolla, Carlo M. 1976. Public health and the medical
lished his findings on anthrax, a deadly illness of profession in the Renaissance. London.
animals, especially cattle and sheep. He provided Debus, Allen G., ed. 1974. Medicine in seventeenth century
the first proof that a specific microorganism could England. Berkeley and Los Angeles.
cause a particular disease in an animal. Koch's new Foster, W. D. 1970. A history of medical bacteriology and
techniques for obtaining pure cultures and staining immunology. London.
pathogenic bacteria further advanced the fledgling Foucault, Michel. 1973. The birth of the clinic, trans. A. M.
field of microbiology and led to a reformulation of Sheridan Smith. New York.
Henle's postulates. According to Koch, three criteria Garrison, Fielding H. 1929. An introduction to the history
were needed to implicate a particular microorgan- of medicine. Philadelphia.
ism in the etiology of a certain disease. First, the King, Lester S. 1958. The medical world of the eighteenth
century. Chicago.
parasite must be present in every case of the disease
1963. The growth of medical thought. Chicago.
and under circumstances that could account for the Nasr, Seyyed H. 1968. Science and civilization in Islam.
clinical course and pathological changes of that dis- Cambridge, Mass.
ease. Second, this agent should not be present in any Penn, M., and M. Dworkin. 1976. Robert Koch and two
other disease as a fortuitous and nonpathogenic para- visions of microbiology. Bacteriological Reviews 40:
site. Finally, after being fully isolated from the sick 276-83.
organism and repeatedly grown in pure culture, the Phillips, E. D. 1973. Greek medicine. London.
parasite should be able to induce the same disease if Risse, Guenter B. 1986. Hospital life in Enlightenment
inoculated into another animal. Scotland. New York.
The last two decades of the nineteenth century Rothschuh, Karl E. 1973. History of physiology, trans, and
witnessed an unprecedented string of bacteriological ed. Guenter B. Risse. Huntington, N.Y.
Shryock, Richard H. 1947. The development of modern
discoveries based on the Henle-Koch postulates, in-
medicine. New York.
cluding the agents responsible for typhoid fever, lep- Singer, Charles, and E. A. Underwood. 1962. A short his-
rosy, and malaria (1880), tuberculosis (1882), cholera tory of medicine. Oxford.
(1883), diphtheria and tetanus (1884), pneumonia Temkin, Owsei. 1973. Galenism: Rise and decline of a
(1886), plague and botulism (1894), dysentery (1898), medical philosophy. Ithaca, N.Y.
and syphilis (1905). Whereas Koch and his co- Temkin, Owsei, and C. L. Temkin, eds. 1967. Ancient
workers devoted much time to the development of medicine. Baltimore.

from entering and harming a human body by means
1.2 of signs and symbols demonstrating an alliance with
History of Chinese Medicine superior metaphysical powers, and they had to be
removed from the body either through the casting of
oral or written spells or with the help of substances
designed to kill or chase away (for instance, through
Premedical Health Care their odor) unwanted intruders. Several clues sug-
A concern with illness has been documented in gest that among the origins of acupuncture may
China for three millennia; the earliest written evi- have been attempts to pierce, with symbolic swords
dence extant today on the theoretical and practical and lancets, afflicted, aching body regions thought
consequences of this concern dates from approxi- to be invaded by some outside evil.
mately the eleventh century B.C. At that time, and Ancestral and demonological notions of health
for centuries to come, it was assumed that the well- and illness are mentioned here for two reasons.
being of the living - be it related to success on the First, they have survived in Chinese culture until
battlefield, to an abundant harvest, or to physical the present time as important aspects of the overall
health - depended to a considerable extent on their system of conceptualized and practical health care,
interactions with the nonliving members of the com- particularly in the treatment of mental and chil-
munity (i.e., with their ancestors). An adherence to dren's illnesses. Second, Chinese medicine, docu-
specific norms was thought to guarantee social and mented since the second century B.C. and developed
individual health; transgressions were known to as a system of ideas and practices based on insights
cause the wrath of the dead, who then had to be into the laws of nature rather than on metaphysics,
propitiated with sacrifices. The communication be- still embodies some of the fundamental tenets of
tween the living and the nonliving that was neces- these earlier approaches to understanding health
sary to establish the cause of an affliction and to and healing, namely an emphasis on cause—effect
identify an appropriate remedy was recorded on relationships and a localistic-ontological notion of
bones and turtle shells, many of which were found in disease.
the soil, especially in the province of Henan, earlier
this century. Whether the belief in ancestral inter- Traditional Chinese Medicine
vention was supplemented by a pragmatic applica- An almost complete afterworld household, closed in
tion of drugs or other empirically valuable means of 167 B.C., was unearthed from the now-well-known
therapy was not documented in written form at this Ma-wang-tui site near Ch'ang-sha in Hunan be-
early time. tween 1972 and 1974. This tomb of a noble family
Political changes during the first millennium had been equipped with virtually everything a de-
B.C., when the Chou dynasty fell into a period of ceased person was thought to need in his or her
turmoil with several centuries of civil war, may have subsequent existence, including 14 manuscripts on
been responsible for the rise of a new worldview. various aspects of health care. These manuscripts
Even though a belief in the effect of ancestral curses marked the beginning of documented Chinese medi-
or blessings on the health of the living has survived cine and revealed that it was on the verge of break-
in Chinese culture well into the twentieth century, ing away from metaphysical health care. Thus, we
especially among some rural strata of the popula- may assume that they also reflected the earliest
tion, Chou sources indicate a change in emphasis. phase in the development of medicine in China, that
The physical health and illness of the individual is, the development of a system of health care beliefs
(and, in the case of epidemics, of society) were and practices focusing specifically on the illnesses of
thought of at this time predominantly as an outcome the human mind and body rather than on human
of successful protection against the possibility or social and individual existence as a whole.
manifestation of an onslaught of not only visible but The tomb dates from a period between the second
also invisible enemies (i.e., demons). century B.C. and the first century A.D., when Chi-
In contrast to ancestors, demons, who were not nese medicine took on its basic shape. This appears
related to specific living persons as deceased rela- to have been a quite dynamic era. As early as the
tives, were not believed to desist from harming hu- first century, various schools of medical thought had
mans even if they adhered to certain moral princi- been founded and had already produced diverging
ples. Moreover, demons could not be propitiated ideas. These were compiled under the name of the
through sacrifice. Rather, they had to be prevented mythical Yellow Emperor and have become the clas-

1.2. History of Chinese Medicine 21
sic scripture of traditional Chinese medicine, that is, oped within. The individual units were linked
the Huang-ti nei-ching (The inner classic of the Yel- through a system of channels, thought to transport
low Emperor). resources from one place to another and join the
An attempt at systematizing the rather heteroge- units to the outside world. The terminology used to
neous contents of the Huang-ti nei-ching, and at describe the structure and workings of the organism
drawing diagnostic and clinical conclusions from an is largely metaphoric and is based on images from
assumed circulation of vapors in the human body, the geographic, economic, and social environment of
resulted in the second major literary work of Chi- the Ch'in and Han dynasties in China.
nese medicine, the Nan-ching, probably of the first The resources or goods to be passed through the
century A.D. This work is also of unknown author- organism were given the name ch'i in the Huang-ti
ship and was subsequently associated with an ear- nei-ching. This term denotes essential vapors
lier (about the sixth century B.C.) semilegendary thought to be the carriers of life. Similar to the devel-
itinerant physician named Pien Ch'io. opment of ancient European concepts of pneuma and
Pharmaceutical knowledge was recorded with as- spiritus, the concept of ch'i may have originated from
tonishing sophistication in a collection of prescrip- observations of such phenomena as suffocation and
tions found among the Ma-wang-tui scripts named "empty vessels" (arteries = aer tereo = "carriers of
Wu-shih-erh ping fang (Prescriptions against 52 ail- air") in a corpse. The Huang-ti nei-ching described a
ments) by modern researchers. At about the time of continuous circulation of these vapors through the
the compilation of the Nan-ching (and coinciding organism, ascribing greater importance to them than
with the appearance of the materia medica of to blood. Illness occurred in an individual organism
Dioscorides in A.D. 65 in the West), Chinese pharma- in the same way that crisis emerged in a complex
ceutical knowledge found its own literary form when state economy. This might be because one or more of
the first Chinese herbal was compiled, which became the functional units failed to fulfill their duties, or
known by the title Shen-nung pen-ts'ao ching (The were inadequately equipped with ch'i, or did not pass
divine husbandman's classic on materia medica). Its ch'i on. Also, the transportation system might be
real author is unknown, and like the other works blocked, thereby preventing the circulation of re-
discussed, this classic was linked to a mythical cul- sources. All of these problems could be caused by the
ture hero, Shen-nung, who is also credited with the person concerned — for example, through an un-
development of agriculture and markets as well as healthy life-style - or by environmental conditions to
with the establishment of drug lore. which the person was unable to adapt.
The purpose of Chinese medicine, like that of all
Basic Perspectives medicine, is to protect individuals from an untimely
The Ma-wang-tui manuscripts, the Huang-ti nei- loss of health, one of their most essential possessions.
ching, the Nan-ching, and the Shen-nung pen-ts'ao According to the Huang-ti nei-ching, a life span of
ching are the main sources for our current under- 100 years should be considered normal, and as the
standing of the early developmental phase of Chi- unknown author concluded, it is only because civi-
nese medicine, even though the last three may have lized people are unable to lead healthy lives that they
undergone considerable revisions in later centuries must resort to medicine for help. The prevention and
and cannot be considered genuine Han dynasty treatment of illness were attempted in Chinese medi-
sources in their entirety. Still, the picture emerging cine through the two basic approaches of localistic-
from studies of these sources so far reveals the forma- ontological and holistic-functional reasoning.
tion of several complex and multifaceted approaches An ontological approach views diseases either as
to health care, all of which were associated with abstract hostile entities themselves or as the result
basic social, economic, and ideological changes pre- of an intrusion of some normally innocuous environ-
ceding and following the unification of the Chinese mental agent into the human organism. One of the
Empire in 221 B.C. Ma-wung-tui texts suggests the existence of a tangi-
Central to Chinese medicine is its perception of ble ontological perspective by relating the notion of
the human organism. Corresponding to the socioeco- small animals (such as worms or insects) entering
nomic structure of the unified empire, the human the body to cause destruction at well-defined loca-
organism was described in Han sources as a system tions. This internal destruction was thought to be-
of individual functional units that stored, distrib- come visible in the failure of bodily functions or in
uted, and processed resources, which were brought the destruction of external parts of the body that
into the organism from the outside or were devel- were associated with the internal functional units

affected first. The history of leprosy in Chinese medi- in the same way that troops move through a country
cine, traceable from Ch'in sources written between from one place to another, the ontological perspec-
252 and 221 B.C., is one example of the persistence tive of Chinese medicine assumed that evil intruders
of such ontological thoughts through two millennia could be transmitted from one location in the body to
of Chinese medical history. It is also a good example another. Transmission was thought to occur in accor-
of the early ontological notions in China that paved dance with clearly defined mutual relationships be-
the way for an understanding and acceptance of tween the various upper and lower, inner and outer
Western bacteriology, morphological pathology, and, regions of the body. An early example of this thought
finally, chemotherapy in the nineteenth and twenti- can be found in the biography of Pien Ch'io compiled
eth centuries. by Ssu-ma Ch'ien in 90 B.C.
In addition to such tangible agents as worms and Closely linked to the ontological perspective of
insects, the ontological perspective views the envi- Chinese medicine is a functional view that is re-
ronment as filled with agents (such as heat, cold, corded in medical literature beginning with Han
humidity, dryness, and wind) that are essential com- dynasty sources. This approach to identifying and
ponents of nature and that may turn into "evils" curing illness is concerned mainly with diagnosing
that harm humans upon entering their bodies either functional disturbances in the human organism,
in undue quantities or at inappropriate times. which is considered to be a complex structure consist-
"Wind" in particular has remained a central etio- ing of various mutually interrelated functional
logic category in Chinese medicine through the ages, units. The functional view focuses on processes and
and it is this very concept of wind that demonstrates on functional relationships among the subsystems
the continuation and transformation of basic de- constituting the organism, and it assumes that the
monological tenets in the history of Chinese medi- same illness may affect several functions at the
cine. Originally conceived of as a spirit entity, the same time.
wind was believed to live in caves and cause harm to For example, a specific functional unit may be
humans when it left its residence. Yet in the Huang- harmed by wind. There result various pathological
ti nei-ching there is a shift to the concept of wind as a conditions, such as aversion to wind or fever, head-
natural phenomenon active as a result of the move- ache, and sweating without external reason. Or the
ment, through heaven, of a superior spirit named "liver" (seen here not as a tangible organ but as a set
T'ai-i. Harm was caused by wind now only if it blew of functions) may be marked by a depletion of ch'i,
from what were considered inappropriate cardinal which is accompanied by the growth of a shade in
directions in the course of the year (as might be one's eyes. Treatment may be directed at the ail-
expected in an agricultural society) or if it met hu- ment in the liver, or it may be focused solely on the
mans with constitutions susceptible to harm. Then, secondary problem in the eyes. Although the first
beginning with the works of Chang Chi in the sec- example reminds one of Western categories such as
ond to third century A.D., the wind came to be seen "disease" and "symptoms," the second demonstrates
solely as an environmental agent, albeit one that that the terms illness, disease, and symptom do not
could strike humanity and cause a host of illnesses. entirely overlap in Chinese and Western medicine
In addition to identifiable environmental influ- and should be used only with great care in a com-
ences that could change from "normal" (cheng) to parative context.
"evil" (hsieh), abstract "evil" or "malicious" (o) en- The perspectives outlined here did not preclude the
tities could enter the organism and cause illness. realization that one individual organism might be
These assaults were thought of not only as invasions affected at one time by two or more mutually indepen-
of the natural environment into the human body, but dent illnesses, each of which had to be named and
also as flare-ups between various functional units treated separately. To make matters more compli-
within the body itself. If, for instance, ch'i normally cated, one identical cause could result in two simulta-
filling the spleen was exhausted beyond some accept- neous, yet separate, illnesses. Conversely, two sepa-
able degree, agents from the liver might turn evil rate causes could bring about one single illness, with
and invade the spleen to take over its territory. The each of these situations requiring, theoretically at
language used to describe these processes, beginning least, different therapeutic treatments.
with Han dynasty sources and throughout the his-
tory of Chinese medicine, reflects the experience of Diagnosis
the long period of "Warring States" that preceded Some of the Ma-wang-tui texts refer to various ves-
the unification of the Chinese Empire. Furthermore, sels thought to pervade the body without intercon-

nection. Specific irregularities in the contents and Greece (possibly stimulated by a common origin, the
movements of each of 11 such vessels revealed spe- location of which is unknown) around the sixth cen-
cific illnesses. The Huang-ti nei-ching, however, de- tury B.C., when it became the theoretical underpin-
scribed 12 vessels, or conduits, which were intercon- ning of the functional approach to an understanding
nected. This text advocated the feeling of pulses at of health and illness.
various locations of the body to examine movement The (most likely older) ontological understanding
in the individual sections of the vessel circuit and to of illness is based on a recognition of struggle, at-
diagnose the condition of the functional units associ- tack, and defense as normal modes of interaction in
ated with these sections. Finally, the Nan-ching pro- nature. Both human behavior and the daily observa-
posed the feeling of the pulses at the wrists only and tion of attack and defense among other animals and
developed complicated methods for extracting de- plants supported this worldview.
tailed information on the origin, present location, In contrast — and this is to be regarded as one of the
and possible future courses of an illness. In addition, outstanding cultural achievements of humankind -
the Huang-ti nei-ching and the Nan-ching provided the ideology of systematic correspondence is based on
ample data on the meaning of changing colors in a the concept of harmony as normal, and of a loss of
person's complexion, of changes in a person's voice or harmony as abnormal, states of existence. Like the
mouth odor, and of changes in longing for a specific ontological notion, the notion of systematic corre-
flavor. Furthermore, the Nan-ching recommended spondence drew on sufficient environmental and so-
investigations of the condition of the skin of the cial evidence to be plausible; it gained legitimacy
lower arms and of abdominal palpitations. from its emphasis on the regularity of countless natu-
These diagnostic methods were described in the ral processes, a regularity that was guaranteed by
literature so that an illness could be discovered and the appropriate behavior and location of each per-
categorized from a theoretical (mainly functional) ceivable phenomenon in a complex network of inter-
point of view. Prescription literature, by contrast, relatedness. It holds that inappropriate behavior
did not depend on theory. Rather, it contained list- jeopardizes this regularity, or harmony, and leads to
ings of very simple and more or less obvious symp- crisis. This crisis may occur in nature, in the affairs
toms, such as headache and diarrhea. These were of state, or in the life of an individual, in the last
paired with drug prescriptions for their cures. case leading to illness. Hence, this ideology is holis-
tic in that it views both the individual physical/
Theoretical Foundations and Treatment mental organism and the sociopolitical organism as
The most impressive mode of treatment recorded in corresponding to identical principles, and "health" is
detail in the Ma-wang-tui scripts is drug therapy. a notion transcending them.
More than 200 active drugs and neutral carrier sub- The ideology of systematic correspondence as-
stances were described, as was a highly developed sumes (as this designation by contemporary schol-
pharmaceutical technology. Other therapies in- ars implies) a relationship of correspondence among
cluded massage, minor surgery, hot baths, sexual virtually all tangible and abstract phenomena in
practices, dietetics, and moxa cauterization, in addi- the universe. Phenomena of identical quality are
tion to various magical interventions. Acupuncture grouped within a category, and two or more catego-
was not yet referred to and appeared first in the ries are linked with one another and interact with
already mentioned biography of the semilegendary one another according to certain natural laws. Vari-
physician Pien Ch'io compiled by Ssu-ma Ch'ien in ous schools emerged within the framework of sys-
90 B.C. Because no earlier documentation of nee- tematic correspondence, advocating the existence of
dling exists in China, the origins of acupuncture, two (yin and yang) orfive(five-phases) categories of
possibly the most recent mode of therapy in the all phenomena.
history of Chinese medicine, remain unknown. The yin-yang school was based on a perception of
For about 1,200 years after the emergence of Chi- the unity of two antagonistic categories of all exis-
nese medicine, until the end of the Song dynasty in tence. Day and night are opposites, and yet they
the thirteenth century, a dichotomy prevailed be- form a unity. The same applies to male and female,
tween two major currents. One was the so-called heaven and earth, summer and winter, above and
medicine of systematic correspondence; the other below, dominating and submitting, and so forth. Be-
was pragmatic drug therapy. ginning in the fourth century B.C., day, male,
The ideology of systematic correspondence ap- heaven, summer, above, and dominating were identi-
peared almost simultaneously in China and ancient fied as qualitatively identical and were categorized

as yang, their opposites as yin. The Huang-ti nei- rescue the fatally ill, but were seen as stimuli to
ching contains more sophisticated groupings into correct aberrations from a proper path.
four and six yin-yang subcategorizations, which By contrast, drug lore promised to rescue individu-
may have developed in the meantime. als from illness regardless of whether they adhered to
The second school, the five-phases school, recog- morality and human rites. From the Han through the
nized five categories of qualitatively identical phe- T'ang dynasty, the development of pharmaceutics
nomena, symbolized by five essential environmental was closely tied to persons affiliated with Taoism.
elements: metal, wood, water, fire, and soil. These This phenomenon was obviously related not only to
five categories represented phases in the succession, the Taoist quest for elixirs and drugs of immortality,
and hierarchical stages in the interaction, of certain but also to the value of drug lore for contradicting the
phenomena. For example, the liver was associated Confucian-Legalist linking of social and individual
with the phase of wood, and the spleen was associ- well-being with an adherence to a morally legiti-
ated with the phase of soil. Wood - for instance, as a mated life-style and to government-proclaimed laws.
wood spade — could move soil; hence, a specific rela- Taoists claimed such rites and laws to be the origins
tionship between liver and spleen could be explained of social and individual crisis. Thus, it was only be-
as resulting from a potential of the liver to subdue tween the thirteenth and fifteenth centuries, in the
the functions of the spleen. aftermath of Song Neo-Confucianism, that certain
The Huang-ti nei-ching and the Nan-ching linked Confucian-Legalist and Taoist tenets were united for
these notions of systematic correspondence with a few centuries and that attempts were made to con-
physiology, etiology, and therapy. As a result, the struct a pharmacology of systematic correspondence.
human organism was described as a microcosm of
interrelated functional units associated with the Literature and Specialties
more encompassing categories of all being, and Before the decline of the last of the imperial dynasties
hence with the social and physical environment. Not at the end of the nineteenth century, Chinese medi-
surprisingly, the reasons for maintaining individual cine developed on many levels and in many direc-
health, or for the emergence of illness, closely paral- tions. Even though new insights and data were being
leled the reasons for social and environmental har- accumulated virtually all the time, it maintained its
mony and crisis. The only therapeutic mode within original theoretical foundations; perhaps a peculiar-
this system of ideas was acupuncture (and to a cer- ity of Chinese medical history is that the concept of
tain degree dietary means and moxa cauterization). obsolescence remained almost entirely alien to it.
The Shen-nung pen-ts'ao ching contained virtu- Indeed, before modern Western thought made an im-
ally no references to the concepts of systematic corre- pact, no theory or practice was ever relegated to obliv-
spondence. Pharmaceutics developed along its own ion as outdated (only in pharmaceutics do some
lines from a description of 365 substances in Shen- herbals list "drugs no longer in use"). The notion of a
nung's herbal of the first century, to 850 substances dialectic advancement of knowledge or of "scientific
in the first government-sponsored materia medica in revolutions" does not apply to Chinese medicine. In
659, to more than 1,700 drug descriptions in the fact, one should speak of an expansion rather than of
great herbals of the northern Song published from a progression of knowledge, because the etymology of
960 to 1126. progress implies that something is left behind.
One reason for this dichotomy may be seen in a More than 12,000 titles of premodern Chinese
basic antagonism between Confucian-Legalist think- medical literature from a period of about 2,000 years
ing and the Taoist worldview. Confucian-Legalist are available in libraries in China and other coun-
social ideology has dominated Chinese society- tries today, but not even a handful of these texts
with varying intensity - since the early Han dy- have been translated into modern languages in a
nasty. One of its conceptual foundations is the belief philologically serious way. Hence, only some very
in social order, a social order maintained by the basic historical tenets of traditional Chinese medi-
government through law enforcement and educa- cine are known in the West, and it is imperative that
tion, both of which encourage appropriate legal and access to many sources be provided so that compari-
moral behavior. The medicine of systematic corre- sons can be made with the history of medicine in
spondence was built on identical tenets; health was other cultures. In this connection, it is important to
promised to individuals if they followed a specific note that Chinese medicine developed the same spe-
life-style congruent with Confucian-Legalist ethics. cialties as did traditional European medicine. Sepa-
Needling, moxa, and dietetics were not meant to rate sections in the often very voluminous prescrip-

tion works and individual monographs were devoted tempts by K'ou Tsung-shih, who wrote about the
to such problems as children's diseases, the diseases middle of the thirteenth century, by Chang Yiian-su
of women, skin problems, eye complaints, and throat of the twelfth century, and most important by Wang
ailments. The following provide a few examples: The Haogu to create a pharmacology of systematic corre-
earliest extant title concerned with the diseases of spondence signaled a closing of the most decisive rift
children is the Lu-hsin ching (Classic of the Fon- that had separated the two major traditions of Chi-
tanel), of unknown authorship and compiled around nese medicine for the preceding one and a half mil-
A.D. 907, which was presumably based on sources of lennia. At the same time, however, individual
the fourth century or even earlier. The oldest avail- schools began to appear, and these initiated an in-
able text today on women's diseases and obstetrics is creasing specialization and fragmentation within
the Fu-jen liang fang (Good prescriptions for fe- this unified system - a process that came to an end
males) of 1237 by Ch'en Tzu-ming. A text, lost now, only in the twentieth century.
possibly dating back to T'ang times and indicating The second millennium of Chinese medical his-
the Indian origins of Chinese ophthalmology, is the tory was characterized by the attempts of individ-
Lung-shu p'u-sa yen lun (Bodhisattva Nagarjuna's ual authors to reconcile their own observations and
discourse on the eyes), and a first monograph on experiences with the ancient theoretical guidelines.
leprosy was published by Hsiieh Chi in 1529 under One of the first to suggest a reductionist etiology
the title Li-yang chi-yao (Essentials of the li- was Liu Wan-su, a twelfth-century physician who
lesions). On ailments affecting the throat, the oldest proposed that most illnesses were caused by too
text extant is the Yen-hou mai cheng t'ung lun (Com- much heat and who advocated cooling therapies.
prehensive discourse on vessel [movements] indicat- Chang Ts'ung-cheng, a few decades later, saw the
ing [the condition of] the throat), of unknown author- main course of human illnesses as an intrusion of
ship and dating from approximately 1278. "evil influences," and he founded a school emphasiz-
Although, as has been stressed, Chinese medicine ing "attack and purging" in therapy. His near con-
emphasized an ontological perspective and was quite temporary, Li Kao, in contrast, thought that most
familiar with localistic notions of illness, only a few illnesses were a result of a failure of spleen and
dissections were recorded during the imperial age, stomach to perform their presumed digestive func-
and surgery was never developed much beyond the tions, and he advocated supplementation of these
knowledge needed for performing castrations. Cata- two units as a basic therapy. None of these schools,
ract surgery was introduced from India as early as or any other of the many opinions published in
the T'ang dynasty, but was never really integrated subsequent centuries, achieved even temporary
into Chinese medicine or further developed, despite dominance. Hence, a proliferation of individual per-
the great number of patients who could have bene- spectives characterized the history of Chinese medi-
fited from such operations. cine during these final centuries rather than a suc-
The reasons for such reluctance to explore human cession of generally acknowledged paradigms.
anatomy and develop surgery are unclear; also un- This does not mean, however, that this period
clear is the reason for the failure to expand certain lacked brilliance; several authors made contribu-
knowledge that reached an impressive stage at some tions to their respective fields that were never sur-
early time but went no further. An example is the passed. The Pen-ts'ao kang mu (Materia medica ar-
world's first treatise on forensic medicine, the Hsi ranged according to drug descriptions and technical
yuan lu (The washing away of wrongs) of 1247 by aspects) of 1596 by Li Shih-chen is a most impressive
Sung Tz'u. Although it preceded comparable West- encyclopedia of pharmaceutics touching on many
ern knowledge by several centuries, it remained a realms of natural science. It contains more than
solitary achievement, for no author is known to have 1,800 drug monographs and more than 11,000 pre-
built upon and improved this work. In contrast, phar- scriptions in 52 volumes. In 1601 Yang Chi-chou
maceutical literature was continuously expanded published his Chen-chiu ta-ch'eng (Complete presen-
and amended throughout Chinese history. tation of needling and cauterization) in 10 volumes,
offering a valuable survey of the literature and vari-
The Final Centuries of the Imperial Age ous schools of acupuncture and moxibustion, which
If the Han dynasty was marked by the initial devel- is cauterization by the burning of a tuft of a combus-
opment of Chinese medicine, the Song-Chin-Yuan tible substance (moxa) on the skin (including a chap-
period was the second most dynamic formative peter on pediatric massage), of the preceding one and a
riod in the history of Chinese medicine. The at- half millennia.

Yet despite such monumental works, the dynam- Similarly, acupuncture anesthesia resisted modern
ics of Chinese medical history appear to have slowed scientific explanation, but could be understood on
down subsequently. When in 1757 one of the most the basis of the dialectics of internal contradiction.
brilliant physician-intellectuals of the second millen- Since the demise of the Cultural Revolution, such
nium, Hsu Ta-ch'un, wrote his I-hsueh yuan liu lun theoretical reinterpretations of traditional Chinese
(On the origins and history of medicine), he recorded medicine have coexisted in China with Western
a deplorable "loss of tradition" in virtually every medicine, with the latter dominant on virtually all
respect of theoretical and clinical health care. levels of health care.
The work of Hsu Ta-ch'un, who died in the same Efforts to preserve Chinese medicine include at-
year, 1771, as Giovanni Battista Morgagni, the au- tempts to select those facets of that heterogeneous
thor of De Sedibus et Causis Morborum (On the seats tradition that appear to form a coherent system, that
and causes of diseases), illustrates the fact that tradi- are thought to supplement Western medicine, and
tional Chinese medicine, traditional European medi- that are not considered superstitious. Research on
cine, and even modern Western medicine have more the scientific basis of traditional Chinese medicine is
basic theoretical foundations in common than is usu- being pursued on many levels. Veteran doctors, how-
ally believed. Hsu Ta-ch'un, a conservative who was ever, prefer a continuation of traditional Chinese
not influenced by Western thought and was a sharp medicine in its own right. Although the dialogue
critic of the influences of Song—Chin-Yuan thought between Western medicine and Chinese medicine
on medicine, nonetheless wrote treatises on "intra- goes on, not without tension, the Chinese population
abdominal ulcers" and, following a long tradition of turns to both, selecting whatever it considers best
military metaphors, compared the use of drugs to for a specific problem.
the use of soldiers. One may assume that he would Paul U. Unschuld
have had few difficulties in communicating with
his contemporary Morgagni or in understanding
Western medicine as it later developed. Bibliography
Anon. 1986. "Nan-ching": The classic of difficult issues,
Given the internal fragmentation of traditional trans. P. U. Unschuld. Berkeley and Los Angeles.
Chinese medicine and the fact that it contained Croizier, Ralph C. 1986. Traditional medicine in modern
many of the theoretical foundations of modern Euro- China. Cambridge, Mass.
pean and U.S. medicine, it should be no surprise that Epler, D. C , Jr. 1980. Bloodletting in early Chinese medi-
the latter was quickly accepted in China early in the cine and its relation to the origin of acupuncture.
twentieth century, a process stimulated by a feeling Bulletin of the History of Medicine 54: 337-67.
shared by many Chinese that a decent existence 1988. The concept of disease in an ancient Chinese medi-
could be achieved only by employing Western sci- cal text, the Discourse on Cold-Damage Disorders
ence and technology. Only during the past four de- (Shang-han Lun). Journal of the History of Medicine
and Allied Sciences 43: 8-35.
cades has there been a reassessment of the value of
Harper, Donald. 1982. The Wu-shih Erh Ping Fang: Trans-
traditional medicine in China.
lation and prolegomena. Ph.D. thesis, University of
For decades, traditional Chinese medicine was California, Berkeley.
held in contempt by virtually all prominent Chinese Hillier, S., and T. Jewell. 1983. Health care and traditional
Marxist thinkers. In the 1950s and 1960s, however, medicine in China, 1800-1982. London.
it became apparent that Western medicine, with its Huard, Pierre, and Ming Wong. 1959. La midecine
emphasis on expertise and its many tenets that con- chinoise au cours des siicles. Paris.
tradicted those of dialectical materialism, could not Hymes, R. P. 1987. Doctors in Sung and Yuan. Chinese
be fully integrated into a socialist society, and Chi- Science 8: 9-76.
nese medicine was suddenly perceived to be a politi- Lu, Gwei-djen, and Joseph Needham. 1980. Celestial
cal tool. Chinese Marxist dogmatists began to point lancets: A history and rationale of acupuncture.
out the antagonism between Western medicine, so- Cambridge.
called bourgeois metaphysics, and individualism, on Needham, Joseph, et al. 1970. Clerks and craftsmen in
one side, and dialectical materialism and traditional China and the West. Cambridge.
Spence, Jonathan. 1974. Aspects of the Western medical
Chinese medicine, on the other. Whereas the com-
experience in China, 1850-1910. In Medicine and soci-
plex formulas of traditional Chinese pharmaceutics ety in China, ed. J. Z. Bowers and E. F. Purcell, 40-54.
could not be explained by modern pharmacology, the New York.
second law of dialectics as formulated by Friedrich Sun Simiao. 1985. "Shanghan lun": Traiti des [coups du
Engels offered a satisfactory theoretical foundation. froid], trans, into French by C. Despeux. Paris.

1.3. Islamic and Indian Medicine 27
1987. Prescriptions d'acuponcture volant mille onces of the seventh century A.D., the major centers of
d'or, trans, into French by C. Despeux. Paris. Greek medical learning in the eastern Mediterra-
Sung Tz'u. 1981. The washing away of wrongs, trans. B. E. nean were nourishing.
McKnight. Ann Arbor, Mich. Because of theological constraints, Greek Ortho-
Unschuld, Paul U. 1978. Approaches to ancient Chinese dox scholars were more interested in the Greek sci-
medicine. Dordrecht.
ences, which included medicine and philosophy, than
1979. Medical ethics in Imperial China. Berkeley and
in literature, historiography, and other humanistic
Los Angeles.
1983. Die Bedeutung der Ma-wang-tui Funde fur die
subjects. The Muslim conquerors recognized the ex-
chinesische Medizin- und Pharmaziegeschichte. In cellence of Greek learning, and the Umayyid and
Perspektiven der Pharmaziegeschichte, ed. P. J. Dilg et Abbasid caliphs subsequently sponsored the transla-
al., 389-416. Graz. tion of a large portion of the available scholarly
1985. Medicine in China: A history of ideas. Berkeley works into Syriac and Arabic (Ullmann 1978).
and Los Angeles. The Hellenic culture had in large part been devel-
1986. Medicine in China: A history of pharmaceutics. oped in the Near East and was an integral part of the
Berkeley and Los Angeles. Near Eastern culture inherited by the Muslims. The
1989. Forgotten traditions of ancient Chinese medicine: belief that the Greek sciences were transported from
Translation and annotated edition of the "I-hseh yuan the Occident to the Orient, where they were pre-
liu lun" by Hsu Ta-ch'un of 1757. Brookline, Mass.
served in Arabic translation until their eventual
Van Straten, N. H. 1983. Concepts of health, disease and
vitality in traditional Chinese society: A psychological
repatriation by the Occident, is mistaken. The infu-
interpretation. Wiesbaden. sion of Greek scholarship transformed the Arabic
Wong K. Chimin and Wu Lien-Teh. 1936. History of Chi- language and Islamic culture and must be viewed as
nese medicine: Being a chronicle of medical happen- a major historical process in which Islamic civiliza-
ings in China from ancient times to the present period. tion energetically built on the existing Near and
Shanghai (reprint 1973, New York). Middle Eastern cultures.
The major period of translation spanned the years
from the ninth to the eleventh century and was a
complex process that drew on several routes of cul-
tural transmission. Even before the Muslim con-
quest, numerous Greek texts had been translated
1.3 into Syriac, and many of these as well as a few
Islamic and Indian Medicine original medical works written in Syriac were in
turn translated to Arabic. The transmission of
Greek scholarship into Arabic, which became the
Islamic and Indian medicine originated in distinct learned language, accelerated during the Abbasid
cultural traditions but have been in close contact for era when, beginning toward the end of the eighth
many centuries. The terms Islamic and Indian as century, Harun al-Rashid and his successors spon-
they refer to medicine do not describe static, ideal- sored centers of translation and learning in Bagh-
ized, or monolithic systems that can be categorized dad. Almost all of Galen's lengthy medical texts
by referring to the medical texts of a distant golden were translated by the end of the ninth century, and
age. Medical practices in Islamic and Indian cul- Greek knowledge had also reached the Islamic world
tures were, as elsewhere, eclectic and pluralistic, through Persian sources. The Achaemenid rulers of
evolving in response to complex influences that var- western Iran, who valued Greek knowledge, had
ied according to time and place. This essay briefly founded in the third century A.D. a center of learn-
traces the origins and the major components of the ing at Jundishapur where Greek scholars, captured
two traditions and compares and contrasts their in- in war, could work. In the fifth and sixth centuries
stitutional responses to the challenges of modern A.D., Nestorian Christian scholars, persecuted in
times. Greek Orthodox Byzantium, found refuge in Jundi-
Islamic medicine is based largely on the Greek shapur, then under Sasanid rule. The Sasanid rulers
medical knowledge of later antiquity and is more sponsored numerous translations of Greek medical
properly called Greco-Islamic or Galenic-Islamic texts into Pahlevi. In the ninth century many of
medicine, reflecting the influence of Galen, whose these Pahlevi texts were in turn translated into Ara-
works dominated medical learning in the eastern bic. Finally, the major Indian medical works were
Hellenic world. At the time of the Muslim conquests translated into Arabic or Persian and were accessi-

ble to Islamic physicians from a relatively early date cepts drawn from Greco-Islamic medicine. It was, in
(Ullmann 1978). other words, an effort to incorporate Greek medical
In answer to the often asked question regarding the knowledge into an acceptable Islamic framework.
originality of Islamic medicine, Manfred Ullmann, a The authors of prophetic medicine were generally
specialist in Islamic medicine, has suggested that the not practicing physicians but ulama (specialists of
question is inapplicable because it is inherently Islamic theological and legal sciences), who worked
anachronistic. The physicians (hakims) of the Islamic out "religiously correct" compendia of medical lore.
Middle Ages, he observes, were not interested in dis- In recent years, many prophetic medical works have
covering new knowledge, but rather in developing been printed and can be purchased in bookstores
and commenting on the natural truths learned from throughout the Islamic world.
the ancients (Ullmann 1978). This view, however, Sufis, or mystics, believed that illness should be
may overstate the case, for within the framework treated through prayer or other religious obser-
inherited from the Hellenic sciences, the Islamic vances and not by medical means at all. In addition,
scholars made numerous discoveries. For example, many people believed in astrological influences on
Alhazen (Ibn al-Haytham), a mathematician who disease causation. Astrological medicine was widely
worked in Cairo, used inductive, experimental, and practiced, and most astrological manuals had sec-
mathematical methods inherited largely from Ptole- tions giving medical advice (Savage-Smith 1988).
maic science to discount Greek and Islamic theories The obvious contradiction between natural causa-
of light and vision and to produce a new, more accu- tion, divine causation, and planetary control of
rate and intellectually sophisticated theory (Sabra events was never entirely resolved. The late Fazlur
1972; Omar 1977). Rahman, the noted Muslim philosopher and scholar,
A. I. Sabra (1987) has suggested that scholars while dismissing astrology, confronted the dilemma
study the Islamic sciences as part of Islamic civiliza- of the orthodox theological insistence on total reli-
tion. The question then becomes not whether the ance on God's will and the necessity of seeking secu-
Islamic scholars made original discoveries or how lar medical intervention. He concluded that "the
the Greek sciences were translated into Arabic and Qur'an's position appears to be that God acts through
then into Latin, but rather by what process Islamic natural causation and human volition to further His
civilization appropriated, assimilated, and "natural- purposes" and that whereas many theologians and
ized" the Greek sciences. Sufi leaders clearly advocated resignation to the will
of God at all times, most, when sick, sought medical
According to the Greco-Islamic medical theories, dis- treatment (Kahman 1987). The average person pre-
eases were caused by imbalances of the four humors sumably subscribed to a variety of medical beliefs
of the body: hot, cold, moist, and dry. The matters of without great concern for the obvious contradictions.
the four humors, blood, phlegm, and yellow and In short, in emergencies, all possibilities were to be
black bile, influenced the temperament of individu- tried.
als. When the balance was upset, the body would It might be said that over time the difference
become ill. Thus, an excess of blood would produce a between Greco-Islamic medicine and daily medical
sanguine condition, whereas an excess of phlegm practices resembled the difference between the classi-
would produce a phlegmatic condition, and so forth. cal Arabic and the spoken language. One was formal
The physician's role was to correct the imbalance, and was carefully studied and developed by savants
perhaps by prescribing foods or medicines with "hot" for scholarly discourse. The other was informal, eclec-
or "cold" properties or by removing excess blood. tic, and used for everyday needs.
This system was essentially secular because it did
not ascribe disease causation to supernatural influ- Only a few of the major Greco-Islamic physicians will
ences. When Greek medical works referred to the be mentioned here, in chronological order, to suggest
Greek gods, Muslim translators simply inserted Al- their varied origins and interests. Mesue (Yuhanna
lah when appropriate or made the gods historical ibn-Masawayh), court physician to four Abbasid ca-
figures. liphs during the late eighth and first half of the ninth
Prophetic medicine can be viewed as a "science" centuries, was a renowned clinician and teacher who
that integrated medical knowledge derived from the wrote influential texts on nosology and therapeutics.
hadiths, or sayings and traditions of Mohammed and Joannitius (Hunayn ibn-Ishaq al-Ibadi) was a ninth-
his companions, and local medical customs, magical century physician who studied in Jundishapur,
beliefs, incantations, charms with ideas and con- Basra, and Baghdad. He was proficient in Greek,

Syriac, and Arabic, and was renowned for his excel- is the famous Kitab al-Fusul, which was derived
lent translations of Greek medical texts, which se- largely from Galen.
cured his place in the history of medicine and of Abd al-Latif al-Baghdadi, who died in 1232, was a
Islamic civilization. He also wrote monographs on scientist who demonstrated that simple observation
ophthalmology and other subjects. His contemporary, of human anatomy revealed substantial errors in
Ali ibn Sahl Rabban al-Tabari, who worked for most Galen's anatomic descriptions. Also prominent in
of his life in Rayy, wrote a compendium of medicine the thirteenth century was Ibn Nafis, who studied
based on the works of Hippocrates, Galen, Aristotle, medicine in Damascus and became director of the
Dioscorides, and other authors, mostly from Syriac Mansuri Hospital in Cairo. He wrote al-Mujiz, a
translations. Qusta ibn-Luqa al-Balabakki, who died widely used commentary on Avicenna's Qanun. In it
in 912, practiced in Baghdad and, toward the end of he stated his famous theory of the pulmonary, or
his life, in Armenia. He wrote on the relationship lesser, circulation of the blood, later proved correct.
between mind and body, in addition to other medical, Finally, Ibn Abi Usaybia should be mentioned. An
philosophical, and mathematical treatises. His fa- oculist at the Nuri Hospital in Damascus, he later
mous contemporary, Rhazes (Abu Bakr Muhammad worked at the Mansuri Hospital with Ibn Nafis. He
ibn Zakariya al-RazI), was born in Rayy and prac- compiled Uyun al-Anba ft Tabaqat al-Atibba, a biog-
ticed medicine in Baghdad and at various locations in raphy of more than 400 physicians of Greco-Islamic
Iran. He was a noted philosopher and alchemist who medicine. It remains a major source on the history of
compiled the famous medical texts entitled Kitab al- Islamic medicine (Ibn Abi Usaybia 1882—4; Brockel-
Mansuri and Kitab al-Hawi. He is best known for his mann 1937-49; Ullmann 1978).
exceptionally precise (but not original) descriptions These Greco-Islamic medical scholars were a di-
of diseases such as smallpox and measles. Haly Abbas verse group, among whom were Muslims, Chris-
(Ali ibn al-Abbas al-Majusi), who died in 994, was a tians, Jews, and Zoroastrians. Persian Muslims
physician at the Buwayhid court. He wrote the fa- probably outnumbered those of other origins. Al-
mous Kitab al-Malaki, one of the most concise and though nearly all wrote their major works in Arabic,
well-organized expositions of Greco-Islamic medi- many also wrote in Syriac or Persian, as well as in
cine. At about the same time, Albucasis practiced in Hebrew (written in either Hebraic or Arabic letters)
Cordoba and wrote an encyclopedic study that con- or, later, in Turkish. Regardless of ethnic or cultural
tained an influential section on surgery based on origin, all shared and contributed to the Islamic cul-
Greek sources and his ownfindings.Avicenna (Abu- tural tradition. Most, though by no means all, prac-
Ali al-Husayn ibn-Sina) was a polymath who during ticed medicine at some time in their careers. A few
his checkered career practiced medicine at various lo- were ulama, or lay persons with a special interest in
cations in Iran. Early in the eleventh century he com- medicine. Women are conspicuously absent from the
piled the famous Qanun, afive-volumestudy dealing biobibliographies but are known to have acquired
with physiology, nosology, etiology, symptomatology medical expertise and to have practiced medicine in
and therapy, simple remedies, pathology, and the medieval times (Issa 1928; Goitein 1967).
preparation of compound remedies. This work is a
compilation of medical knowledge of the era that was Medical education was far less structured than in
enormously influential in the Islamic world and in modern times. Medical students studied the medical
the West in Latin translation. He also wrote a book texts independently or sometimes in mosques and
refuting astrology, a "science" held in ill-repute by madrasas (schools) along with the other sciences.
most of the prominent physicians of the era. Averroes Often an aspiring physician studied with one or
(Ibn Rushd) was twelfth-century Aristotelian phi- more masters and acquired practical experience
losopher and government official in Cordoba and through an apprenticeship. There was no formal cer-
Marrakesh who wrote a major medical work divided tification system or formal curriculum. Proof of medi-
into seven parts dealing with anatomy, dietetics, pa- cal expertise depended on the recommendation of a
thology, nourishment, materia medica, hygiene, and physician's teachers, demonstrated familiarity with
therapeutics. His pupil, Maimonides (Ibn Maymun), the medical texts, as well as a reputation established
was, like Ibn Rushd, born in Cordoba. But he left through practical experience. Only much later did a
Spain following Almohad persecution and sought ref- system of certification come into existence, in which
uge in Cairo, where he became court physician and a head doctor (bash hakim), appointed by the ruler,
the official representative of Egypt's large and flour- would issue an ijaza (permission or license) to a
ishing Jewish community. Among his medical works prospective physician testifying to his competence.

Most of the physicians discussed earlier limited the medical theories. Ibn Sallum translated several trea-
realm of their activities to the large cities, usually at tises in Paracelsian medicine from Latin to Arabic,
court or in the homes of the wealthy. Several were modifying them slightly for use in Islamic regions.
directors of major hospitals in Baghdad, Damascus, He is credited with being the first Muslim physician
Cairo, and elsewhere. to subscribe to the new European science and was
Hospitals in Islamic regions were usually funded not himself trained in Greco-Islamic medicine
by waqfs (religious endowments for charitable pur- (Savage-Smith 1987). In the eighteenth and nine-
poses). The concept of waqf funding of hospices for teenth centuries, Muslim physicians from North Af-
the sick, which may have been adapted from Byzan- rica to Iran occasionally used European source mate-
tine custom, remained standard practice in Islamic rials to discuss the etiology and treatment of new
regions until the expansion of the modern nation- diseases such as syphilis and cholera. Muslim schol-
state. For example, in 1662, in Tunis, the ruler ars did not, however, understand or adopt the new
Hamuda al-Muradi established a waqf funded by experimental methods that underlay the Scientific
revenues from designated hotels, shops, public ov- Revolution.
ens, kilns, water pipes, mills, and baths and from the The transmission of European medical knowledge
rent on houses. The funds were for a doctor, nurses, was accelerated in the early nineteenth century
servants, and food for the staff and patients. In addi- when Muhammad Ali, the modernizing ruler of
tion, the funds were to maintain the building itself, Egypt, recruited Antoine Clot-Barthelemy to orga-
which contained 24 rooms and was intended for the nize his medical services. Clot founded a medical
sick and wounded of the army and navy and the poor school in Cairo where European medicine alone was
who had no family to care for them. The charter of taught. European physicians were subsequently
this waqf specifically stated that there was to be no called to Istanbul, Tunis, Tehran, and other Muslim
distinction among Arabs, Turks, or foreigners. In captials to organize modern medical schools and
Tunis and elsewhere, those who could, however, pre- health services. By the early twentieth century, Is-
ferred to seek medical care at home from relatives lamic medicine, which bore little resemblance to
and local practitioners (Gallagher 1983). medical practices of the medieval era, was held in
In the sixteenth and seventeenth centuries when official disrepute and the Greco-Islamic theories
Muslim rulers became aware of the military and themselves had been overturned by the experimen-
commercial expansion of the European powers, they tal methods and systematic observations of modern
did not hesitate to recruit European physicians to Western medicine.
their courts. Although European physicians of the
era could treat most diseases no better than their The term Indian medicine usually refers to Hindu or
Muslim counterparts, Muslim rulers, extrapolating Ayurvedic medicine. It is a medical tradition distinct
from European advances in other fields of science from either Greek or Islamic medicine. Ayurvedic
and technology, suspected that the Europeans could scholars trace its roots to verses from the ancient
(Gallagher 1983). The European physicians had an Vedic hymns, which contain medical doctrines,
advantage because, although they still relied on the mostly of a magicoreligious character, and date from
medical texts of Avicenna, Averroes, and Rhazes, as early as the second millennium B.C. The medical
they were more systematically educated than their doctrines based on treatment with extracts of plants
Muslim counterparts. Often both Muslim and Euro- (vegetable decoctions, oils, and ghees, usually pre-
pean physicians were retained at Muslim courts and pared at home) featured in classic Ayurvedic medi-
were consulted according to the dictates of the ruler. cine are, however, not found in the Vedic hymns.
European physicians at Muslim courts also some- Perhaps they derived from the herbal medicines of
times served as intermediaries, interpreters, and dip- Buddhist monks. The term Ayurveda may have
lomatic representatives. They were generally well served to legitimize the medical system by associat-
compensated and held in high esteem. ing it with the Vedic religious tradition. The term
A few prominent Muslim physicians also sought Veda refers to an abstract idea of knowledge that is
the new European medical knowledge. In the seven- found in all branches of Hindu learning. Ayur means
teenth century, Ibn Sallum, an important physician prolonging or preserving life or the science of longev-
at the Ottoman court, relied on the works of the ity. Ayurveda is, in fact, a code of life. It deals with
sixteenth- and seventeenth-century Paracelsian rebirth, renunciation, salvation, soul, the purpose of
scholars, whose theories of chemistry (later proved life, the maintenance of mental health, and of course
wrong) had emphatically rejected the ancient Greek the prevention and treatment of diseases.

The most important Ayurvedic medical texts are and other impure substances (Basham 1976). Most
the samhitas (the four canonical texts of the Hindu people, however, had no access to the formal or
scriptures) of the mythical savants Caraka and learned Ayurvedic medical tradition and relied on
Susruta. Both are compilations of medical traditions home remedies and consultation with local medical
and exist only in incomplete or copied form. healers. With few exceptions, only the rulers, mili-
Caraka's work was apparently compiled in about the tary leaders, and male members of elite castes had
first century A.D. and that of Susruta in the fourth access to Ayurvedic medicine.
or sixth century. Caraka described more than 200
diseases and 150 pathological conditions. He also Yunani (Ionian or Greek) medicine should also be
mentioned older magical ideas along with the ra- considered a part of the Indian medical tradition.
tional humoral approach based on drug therapy and Yunani medicine was probably introduced into India
diet. Susruta included a long chapter on surgery, with the Turco-Afghan conquests of the thirteenth
which was apparently widely practiced in antiquity century and the expansion of Persian culture in the
but was nearly unknown in later years. fifteenth century. Lahore, Agra, Delhi, and Lucknow
The ideas of Ayurveda have permeated Hindu cul- became renowned centers of Islamic learning where
tural ways of dealing with life and death and sick- the classic medical texts were copied, studied, and
ness and health. Whereas Greek medicine has four reformulated, usually in Arabic. From the thirteenth
humors, Ayurvedic medicine has three humors, or century, Indian physicians attempted to synthesize
dosas, wind, bile, and phlegm, which govern health Islamic and Ayurvedic medicine and there was much
and regulate bodily functions. These are the three borrowing between the two systems (Leslie 1976).
microcosms of the three divine universal forces, Ayurvedic physicians learned to classify and inter-
wind, sun, and moon. Illness results from an imbal- pret diseases in Yunani terms. They began to diag-
ance of the three dosas. Although an essentially nose disease by feeling the pulse of the patient, a
rational understanding of disease and treatment un- practice developed in Yunani but not in Ayurvedic
derlies Ayurvedic medical doctrine, Brahmin myths, medicine. They used mercury, which Muslim physi-
gods, and demons are sometimes cited in the classic cians had borrowed from Europe, and opium and prac-
texts to explain the origins of diseases and the char- ticed alchemy, a science not found in Ayurvedic texts.
acter of medicine. Epidemic diseases, for example, They studied the case histories found in Yunani but
might be caused by drought, excessive rainfall, ca- not in Ayurvedic texts. In turn, the Yunani physi-
lamities sent by the gods in punishment for sins, cians (hakims) borrowed extensively from the
poisonous miasmas, or the influence of planets. The Ayurvedic pharmacopeia and adopted many Ayur-
body is considered to be a manifestation of divine vedic ideas concerning dietary principles. Both sys-
energy and substance, and is a microcosm of the tems were widely used in India's Muslim and Hindu
universe. Whereas Islamic medicine acknowledged communities, and Muslim physicians are known to
its Greek and Indian origins, Ayurvedic medicine have practiced Ayurvedic medicine and Hindu physi-
emerged from the Hindu religious and cultural tradi- cians to have practiced Yunani medicine.
tion (Zimmer 1948; Jolly 1951; Basham 1976; Zyzk Ayurvedic medicine reached its highest point of de-
1985). velopment from the first to the sixth century A.D.,
Medical knowledge was generally transmitted considerably earlier than Islamic medicine, which
from a master practitioner to his pupil. Often, medi- reached its highest point from the ninth to the thir-
cal knowledge was handed down from father to son teenth century. Both traditions lent themselves to so-
for many generations. Medical students also studied phisticated reasoning, earnest speculation, and schol-
at medical establishments attached to large temples arly curiosity, but also to involuted argumentation,
or in schools and universities. In the ideal, abstract distinctions, and increasingly obscurantist
Ayurvedic physicians (vaidyas or vaids) were to be generalizations. In Indian as in Islamic medicine,
Brahmin and thoroughly learned in the Sanskrit there was no systematic experimental research. In
texts. In practice, they were usually from the top the sixteenth and seventeenth centuries, Ayurvedic
three castes (varna), Brahmin, Kshatriya, and and Yunani physicians were even less exposed than
Vaisya, but were sometimes considered to have com- were their counterparts in the Middle East and North
promised their status by the nature of their profes- Africa to the new ideas of the Scientific Revolution.
sion. Brahmins, for example, would often not accept
food from a vaidya because he had entered the homes The British conquest of India, begun in the mid-
of persons of lower caste and had touched excrement eighteenth century, did not immediately disrupt

long-standing medical traditions. In 1822 the Brit- Well before independence in 1947, more than 60
ish colonial authorities established the School of Na- Ayurvedic and Yunani colleges existed throughout
tive Doctors at Calcutta, where students could study India and there were official Boards of Indian Medi-
both Ayurvedic and Western medicine. The British cine in Bombay, Madras, and elsewhere. After inde-
authorities also sponsored courses for the training of pendence, Ayurvedic and Yunani physicians ex-
hakims and recruited them for medical relief proj- pected to win equal status with physicians trained in
ects. Within little more than a decade, however, the the Western medical schools, but despite strikes and
British government had decided that higher educa- other organized protests they did not do so. In 1956
tion in India would follow a Western model and the the government established the Central Institute of
schools and courses in indigenous medicine were Research in Indigenous Systems of Medicine and the
abandoned. In 1841 a British medical surgeon in the Post Graduate Training Centre for Ayurveda in
Bengal medical service found that only four or five Gujarat State and similar institutions elsewhere.
Ayurvedic medical practitioners could read the San- Although the number of Ayurvedic and Yunani col-
skrit texts (Leslie 1976; Metcalf 1985). leges and dispensaries has multiplied since indepen-
Even after the British suspended patronage of in- dence, government funding has been minimal. Many
digenous medical systems, a few princes continued of the colleges teach anatomy, nosology, and other
to sponsor Ayurvedic and Yunani colleges. In 1889 Western medical subjects in addition to the basic
the family of Hakim Ajmal Khan, the famous Mus- courses in Ayurvedic and Yunani medicine, but the
lim reformer and physician, established a Yunani result is popularly regarded as inadequate training
school in Ballimaran and later a pharmacy that pro- in any medical system. Ayurvedic and Yunani practi-
vided Yunani and Ayurvedic medicines. In 1906 tioners, for example, often prescribe antibiotics and
Ajmal Khan established the Tibb (medical) Confer- give injections, but without the understanding of the
ence. Its purpose was to reform and develop Yunani physician educated in Western medicine. According
medicine and to work with Ayurvedic physicians for to Paul Brass, a political scientist specializing in
their shared interests. In 1907 Ayurvedic practitio- modern India, the students in the indigenous medi-
ners established the All-India Ayurvedic Congress, cal schools are popularly perceived to have failed in
which remains the leading Ayurvedic professional secondary school or to have failed to gain admission
association. In 1910 Ajmal Khan expanded his ear- to modern medical or professional schools (Brass
lier organization into the All-India Ayurvedic and 1972). For the treatment of serious ailments, West-
Yunani Tibb Conference. The medical associations ern medicine is preferred by those who can obtain
successfully opposed the Registration Acts that fully and afford it. Nevertheless, the struggle for "medical
certified only allopathic, or Western-trained, British equality" continues.
and Indian physicians. They also called for placing
the ancient indigenous medical systems on a scien- The process of medical professionalization in the
tific basis (Metcalf 1985). Indigenous practitioners Middle East was quite different. In Egypt in the late
established links between their medical concepts nineteenth century, medical works by Avicenna and
and those of modern Western medicine in order to others were published by Cairo's Bulaq Press. This
sanction them. When British authorities moved the could have been a sign of a revival or of a new
capital to Delhi, Ajmal Khan requested and received institutionalization of Islamic medicine. Thus, Ull-
land for an indigenous medical college. With fund- mann (1978) suggests that the manuscripts were
ing from princes and merchants, the foundation published because they were part of a living medical
stone for the Ayurvedic and Yunani Tibb College tradition rather than part of medical history. It is
was laid in 1916 and the college was formally opened probably truer that they were part of Egypt's nation-
in 1921. Despite much ambivalence, both the British alist revival and were valued primarily as part of its
viceroy and Mahatma Gandhi gave their support to cultural heritage. Egyptian medical students stud-
the college because it was an important symbol of ied exclusively Western medicine at the Qasr al-
the Indian cultural revival and of Hindu-Muslim Ayni medical school or went abroad to study in Brit-
cooperation (Metcalf 1986). The Indian National Con- ish or French medical schools. By the post-World
gress, founded in 1920, called for government spon- War I era, most governments in the Middle East
sorship of Indian medicine. In the 1920s and 1930s required practicing physicians and pharmacists to
vaidyas and hakims who had formed professional be licensed, and medical schools specializing in West-
associations in rural areas actively campaigned for ern medicine alone had been established in Istanbul,
government recognition. Beirut, Cairo, Tunis, Tehran, and many other major

cities. In Iran, for example, the modernizing govern- hadiths, and did not consider it part of the Islamic
ment of Reza Shah required all physicians and phar- religious sciences (Metcalf 1982).
macists to be licensed by the early 1930s. Unlicensed In the Middle East, there was no competing medi-
physicians with established practices had to take an cal system associated with a dominant indigenous
examination that, according to Byron Good, an an- religion, and Muslim, Christian, and Jewish physi-
thropologist specializing in Iran, covered internal cians all studied the Greco-Islamic medical theories.
medicine, pharmacology, and traditional Galenic- Although Islamic medicine was not an integral part
Islamic medicine. The license given to these (mojaz, of the Islamic sciences, most people considered it to
or permitted) physicians was not equivalent to that be compatible with correct Islamic values. Because
given by the accredited Western medical schools but not only Ayurvedic but also Yunani physicians
was rather comparable to the medecin tolere license formed professional associations, it would seem that
given to indigenous practitioners in French colonies. the "unique origin" and the "religious versus secular
To pass the exam, the candidates had to study Euro- or foreign origin" explanations can only partially
pean medical texts in order to familiarize them- explain the different responses to modern medicine
selves with the new medical theories and practices. and to colonial rule. An additional explanation may
This resulted in a modification of existing medical lie in the fact that the Middle East was closer to the
practices, and after the early 1930s all new physi- European metropoles than was India, making its
cians and pharmacists had to hold licenses from the exposure to European political and cultural influ-
accredited medical schools (Good 1981). ence more intense. The main support for Ayurvedic
The unlicensed indigenous practitioners in Egypt, and Yunani professional organizations has, in fact,
Iran, and elsewhere - health barbers, midwives, come not from the main cities of India but from the
bonesetters, herbalists - continued to have clients, provinces. A further explanation may be found in
of course, because most people did not have access to British colonial administrative policies. The British
European medicine, which was expensive and con- authorities in India initially attempted to preserve
fined to the large cities. But such practitioners did local traditions. They even combined the indigenous
not themselves organize in order to establish medi- and European systems in their new medical schools,
cal schools, pharmaceutical companies, or journals where courses were taught in Sanskrit and English.
specializing in Greco-Islamic medicine. The process was quite different in the Middle East
and North Africa because in the nineteenth century,
There are several possible explanations for these when the British and French established colonial
very different responses to the new dominance of rule, indigenous ruling elites such as Muhammad AH
Western medicine. Ralph Croizier (1968), a special- of Egypt and his successors had for some time been
ist in Chinese medical systems, has suggested that trying to strengthen their own power by learning the
Islamic medicine differed from Ayurvedic and Chi- secrets of European power. India's rulers had not had
nese medicine because it did not claim that it con- such a long exposure to European science and technol-
tained special knowledge unknown in the West. In- ogy before the onset of colonial rule. Indigenous rul-
deed, unlike the Hellenic medical theories shared by ers in India had not, therefore, been able to emulate
both Islamic and pre-Renaissance Western medicine, Muhammad Ali of Egypt or the other modernizing
the ideas of Ayurvedic medicine were nearly un- rulers of the Middle East, for they had been relegated
known to Western scholars until the colonial era. to a largely ceremonial and traditional role in the
The unique origin of Ayurvedic medicine therefore British raj. The sequential establishment of colonial
may have distinguished it from Islamic medicine. rule may thus have contributed to the difference in
Another explanation may be that the Ayurvedic medical professionalization. Furthermore, as the
texts were believed to have originated in Hindu holy nineteenth century progressed, the discovery of qui-
scripture, whereas the Greco-Islamic medical texts nine, smallpox vaccination, new methods of public
were clearly of non-Islamic, secular origin. Barbara health sanitation, anesthesia, antisepsis, and other
Metcalf, a historian of India and Pakistan, has ob- advances made the prevention and treatment of dis-
served, however, that, in Muslim India, Yunani medi- ease more effective and the modern medical profes-
cine was considered to be an ancillary dimension of sion in general more confident. The Ayurvedic and
religion and its practitioners were expected to be Yunani physicians, protected by British colonial poli-
pious men. Yet, as she cautions, Muslim scholars cies, managed to upgrade their skills by adopting new
were aware that Yunani medicine did not contain methods of medical intervention learned from Euro-
the truths of the religion as did the Quran and the pean medicine and, rather like practitioners of home-

opathy and chiropractic in the West, were able to and learned magic-religious medicine (Leslie 1976).
obtain a degree of official recognition. Yet all must be considered part of Indian medicine.
Finally, because the ruling elites of the Middle East Similarly, in the Middle East, one must distin-
and North Africa had opted for European medicine guish between the classical Islamic medical tradi-
long before the colonial era, indigenous practitioners tion; the everyday practices of the health barbers,
in these regions, unlike their counterparts in India, herbalists, midwives, bonesetters, and religious heal-
had no support from their local (Muslim) rulers and ers; and, of course, Western medicine. Throughout
none from their European colonial rulers. Because the Islamic world, Muslim fundamentalists are espe-
they had been represented at most by a head doctor cially active in the medical schools. But outside of
appointed by the ruler, they had no organized means India and, to a lesser extent, Pakistan, they have
of protest. In contrast to the authoritarian, central- given no thought to developing Islamic medicine
ized political systems of the Middle East, the constitu- along Western institutional lines. They argue that
tional form of government established in India in the medical sciences have no nationality, but that (mod-
twentieth century lent itself to lobbying by special ern or Western) medicine should be administered
interest groups such as professional associations. The according to Islamic law. Thus, charitable clinics
result is a dual system of officially recognized medical attached to fundamentalist mosques dispense West-
education, professional organization, and certifica- ern medicine, and the fundamentalists call merely
tion in India and a single system in the Middle East for the revival of the comprehensive worldview and
and North Africa. Nevertheless, in all these regions, the humanistic concern that, they contend, charac-
as in the West, a wide variety of medical practitioners terized the Islamic medical system. They advocate
continue to nourish. what would in the West be called the holistic ap-
Apologists for the Islamic and Indian medical tra- proach to patient care, with modern medicine subsi-
ditions argue that Western medicine cannot treat all dized through the legal Islamic taxes and accessible
diseases. They correctly observe that many diseases to all.
have a cultural component that a local healer famil- Nancy E. Gallagher
iar with the beliefs of the patient might treat more
satisfactorily than a counterpart trained in Euro- Bibliography
pean medicine. It is widely recognized that diseases Basham, A. L. 1976. The practice of medicine in ancient
partly caused by psychological stress can be more and medieval India. In Asian medical systems, ed.
effectively treated by healers who understand the Charles Leslie, 18—43. Berkeley and Los Angeles.
religious, cultural, and political beliefs of the pa- Brass, Paul R. 1972. The politics of Ayurvedic education: A
tient. Recognizing this and, more important, the un- case study of revivalism and modernization in India.
avoidable fact that the majority of the world's popula- inEducation andpolitics inlndia: Studies in organiza-
tion does not have access to modern medicine, the tion, society, and policy, ed. Susanne H. Rudolph and
World Health Organization has been attempting to Lloyd I. Rudolph, 342-71. Cambridge.
upgrade existing indigenous medical traditions Brockelmann, C. 1937-49. Geschichte der arabischen Lit-
teratur. Leiden.
rather than to replace them with modern medicine.
Croizier, Ralph. 1968. Traditional medicine in modern
In practice this has meant studying local remedies China: Science, nationalism and the tensions of cul-
with the techniques of modern science in order to tural change. New York.
distinguish between effective and harmful practices Dols, Michael. 1984. Medieval Islamic medicine: Ibn
and to train practitioners to modify these methods in Ridwan's treatise "On the prevention of bodily ills in
accord with their findings. Success has been very Egypt." Berkeley and Los Angeles.
limited, however. Dunn, Fred. 1976. Traditional Asian medicine and cosmo-
Today, in India, as Charles Leslie, an anthropolo- politan medicine as adaptive systems. In Asian medi-
gist specializing in Indian medicine, has pointed out, cal systems, ed. Charles Leslie, 133-58. Berkeley and
one must distinguish between the Ayurvedic medi- Los Angeles.
Elgood, Cyril. 1951. A medical history of Persia and the
cine of the Sanskrit classic texts; the Yunani medi-
Eastern Caliphate. Cambridge.
cine of the classic Arabic texts; the syncretic Filliozat, J. 1964. The classical doctrine of Indian medi-
Ayurvedic and Yunani medicine of the traditional cine. Delhi.
culture; contemporary professionalized Ayurvedic Gallagher, N. 1983. Medicine and power in Tunisia, 1780—
and Yunani medicine (both of which have borrowed 1900. Cambridge.
from modern Western or allopathic medicine); folk Goitein, Shlomo. 1967. A Mediterranean society, Vol. 1.
medicine; popular culture; homeopathic medicine; Berkeley.

1.4. Disease, Human Migration, and History 35
Good, Byron. 1981. The transformation of health care in

modern Iranian history. In Modern Iran: The dialec- 1.4
tics of continuity and change, ed. Michael E. Bonine
and Nikki R. Keddie, 59-82. Albany, N.Y.
Disease, Human Migration,
Gupta, B. 1976. Indigenous medicine in nineteenth- and and History
twentieth-century Bengal. In Asian medical systems,
ed. Charles Leslie, 368-78. Berkeley and Los Angeles.
Ibn Abi Usaybia. 1882-4. Tabaqat al-atibba', ed. A. There is a story told among the Kiowa Indians of
Muller. Cairo. North America's southern Great Plains about the
Issa, Ahmed. 1928. Histoire des Bimaristans (hdpitaux a arrival in their midst, in a time long past, of a
I'ipoque islamique). Cairo.
stranger in a black suit and a tall hat. This
Jolly, Julius. 1951. Indian medicine. Poona.
Leslie, Charles. 1976. The ambiguities of medical revival-
missionary-appearing figure is confronted by Sayn-
ism in modern India. In Asian medical systems, ed. day, a mystic hero of the Kiowa.
Charles Leslie, 356—67. Berkeley and Los Angeles. "Who are you?" asks the stranger.
Metcalf, Barbara Daly. 1982. Islamic revival in British "I'm Saynday. I'm the Kiowa's Old Uncle Saynday. I'm the
India: Deoband, 1880-1900. Princeton, N.J. one who's always coming along. Who are you?"
1985. Nationalist Muslims in British India: The case of "I'm smallpox."
Hakim Ajmal Khan. Modern Asian Studies 19: 1-28. "Where do you come from and what do you do and why are
1986. Hakim Ajmal Khan: Rais of Delhi and Muslim you here?"
"leader." In Delhi through the years: Essays in urban "I come from far away, from across the Eastern Ocean. I
history, culture and society, ed. R. E. Frykenberg, 299- am one of the white men — they are my people as the
315. Delhi. Kiowa are yours. Sometimes I travel ahead of them, and
Meyerhof, M. 1984. Studies in medieval Arabic medicine. sometimes I lurk behind. But I am always their compan-
London. ion and you will find me in their camps and in their
O'Flaherty, Wendy Doniger. 1980. Karma and rebirth in houses."
classical Indian traditions. Berkeley and Los Angeles. "What do you do?"
Omar, Saleh Beshara. 1977. Ibn al-Haytham's optics: A "I bring death. My breath causes children to wither like
study of the origins of experimental science. Minne- young plants in the spring snow. I bring destruction. No
apolis. matter how beautiful a woman is, once she has looked at
Rahman, Fazlur. 1987. Health and medicine in the Islamic me she becomes as ugly as death. And to men I bring not
tradition. New York. death alone but the destruction of their children and the
Sabra, A. 1.1972. al-Haytham, Ibn. Dictionary of scientific blighting of their wives. The strongest warriors go down
biography. New York. before me. No people who have looked at me will ever be
1987. The appropriation and subsequent naturalization the same." (Crosby 1986)
of Greek science in medieval Islam, a preliminary
statement. History of Science 25: 223-43. Stories such as this abound among indigenous peo-
Savage-Smith, E. 1987. Drug therapy of eye diseases in ples throughout the world. Sometimes they are sim-
seventeenth-century Islamic medicine: The influence ple sayings, as among the Hawaiians: "Lawe li'ili'i ka
of the "New Chemistry" of the Paracelsians. Phar- make a ka Hawai'i, lawe nui ka make a ka haole" -
macy in History 29: 3-28. "Death by Hawaiians takes a few at a time; death by
1988. Gleanings from an Arabist's workshop: Current white poeple takes many." Among some, such as the
trends in the study of medieval Islamic science and Maori of New Zealand, they are more cryptic: White
medicine. ISIS 79: 246-72. people and their diseases are "he taru tawhiti" — "a
Ullmann, Manfred. 1978. Islamic medicine. Edinburgh. weed from afar." And among still others elaborate
Zimmer, Henry R. 1948. Hindu medicine. Baltimore. systems of disease differentiation have emerged, as
Zysk, Kenneth G. 1985. Religious healing in the Veda.
among the Southwest American Indian Pima and
Transactions of the American Philosophical Society
75:7.
Papago, who distinguish kd.cim mumkidag, or "stay-
ing sicknesses," from 'dimmeddam, or "wandering
sicknesses." Staying sicknesses are those the Indians
have always had; they are noncontagious, and whom
they afflict and the appropriate response to them are
well understood. Wandering sicknesses, in contrast,
originated among other, distant peoples, principally
white peoples; they are relatively new to the Indians,
are highly contagious and indiscriminate in whom

they attack, and are "wrong" because there is no way trous to the newly contacted, nonimmune communi-
to defend against them (Bahr et al. 1974). ties. Their travels were rarely extensive, however, at
To some Western readers these may seem like least in the early centuries of animal husbandry,
quaint notions among simple peoples. In fact, they agriculture, and urbanization.
are clear-eyed and accurate recognitions of historical A major problem at this stage of social develop-
and ongoing reality. For millennia upon millennia, ment was founded on the concentration of humans in
over most of the earth's surface, the vast majority of the new protourban centers, initially in the Middle
humankind lived in relatively isolated enclaves. Dis- East and later elsewhere. First, the people in such
eases, of course, existed in those enclaves, but among locales were dependent on those in the surrounding
most peoples for most of that time, none of the dis- countryside for food supplies; any depletion of those
eases were so-called crowd-type ecopathogenic infec- supplies, because of drought or other natural disas-
tions such as smallpox, yellow fever, typhoid, mater, spelled catastrophe for the urban dwellers. In
laria, measles, pertussis, polio, and so on (Newman addition, the concentration of a large number of peo-
1976). Nor for most of the history of humankind did ple in a relatively small geographic area greatly
the majority of the world's populations suffer from increased the opportunity for the infectious commu-
such afflictions as hypertension, diabetes, obesity, nication of various diseases from one human host to
gallstones, renal stones, coronary heart disease, ap- another. On occasion, and in the short term, this
pendicitis, diverticular disease, and more, including resulted in epidemic outbreaks of disease. Generally,
various forms of cancer (Trowell and Burkitt 1981). however, and in the long term, it probably meant the
During these huge stretches of time, before hu- creation of endemic diseases that did not erupt like
mans developed the ability to move great distances firestorms, but that gnawed away at the well-being
into areas inhabited by other humans, population of the community and in part undermined its ability
growth among these generally quite healthy people to reproduce.
was restrained by the same phenomenon that re- A larger consequence of the urbanization-disease
strained growth among other animals - limited re- dynamic was that urban populations were often un-
sources. With the rise of agriculture, however, the able to sustain themselves without external support
domestication of animals, and the first appearance and a steady stream of in-migration from the coun-
of urban communities in Sumeria about 5,000 years tryside. This was a perpetual problem from the time
ago, the resource restraint on population growth be- of the rise of urban centers until the nineteenth
gan to loosen. But another restraint emerged - century; throughout this period, observes William
infectious disease. H. McNeill (1979), "rural peasantries [were re-
quired] to produce a surplus of children as well as a
Early Urban Environments surplus of food to sustain urban life and the civilized
Before the domestication of various kinds of birds social structures cities created."
and mammals, hunter-gatherer societies had little This is not to say, however, that in-migrating ru-
everyday contact with large numbers of animals ex- ral peasants were greeted as saviors of civilization.
cept, in some cases, dogs. As humans learned to On the contrary, they were fodder to be wasted in the
contain, control, and breed pigs, sheep, cattle, goats, interests of civilization's continuance. As Lawrence
horses, and fowl, however, they were forced to share Stone (1977), among others, has vividly shown, as
those animals' environments. Although their dilate as the seventeenth, eighteenth, and nineteenth
etary protein intake thus increased, so too did their centuries, the centers of Western civilization were
exposure to pox viruses, distemper, measles, influ- cesspools of disease, exploitation, starvation, and
enza, and other maladies, all diseases carried by the death. In Manchester, England, for example, for
newly domesticated creatures in their midst. much of the nineteenth century, the mortality rate
Damaging as these diseases were when first en- for children under 5 was around 50 percent (Forbes
countered, in time they became the troublesome, but 1986). All during this time urban dwellers in Europe
relatively nonlethal childhood diseases of the were dying of bubonic plague, smallpox, syphilis,
evolved stockbreeding societies. The diseases, along typhus, typhoid fever, measles, bronchitis, whooping
with the animals, in effect became domesticated, but cough, tuberculosis, and other diseases (e.g., Matos-
only for the specific people who had endured the sian 1985), which still had not spread to what - to
lengthy immunization process. As these people Europeans, at least - were the most remote portions
moved from place to place, encountering other of the globe.
groups, they deposited pathogens that were disas- Migration outward to the Caribbean, the Ameri-

cas, and the Pacific from the densely packed, Athens in the fifth century B.C. being the classic
disease-infested urban centers of Europe and then example (Shrewsbury 1950)-those early civiliza-
Asia - with an involuntary assist from Africa - tions remained sufficiently separate from one an-
probably created the greatest explosion of epidemic other that biological and social stability was more
disease and the worst human catastrophe the world the rule than the exception.
has ever seen. Before turning to that holocaust, This began to change at about the time of the
which began in the late fifteenth century, it is worth Christian Era (to use the Western chronological
glancing at the first great disease exchange that guidepost) as overland caravans and open-sea ships
brought both China and Rome nearly to their knees expanded trade throughout the Middle East, Asia,
long before the peoples of the Pacific or the Americas and Europe. The outer extremes of that new network
would experience the initial forays of bacteria and of commerce - China and Rome - were also the least
viruses. experienced in terms of previous trade interactions
and cosmopolitan disease. To use the earlier-noted
Disease and Commerce Pima and Papago Indian terminology, both China
In his well-known study Plagues and Peoples, and in and Rome were well adapted to their own "staying
subsequent writings as well, the historian William sicknesses," but unlike the more trade-experienced
H. McNeill has shown that a useful way to under- peoples in much of India and the Middle East they
stand the evolution of human society is to examine had little experience with the "wandering sick-
the complex interactions between and among micro- nesses" that existed outside their realms. As a conse-
parasites and macroparasites. Microparasites, in quence, whereas most of India and the Middle East
this context, are the microscopic organisms that live seem to have experienced no major pathogenic demo-
off human tissue, sometimes carrying disease and graphic reactions to the new expansion of commerce,
death, sometimes provoking immune reactions in China and Rome were convulsed by it.
their host that destroy the microparasites, and some- In the late second century A.D. both Rome and
times developing a reciprocal relationship that al- China were probably overwhelmed by pestilence. In
lows both host and parasite to survive in a state of Rome the so-called Antonine plagues of A.D. 165-80
relative equilibrium. In the last case, the host may were followed less than a century later by another
become a carrier of infection, capable of spreading it round of empirewide pandemic. Although it is impos-
to others although he or she remains symptomless. sible, at this distance, to determine what diseases
Macroparasites, in the traditional sense, are preda- entered Rome and caused such havoc during these
tory animals such as lions and wolves that feed on times, opinion has long centered on smallpox or
the flesh of other animals - but McNeill suggests something similar or ancestral to it as the primary
that, in a more metaphorical sense, humans who agent (Hirsch 1883; McNeill 1976). No doubt, how-
seize the goods of others or who compel others to ever, other newly introduced infections (including,
provide services are also macroparasites. Like micro- probably, measles) were present as well. The result
parasites, macroparasites of this sort sometimes kill was severe and prolonged population decline and,
their hosts in the immediate assault, but more often perhaps consequently, political upheaval.
they develop a long-term exploitative relationship, A very similar epidemiological and social pattern
again a state of relative equilibrium, albeit to the developed in China during the same early centuries
much greater advantage of the parasite than the of this era (McNeill 1976). In short, the mobility of
host (McNeill 1976, 1980). commerce, to a degree unprecedented in previous
Throughout the course of human evolution there world history, introduced new and devastating waves
have been long stretches of time when it seems that of microparasitism to geographic locales that previ-
states of equilibrium have existed among the masses ously had existed in widely separated realms; the
of people and the microparasites and macroparasites consequent population collapses probably gave rise to
that lived off their bodies and their labor. To be sure, upheaval in the macroparasitic equilibrium (how-
during these times neither the physical nor the so- ever uneasy it may already have been), with eventual
cial conditions of the majority of humankind may deterioration and collapse of the existing political
have been ideal, but neither were they often in a orders - the Roman and Han empires - altogether.
state of crisis. This was true even in the early centu-
ries of urban society discussed earlier: Although cer- The European Middle Ages and After
tainly punctuated from time to time by epidemic or The thousand years following the second- and third-
political upheaval - usually in tandem, the case of century Roman and Chinese pandemics witnessed

recurring bouts of disease upheaval, but generally many maladies and other intolerable diseases do daily
these were confined to specific geographic areas. In happen. (Robertson 1968)
particular, it seems that the Mediterranean world
experienced major epidemiological assaults during The worst of those "many maladies and intolera-
the middle to later centuries of the first millennium ble diseases" descended on Europe from China
A.D., due in large part to that locale's openness to through the trade routes of the Mediterranean, mov-
migrations and seaborne contagions. To some extent ing through southern Russia and the Crimea be-
in response to this, European civilization began a tween 1331 and 1346, finally exploding across the
slow northward shift (Biraben and Le Goff 1969). length and breadth of the Continent between 1346
The early medieval period in northern Europe was and 1350. By the time this first wave of the bubonic
one of a relatively large number of disease out- plague pandemic, the Black Death, had passed, at
breaks, but few of major epidemic consequence least a third of the population of Europe had died.
(Bonser 1944). As McNeill (1976) notes, "A pattern Then it returned in the 1360s and 1370s to kill
of increasing frequency but declining virulence of again, though each new visitation brought progres-
infectious disease is exactly what a population learn- sively lower death rates as immunity to the disease
ing to live with a new infection experiences as the began to develop.
accommodation between hosts and parasites moves The weight of evidence suggests that in the wake of
toward a more stable, chronic state." In sum, a the plague nothing remained the same. It is perhaps
parasite-host equilibrium was emerging. To be an exaggeration to label the Black Death the "cause"
sure, by modern standards mortality from endemic of events ranging from the Peasants' Revolt to the
diseases was high - and the urban centers were still Reformation, as some have done, but there is no doubt
unable to maintain growth without significant in- that spiritual and political faith were profoundly
migration from the countryside — but overall the shaken by it. Certainly this disequilibrium - when,
population of Europe probably tripled during the as one nineteenth-century historian put it, "faith dis-
half-millennium between 800 and 1300. appeared, or was transformed; men became at once
By any standards, however, the fourteenth- skeptical and intolerant" (Jusserand 1891) - made
century population of Europe was far from robust. an important contribution to the great social changes
The famous agricultural revolution of the Middle that occurred in Europe from the fifteenth to the
Ages had greatly increased European nutritional seventeenth century.
levels, thus undergirding the relatively rapid popula- During those later centuries epidemics continued
tion growth (White 1962), but it was a precarious to haunt the Continent, and population recovery was
foundation for population maintenance. England, slow (Flinn 1981). As before, the cities could not
for example, was hit by major famines between 1315 sustain themselves without constant in-migration
and 1317, although less disastrous times of starva- from the countryside. As one writer has flatly stated,
tion were common as agricultural yields declined by during these centuries "immigration to the towns
nearly 20 percent in the first half of the century was vital if they were to be preserved from extinc-
(Braudel 1973). Then, in midcentury, plague struck. tion" (Mols 1973). Until the eighteenth century, how-
For some centuries migrations from Europe to the ever, the geographic extent of most Europeans' inter-
Middle East had been growing, beginning with nal urban migrations appears to have been quite
small pilgrimages and culminating in the Crusades. small: Apart from the forced migrations caused by
These population movements generated trade net- warfare, as one large study has shown, the majority
works, which themselves gave impetus to the cre- of those people who moved at all during their life-
ation of new and larger urban centers in Europe - times were unlikely to have migrated more than 10
centers of extreme crowding and extraordinarily miles from their original home (Clark 1979).
poor public health conditions. As one English legal The crucial point, however, for present purposes at
statute of the fourteenth century described things, least, is that by the close of the fifteenth century,
as a prelude to a futile effort at correction: Europeans had accumulated and exposed one an-
So much dung andfilthof the garbage and entrails as well other to an enormous number of what had evolved
as of beasts killed, as of other corruption, be cast and put into chronic infectious diseases - including measles,
in ditches, rivers, and other waters, and also in many mumps, influenza, chicken pox, smallpox, scarlet fe-
other places, within, about, and nigh unto divers cities, ver, gonorrhea, and tuberculosis, to name but a few.
boroughs, and towns of the realm, and the suburbs of Although occasionally breaking out in epidemic epi-
them, that the air there is greatly corrupt and infect, and sodes, these diseases had principally become slow

killers, many of them preying largely on children, them. Unlike even the worst epidemics the Europe-
nearly half of whom died before reaching their tenth ans had historically had to endure, including the
birthday (Flinn 1981), or the aged. infamous Black Death, the biological invaders of the
It was neither children nor the aged, however, who Caribbean came in a swarm: A variety of scourges
manned the sailing ships that, near the turn of the hit them all at once. In their confined island worlds
fifteenth century, began the most extensive explora- there was nowhere to hide.
tions and migrations the world had ever witnessed The island of Hispaniola was the first to be hit. In
and, as already mentioned, in the process created 1492, when contacted by Columbus, its population
what may well have been the worst series of human may have been as large as 8 million; less than half a
disasters in history. century later its people were, for all practical pur-
poses, extinct (Cook and Borah 1971). The pattern
Africa and the Caribbean was the same throughout the islands of the Carib-
The massive African continent, with a commerce, bean. Diseases descended on the natives in clusters.
migration, and disease history that was at least And with no one in the community having any resis-
Europe's match, loomed large in the imagination of tance, everyone fell sick at the same time. With no
the earliest open-sea European explorers. With all one left to haul water or feed children or provide
its riches, however, as Alfred Crosby (1986) has comfort to anyone else, nutritional levels plum-
commented, "Africa was a prize well within Euro- meted and despair swept over the populace — further
pean reach, but it seared the hand that tried to hold reducing their resistance to infection.
it." In addition to malaria, one of the most destruc- As the first epidemic waves passed, longer-term
tive diseases humans have ever faced, so extensive illnesses like tuberculosis and gonorrhea took hold,
was the barrage of African diseases that greeted reducing the island populations still further while
the Europeans - in Crosby's words, "blackwater fe- undermining their reproductive potential and thus
ver, yellow fever, breakbone fever, bloody flux, and any possibility of recovery. In this condition the na-
a whole zoo of helminthic parasites" - that Africa tives were yoked to forced labor by the Spanish in-
quickly became known as the "white man's grave." vaders. With the failure of native labor to produce as
Even as late as the nineteenth century it was rou- desired, the Europeans turned to Africa for their
tine for British troops stationed on the Gold Coast work force. This spelled the end for the Caribbean's
to lose half their number in a single year to the native island peoples, for the enslaved Africans
ravages of African disease, and European soldiers brought with them the diseases that earlier had
stationed alongside black troops in West Africa died made their continent the storied "white man's
from disease at a rate 15 to 20 times higher than grave." Whipsawed between the diseases that had
their African counterparts (Curtin 1968). The Euro- been accumulating in Europe and Africa for millen-
peans, of course, returned some of these favors with nia, the island natives at last ceased to be (Kiple
diseases of their own to which the Africans had 1984).
little or no resistance - in particular, syphilis and In the centuries that followed, down to the pres-
tuberculosis, which took a heavy toll among their ent, the European and African diseases did most of
African recipients. their damage to the populations native to the other
Whereas some explorers plied the African trade, continent - tuberculosis, smallpox, and pneumonia
others ventured deep into the Atlantic. There they attacking the African immigrants, malaria and yel-
encountered peoples living in the most salubrious of low fever assaulting the Europeans. Demographi-
island environments, peoples with no domesticated cally, the Africans triumphed: Today the descen-
animals and no history of almost any of the diseases dants of African slaves dominate the populations of
Europeans had had to live with for centuries and the Caribbean. As Kenneth Kiple (1984) has clearly
even millennia. In their great isolation, the natives shown, however, new catastrophes now lie in wait as
of the Caribbean had long since come to biological population pressures build in the region and the
terms with the relatively few microparasites in their safety valve of out-migration threatens to close.
midst. In this sense, they were probably similar to
the Old World populations of thousands of years The Americas
earlier. Predictably, European contact was calami- Following their invasions of the Caribbean, the
tous for them. The Caribbean island natives, living sixteenth-century European explorers headed for
in fairly dense coastal settlements, were over- the American mainland. Again, they encountered
whelmed by the barrage of diseases that rolled over peoples with no previous exposure to the diseases

the Europeans bore so easily - and again the result Patuxet tribe was extinguished in two years and the
was a holocaust. Massachusett tribe fell by 97 percent in two decades,
Whereas it now appears that influenza, carried by to Guatemala, where the highland population alone
pigs aboard Columbus's ships, may have been the dropped by 94 percent in little more than a century
initial principal killers in Hispaniola (Guerra 1985, (Axtell 1985; Lovell 1985). Other examples abound.
1988), on the American mainland the initial major Terrible as the epidemic invasions were in all these
cause of death was smallpox (Crosby 1972; Dobyns cases, it is now becoming evident that viral and bacte-
1983). Death rates were much higher in coastal than rial assaults, by themselves, do not sufficiently ac-
in inland areas, those in the former often approach- count for such large population losses. As in the Ca-
ing the extermination-level rates of the Caribbean ribbean, it appears likely that in the rest of the
(Borah and Cook 1969). Inland areas, however, Americas the epidemics initiated a process of col-
though faring somewhat better in a comparative lapse, which then was exacerbated by the rapid with-
sense, still suffered at a level that strains comprehen- ering away of village life and social supports, along
sion. The population of central Mexico, for example, with the pervading sense of despair and helplessness
appears to have dropped by one-third, from about 25 that was a natural concomitant of the epidemic fire-
million to less than 17 million, in a single decade storm (Neel 1977). In addition, comparative research
following European contact. Within 75 years it had now suggests that the fundamental cause of the most
fallen by 95 percent (Cook and Borah 1960; Borah drastic population declines may well have been an
and Cook 1963). overwhelming degree of infertility directly caused by
So rapidly did the viruses and bacteria spread up the waves of smallpox, tuberculosis, measles, and
and down and across the North and South American venereal infection that attacked these epidemiologi-
continents that historians have been unable to trace cally virginal populations (Stannard 1990).
their paths with any precision. It is now clear, how-
ever, that the diseases moved across the land at a The Pacific
much faster pace than did the men who brought The Pacific - from the continent of Australia to the
them, destroying whole populations long before islands of Hawaii - was the last major region of the
their very existence could be known by the Euro- world affected by the great era of European explora-
pean invaders (Ramenofsky 1987). tion in the sixteenth, seventeenth, and eighteenth
Although the overall size of the population in the centuries. The same lugubrious tale of explosive epi-
Americas at the time of European contact and its demics and drastic population decline that we have
subsequent rate of collapse have long been a subject encountered in the Americas was repeated here.
of much controversy, it is becoming increasingly ap- The lengthy ocean voyages required to reach the
parent that both numbers represent magnitudes Pacific screened out the danger of smallpox during
that earlier scholars had never imagined. It is possi- the earliest years of exploration, although in time
ble, in fact, that the pre-Columbian Americas con- smallpox epidemics did devastate native populations
tained more than 100 million persons - more than throughout the entire region (for examples from Aus-
resided in Europe, including Russia - at the time of tralia, Pohnpei, and Hawaii see Greer 1965; Butlin
the European arrival (Dobyns 1966). 1983; Campbell 1985; and Hanlon 1988). Influenza
Recent regional estimates continue to support the may have been restrained to some extent by the
thesis, originally propounded by Sherburne Cook and same distance-screening process, although influ-
Woodrow Borah, that massive and sudden depopula- enzalike epidemics were reported in many early rec-
tion was the rule in early native European contact sit- ords and ongoing research on the spread of influenza
uations throughout the Americas: From Peru, where viruses suggests ways in which the distance re-
a population of about 9 million dropped to 600,000 straint may have been overcome (Hope-Simpson and
during the century following contact (a 93 percent Golubev 1987). Of greatest importance in the first
decline rate), to Nicaragua, where it fell by more than decades of Western contact, however, were tuberculo-
92 percent (Cook 1981; Newson 1987); from Califor- sis (which can explode with epidemiclike intensity
nia, where the native population declined by 95 to 98 in a previously uninfected population; see, e.g., Du-
percent before bottoming out in the nineteenth cen- bos 1965) and venereal diseases.
tury (Thornton 1987), to Florida, where it appears to An account of the devastation visited on the Pa-
have fallen by 75 percent in only 15 years and 95 cific is as lamentable as is the account of what hap-
percent within the first century of European contact pened in the Americas. In southeastern Australia
(Dobyns 1983); from New England, where the about 95 percent of the aboriginal population died

off in slightly more than 60 years (Butlin 1983). In The problem, however, is much more complex. In
New Zealand the native population fell by about 60 addition to the fact that immigrants to many parts of
percent in 70 years and at least 75 percent in a the world suffer greatly increased incidences of coro-
century (Lewthwaite 1950; Pool 1977). In the Mar- nary heart disease and various forms of cancer - as,
quesas Islands the population dropped by 90 percent for example, Japanese immigrants to the United
in 65 years and by 96 percent in just over a century States (Waterhouse et al. 1976; Robertson et al.
(Dening 1980). In Hawaii the native population was 1977) - there is the ongoing tragedy of the acquired
halved within 25 years following Western contact immune deficiency syndrome (AIDS), which should
and reduced by at least 95 percent in a little more be sufficient to quell undue optimism. It is far from
than a century (Stannard 1988). There are many impossible, as Joshua Lederberg (1988) has noted,
more examples. that the AIDS viruses will continue to mutate, per-
As with the natives of the Caribbean and the haps even, in his words, "learning the tricks of air-
Americas, a primary cause of the Pacific peoples' borne transmission," and, as he says, "it is hard to
vulnerability to the introduced infections was their imagine a worse threat to humanity than an air-
lack of immunity to the new diseases and the fact borne variant of AIDS."
that they were assaulted by a barrage of them simul- Of course, that may not - indeed, probably will
taneously. In addition, some genetic factors may have not - happen. But it may. Even if it does not, the great
also played a part. Because initial populations were ease of human mobility and migration, along with
relatively small in each newly settled island, the the ability of our worst diseases to sustain them-
evolved gene pool in each case was probably rela- selves, ensures that - with or without virgin-soil
tively small, making large-scale die-offs more likely populations in the traditional sense - we have not
than would be the case in populations with a more seen the last mobility-caused infectious catastrophe.
complex and heterogeneous composition. Like Ameri- David E. Stannard
can Indians, who also grew from a comparatively
small population of early immigrants and who were Bibliography
isolated from the world's gene pools and great disease Axtell, James. 1985. The invasion within: The contest of
experiences for a vast period of time, Polynesians, for cultures in colonial North America. New York.
example, show a remarkably narrow range of blood Bahr, Donald M., et al. 1974. Piman Shamanism and
types, with an almost complete absence of type B staying sickness (Kd:cim Mumbidag). Tucson, Ariz.
(Morton et al., 1967; Mourant 1983). Biraben, J. N., and Jacques Le Goff. 1969. La peste dans le
In the Pacific, as in the Americas, the populations Haut Moyen Age. Annales: Economies, Sociites,
that were not extinguished by their contact with the Civilisations 24: 1492-1507.
West in time began to recover. Partly because of the Bonser, Wilfred. 1944. Epidemics during the Anglo-Saxon
development of acquired immunities, and partly be- period. Journal of the British Archaeological Associa-
tion 9: 48-71.
cause of amalgamation with the races that had
Borah, Woodrow, and Sherburne F. Cook. 1963. The ab-
brought the new diseases (among Hawaiians, for original population of central Mexico on the eve of the
example, the worst health profile today remains that Spanish conquest. Berkeley and Los Angeles.
of so-called pure Hawaiians, whose numbers have 1969. Conquest and population: A demographic ap-
dwindled to less than 1 percent of those at the time proach to Mexican history. Proceedings of the Ameri-
of Western contact), the Pacific's native people now can Philosophical Society 113.
have birthrates higher than most of the immigrant Braudel, Fernand. 1973. Capitalism and material life,
populations in their homelands. 1400-1800. New York.
Butlin, N. G. 1983. Our original aggression: Aboriginal
Conclusion population of southwestern Australia, 1788—1850.
It is easy, in light of the historical record, to believe Sydney.
that migration-caused health disasters are a thing of Campbell, Judy. 1983. Smallpox in aboriginal Australia,
1829-31. Historical Studies 20: 536-56.
the past. There are, after all, few if any hermetically
1985. Smallpox in aboriginal Australia, the early 1830s.
remote populations left on earth; and as we have Historical Studies 21: 336-58.
seen, from Rome and China in the second century Clark, P. 1979. Migration in England during the late sev-
A.D. to the Pacific in the eighteenth and nineteenth enteenth and early eighteenth centuries. Past and
centuries - as well as parts of South America in the Present 83: 57-90.
twentieth century — virgin-soil conditions were the Cook, David Noble. 1981. Demographic collapse: Indian
seedbeds of the great disease holocausts. Peru, 1520-1620. Cambridge.

Cook, Sherburne E, and Woodrow Borah. 1960. The Indian Matossian, Mary Kilbourne. 1985. Death in London. Jour-
population of central Mexico, 1531—1610. Berkeley nal of Interdisciplinary History 16: 183-97.
and Los Angeles. McNeill, William H. 1976. Plagues and peoples. New York.
1971. The aboriginal population of Hispaniola. In Es- 1979. Historical patterns of migration. Current Anthro-
says in population history: Mexico and the Caribbean, pology 20: 95-102.
Vol. 1, ed. S. F. Cook and W. Borah, 376-410. Berkeley 1980. The human condition. Princeton, N.J.
and Los Angeles. Mols, R. P. R. 1973. Population in Europe, 1500-1700. In
Crosby, Alfred W. 1972. The Columbian exchange: Biologi- The Fontana economic history of Europe, Vol. 2, ed. C.
cal and cultural consequences of 1492. Westport, M. Cipolla. London.
Conn. Morton, Newton, et al. 1967. Genetics of international
1986. Ecological imperialism: The biological expansion crosses in Hawaii. Basel.
of Europe, 900-1900. Cambridge. Mourant, A. E. 1983. Blood relations: Blood groups and
Curtin, Philip D. 1968. Epidemiology and the slave trade. anthropology. Oxford.
Political Science Quarterly 83: 190-216. Neel, J. V 1977. Health and disease in unacculturated
Dening, Greg. 1980. Islands and beaches — discourse on a Amerindian populations. In Health and disease in
silent land: Marquesas, 1774—1800. Honolulu. tribal societies, ed. P. Hugh-Jones et al., 155-77.
Dobyns, Henry F. 1966. An appraisal of techniques for Amsterdam.
estimating aboriginal American population with a Neel, J. V., et al. 1970. Notes on the effect of measles and
new hemispheric estimate. Current Anthropology 7: measles vaccine in a virgin-soil population of South
395-416. American Indians. American Journal of Epidemiology
1983. Their number become thinned: Native American 91: 418-29.
population dynamics in eastern North America. Knox- Newman, Marshall T. 1976. Aboriginal New World
ville, Tenn. epidemiology and medical care, and the impact of Old
Dubos, Rene. 1965. Man adapting. New Haven, Conn. World disease imports. American Journal of Physical
Flinn, Michael W. 1981. The European demographic sys- Anthropology 45: 667-72.
tem, 1500-1820. Baltimore. Newson, Linda A. 1987. Indian survival in colonial Nicara-
Forbes, Thomas R. 1986. Deadly parents: Child homicide gua. Norman, Okla.
in eighteenth and nineteenth century England. Jour- Pool, D. Ian. 1977. The Maori population of New Zealand,
nal of the History of Medicine and Allied Sciences 41: 1769-1971. Auckland.
175-99. Ramenofsky, Ann F. 1987. Vectors of death: The archaeol-
Greer, Richard. 1965. O'ahu's ordeal: The smallpox epi- ogy of European contact. Albuquerque, N.M.
demic of 1853. Hawaii Historical Review 1. Robertson, D. W, Jr. 1968. Chaucer's London. New York.
Guerra, Francisco. 1985. La epidemia americana de Influ- Robertson, T. L., et al. 1977. Epidemiologic studies of coro-
enza en 1493. Revista delndias (Madrid) 176: 325-47. nary heart disease and stroke in Japanese men living
1988. The earliest American epidemic: The influenza of in Japan, Hawaii, and California. American Journal
1493. Social Science History 12: 305-25. of Cardiology 39: 239-49.
Hanlon, David. 1988. Upon a stone altar: A history of the Shrewsbury, J. F. D. 1950. The plague of Athens. Bulletin
Island ofPohnpei to 1890. Honolulu. of the History of Medicine 24: 1-25.
Hirsch, August. 1883. Handbook of geographical and his- Stannard, David E. 1988. Before the horror: The popula-
torical pathology, Vol. 1, trans. C. Creighton. London. tion ofHawai'i on the eve of Western contact. Honolulu.
Hope-Simpson, R. E., and D. B. Golubev. 1988. A new 1990. Disease and infertility: A new look at the demo-
concept of the epidemic process of influenza A virus. graphic collapse of native populations in the wake of
Epidemiology and Infection 99: 5—54. Western contact. Journal of American Studies 24:
Jusserand, J. J. 1891. English wayfaring life in the Middle 325-50.
Ages. London. Stone, Lawrence. 1977. The family, sex and marriage in
Kiple, Kenneth F. 1984. The Caribbean slave: A biological England, 1500-1800. New York.
history. Cambridge. Thornton, Russell. 1987. American Indian holocaust and
Lederberg, Joshua. 1988. Pandemic as a natural evolution- survival: A population history since 1492. Norman,
ary phenomenon. Social Research 55: 343—59. Okla.
Lewthwaite, Gordon. 1950. The population of Aotearoa: Trowell, H.C., and D. P. Burkitt. 1981. Western diseases:
Its number and distribution. New Zealand Geogra- Their emergence and prevention. Cambridge, Mass.
pher 6: 32-52. Waterhouse, J., et al. 1976. Cancer incidence in five conti-
Lovell, W. George. 1985. Conquest and survival in colonial nents, Vol. 3. Lyon.
Guatemala: A historical geography of the Cuchumatan White, Lynn, Jr. 1962. Medieval technology and social
Highlands, 1500-1821. Montreal. change. New York.

PART II
Changing Concepts of Health and
Disease

II.l. Concepts of Disease in the West 45
words in general, can be discerned more accurately

by what we do with them than what we say about
Concepts of Disease in the them.
There have been countless attempts to define ill-
ness, disease, and health (Faber 1923; Riese 1953;
Lush 1961; Meador 1965; Hudson 1966; Niebyl 1971;
Boorse 1975; Burns 1975; Engel 1977; Temkin 1977;
The semantic and logical quagmires that await any- Taylor 1979; King 1982; Sundstrom 1987). Most
one audacious enough to safari through the changing share certain features, but it remains a practical
concepts of disease, illness, and health are por- certainty that no mortal could come up with short
tended by a cursory analysis of the definition formu- definitions of these words that would satisfy all who
lated by the World Health Organization. "Health," have an interest in them.
we are informed, "is a state of complete physical, Although they will not be treated in what follows,
mental and social well-being and not merely the even traditional definitions of death are no longer
absence of disease or infirmity" (Caplan, Engel- sufficient. This is due, in part, to the same develop-
hardt, and McCartney 1981). Aside from the fact ments in knowledge and technology that have forced
that this seems more realistic for a bovine than a us continually to redefine our notions of health and
human state of existence, problems abound in what disease. Death, according to Webster's Third New
appears to be a fairly straightforward statement. International Dictionary, is the "cessation of all vital
The word "complete" immediately removes the defi- functions without capability of resuscitation." But
nition from the realm of human reality. What is we now have a state of existence that may last many
complete mental well-being, or physical for that mat- minutes in which there are no apparent vital func-
ter? Worse still, the phrase "complete social well- tions, but during which the capability of resuscita-
being" is so freighted with individual interpretation is unknown. What do we call such a state of
tions that it alone renders the definition useless, if existence? This confounding of traditional defini-
not pernicious. tions by today's knowledge and technology leads to
This essay concentrates on ideas of physical such strange article titles as "Prevention of Recur-
health and disease, which is not to minimize the rent Sudden Death" (Rapaport 1982).
importance of psychiatric disease, but rather to ad- The judicious historian, after even a dampening
mit that concepts of mental health and illness, al- immersion into the literature of changing concepts of
though sharing most of the definitional difficulties disease, will conclude that the subject is unmanage-
of physical health and disease, are even more diffi- able in a brief essay. Accordingly, what follows ex-
cult to handle. In large part this is because with cludes non-Western concepts of disease and focuses on
mental illness we lack the kinds of objective tools to the tension between those who believed diseases were
measure brain function that have helped, though real entities with an existence of their own (ontolo-
not resolved, questions of what constitutes health gists) and the opposing camp, which held that disease
and disease in the physical realm. This is not, how- should be viewed properly as illness, as a unique
ever, to deny the interconnectedness of the psychic process in one person over time (physiologists).
and the physical, which is assumed in all of what The ontology-physiology tension has persisted be-
follows. cause physicians perceive that, at a minimum, they
Perhaps no one sentence captures the history of must have a reasonably precise definition of what
changing notions about disease better than a para- they mean by disease in order to distinguish them-
phrase of Humpty Dumpty's haughty admonition: selves as professionals. Try to imagine convincing a
"When I use the word disease, it means just what I patient to submit to exploratory abdominal surgery
choose it to mean - neither more nor less." Disease without using a diagnostic term; or to study pathol-
has always been what society chooses it to mean - ogy without the use of disease names; or to mount
neither more nor less. A number of important consid- fund-raising campaigns without words such as can-
erations lead to this generalization. Among these cer or muscular dystrophy. The essential contra-
are the following: (1) The definition of disease has diction that practitioners have confronted over the
varied with time and place in history; (2) the names centuries is that understanding disease demands
assigned to diseases are ultimately abstractions, al- thinking in abstract generalizations, but the prac-
though it is useful at times to act as though they are tice of medicine deals with ailing individuals.
real; (3) what we mean by diagnostic terms, as with The question of disease vis-a-vis illness is not sim-

46 II. Changing Concepts of Health and Disease
ply an intriguing philosophical persistency, al- biological aspects unique to diseases. A current ex-
though it has been a source of much intellectual ample is the acquired immune deficiency syndrome
enjoyment as well as frustration. The viewpoint (AIDS). The period of time between infection with
adopted has definite implications for what physi- the human immunodeficiency virus (HIV) and the
cians do in practice. Lord H. Cohen perceived five body's development of a testable antibody response
dangers in an inordinate ontological orientation: can be as long as a year. One practical consequence
of this inherent characteristic of the virus is that,
It promotes a "penny-in-the slot machine" approach to during this period of time, blood that tests negative
diagnosis by seeking for pathognomonic signs, especially for the antibody may be transfused and infect recipi-
the short cuts of the laboratory; . . . it suggests that diagno- ents. Furthermore, the period between infection
sis is arrived at by comparing an unknown with a cata- with the virus and development of the clinical dis-
logue of knowns; the method of recognizing an elephant by ease may be 8 to 10 years or longer. This trait of the
having seen one before;... it reduces thought to a mini- HIV greatly confounds the question of who should be
mum; ... it is of little help and may be positively mislead-
ing where the disease process varies significantly from the tested for AIDS and what a positive test means.
usual; and ... it leads to all those dangers associated with Thus, even as we correctly emphasize the role of
a label which Cowper implied when he wrote of those - cultural factors in the spread of AIDS (homosexual
"who to the fascination of a name, surrender judgment, activity and intravenous drug use), we may not for-
hoodwinked." (Lush 1961) get the central importance of the biological charac-
teristics of the virus itself.
In this view, the diagnostic label attached to a This critical significance of the nature of the dis-
patient tends to dictate the treatment that follows. If ease appears in earlier historical examples as well.
the patient is jaundiced, has pain in the right upper One of the most intriguing mysteries in the history
abdomen that radiates through to the back beneath of disease is that the Greeks, in the words of Karl
the scapula, and the X-ray demonstrates gallstones, Sudhoff, were "blind to the fact of contagion" (Ad-
the diagnostic label is cholelithiasis and the treat- ams 1886; Garrison 1929). The enigma is darkened
ment is removal of the stones. "Surgery does the by the fact that some of the diseases they described
ideal thing," wrote a health columnist around 1930 so well are contagious - mumps and childbed fever,
in a statement of pristine ontology, "it separates the for example.
patient from his disease. It puts the patient back to Nonetheless, contagionism was never completely
bed and the disease in a bottle" (Clendening 1931). eliminated from medical thinking after the accep-
But are such patients really separated from their tance of the Jewish Old Testament as a holy book in
diseases? They retain the genetic predisposition or the Christian religion. In large part this was be-
eating habits or whatever produced the gallstones cause of the attention accorded leprosy, which in-
originally. Somehow it seems insufficient to speak of creased with the return of the Crusaders from the
separating patients and diseases with such ready Middle East. The notion of disease as contagious was
surgical facility. even more strongly reinforced by the sweeps of bu-
A complete reliance on the opposite notion of ill- bonic plague in the fourteenth century. In a passage
ness has hazards of a different sort. Physicians who from his work On Plague, the fourteenth-century
think largely in terms of illness aptly consider the Arabic physician Ibn al-Khatib wrote, "The exis-
whole patient, but if they are ignorant of the natural tence of contagion is established by experience,
history of the disease, they may miss the diagnosis study, and the evidence of the senses, by trustworthy
and, for example, operate needlessly or too late. reports on transmission by garments, earrings; by
A number of commentators have accepted as fact the spread of it by persons from one house, by infec-
that disease is ultimately defined by the words and tion of a healthy sea-port by an arrival from an
deeds of those persons constituting a given society. infected land" (Arnold 1952). Even though the
They agree as well that physicians usually have had writer had no inkling of the intermediate role played
an important voice in these social definitions. What by the flea and common house rat in the spread of
is often neglected at this point is the role that the plague, the patterns of spread convinced him that
biology of diseases has played in shaping societal the disease was contagious.
conceptions of the nature of disease (Risse 1979).
Granted that cultural, social, and individual con- Historical Survey
siderations contribute to the expression of diseases As revealed by what physicians say and do, an onto-
in society, we may not overlook the importance of the logical orientation dominates our late-twentieth-

ELI. Concepts of Disease in the West 47
century thinking, but this was not always so. Histori- causation, constructed a system of definite disease
cally, the dominance of ontological and physiological entities. Neither approach was entirely sufficient.
thinking shifted time and again. Concepts of disease As has been said, "Hippocrates did the wrong thing
in ancient Israel, Egypt, and Mesopotamia were too well; the Cnidians did the right thing badly" (Jones
diffuse and vague to fit easily into ontological or 1952).
physiological compartments. In the Golden Age of As Greek culture spread first to Alexandria and
Greece, however, physiological thinking is easily then to Rome, the Hippocratic tradition was but one
identified. Plato needed no formal medical experi- of many Greek schools of thought. Hippocratism is
ence to see the deficiencies of compartmentalizing cherished today because it is more congenial to mod-
human illness. In Charmides he has Socrates say the ern medicine than the other competing systems of
following: "If his eyes are to be cured, his head must the time. In Alexandria the ontological approach was
be treated; and then again they say that to think of advocated by Erasistratus, who in the third century
curing the head alone and not the rest of the body B.C. wrote books on gout, dropsy, and paralysis. In
also, is the height of the folly. And arguing in this the second century A.D., Galen returned the empha-
way they apply their methods to the whole body, and sis to the Hippocratic theme, saying in effect that a
try to treat and heal the whole and the part to- disease is not only a change in a body, but also a
gether." And a bit further on, "The great error of our change in a particular body. After the decline of
day in the treatment of the human body [is] that Rome, the Hippocratic-Galenic tradition survived in
physicians separate the soul from the body" (Jowett the Greek-speaking East, where it was picked up and
1892). modified by the Arabs and returned to the Latin West
The Hippocratic approach was also decidedly phys- beginning in the eleventh and twelfth centuries.
iological. Not only did the Hippocratics see the pa- Characteristically, however, throughout Western
tient as an integrated whole, they appreciated the history, neither the physiological nor the ontological
need to study ailing individuals in the context of notion disappeared completely, even as one or the
their total environment, as evidenced in Airs, Wa- other was dominant. In the ninth century, Rhazes
ters, Places. Yet Hippocratic physicians could not was echoing the ontological when he distinguished
escape the essential dichotomy between illness and between measles and smallpox. In the sixteenth cen-
disease. In part this was because they were superb tury, Paracelsus not only broke with Galen's version
clinical observers. They described a number of cases of disease causation (i.e., the doctrine of the four
so faithfully that we can affix modern diagnostic humors) but refuted Galen's conception of the nature
names to them with certainty. At times they even of disease itself. For Paracelsus there were as many
gave specific names to these symptom complexes, specific diseases as there were "pears, apples, nuts,
such as pneumonia and pleurisy. and medlars." In his strong opinion Paracelsus influ-
If the Hippocratics were so sensitive to the differ- enced the physician-chemist Jean Baptistie van
ences in individual episodes of illness, how did they Helmont, who believed disease was "due to a cre-
deal with the similarities they detected in specific ative 'seed' which gets hold of a part of the material
syndromes to which they gave names? The answer is frame of the body and 'organises' it according to its
that they considered both, but neither to the exclu- own schedule of life" (Pagel 1972). For Paracelsus
sion of the other (Temkin 1977). One takes account and van Helmont it was the disease, not the patient,
of the symptoms, because the nature of the disease is that varied (Pagel 1972). The move of these two men
important, but so too is the unique nature of the toward ontology presaged the arrival of the "arch-
individual. The wise physician works not with the ontologist" of the seventeenth century, Thomas
ontoiogical red and physiological yellow, but with Sydenham.
the orange that results. A return to Hippocratic Although he never worked out a detailed system
holism has been advocated recently under the rubric himself, Sydenham believed diseases could be classi-
of a "biopsychosocial" model (Engel 1977). fied in much the same way as Linnaeus would later
In asking why the balance seen as ideal to the group plants. In an oft-quoted passage Sydenham
Hippocratics did not become and remain the domi- (1848) wrote the following:
nant outlook, it must be remembered that Hippo-
cratic thought did not rule the Hellenistic period. Nature, in the production of disease, is uniform and consis-
Indeed, contemporaneously with developing Hippo- tent; so much so, that for the same disease in different
cratism, the nearby Cnidians, although postulating persons the symptoms are for the most part the same; and
an erroneous single common pathway for disease the selfsame phenomena that you would observe in the

sickness of a Socrates you would observe in the sickness of
fluid. In the nineteenth century, disease would be
a simpleton. Just so the universal characters of a plant are
denned as a deviation from the normal. Because
extended to every individual of the species; and who- physiological normality had a range, disease, in a
ever . . . should accurately describe the colour, the taste,
sense, was a departure from the limits of range
the smell, the figure, etc., of one single violet, would find
within which health was balanced. In different
that his description held good, there or thereabouts, for all
terms, Brown and his eighteenth-century kin, with
the violets of that particular species upon the face of the
earth. their ideas of too much or too little, were using
deviation from the normal as the definition of dis-
To do this with any hope of accuracy, Sydenham ease. Their problem was that they lacked the knowl-
realized that physicians must return to the Hippo- edge and technology needed to confer objectivity on
cratic seat at the bedside. Beginning in 1666 he used the various ranges of physiological normality.
this method to execute detailed descriptions of small- The French clinical school of the first half of the
pox, syphilis, dysentery, gout (his personal nemesis), nineteenth century exploited the investigative tool
and measles, which he differentiated from scarlatina. called the clinical-pathological correlation. This
Although he would later be acclaimed the "En- was the system used effectively by Giovanni Battista
glish Hippocrates," this honor is not related to his Morgagni a half-century earlier, which had led him
conception of disease. As noted, the Hippocratics de- to conclude that diseases originated locally in the
scribed individual illnesses, which they perceived as organs of the body, and not in some imbalance of the
unique events limited in time. Sydenham, con- vague fluidal humors. The process remains one of
versely, strove to discover syndromes that, because the most effective teaching devices in medicine -
of their general characteristics, could be recognized obtaining a detailed history and physical examina-
when encountered in another patient. As Henry tions, which change following the natural course of
Sigerist (1971) put it, "Hippocrates wrote the histo- the disease, and finally submitting to the judgment
ries of sick persons, but Sydenham wrote the history of the autopsy table.
of diseases." French clinicians Jean Nicolas Corvisart and
The greatest attempt to accomplish the goal of Rene Laennec raised this exercise to such excellence
classification that Sydenham espoused came in the that it became known as la methode. In the process,
eighteenth century at the hands of Frangois Boissier many diseases that had never existed by name or
de Sauvages when he published Nosologia metho- had been confused with others were sorted out in
dica, in which diseases were divided into 10 classes, such a way that they could be detected in living
40 orders, and so on, to 2,400 species (Sauvages patients. This naturally gave great impetus to onto-
1768). For the most part he was unwittingly describ- logical thinking.
ing symptoms and syndromes, not disease entities. As it turned out, however, a more forceful and
Yet the idea was widely emulated. It appealed to effective contemporary personality belonged to the
clinicians, who had only to classify their patients' antiontologist Frangois Broussais. For Broussais, dis-
conditions correctly: Proper treatment followed as a ease occurred when certain structures were exces-
matter of course. sively stimulated. Such stimulation (irritation) pro-
During the seventeenth century the iatromecha- duced visible inflammatory lesions, which in his
nists came to the fore. This departure was led by scheme centered in the stomach and intestines.
Francois de la Boe, also known as Sylvius, who fol- There were then no such specific diseases as diphthe-
lowed van Helmont's lead in the development of ria and typhoid; these were considered merely varia-
iatrochemistry and its cousin, the iatrophysics cham- tions of inflammations. In part due to Broussais's
pioned by Giorgio Baglivi. The details of their sys- influence, between 1800 and 1880 ontology was
tems need not be explored here, neither do those of pushed into the remote reaches of medical thinking.
the eighteenth century, the "century of medical sys- In his turn, Broussais would yield to the laboratory
tems," featuring the theories of Friedrich Hoffmann, data produced by such physiologists as Francois
William Cullen, John Brown, and Benjamin Rush. Magendie and Claude Bernard, and even more deci-
Though their systems were ephemeral, the ideas sively to the apparently irrefutable proof that spe-
of these men retained one element of humoralism, cific microbes caused specific diseases.
which linked them to the nineteenth century. In As noted, an important conceptual emphasis of the
general, they held that disease was due to an nineteenth century was the idea of disease as devia-
imbalance - too much or too little of something, tion from normal. The idea existed as early as
whether stimuli, or spasm of the arteries, or nervous Plato's Timaeus and, of course, was basic to the

II.l. Concepts of Disease in the West 49
enduring humoral pathology. The word normal has a ence of developments, the ontological view returned
number of meanings, only two of which are germane at the turn of the twentieth century more powerfully
here. The first is the notion of conforming to a type, than ever before (Faber 1923).
to an ideal or an object of desire, and thus is a value Still, as always, the concept of disease could not be
judgment. The second refers to something that is reduced to black or white. New questions arose.
usual and that can be determined by enumeration What does one do with "Typhoid Mary" Mallon,
(King 1982). whose gallbladder teemed with typhoid bacillus but
The problem of normality as it confounded medi- caused Ms. Mallon no symptoms at all? The bacteri-
cal practice was not a matter of accepting the defini- ologist labeled this the "carrier state," which may
tions just given, but offixingthe ranges of normality have comforted science, but not society. Everywhere
and agreeing to the magnitude of departure from that Mary went typhoid was sure to follow. Was she
these ranges that should be labeled disease. The diseased? Certainly in the eyes of public health au-
promise of a practical solution to this age-old prob- thorities and society. But was she ill? Not to Mary
lem expanded in the nineteenth century with rap- herself.
idly developing methods of quantifying physiologi- To accommodate the increasing accuracy with
cal functions. which late-nineteenth-century scientists could de-
As the century progressed, these methods came to fine normality, practicing physicians had to reenlist
include a host of chemical determinations and tools, an old friend, impairment, or as they called the up-
such as the clinical thermometer, the X-ray, and a dated concept, impediment. Impediment implied
portable blood pressure apparatus. Their important that, before a departure from the still-imprecise
common denominator was an unprecedented objec- boundaries of normality could be labeled disease, a
tivity. As experience was added to these new tech- person must suffer physical or social impairment to
nologies, clinicians increasingly held that old and a significant degree.
new notions of what constitued disease must satisfy In the seventeenth century, Daniel Sennert had
the new methods of quantification. The whole pro- defined health and disease in terms of a person's
cess was reinforced in the last quarter of the nine- ability to perform in a natural way. In the eigh-
teenth century by the establishment of the concept teenth century, Hermann Boerhaave used the pres-
of specific etiology with the final vindication of the ence or absence of impairment in a strikingly simi-
germ theory of human disease. Not only were there lar fashion. Boerhaave also specifically anticipated
specific diseases, but each apparently had a specific one of the major problems of disease as impediment:
cause. No longer was the notion of disease as devia- Suffering the same objective physical deficiency, per-
tion from the normal burdened by such vague and sons differed in their subjective perception of impair-
unquantifiable etiologic agents as the four humors ment (King 1982). The quadriplegic confined to a
or nervous energy. wheelchair for years would feel little impairment
Now the agent responsible for the deviation from from an attack of polio involving his lower limbs. Yet
health in tuberculosis could be seen under the micro- a previously healthy person would experience para-
scope. It could be recovered from human sputum plegia as a catastrophic impediment.
grown in pure culture, injected into healthy guinea Beyond this, there were differences between what
pigs, where it produced a characteristic tissue reac- scientists considered unacceptable departures from
tion and clinical picture, recovered from the tubercu- normality and how these variations were consid-
lous animal, grown again in pure culture, and on ered by patients. Enumerating blood pressure read-
and on. More impressive proof that disease was real ings in thousands of persons led medical scientists
would be difficult to imagine. If not diseased, what to classify any determination above, say, 160 over
was one to call a cavity-ridden lung from which 95 as the disease hypertension. The problem was
identical pathogenic microbes could be recovered in that many patients with such elevations experi-
every instance? enced no impediment whatever - indeed, felt per-
Social forces added to the swing back to ontology. fectly well. What was the practitioner to do in this
The rise of hospital practice brought together many instance? He might argue that, even if these per-
patients whose diseases were, for practical purposes, sons were not impaired at the time, there was a
identical. Such devices as the ophthalmoscope and significant probability that they would be in the
laryngoscope gave impetus to specialization, which future. But, again, not always. Some persons car-
in turn gave practitioners exposure to a large num- ried their elevations without symptoms to the age
ber of similar clinical pictures. Out of this conflu- of 80 and died of unrelated causes.

Confounding all this was the question of what Conclusion
constituted significant impairment. The cardiac neu- Many health professionals continue to define dis-
rotic may be almost totally impaired by a fear of the ease and health simply in terms of each other. This
heart attack that claimed his father and grandfather school of thought contends that the two are on a
at early ages. He may refuse to get out of his easy spectrum, their extremes - serious disease and ex-
chair even though repeated thorough medical exami- cellent health-being at opposite ends. There is a
nation including sophisticated indicators of heart heuristic value in this viewpoint, but it poses seri-
disease have all been negative. In practical terms, ous problems in the real world of medical practice.
the hypertensive is diseased but not ill and the neu- The problems are related in part to medicine's abil-
rotic is ill but not diseased. Such a framework can ity to fix points on the spectrum of disease more
satisfy the needs of the practitioner, but it likely discretely than in the region of health. When pa-
leaves the philosopher unfulfilled. tients tell health professionals that they are "not
quite up to par" or are feeling "very sick," there are
Functional Disease often objective means for translating these expres-
The word function has been in English usage for sions into useful information. Beyond this, the con-
some 400 years. Earlier in medical terms it meant cept of illness has reasonably finite points on the
both the physiological activity of an organ and the spectrum. At its extreme, hospitalized patients are
psychological activity of the brain. This dual usage classified as serious, critical, very critical, and, ulti-
persisted into the 1830s, after which neurologists mately, deceased.
began classifying diseases as organic and functional, Even though the concept of relative health can be
the latter reserved for conditions in which current traced to the ancient Greeks, the spectrum of health
technology could not demonstrate structural alter- (as opposed to illness) has no such clear points or
ations (Trimble 1982). distinctions (Kudlien 1973). Patients may state that
Later in the century the concept of functional dis- they feel very good or are in excellent or perfect
ease spread to medicine generally. Between 1867 and health, but even if there is a reason to objectify their
1869 Adolf Kussmaul introduced a tube into the stom- assessments, there are no logical or technological
ach to relieve gastric dilation. He realized that, in tools for performing the task. If the examination and
addition to relieving the patient's symptoms, the tech- laboratory results are normal, a patient will gener-
nique could be used to study the function of the stom- ally be classified simply as healthy. Any qualifica-
ach as well. The idea was picked up by Ottomar Rosen- tion of a statement about health, such as "almost
bach, who used the term ventricular insufficiency to healthy," moves the patient to a point on the spec-
indicate a disproportion between the muscular re- trum that coincides with slightly impaired or ill. A
serve of the stomach and the physiological demands measure of the difficulties here is seen in one au-
on it. From this grew a vast range of tests designed to thor's suggestion, then rejection, of the idea that
determine the functional capacity of a bodily struc- health could be quantified by fixing a point on the
ture in health and disease. The model forms the basis scale and allowing health to be two standard devia-
of much of clinical laboratory medicine today. But tions from the norm (Caplan et al. 1981).
once again semantic confusion entered the scene as One reason for this state of affairs is that, from the
evidence that psychological activity as well as struc- standpoint of time, health is on a generally unidirec-
tural changes could produce profound disturbances in tional spectrum directed toward illness and death.
bodily function. Things are a bit more complicated than the old saw
After the work of Sigmund Freud, the word func- "We are all dying from the moment of conception,"
tional returned largely to its psychological meaning, but the element of truth in looking at human exis-
and today is used indiscriminately to mean dis- tence in this way may help us understand why
turbed function of the nervous system, or as a word health and disease are not au fond a tension or
for symptoms that do not fit prevailing diagnostic balance. True, for many years we may be in the
terms, as well as a euphemism for a variety of psychi- healthy range of the spectrum, but during this time,
atric disorders and the antithesis of what is meant our unidirectional genetic program (as best we now
by organic disease. When used without qualifica- understand it) is moving us inexorably toward dis-
tion, it can only lead to confusion. As was said of the ease. True, also, in a given illness episode, we may
sobriquet psychogenic, "it would be well... to give it reverse the direction and return to the spectrum of
decent burial, along with some of the fruitless contro- subjective and objective health, but this turnabout is
versies whose fire it has stoked" (Lewis 1972). temporary. The key element, time, remains unidirec-

II. 1. Concepts of Disease in the West 51
tional. Even as we move out of a given illness to The question: does disease exist or are there only sick
health, we are advancing toward death, much as we persons? is an abstract one and, in that form, does not
are both gaining and losing ground as we walk allow a meaningful answer. Disease is not simply either
against the direction of a moving sidewalk. the one or the other. Rather it will be thought of as the
In desperation someone once denned disease as circumstances require. The circumstances are repre-
something people go to doctors for. As simplistic as sented by the patient, the physician, the public health
man, the medical scientist, the pharmaceutical industry,
this seems, and as unsatisfying as it may be to medi- society at large, and last but not least the disease itself.
cal historians and philosophers, there is more than a For our thinking about disease is not only influenced by
germ of truth in the definition. Indeed, it reminds us internal and external factors, it is also determined by the
of the original meaning of our elusive term - dis- disease situation in which we find ourselves. (Temkin
ease. It covers situations in which the "patient" is 1977)
simply ill at ease, without regard to the finer nu-
ances of normality and impediment. Originally the Claude Bernard (1865) held that seeking the
word had no connection to pathological conditions, cause of life or the essence of disease was wasting
so that one might be said to be reluctant to dis-ease time in "pursuing a phantom. The words life, death,
oneself by attending a lecture on changing concepts health, disease, have no objective reality." Here Ber-
of disease (Garrison 1966). nard was only partly right. It is not a waste of time
The older definition of dis-ease applies to much of to struggle with these definitions. There is much to
what physicians do nowadays. The young graduate be gained if the task does nothing more than force
student is dis-eased by a pregnancy that threatens to society, and especially medical people, to think of the
disrupt her academic career. The ensuing elective consequences each time they use words to describe
abortion relieves her dis-ease, but it is difficult to fit disease and health. The process is a waste of time
a normal pregnancy into any system of illness- only if one enters into it with the exclusive goal of
disease considered so far. Some might contend that arriving at universal and timeless definitions.
the student suffers an impediment, and in career Robert P. Hudson
terms, that might be true. But we would seem to be
headed for even murkier depths if we translated into Bibliography
disease the impediment occasioned by a physiologi- Adams, Francis. 1886. The genuine works of Hippocrates,
cal alteration so profoundly normal that the species Vol. 1. New York.
would die out in its absence. Arnold, Thomas. 1952. The legacy of Islam. London.
Many encounters between patients and physi- Bernard, Claude. 1865. Introduction & I'itude de la
cians result from similar social and cultural pres- medecine experimentale. Paris.
sures. The middle-aged executive who resorts to plas- Boorse, Christopher. 1975. On the distinction between
tic surgery to eliminate his perfectly normal, and disease and illness. Philosophy and Public Affairs 5:
49-68.
even honorable, facial wrinkles is dis-eased, as are
Burns, Chester R. 1975. Diseases versus healths: Some
most who undergo cosmetic surgery. And, of course, legacies in the philosophies of modern medical sci-
the vast majority of persons seeking psychotherapy ence. In Evaluation and explanation in the biomedical
are dis-eased, in that it is basic to human existence sciences, ed. H. T. Engelhardt, Jr., and S. F. Spicker.
to experience anxiety, insecurity, loneliness, and Boston.
even depression. Certainly when physicians treat Caplan, Arthur L., H. Tristram Engelhardt, Jr., and
persons whose complaint is not only diagnosed as James J. McCartney. 1981. Concepts of health and
normal, but almost universal, dis-ease in the older disease: Interdisciplinary perspectives. Reading, Mass.
sense must be involved rather than disease as it has Clendening, Logan. 1931. Modern methods of treatment.
been analyzed in the ontological or physiological St. Louis, Mo.
meanings. Engel, George L. 1977. The need for a new medical model:
It is properly humbling to attempt to summarize A challenge for biomedicine. Science 196: 129-36.
an essay that one realizes has not succeeded com- Faber, Knud. 1923. Nosography in modern internal medi-
cine. New York.
pletely in its aim. Under these circumstances, the Garrison, Fielding H. 1929. An introduction to the history
temptation is to suggest that the question being of medicine. Philadelphia.
asked is not a proper one in the sense that it cannot 1966. Contributions to the history of medicine. New York.
be answered by logic or experiment. Indeed, one of Hudson, Robert P. 1966. The concept of disease. Annals of
the more cogent summaries of our conundrum was Internal Medicine 65: 595-601.
expressed in precisely these terms by Owsei Temkin: Jones, W. H. S. 1952. Hippocrates, Vol. 2. London.

Jowett, Benjamin, trans. 1892. The dialogues ofPlato, Vol.
1. New York. II.2
King, Lester S. 1982. Medical thinking: A historical pref-
ace. Princeton, N.J.
Concepts of Disease in East
Kudlien, Fridolf. 1973. The old Greek concept of "relative" Asia
health. Journal of the History of the Behavioral Sci-
ences 9: 53-9.
Lewis, Aubrey, 1972. "Psychogenic": A word and its muta- In the inscriptions that record the divinations of
tions. Psychological Medicine 2: 209—15. Shang dynasty China (eighteenth to eleventh centu-
Lush, Brandon, ed. 1961. Concepts of medicine: A collec- ries B.C.), we find a number of diagnostic queries
tion on aspects of medicine. New York.
like this: "Divining this tooth affliction. Should we
Meador, Clifton K. 1965. The art and science of non-
disease. New England Journal of Medicine 272: 92-5. hold a festival for Fuyi?" Fuyi refers to a Shang
Niebyl, Peter H. 1971. Sennert, van Helmont, and medi- ancestor, and the concern about a propitiatory festi-
cal ontology. Bulletin of the History of Medicine 45: val reflects the belief, frequently voiced in the ora-
115-37. cles, that sickness arises from the anger and envy
Pagel, Walter. 1972. Van Helmont's concept of disease — to of ancestors toward their descendants (Hu 1944;
be or not to be? The influence of Paracelsus. Bulletin Miyashita 1959). If the welfare of the dead de-
of the History of Medicine 46: 419-54. pended on the rituals of the living, the resentments
Rapaport, Elliot. 1982. Prevention of recurrent sudden of the dead were something to which the living
death. New England Journal ofMedicine 306:1359-60. remained ceaselessly vulnerable.
Riese, Walther. 1953. The conception of disease, its history, Disease thus first appears in China embodied in
its versions, and its nature. New York. dangerous others, as a menace from without. After
Risse, Guenter B. 1979. Epidemics and medicine: The in- the Shang dynasty, the focus of concern would
fluence of disease on medical thought and practice.
Bulletin of the History of Medicine 53: 505-19.
broaden and shift from disgruntled ancestors to para-
Sauvages, Francois Boissier de. 1768. Nosologia me- sites and poisons, demons and witchcraft spells. But
thodica sistens morborum classes. Amsterdam. whomever or whatever the Chinese accused of inspir-
Sigerist, Henry E. 1971. The great doctors: A biographical ing sickness, the defining feature of the earliest con-
history of medicine. New York. ceptions of disease was their independence from a
Sundstrom, Per. 1987. Icons of disease. Kristianstads conception of the body. In other words, the peculiari-
Boktryckeri. ties of an individual's somatic condition were no
Sydenham, Thomas. 1848. The works of Thomas Syden- more relevant to understanding a fever or a tooth-
ham, M.D., Vol. 1, ed. R. G. Latham. London. ache than they were for explaining why one's crops
Taylor, F. Kraupl. 1979. The concepts of illness, disease were destroyed in a storm. The fact that an affliction
and morbus. London. happened to attack the body was incidental. The
Temkin, Owsei. 1977. The double face of Janus and other vengeful spirits that brought sickness could just as
essays in the history of medicine. Baltimore. easily have inflicted drought and famine.
Trimble, Michael R. 1982. Functional diseases. British
Medical Journal 285: 1768-70. This accounts in part for why a collection of cures
such as the Wushier bing fang (Recipes for fifty-two
ailments) of the late third century B.C. tells us so
much, on the one hand, about noxious demons and
the techniques for exorcizing them and teaches us so
little, on the other hand, about the afflicted body
itself (Harper 1982). For whether a shaman literally
beat the disease out of the patient or appealed to
benevolent divinities for assistance, whether de-
mons were coaxed out with magical formulas or
transferred sympathetically to other objects, the
treatment of disease, like the diagnosis, concen-
trated on agents alien to the self. The body merely
provided the stage for the drama of sickness; it was
not an actor.
This was a remarkably influential vision of dis-
ease. For instance, a dictionary of the later Han

II.2. Concepts of Disease in East Asia 53
dynasty (25-220), the Shiming, glosses yi (epidemic being compelled to drink a cup of wine in which he
disease) as yi (corvee), explaining that diseases thinks he sees a snake. Only when he is made to
were the corvee imposed on humans by demons. realize that what he saw in the wine was merely the
From the Sui (581-618) through the Yuan (1279- reflection of an archer's bow hanging on the wall
1368) dynasties, professors and masters of exor- does he recover (Li 1960). The close identification of
cistic rituals and incantations (zhoujin) constituted body and self went hand in hand with a subtle aware-
a part of the official medical bureaucracy, alongside ness of the many ways in which human beings could
professors of such other medical specialties as acu- make themselves sick.
puncture and massage (Kano 1987). At a more popu- According to the most devoted and influential stu-
lar level, the folklore of medieval Japan abounds in dents of the body, however, the real essence of dis-
accounts of beguiling fox spirits that seduce or pos- ease was depletion. The experts of yangsheng, or
sess young men and women and cause them to "the cultivation of life," envisaged the body as the
waste away, go mad, or die (Veith 1965). And even container of a precious and finite vitality. If properly
today, a Korean shaman will acknowledge in his conserved, this vitality could sustain one for a hun-
healing chant "ghosts of the drowned, ghosts who dred years, free of all affliction, and free even of the
were shot. . . maiden ghosts, bachelor ghosts" (Ken- ravages of age. True health found its proof in ever-
dall 1985). youthful longevity. If most people succumbed to dis-
In the evolution of East Asian disease conceptions, abilities and senescence, and died before reaching
therefore, the imagination of menacing outsiders rep- their hundredth year, if most, in short, were sick, it
resents not a transient stage of superstitions, which was because they depleted the body by squandering
the rise of philosophy would supersede, but a the- this vitality.
matic pole to which reflection on sickness would re- Ghosts and malevolent spirits were not involved.
peatedly return. At the same time, by the late Zhou Yet the body was still surrounded by enemies. Early
(770-403 B.C.) and Warring States (403-221 B.C.) historical and philosophical texts refer frequently to
periods, suspicions of supernatural mischief were al- individuals struck down by wind or cold, rain or
ready slipping from the intellectual mainstream. In scorching heat. Wind and cold especially loomed
the philosophical ferment of these periods, a new large as noxious forces. To winds fell the blame for
conception of disease was emerging - one that would afflictions ranging from sneezing and headaches to
seek the origins of sickness not in the whims of some paralysis and madness, and proverbial wisdom
dangerous other, but in the desires of the self. would soon have it that "the myriad ailments all
arise from wind." As for cold, the study of the fever-
In the late Zhou and Warring States periods, disease ish disorders to which it gave rise would eventually
became a reflection of somatic condition, and so- become the subject of the most influential treatise of
matic condition, a reflection of the self. For the Con- the pharmacological tradition, Zhang Ji's Shanghan
fucian and Taoist philosophers of this era, the body lun (Treatise on cold afflictions), written around the
was the dynamic product of experience, a reality end of the second century. Wind, cold, and other
continually shaped and reshaped by how one was meteorological elements thus replaced the demons
living and had lived. Shen, "the body," was the same and spirits of shamanistic medicine as embodiments
shen emphasized by the ideals of xiushen, "self- of the dangerous outsider. Like demons and spirits,
cultivation," and deshen, "self-possession": It was they were objective pathogens that penetrated and
the embodied self, a lifetime of decisions and indeci- roamed throughout the body; and like demons and
sions made manifest. spirits, they figured both as the cause of disease and
The failings of the body, therefore, were insepara- as the disease itself.
ble from failures of self-mastery. Sickness in this But wind and cold differed from demons and spir-
view had little to do with ancestral ire or demonic its in one critical respect: Their pathogenic char-
cruelty. It arose principally from within, from im- acter was contingent on the condition of the body.
moderation and carelessness, from gluttony and They would invade only when the body was vulnera-
overexertion, from protracted grief and explosive an- ble, or more precisely, depleted. As the Lingshu of
ger, and sometimes from the mere imagination of the Han dynasty later explained: "Unless there is
dangers. One man falls ill after experiencing a terri- depletion, wind, rain, cold and heat cannot, by them-
fying dream and is cured only when a clever physi- selves, injure a person. A person who suddenly en-
cian suggests that the dream was one reserved for counters brisk winds or violent rains and yet does
future kings. Another suffers severe cramps after not become ill is a person without depletion" (Chen

1977). In a body brimming with vitality there was no of the vital spirit," and when the eyes and ears
room for noxious influences to enter. dwelled on pleasures of sight and sound, this vital
The depletion of vitality was thus doubly noxious. spirit streamed outward, depleting the body and in-
It left one vulnerable to the virulence of wind, cold, viting affliction (Liu 1965). This movement of the
and other climatic pathogens. More immediately, spirit toward the desired object was the very essence
however, depletion was itself a form of sickness, a of desire. Literally, as well as figuratively, desire
diminution of possibilities: It meant that even with- entailed a loss of self: Physical depletion and lapses
out the intrusion of alien influences the senses and in self-possession were just different views of the
limbs that should be strong and unimpaired until unique phenomenon of sickness. Conversely, somatic
age 100 might already be weak or failing at age 50 integrity and emotional self-mastery coalesced in
or 60. the notion of health. As the philosopher Han Fei of
The leitmotif of yangsheng reflection on the body, the early third century B.C. summarized it: "When
therefore, was bao, "preservation" — "preserving the the spirit does not flow outward, then the body is
body" (bao shen), "preserving the vital essence" complete. When the body is complete, it is called
(bao zhen), "preserving life" (bao sheng). To main- possessed. Possessed refers to self-possessed" (Li
tain the body intact, to protect it against attacks 1960).
from without by carefully conserving and contain- The secret of health thus lay in a mind devoid of
ing vitality within — such was the heart of the "cul- desire. Such was the lesson of the "cultivation of life"
tivation of life." But preservation was difficult. A in the Warring States period; and such also was the
considerable disparity separated the attentions re- lesson of medical theory as it first crystallized in the
quired to preserve vitality and the ease with which classical treatises of the Han dynasty (206 B.C. to
it slipped away, for preservation demanded concen- A.D. 220). But in the latter case the meaning of the
tration whereas the outflow of vitality often accom- lesson was more complex, because the meaning of
panied the experience of pleasure. If the depletion disease was more complex.
of vitality constituted the root of disease, the roots
of depletion lay in desire. Classical medicine yoked together what were in fact
This was most apparent in sexual intercourse. Al- two conflicting images of the body and its afflictions.
ready in the sixth century B.C., we find a physician On the one hand, the key theoretical treatises of the
tracing the illness of the duke of Jin to his fre- Han dynasty - the Huangdi neijing, consisting of
quentation of concubines (Li 1960). Later Chinese the Suwen and the Lingshu, and the Nanjing-
and Japanese writings on regimen would even spec- perpetuated yangsheng intuitions of the vital self
ify the precise number of times per month or year to warding off the dangers of the world around it. Body
which intercourse should be limited (Kaibara 1974). was clearly separated from nonbody by the protec-
On few points would opinion be as unanimous: Se- tive barrier of the skin, which both sealed in vitality
men was the distilled essence of life, and there could and kept out noxious winds and cold. The two key
be no surer path to debility and early death than to terms of etiologic analysis, depletion and repletion,
exhaust one's supply in frequent intercourse. Al- preserved in their definitions the distinction be-
though moral strictures against pleasure per se were tween what is healthy and proper to the body (zheng)
rare, philosophers and physicians constantly warned and what is pathogenic and alien to it (xie): Deple-
against the physical drain of sexual indulgence. It is tion (xu) was a "deficiency in the body's vitality
revealing that the response in classical China to the (zhengqi)," repletion (shi), an "excess of noxious in-
temptations of the flesh was not mortification, but fluences (xieqi)."
rather the art of the bedroom (fangzhong) — psycho- Yet already in these definitions a new and alterna-
physical techniques centered around the prevention tive conception of disease was clearly emerging for
of ejaculation and the "recycling" of semen within the main distinction between depletion and reple-
the body (Van Gulik 1974). tion was not the opposition of inner and outer, but
The expenditure of vital essence in intercourse rather the complementary nature of deficiency and
was, however, just one form of the intertwining of excess. Subtly, but surely, the earlier rhetoric of de-
desire and depletion. Vitality could slip away from fense and attack was giving way to the new logic of
all the orifices: It flowed out of the eyes as one balance and compensation; fears of threatening out-
became absorbed in beautiful sights, and from ears siders were being supplemented, and to an extent
as one lost oneself in rapturous harmonies. The ori- supplanted, by a conception of disease as unequal
fices were, the Huainan zi explained, "the windows distribution.

In the schemes that articulated the emerging etiol- foods, appropriate activities, and even appropriate
ogy of imbalance (the dialectic of yin and yang and feelings. For example, in spring, the Huangdi neijing
the five-phase cycle [wuxing] of wood, fire, earth, advised:
metal, and water), the dichotomy of body and
nonbody had little significance. Cosmic events and The myriad things nourish, engendered by heaven and
somatic eventsfiguredon the same plane: Deep grief earth together. Going to sleep at nightfall one should get
up early and stride leisurely in the garden. Letting down
could cause the repletion of yin and the depletion of one's hair and putting oneself at ease, one should give rise
yang, but so too could winter cold; a state of replete to ambitions. Engender and do not kill. Give and do not
wood and depleted earth might involve a hyperac- take away. Reward and do not punish. This is what is
tive liver (a wood organ), but it might also stem from appropriate to the spirit of spring. (Chen 1977)
easterly winds (also associated with wood). More-
over, both body and nonbody were subject to the Failure to follow the spirit of the season, motivations
same universal law of rhythmic change, the alterna- and actions out of phase with cosmic transformation,
tion of hot (yang) and cold (yin), the cycle of spring resulted in deficiencies and excesses of yin and yang
(wood), summer (fire), fall (metal), and winter (wa- and thefivephases, that is, in disease. The principle
ter). With indefinite and infinitely permeable bound- governing health and sickness was thus simple:
aries, the body was seamlessly fused to a world cease- Those who followed theflow(xun) flourished; those
lessly transforming itself (Chiu 1986). who opposed it, fell ill or died.
Disease in the Han dynasty became above all a As part of the cosmos, human beings were natu-
seasonal phenomenon. Earlier observers had al- rally attuned to seasonal rhythms. Yet this at-
ready recognized that different afflictions tended to tunement, like the intact body prized by proponents
characterize different seasons. The Zhou li (Rituals of yangsheng, was an ideal frequently compromised
of the Zhou dynasty) observed, for instance, that in actuality by unruly passions. The Lushi chunqiu
headaches were prevalent in spring, whereas sum- explained: "What fosters life is following the flow
mer was characterized by the spread of scabieslike (xun); but what causes life to depart from the flow
itching, autumn by malarial and other fevers, and (bu xun) is desire" (Li 1960). Desire here referred not
winter by respiratory disorders (Lu and Needham to the depletion of vitality, but to disruptions in the
1967). Also widely noted was the fact that the same smooth and balanced circulation of influences, to
climatic pathogens of wind and cold had different rigid attachments that resisted cosmic rhythms, and
effects in different seasons. Unseasonal weather, to impulses that deviated from the directions of sea-
such as cold in summer, posed special dangers and sonal change. If desire in the etiology of depletion
often engendered epidemics. implied a partial loss of self, desire in the etiology of
The Han medical classics, however, went further imbalance entailed forgetting that the self was but
and situated the seasonality of disease in the sea- one part of a much larger, ever-evolving world.
sonality of the human body itself. According to the The cosmic dimensions of Han medical thought
Nanjing, the most vigorous organ in spring should mirrored the expansive ambitions of the first great
be the liver; in summer the heart should dominate; age of universal empire. In the same way that the
in autumn the lungs; and in winter the kidneys. In political vision of universal empire would survive
spring the pulse should begin to rise, gently, but the rise and fall of subsequent dynasties, so the
growing like the first primaveral shoots; in summer vision of the body as a seasonal microcosm would
it should be strong and overflowing; in autumn it continue, along with yangsheng ideals of somatic
should be slower and more constricted; and in winter integrity, to define medical orthodoxy for nearly two
it should lie deep as if in hibernation. To the discern- millennia. Yet the views of orthodox physicians did
ing physician, each season exhibited its distinct not by any means represent the views of all. In the
physiology, and it was only with respect to this sea- chaos of the disintegrating Han empire, there
sonal physiology that the standards separating emerged an alternative approach to illness that had
health from sickness could be defined. The same a far greater and immediate impact on the popular
signs, considered perfectly normal for one season, imagination - an approach concerned not with the
might certify disease in another. cosmic systems, but with individual morality and its
Health, therefore, was a state of dynamic at- consequences.
tunement in which the directions of an individual's
energies paralleled the ebb andflowof the cosmos as Intimations of sickness as punishment can be traced
a whole. For every season there were appropriate as far back as Shang fears of ancestral ire, and the

moral failings of more than one emperor in the early 907), this belief posited the existence of three small
Han dynasty (206 B.C. to A.D. 8) would be blamed creatures {shi) who inhabited various regions of the
later for the epidemics that devastated their people. body and who recorded all the individual's evil yearn-
But especially in the late Han dynasty (25-220), ings and deeds. Then, once every 60 days, on the
with the rise of religious Taoism, and the Six Dynas- gengshen night of the astrological cycle, these shi
ties (222-589) period, with the influx of Buddhism, would leave the body while the person slept, and fly
the equation of sickness and personal transgression up into heaven. There they would report to the heav-
came to pervade popular consciousness (Kano 1987). enly emperor (shangdi) on the wrongdoings that
With the diffusion of these religions, reflection on they had witnessed, and the heavenly emperor
disease assumed an introspective aspect as religious would mete out punishment in the form of disease
healing turned increasingly toward the scrutiny of and shortened life. It was thus imperative for all
personal memory and conscience. who hoped to escape illness and live long lives to
Zhang Lu, leader of a Taoist rebellion in the early somehow restrain or purge these shi.
third century, thus required the ailing first to spend This was the origin of the custom whereby entire
time in a "chamber of silence," where they explored communities gathered together on gengshen night
their consciences for the possible transgressions un- and stayed up until dawn to prevent the shi from
derlying their afflictions. Disease was the result of escaping the body. The custom had many variants:
past sins, and recovery required the confession of Some villages would spend the night reciting Lao
these sins (Unschuld 1985). The Buddhist concept of Zi's Daode jing; others would revel in drink and
karmic disease (yebing) also traced sickness (bing) to merriment; and in eighth-century Japan the impor-
an individual's past actions (Sanskrit, karma; Chi- tation of the thxee-shi theory gave Heian aristocrats
nese, ye). Karmic analysis diverged somewhat from an excuse for all-night music and poetry competi-
Taoist intuitions in that these actions might go back tions. Although some philosophers, like Liu Zong-
many reincarnations, beyond conscious recall and yuan, denounced the idea of the shi as superstition,
beyond confession — thus explaining such puzzling gengshen practices flourished and spread through-
phenomena as congenital diseases and the afflic- out East Asia, surviving in rural areas well into the
tions of the virtuous. But in the popular understand- twentieth century (Kubo 1961).
ing, Buddhist precepts of karmic consequence and The popularity of three-s/ii etiology derived in no
Taoist teachings of sickness and sin tended to co- small part from the fact that it united many streams
alesce into the same basic lessons: Good actions are of East Asian reflection on disease. Though the three
rewarded, and misbehavior eventually punished; shi were originally conceived as small humanoids,
the ailments of today have their origins in the wrong- they quickly became assimilated into traditions go-
doings of yesterday. ing back to the Shang about the infestation of the
Folk religion frequently framed these lessons in a body by parasites and poisonous insects, and the
divine bureaucracy. Unlike the often-unpredictable same drugs were used against them as were habitu-
ancestral spirits of the Shang, the divinities of Han ally used to purge parasites. The notion that they
and Six Dynasties religion frequently resembled gov- would betray one only on particular nights fed, of
ernment officials, keeping track of a moral ledger of course, into medicoastrological associations of health
good and evil deeds (Eberhard 1967). For each trans- and cosmic rhythm. And in their role as keepers of the
gression, appropriate afflictions were imposed, and moral ledger, the three shi internalized the account-
days were detracted from one's allotted lifetime; ing of merits and demerits that linked sickness to sin.
meritorious acts, conversely, earned relief from sick- Finally, the theory of the three shi reaffirmed the
ness, and the restoration of longevity. The bureau- conviction that sickness was somehow tied to de-
cratic regularity of this scheme even allowed the sire. According to some accounts, it was the pres-
early fourth-century Taoist Ge Hong to specify the ence of these shi that explained the pullulation of
number of days subtracted from one's life for each desires in the human heart; other accounts, con-
level of demerit. versely, stressed how killing off desire was the only
The idea of moral accounting also formed the core way the shi could be exterminated. But all accounts
of what was perhaps the most intriguing conception of the shi and their dangers underlined their inti-
of disease in medieval East Asia, namely the theory mate connection to human beings as creatures of
of the body's three "corpses," or shi. Originating in passion. Sickness and desire, which had, with differ-
China no later than the early fourth century and ent implications, been tied together by the yang-
attaining its mature form by the Tang dynasty (618- sheng thinkers of the Warring States period and by

the medical classics of the Han dynasty, were again Whereas in Han medicine the marriage of the
united in medieval religion. etiology of imbalance with the etiology of depletion
had been at best an uneasy alliance, their strategic
The physicians of the Song (960-1126) and Yuan extensions in Song and Yuan medicine often blended
(1279-1368) dynasties inherited a tradition of medi- smoothly together. Thus, desire, without entirely los-
cine that knew disease under two guises. On the one ing its long-standing associations with the depleting
hand, there was the disease of theory, sickness as outflow of vitality, was recast as yang fire. Zhu
elucidated by the complementarity of somatic deple- Zhenheng's identification of the crux of vulnerabil-
tion and alien intrusion and by the system of yin and ity in excess yang and deficient yin referred, among
yang and the five phases. On the other hand, there other things, to the propensity of emotional agita-
was disease as it had been observed and experienced tion (yang) to predominate over rest and collected
by physicians and patients over the course of a mil- self-possession (yin). For him it was especially the
lennium. As evidenced by the sprawling seventh- inner feverishness (fire) generated by the tumult of
century nosological compendium of Chao Yuanfang, passions that dispersed and dried up the moist vital
the Zhubing yuanhou lun (On the origins and symp- essence (water) and gave rise to depletion. Similarly,
toms of all diseases), this tradition was protean and Li Gao, who insisted on sound digestion as the pivot
unwieldy, with seemingly limitless combinations of of sickness and health, analyzed the critical impact
ever-diverse symptoms (Chao 1955). A great dis- of emotional unrest in terms of the effect of fire
tance separated the perspicuity of theory from the (passions) on the earth-associated organs of the
dense tangle of experience. The key theme of Song spleen and stomach. By translating in this way the
and Yuan reflection on disease was the quest to analysis of depletion into the schemes of yin and
reduce that distance. yang and the five phases, these physicians framed
The quest translated into two basic strategies. the understanding of disease in a single comprehen-
One strategy aimed at refining the classical etiology sive and integrated system.
of depletion. Although recognizing that a complex The new technology of printing ensured the broad
variety of factors converged in the genesis of disease, dissemination of Song and Yuan medical treatises,
many physicians from the Song and Yuan periods and these were assiduously studied not only by Chi-
onward nonetheless sought to isolate a single crux of nese physicians in the Ming and Qing dynasties, but
vulnerability. Li Gao, for instance, argued in the also by their counterparts in Yi dynasty Korea
thirteenth century that "the hundred illnessess all (1392-1910) and Tokugawa Japan (1600-1868)
arise from [disorders of] the spleen and stomach" (Fujikawa 1980). No small part of the persisting
(Beijing zhonqui xueyuan 1978). By contrast, his myth of Chinese medicine as based on a timeless,
contemporary Wang Haogu sought the predisposing monolithic theory is due to the resultant identifica-
origins of sickness in depleted kidneys (conceived as tion, throughout East Asia, of medicine with the
the repository of semen), whereas Zhu Zhenheng of systematizing tradition established by Song and
the fourteenth century focused on the tendency of Yuan physicians.
human beings to experience "a superfluity of the In reality, of course, Song and Yuan medicine it-
yang element, and a deficiency of the yin" (Beijing self comprised many diverging viewpoints, and sub-
zhonqui xueyuan). Later, in the Ming (1368-1662) sequent periods witnessed a widening spectrum of
and Qing (1662-1912) dynasties, still other physi- ideas. Zhang Congzheng at the turn of the thir-
cians would blame the depletion of a variously de- teenth century, for instance, rejected the prevailing
fined organ known as the "gate of life" (mingmen) focus on inner depletion and attunement and urged
(Beijing zhongyi xueyuan 1978). that intrusive attack was the primary fact of dis-
The other strategy sought to extend the classical ease. His nosology, accordingly, recognized six basic
etiology of imbalance, to articulate exhaustively the kinds of disease, corresponding to the six climatic
paradigms of yin and yang and the five phases so pathogens of wind, cold,fire,humidity, dryness, and
that they might provide a more adequate language heat. Later, in extensive investigations into epidem-
for describing the rich variability of symptoms and ics in the Qing dynasty, Wu Youxing, born just be-
syndromes. This produced a highly abstract perspec- fore the middle of the seventh century, and Wu Tang,
tive, which translated the concrete pathogens of born a century later, probed even deeper into extrin-
wind, cold, and heat into the transparent logic of sic causation. They distinguished between common-
dialectical balance and seasonal rhythms; but it also place infiltrations of cold and other climatic agents,
produced a more unified approach to disease. which occurred through the pores, and epidemic fi-

ery afflictions (wenbing), which entered through the manifest a distinct preference for understanding dis-
mouth and nose (Beijing zhongyi xueyan 1978). eases in terms of climatic and somatic etiologies -
Beyond China's borders, there were outright crit- chilling wind, change of seasons, sagging stomach,
ics as well as devoted followers of this systemizing acidic blood, imbalance in the autonomic nervous
tradition. In the late seventeenth and eighteenth system, or simply weak nerves (Kleinman 1980;
centuries, the Ancient Practice school (kohoha) of Ohnuki-Tierney 1984).
Japanese medicine rallied specifically around the Such concepts as the autonomic nervous system
overthrow of the Song-Yuan spirit of system. It in- and blood pH derive, of course, from modern science,
spired some radical conceptions of disease, such as but the general attachment to somatic symptoms
Yoshimasu Todo's eighteenth-century theory that all and analyses surely goes back thousands of years.
disease arises from one poison and Goto Konzan's Desires and emotions figured centrally in tradi-
earlier notion that all disease results from stagna- tional East Asian conceptions of disease, but they
tion in the flow of vital energy (Fujikawa 1980). were never based in some disembodied psyche. They
Although these theories themselves did not have a were invariably intertwined with somatic experi-
lasting impact, the critical ferment they represented ence. Thus anger, for Han physicians, entailed the
inspired physicians and scholars in late-eighteenth- rise of the vital spirit, fear the sinking of the spirit,
century Japan to undertake the first serious studies joy its relaxation, and grief its dissipation. The
of Western medicine in East Asia. yangsheng thinkers before them saw self-possessed
freedom from desire and the physical containment of
Students of medicine and health care in contempo- vitality as one and the same reality. If, as anthropolo-
rary East Asia have stressed the persisting plurality gists report, patients in East Asia manifest an un-
of disease conceptions (Kleinman et at. 1975; Leslie usual sensitivity to and interest in the body, this
1976). As in the past, the advent of new approaches sensitivity and interest are perhaps related to a long
to disease, and in particular the introduction of ideas cultural tradition that conceived of the body as the
from the West, has led not to the abandonment of dynamic product of lived life, that is, as the embod-
traditional assumptions, but simply to a more com- ied self.
plex skein of beliefs and practices. Shigehisa Kuriyama
Some aspects of medical pluralism are obvious. A
Korean healer who specializes in exorcizing noxious Bibliography
spirits may also refer patients to acupuncturists and Beijing zhongyi xueyuan (Peking Academy for Chinese
hospitals (Kendall 1985). Acupuncture texts pub- Medicine). 1978. Zhongyi gejia xueshuo jiangyi. Hong
lished in Taiwan today habitually refer to both the Kong.
nosology of cosmopolitan medicine and the language Chao Yuanfang. 1955. Zhubing yuanhou lun. Beijing.
of yin and yang. Chen Menglei. 1977. Gujin tushujicheng, Vol. 42. Taipei.
Chiu, Martha Li. 1986. Mind, body, and illness in a Chi-
There are also subtler forms of syncretism. The
nese medical tradition. Ph.D. dissertation, Harvard
ostracism of tuberculosis patients and their families University.
in early-twentieth-century Japan, for example, com- Eberhard, Wolfram. 1967. Guilt and sin in traditional
bined a vague understanding of modern theories of China. Berkeley and Los Angeles.
infection and heredity with traditional notions of Fujikawa Yu. 1980. Fujikawa Yu chosakushu, Vol. 1. Kyoto.
contagious pollution and sickness as sin (Namihira Harper, Donald. 1982. The Wu shih erh ping fang: Transla-
1984; Johnston 1987). But perhaps the most intrigu- tion and prolegomena. Ph.D. dissertation, University
ing manifestations of the ever-present past have to of California, Berkeley.
do with the actual experience of illness. Hu Houxuan. 1944. Yinren jibing kao. In Jiaguxue
Medical anthropologists have observed that pa- Shangshi luncong. Chengdu.
tients in East Asia tend to experience all illness as Johnston, William. 1987. Disease, medicine, and the state:
A social history of tuberculosis in Japan, 1850-1950.
illnesses of the body. That is, whereas a North Ameri-
Ph.D. dissertation, Harvard University.
can patient might complain principally of anxiety or Kaibara Ekiken. 1974. Yojokun: Japanese secret of good
depression, a Chinese patient will complain rather health, trans. Kunihiro Masao. Tokyo.
of palpitations, digestive disorders, or suffocating Kano Yoshimitsu. 1987. Chugoku igaku no tanjo. Tokyo.
sensations in the chest (men), focusing on physical Kendall, Laurel. 1985. Shamans, housewives, and other
rather than emotional symptoms. Moreover, rather restless spirits: Women in Korean ritual life. Honolulu.
than seeking psychological explanations such as Kleinman, Arthur. 1980. Patients and healers in the con-
stress or frustration, Chinese and Japanese patients text of culture. Berkeley and Los Angeles.

II.3. Concepts of Mental Illness in the West 59
Kleinman, Arthur, et al. eds. 1975. Medicine in Chinese contemporary psychiatric thought. Some have ar-
cultures: Comparative studies of health care in Chi- gued that if the myriad types of disorders bedeviling
nese and other societies. Washington, D.C. humankind were ranked by the net misery and inca-
Kubo Noritada. 1961. Koshin shinko no kenkyu. Tokyo. pacitation they caused, we would discover that psy-
Leslie, Charles, ed. 1976. Asian medical systems: A com- chiatry captures a larger share of human morbidity
parative study. Berkeley and Los Angeles. than does any other medical specialty. It seems
Li Fang, ed. 1960. Taiping youlan, Vol. 4. Shanghai.
ironic - if not tragic - that a clinical field of such
Liu An. 1965. Huainan zi. In Sibu beiyao, Vol. 78. Taipei.
Lu Gwei-djen and Joseph Needham. 1967. Records of dis-
magnitude is at the same time distinguished among
eases in ancient China. In Diseases in antiquity, ed. D. its peers by a conspicuous lack of therapeutic and
Brothwell and A. T. Sandison, 222-37. Springfield, 111. philosophical consensus. That the discipline lacks a
Miyashita Saburo. 1959. Chugoku kodai no shippeikan to set of internal standards by which to differentiate
ryoho. Tohogakuho 30: 227-52. unequivocally the correct theory from the false, or
Namihira Emiko. 1984. Byoki to chiryo no bunka jinrui the efficacious therapy from the useless, is an open
gaku. Tokyo. secret. In a sense, if the disputing psychiatric camps
Ohnuki-Tierney, Emiko. 1984. Illness and culture in con- are all equally able to claim truth, then none is
temporary Japan. New York. entitled to it. Consequently, there exists not one
Parish, Lawrence Charles, and Sheila Gail. 1967. Ancient psychiatry, but many psychiatries, a simple fact that
Korean medicine. Transactions and Studies of the Col- alone has had enormous ramifications for the field's
lege of Physicians of Philadelphia 38: 161-7.
comparatively low medical status and conceptual
Unschuld, Paul. 1985. Medicine in China: A history of
ideas. Berkeley and Los Angeles.
disarray. Everywhere recognized and yet nowhere
Van Gulik, R. H. 1974. Sexual life in ancient China. Leiden. fully understood, insanity continues to challenge us
Veith, Ilza. 1965. Hysteria: The history ofa disease. Chicago. as a problem that demands attention and yet defies
Yu Yunxiu. 1972. Gudai jibing minghou shuyi. Taipei. control.
Situated so uneasily within the medical domain,
the subject of mental illness poses a challenge of
singular difficulty for the geographer and historian
of human disease. One typically locates disease in
II.3 place and time by first asking an array of standard
questions: What are its immediate and predisposing
Concepts of Mental Illness in causes? How does it normally progress? Upon whom
the West is it most likely to befall? For example, in this vol-
ume any of a number of essays on infectious diseases
We are not ourselves when nature, being oppressed, (cholera, smallpox, plague) may begin with a tightly
commands the mind to suffer with the body.
drawn narrative of how the disease unfolds in an
Shakespeare, King Lear
untreated victim, knowable to the patient or casual
Mental disease refers, at present, to disorders of observer by conspicuous signs and symptoms and to
perception, cognition, emotion, and behavior. The the medical investigator by the additional involve-
disorder may be mild or severe, acute or chronic, and ment of organ or systemic changes. We learn about
may be attributed to a defect of mind or body or of the life course of the offending infectious agent and
some unknown combination of the two. A diagnosis about the mechanisms by which it wreaks physiologi-
of mental illness is the judgment that an individual cal havoc.
is impaired in his or her capacity to think, feel, or Once a clinical portrait and a chain of causation
relate to others. In mild cases, the impairment may have been well established, it is possible to position
intrude on a person's ability to gain satisfaction a disease on the social as well as geographic land-
from meeting the challenges of everyday life. In se- scape; its prevalence by age, sex, social class, and
vere instances, an individual may be thought so nation may be determined with some justification.
dangerous or incompetent that sequestration within At the same time, the work of the medical historian
a psychiatric facility is necessary, with a resulting comes into focus. Paradoxically, as the present be-
loss of rights normally granted to citizens. comes clearer, so does the past. Using our clinicobio-
logical model as a guide, we can search the historical
The Problem of Mental Illness record for answers to additional questions: When did
The simple title of this section belies the extraordi- the disease first appear and how did it migrate?
nary scope, complexity, and controversial state of Over the centuries, how wide has been its trail of

morbidity? We can also reconstruct the story of when filter, then, do we apply to the past? Do we look for
and how medicine, in fits and starts, first isolated anxiety disorders as interpreted by the behaviorist,
the entity as a specific disease and then unraveled neuropharmacologist, or psychoanalyst?
its pathogenic mechanisms. Indeed, endeavors such Current philosophical critics of psychiatry, such as
as this volume are indicative of the high confidence Thomas Szasz, advise us to abandon the effort. Szasz
we have that our current nosology (fashioned by contends that, strictly speaking, mental illnesses
such triumphs as bacteriology and molecular biol- are not valid medical entities and thus their stories
ogy) does, in fact, mirror the contours of biological have no place in any compendium on human disease.
reality. We are certain that typhus and cancer are Madness exists, to be sure, but it is a quality of
not the same disease, and thus tell their stories personhood, not of body or disease. Problems of liv-
separately. ing are manifold and serious, but without positive
Contemporary psychiatry, however, provides us evidence that an individual's condition is due to a
with no map of comparable stability or clarity. When physiological cause, the physician has no business
the standard array of aforementioned questions are intervening. Unless psychiatrists can meet the best
applied to a mental disorder, satisfactory answers standards of scientific medicine, they should be
fail to emerge. Indeed, for a given mental illness thought of as modern quacks, laughable if not for
psychiatrists would be hard-pressed to point to any their countless victims. According to Szasz, labeling
unambiguous anatomic markers, to describe its someone a schizophrenic in the late twentieth cen-
pathophysiological process, or to explain its cause tury is no different from calling someone a witch in
with a model that is intuitive, testable, and con- 1680 or a communist in 1950. It means that you
forms to prevailing biological wisdom. Lacking in disapprove of them, wish them ill, and have con-
these familiar desiderata of scientific medicine, a spired with the community to punish them.
mental disorder such as paranoia simply is not Any critique that brings to light real and potential
granted the same level of ontological certainty that abuses of psychiatry is laudable. As a general histori-
is ascribed to an "organic" disease like leukemia. cal framework, however, Szasz's approach is limited,
Until such time as we solve the age-old conundrum in that it conflates a philosophical ideal of what
of the relations between mind and body, discovering medicine should be with what the historical record
a formula that converts states of consciousness to shows it in fact is. A significant portion of current -
properties of matter (or vice versa), it is likely that and virtually all of past - medicine fails to meet
such barriers will persist. similar tests of scientific purity. Are there only a few
Visibly unmoored to fixed biological truths, classi- "real" physicians? It is easy to forget that the crite-
fications of mental disease thus seem capable of infi- ria of what constitutes "good" medical science are
nite drift. In consequence, the task of writing a his- not fixed, but evolve. For example, controlled clini-
tory or geography of any given psychiatric illness cal trials became the ideal only after World War II.
might be regarded as a pointless, premature exer- We may be chagrined to learn, just a few decades
cise. What exactly are we trying to map? If we follow from now, that our remaining "real" physicians were
the development of the word neurosis, we find that quacks, too.
in one century it refers to exclusively nonorganic A better approach is to revisit categories of mental
conditions, and in a century earlier, it includes or- disorder in their original historical context, to see
ganic disorders. If we disregard this problem as one how they fit within prevailing conceptions of
of mere wordplay and try to identify the actual condi- disease - not to define an illness according to an
tions that were labeled to such mischievous effect, abstract standard, but to derive its meaning from
another quandary develops. It is difficult enough to the actual interpretations of patients and physi-
establish whether a given mental disease appears in cians. Otherwise, we are left with the absurdity that
another country, let alone in a distant time. That only those doctors who employ correct therapeutics,
different eras produce variant mental diseases is and conceptualize in terms of true disease categories
more than plausible. Unfortunately, there exists no (as judged by today's knowledge), have the right to
assay of human experience that can bridge the past. be called physicians. Rather, we might follow the
Though the bones of a mummy may reveal to X-rays lead of Donald Goodwin and Samuel Guze and sim-
whether a pharaoh suffered from arthritis, they reply consider as diseases those conditions linked to
main silent as to his having suffered a major depres- suffering, disability, and death, which the lay and
sion. Finally, each of the many psychiatries has its medical community regard as the responsibility of
own guide to understanding mental disease; which medicine. As much recent writing in the history of

medicine argues, the "existence" of a disease can be they were embraced as tangible manifestations of a
as much a matter of social convention as a question divine universe that was otherwise liminal.
of its biological reality. More to the point, religion, magic, and medicine in
This alternative approach to the history of mental this eclectic age were viewed as overlapping - not
disease will also sidestep the pitfalls associated with incommensurate - domains. Loss of reason was at-
following the story of any particular psychiatric distributed to any combination of natural illnesses,
order through the centuries. The goal of this essay is grievous misfortunes, evil spirits, and deeds so sin-
to reconstruct the stages and processes by which ful as to incur God's direct wrath. Insanity thus
insanity came to be seen first as a medical problem became the proper business of astrologers as well as
and then as a matter for specialized expertise. Par- physicians, and of clergymen as well as lay adepts.
ticular attention will be given to the interactions Moreover, these roles often merged. A healer of sick
between lay and medical conceptions of mental ill- souls might offer counseling to assuage a spiritual
ness, in which physicians become drawn to issues of affliction in combination with a therapeutic regimen
social concern and, in turn, their theories are incor- to restore a humoral balance. A course of physic
porated into social thought; to the fit between the might be accompanied by a magic spell and imple-
specific professional agenda of physicians and the mented according to the patient's horoscope. For the
medical conceptions they espoused; and to the chal- Renaissance doctor, an individual instance of mad-
lenges as well as opportunities that advances in gen- ness was a thorny interpretative challenge, for its
eral medicine posed for psychiatric practitioners. In meaning might be located in bodily corruption, in
so doing, we might arrive at a better appreciation of devilry, or even in the signs of sainthood.
what is embedded within our current categories of These entangled threads, however, pull apart in
mental illness and a clearer perception of what is the the seventeenth century as a consequence of intel-
social function of psychiatry as a medical discipline. lectual and social revolutions. A foundation was
being constructed for a naturalistic interpretation
Early Modern Europe to the Seventeenth of insanity that would eventually overshadow super-
Century natural and religious frameworks. First, the scien-
In this period, no single approach to the problem of tific revolution that culminated in the work of Fran-
insanity dominated. Although categories of insanity cis Bacon and Isaac Newton placed science and the
in the Renaissance derived mainly from the classical experimental method at the forefront of human
system of mania, melancholy, and dementia, which achievement. The universe was beheld as a clock-
were based on the broad medical doctrine of bodily work whose structure and mechanism could be
humors, the implications were diverse in practice. understood - and eventually manipulated — by ra-
Physicians and lay people alike typically depicted tional human investigation. As the macrocosm
mad persons as wild beasts, devoid of reason. Brutal could be found in the microcosm, such investiga-
handling of the insane was commonplace. Yet a pat- tions explored the physiology of the human body;
tern of hospital care for the insane had been emerg- the most notable was William Harvey's demonstra-
ing since the late Middle Ages. The famous English tion of the function of the heart and circulatory
hospital of St. Mary of Bethlehem, later known as system.
"Bedlam," was founded in 1450 as an institution to Attention was also drawn to the mechanisms by
care for those who had "fallen out of their wit and which the soul commanded the body - the search
their health." Moreover, in that age a belief pre- was on for the sensorium commune, the organ that
vailed that melancholies and some mad persons held might mediate between passions, sensations, and
powers similar to those of saints, such as talking in body humors. The pineal gland, the organ suggested
tongues and prophesying. Erasmus himself wrote by Rene Descartes during the first half of the seven-
that Christianity is a form of madness. This tradi- teenth century, was one of many candidates pro-
tion stemmed from the rediscovery of Plato's teach- posed at the time. Descartes's philosophical tour de
ings, that human beings are compound beings, part force of dualism, although known for its splitting the
heaven and part earth. When the organic part is analysis of mind from the analysis of body, nonethe-
disturbed, as in madness, the soul becomes partially less spurred research into the somatic mechanisms
liberated. Poets, seers, and lovers might all exhibit that commute a volition into an action. The
true mania. And because this was a time when reli- seventeenth-century work of Thomas Willis, who is
gion infused everyday life, visions were not rejected often considered the father of neuroanatomy, stands
as deformed thoughts of diseased minds. Rather, out for its pioneering efforts to place the brain at the

center of human action - and disease. For example, around innovative theories of social contract and
Willis's studies on women with hysteria led him to willful association, it was the inner choices behind
conclude that the disease originated in the brain, not assent that were open to dispute and control. Not yet
in the uterus, as maintained in classical doctrine. His sorted out, however, was the exact role that physi-
teachings, later expanded by such students as John cians would play in constructing, and responding to,
Locke, directed investigators to uncover the role of this new "counterreality."
the nervous system as the basis of human experience
and knowledge. Paralleling the interest in the so- The Enlightenment
matic mechanisms of self was a focus on the range The eighteenth-century period of the Enlighten-
and force of the passions. Of special interest were the ment has been characterized as the Age of Reason,
late-sixteenth- and early-seventeenth-century physi- when the powers of mind reached out to command
cians Thomas Wright, who discussed how patients' both nature and human affairs. The goal was the
mental states could be critical to their recovery from perfectibility of "man" and of "man's lot" on earth,
illnesses, and Robert Burton, whose Anatomy of Mel- and the means to this end was rationality tempered
ancholy (1621) stressed the psychological causes and by direct observation. Within this context, all that
cures of insanity. held back or confounded the development of civiliza-
Major social upheavals were also underway. Fol- tion - whether particular individuals or society as a
lowing the midcentury English Revolution, in which whole - came under heightened scrutiny, a problem
religious enthusiasts temporarily gained power, re- to be solved by the reasoned application of science
spectable people repudiated religious fanaticism in and medicine. Madness, or, as some might put it,
all its forms. Embracing the rationalist worldview of "unreason," stood out as a dark challenge to the
scientists and natural philosophers, the educated light of progress. Indeed, this was the era in which
classes ridiculed astrologers and empirics, in the physicians discovered that the insane presented a
process abandoning therapies based on religious and significant and distinct institutional population,
magical means. The way was clear for the nascent one amenable to medical intervention; that society
scientific communities to construct new interpreta- was wracked by distressing conditions composed of
tions of health and illness. In turn, the consolidation psychic as well as physical ailments; and that the
of the naturalist model had important consequences source of most diseases was traceable to the newly
for the cultural boundaries of insanity. During the dissected nervous system. Because of the numerous
Reformation, Puritan ministers often demonstrated ties forged between medicine and the problem of
the powers of their practical divinity by healing sick insanity, many consider the modern concept of men-
souls. Considering themselves "physicians of the tal illness to have been itself an Enlightenment
soul," they led afflicted individuals through intense product.
rituals of community prayer and healing fasts. Such In traditional histories, modern psychiatry dawns
potentially helpful ties between learned religion and with the legendary moment in 1795 when Philippe
popular culture were lost, however, in the rush to Pinel, chief physician of the Salpetriere asylum for
remove demons from psychopathology. women, struck the chains from the inmates. The
In addition, the naturalist model allowed for a mad were no longer to be considered mere brutes
novel form of ideological warfare. Where Anglican deprived of reason, amusing grotesqueries, but as
pamphleteers might be labeled heretics by their reli- afflicted persons in need of pity, humane care, and
gious enemies, the favor was returned when they enlightened physic.
denounced these foes as sufferers of a mental disease. Applying the principle of direct clinical observa-
Madness thus emerged as a form of "counterreality," tion, Pinel reorganized categories of mania, melan-
an appellation that marginalized the religious fanat- cholia, dementia, and idiocy to reflect specific, identi-
ics who so recently had destabilized the nation. Be- fiable symptom clusters derived from his cases. For
fore the Restoration, a time when talking directly to example, he distinguished between mania with delir-
God was still thought possible, hallucinations and ium and mania without delirium - a disturbance of
delusions were not especially important signs of in- will without intellectual deficit. (Later, Pinel's
sanity. Afterward, however, such experiences were nosological stance would revolutionize general medi-
considered the very essence of madness. In the hierar- cine.) Mental illness resulted when persons of unfor-
chical world order before the Revolution, it was one's tunate hereditary stock were overwhelmed by their
willingness to obey that determined one's insanity. social environment, poor living habits, a disruption
In the new political order, which was constructed in routine, or unruly passions. Physical factors, such

as brain lesions, fever, and alcoholism, were thought curred mostly in the small private asylums patron-
possible but not as common as "moral" or psycho- ized by the higher classes, which were directed by
genie factors. Asylum statistics revealed that men- lay as well as medical superintendents. The forma-
tal illness was, surprisingly, an intermittent or tem- tion of relations between nascent psychiatry and its
porary condition, curable if treated before it had a clientele remains a complicated, poorly understood
chance to become somatically ingrained. The physi- story. Clearly, though, the growing institutional
cian's best weapon was discovered to be the hospital populations sharply focused both social and medical
itself, for its strict regimens were the very tools by attention on severe madness as a problem requiring
which the superintendent might instill into his solution.
charges an inner discipline, emotional harmony, and An exclusive concentration on the institutional
the habits of productive citizenship. In linking, in history of psychiatry may also obscure the broader
one stroke, progressive reform to medical advance social currents that already were greatly expanding
and, in another stroke, the stability of a patient's the concept of mental illness. Milder forms of insan-
inner psychic milieu to the proper management of ity, such as hypochondriasis and hysteria, had by
the external hospital environment, Pinel set in mo- Pinel's day gained a status as the period's quintes-
tion the optimistic expansion of institutionally sential medical complaint. These conditions, also
based psychiatry. known as the vapors, spleen, melancholy, or later
Recent critics, such as Michel Foucault, view Pi- "nerves," referred to an irksome cluster of psycho-
nel's accomplishment less favorably. Physical chains logical and somatic (especially gastric) complaints,
were indeed removed, but only to be replaced by ranging from ennui to flatulence. Through such
internal ones, more insidious for their invisibility - works as Richard Blackmore's Treatise of the Spleen
shame and guilt can be just as constraining as iron. and Vapours (1725) and George Cheyne's The En-
Through the guise of humane treatment, patients glish Malady (1733), the valetudinarian "hypochon-
were coerced into conforming to putative "normal," driack," known by oppressive moodiness, oversensi-
"healthy" standards of conduct. Moreover, critics tive skin, and bad digestion, became enshrined as a
like Foucault hold, it was no accident that insanity stock Enlightenment figure.
was placed under the purview of the large central- The arrival of the "nervous" disorders coincided
ized institutions of Paris, since Pinel's model fit well with the emergence of new social functions for the
with the demands of the emerging political order. concept of mental illness. Woven out of the perceived
The growing asylum populations were themselves interactions between psyche and soma, tempera-
only a part of a larger phenomenon. Those who, for ment and life-style, such conceptions offered a fac-
whatever circumstances, failed to fulfill their duties ile interpretative matrix for connecting to issues
as citizens within the new state became managed that stretched beyond personal health. In particular,
increasingly through civic institutions, be they alms- members of polite society found in the "hypochon-
houses, jails, workhouses, hospitals, or asylums. Phy- driack" disorders a rich social resource. Such com-
sicians, in reaching out to asylum inmates through plaints enabled one to mull endlessly over the minor
an expanded medical view of insanity, were at the discomforts of life and were also a self-replenishing
same time complicit in cementing the new political well for claims on others' sympathy. But they served
realities. Pinel may indeed have rescued asylum in- a more subtle function as a conspicuous indicator of
mates from base neglect, but the benevolent pa- social location, for those believed at risk for the
ternalism of the "clinical gaze" has had its toll. ailments were only those of a truly refined and ex-
Henceforth, "modern man" is enslaved within a quisite temperament. In the words of the Encyclope-
medicalized universe, for there can be no form of dia Brittanica (1771), hypochondriasis was a "pecu-
protest that cannot be interpreted, and thus dis- liar disease of the learned." Indeed, James Boswell
missed, as pathological in origin. wrote that the suffering hypochondriacks — himself
Foucault's approach has since been shown to be included - might console themselves with the knowl-
not wholly satisfactory. True, it was in this period edge that their very sufferings also marked their
that the institutional face of insanity was dramati- superiority.
cally revealed. The pattern is not uniform, however. When "furious distraction" or severe mania was
The model works best in such contexts as France and the hallmark of the psychically afflicted, the designa-
Germany, where larger asylums for the poor evolved tion of insanity was tantamount to banishment from
within a spirit of centralized authority and medical normal society. In contrast, hypochondriasis was a
police. By contrast, in England, such growth oc- form of social promotion. There was a collective func-

tion, too. Contemporaries explained the dramatic groundwork by which general medicine was to break
outcropping of the malady as a direct consequence of away from the neohumoral systems that had domi-
the unnatural circumstances imposed by the new nated since the Renaissance.
urban, "civilized" life-style. Sedentary living, rich Cullen's nosology, in which diseases were classi-
food, populous towns - all were thought to exact a fied on the basis of the patient's presenting symp-
toll, the price of progress. In short, through the innu- toms, be they physical or mental, was essentially
merable discourses on hypochondriasis, the anxi- psychosomatic in orientation. Medical interest in
eties and ambivalences of a rising class found a the inner contents of self also followed in the wake of
favorite means of expression. Lockean theorists who were building a new psychol-
The new power of the disease categories did not ogy of mental associations, and of William Battie
remain for long the exclusive property of the higher and others of the eighteenth century who were ex-
classes. By the end of the eighteenth century, physi- ploring the role of the passions in determining men-
cians were chagrined to find that tradesmen and tal and physical harmony. Perhaps the best example
domestic servants were equally likely to exhibit of the strength of the psychosomatic model can be
hypochondriack or hysteric complaints. As it hap- seen in the heroic treatments of the insane, which
pened, when elite physicians looked to the hospital included the notorious dunking chair. This interven-
infirmary for new sources of medical advance, they tion was not simply an expression of random cruelty
were confronted with the realities of the sick poor. or cultural atavism. Rather, it was a logical product
Institutional portraits of disease thus clashed with of the belief that mental shocks were akin to physio-
those derived from private practice - the democrati- logical action, with effects as powerful as those in-
zation of hysteria and hypochondriasis was but one duced by bleeding or purging. Terrifying the mind
consequence. The poor, for their part, had discov- was a medical recourse used for a broad range of
ered that the nervous disorders served as entry tick- pathological conditions.
ets to one of the few sources of medical charity then To explain the proliferation of the psychosomatic
available. model in this period, sociologists and historians
The popular appeal of the new concepts of mental look to the nature of the patient—physician relation-
illness must also be attributed to developments in ship. Because medical practice consisted of private
medical research and theory that stressed the impor- consultations, where physicians were dependent on
tance of the nervous system to all pathology and that satisfying the whims as well as the needs of their
presumed a psychosomatic model of interaction be- wealthy patrons, medicine was patient-oriented.
tween mind and body. The trend stems from Willis, Treatment was formulated to satisfy the client, a
who looked to the brain as the fundamental organ; tailored reading of life-style, circumstances, and
his model, though, remained humoral, based on poi- habits, with heroic treatments applied in response
sonous "nervous liquors." As the extensions of the to demands for dramatic action. Similarly, Cullen's
nervous system became further elaborated in the symptom-based nosology was based not on direct
eighteenth century through the work of Giovanni physical examination — the physician's own do-
Morgagni, Albrecht von Haller, and Robert Whytt, a main - but on patients' descriptions of their com-
new medical system appeared that was based on the plaints. Given these circumstances, it was the total-
"irritability" and "sympathy" of the muscles and ity of the sick-person's experience that gave unity to
nerves. The renowned Scottish physician William the day's medical theories, a phenomenological ori-
Cullen went so far as to declare that the majority of entation in which psychic complaints were on a
all diseases were caused by either too much or too level ontological footing with somatic disturbances.
little nervous "tone," a pathological condition that Medical priorities - and hence realities - were thus
he termed a neurosis. Neuroses, as defined by Cul- set by what patients considered bothersome. We
len, were afflictions of sense and motion that lacked must remember that physicians as professionals
fever or localized defect - a "functional" as opposed were only then developing an institutional base,
to structural condition. Subsumed within this new such as the hospital, wherein they might control
category were such afflictions as hysteria, epilepsy, their patients and establish internally derived stan-
tetanus, asthma, and colic. (Cullen's model of neuro- dards of research and treatment.
ses persisted well into the late nineteenth century.) Finally, the ties forged between the problem of
Through Cullen and his followers, the nervous sys- mental illness and medicine must be placed in the
tem was elevated to central importance within physi- context of the new social meaning of health and the
ology, pathology, and nosology, laying the conceptual expansive role of physicians in the Enlightenment.

Historians have described how in this period health were considered amenable to medical intervention,
itself become a goal, if not an obligation, for individu- mental afflictions became important social resources
als and society to pursue, a secular gauge of progress for the expression of individual and collective anxi-
that could be accomplished in the here and now. In eties. Physicians discovered in the growing popular-
response to a thirst for practical knowledge, medi- ity of these conditions not only a fresh source of
cine was "laid open," translated from Latin texts, patients and an institutional base, but new service
and popularized in an explosion of pamphlets and roles for themselves as social critics and experts —
health guides. Health as a commodity generated a madness became the very measure of civilization.
tremendous market for physicians' services and, in Thomas Trotter, enlarging on the work of Cheyne,
the age of Franz Anton Mesmer and electricity, for claimed that the nervous diseases resulted when citi-
any treatment remotely fashionable. Psychic disor- zens' life-styles and occupations did not fit their
der was a particularly fertile niche for physicians to constitutions and temperament. He warned that En-
exploit. This was especially true after it was linked gland, owing to a combination of its peculiar cli-
by the neurosis model to a broad range of everyday mate, free government, and wealth, was the most
conditions and once its curability in even severe threatened country. The survival of civilization,
forms was demonstrated. (The work of Pinel and the with its complex social differentiation of labor, de-
dramatic turnabout in behavior of mad King George pended on the decreasingly likely event of persons
HI was particularly effective in this regard.) working within their proper stations in life - lest
Medicine, denned as keeper of the welfare of the the nation degenerate into one of idiots and slaves.
human race, extended far beyond matters of individ- Physicians bore the responsibility for "diagnosing"
ual treatment and grew into an Enlightenment meta- the need for adjustments in the biological - and
phor for broad political reforms. Guiding thinkers social - hierarchy.
such as the philosophes saw themselves as nothing We must not, however, overstate the extent of in-
less than medical missionaries who cured the ills of sanity's "medicalization." Persons were transported
society itself. Since the individual was a product of to asylums not so much because medical treatment
society and nature, the science of physiology came to was considered necessary as because these people
signify the proper functioning of the social as well as were perceived to be dangerous or incompetent. The
individual body. Moral philosophy and biology joined insanity defense had become an increasingly popu-
in the new science of man; theories of the perfectibil- lar resort in criminal trials, yet the examination of a
ity of human society were interlaced with secular defendant's mental status was as likely to be per-
theories of health. Thus, Pinel's striking of the chains formed by a lay authority as by a medical one. And
was understood to be as much an act of civic benevo- there existed as yet no professional grouping of psy-
lence as the first step of a new "medical" approach. chiatrists, let alone regular physicians, who had spe-
Medical progress and benevolent reform commin- cialized knowledge of the insane. The concept thus
gled, a shared task. Furthermore, the problem of men- remained a product mostly of general culture, trans-
tal illness and the proper development of mind were parent for all to read and make judgments upon.
of special fascination in an age obsessed with how
reason was self-consciously mastering nature and re- 1800 to 1850
constituting society. Through a cause cel6bre like the In the first half of the nineteenth century the treat-
case of the Wild Boy of Aveyron, the original feral ment of mental illness was marked by two trends: a
youth, and the contention of Pierre Cabanis that the wave of asylum building and the differentiation of a
brain excreted thought like the liver excreted bile, small band of medical professionals who claimed
the belief was growing that the forward movement of mental disorders as their special domain. These two
civilization might depend on scientific forays into the developments were linked through a materialist
darkness of human pathology. model of mental physiology that had reformist conno-
In sum, madness during the Enlightenment be- tations and the arrival of new categories of mental ill-
came a central cultural concern. Mental afflictions ness that advanced the value of psychiatric expertise.
were newly visible in the asylums, in the rise of Written as only a modest, local report of the way
hypochondriasis and related disorders, and in the Quakers cared for their small number of lunatics,
investigations into the functions of the nervous sys- Samuel Tuke's Description of the [York] Retreat
tem. With the expansion of the concept of mental (1813) nevertheless launched a worldwide movement
illness to include conditions that were not drasti- of asylum construction. In this system of care later
cally removed from everyday experience and that known as "moral treatment," the asylum was envi-

66 II. Changing Concepts of Health and Di
sioned as a functional microcosm of society at large of psychiatry as a profession is typically traced to thi:
where troubled persons might reconform to proper 1840s, when these medical superintendents, or "men-
social behavior through a vigorous program of occu- tal alienists," banded together to form specialized
pational therapy and moral suasion. Chains were to organizations and medical journals. (For example,
be replaced by admonitions, bars by comfortable fur- the forerunner of today's American Psychiatric Asso-
nishings, and the inmates' mania quelled by distract- ciation began in 1844 as the Association of Medical
ing amusements. In the words of John Connolly, an Superintendents of American Institutions for the In-
asylum pioneer known for his popularization of the sane; this predated by four years the American Medi-
"nonrestraint" method, the combined psychological cal Association.)
effect of enlightened architecture and behavioral The challenge for the first psychiatrists was to ex-
management had rendered the asylum a "special ap- pand both their institutional base and their claim to
paratus for the cure of lunacy." Originally designed specialized knowledge. The former goal was ad-
for fewer than 30 patients, the new asylums were vanced by championing the idea that insanity was
artificial family environments, heavily dependent on curable if its victims were removed at once from their
the talents and personality of the superintendent. homes to asylums, where they might receive the full
His burdens included intimate contact with patients advantages of moral treatment - in combination
and their families; the judicious meting out of an with a regular medical regimen. Moral treatment as
array of mild rewards and punishments; and immedi- a nonmedical practice was thus neatly coopted. In
ate attention to the smallest administrative problem. turn, the growing empire of asylums crystallized the
A commanding presence, diplomacy, boundless sym- young profession around a privileged therapy. Pa-
pathy, worldly wisdom, moral probity, and frugality tients were locked in, but just as significantly, medi-
were all characteristics essential to the task. A medical competitors were locked out. The alienists also
cal background was not a necessary qualification - made progress in advertising their expertise. In
and by no means was it a sufficient one. France, when the Napoleonic code made provision for
The Tuke model of moral treatment was particu- a legal defense of not guilty by reason of insanity,
larly fruitful in developing asylums in the United alienists attracted national attention by their in-
States, a success attributed to several factors. As volvement in celebrated homicide trials. In advocat-
civic responsibilities shifted from town to county and ing social if not legal justice for insanity's unfortu-
later to state government, officials looked to the nate victims, the alienists were advancing a political
centralized asylum as the rational (albeit more ex- cause of liberal philanthropy (in the heat of Restora-
pensive) site of humane care not available in local tion politics) and also a professional one, the eleva-
jails, almshouses, or homes. Also, it has been argued tion of their status to that of experts.
that in the troubled times of Jacksonian America the The alienists seized on the concept of monomania,
well-ordered asylum gained favor as an innovative a term coined by Jean Etienne Esquirol around
symbol of social control. Moreover, families increas- 1810, to argue that a person could be driven by
ingly looked to the asylum as a solution to their delusions to perform acts for which he or she was not
terrible burdens. It is not clear whether this was due responsible. Descended from Pinel's manie sans de-
to social changes that rendered them either unwill- lire, monomania referred to a nosological region in-
ing or unable to provide home care, or whether they termediate between mania and melancholia. Unlike
had become convinced by the vaunted success of those with nervous or hypochondriack disorders,
asylum cures. In either case, the unquestioned ease which comprised the gray zones between everyday
with which patients were shipped to asylums had preoccupations and total loss of mind, monomaniacs
prompted even Connolly to warn that the proof of an were indeed quite insane, but only in one part of
individual's sanity was quickly collapsing into the their mind, and perhaps intermittently so. A morbid
simple question of whether he or she had ever been perversion of the emotions did not necessitate a cor-
institutionalized. responding loss of intellect. The defining characteris-
Although when first constructed the asylums were tic of the disorder was that, save for a single delusion
as likely to be managed by lay authorities as by or disturbance of mind, an afflicted individual might
medical ones, their growth nevertheless provided a appear entirely normal. Here, then, was a semiotic
base for a new breed of physicians whose practice wall that could not be breached by lay or even
was limited to mental problems. Such posts were nonspecialized medical knowledge. Significantly, at
often quite attractive, and an esprit de corps devel- the trials the alienists employed neither arcane tech-
oped among the elite who occupied them. The origin nique nor extensive jargon. Their claim to expertise

was the discerning eye of a seasoned clinician, a skill and physiological models merged: The well-ordered
that was honed on asylum populations where insan- asylum restored the patient by keeping the brain in
ity was visible in all of its protean and elusive forms. a tranquil condition.
Knowledge does not have to be exceedingly learned
to be restrictive. It was a sufficient argument that 1850 to 1900
only those with extensive asylum experience could The late nineteenth century witnessed an explosion
reliably distinguish the true monomaniac from the of interest in the problems of mind and mental prob-
false. lems, one that extended across the cultural landscape
The term monomania seems to have fallen into into art, literature, science, and politics. A new fron-
fast decline in France after 1838, immediately follow- tier had been opened: the human interior. Thus com-
ing the passage of legislation that provided greatly menced a wave of ambitious explorations into the
expanded roles for alienists in France. In success, conscious - and later unconscious - mind, with the
the term lost its ideological edge. Elsewhere, similar aim of understanding what qualities of the self
concepts of partial insanity and moral insanity within were necessary to sustain civilization with-
(coined by J. C. Prichard in 1835) took root, which out. With the formal appearance of the human sci-
played equally vital roles in demonstrating that ences, fragmented into the disciplines of anthropol-
questions of lunacy were matters best left to experts. ogy, sociology, psychology, economics, and history,
Expansion of the profession depended on communi- and a similar specialization in medicine that gener-
ties that held potentially antagonistic viewpoints, a ated the modern professions of neurology, neurophysi-
situation that presented the alienists with a difficult ology, neuroanatomy, and even psychiatry, a dizzying
balancing act. On one hand, ties were maintained to growth occurred in the number and variety of schools
the nonmedical constituencies who were driving for- of thought on the structure and function of the human
ward institutional reform. On the other hand, gen- mind. From this point forward, any attempt to sys-
eral medicine was making great strides in the Paris tematize the development of psychiatric conceptions
clinics, where the anatomopathological approach to is vastly more complex and unwieldy. Indeed, any
the localization of disease was launching modern disease category that even remotely touches on hu-
medicine. A new medical standard had to be met. man behavior would henceforth have multiple, and
These separate goals found mutual expression in the perhaps contradictory, meanings - depending on who
doctrine of phrenology, a powerful movement in Eu- employed it, and where. Hysteria meant different
rope and the United States that was based on the things to the novelist than to the alienist or general
late-eighteenth- and early-nineteenth-century work practitioner, to the French psychologist than to the
of Franz Joseph Gall and Johann Spurzheim. Hold- German investigator, to the neurologist in Paris than
ing to the twin assumptions that psychological facul- to his or her colleague in Nancy.
ties were localized in specific regions of the brain In addition to the interest spawned by these intel-
and that cranial morphology was a guide to brain lectual currents, the subject of mental disorders
structure, the doctrine popularized "reading bumps drew impetus from "below," from powerful social con-
on a head" as a means of revealing an individual's cerns. On several fronts, much more now appeared
innermost talents and deficits. Although later gen- to be at stake, for the individual and for society, in
erations heaped abuse on it, phrenology has since the realm of the troubled self.
been credited with disseminating into general cul-
ture a materialist philosophy in which the brain was The Asylum and Society
the organ of the mind and with motivating research- The once-small asylum had swelled in size and popu-
ers in several fields to explore mental physiology as lation far beyond what its creators had initially
a serious pursuit. For the alienists, phrenology pro- hoped - or had farsightedly dreaded. A typical pub-
vided a framework for considering disordered person- lic mental institution in the United States now
ality, one that incorporated society, the asylum, and housed hundreds of inmates, resembling more a
general medicine. Through this model, alienists par- small town than an intimate extension of a house-
ticipated in the movement to better society through hold. Simply put, the superintendents had oversold
useful knowledge, explained the effectiveness of their product; patients streamed into the institu-
moral treatment as a program that strengthened tions faster than they could be cured. And through
specific mental faculties, and followed the organi- accretion, or what contemporaries referred to as
cists' lead in insisting that insanity could be attrib- "silting up," the small but significant percentage of
uted to brain lesions. Moreover, the psychological patients who would prove untreatable now occupied

a majority of the beds. The public costs of indefi- morphosed well beyond mere "irritation." Since even
nitely maintaining tens of thousands of such unpro- Trotter's time, neurological investigators scored ma-
ductive members of society (as well as of building jor accomplishments in understanding how the brain
additional beds to treat the incoming curables) were mediates between sense impressions and motive ac-
indeed staggering. tion. In the age of the telegraph and the dynamo, of
In subtle ways, the institutions' success in attract- centralized bureaucracy and the division of labor,
ing patients had the unintended effect of heightening the new model of the nervous system - one part wir-
fears that the problem of mental illness was somehow ing diagram and one part administrative flowchart -
worsening. What was only newly visible to the public offered an intuitive, adaptable framework for ex-
was considered but newly existent. Moreover, the plaining how human thought or action was guided,
simple bureaucratic act of generating institutional executed, and powered. Any number of confusing
records itself distorted clinical perceptions. As hospi- conditions or troubles could now be plausibly ex-
tal tallies began to reveal that the same patient plained by the lay public and medical personnel
might be released only to be readmitted years later, alike as simply a case of "nerves" - which at once
and that new admittees were often related to past said everything, and nothing. Indeed, so popular was
inmates — graphic illumination of insanity's fear- the new framework that some have referred to the
some generational grip - mental disorders of the day late nineteenth century as the "nervous" era.
were concluded to be far more virulent and insidious
than when the institutions originally opened. Such
fears were compounded by the consequences of slow Secondary Gains
but profound demographic shifts that reinforced ra- A diagnosis is never socially neutral because the
cial stereotypes. Where asylums based on the Quaker "sick role" associated with an illness has practical
model of moral treatment assumed a homogeneous consequences for the patient that are as real as any
population, in that physician, patient, and commu- physical manifestations of pathology. In the Victo-
nity shared similar religious and social values, the rian world of moralism and industry, where individu-
public institutions had become cultural mixing pots als were tightly bound by standards of duty and
filled with diverse immigrant and working-class economic performance, the role of the nervous in-
populations. Alienists, now mostly salaried employ- valid was promoted to central stage. Legitimated by
ees of the state and no longer beholden to families for the growing prestige of scientific medicine, this and
private fees, became even further removed from the other categories of disease provided one of the few
cultural milieu of their charges. Severe mental ill- socially acceptable opportunities for many persons
ness thus loomed as a social problem of paramount to step away from, at least temporarily, their every-
importance, one that had become even more grave. day obligations. Because of their protean nature,
nervous disorders were particularly well suited for
exploitation as a social resource. While virtually any
"Nervous" Disorders mysterious symptom or combination of symptoms
At the same time, the public had become obsessed might indicate an underlying nervous condition, phy-
with ailments of a less serious but more commonplace sicians had precious few criteria by which to rule out
nature, especially those conditions in which mental such a disorder. The presence - and departure - of a
and physical attributes blurred together. Rapid in- nervous ailment was decided more by the patient
dustrialization and urbanization brought forth dra- than by the physician, to the immense frustration of
matic transformations in the family, workplace, and the latter. Nervous diseases, often with simple and
society. In turn, the anxieties and inner conflicts that well-known components, were thus available to all.
arose from survival in the fast-changing modern This is not to say that these conditions were with-
world found expression in a slew of somatic com- out drawbacks. On the contrary, the distress and
plaints, ranging from dyspepsia and skin disorders to limitations on existence associated with a sick role
hysteria and hypochondriasis. Cullen's and Trotter's are often quite drastic. For example, historians have
neuroses had been resuscitated - but with a twist. explained the outbreak of hysteria in this period as
Owing to the rise of the middle class, a higher level emanating from the conflicting and impossible de-
of literacy, and the formation of a consumer culture mands placed on women. Although such a "flight
oriented to such things as the creation of markets for into illness" offered some measure of reprieve, even
health remedies, such "fashionable" diseases pene- allowing the exactment of a small manner of domes-
trated faster and deeper into society. Moreover, the tic tribute, it exposed these women to painful treat-
unifying metaphor - the nervous system — had meta- ments, left the underlying conflicts unresolved, and
H.3. Concepts of Mental Illness in the West 69
reinforced their dependency. Benefits were gained at surfaced by midcentury, enshrouding the young pro-
a definite cost, but for many, such a flight nonethe- fession of alienisme in an unexpected fatalism. Worse
less remained a viable option. yet were the political circumstances of the Second
The example of hysteria is only one illustration of a Empire (1852-71), in which the materialist basis of
pervasive trend, the appearance of medical disorders mental physiology was linked to the suspect ideas of
as significant resources for the indirect negotiation of Republicanism and atheism. Although their institu-
social conflicts. In addition to the battleground of tional posts afforded some degree of protection,
household or gender-related politics, a person's alienists nevertheless were under siege. In the dec-
health status might figure heavily in such polarized ade of the 1860s, for example, their public lectures
issues as the responsibility of corporations to protect were suppressed by government decree. The pessi-
the public, fitness for employment or military ser- mism of the profession found expression in the theory
vice, and criminal trials. Thus, victims of train of degeneration, or morbid heredity, which derived
wrecks (a notorious hazard of the industrial world) from the publication of B. A. Morel's Treatise on the
might be awarded some compensation on the basis of Physical, Intellectual, and Moral Degeneracy of the
their suffering from the vague syndrome of "railway Human Race (1857) and J. J. Moreau de Tours's Mor-
spine"; mothers accused of infanticide might be bid Psychology and Its Relationship to the Philosophy
judged temporarily insane rather than be sent to of History (1859). Drawing together currents in biol-
prison; and battle-weary soldiers might be diagnosed ogy, medicine, and social thought, degeneration
as suffering from irritable heart syndrome rather theory was perhaps the most significant influence on
than face execution as deserters. late-nineteenth-century psychiatry.
In answering the call to pronounce judgment on The degeneration model asserted that hereditary
matters with such public consequences, physicians factors were the primary cause of insanity, pathol-
were expanding their authority over everyday af- ogy occurring when a weak disposition was over-
fairs. As indicated in the examples just given, some whelmed by intoxicants (alcohol, malaria, opium,
of the more volatile health debates touched on cretinous soil), social milieu, or moral sickness. Com-
neuropsychiatric conditions, an area of medicine in bined effects of physical and moral injuries were
which diagnostic and explanatory models were insuf- especially treacherous. The distinguishing feature of
ficiently powerful to enable a designated "expert" to the degenerationist model was its developmental (or
deliver a verdict that would remain uncontested. "genetic," in its original meaning) orientation.
Many opportunities for professional growth were Even as enthusiasm for lesion-based systems of
opened, but the path was uncertain. psychiatry waned, a new intellectual foundation was
Thus, in the second half of the nineteenth century, emerging from the biological theories of Jean Bap-
mental disorders gained a commanding social pres- tists Lamarck, Herbert Spencer, and later Charles
ence due to the perceived threat of the asylum popu- Darwin. With evolution supplanting pathological
lation, the profusion of nervous disorders, and their anatomy as the core biology, questions of process
linkage to a range of polarized issues. This social overshadowed those of structure. Static taxonomies
interest was mirrored by the attention of diverse of disease thus gave way to dynamic systems, in
groups of learned scientists and physicians who com- which most mental disorders were stages of a uni-
peted for the privilege of claiming thefieldof mental tary disease, stratified not by anatomic location but
disorders as their own. Such groups varied greatly in by a defined temporal order. Simple ailments were
their institutional location, professional service role, linked to severe ones, as the seed is to the tree.
scientific orientation, and political aims. Their dispa- Mental illness now had a plot.
rate agendas led to a jumble of theories regarding For the French alienists, the degeneration model
insanity; in turn, these theories both strengthened provided a way to navigate past the Scylla and
and limited the professional opportunities of their Charybdis then facing the profession, the dual haz-
proponents. Let us visit, in turn, the asylum ards posed by either holding to materialist positions
alienists, three types of neurologist (the researcher, that invited political attack or abandoning these in
the private practice consultant, and the urban clini- favor of psychological models that were insuffi-
cian), and university psychiatrists. ciently "scientific" to silence medical critics. Morel's
solution was to argue that a specific case of mental
Asylums and Their Keepers illness was the expression of a "functional" lesion of
the nervous system, one based on its performance as
French Alienists and Degeneration Theory. In an integrated whole. Although an organic mecha-
France, the manifold problems of asylum psychiatry nism was presumed (satisfying demands for scien-
tine rigor), its elaboration was considered unneces- Such stories provided alienists a rich harvest from
sary for understanding the clinical significance of which to manufacture their most valued product:
mental illness. Moreover, the integrationist stance advice. Moreover, given the Lamarckian assumption
remained agnostic on the precise interaction be- of the day, that a person's habits over time were
tween mind and body. Religious conservatives need eventually transmitted to future generations as heri-
not be enthusiastic supporters of the degenerationist table traits, it was not just an individual's life, but
model, but at minimum it was palatable; although the life of the nation, that was at risk. With dissolu-
the soul no longer held a perpetual lease on the body, tion as the key to insanity, mental illness acquired a
neither was it in immediate danger of eviction. definite moral as well as biological structure. Unless
Morel himself was deeply religious, finding in the the alienists' warnings were heeded, a generation of
degenerationist model a biological statement of origi- dissolute citizens wouldfloodthe country with ner-
nal sin. vous children, and insane grandchildren in even
The theory states that the development of the indi- greater numbers. Madness was the very destiny of a
vidual is a reenactment of that of the species as a people unfolded.
whole, a viewpoint later encapsulated in Ernst Hein- Alienists thus trumpeted themselves as advisers
rich Haeckel's famous phrase "Ontogeny recapitu- on matters of social policy, alone competent to pilot
lates phylogeny." Civilization's forward progress had civilization past hidden reefs. Their message was
depended on the triumph of government and order especially poignant in France in the 1870s, when the
over barbarism and base desires. Individual survival country was recovering from the devastating mili-
depended on no less. If anarchy and mob rule were tary loss to the Prussians and from the turmoil of the
evidence of a breakdown in the social order, a rever- Paris Commune. It seemed that one had to look no
sion to an earlier — and hence evolutionary lower - further than the specter of working-class mobs to see
state, then madness was its equivalent in the individ- the link between social revolution and morbid degen-
ual, an atavism from a time when emotions ruled eracy. The model gained popular credence through
the intellect. Because we are biological as well as the work of Cesare Lombroso, an Italian author who
spiritual entities, the animal beneath the skin can devised popular categories of criminal insanity. As
only be controlled, never exorcised. Mental compo- we shall see, aspects of the degenerationist model
sure depended on an interminable conquest of desire penetrated virtually all major conceptual systems of
by discipline. mental illness espoused in the late nineteenth cen-
Although heuristically powerful, the degenera- tury. Indeed, the model resurfaces even today, when-
tionist framework offered no immediate therapeutic ever life-style is evoked as a basis for understanding
advantage for institutional practice. Rather, its disease.
strength lay in its expansion of psychiatric author-
ity beyond the walls of the asylum. With overfilled Neurology
institutions belying the curability of severe mental The latter half of the nineteenth century was neurol-
illness, alienists faced the prospect of becoming an ogy's "golden age," in research, private practice, and
alliance of mere custodians, should no dramatic the urban teaching clinic. Each of these three neuro-
treatment appear. Instead, alienists looked out- logical domains had significant repercussions in the
ward, recasting their medical responsibility to in- medical conceptualization and treatment of madness.
clude prophylaxis — society would be served best by
staunching the flow of inmates at its source. The British Experimental Neurology and Epilepsy.
new explanations of madness provided alienists Through the efforts of mostly British, German, and
with a blueprint for such extramural intervention, Russian investigators, the reflex became the building
one that augmented and did not undermine their block of neurophysiology. In the 1830s Marshall Hall
institutional base. demonstrated the importance of the reflex system in
Asylums provided alienists with a unique vantage maintaining all vital bodily activities. Following the
from which to observe directly countless broken British philosophical tradition of volitionalism, how-
lives. Every new admission was an object lesson in ever, purposive acts and thought processes were left
the fragility of normal life, of how a single path inviolate. Such dualism of mind and body came under
wrongly taken — perhaps a pint of gin, an act of assault by Thomas Lay cock. Drawing on German
masturbation, or a flirtation with prostitution - science, in which a natur-philosophie orientation pre-
might set a once vigorous individual on a course of sumed a unity of man in nature and a continuous
dissolution that would end in a locked asylum ward. evolution from animal to man, Laycock argued for a

gradual blending of automatic acts, reflexes, in- cated by overactivity in the lower centers. Empirical
stincts, emotions, and thought. Laycock's student, proof of the connection could be found in the asy-
John Hughlings Jackson, is often described as the lums, all of which housed a significant number of
true originator of modern neurology. Incorporating epileptics. For some time to follow, the ignominy
Hall's and Laycock's ideas, Jackson went furthest in associated with the biological corruption of the epi-
constructing a neurological basis for human action. leptic would spill over into categories of mental ill-
In his classic research on the localization of epilepsy ness. Not clearly inferable from Jackson's work, how-
(the major epileptic syndrome long bore his name), ever, was the actual involvement the neurologist
Jackson focused on the pattern by which nervous was to have with the problem of mental illness, for
functions disappear in the course of a fit; here was an although a solution to grave mental illness might
indirect means of peering into the functional organi- come from a cure for epilepsy, this awaited much
zation of the brain. further neurophysiological research. The divide be-
Combining Spencer's evolutionary cosmology with tween neurology and mental illness was a matter of
the degenerationist outlook, Jackson constructed a professional location as well as knowledge, in that
topology of self in which the nervous system was few neurologists had access to asylum patients. As
hierarchically layered according to the evolutionary for the noninstitutional population, Jackson's prefer-
scale. At the lowest or most "primitive" level was the ence for disease models based on clear organic
spinal system, which was controlled by the "middle" mechanisms led him to declare that "functional" dis-
level, the motor system; this in turn was mastered orders were best left to other aspiring specialties
by the "highest" level, the frontal lobes - the organ such as gynecology and obstetrics.
of the mind and the acme of evolution. Epilepsy
could now be understood as nothing less than a body Neurology and Neurasthenia in the United States.
caught in the visible throes of dissolution. This an- Neurology as a viable profession in the United
swered Jackson's clinical puzzle concerning why ab- States dates from the Civil War, which produced a
errations of conscious thought were the first epilep- larger number of soldiers with nerve injuries and
tic symptoms to appear; nervous functions were lost severe emotional disorders requiring specialized
in precisely the reverse order of their evolution. care. After the war, neurology rode the wave of spe-
Much of the appeal of the degenerationist model cialism that was transforming urban medicine. Phy-
resulted from its resonance with fundamental sicians with graduate training in European medical
changes then occurring in the social fabric. Issues of science hoped to build alternative medical careers by
social differentiation and hierarchy surfaced in the limiting their practice to areas that might benefit
wake of nationalism which pitted one country's heri- from specialized knowledge. Cities provided both the
tage and international standing against another's; requisite critical mass of varied clinical material
industrialism, which produced a vast laboring un- and the pool of motivated, affluent citizens to sup-
derclass; and imperialism, which placed whole coun- port these ventures.
tries of "primitives" under European stewardship. In 1869 New York neurologist George M. Beard
With religious authority in decline, models of scien- diagnosed Americans as especially prone to nervous
tific naturalism were expected to provide a rational exhaustion. His conception of neurasthenia - liter-
social order in step with the times. Jackson's model, ally weak nerves - achieved international usage as
which dovetailed a neurological "localization of supe- a major trope of the Victorian era. The condition
riority" with Spencer's dictum that "separateness of referred to a cluster of distressing, often vague
duty is universally accompanied by separateness of symptoms that ranged from simple stress to severe
structure," exemplifies the fact that in the Victorian problems just short of certifiable insanity. Bodily
era visions of the external world could be disaggrega- complaints such as headaches and hot flashes ap-
ted from those applied to the internal one. Jackson's peared alongside psychological ones such as lack of
accomplishment was a paradigm that continues to interest in work or sex and morbid fears about
influence us today, one that all too neatly converged trivial issues. Thus burdened, neurasthenics re-
neurological, evolutionary, and social stratifications treated from the fulfillment of obligations to their
into a spatial metaphor of unusual power. families, employers, or social groups. The physio-
With Jackson's model, the degenerationist model logical link common to all these cases, Beard sug-
of insanity now has a firm neurological basis. As gested, was the depletion of the vital nervous
Jackson himself argued, mental illness resulted forces.
from the dissolution of the higher centers, compli- Neurasthenia's prevalence in the modern era was

no mystery, Beard argued. The telegraph, railroad, knowledgeable physician might have been able to
daily press, crowded quarters, and financial market understand the development of a mental pathology,
had rendered life simultaneously more hectic, in- based on a reading of the balance of the organism as a
tense, and stressful. Civilization placed demands on whole. Now, however, only a nerve specialist was
our nervous systems that nature had never antici- qualified. And as an untreated cold might lead to
pated. Reminiscent of earlier interpretations of hypo- pneumonia, so a nervous complaint not handled by a
chondriasis, the eighteenth-century "English mala- neurologist might be the portal to an asylum. In
day," the presence of neurasthenia served as a short, by establishing the principle that troubling
marker of advanced society. Once again, mental ill- but otherwise unremarkable mental states might
ness was a conspicuous price of progress. Americans, produce morbid bodily changes as dramatic as any
world leaders in industrialization, paid dearly. Here, physical insult, Beard and his followers were con-
too, patterns of incidence were interpreted as clues structing a neuropathology of everyday life.
to social hierarchy. Men thought most likely to suc- The strength of Beard's model lay not in its origi-
cumb were those at the vanguard of social advance, nality but in its artful extension of medical and
such as inventors and entrepreneurs. Women, whose social trends. Indeed, by this time, nervous condi-
smaller brains were dominated by their reproduc- tions represented to family physicians a significant
tive systems, might be overcome by the daunting portion of their practice and were also responsible in
task of running a Victorian household or by exces- large measure for the booming market in health
sive intellectual effort. The ranks of the lower products and services. At first, neurologists followed
classes, to be sure, did yield a significant number of uninventive therapeutic programs, endorsing the
neurasthenics. But since their hardier constitutions standard use of mild tonics and sedatives, dietary
would bear up under all but the worst shocks, such restrictions and supplements, massages, low-current
as alcoholism or inveterate depravity, the condition electrical stimulation, and visits to water spas and
in them was more a badge of shame than one of other health resorts. The goal was to help patients
honor. restore their "strength" and to maintain a healthy
For practicing neurologists, the concept of neuras- "nervous tone." Morbid thoughts and other dangers
thenia brought order to chaos and provided a defensi- of introspection were to be derailed through outdoor
ble base for the profession's enlargement. The bewil- exercise and cheerful admonitions by the doctor and
dering array of ailments that fell under the category family.
of "functional" disorders (all those without gross ana- The neurasthenic model also gained impetus as an
tomic damage or known organic cause, such a hyste- articulation of a Victorian conception of self, one
ria and hypochondriasis) were unified into a single that incorporated health's new moral meaning. Char-
clinical picture that was comprehensible to both neu- acter was indeed a matter of destiny, but neither
rologist and patient. Briefly stated, nervous energy heredity nor rational intent solely determined one's
was a precious quantity that must neither be squan- fortunes. Rather, it was one's will that mediated
dered nor misdirected; temporary habits eventually between what one could be and what one should be.
became fixed pathways in the brain and might even Not all persons were created equal, nor were they
be transmited to the next generation. forced to meet stresses and tests of comparable sever-
The reality of the functional diseases had been an ity. Nevertheless, what individuals made of their
open question for the public, which was often far lots was inescapably their responsibility. In this
more skeptical than many medical experts. The neur- worldview, health became a secular measure of
asthenic model, although lacking a precise organic moral character. Although illness in general was no
mechanism, was able to relegitimate these disorders longer interpreted as a direct manifestation of God's
by imparting the cachet of a state-of-the-art scientific wrath, conditions that resulted from a damaged con-
theory. Furthermore, the emphasis on brain physiol- stitution were read as the certain consequences of
ogy was consistent with the growing emphasis in immoral or unnatural habits - a failure of will. Ob-
biology and medicine on the central nervous system servers noted that unlike malaria or the pox, which
as the dominant bodily system. This displaced the might attack the weak and the strong indifferently,
open-ended physiological models of the eighteenth mental diseases fell only on those who lacked self-
and early nineteenth centuries in which pathogenic control. The concept of neurasthenia, which focused
processes might arise from the influence of any of a on activities that damaged the will itself, thus pro-
number of interconnected systems that included the vided an adaptable matrix for the consideration of
liver, stomach, circulation, or nerves. Previously, any human character.

The special business of neurologists, in addition to Charcot's Parisian Teaching Clinic and Hysteroepi-
providing the usual treatments for nervousness, was lepsy. Although Esquirol, in the 1840s, ignored
to offer individuals the expert guidance necessary to hysteria as an uncertain diagnosis of little signifi-
avoid permanent or worsened injury to the constitu- cance, by the 1880s the condition had risen to a
tion, advice based on their putative knowledge of newfound prominence. This turnabout was directly
brain function and human affairs. Thus construed, attributable to the efforts of Jean Martin Charcot,
the role of neurologists combined both intimacy and an internationally renowned neurologist whose
scientific objectivity. On one hand, neurologists were teaching clinic at the Salpetriere Hospital greatly
to be consulted by patients on an expanding variety influenced a generation of students who were des-
of personal issues, ranging from major life decisions, tined to become leaders in medicine. At the height of
such as the advisability of marriage, to minor points his clinical and pedagogic career, Charcot committed
of life-style, such as the amount of fat to be included his full resources to the vexing problem of hysteria.
in one's diet. The role of adviser merged with that of If successful, one more trophy would be added to his
confessor: Critical to the success of the treatment collection that boasted classic descriptions of amyo-
was the patient's full disclosure of all behavior, no trophic lateral sclerosis, multiple sclerosis, tabes,
matter how disreputable. Indeed, it was precisely on and locomotor ataxia.
questions of damage caused by vices that medical Charcot insisted that hysteria was like any other
treatment so often appeared to hinge. Medical pen- neurological disorder, with a definite, even predict-
ance, as outlined by neurologists, became the new able, clinical course. The truth of hysteria would
absolution. On the other hand, in the interest of surely be revealed once exhaustive clinical observa-
invading clinical territory already inhabited by ei- tion was combined with the experimental method
ther alienists or family physicians, neurologists recently outlined by Claude Bernard. The Salpe-
were obliged to base their expertise on the emerging triere provided Charcot with the resources necessary
laboratory and clinical science of the brain. This for just this kind of medical campaign: a concentra-
dual obligation of scientist and counselor proved dif- tion of scientific equipment and trained personnel to
ficult to reconcile. perform exacting measurements and a reliable sup-
Neurologists learned soon enough what alienists ply of clinical material. The clinic's social structure
had discovered already: Mental disorders are more was an equally important factor. The rigorous pro-
managed than cured. Furthermore, such close inter- gram of experimental study that Charcot envisioned
vention in patients' lives yielded a clinical paradox. necessitated privileged access to human bodies, ac-
A nervous complaint, successfully treated, might dis- cess that was of a scale and manner inconsistent
appear only to be replaced by another; or a wide with the realities of private practice, where permis-
range of treatments might prove equally effective - sion would have to be negotiated case by case, if it
for a time. Even as they were constructing elaborate was obtainable at all. Indeed, Charcot's experimen-
scientific justifications for their clinical interven- tal protocols called for the incessant monitoring of
tion, neurologists were discovering that it was not so every conceivable physiological index, including
much the specific medical treatment that mattered hourly urinary output and vaginal secretions; these
as it was the discipline that patients exhibited in humiliations might be followed by the application of
adhering to the treatment plan. With this in mind, painful ovarian compresses. At the Salpetriere, a
S. Weir Mitchell perfected his famous "rest cure," in public charity hospital, Charcot could ignore rebuffs
which patients were isolated from their families and to such requests, for its wards were filled with lower-
placed in the full care of a neurologist and nurse. class women over whose bodies the physician in
Stripped of all power to make decisions, and con- chief held full dominion.
signed to a state of ultradependency (which included After some effort, Charcot announced his discov-
such things as spoon-feedings), patients were sup- ery that hysteria indeed had a definite clinical form.
posed to rebuild their willpower completely. Focus A true hysteric attack passed through four complex
thus shifted away from external signs and symptoms stages, beginning with hysteroepileptic spasm of
to the dynamics of the patient-physician relation- tonic rigidity and ending with a resolution in grand
ship. The resistance of the patient to being cured theatrical movements. Hysteria's elusive "code" had
became a new index of pathology. Ostensibly follow- been broken. At his celebrated clinics, which the
ing a somatic program, New York neurologists un- elite of Paris attended, Charcot was able to demon-
easily awakened to the reality of psychological as- strate the disease in its full glory through hypnotic
pects of nervous disorders. induction on patients known for their spectacular

fits. Because the code was essentially visual, an disease would not come from asylum managers, who
iconographic reading of the outward manifestations lacked training in recent medical advances, or from
of the body, Charcot devised the technique of making academic psychologists, who had no direct contact
extensive drawings and photographic recordings so with patients, Griesinger decided to bring psychiat-
that clinicians not present might "see" the disease in ric patients into his own general clinic. Although he
its natural progressions. was known for his promotion of the doctrine that all
Charcot's model of hysteria tapped into several cur- mental disease was in fact brain dysfunction, Grie-
rents that aided neurologists in the extension of their singer's major focus was on the process by which a
social and professional base. With hysteria mastered person's ego, the integrated self, disintegrated. Re-
by science, they now had a justification for reaching jecting nosological systems based on faculty psychol-
outside the walls of the clinic to treat the masses ogy, which led to a diverse array of symptom-based
afflicted with its milder forms. Since Charcot's hyste- disease categories, Griesinger maintained that in-
ria was constructed in a degenerationist mold, neu- sanity was a single morbid process, differentiated by
rologists would have a new basis for commenting on stages of degeneration. This point was reinforced by
such worrisome social problems as crime, adultery, his acknowledgment of the inherent closeness be-
and mob unrest. Furthermore, in the reversal of po- tween sanity and insanity and of the existence of
litical fortunes that followed the installation of the borderline conditions.
Third Republic, secular models of behaviors became In Griesinger's approach, a mentally ill person
useful in anticlerical vendettas. Charcot, for exam- was someone who no longer had the same desires,
ple, went so far as to identify one type of fit as "reli-habits, and opinions and thus was estranged from
gious possession" and to denigrate past examples of him- or herself (alienated). This judgment could be
stigmata and other miraculous displays as forms of made only by reference to a patient's premorbid
hysteria. Finally, the model provided the first wave life, a history that must include family background,
of a promised series of incursions by neurologists into mode of living, emotional state, and even the na-
a clinical domain that was still dominated by ture of the patient's thoughts on world affairs. Once
alienists. Charcot, first holder of a French chair on a full portrait of the individual was constructed
nervous diseases, was establishing the institutional (from in-depth interviews with family and friends),
precedent for such an expansion. symptoms that at first seemed bizarre were now
understandable - perhaps even predictable. More-
Academic Psychiatry over, the importance of any specific contributing
cause, such as alcoholism or prostitution, could not
German University Psychiatry and the New Nosology. be ascertained without reference to the individual's
Through the creation of university chairs of psychia- case history. Mental illness originated as a conflu-
try, a pattern that began in Berlin (1864) and Got- ence of multiple factors, psychological as well as
tingen (1866), Germany soon took the lead in estab- somatic, that interacted early in life, when char-
lishing the academic study of mental illness. Unique acter was being formed. Developmental knowledge
to the German approach was a psychosomatic orien- of mental illness thus was joined to a contextual
tation that held to a fundamental parity between reading of the patient's past.
mental, somatic, and even environmental forces and With Kraepelin, the German clinical school of
insisted that this parity also be reflected in the rela- psychiatry reached its zenith. Trained as a neuro-
tions among academic disciplines. Thus, both psy- anatomist, an experimental psychologist under Wil-
chology and neuropathology might be joined in a helm Wundt, and a mental hospital physician, Krae-
common medical investigation. Legitimated as an pelin brought a diverse background to the problem
integral part of mainstream medicine, psychiatry of mental illness. Insisting on a combination of neu-
also shared in the developments that propelled Ger- rological, neuroanatomic, psychological, and even
many to the position of world leader in medicine by anthropological studies, Kraepelin held that the
the end of the nineteenth century. Led by Wilhelm case study was the sine qua non of psychiatric inves-
Griesinger and then Emil Kraepelin, the German tigation. Combining Griesinger's clinical conception
school of psychiatry created a lasting framework for of a unified personality with Rudolph Virchow's
classifying mental disorders. new principle of diseases as separate entities,
Griesinger was an accomplished internist who Kraepelin closed the century with a classificatory
also lectured on medical psychology at Tubingen. system that has been recognized as the foundation
Believing that further medical progress in mental of modern psychiatry.

Where Griesinger blended one mental disorder tions, mild as well as severe, was met by an equally
into another, just as hues subtly progress in a single strong response from a broad array of learned disci-
color spectrum, Kraepelin differentiated conditions plines. Both inside the asylums and outside, a vast
on the basis of essential clinical syndromes, as re- terrain of clinical problems was opened for cultiva-
vealed by their signs, course, and outcome. Drawing tion by practitioners and researchers representing
from published case reports as well as his own clini- diverse specialties. Since the late Victorian era was
cal work, Kraepelin grouped Morel's dementia the period in which science and medicine forged
precoce, Ewald Hecker's hebephrenia (1871), and their modern image as engines of power, faith grew
Karl Kahlbaum's catatonia (1874) into a single cate- that even problems as elusive and intractable as
gory of mental disease termed dementia praecox, mental illness might be mastered by empirical inves-
which began at puberty and progressed inevitably tigation. Moreover, positioned at the nexus of major
toward early senility and death. Manic-depression, social and scientific concerns, the mystery of insan-
which was known by its favorable prognosis, and ity gained a special poignancy. As human beings
paranoia were identified as the second and third were increasingly revealed to be products of nature,
types of major psychosis. Into separate divisions and a nation's destiny a matter of its biological as
Kraepelin placed the neuroses (hysteria and epi- well as cultural heritage, the unnatural in humans
lepsy), psychopathic states (compulsive neuroses became a counterpoint to the advance of civilization.
and homosexuality), and states of idiocy. Confusion Merged together were issues of brain and behavior,
as to which disease was afflicting a mental patient willpower and productive vitality, and even national
would not last forever, for it was only a matter of harmony and international struggle. In this context,
time before the disease would resolve into an the derangement of an individual was a sign of a
endpoint that identified the underlying syndrome. larger social decay, which required immediate solu-
For example, true neurasthenia was rare, since most tion by the new hero of civilization, the scientist.
diagnosed cases were simply early instances of a The joining of the new medical science to the prob-
major psychosis or a complication of a cardiac or lem of mental illness was extremely problematic,
bowel irritation. however, for several reasons. First, there was no one
Clinicians worldwide celebrated the immediate ap- specialty that controlled the field. The profession of
plicability of Kraepelin's nosology to their practices,psychiatry is a creation of the twentieth, not the
for cases of his major syndromes were easily recog- nineteenth, century. As we have seen, alienists and
nized in any asylum. Moreover, here was a system of the various types of neurologists each brought to the
mental disease that was based on the highest stan- subject their distinct professional agendas, resulting
dards of clinical medicine, one that incorporated a in the proliferation of widely varying conceptual ori-
program for continued empirical revision. Contempo- entations. In practice, no single model proved able to
raries did recognize that Kraepelin's work, at heart bridge the gulf between the disorders that appeared
a descriptive system, offered little explanation of in the asylums and those that surfaced in everyday
mental illness, suggested few novel treatments, and life.
indicated mostly fatalistic prognoses. It was a suffi- Second, scientific models of brain and behavior
cient triumph, however, for Kraepelin to have liber- were in transition, proving to be fickle sources of
ated the study of insanity from its ancient classifica-legitimation. Although a new form of scientific
tions of melancholia and mania, as well as from the knowledge can confer respectability on a particular
more recent and confusing additions of partial specialty, the benefit is not permanent. The alienists
insanities, which continued to multiply, and of neur- of the early nineteenth century, who had predicated
asthenia, which threatened to dissolve all distinc- their expertise on the presumption that lesions of
tions. (In addition, by incorporating a measure of the brain affected specific mental functions, found
despair into the clinical diagnosis, Kraepelin to their prestige fading as neuroanatomic findings
some extent relieved asylum psychiatrists of their failed to confirm their theory. The introduction of
obligation to cure, allowing attention to be concen- the degenerationist model extended the reach of
trated on description and study.) Accurate diagnosis alienists outside of the asylum, but did little to allow
was to be the avatar of the new scientific psychiatry. the new medical science to peer within it.
Private-practice neurologists were all too happy to
The Problem of the New Science. We have thus seen point out, soon enough, that alienists in their splen-
how, in the second half of the nineteenth century, the did isolation had let the latest science pass by. To
great social interest in the problem of mental afflic- bolster their own status as experts, they pointed to

new theories of an integrated nervous system that mension of mental disorders within a scientific frame-
supported their reading of the constitutional haz- work remained a confounding problem.
ards of particular life-styles. Beard's model of neuras-
thenia drew strength from its equal mixing of na- 1900 to 1950
ture and nurture, whereby a single disease category The first half of the twentieth century is marked by
contained an expansive matrix of moral and biologi- two somewhat opposing currents in the conception of
cal elements, a framework that empowered the clini- mental illness: the entrance of the Freudian model
cian to intervene as both counselor and scientist. In of psychodynamics and a rash of somatically ori-
due course, however, this approach was undermined ented theories and treatments. Furthermore, when
by the further elaboration of the brain's fine struc- medical schools began to offer systematic instruction
ture and a new emphasis on specific disease entities. in the medical treatment of insanity, they united
Further knowledge of nature had constrained nur- "nervous and mental disorders" in a single curricu-
ture's sphere of influence. lum as dictated by the new nosology, thus bridging
Third, science often creates or distorts the very the historical gap between the asylum and private
objects it putatively observes. This simple fact led to practice. The modern profession of psychiatry was
subtle, unintended consequences in the arena of men- born.
tal disorders. For example, Charcot discovered this
paradox, to his misfortune, yielding one of the grand Freud and the Unconscious
ironies in the development of the human sciences. In The realm of human activity and experience that
the rigorously controlled order of the neurological lies outside normal consciousness was attracting con-
ward, Charcot's patients were indirectly cued to pro- siderable literary and scholarly attention in the late
duce symptoms in the exact sequence and form pre- nineteenth and early twentieth centuries. Psycho-
dicted by his theory. When it became clear that only logical novels shared the theme that the rational
patients in the Salpetriere manifested "pure" hyste- intellect had only a limited ability to shape our lives.
ria, contemporaries soon ridiculed Charcot for perpe- Neurological investigators, constructing ever more
trating theatrical creations as true clinical syn- complex systems of reflex integration, described as
dromes. In his original act of constructing hysteria unconscious those bodily activities that did not re-
as a regular neurological syndrome, Charcot had quire continuous volitional monitoring. Noncon-
already set in motion his own undoing. scious mentation was also investigated by academic
Another example is provided by the difficulties of psychologists, although the concept was often re-
private-practice neurologists in confronting neuras- jected as oxymoronic. Some psychologically oriented
thenia. Beard and his followers, unlike Charcot, did neurologists, such as Charcot's rival Hippolyte
not create their patients' symptoms outright, but Bernheim, became interested in the powers of the
they did fall into a different kind of trap. Patients mind over body - ideodynamism — through the dra-
termed neurasthenics had come to these physicians matic effects of hypnosis and suggestion. The work
with an array of mysterious, but nonetheless truly of Morton Prince, Boris Sidis, and Pierre Janet fo-
bothersome ailments. Neurologists were thus in the cused attention on the clinical significance of minds
position of having to construct a new reality out of the that have disintegrated, or even divided. Janet devel-
material presented to them, a role that was becoming oped an extensive theory of psychasthenia, parallel-
increasingly common in the nineteenth century as ing neurasthenia, that referred to the inability of a
science-based professions were expected not only to weakened mind to maintain a unified integrity. Neu-
manipulate nature, but to construct a new map of rotic symptoms resulted from traumatic memories,
reality itself. However, the very act of legitimating such as unfortunate sexual episodes, that had been
the patients' complaints as a new disease trans- "split off" from the main consciousness. Cathartic
formed the delicate social balance of what was at treatment was the cure.
stake in the symptoms. Indeed, as Mitchell realized, Perhaps the strongest exponent of the unconscious
the dynamics of the patient-physician relationship before Freud was Frederic W. H. Myers, a nineteenth-
was itself somehow related to the expression of the century British psychologist known mostly for his
disorder. Since the organic models of disease provided advancement of psychicalist (paranormal) research.
no means of recognizing these secondary effects, neu- Myers popularized the theory of the subliminal self as
rologists were forced to belabor a theory whose very a hidden domain that was vast and profound, provid-
dissemination had changed the clinical reality under ing the basis for all psychic life. Incorporating such
observation. How to integrate the psychological di- phenomena as genius, hypnosis, and even telepathy,

H.3. Concepts of Mental Illness in the West 77
Myers cast the unconscious world in a highly spiri- Civilization and Its Discontents (1929), Freud turned
tual, positive light, establishing a rationale for the his attention to the interaction between individuals'
use of psychotherapy as a tool for unleashing the desires and society's demands, highlighting the rela-
inner creative forces. In the United States, religious tion between repression and culture.
healing cults like Christian Science and the Emman- From in-depth clinical studies, Freud assembled a
uel movement made psychotherapy synonymous model of the mind as a dynamic battleground where
with a practical means of tapping into the subcon- libidinous energies surge from the unconscious
scious, the reservoir in human beings of God's spirit through a preconscious stage and then to conscious-
and power. ness, but only after intensive censorship that misdi-
Sigmund Freud was a Viennese neurologist trained rects the energy to less threatening endpoints. Inter-
in neuroanatomy, neurophysiology, and neuropsy- nal harmony is maintained at the price of continual
chiatry, who also boasted a deep knowledge of litera- suppression of unwanted thoughts and memories;
ture and anthropology. Freud's own journey into the anxiety is the internal warning that the dynamic
hidden self, an exploration that commenced with equilibrium is becoming unstable. Psychopathology
The Interpretation ofDreams (1900), has been gener- results from the desperate attempts by the ego -
ally recognized as one of the monumental intellec- weakened by childhood trauma and saddled by inse-
tual achievements of our time. Only a sketch of his curity and guilt - to maintain control in the face of
work can be attempted here. Although the therapeu- intrapsychic conflict. At low levels of stress, the ego
tic merit of psychoanalysis remains a controversial copes through simple defense mechanisms, such as
issue, there can be little doubt that the Freudian displacement, projection, and denial. Higher levels
model of human action has had a tremendous and may yield full psychoneurotic symptoms such as pho-
pervasive influence in many areas of culture. In his bias, hysteria, and compulsions. For example, a hys-
early publications, Freud argued for the importance terical paralysis of the legs might afflict a young
of the unconscious in directing most of our waking actor who, although feeling otherwise normal stage
activities and all of our nocturnal ones. Conscious- fright, is unable to confront his fears because of long-
ness represented only a fraction of our true selves. In internalized parental demands that he not admit
contrast to the ideas of Myers and other supporters failure (associated with some childhood trauma).
of psychotherapy, Freud's conception of the uncon- The paralysis allows the actor to sidestep the conflict
scious referred to a realm of primitive, even carnal, and even the very fact that that is what he is doing.
desires that followed its own irrational inner logic of Such symptoms may allow psychic survival, but
wish fulfillment. Indeed, our entire mental appara- they exact a heavy price in inflicting a diminished
tus, even our conscious selves, depended on the en- level of existence. At the highest level of stress, the
ergy, or libido, that derived from the unconscious. unconscious demands overwhelm the ego's defenses,
Our path to normal adulthood consisted of success- resulting in psychotic disintegration.
fully negotiating certain developmental challenges, A distinguishing characteristic of Freud's system
which included the oral, anal, and genital stages, was the insistence that mental disorders had mean-
and resolution of the notorious Oedipal conflict. De- ings. Being neither random nonsense nor mere neu-
velopmental aberrations could be traced to the after- rological defects, such symptoms were in fact cre-
effects of sexual conflicts in childhood. ative responses to specific problems that confronted
In his later work, Freud developed a tripartite a troubled individual. (Freud thus departed from
metapsychology of self, comprised of the id, the pool Janet's model of neurosis as a product of a weakened
of unconscious desires and memories; the ego, the mind, seeing it instead as resulting from a mind that
core adaptive mechanism, which was built on terri- was all too vigorous.) A psychopathological symptom
tory reclaimed from the unconscious as the infantile was like a key to an unidentified lock; the clinical
pleasure principle was superseded by the mature challenge was to make the shape of the lock visible.
reality principle; and the superego, the ego's censor, Psychoanalysis was to provide the clinician with the
a mostly unconscious system of rules and mores in- knowledge and tools necessary for recognizing what
ternalized from parental and societal instruction. the immediate conflict was and then tracing back-
The ego, the component of self we most identify with, ward to the distant trauma that had engendered this
is a partly conscious and partly unconscious struc- particular symptom formation. Until the underlying
ture that must continually mediate between the de- conflict was disinterred, neurotics were condemned
sires of the id and the restrictions of the superego. to react inappropriately to current challenges, unwit-
Toward the end of his career, in such publications as tingly seeing in them replays of a past battle that

could no longer be won. Therapy consisted of analyz- analysis for some time remained targeted mainly
ing unconscious material, as revealed in dreams, on neuroses, his psychodynamic model was of suffi-
slips of the tongue, and free associations, and a care- cient heuristic strength to encompass psychotic dis-
ful manipulation of the patient-physician relation- orders as well. The combination of Freud and Krae-
ship, in which patients made visible their neurotic pelin was a nosological framework that integrated
structures by transferring onto the therapist their private practice and institutional systems of mental
unresolved emotions. The couch was to become a disorder - the beginning of modern psychiatry.
dissecting table for the dispassionate analysis of psy- Psychoanalysis provided a fresh solution to the
chic morbidity. In time, patients, liberated from ex- vexing problems facing neurologists who had built
ternalized demands and guilt, would be free to re- their practices on theories of neurasthenia, already
integrate their desires into more authentic, stronger in decline. Where psychological interactions of pa-
selves. Deprived of their function, the symptoms tient and physician were devilish problems for prac-
would simply cease to exist. titioners following organically justified systems,
After Freud, the analysis of human behavior Freud's psychogenically based models turned a liabil-
would never again be simple. Henceforth, the sur- ity into a virtue. As a high technique of the mind,
face or manifest meaning of any action might belie created by a distinguished Viennese physician, psy-
multiple hidden or latent desires that would have to choanalysis co-opted religiously suspect psychother-
be decoded. The nineteenth-century hierarchical apy, transforming it into a medically legitimate tool
model of reason mastering desire was humbled by that office practitioners could adopt. Even better, for
the realization that there existed no pure rational those physicians who relied on uncertain methods of
part of self that acted without the distorting influ- suggestion, hypnosis, or enforced discipline, psycho-
ence of the unconscious; and every noble accomplish- analysis provided a direct means of handling those
ment of civilization was now sullied as a by-product nervous patients who undermined the doctors' com-
of excess libido. The lines between sanity and insan- petence by refusing to get better. The fault was
ity, and between normality and abnormality, were thrown back into the patient as "resistance."
forever blurred, for each individual existed in a dy- In the United States, which would become the
namic equilibrium in which unconscious forces held largest supporter of Freud's theories (rejected as
sway every night and at times during the day. Fur- "Jewish psychology" in his homeland), not only psy-
thermore, in making a distinction between our in- chologically oriented neurologists but many psychia-
stinctual aims and their objects (the aim of the sex trists as well welcomed the new model. Even though
drive was reproduction; the object was one's lover), psychoanalysis was irrelevant in the institutional
Freud severed the connection whereby mental dis- context, which represented the majority of psychiat-
ease was equated with behavior contrary to instinct. ric care, the advent of a system that brought with it
Normal desires could lead to perverse acts, and vice the trappings of learned study and European pres-
versa. Judgments of mental illness were no longer tige was welcomed by many as a means of raising
simply statements of what was "unnatural." the status of what was widely regarded as the most
Freud's immediate effect within psychiatry was backward of medical specialties. This interest was
to achieve for the neuroses what Kraepelin had particularly strong in research institutes, which
accomplished for the psychoses. In Kraepelin's sys- many states had created in this period to serve as
tem, neuroses were an unsettled mixture of somatic catalysts for scientific advance.
and functional disorders. Freud directed psycho- The precise manner in which the Freudian doc-
analysis at the latter group, heightening the distinc- trine rose to prominence in general culture is still
tion by the use of the term psychoneurosis. Thus, not well understood. As one example, recent histori-
certain disparate conditions, such as hysteria, obses- cal work suggests that World War I played a precipi-
sions, compulsions, and phobias, were united in a tating role in Britain when a large number of sol-
single category, yet each retained its own integrity diers broke down in battle. That anyone might act
as a clinical syndrome, recognizable in case histo- insane, given sufficient stress, was forceful testi-
ries. So successful was Freud's approach that soon mony of sanity's fragility. Neurologists diagnosed
the original somatic connotation of neuroses was these soldiers as suffering from "shell shock," origi-
entirely lost and the term psychoneurosis was nally interpreted in terms of a somatic injury. Nei-
dropped as redundant. Freud went even further ther reflex hammer nor rest cure proved useful, how-
than Kraepelin, however, in providing a model that ever. The best success was obtained by physicians
was causal as well as descriptive. Although psycho- who applied a form of Freudian psychotherapy to

relieve the trauma. Overnight, psychoneuroses tive in the creation of standardized systems of no-
gained national currency. Those neurologists in- menclature. Military experience and the growth of
volved in the war effort were precisely the ones who centralized reporting bureaus highlighted the rteed
would later gain for Freudianism a solid profes- for diagnostic uniformity. The first Diagnostic and
sional footing in Britain. Statistical Manual, Mental Disorders (DSM), created
in 1950, reflected the extension of the Kraepelin and
Biology Freudian systems, augmented by new theories of
In the 1920s and 1930s, virtually every branch of personality. Earlier, dementia praecox had been re-
biomedical science sought to apply the tools of experi- conceptualized by Swiss psychiatrist Eugen Bleuler
mental medicine to the problem of psychiatry. In- into the schizophrenias (hebephrenia, catatonia,
deed, given the isolation of the asylum from centers paranoia), a term that referred to the splitting of
of medical advance, it was an even bet whether the thoughts from affects. Incorporating some aspects of
next scientific breakthrough would emerge from psychoanalysis. Bleuler emphasized the develop-
within psychiatry or from an outsidefield.The para- ment of the psychotic mental process.
digm was syphilis, whose tertiary state, general pe- In contrast to Kraepelin, Bleuler argued that favor-
resis, had been responsible for up to 20 percent of able outcomes were possible in many cases. The DSM
mental hospital admissions. In 1897 Richard von followed Bleuler in its description of the category of
Krafft-Ebing demonstrated the long-suspected con- major psychoses, referring to personality disintegra-
nection between syphilis and paresis, a link soon tion and a failure to relate effectively to people or
confirmed by the Wasserman test. The culpable spiro- work. Included within this group were the schizophre-
chete was identified in paretic brains by Hideyo nias, as well as paranoia, manic-depression, and invo-
Noguchi in 1913. Finally, in 1917 the Austrian physi- lutional psychosis (depression of old age). The second
cian Julius von Wagner-Juaregg developed a method major category consisted of psychoneuroses, de-
of fever therapy to halt further paretic deterioration; scribed in Freudian terms as disorders caused by the
in 1927 he was awarded the Nobel Prize. The success unconscious control of anxiety through the use of
of a purely organic solution to a major psychiatric defense mechanisms. These included anxiety reac-
disorder suggested that other such achievements tions, dissociation, conversion reaction, obsessive-
were sure to follow. compulsion, and depression. The third category, com-
Leading researchers thus pursued metabolic, endo- prising personality disorders, was differentiated by
crine, neurophysiological, and even toxicological its stress on behavioral as opposed to emotional dis-
models for psychopathology. Constitutional theories turbances. Described in this category were such popu-
were advanced by the German Ernst Kretschmer, lar terms as sociopath, antisocial behavior, and sexual
who correlated body types to predispositions for spe- deviate.
cific mental illnesses. Franz Kallman investigated As a shift from earlier attempts at standard psychi-
the genetics of mental illness by studying schizo- atric nosology, which were directed toward inpatient
phrenic twins. I. V. Pavlov launched a model of ex- populations, the DSM reflected the new reality of
perimental neurosis in which animals frustrated in psychiatry's burgeoning private-practice base, as
conditioned learning tests developed forms of mental well as the experiences of military psychiatrists,
breakdowns. The introduction of a wave of somatic whose observations on broad populations revealed
treatments for mental illness in the middle 1930s that the vast majority of psychopathologies did not
transformed psychiatric practice. Insulin shock, me- fit the earlier classifications. Published statements
trazole shock, electric shock, and psychosurgery had of nosology do not necessarily reflect full clinical
dramatic effects on patient behavior, raising hopes reality, however. The DSM was by no means univer-
that the fatalism associated with severe mental ill- sally adopted. It reflected more the penetration of
ness might prove untrue. Psychosurgery in particu- Freudian psychiatrists into the power structure of
lar was believed to restore chronic schizophrenics to the profession than it did any dramatic shift in the
productive citizenship. Its inventor, Portuguese neu- state hospitals, where niceties of diagnosis were con-
rologist Antonio Caetano de Egas Moniz, was sidered superfluous to the daily choice of treatment
awarded the 1949 Nobel Prize in medicine. plan.
Classification at Midcentury After 1950

After World War II, professional organizations such In the decades following World War II, psychiatry as
as the American Psychiatric Association became ac- a medical profession experienced tremendous expan-

sion. In the United States the advent of community institutional milieu, and even the very act of psychi-
mental health centers and third-party payments atric labeling in determining patterns of mental dis-
swelled the ranks of noninstitutional practitioners. order. Anthropologists have brought the power of
The shift away from the state hospital, the historical cross-cultural study to the problem of mental illness,
center of the profession, redirected momentum to- showing that what was assumed to be biologically
ward mild disorders and their treatment through fixed often was in fact "culture bound," a local prod-
counseling. Psychodynamically oriented psychia- uct, specific to place and time. Within any major
trists found their authority further magnified as a U.S. city are subpopulations who conceptualize —
new army of clinically trained psychologists, social and experience - disease in incommensurate ways.
workers, and guidance counselors looked to them for Moreover, if a diagnosis of mental illness reflects a
professional training and supervision. Psychother- judgment as to adaptive functioning, mental disor-
apy, though not necessarily Freudian psychoanaly- ders can no longer be held to be natural, universally
sis, became viewed by the middle class as both useful true categories of illness, for what is adaptive in one
and affordable. Psychiatrists and their proxies in the local culture is maladaptive in another. These stud-
allied professions offered a colorful array of different ies of health and healing have also brought to light
forms of counseling, which included behavior ther- the manifold ways in which concepts of disease and
apy, group therapy, client-centered therapy, existen- therapeutic rituals enter into the complex web of
tial therapy, and even primal scream therapy. power relations we call society.
At the same time, dramatic developments occurred Psychiatric conditions, which touch on our most
in somatically oriented treatment and research. The intimate concerns and relationships, are especially
introduction in the mid-1950s of the major tranquiliz- rich cultural resources and have embedded meanings
ers, such as chlorpromazine, revolutionized hospital and structures not easily seen - and often denied by
care. By dampening hallucinations and other florid the professional culture of scientific medicine. Men-
psychotic symptoms, the new drugs quieted ward life tal illness is a fundamentally messy construct, an
and encouraged new "open-door" hospital policies. irreducible mixture of personal, social, cultural, and
Also, they accelerated the process of deinstitutionali- scientific beliefs.
zation, helping many patients to achieve a level of
functioning consistent with some form of extramural Classification in the 1980s
existence. Tranquilizers were soon followed by other In 1980, the third version of the DSM was released,
classes of psychoactive drugs, such as antidepres- signaling a new departure in psychiatric nomencla-
sants and the use of lithium in the treatment of ture. Responding to calls for a diagnostic system that
manic-depression. The growing importance of psy- might elevate psychiatry's status as a scientific disci-
chopharmacology spurred neurophysiological re- pline, the DSM task force pared down medical classifi-
search, leading to suggestive models of neurotrans- cation to its most basic elements, the description of
mitter deficiencies as the mediating cause of severe known phenomena, usefully arranged. Without ques-
mental disorders. Other biological research has pur- tion, the most stable and powerful nosologies are
sued genetic interpretations of the tendency of severe those based on proven etiology. For example, identifi-
mental disorders to run in families. In recent years, cation of the culpable spirochete made it possible to
there has been a clear shift within psychiatry to the distinguish paresis from senility. Because debate still
somatic orientation. surrounds the true cause of any mental disorder, the
One of the striking developments of the postwar DSM argues that it is premature for psychiatry to
years in the conceptualization of mental disorders construct etiologically based systems. At present, we
has been the influence of the social sciences, espe- find that phobic disorders can have Pavlovian, Freud-
cially sociology and anthropology. Once behavior is ian, or somatic explanations. In disagreeing about
understood to reflect the matrix of psychological, theory and treatment, however, clinicians neverthe-
social, and cultural forces that mold an individual, it less can reach a consensus on the identification of a
is a natural progression to assume that abnormal or disorder.
impaired behavior is likewise shaped and should be The stated goal of the DSM-III is simply to provide
investigated with these additional tools. Again, the a set of criteria and procedures by which all camps of
literature is much too large to provide other than a psychiatrists might speak a common diagnostic lan-
bare outline. Sociologists have reported on such in- guage. In the interest of ensuring interrater reliabil-
fluences as social class, role conflicts, social control, ity, disorders were to be denned unambiguously and
life stress, social integration, family interactions, based on checklists of easily verified data. The diag-

nostic categories were themselves to be constructed sis shifts power into the hands of the statistical re-
in the form of statistically significant clusters of searcher and away from the clinician. DSM-III sets
symptoms, derived from extensive field trials and in place procedures for the continued revision of
empirical reports. Without etiology, psychiatric ail- diagnostic categories, whose organization may soon
ments can be referred to only as syndromes or disor- reflect more of what seems "statistically significant"
ders, not specific diseases. Indeed, it is expected that than the realities of clinical practice. On the other
elements from several different disorders might ap- hand, the symptom-based nosology also harkens
pear in any one individual. The authors of DSM-III back to the eighteenth century, when patients' sub-
argue that the quest for scientific purity has not, jective assessments of their problems set the pace of
however, negated all clinical utility. Tightly defined medical practice. In DSM-III homosexuality was
and empirically tested descriptions of syndromes do eliminated from the rolls of mental disorders-
allow practitioners to predict a patient's course and except when it is considered bothersome by the pa-
outcome, and they provide some guidance in treat- tient. Squeezed between deference to patients' self-
ment choice. For example, the identification of a rating scales and statistical priorities, the clinician
major depressive syndrome alerts the clinician to has less room to form independent diagnoses.
the likelihood of the patient's having a future hypo-
chondriacal reaction.
As of 1980 the DSM outlined the following catego- Mental Illness and Psychiatry: Retrospect
ries: disorders of childhood or infancy (hyperactivity, and Prospect
anorexia, retardation, autism); known organic cause From our historical survey, several themes emerge
(diseases of old age, drug-induced); disorders of concerning the linked development of psychiatry
schizophrenia (disorganized, catatonia, paranoid, un- and conceptions of mental illness. Psychiatry as a
differentiated); paranoid disorders (without schizo- learned discipline contains no one school of thought
phrenic signs); affective disorders (bipolar, major that is sufficiently dominant to control the medical
depressive); anxiety disorders (phobias, obsessive- meaning of insanity. Given the administrative reali-
compulsive); somatoform (conversion disorder, hypo- ties within which mental health professionals cur-
chondriasis); dissociative (fugue states, amnesia, rently labor, the move to a standardized diagnostic
multiple personality); and personality disorders. Per- system may nonetheless win out. It is important for
haps the most controversial change in the new ap- the various factions to share a common language,
proach was the elimination of the category of psycho- but this is not the same as reaching a consensus on
neuroses. In the "atheoretical" approach, disorders why someone is disturbed and what should be done
were grouped according to symptoms, not underlying about it - two components of illness as a cultural
psychic mechanism. Neurotic disorders thus resolve reality.
into various forms of anxiety states. Also removed This difficulty reflects in part psychiatry's unique
was the heading ofpsychosis, which had included the evolution as a medical specialty. Common sociologi-
major affective disorders; experience showed that cal wisdom holds that the livelihood of a scientific
many patients labeled psychotic did not have psy- specialty depends on its capacity to defend the pe-
chotic features. Involutional melancholia was col- rimeter of its knowledge base. This task has always
lapsed into ordinary depression, because no evidence been problematic for psychiatrists, for the borders
surfaced to show that it was unique. between lay and learned conceptions of madness re-
It is, of course, far too early to make informed main indistinct, a situation that also pertains to the
judgments about the consequences of the new DSM. relations between psychiatry and other disciplines,
However, some trends can be discerned. First, medical as well as nonmedical. To begin with, men-
DSM-III clearly marks a loss of professional author- tal disorders are not restricted to the controlled envi-
ity by psychoanalysis, one that will worsen. Much rons of the analyst's couch or laboratory bench, but
of the need for teaching Freudian theory to the are manifested in the home, school, or office, as dis-
mass of workers within the allied mental health ruption in love, work, or play. When the very stuff of
professions - most of whom would never practice madness is reduced to its basic elements, we find
true psychoanalysis - was based on the need to ex- nothing more than a tangled heap of curious speech
plain the psychiatric diagnostic system. acts and defiant gestures, odd mannerisms and per-
Second, a more subtle and unpredictable effect of plexing countenances - surely nothing as removed
DSM-III concerns its diminution of the value of clini- from everyday experience as is the retrovirus, the
cal judgment. On one hand, its "atheoretical" empha- quark, or the black hole. Available for all to see and

interpret, psychiatric phenomena thus form an epis- was no clinical problem that could be said to lie
temological terrain that is not easily defended by a outside the physician's grasp. But as the physiologi-
band of professionals who look to stake claims on the cal and bacteriological terrain came into sharper
basis of privileged, expert knowledge. focus, so too did those areas in which medicine was
Psychiatry's turf is also vulnerable at its flank, admittedly ignorant. Paradoxically, as our scientific
from adventurers in other learned disciplines who knowledge becomes increasingly sure, leading to
find that their own research endeavors, logically ex- ever higher expectations, those problems that can-
tended, encompass some aspect of mental illness. not be solved develop an increased capacity to
Thus, as a performance of the body, insanity has threaten our faith in science. "Functional" or "nonor-
routinely been investigated by all the tools available ganic" disorders, whose explanation as well as cure
to biomedical scientists and clinicians. Commenta- remain outside the boundaries of regular medicine,
tors have often noted that, as soon as a valid biologi- thus become disturbances not only within an individ-
cal model is found to exist for a specific mental disor- ual but within the system of medicine as well. It is
der (as in the case of syphilis and general paresis), psychiatry's intraprofessional obligation to deal
that condition is moved out of the purview of psychia- with these problems, shoring up the faith that, al-
try and is claimed by some otherfield- perhaps neu- though no precise medical answers yet exist, they
rology or endocrinology. Over time, the condition are still medical problems - and not yet the business
even ceases to be considered psychiatric. And now of the astrologer or faith healer. Ironically, psychia-
that madness is known to have a cultural reality as try is despised by the rest of medicine for this lowly,
well as a biological one, psychopathology has become but vital role.
a proper focus of most social sciences as well. A more fundamental service role has been that of
Unable to police its own borders, it is no wonder responding to personal crisis. As a specific construct,
that psychiatry remains a confusing, polyglot world, the term schizophrenia may one day find its way into
one that reflects the input of myriad disciplines and the dustbin that holds neurasthenia, chlorosis, and
sources. The surfeit of conceptual approaches to the other long-abandoned medical concepts. But the suf-
problem of mental illness has often been cited as fering and torment felt by persons so afflicted are
evidence that psychiatrists are a singularly conten- not as easily dismissed, nor is the distress of their
tious or poor-thinking lot. A popular professional families. Patients and their families look to the psy-
response has been to invoke a "biopsychosocial" chiatrist to intervene in a situation where there is
model of disease (expressed, e.g., by the multiaxial often little hope, to "do everything possible" to make
system of DSM-III), one that is interdisciplinary and the person whole again.
multidimensional. The root of the problem is deeper, Put simply, psychiatry is the management of de-
however. As mental disorders reflect the entirety of spair. This is the heart of the psychiatrist's social
a person, so the study of insanity comes to reflect the function, to care for those whose problems have no
present contradictions inherent in our universe of certain cure or satisfactory explanation, problems
scholarly disciplines. Our various knowledge sys- that often place a serious burden on society. To a
tems are unified more in rhetoric than in reality. large extent, this function stems from psychiatry's
The status of psychiatry and of the concept of mental historical ties to the asylum, an institution into
illness suffers for making this situation visible. which poured a new class of social dependents. But
Our historical survey provides us with another psychiatry is more than custodial care that can be
approach to the problem of mental illness, one that supervised by hospital administrators. Apparently,
focuses not so much on the intellectual boundaries of we find a measure of emotional security in entrust-
knowledge as on the professional and social function ing these special woes to a group of trained profes-
of psychiatry. First, we have seen how modern psy- sionals who have dealt with similar matters, believ-
chiatry emerged not in isolation, but in relation to ing that practical wisdom comes with experience; to
other areas of medicine: Psychiatry's peculiar do- those who can link our seemingly unique problems
main is precisely those problems that baffle regular with past cases and thus somehow lessen the alien-
medicine. (The rise of the "nervous" disorders pro- ation and shame. The additional value of a medical
vides an excellent example of this phenomenon.) In degree is the promise that with it comes a trained
the late nineteenth century, as medicine gained sta- intellect, a calm authority in response to crisis, and
tus as a scientific discipline, this role attained a access to all available medical tools that might yield
special significance. Before, when virtually all of even a remote possibility of benefit, even if they are
medicine was based on uncertain knowledge, there not yet understood.

In sum, psychiatry is a field defined not by refer- curred. In the past, part of a physician's medical
ence to a specific part of the human body, like podia- authority stemmed from the assumption that he or
try, or a specific class of people, like gerontology, or she was learned in the ways of people and society, a
even a specific disease process, like oncology. knowledge that was seen as legitimating his or her
Rather, it is a field demarcated by our collective right to intervene in intimate human affairs. Psycho-
helplessness in the face of human problems that by analysts, among the most scholarly of physicians,
all appearances should be solvable and understand- were thus looked upon as effective doctors. Now,
able through medical science, but as yet are not. however, such broad cultural learning is no longer
Hence, what comprises mental illness is fundamen- considered an appropriate route to a career that de-
tally a moving target, a hazy area that is redrawn mands the absorption and analysis of a tremendous
by every generation and local culture as new prob- volume of scientific facts. Whether psychiatry will
lems and dilemmas arise. Specific categories of men- dissolve into two separate professions, one of lay
tal disorder are formed at the interface of social counseling and the other of purely biological treat-
concern and professional interests, much in the way ment, remains to be seen. Yet there is also a possibil-
that the pressures of tectonic plates produce new ity that general medicine will reintegrate the spe-
features of the physical landscape. Thus, shifts in cial function of the healing relationship into its list
either cultural anxieties or professional priorities of medical priorities. Perhaps in this psychiatry
can shape the clinical geography. We have also seen might lead the way.
that this border is a dynamic one, as professionals Jack D. Pressman
both respond to and in turn shape these areas of
concern. That a given disease, once understood, is
no longer considered psychiatric is thus not so Bibliography
much a loss for psychiatry as it is an indication of Ackerknecht, Erwin H. 1968. A short history of psychiatry,
what has been psychiatry's true function. Once a 2d edition. New York.
disorder is well understood, psychiatry's proper busi- Armstrong, D. 1980. Madness and coping. Sociology of
Health and Illness 2: 296-316.
ness with it has in fact come to an end.
Ayd, F. J., and B. Blackwell, eds. 1970. Discoveries in
Now we have a perspective from which to view, in biological psychiatry. Philadelphia.
retrospect and prospect, the peculiar geography of Burnham, J. 1978. The influence of psychoanalysis upon
mental illness. Looking backward at the history of American culture. In American psychoanalysis: Ori-
the conditions associated with mental illness, at gins and development, ed. J. Quen and E. Carlson, 52-
such things as hypochondriasis and monomania, we 72. New York.
see an archaeological record not to be dismissed as Bynum, W. F. 1981. Theory and practice in British psychia-
mere professional folly, but a record of life's trage- try from J. C. Prichard (1785-1848) to Henry Mauds-
dies, large and small. No matter how successful sci- ley (1835-1918). Nihon Ishigaku Zasshi 27: 1-22.
ence will be in the future in providing additional 1983. Psychiatry in its historical context. In Handbook
ofPsychiatry, Vol. 1, ed. M. Shepherd and O. Zangwill,
tools to alter the mind or brain, some of us neverthe-
11-38. Cambridge.
less will be overwhelmed by life's new challenges, 1984. Alcoholism and degeneration in 19th-century Eu-
finding our own internal resources insufficient. For ropean medicine and psychiatry. British Journal of
some, whether because of faults of biology, environ- Addiction 79: 59-70.
ment, or will, the collapse will be complete. That is Bynum, W. F., Roy Porter, and Michael Shepherd, eds.
the reality of mental disorders, which is surely not 1985-8. The anatomy of madness: Essays in the his-
soon to disappear. tory of psychiatry, 3 vols. London.
What the future holds for the organization of psy- Carlson, E. T., and N. Dain. 1962. The meaning of
chiatry as a medical specialty is not easily predicted. moral insanity. Bulletin of the History of Medicine
The special task of psychiatrists, in managing the 36: 130-40.
unmanageable, is increasingly difficult to perform Cooter, R. 1976. Phrenology and British alienists, c. 1825-
1845. Medical History, 20: 1-21, 135-51.
as it becomes harder to maintain the dual role of
Dain, N. 1964. Concepts of insanity in the United States,
counselor and medical scientist. As medicine in gen- 1789-1865. New Brunswick, N.J.
eral relies on ever stricter laboratory standards of Davidson, A. 1988. How to do the history of psychoanaly-
what is real or valid, the definition of what consti- sis: A reading of Freud's three essays on the theory of
tutes a good doctor becomes that much narrower. sexuality. In The trial(s) of psychoanalysis, ed. F.
The decline of the status of psychoanalysis, for exam- Meltzer, 39-64. Chicago.
ple, may reflect the shrinkage that already has oc- Donnelly, M. 1983. Managing the mind. London.

Eisenberg, L. 1988. Editorial: The social construction of Mechanic, David. 1978. Medical sociology, 2d edition. New
mental illness. Psychological Medicine 18: 1-9. York.
Ellenberger, H. 1970. The discovery of the unconscious: Midelfort, E. 1980. Madness and civilization in early mod-
The history and evolution of dynamic psychiatry. New ern Europe. In After the Reformation: Essays in honor
York. ofJ. H. Hexter, ed. B. Malament, 247-65. Philadephia.
Fischer-Homberger, E. 1972. Hypochondriasis of the eigh- Mora, George. 1980. Historical and theoretical trends in
teenth century - neurosis of the present century. Bul- psychiatry. In Comprehensive textbook of psychiatry,
letin of the History of Medicine 46: 391-9. 3d edition, ed. Harold Kaplan, Alfred Freedman, and
Foucault, M. 1965. Madness and civilization: A history of Benjamin Sadock, 4-98. Baltimore.
insanity in the Age of Reason, trans. R. Howard. New Parry-Jones, W. L. 1972. The trade in lunacy. London.
York. Porter, R. 1979. Medicine and the Enlightenment in
1987. Mental illness and psychology, trans. A. Sheridan. eighteenth-century England. Bulletin of the Society of
Berkeley and Los Angeles. the Social History of Medicine 25: 27-40.
Gay, P. 1988. Freud, a life of our time. New York. 1981. Being mad in Georgian England. History Today
Geyer-Kordesch, J. 1985. Cultural habits of illness: The 31: 42-8.
enlightened and the pious in eighteenth-century Ger- 1983. The rage of party: A glorious revolution in En-
many. In Patients and practitioners, ed. R. Porter, glish psychiatry? Medical History 27: 35-70.
177-204. Cambridge. 1987. Mind-forg'd manacles: A history of madness in
Goldstein, J. 1982. The hysteria diagnosis and the politics England from the Restoration to the Regency. Cam-
of anticlericalism in late nineteenth-century France. bridge, Mass.
Journal of Modern History 54: 209-39. Powell, R. 1979. The "subliminal" versus the "subcon-
1987. Console and classify: The French psychiatric pro- scious" in the American acceptance of psychoanalysis,
fession in the nineteenth century. New York. 1906-1910. Journal of the History of Behavioral Sci-
Goodwin, D., and S. Guze. 1984. Psychiatric diagnosis, 3d ence 15: 155-65.
edition. New York. Ray, L. J. 1981. Models of madness in Victorian asylum
Gosling, F. G. 1987. Before Freud: Neurasthenia and the practice. Archives of European Sociology 22: 229-64.
American medical community. Urbana, 111. Risse, G. 1988. Hysteria at the Edinburgh infirmary: The
Grob, G. 1973. Mental institutions in America: Social pol- construction and treatment of a disease, 1770—1800.
icy to 1875. New York. Medical History 32: 1-22.
1983. Mental illness and American society, 1875-1940. (In press). The great neurosis: Clinical constructions of
Princeton, N.J. hysteria, 1876-1895.
Hale, N. G. 1971. Freud and the Americans. New York. Rosenberg, C. 1968. The trial of the assassin Guiteau:
Hunter, R., and I. Macalpine. 1963. Three hundred years of Psychiatry and law in the Gilded Age. Chicago.
psychiatry, 1535—1860. London. 1989. Body and mind in the nineteenth-century medi-
Jacyna, L. S. 1982. Somatic theories of mind and the inter- cine: Some clinical origins of the neurosis construct.
ests of medicine in Britain, 1850-1879. Medical His- Bulletin of the History of Medicine 63: 185-97.
tory 26: 233-58. Rothman, D. 1971. The discovery of the asylum: Social
Jewson, N. 1974. Medical knowledge and the patronage order and disorder in the New Republic. Boston.
system in 18th-century England. Sociology 8: 369-85. 1980. Conscience and convenience: The asylum and its
Jimenez, M. A. 1987. Changing faces of madness: Early alternatives in progressive America. Boston.
American attitudes and treatment of the insane. Hano- Rousseau, G. S. 1976. Nerves, spirits and fibres: Towards
ver, N.H. defining the origins of sensibility. Studies in the Eigh-
Kleinman, Arthur. 1988. Rethinking psychiatry. New York. teenth Century 3: 137-57.
Lawrence, C. 1979. The nervous system and society in the Scull, A. 1975. From madness to mental illness: Medical
Scottish Enlightenment. In Natural order: Historical men as moral entrepreneurs. European Journal of
studies of scientific cultures, ed. B. Barnes and S. Sha- Sociology 16: 218-51.
piro, 19—40. London. ed. 1981. Madhouses, mad-doctors, and madmen. London.
MacDonald, M. 1981. Mystical bedlam: Madness, anxi- 1982. Museums of madness: The social organization of
ety and healing in seventeenth-century England. insanity in nineteenth-century England. New York.
Cambridge. Shortt, S. E. D. 1986. Victorian lunacy: Richard M. Bucke
1982. Religion, social change, and psychological healing and the practice of late nineteenth-century psychiatry.
in England, 1600-1800. In The church and healing, New York.
ed. W. J. Shields, 101-25. Oxford. Showalter, E. 1980. Victorian women and insanity. Victo-
1986. The secularization of suicide in England, 1600- rian Studies 23: 157-80.
1800. Past and Present 111: 50-100. Sicherman, Barbara. 1977. The uses of a diagnosis: Doc-
McGrath, W. 1986. Freud's discovery of psychoanalysis. tors, patients, and neurasthenia. Journal of the His-
Ithaca, N.Y. tory of Medicine 32: 33-54.

II.4. Sexual Deviance as a Disease 85
Smith, R. 1973. Trial by medicine: Insanity and responsi- by behavioral psychologists. Perhaps both groups
bility in Victorian trials. Edinburgh. maintain the classification as a way of justifying
Smith-Rosenberg, C. 1972. The hysterical woman: Sex their intervention or of promising a cure.
roles and conflict in nineteenth-century America. So-
cial Research 39: 652-78.
Spitzer, R., and Janet Williams. 1980. Classification in Medical Background
psychiatry. In Comprehensive textbook of psychiatry, Though physicians throughout recorded history
3d edition, ed. Harold Kaplan, Alfred Freedman, and have been interested in diseases and infirmities that
Benjamin Sadock, 1035-72. Baltimore. affect sexual performance, the concept that certain
Stone, L. 1982. Madness. New York Review of Books 16 forms of sexual behavior constitute a disease in and
Dec:128-36.
of themselves is a modern phenomenon. It also
Sulloway, F. 1979. Freud: Biologist of the mind. New York.
seems to be restricted to western Europe and people
Szasz, T. 1972. The myth of mental illness. London.
Temkin, Owsei. 1971. The falling sickness: A history of
and cultures descended from or influenced by west-
epilepsy from the Greeks to the beginnings of modern ern European culture.
neurology, 2d edition. Baltimore. One reason for the development of the concept of
Tischler, G., ed. 1987. Diagnosis and classification in psy- sexual "deviation" as a disease can be found in some
chiatry: A critical appraisal ofDSM-III. New York. of the early modern challenges to the humoral
Tomes, Nancy. 1984. A generous confidence: Thomas theory of medicine. Early in the eighteenth century,
Storykirkbride and the art of asylum-building, 1840- the great clinician Hermann Boerhaave, a dominant
1883. Cambridge. figure in medical thought, had written in his Institu-
Zilboorg, Gregory, and George W. Henry. 1941. A history of tiones Medicae (1728) that the rash expenditure of
medical psychology. New York. semen brought on lassitude, feebleness, a weaken-
ing of motion, fits, wasting, dryness, fevers, aching
of the cerebral membranes, obscuring of the senses,
particularly that of sight, decay of the spinal cord,
fatuity, and similar evils. Though Boerhaave's idea
II.4 undoubtedly was based on observations of the gen-
Sexual Deviance as a Disease eral lassitude usually afflicting men and women af-
ter orgasm, it was also an encroachment of tradi-
tional Christian teaching about sex into the medical
Sexual "deviance" is technically any deviation from field.
the sexual norm. Sexual disease, a new diagnostic Boerhaave's observations of sex as a causal factor
category in the eighteenth century, was classed as a in some forms of illness also fit into a new medical
syndrome and seems in retrospect to have been an theory known as "vitalism," based on the work of
iatrogenic one based more on philosophical and Georg Ernst Stahl as well as others. Stahl (1768)
moral grounds than on any medical ones. The dis- had taught that there was a unity of soul and body, a
ease entity, however, was fitted into some of the unity symbolized by the anima, which protected the
medical theories of the time, and as these theories body from deterioration. When the tonic movements
were challenged and undermined, modifications of normal life were altered by the body or its organs,
were made in order to justify maintaining certain disease supervened. Disease was thus little more
forms of sex behavior in the category of disease. than the tendency of the anima (or of nature) to
In recent decades much of the sexual behavior reestablish the normal order of these movements as
previously classed as disease has been removed from quickly and efficiently as possible.
that category. This redefinition has been based on a A contemporary (and rival) of Stahl, Frederich
better understanding of sexual behavior. It has also Hoffmann, equated life with movement, whereas
been a result of the protests of some groups who death corresponded to the cessation of movement.
reject being classed as ill or sick and having their The living organism was composed offibershaving a
behavior categorized as pathological, emphasizing characteristic neurogenic tonus (the capacity to con-
the iatrogenic component of the disease. Nonethe- tract and dilate being regulated by the nervous sys-
less, efforts are being made to maintain other kinds tem) centered in the brain. When tonus was normal,
of sexual activity under the rubric of disease. Gener- the body was healthy, but every modification of
ally, these are activities that are regarded as unac- tonus brought a disturbance of health. Thus, a man
ceptable by society or viewed as compulsive behavior who indulged in masturbation gradually damaged

his memory because of the strain on the nervous posed to impregnate his sister-in-law, which he was
system. ordered to do by his father Judah:
Building on this foundation were other physi-
cians, including John Brown and Theophile de And Onan knew that the seed should not be his;
Bordeu. Brown's medical philosophy, summarized in and it came to pass, when he went in unto his brother's
his Elements of Medicine (1803), is based at least in wife,
part on his own experience with gout. In theorizing that he spilled it on the ground,
lest that he should give seed to his brother.
about his gout, he concluded that "debility" was the And the thing which he did displeased the Lord;
cause of his disorders and that the remedy was to be wherefore He slew him also.
sought in "strengthening measures." To overcome
his gout he had to strengthen himself, avoid debili- Though the story has often been interpreted as a
tating foods, and treat himself with wine and opium. prohibition against masturbation, the act described
Whether his gout was cured remains debatable, is coitus interruptus; the punishment seems to have
but from his experience he erected a medical philoso- been meted out not so much for Onan's having
phy known as "brunonianism." Basic to his belief spilled the seed as for his having refused to obey the
system was the notion of excitability, denned as the Levirate requirement that he take his brother's wife
essential distinction between the living and the as his own.
dead. The seat of excitability was the nervous sys- Around 1700 an anonymous writer, perhaps in
tem, and all bodily states were explained by the London, wrote a work in English dealing with
relationship between excitability and excitement. onania. This had a wide circulation and was trans-
Too little stimulation was bad, whereas excessive lated into several languages. The first U.S. edition
stimulation had the potential of being worse because was published in Boston in 1724 under the title of
it could lead to debility by exhausting the excitabil- Onania; or, the Heinous Sin of Self-Pollution, and all
ity. Excitability was compared to fire. If there was its Frightful Consequences, in both Sexes, Consid-
not enought air (insufficient excitement), the fire ered. With Spiritual and Physical Advice to those,
would smolder and die out, but under a forced draft who have already injur'd themselves by this Abomina-
(too much excitement), the fire would burn exces- ble Practice. And Seasonable Admonition to the
sively, become exhausted, and go out. Youth (of both SEXES) and those whose Tuition they
This led Brown to conclude that there were two are under, whether Parents, Guardians, Masters, or
kinds of diseases, those arising from excessive ex- Mistresses. To which is Added, A Letter from a Lady
citement (sthenia) and those from deficient excite- (very curious) Concerning the Use and Abuse of the
ment (asthenia). Too much stimulation carried an Marriage-Bed. With the Author's Answer thereto.
asthenic ailment into a sthenic one. Contact be- The author attributed a number of "corruptions of
tween the sexes, through kissing and being in each the body" to "self-pollution," including palsies, dis-
other's presence, gave an impetuosity to the nerves, tempers, consumptions, gleets, fluxes, ulcers, fits,
and intercourse itself, though it gave temporary re- madness, childlessness, and even death itself. Some
lief, could release too much turbulent energy if car- of these ideas were derived from Boerhaave, but the
ried to excess and could thus cause difficulty. Taking author went so far as to imply that onanism could
a somewhat different approach but ending up with a affect offspring, who were likely to be born sickly
similar conclusion was de Bordeu, who maintained and ailing.
that the lymphatic glands as well as the muscular A copy of the book eventually passed into the
nervous system had vital activity. Secretions, includ- hands of the distinguished Swiss physician Simon
ing seminal secretion, drained the vital essences re- Andre Tissot, doctor to a pope, a correspondent of
siding in every part of the body. Francois Voltaire and Jean Jacques Rousseau, and a
researcher very much interested in the prevention of
Onanism disease. In Lausanne, Tissot (1758) had printed his
At the same time these medical authors were devel- own Tentamen de Morbis ex Manusturpatione, which
oping new theories of medicine, concern over went through many editions and translations. Later
onanism was increasing. The concept of onanism is editions, including Tissot's own French version,
based on the story in Genesis 38:7-10 of Onan, who, were entitled Onanism. The English translation by
following the Levirate custom, was supposed to take A. Hume was published in 1776. There were many
over the wife of his deceased brother Er, who had printings and editions in most Western languages.
been killed by Jehovah. In addition, Onan was sup- Although he considered the earlier treatise on

onania truly chaotic and the author's reflections that deprived them of decency and reason by lower-
nothing but theological and moral trivialities, Tissot ing them to the level of the most lascivious and
did adopt some of the concepts it contained (includ- vicious brutes. Even worse than simple masturba-
ing the association of sexual activity with insanity). tion in women was mutual clitoral manipulation
More important, he put onanism into the theoretical that caused them to love one another with as much
medical framework of the day. Tissot believed that fondness and jealousy as they did men. Onanism was
the physical body suffered from continual wastage, far more pernicious than excesses in simple fornica-
and unless this was periodically restored, death tion, although both were dangerous. Onanism was
would result. Much could naturally be restored particularly debilitating to those who had not yet
through nutrition, but even with an adequate diet attained puberty, because it tended to destroy the
the body could waste away through diarrhea, loss of mental faculties by putting a great strain on the
blood, and, more important for the purposes of this nervous system.
chapter, seminal emission. The importance of semen Tissot's explanation gained a number of followers
to the male, Tissot observed, was documented by the not only because it fit into some of the general medi-
effect it had on physiognomy, because semen was cal theories, but because it was consistent with gen-
what caused the beard to grow and the muscles to eral superficial observations. It also tied into the
thicken. Proof of this influence came from the fact general anxiety about sexual activity that was so
that these physiognomic effects could be eliminated much a part of the Western Christian tradition.
by amputation of the testicles. Though Tissot recog- Many of the sequelae that Tissot associated with
nized that semen was lost in the process of "replen- onanism we now know derive from sexually trans-
ishing" the human race, he held that too great a loss mitted diseases such as syphilis, gonorrhea, genital
(from too great a frequency) was dangerous and herpes, and others, all of which at that time were
hence sexual intercourse had to be limited if health often explained by the concept of onanism. More-
was to be preserved. Tissot asserted that involun- over, it was observed that individuals in some men-
tary emissions such as "wet dreams" were also weak- tal institutions frequently masturbated, as did those
ening. Most dangerous, however, was the "unnatu- who were developmentally disabled, and rather than
ral loss" of semen through masturbation. being regarded as a consequence of institutionaliza-
Masturbation (or onanism) comprised a broad cate- tion, it was believed to be a cause. The decline in
gory of sexual activities. For men, it included all male potency and sexual activities with age were
seminal emissions not intended for procreation, and indicative, according to Tissot's theory, of the dan-
thus in effect every sexual activity not leading to gers of having lost semen or vital fluids earlier in
procreation was not only a cause of illness but an life. The neatness of Tissot's explanation was that it
illness in itself. Tissot defined the sequelae of mas- not only squared with current medical theory but
turbation as the following: (1) cloudiness of ideas explained so many previously unexplained illnesses
and sometimes even madness; (2) decay of bodily and diseases.
powers, resulting in coughs, fevers, and consump- In sum, if a syndrome can be defined as the concur-
tion; (3) acute pains in the head, rheumatic pains, rence or running together of signs and symptoms
and an aching numbness; (4) pimples on the face, into a recognizable pattern, then onanism furnished
suppurating blisters on the nose, breast, and thighs, such a pattern. As Tristam Engelhardt (1974) put it,
and painful itching; (5) eventual weakness of the onanism was more than a simple pattern, because a
power of generation, as indicated by impotence, pre- cause was attributed to the syndrome, providing an
mature ejaculation, gonorrhea, priapism, and tu- etiologic framework for a disease entity. If the devel-
mors in the bladder; and (6) disordering of the intes- opment of the concept of disease is seen as a progres-
tines resulting in constipation, hemorrhoids, and so sion from a collection of signs and symptoms to their
forth. Though Tissot recognized that not everyone interrelation in a recognized causal mechanism,
addicted to onanism was so cruelly punished, he felt then the disease of onanism was fairly well evolved.
that most were, and that everyone was afflicted to Once established as a disease entity, onanism had
some degree or another. a long and varied life, adapting to new developments
Onanism affected women even more than men in medicine and in society. One of the leading expo-
because in addition to most of the male sequelae, nents of Tissot's ideas was Benjamin Rush (1794-8),
onanism left women subject to hysterical fits, incur- the dominant medical figure in the United States
able jaundice, violent stomach cramps, pains in the of the late eighteenth and early nineteenth centu-
nose, ulceration of the matrix, and uterine tremors ries. Rush, after studying in Edinburgh, returned to

the United States to introduce a variation of John than the lower social classes. In other words, as
Brown's medical beliefs whereby all disease was con- humanity advanced, it became more and more neces-
sidered to be the result of either a diminution or sary to save nervous energy.
an increase of nervous energy. Because sexual in- Those who were unable to control their sexuality
tercourse was a major cause of excitement, care- not only would suffer physical debilities but would
less indulgence in sex inevitably led to a number of become homosexuals, which was a consequence of
problems, including seminal weakness, impotence, youthful masturbation according to such nineteenth-
dysuria, tabes dorsalis, pulmonary consumption, dys- century writers as John Ware (1879), Joseph Howe
pepsia, dimness of sight, vertigo, epilepsy, hypochon- (1889), James Foster Scott (1899), and Xavier Bour-
driasis, loss of memory, manalgia, fatuity, and death. geois (1873). The alleged correlation of sexual activ-
Rush, however, also cautioned against abnormal re- ity with nervous energy, which in turn was associ-
straint in sexual matters because it too could pro- ated with intellectual development, led some writers
duce dangers. such as Edward Clarke (1874) to argue that, because
The syndrome of onanism was seized on by a wide menstruation was a result of nerve stimulation,
variety of popularizers as well, some physicians and women should not engage in mental activity at all.
some not. In the United States, Sylvester Graham Some even argued that menstruation itself was
(1838) concluded that excessive sexual desire led to pathological.
insanity, and insanity itself incited excessive sexual
desire. In fact, the influence of sexual desire was so Challenges to the Diagnosis and New
pervasive that it could disturb all the functions of Classifications
the system, causing a general debility. Claude- The idea of sexuality as a disease entity was under-
Francois Lallemand, a French surgeon, was con- mined, in part, by a better understanding of sexually
cerned with the involuntary loss of male semen, transmitted diseases and their sequelae, which came
spermatorrhea, which he felt would lead to insanity. about during the last part of the nineteenth century.
This caused his U.S. translator (1839) to report that The discovery and acceptance of the germ theory
55 of the 407 patients in the Massachusetts State also undermined the belief that sexual activity
Lunatic Hospital at Worcester had become insane caused ailments such as tuberculosis. Medicine, how-
from the effects of masturbation. ever, did not abandon its emphasis on the disease
William Acton (1871), an English physician, had a potential of nonprocreative sex. It was simply placed
somewhat different view of the dangers of sexual in another category.
activity, arguing that God had made women indiffer- The latter is usually associated with the efforts of
ent to sex in order to prevent men's vital energy from Carl Westphal, professor of psychiatry at the Univer-
being totally depleted. John Harvey Kellogg (1882), sity of Berlin, who was influenced by the German
another popularizer in the United States, held that homosexual movement. Led by such individuals as
the nervous shock accompanying use of the sexual Karl Heinrich Ulrichs (1881) and Karoly Kertbenny
organs was the most profound to which the nervous (1905), that movement sought to establish that ho-
system was subject, and even those who engaged in mosexuality was inborn. In 1869 Carl Westphal had
procreation would have to place rigid limitations on published the case histories of a young woman who
themselves or else insanity would result. from her earliest years liked to dress as a boy and of
Because the dangers of sexual activity were so a young man who liked to dress as a woman. From
great, one problem with the new syndrome was to these cases he argued that sexual abnormality was
explain why the human race had not died out ear- congenital, not acquired. He called the phenomenon
lier. George M. Beard (1884) believed that it had not "contrary sexual feeling" and insisted that, although
been necessary for earlier generations to be so con- neurotic elements were present in such individuals,
cerned about excessive sexual activity because their they were not insane (Bullough 1989).
lives had been simpler. It was the growing complex- If the "contrary sexual feeling" was inborn, was it
ity of modern civilization and evolutionary develop- also incurable? Jean Martin Charcot, the director of
ment that put so much stress on men and women. the Salpetriere Hospital, and a colleague had at-
Consequently, a larger and larger number of them tempted to cure several cases of "contrary sexual
were suffering from nervous exhaustion. This ex- instinct" or "sexual inversion" with only modest suc-
haustion, he held, was particularly serious among cess and concluded in an 1882 publication that inver-
the educated and intelligent workers in society, who sion was a constitutional nervous weakness due to
represented a higher stage on the evolutionary scale hereditary degeneration.

This concept was further developed by Paul ality was caused by environmental rather than con-
Moreau (1887), who theorized that in addition to the stitutional factors and was, by implication, curable.
usual senses of sight, hearing, touch, taste, and feel- Some groups, however, still looked upon it as inborn,
ing, humans had a sixth sense, a genital sense that, though treatable if not curable. In any case, varia-
like the others, could suffer physical or psychic in- tions in sexual behavior were now regarded as com-
jury without damage to the other senses. This pro- ing under the jurisdiction of psychiatrists, and there
pensity to injury stemmed from either a hereditary they have remained.
taint or a predisposition to perversion provoked by Certain forms of variant sexuality, such as homo-
certain other factors such as age, proverty, constitu- sexuality, are no longer regarded as an illness, and
tion, temperament, and seasons of the year. The masturbation is considered as normal behavior.
result could be sexual inversion, nymphomania, saty- Much of this latest change in attitude grew out of
riasis, bestiality, rape, or profanation of corpses. The challenges to the research methodologies and theo-
only way to deal with these individuals so afflicted ries that had originally classified much of human
was to turn them over to asylums, where they could sexual behavior as an illness.
be cared for. Not everyone agreed with this, however. One challenge was made by Alfred Kinsey and his
One of the early researchers who was most impor- colleagues (1948), whose data on what actually con-
tant in influencing public opinion was Richard von stituted sexual behavior resulted in a redefinition of
Krafft-Ebing, whose Psychopathia Sexualis, first some of the norms. A second kind of challenge was
published in 1886, remained in print until the 1980s. aimed at the research of earlier physicians and psy-
He combined several prevailing nineteenth-century chiatrists. Most of the theorizing of Tissot and his
theories to explain sexual "perversion": (1) the idea successors had been rejected as germ theory gained
that disease was caused by the physical nervous sys- credence and the endocrinological forces involved in
tem, (2) the notion that there were often hereditary sexuality came to be understood. This left psychia-
defects in this system, and (3) the concept of degener- trists as the only major group to maintain the conten-
acy. Civilization, he claimed, was possible only be- tion that deviant sexual behavior could be illness.
cause lust had been tempered by altruism and re- Prominent among them were psychoanalysts, who
straint, based on the knowledge that sexual excess were attacked by a number of researchers in the
weakened the body. The purpose of sex was reproduc- 1960s and 1970s for working with small samples,
tion, and sexual activities not undertaken with this not using control groups, and not taking into ac-
ultimate purpose in mind were "unnatural practices" count cultural differences.
and a perversion of the sexual instinct. Though Attitudes toward nonprocreative sex also changed
Krafft-Ebing distinguished between innate and ac- with the widespread adoption of contraceptives and
quired perversion, even acquired perversion existed the acknowledgement that sex was an enjoyable ac-
only when there was hereditary weakness in the ner- tivity for both men and women. The recognition that
vous system, and onanism was a causal factor in this. people engaged in sex for pleasure as well as for
Differing from Krafft-Ebing somewhat was Sig- procreation also weakened hostility to forms of sex-
mund Freud (1913, 1922a, 1922b, 1924-50, 1938), ual activity other than conventional heterosexual
his younger and even more influential contempo- intercourse and raised questions about medical cate-
rary. Freud agreed that variant sexual behavior gorization. The knowledge that other cultures and
came from misdirected sexual drives, but he held peoples had attitudes toward sex that were radically
that the cause of the misdirection lay in the nervous different from those of Westerners was also impor-
system and the mind through which the instinctual tant in challenging the western European and U.S.
drive operated. Though Freud himself paid compara- notion of sexual deviation as disease. Finally, in
tively little attention to most forms of variant sexual 1974 homosexuality was eliminated from the Diag-
behavior, his followers seized on his concepts to em- nostic and Statistical Manual (DSM) of the Ameri-
phasize environmental and accidental causes of vari- can Psychiatric Association as a category of illness.
ant sexual impulses. Not all forms of "deviant" sexual behavior, how-
Later behaviorists carried this kind of thinking to ever, have been removed from the DSM, and in fact
an extreme, so that the practical result of both Freud- there remains a strong tendency to categorize as ill
ianism and the learning psychologies was to suggest individuals who are pedophiles, exhibitionists, or
that everyone had the ability to channel his or her necrophiliacs and those who engage in numerous
drives. Although they differed about specific factors, other more or less forbidden sexual activities. There
followers of Freud usually agreed that deviant sexu- is also a counter-movement as of this writing to estab-

lish a new category — that of sexually compulsive 1922a. Leonardo da Vinci, trans. A. A. Brill, London.
people - perhaps to get them into the offices of behav- 1922b. Three contributions to sexual theory. New York.
ioral psychologists to be treated through behavior 1924-50. Collected papers. London.
modification. Thus, although theories have changed 1938. Basic writings. New York.
and challenges to previous categorizations have been Graham, Sylvester. 1838. A lecture on epidemic diseases,
generally and particularly the spasmodic cholera.
mounted, there remains a strong belief in the helping
Boston.
professions that socially unacceptable sexual behav- 1848. A lecture to young men, on chastity, intended also
ior is an illness or at least a behavior problem of one for the serious consideration ofparents and guardians,
sort or another. Since the time of Tissot these profes- 10th edition. Boston.
sions have essentially replaced religion in determin- Greenberg, David. 1988. The construction of homosexual-
ing what sexual activity is permissible and what ity. New York.
should continue to be stigmatized. Howe, J. W. 1889. Excessive venery, masturbation, and
Vern L. Bullough continence. New York.
Kellogg, J. H. 1882. Plain facts for old and young. Burling-
ton, Iowa.
Bibliography Kertbenny, K. M. 1905. Section 143 des Preuszischen Straf-
Acton, William. 1871. The functions and disorders of the gestzbuchs vom 14. April 1851 und seine Aufrechter-
reproductive organs in childhood, youth, adult age, haltung, and Section 152 in Entwurfe eines Straf-
and advanced life considered in their physiological, gesetzbuchs fur den norddeutschen Bund, reprinted
social, and moral relations, 5th edition. London. Jahrbuch fur Sexuelle Zwischenstufen 7: 3—66.
Bayer, Ronald. 1981. Homosexuality and American psy- King, A. F. A. 1875-6. A new basis for uterine pathology.
chiatry. New York. American Journal of Obstetrics 8: 242—3.
Beard, George M. 1884. Sexual neurasthenia, its hygiene, Kinsey, Alfred, Wardell Pomeroy, and Clyde Martin. 1948.
causes, symptoms, and treatment, ed. A. D. Rockwell. Sexual behavior in the human male. Philadelphia.
New York. Kinsey, Alfred C , Wardell B. Pomeroy, Clyde E. Martin,
Boerhaave, H. 1728. Institutiones medicae. In Opera and Paul H. Gebhard. 1953. Sexual behavior in the
medica universa. Geneva. human female. Philadelphia.
Bourgeois, Dr. X. 1873. The passions in their relations to Krafft-Ebing, R. von. 1886. Psychopathia sexualis.
health and disease, trans. Howard F. Damon. Boston. Stuttgart.
Brown, John. 1803. The elements of medicine, rev. by Lallemand, C.-F. 1839. On involuntary seminal discharges,
Thomas Beddoes. 2 vols. in 1. Portsmouth, N.H. trans. W. Wood. Philadelphia.
Bullough, Vern L. 1975. Sex and the medical model. Jour- MacDonald, R. H. 1967. The frightful consequences of
nal of Sex Research 11: 291-303. onanism. Journal of the History of Ideas 28: 423—31.
1976. Sexual variance in society and history. Chicago. Moreau, Paul. 1887. Des aberationsde sens genetique. Paris.
1989. The physician and research into human sexual Onania; or, the heinous sin of self-pollution, and all its
behavior in nineteenth-century Germany. Bulletin of frightful consequences, in both sexes, considered. With
the History of Medicine 63: 247-67. spiritual and physical advice to those, who have al-
Bullough, Vern L., and Bonnie Bullough. 1987. Women ready injur'd themselves by this abominable practice.
and prostitution. Buffalo, N.Y. And seasonable admonition to the youth (of both
Bullough, Vern L., and Martha Voght. 1973a. Homosexual- SEXES) and those whose tuition they are under,
ity and its confusion with the "Secret Sin" in nine- whether parents, guardians, masters, or mistresses. To
teenth century America. Journal of the History of which is added, a letter from a lady (very curious)
Medicine and Science 28: 143-56. concerning the use and abuse of the marriage-bed.
1973b. Women, menstruation, and nineteenth century With the author's answers thereto. 1724. Boston.
medicine. Bulletin oftheHistory ofMedicine 47:66-82. Rush, Benjamin. 1794—8. Medical inquiries and observa-
Charcot, Jean Martin, and Valentin Magna. 1882. Inver- tions upon the diseases of the mind. Philadelphia.
sion du sens genital perversions sexuelles. Archives Scott, J. F. 1899. The sexual instinct. New York.
de neurologie III and IV. Shyrock, Richard H. 1947. The development of modern
Clarke, Edward H. 1874. Sex in education; or a fair chance medicine, 2d edition. New York.
for girls. Boston. Stahl, Georg Ernst. 1768. Theoria medica vera. Hulle.
Engelhardt, H. Tristram, Jr. 1974. The disease of mastur- Tissot, Simon-Andre. 1758. Tentamen de morbis ex
bation: Values and the concept of disease. Bulletin of manusturpatione. Lausanne.
the History of Medicine 48: 234-48. 1776. Onanism: Or a treatise upon the disorders of mas-
Freud, Sigmund. 1913. Die drei Grundformen der Homo- turbation, trans. A. Hume. London.
sexualitat. Jahrbuch fur Sexuelle Zwischenstufen 15: Ulrichs, K. H. 1881. Memnon: Die Geschlechtsnatur des
Parts 2, 3, 4. mannliebenden Urnings. Scheliz.

II.5. Concepts of Heart-Related Diseases 91
Ware, John. 1879. Hints to young men on the true relations tion of heart failure. However, because prevailing
of the sexes. Boston. disease theories placed little importance on the local-
Weinberg, Martin S., and Colin J. Williams. 1974. Male ization of lesions in the body, Auenbrugger's tech-
homosexuals: Their problems and adaptations. New nique attracted little attention. His work was to
York. gain greater attention as a result of a political up-
Westphal, C. F. 0. 1869. Die kontrare Sexualempfindung. heaval in a nearby country.
Archiven fur Psychiatrie und Nervenkrankenheit 2:
The French Revolution not only reshaped the politi-
73-108.
cal structure of France, but also radically changed
the institutions that controlled hospitals and medical
schools. Physicians practicing in these institutions
changed the perception of disease. Their emphasis
on the importance of specific lesions in the body
n.5 stimulated a desire to correlate clinical physical
findings with anatomic lesions found at autopsy.
Concepts of Heart-Related Every day, Parisian physicians in the early nine-
Diseases teenth century went from bedside to bedside, exam-
ining patients with all manner of diseases, and all
too often they had the opportunity to correlate their
In 1628 William Harvey, physician to St. Bartholo- physical findings with those found at autopsy. In
mew's Hospital, London, used quantitative, experi- this milieu, Rene Laennec invented the stethoscope
mental methods to show that the blood must move in for listening to sounds in the chest. Auenbrugger's
a circle, rather than being continuously regenerated technique of percussion became widely used when it
as earlier theories had proposed. In addition, Harvey was discovered that lesions could be localized in the
showed that the heart supplies the power to send the chest with Laennec's stethoscope. Although both of
blood on its circuit around the body. Harvey's revolu- these techniques were used primarily to diagnose
tionary ideas reflected ancient thought about the diseases of the lung, they were also used to diagnose
perfectibility of circular motion as much as they did heart problems.
new ideas about the value of experimental evidence. Auscultation with the stethoscope was not immedi-
Nonetheless, in many ways and by most accounts, ately accepted. It was a skill that took time and
the year 1628 marks the beginning of current West- practical experience to learn, and one that could
ern ways of looking at the heart and its diseases. yield misleading results. Furthermore, it was of no
However, although Harvey's demonstration of car- help in diagnosing many cardiac diseases that did
diac physiology in animals seemed logically applica- not produce physical signs and could be diagnosed
ble to human beings, it failed to lead immediately to only by the patient's own sensations. One of these
any dramatic changes in the diagnosis or treatment diseases was manifested by chest pain and is now
of human heart disease. Over the next few centuries understood to be caused by occlusion of the coronary
many people tried to discover what was going on arteries of the heart.
within the thoraxes of patients who showed the de-
bilitating signs of cardiac disease. Their notions
about heart disease were reflected in the diagnostic Diagnosis by History: Coronary Heart Disease
techniques they thought appropriate. In addition to anatomic studies, eighteenth-century
practitioners published descriptions of coronary
heart disease based on patients' reports of char-
Diagnosing Heart Disease acteristic symptoms. (Coronary heart disease, as
we now use the term, encompasses such entities
Physical Diagnosis as angina pectoris and myocardial infarction, or
During the mid-eighteenth century, Leopold Auen- "heart attack.") In 1768 William Heberden of Lon-
brugger, working in Vienna, described a new diag- don gave a lecture at the College of Physicians of
nostic technique. By percussing the chest - that is, London, published in 1772, in which he coined the
by striking the chest and both listening to and feel- term angina pectoris and differentiated it from
ing the reverberation - he was able to tell, to some other pains in the chest:
extent, what lay within. His method enabled him to
ascertain the size of the heart and to determine the They who are afflicted with it, are seized while they are
presence of fluid in the chest, a common manifesta- walking, (more especially if it be up hill, and soon after

eating) with a painful and most disagreeable sensation in permanent record of the cardiac pulsations on a
the breast, which seems as if it would extinguish life, if it drum of smoked paper. Marey used this instrument
were to increase or to continue; but the moment they stand to record the pressure within the heart of a horse. He
still, all this uneasiness vanishes. ... In all other respects, also recorded pressure tracings from the arteries
patients are, at the beginning of this disorder, perfectly that could be felt on the surface of the human body.
well. . . . Males are most liable to this disease, especially In the 1890s the English physician James Mac-
such as have past theirfiftiethyear.
kenzie developed the polygraph, an instrument that
Heberden focused on the clinical manifestations of recorded the pulsations of the arteries and veins
the disease, not on its cause. However, others had directly onto a continuous strip of paper. With this
earlier described disease of the coronary arteries. device he was able to describe many abnormalities of
The English surgeon John Hunter, after finding this the pulse and to identify the cardiac causes of sev-
condition during an autopsy on a person who had eral of these. His work was advanced by the London
died in a fit of anger, declared: "My life is in the physician Thomas Lewis, who analyzed abnormal
hands of any rascal who chooses to annoy me." cardiac rhythms with the electrocardiogram (EKG),
Hunter's words proved true. He collapsed and died in a new instrument that could record the electrical
1793, presumably of a myocardial infarction, soon signals generated by the heart. Invented in 1902 by
after leaving an acrimonious meeting. Willem Einthoven, the EKG earned its inventor the
Many different manifestations of coronary heart 1924 Nobel Prize in medicine or physiology.
disease were noted over the next century. Although Because Lewis and Mackenzie were working
the first diagnosis before death was probably made in within a social system that placed a high value on
1878, recognition of coronary heart disease did not the clinical skills of the physician and a low value on
become widespread until its diagnosis by technologi- the use of technology, neither thought of the EKG
cal means became common early in the twentieth machine as an instrument that could replace the
century. That new technology was derived in some senses of the skilled bedside observer. However,
ways from one of the oldest forms of diagnosis - working in a climate in which the role of the physi-
feeling the pulse. cian was not so socially important, James Herrick of
Chicago saw the value of the EKG for diagnosing
Mechanical Diagnosis: The Pulse and the diseases that could not be diagnosed with the un-
Electrocardiogram aided senses. Coronary artery disease was one such
People have felt the pulse to diagnose disease since disease. Herrick's clinicopathological description of
antiquity. Attempts to analyze the pulse have in- it in 1912 received little attention; however, after his
cluded timing its rate and noting its pattern, particu- collaboration in 1918 and 1919 with Fred Smith to
larly any abnormalities in its rhythm. John Floyer, describe the characteristic EKG changes, Herrick's
who in 1709 constructed a portable clock with which definition of the disease entity became widely recog-
to time the pulse, noted that the natural pulse rate nized. This was an early example of a pattern to be
varied according to a person's place of residence, age, repeated throughout the twentieth century - a dis-
and sex. ease first described clinically would become more
A very slow pulse, one of the most striking abnor- widely accepted once it was defined in terms of a
malities, was often associated with intermittent loss laboratory technique.
of consciousness, or syncope. This condition has
come to be known as Stokes-Adams (or occasionally Hemodynamic Diagnosis: Diagnosis by
Adams-Stokes) disease, after two Dublin physi- Measuring Physiology
cians, Robert Adams and William Stokes, each of In a sense, the development of hemodynamic diagno-
whom described characteristics of the disease in the sis was returning full circle to the issues of pressures
first half of the nineteenth century. Today this condi- and volumes in the heart that Harvey was working
tion is treated with pacemakers (described later). with in 1628. Harvey had been unable to measure
Early attempts to understand the cause of a slow these parameters in human hearts. Physicians' daily
beat led to the development of mechanical devices use of these measurements today is in large part the
for analyzing heartbeat. result of a self-experiment performed in 1929.
In 1859 the French physiologist Etienne-Jules During the spring of 1929, while working in the
Marey drew on the earlier work of German physiolo- relatively unsophisticated setting of a small German
gists such as Carl Ludwig, inventor of the kymo- country hospital, Werner Forssmann became fasci-
graph, to devise an instrument that could produce a nated by the work of nineteenth-century French

physiologists such as Marey, and particularly by a low. More important, he showed that it was practical
diagram showing Marey's recorded pressures from a and safe to insert a catheter routinely into the right
horse's heart. Forssmann decided to perform the pro- side of the human heart.
cedure Marey had used on himself by passing a ure- During the next few years, Richards, Cournand,
thral catheter from the main vein in his arm up into and their colleagues designed a new catheter that
his heart, hoping to provide a new, more effective was easier to maneuver and constructed a measur-
means of delivering medication. Despite his supervi- ing device that enabled them to record simulta-
sor's refusal to grant him permission, Forssmann neously four different pressure tracings along with
was determined to perform the experiment. How- the EKG. In 1942 they advanced the catheter into
ever, he needed the cooperation of the surgical nurse the right ventricle, and in 1944 into the pulmonary
who controlled access to the necessary instruments. artery, thus making it possible to measure the
Forssmann was eventually so successful in convinc- hemodynamic pressure and the amount of oxygen
ing her of the safety and importance of the experi- present in the blood at each stage of passage through
ment that she insisted he perform the experiment on the right side of the heart. Funded by the federal
her. Forssmann, however, persuaded the nurse to lie government through the Committee on Medical Re-
down on a cart, where he strapped her down, claiming search, from 1942 to 1944 this group studied more
the action to be a "precaution against falling off." than 100 critically ill patients suffering from trau-
With the nurse thus immobilized, Forssmann in- matic shock, hemorrhagic shock, burn shock, and
serted the catheter into his own arm, pushed it shock caused by rupture of an internal organ. They
through the veins into his heart, and then released outlined the profound effects of reduced circulating
the nurse. She helped him walk down the stairs into blood volume on cardiac output, particularly on the
the basement, where an X-ray image confirmed that flow of blood to peripheral organs and the kidneys,
the catheter was indeed within his heart. The experi- and described how the condition could be reversed by
ment earned Forssmann some praise, but much more replacement of the appropriate volume of blood. La-
hostility, and as a result, he left academic medicine ter, they used the same catheterization technique to
and did no more work on cardiac catheterization. diagnose congenital cardiac defects: An abnormal
But others went forward with Forssmann's method. opening between the cardiac chambers was detected
In 1932 Dickinson Richards, Jr., and Andre Cour- by means of pressure and oxygen measurements
nand began collaborating on studies of the heart and made with the catheter. Similarly measuring the
circulation at New York Hospital. They started with pressure in the cardiac chambers was found to be
the assumption that the heart, lungs, and circulatory valuable for diagnosing acquired cardiac defects, par-
system form a single system for the exchange of gases ticularly diseases of the heart valves.
between the environment and the organism. In order Richards and Cournand shared the 1956 Nobel
to calculate the cardiac output, they needed to obtain Prize in medicine or physiology with Forssmann.
blood samples from the right atrium, the cardiac Not long after the discovery that right-sided pres-
chamber that collects blood from the body before sures could be measured, others extended the tech-
pumping it to the lungs to receive more oxygen. After nique to measure pressures on the left side of the
practicing Forssmann's technique on laboratory ani- heart. The procedure has greatly aided our under-
mals for four years, Cournand, Richards, and their standing of the pathophysiology underlying various
colleagues determined that the passage of catheters forms of congestive heart failure. The invention of
into animals' hearts did not significantly interfere electronic devices for measuring pressures has en-
with cardiac functioning. abled physicians to analyze the pulsatile pressure
Although their first attempt to perform the proce- tracings in various disease states. Other investiga-
dure on a patient, in 1940, was unsuccessful, they tors have shown how injecting dye into the heart can
were encouraged to continue their efforts by senior aid in diagnosis. Today, the passing of diagnostic
investigators studying cardiac output determined by catheters into the heart is such a routine procedure
the ballistocardiogram, an instrument that recorded that patients may not even spend a night in the
the motion of the body caused by the heartbeat. hospital.
Cournand was eventually able to insert a catheter These techniques for hemodynamic monitoring
into a human heart and to compare the directly have come to define and dominate places in hospitals
measured cardiac output with that determined by set aside for the care of critically ill patients. Some
the ballistocardiogram. He showed that cardiac out- intensive care units are designed specifically for the
put as measured by the ballistocardiogram was too care of patients suffering from coronary artery dis-

ease. Physicians and nurses working in coronary ing doom, soldiers with this syndrome were initially
care units, which first became widespread in the treated by the British military with extended hospi-
United States in the 1960s and 1970s, utilize both tal bedrest. The presence of a cardiac murmur was
hemodynamic monitoring and EKG monitoring of taken as ipso facto evidence of heart disease. How-
the pulse, the latter to detect and correct life- ever, as the war continued, lasting far longer than
threatening cardiac dysrhythmias. In other inten- originally anticipated, heart disease became a seri-
sive care units, cardiac catheters are used to monitor ous military, economic, and political problem. It was,
the cardiac function of patients suffering from a in fact, the third most common reason for military
wide variety of noncardiac disorders. Although they discharge. Yet heart disease held out far more hope
are useful for some groups of patients, whether coro- of treatment and return to service than did the most
nary care units are necessary for all patients with common cause of discharge, "wounds and injuries."
myocardial infarction remains unclear. Nonetheless, the long convalescence strained both
Western ideas about what constitutes heart dis- the military hospitals and the political fortunes of
ease are based increasingly in technological diagno- England's leaders, who were forced to institute a
sis and on the ability to invade the thorax in order to military draft in 1916. Given these political exigen-
make diagnoses and also to intervene. Along with cies, physicians working for the Medical Research
the increased use of technology has come the un- Council reconceptualized the disease as the "effort
stated but generally pervasive assumption that diag- syndrome." They decided that heart murmurs were
nosis has finally become objective, transcultural, important only insofar as they impaired the ability
and reflective of some natural, inevitable underly- of the soldier to work, and then prescribed a series of
ing diagnostic system. The validity of this assump- graded exercises rather than hospitalization and bed-
tion is doubtful. Historical analysis shows that the rest. The result was that many soldiers previously
definition of heart disease, as well as of the specific declared "unfit for service" were reclassified as "fit."
diseases and their appropriate diagnostic tests, is a All of this demonstrates that some notions about
product of both biology and culture. what constitutes heart disease are informed by so-
cial needs.
Changing Concepts: What Constitutes Physicians' ideas have continued to be shaped by
Heart Disease? social context. Studies of the incidence of heart dis-
Concepts about what constitutes heart disease have ease in black Americans early in the twentieth cen-
changed a great deal in the past century. For exam- tury were influenced by the cultural context in which
ple, the corresponding section of a predecessor to this they were written. Many investigators concluded
work, August Hirsch's Handbook of Geographical that coronary artery disease was rare in black people,
and Historical Pathology (1883-6) is entitled "Dis- largely because black people were considered less
eases of the Heart and Vessels," not diseases of the likely to experience stress, owing to their assumed
heart, and one of the main topics is hemorrhoids. disinclination to hurry or worry about their lot in life,
Anatomic linkage of the heart and vessels into a and because they were presumed to be less intellectu-
single unit was common in the nineteenth century, as ally alert than the "refined, intellectual" classes.
is shown by such titles as Diseases of the Heart and In the late twentieth century, culture has contin-
Aorta and Diseases of the Heart and Great Vessels. ued to have an impact on our definitions of heart
Around the end of the nineteenth century, however, disease. For example, Lynn Payer has pointed out
the conceptualization of heart disease changed funda- that failure to appreciate that the West German
mentally. As Christopher Lawrence has pointed out, concept of heart disease differs from the U.S. concept
British physicians started to think about the heart in could lead to the erroneous conclusion that death
terms of its functional capacity rather than in terms rates from ischemic heart disease are lower in West
of its anatomy. This led them to regard cardiac mur- Germany than in the United States. In fact, the
murs, such as would be detected by a stethoscope, as rates are approximately the same, but that type of
less important than physiological measurements of heart disease is more likely to be called "ischemic
function. heart disease" in the United States and "cardiac
This conceptual change was particularly apparent insufficiency" in West Germany.
in discussions of a soldier's disease described at one
time as "DaCosta's syndrome" and later, at the start The Rise of Cardiac Diseases
of the First World War, as "soldier's heart." Afflicted Changes in disease classification reflect both social
by breathlessness, fatigue, and a feeling of impend- and biological events. Even after accounting for

changes in definitions, it seems clear that there has nancial support from the antituberculosis movement,
been a significant change in the types of disease primarily the National Tuberculosis Association.
from which people die. During the twentieth cen-
tury, our methods of classification have helped to Coronary Disease
make heart disease an increasingly important cause Coronary disease has become the major form of
of death and disability. The predominant causes of heart disease in industrialized countries. As such, it
sickness and death were once infectious diseases. In has become a major object of attention for health
the mid-nineteenth century, for example, tuberculo- care workers. Much of that attention has been fo-
sis accounted for an estimated one-seventh of all cused on explaining the geographic and historical
deaths in western Europe. Yet the impact of infec- changes in the pattern of disease.
tious diseases has subsequently decreased in many Heart disease caused 979,000 deaths in the United
parts of the world, partly because of improved living States in 1986. Accounting for 47 percent of all
conditions and partly because of improved treatment deaths, it is by far the leading cause of death, with
with antibiotics. myocardial infarction the most common diagnosis.
Two major forms of heart disease related to infec- Many more people suffer from heart disease than die
tious agents have undergone a dramatic shift in from it. In the United States, there were an esti-
pattern. Rheumatic fever, a disease related to infec- mated 57,700,000 people with cardiovascular dis-
tion with a specific streptococcus that can cause ease in 1983, 21,500,000 of whom had heart disease
heart disease, was once a major cause of heart dis- and 7,200,000 of whom had coronary heart disease.
ease in Western countries. In industrialized coun- Of those with heart disease, 12,600,000 were under
tries, it has now become a relatively minor cause of age 65, as were 3,200,000 of those with coronary
heart disease, with a prevalence as low as 0.6 per heart disease. The physical activity of one-quarter of
1,000 school-aged children in the United States and those with heart disease was limited, making the
0.7 per 1,000 in Japan. In other parts of the world, condition an important cause of disability as well as
however, rheumatic heart disease remains a serious death.
problem; the prevalence per 1,000 school-aged chil-
dren has been reported to be in the range of 15 to 20 Declining Coronary Death Rate in the United
for Algeria, Bolivia, and Thailand. States
Endocarditis, an infection of the heart valves, car- At the turn of the nineteenth century, heart disease
ried an almost certain death sentence before the was the fourth leading cause of death in the United
advent of antibiotics. At one time, endocarditis in States, behind pneumonia and influenza (combined),
the United States primarily afflicted people with tuberculosis, diarrhea, enteritis, and ulceration of
valvular disease caused by rheumatic heart disease. the intestines. All of these produced death rates in
The changing pattern of this illness reflects changes excess of 100 per 100,000 population. A sharp up-
not only in treatment but also in life-style. Now ward trend in coronary disease became apparent
endocarditis is far more often a disease of intrave- around 1920, and coronary disease was recognized
nous drug abusers. with increasing frequency throughout most of the
Another result of the decline of infectious dis- first 50 years of the twentieth century. By 1940 only
eases has been an increase in the average life expec- two disease categories with death rates of more than
tancy. People now live long enough to succumb to 100 per 100,000 remained: cancer and diseases of the
diseases that take time to develop, which is the case heart. The death rate from heart diseases then be-
with many cardiac diseases, particularly coronary gan a dramatic series of changes.
heart disease. And again life-styles have changed. As Figure II.5.1 shows, the death rate reached a
A lack of physical activity and a change in diet may peak in 1963 and has declined continuously since
contribute to the increased incidence of coronary then. There was some initial concern about whether
heart disease. the decline was real or only a product of a 1968
Finally, the development of cardiology as a major change in disease classification. But now there is
field of specialization in the United States is indebted little doubt that the death rate for coronary heart
in large part to the earlier campaign against tu- disease in the United States has fallen dramatically
berculosis, which prompted the development of the since the 1960s. However, that decline has not been
voluntary health movement. The first U.S. cardiol- evenly distributed. The mortality rate for heart dis-
ogy organization, the American Heart Association, eases in California, for example, peaked relatively
drew substantial intellectual, organizational, and fi- early, around 1955, and the subsequent decline there

240
220-
S 200-
a.
§
180-
160-
140-
a
xu 120 -
100
1940 1990
Australia Canada Sweden Ireland Poland
Figure II.5.1. Rate of coronary heart disease per 100,000 Country

people in the United States (age-adjusted to 1940 age
distribution). (Data from Vital Statistics of the United Figure II.5.2. Annual change in mortality from ischemic
States, as prepared by the National Heart, Lung, and cardiac disease, 1968-77 (men aged 40 to 69). (Data
Blood Institute; data for 1987 provisional.) from WHO MONICA 1988.)
tion's Multinational Trends and Determinants in

was repeated in other parts of the United States Cardiovascular Disease (MONICA) has made one
throughout the 1960s and 1970s. By 1986 the death such attempt. With 41 projects in 21 countries, MON-
rate for coronary heart disease was 55 percent of the ICA is helping to make cardiovascular disease a focus
1966 rate, and the decline in the death rate for all of international and cross-cultural comparisons.
cerebrovascular diseases was proceeding three times Only AIDS has received similar worldwide attention.
faster than the decline for all other causes of death Studies of changing patterns of cardiac disease
combined. have contributed to the invention of risk factor, a
concept that is receiving widespread attention as a
Worldwide Variation in Coronary Diseases way of conceptualizing the cause of many diseases.
Such countries as Australia, New Zealand, and Can- Unlike infectious diseases, which are defined in
ada have experienced similar declines in the death terms of a single, specific agent, risk factor is con-
rate from coronary disease among men. Other coun- ceptualized on an epidemiological and probabilistic
tries, however, have experienced significant in- basis.
creases in death rates, as revealed in Figure II.5.2.
These have included countries, such as Scotland and Risk Factors for Coronary Heart Disease
Northern Ireland, with death rates initially compara- Much of our current explanation for the historical
ble to that of the United States, as well as countries, and geographic differences in death rates from coro-
such as Poland and Switzerland, initially having nary heart disease derives from the concept of risk
death rates much lower than that of the United factor. A number of long-term prospective studies
States. have enhanced the utility of this concept. The most
Some of the increase may be due to the impact of widely known study is the Framingham Heart
industrialization. In China, for example, infectious Study, in which 5,209 men and women have been
diseases such as tuberculosis and nutritional defi- carefully examined every two years since the investi-
ciencies were the major causes of morbidity and mor- gation began in 1948 in Framingham, Massachu-
tality, with cardiovascular disease of little concern setts. Studies such as this have identified a number
until the late 1950s. Even among industrialized coun- of factors that contribute to the likelihood of develop-
tries, the rate of death from cardiovascular diseases ing coronary heart disease. Some of these cannot be
has varied widely, from 913 per 100,000 in Finland modified. For example, men are more likely to suffer
(for men aged 40 to 69 in 1975) to 379 in Japan. from heart disease than women; older people are
Attempts have been made to explain these differ- more likely to develop the disease than younger
ences in disease rate. The World Health Organiza- ones; and those having a family history of early

cardiac disease are at greater risk than those within the development of coronary heart disease re-
out such a history. mains unclear, recent studies suggest that the type
However, other factors can be modified. Cigarette A personality may actually improve longevity after
smoking dramatically increases the likelihood of a a myocardial infarction.
coronary event and represents the greatest and most Alcohol intake in small quantities - two or fewer
preventable cause of heart disease. Once a person drinks per day - may diminish the risk of develop-
stops smoking, the risk rapidly declines to a level ing coronary disease. However, alcohol in greater
approximately the same as it would be if the person amounts is clearly associated with greater morbid-
had never smoked. High blood pressure and diabetes ity and mortality from both cardiac and noncardiac
are also important risk factors. disease.
A positive relationship between blood cholesterol
level and the development of heart disease has been Explaining Change
clearly demonstrated. Almost no Japanese men have Many investigators have attempted to use the con-
serum cholesterol levels above 200 mg/dl, whereas cept of risk factor to explain geographic and histori-
almost no Finnish men have concentrations below cal changes in the rate of death from coronary heart
that level. Consistent with the hypothesis that choles- disease. The decline in the U.S. death rate may
terol is associated with death from coronary heart have been due partly to improved medical interven-
disease, the death rate from coronary heart disease in tions, including the widespread establishment of
Finland is more than 10 times that in Japan. Histori- coronary care units, improvements in prehospital
cal analysis has shown that the death rate from heart resuscitation and care, better surgical and medical
disease in Europe fell during the Second World War, treatment of those with known heart disease, and
presumably as a result of a lack of foods that elevate more extensive treatment of the large proportion of
serum cholesterol level. Most population-based stud- the population with hypertension. The decline may
ies have shown a consistently positive relationship also have been due in part to changes in life-style.
between increased serum cholesterol level in the Cholesterol consumption peaked in 1959, and the
form of low-density lipoprotein and the rate of heart percentage of North Americans who smoke has de-
disease. At high levels the association is particularly clined steadily over the past few decades. However,
strong; the risk of death for persons having choles- a significant part of the change cannot be fully
terol values in the top 10 percent is four times the risk explained.
of persons in the bottom 10 percent. There is now good Although coronary heart disease appears to be an
evidence that lowering cholesterol level with drug increasing cause of death in developing countries,
therapy will lower the death rate from coronary dis- accounting for 15 to 25 percent of all deaths as the
ease. This effect of reducing cholesterol level is most mean life expectancy reaches 50 to 60 years, more is
beneficial for those having the highest levels, but the required to explain the rates of death from coronary
value of reducing cholesterol level for those without heart disease than merely to blame increasing indus-
elevated cholesterol remains unclear. trialization. People moving from one industrialized
Exercise has a beneficial effect on the types of country to another tend to develop the susceptibility
lipids circulating in the bloodstream. Although obe- to heart disease prevalent in the host country, sug-
sity is associated with hypertension, whether obe- gesting that other environmental factors play an
sity is an independent risk factor for coronary heart important role in determining the incidence of heart
disease is as yet unclear. disease. Striking confirmation of this comes from a
In the 1950s some U.S. investigators argued that study of 11,900 people of Japanese ancestry living in
people who were hard-driving, competitive, overcom- Japan, Hawaii, and California. Those living in Ja-
mitted, impatient perfectionists and who found it pan had the lowest incidence of heart disease, those
difficult to relax-these with the so-called type A living in Hawaii had an intermediate incidence, and
personality - were at increased risk for coronary those living in California the highest. The best pre-
heart disease. These findings have been a subject of dictor of the incidence of heart disease among those
intense debate. Some studies of workers in Great living in California was not the presence of known
Britain have identified civil service manual work- risk factors, but the extent to which those Japanese
ers, not those with the hard-driving behavior indi- who had moved from Japan to California continued
cated in the original research, as those at greatest to adhere to traditional Japanese values: those who
risk from their behavior type. Although the exact retained more of these values had a lower rate of
role of type A behavior as an independent risk factor heart disease.

Geographic Variation in Types of Heart fetus. By bouncing sound waves off the interior of
Disease the heart, a picture can be generated that reflects
In many parts of the world, other types of heart the heart's anatomy, and by the use of small air
disease are more common than coronary heart dis- bubbles to provide contrast, the passage of blood can
ease. Endomyocardial fibrosis, for example, is com- also be traced. The echocardiogram's greatest advan-
mon in the tropical rain forest belt of Africa and tages lie in its complete safety (so far as is now
South America. The disease has a characteristic known) and freedom from pain.
pathological process and leads to heart failure, ac- Other imaging techniques applied to cardiac dis-
counting for up to 20 percent of patients with heart ease include tagging blood constituents with radioac-
failure in Uganda, the Sudan, and northern Nigeria. tive substances (which can be used to measure both
It can affect people who live in the area as well as function and bloodflow)and both computerized ax-
those who visit from other parts of the world. Al- ial tomography and magnetic resonance imaging.
though its precise cause is unknown, and in some The latter two techniques make use of digital pro-
instances it may be due to a parasitic infection, the cessing and imaging to provide cross-sectional im-
underlying cause may be an increase in the number ages based on a computerized reconstruction of the
of eosinophils. In many parts of South America, the information provided by scanning from many differ-
parasite Schistosoma mansoni is a common cause of ent directions. In addition, computerized axial to-
heart disease. Also common in South America is mography and positron emission tomography are
Chagas' disease. Other heart diseases having charac- now being used to measure the metabolic state of the
teristic geographic patterns include some forms of heart muscle.
congenital heart disease that are more significant Treatment of patients with acute myocardial in-
for people who live at high altitudes, where the con- farction has evolved from observing and supporting
centration of oxygen in the inspired air is reduced. the patient to attempting to intervene in the disease
Peripartum cardiac failure is developed by up to 1 process itself. Typically, patients with myocardial
percent of women in northern Nigeria during the infarction suffer from an obstruction of one of the
postpartum period. Occurring most often in July, it coronary arteries that supply blood to the heart. Two
seems to be caused by a combination of extreme methods for relieving that obstruction are now being
heat, exhaustion exacerbated by the traditional cus- used, one mechanical and one in which medication
tom of lying on a bed over a fire, and eating food rich dissolves the blockage. The mechanical intervention
in lake salt. Thus, peripartum cardiac failure ap- is percutaneous transluminal coronary angioplasty
pears to be largely a result of cultural patterns. In (PCTA), during which a catheter is directed into the
this respect it resembles coronary heart disease, coronary artery and expanded in order to clear the
which is linked to Western culture in ways that we lumen. Since its introduction in 1977, PCTA has
identify as risk factors and in ways that we do not become widely used for the treatment of coronary
fully understand, as exemplified by the impact of disease. The number of procedures performed in the
Japanese cultural values on coronary disease just United States rose from 32,206 in 1983 to 175,680 in
described. 1987. The procedure has also become popular in
other countries, with approximately 12,000 proce-
Recent Changes dures being done in the Federal Republic of Ger-
Perhaps because of the prevalence of cardiac disease many and 10,048 in Japan during 1987. The initial
as well as the symbolic significance of the heart, success rate approaches 95 percent at some institu-
concern for heart-related diseases has been central tions, but a significant percentage of patients experi-
to much of what we have come to identify as late- ence later failure. PCTA continues to be used for
twentieth-century medicine. That includes both people who suffer from symptoms caused by an ob-
"high-tech" innovations and preventive medicine struction of the coronary arteries, but who have not
strategies, such as risk-factor intervention and life- yet suffered death of the heart muscle. The tech-
style modifications. nique has been attempted as well with patients who
The echocardiogram is a "high-tech" approach to have recently suffered death of the heart muscle,
cardiac diagnosis based on the reflection of sound causing myocardial infarction, but recent studies
waves in the body. The technique was first demon- suggest that it is not as useful for urgent therapy.
strated in the 1950s, and recent advances have Tissue-dissolving agents include products of re-
greatly increased the quality of the images, such combinant DNA technology. These agents should be
that it is possible to diagnose heart disease even in a administered soon after a person suffers a heart at-

tack in order to dissolve the clot before irreversible Stokes-Adams disease; more recent models can be
damage has been done to the heart muscle. Al- programmed to respond to changing conditions in a
though PCTA requires rapid transportation of a variety of ways. A new device can electrically shock
heart attack patient to the hospital, often via helicop- the heart out of an uncoordinated rhythm called
ter, treatment with clot-dissolving agents can be ini- ventricular fibrillation. This automatic implantable
tiated before the patient reaches the hospital. This defibrillator, first used in 1982, appears to be helpful
therapy must be closely monitored, however, mak- for patients who suffer from arrhythmias that are
ing hospitalization necessary for optimal treatment. difficult to control.
This may negate studies from the 1970s that showed Unlike the stomach or the limbs, for example, a
that hospitalization made no difference in the prog- person's heart cannot stop functioning for long or the
nosis of patients suffering from an uncomplicated person will die. This fact made operations on the
myocardial infarction. The optimum therapy for pa- heart difficult to contemplate during the nineteenth
tients with myocardial infarction is being evaluated. century, when great advances were being made in
The first successful transplantation of a human surgery on other organs. Some leading surgeons of
heart into another human being was performed in the day flatly asserted that surgery on the heart
South Africa by Christian Barnard in 1967. Trans- would always be impossible. Nonetheless, early in
plantation was at first reserved for critically ill pa- the twentieth century, surgical treatment of valvu-
tients not likely to survive for long. However, a se- lar heart disease was attempted. From 1902 to 1928,
ries of advances, primarily in the posttransplant 10 attempts were made to cure mitral stenosis (a
management of patients, has led to a dramatic in- narrowing of the valve leading to the main pumping
crease in survival after transplantation and to a chamber of the heart); 8 of the patients died. Be-
tendency to carry out the procedure on patients with cause of the dismal outcomes, no one attempted an-
severe heart failure much earlier in the course of the other such operation until the mid-1940s. Starting
disease. As a result, the number of transplantations in the 1950s, the availability of cardiac bypass in the
performed worldwide increased from 3,000 in 1986 form of an effective pump and oxygenator enabled
to more than 6,800 by January 1988. The five-year surgeons to work on a still, "open" heart rather than
actuarial survival worldwide exceeded 70 percent on a beating organ. Valve replacements became rela-
and was more than 80 percent for some subgroups. tively easy. Coronary artery bypass grafting (sur-
Moreover, more than 80 percent of survivors were gery to bypass blocked coronary arteries) is now a
able to return to their previous occupations or compa- common means of treating coronary artery disease.
rable levels of activity. The success of cardiac trans- Whereas at first surgeons bypassed only one or two
plantation prompted Medicare, the primary federal obstructed vessels, now many more are commonly
means of payment for elderly U.S. citizens receiving bypassed during a procedure.
health care, to fund heart transplantations. It did so, Our ability to replace diseased valves has also
however, at only a few locations, selected on the greatly increased. Some patients suffering from ab-
basis of results and experience, thus linking reim- normal heart rhythms can be helped by heart sur-
bursement with some measure of quality. Although gery designed to interrupt abnormal conduction
not all heart transplantations are covered by Medi- pathways within the heart. Some centers are investi-
care, many insurance plans have indicated an intent gating a heterotopic prosthetic ventricle, a mechani-
to employ Medicare criteria in deciding which insti- cal device designed to support a failing heart until a
tutions will be paid for the procedure. suitable transplant can be procured. Others have
That some patients suffer from an abnormally attempted to use an artificial heart for long-term
slow heartbeat has been known for some time. Cur- support. Such a device would not be subject to the
rent treatment for many of them (perhaps too many) immunologic phenomena associated with transplan-
is provided by an artificial pacemaker. Thefirstpace- tation and would obviate the need to locate a donor
maker was implanted in 1959, and now more than heart. However, problems with clots and hemolysis
200,000 pacemakers are implanted each year world- have thus far severely limited the attractiveness of
wide, approximately half of these in the United this option.
States. The pacemaker, which usually weighs about
40 grams, is connected to the heart by wires and is Coda
powered by lithium batteries that commonly last 7 The heart continues to have a central place in West-
to 10 years. At first pacemakers produced electrical ern medicine. Heart diseases are common, and many
pacing signals at a constant rate in order to treat of the most prominent new approaches to disease in

the past few decades have been directed at heart City from 1938-1967. American Journal of Medicine
disease. Cardiologists have become the most power- 51: 83-96.
ful subspecialists in internal medicine. Criqui, Michael H. 1987. The roles of alcohol in the
But the heart has long been central to the broader epidemiology of cardiovascular disease. Ada Medica
Western culture as well. The heart is seen as the seat Scandanavia, Suppl., 717: 73-85.
of the emotions - as in the expressions a "broken Davidson, N. M., and E. H. O. Parry. 1978. Peri-partum
cardiac failure. Quarterly Journal of Medicine, New
heart," "crimes of the heart," a "bleeding heart," and
Ser., 47: 431-61.
a "change of heart." The heart is also the source of Davies, J. N. P. 1956. Endomyocardial fibrosis. In Cardio-
strength: "Take heart!" or "You've gotta have heart." vascular epidemiology, ed. Ancel Keys and Paul D.
The heart is metaphorically the site of a central White, 106-10. New York.
issue or concern, as in the "heart of the country" or DeVries, William C. 1988. The permanent artificial heart:
the "heart of the issue." Finally, the heart is often Four case reports. Journal of the American Medical
seen, both metaphorically and literally, as the source Association 259: 849-59.
of life, and its failure is considered both a cause and Dimsdale, Joel E. 1988. A perspective on Type A behavior
a marker of death. Concepts of heart disease are and coronary disease. New England Journal of Medi-
drawn from general cultural concepts of what it cine 318: 110-12.
means to be human, and studies of how and when Dock, George. 1939. Historical notes on coronary occlu-
they change will increase our understanding not sion: From Dock to Osier. Journal of the American
only of the history of medicine but of history in Medical Association 113: 563-8.
Dodu, R. A. Silas. 1988. Emergence of cardiovascular dis-
general.
ease in developing countries. Cardiology 75: 56-64.
JoelD.Howell Farrar, David J., et al. 1988. Heterotopic prosthetic ventri-
cles as a bridge to cardiac transplantation: A multi-
Bibliography center study in 29 patients. New England Journal of
Ackerknecht, Erwin H. 1967. Medicine at the Paris hospi- Medicine 318: 333-40.
tals, 1794-1848. Baltimore. Fishman, Alfred P., and Dickinson W. Richards, Jr. 1964.
Andy, J. J., F. F. Bishara, and O. O. Soyinka. 1981. Rela- Circulation of the blood: Men and ideas. New York.
tion of severe eosinophilia and microfilariasis to Forssmann, Werner. 1974. Experiments on myself: Mem-
chronic African endomyocardial fibrosis. British oirs of a surgeon in Germany, trans. Hilary Davies.
Heart Journal 45: 672-80. New York.
Auenbrugger, Leopold. 1936 (orig. 1761, trans. John Fowler M. B., and John S. Schroeder 1986. Current status
Forbes 1824). On percussion of the chest. Bulletin of of cardiac transplantation. Modern Concepts of Cardio-
the History of Medicine 4: 379-403. vascular Disease 55: 37.
Bedford, D. Evan. 1951. The ancient art of feeling the Fox, Renee C, and Judith P. Swazey. 1970. The clinical
pulse. British Heart Journal 13: 423-37. moratorium: A case study of mitral valve surgery. In
Biorck, Gunnar. 1956. Wartime lessons on arteriosclerotic Experimentation with human subjects, ed. Paul A.
heart disease from northern Europe. In Cardiovascu- Freund, 315-57. New York.
lar epidemiology, ed. Ancel Keys and Paul D. White, Fragomeni, Luis Sergio, and Michael P. Kaye. 1988. The
8-21. New York. Registry of the International Society for Heart Trans-
Block, Peter C, et al. 1988. A prospective randomized trial plantation: Fifth Official Report -1988. Journal of
of outpatient versus inpatient cardiac catheterization. Heart Transplantation 7: 249-53.
New England Journal of Medicine 319: 1251—5. Frank, Robert. 1988. The telltale heart: Physiological in-
Bourassa, Martial G., et al. 1988. Report of the joint ISFC/ struments, graphic methods, and clinical hopes,
WHO task force on coronary angioplasty. Circulation 1854-1914. In The investigative enterprise: Experi-
78: 780-9. mental physiology in nineteenth-century medicine, ed.
Brett, Allan S. 1989. Treating hypercholesterolemia: How William Coleman and Frederick L. Holmes, 211-90.
should physicians interpret the published data for pa- Berkeley and Los Angeles.
tients? New England Journal ofMedicine 321: 676-80. Fye, W. Bruce. 1985a. Cardiology in 1885. Circulation 72:
Burch, G. E., and N. P. de Pasquale. 1964. A history of 21-6.
electrocardiography. Chicago. 1985b. The delayed diagnosis of myocardial infarction:
Chazov, E., R. G. Oganov, and N. V. Perova, eds. 1987. It took half a century! Circulation 72: 262-71.
Preventive cardiology. Proceedings of the Interna- Goldman, Lee, and Francis E. Cook. 1984. The decline in
tional Conference on Preventive Cardiology, Moscow, ischemic heart disease mortality rates: An analysis of
June 23-6, 1987. London. the comparative effect of medical intervention and
Cherubin, C. E., and H. C. Neu. 1971. Infective endo- changes in lifestyle. Annals of Internal Medicine 101:
carditis at the Presbyterian Hospital in New York 825-36.

Hall, A. Rupert. 1960. Studies on the history of the cardio- Cholesterol Education Program Expert Panel on De-
vascular system. Bulletin of the History of Medicine tection, Evaluation, and Treatment of High Blood Cho-
34: 391-413. lesterol in Adults. Archives of Internal Medicine 148:
Harvey, William. 1928 (orig. 1628, trans. G. L. Keynes). 36-69.
An anatomical disquitation on the motion of the heart National Heart, Lung, and Blood Institute: Fact Book, Fis-
and blood in animals (De motu cordis). London. cal Year 1987. 1987. Bethesda, Md.
Heberden, William. 1941 (1772). Account of a disorder of Olsen, Eckhardt G. J., and Christopher J. F. Spry. 1985. Re-
the breast. In Classics of cardiology, Vol. 1, ed. Freder- lation between eosinophilia and endomyocardial dis-
ick A. Willius and Thomas E. Keys, 221-4. New York. ease. Progress in Cardiovascular Diseases 27: 241—54.
Hill, J. D., J. R. Hampton, and J. R. A. Mitchell. 1979. Payer, Lynn. 1988. Medicine and culture: Varieties of treat-
Home or hospital for myocardial infarction: Who ment in the United States, England, West Germany,
cares? American Heart Journal 98: 545-7. and France. New York.
Hirsch, A. 1883. Handbook of geographical and historical Pernick, Martin S. 1988. Back from the grave: Recurring
pathology, Vol. 1, trans. C. Creighton. London. controversies over defining and diagnosing death in
Howell, Joel D. 1984. Early perceptions of the electrocar- history. In Death: Beyond whole-brain criteria, ed.
diogram: From arrhythmia to infarction. Bulletin of Richard M. Zaner, 17-74. Dordrecht.
the History of Medicine 58: 83-98. Pisa, Z., and K. Uemura. 1982. Trends of mortality from
1985. "Soldier's heart": The redefinition of heart disease ischaemic heart disease and other cardiovascular dis-
and specialty formation in early twentieth-century eases in 27 countries, 1968-1977. World Health Statis-
Great Britain. Medical History, Suppl. No. 5: 34-52. tics Quarterly 35: 11-47.
1988. Hearts and minds: The invention and transforma- Ragland, David R., and Richard J. Brand. 1988. Type A
tion of American cardiology. In Grand rounds: One behavior and mortality from coronary heart disease.
hundred years of internal medicine, ed. Russell C. New England Journal of Medicine 318: 65—9.
Maulitz and Diana E. Long, 243—75. Philadelphia. Renlund, Dale G. et al. 1987. Medicare-designated centers
Johnson, Stephen L. 1970. The history of cardiac surgery, for cardiac transplantation. New England Journal of
1896-1955. Baltimore. Medicine 316: 873-6.
Keys, Ancel. 1980. Seven countries: A multivariate analy- Roberts, Stewart R. 1932. Nervous and mental influences
sis of death and coronary heart disease. Cambridge, in angina pectoris. American Heart Journal 7: 21-35.
Mass. Rose, G., and M. G. Marmot. 1981. Social class and coro-
Laennec, R. T. H. 1821. A treatise on diseases of the chest, nary heart disease. British Heart Journal 45: 13—19.
trans. John Forbes. London. Shaper, A. G., M. S. R. Hutt, and Z. Fejfar, eds. 1974.
Lawrence, Christopher. 1985. Moderns and ancients: The Cardiovascular disease in the tropics. London.
"new cardiology" in Britain, 1880-1930. Medical His- Shaper, A. G., Goyas Wannamethee, and Mary Walker.
tory, Suppl. No. 5: 1-33. 1988. Alcohol and mortality in British men: Explain-
Leaf, Alexander. 1989. Management of hypercholester- ing the U-shaped curve. Lancet 2: 1267-73.
olemia: Are preventive interventions advisable? New Smith, Dale C. 1978. Austin Flint and auscultation in
England Journal of Medicine 321: 680—4. America. Journal of the History of Medicine 33:
Leibowitz, J. O. 1970. The history of coronary heart dis- 129-49.
ease. London. Stallones, Reuel A. 1980. The rise and fall of ischemic
Lewis, Thomas. 1925. The mechanism and graphic regis- heart disease. Scientific American 243: 53—9.
tration of the heart beat. London. TIMI Research Group. 1988. Immediate vs delayed cathe-
Liss, Ronald Sandor. 1967. The history of heart surgery in terization and angioplasty following thrombolytic
the United States (1938-1960). Zurich. therapy for acute myocardial infarction. Journal of the
McKenzie, James. 1902. The study of the pulse, arterial, American Medical Association 260: 2849—58.
venous, and hepatic, and the movements of the heart. Topol, Eric J. 1988. Coronary angioplasty for acute myo-
Edinburgh. cardial infarction. Annals of Internal Medicine 109:
MacMurray, Frank G. 1957. Stokes-Adams disease: A 970-80.
historical review. New England Journal of Medicine Townsend, Gary L. 1967. Sir John Floyer (1649-1734) and
256: 643-50. his study of pulse and respiration. Journal of the His-
Marmot, M. G., and S. L., Syme. 1976. Acculturation and tory of Medicine 22: 286-316.
coronary heart disease in Japanese-Americans. Ameri- Weiss, Morris W. 1939. The problem of angina pectoris in
can Journal of Epidemiology 104: 225—47. the negro. American Heart Journal 17: 711-15.
Mitchell, S. Weir. 1971 (orig. 1891). The early history of WHO MONICA Project Principal Investigators. 1988. The
instrumental precision in medicine. New York. World Health Organization MONICA Project (Moni-
National Cholesterol Education Program Expert Panel on toring trends and determinants in cardiovascular dis-
Detection, Evaluation, and Treatment of High Blood ease): A major international collaboration. Journal of
Cholesterol in Adults. 1988. Report of the National Clinical Epidemiology 41:105—14.

Williams, Richard Allen. 1987. Coronary artery disease in of the breast have a crablike appearance or perhaps
blacks. Journal of Clinical Hypertension 3: 21S—24S. because the pain that cancer can produce resembles
World Health Organization. 1982. Prevention of coronary the pinching of a crab. Similarly, neoplasm, meaning
heart disease. Technical Report Series No. 678. Geneva. "new formation," and oncology, literally the "study
1988. Rheumatic fever and rheumatic heart disease. of masses," are derived from the Greek, as is the
Technical Report Series No. 764. Geneva. word tumor.
Ying-kai, Wu, Wu Zhao-su, and Yao Chong-hua. 1983.
Epidemiological studies of cardiovascular diseases in
Hippocratic medicine attributed tumors —which
China. Chinese Medical Journal 96: 201—5. included all sorts of swellings - to an abnormal ac-
cretion of humors. Although some remedies are men-
tioned, aphorism VI.38 advocates conservatism: "It
is better not to apply any treatment in cases of occult
cancer; for, if treated, the patients die quickly; but if
not treated they hold out for a long time." Galen
II.6 sought to differentiate more clearly cancers from
Concepts of Cancer inflammatory lesions and gangrene. Cancer was
held to be caused by black bile; if the cancer ulcer-
ated, the black bile was undiluted; if there was only
In past centuries people feared epidemic diseases a tumor, the pathogenic humor had been diluted.
with their sudden onset, ghastly symptoms, agoniz- Carcinoma of the breast was probably the earliest
ing death for many, and sometimes disfigurement or actual neoplasm for which surgical eradication was
physical impairment for survivors. Today, especially attempted. Leonides of Alexandria, who slightly pre-
in the developed world (with a few notable excep- ceded Galen, is known to have progressively incised
tions), the dread of epidemic contagion seems almost and cauterized, both to prevent bleeding and to de-
as anachronistic as the burning of witches. It has stroy the neoplasm. Galen, conversely, recommended
been replaced by the dread of cancer. As with the that bleeding be permitted, presumably for the patho-
epidemics of yesterday, the basic causes of cancer genic humor to be drained. Some surgeons performed
remain shrouded in mystery, while its effects in a total mastectomy. Little was written about the heal-
terms of human suffering are all too well known. ing of these terrible procedures, but Rhazes warned
Cancer is a process whereby a loss of control of in the ninth century that those who performed sur-
normal cell division and multiplication produces a gery on a cancer generally only caused it to worsen
tumor that can invade adjacent tissues and metasta- unless it was completely removed and the incision
size, that is, implant cancerous cells at a site that is cauterized.
noncontiguous to their origin, where abnormal mul- Although barber-surgeons probably incised and
tiplication continues. When cancer originates in con- excised boils and warts in the belief that they were
nective tissues (mainly bone or muscle), it is called curing cancer, it seems likely that few cancers were
sarcoma; when it originates in epithelial tissues (lin- treated surgically until relatively modern times.
ing tissues and organs such as the breast, lungs, or Ambroise Pare wrote toward the end of the sixteenth
stomach), it is called carcinoma. The latter is by far century that those who pretended to cure cancer
more common. Invasive tumors occur in all complex surgically only transformed a nonulcerous cancer
species and probably antedate the advent of verte- into an ulcerated one. "I have never seen a cancer
brates. The oldest paleopathological evidence is lim- cured by incision, nor known anyone who has." Nev-
ited to lesions that affected bones, such as those ertheless, in the seventeenth century, Wilhelm Fab-
found in dinosaurs. Tumors have been found in Egyp- ricius of Hilden described the removal of axillary
tian mummies dating from 2000 to 3000 B.C., and nodes in a breast cancer operation and provided ade-
physicians of that ancient land knew of and treated quate descriptions of operations for other cancers.
patients for cancers of several sites. The discovery of the lymphatic system by Gas-
Certainly the ancient Greeks were familiar with parro Aselli in 1622 directed medical attention away
this disease, or perhaps better, this group of dis- from the black bile theory, which no one had demon-
eases. The condition is discussed in the Hippocratic strated, toward abnormalities of the lymphatic struc-
corpus, and in fact its nomenclature is dominated by tures in the causation of cancer. Basically, the idea
Greek words. Hippocrates himself is credited with was that cancer was an inflammatory reaction to
having named the disease cancer from karcinos, the extravasated lymph, the type of lesion depending on
Greek word for crab, perhaps because some cancers its qualities. About 150 years later John Hunter

II.6. Concepts of Cancer 103
modified the lymph theory by defining "coagulating research is usually viewed as a twentieth-century
lymph" (i.e., blood serum), as opposed to true lymph, undertaking and, despite its antiquity, the disease
as that component of blood that clotted spontane- itself is viewed as largely a twentieth-century phe-
ously when it was extravasated. It was this "lymph," nomenon. As infectious ailments have receded, can-
when it was contaminated by a "cancerous poison" cer, along with cardiovascular diseases, has been
and oozed into tissues, that Hunter viewed as the perceived to be the greatest single health problem
cause of cancer. Quite presciently, he described me- facing the developed world. Actually, cancer pre-
tastases as "consequent cancers" that reached dis- sents a set of problems, because the term should be
tant parts via lymphatic channels. considered a collective noun. The World Health Or-
A more transitory hypothesis advocated particu- ganization has classified some 100 kinds of cancer
larly by the German Daniel Sennert and the Portu- depending on their sites of origin, a figure that may
guese Zacutus Lusitanus early in the seventeenth be too conservative.
century was that cancers, at least when ulcerated, It is generally estimated that some form of cancer
were, like leprosy, contagious. Popular fear of the will develop in one-third of the inhabitants of the
contagiousness of cancer persisted into the twenti- industrialized world. Moreover, the probability is
eth century. The first accurate etiologic observation increasing. Less than two decades ago it was calcu-
about any cancer can be attributed to the London lated that one in four would develop cancer - with
surgeon Percival Pott, who reported in 1775 that even those odds prompting the charge that cancer
many men who had worked as chimney sweeps since represents the "failure of medicine" (Braun 1977).
boyhood and were routinely lowered into narrow Certainly this seems to be the case when a compari-
chimneys suffered scrotal cancer. He linked this ob- son is made with medicine's triumphs against epi-
servation to the irritating effect of chronic contact demic illnesses, which came one on top of the other
with soot and thereby identified the first occupa- after the advent of the germ theory. Although we are
tional cancer. well into the second century since the beginnings of
The impact of microscopy on cancer research cell theory, cures for cancer have thus far largely
came very slowly. Robert Hooke, the pioneering eluded scientific medicine. Nor has Virchow's obser-
seventeenth-century microscopist who coined the vation that irritants could summon forth cancerous
term cell, thought that tissues were composed of cells proved very helpful in cancer prevention-
fibers - a hypothesis that persisted into the nine- although irritants are among the foci of cancer re-
teenth century. Not until after 1830, when Joseph J. search today.
Lister designed the first achromatic microscope The concept of autonomy suggests that once a cell
lenses, did progress in histology begin, made mostly has become truly cancerous it is beyond bodily con-
by German investigators. The first new concept, trol. The concept was established around the turn of
advanced by Theodor Schwann and supported by the century by Arthur Hanau, Leo Loeb, and Carl
Johannes Mueller, was that all tissues were com- O. Jensen, who transplanted cancer cells into
posed of microscopic cells, not fibrils. Yet the lym- healthy animals and plants of the same species and
phatic theory was not easily abandoned, and cells observed the unrestrained growth of new cancers in
were thought to derive from "blastema," which was the previously healthy hosts. Yet the fact that can-
organized from intercellular fluids. In 1854, how- cers, once established, can enter a stage of remis-
ever, Rudolph Virchow questioned the existence of sion - sometimes permanently - argues that the
the unidentified blastema, and in the following body can rally to retard or even reverse previously
year he stated the principle that all cells originated uncontrolled cell proliferation.
from cells and postulated that neoplasms developed Following these transplantations, the next ad-
from immature cells. But even then the spread of vances in research were made when cancer was pro-
cancer was considered to result from some sort of a duced experimentally in plants and animals by the
humor rather than the dissemination of cells. In administration of various chemical, physical, and
1867 Edwin Klebs advanced the opinion that most biological agents. These experiments revealed, for
cancers originated in epithelial tissues (carcinomas example, that some 150 different viruses cause tu-
in modern terminology), and coincidentally, Wil- mors in living organisms, that ultraviolet light and
helm Waldeyer applied the old, previously unspe- X-rays as well as radioactive substances such as
cific term sarcoma to neoplasms that arose in con- radium and uranium induce cancer, and that coal
nective tissues. tars, dyes derived from them, and other substances
Despite these scientific developments, cancer can also induce the disease. Moreover, even natu-

Table II.6.1. Ten most common invasive neoplasms Table II.6.2. Deaths due to cancer
and estimated new cases as percentage of all new as percentage of all deaths
cases in the United States, 1990 according to sex and age group,
United States, 1986
Neoplasm Percentage Cases
Age Male (%) Female I
Male
Prostate 21.1 30,000 1-14 10.0 11.6
Lung 19.6 92,000 15-34 5.9 14.0
Colon 10.0 26,000 35-54 21.4 41.0
Bladder 6.9 6,500 55-74 30.2 34.6
Rectum 4.6 4,000 75 + 19.2 13.8
Non-Hodgkin's lymphomas 3.6 9,500 Total 22.7 21.8
Leukemias 3.0 Q Qftft
y,ouu
Kidney 2.9
6,100
Stomach 2.7 8,300
Pancreas 2.6 12,100
Total 77.0 204,300
Table 1[1.6.3. Most common cancers as causes of
Female death from cancer, according to sex and age group,
Breast 28.8 44,000 United States, 1986
Colon 11.1 27,300
Lung 10.6 50,000 Male Female
Uterus 6.3 4,UUU
Rectum 4.0 3,600 Age Cancer Percentage Cancer Percentage
Ovary 3.9 12,400 1-14 Leukemia 37.0 Leukemia 35.6
Non-Hodgkin's lymphomas 3.3 8,700 15-34 Leukemia 18.5 Breast 18.8
Pancreas 2.8 12,900 35-54 Lung 34.4 Breast 30.8
Cervix 2.6 6,000 55-74 Lung 39.2 Lung 23.3
Bladder 2.5 3,200 75+ Lung 26.9 Colon and 17.9
Total 75.9 172,100 rectum
rally occurring substances in the body, such as the U.S. cancer statistics offers some quantification of
sex hormone estrogen, have been shown to cause the impact of the disease in relation to age, sex, and
cancer when given to experimental animals. race (see Tables II.6.1 through II.6.4). The three
The extent to which the incidence of cancer is most common cancers of men, those arising in the
increasing is a complicated issue. It is predomi- prostate, lung, and colon, comprise about 50 percent
nantly an illness of middle age and, with the excep- of new cases and 55 percent of deaths due to cancer.
tion of a few forms, such as certain leukemias, it is The three most frequently occurring cancers of
relatively rare in children. Thus, people in the devel- women, breast, colon, and lung, also comprise about
oped world, having escaped famine and epidemic 50 percent of new cases and account for 50 percent of
disease, have had their life expectancy extended be- deaths. As a proportion of all deaths, those from
yond 50 years of age into that age in which the cancer do not increase linearly with age. This is
frequency of cancers becomes increasingly high. Al- mainly because of the accidental deaths of children
though a shift in the age distribution of a population and young adults, on the one hand, and cardiovascu-
affects the actual incidence of cancer, the statistics lar diseases in the elderly, on the other. Of deaths
have also shown artifactual increases. These are due from cancer in women, the peak, 41.0 percent, occurs
to vast improvements in the diagnostic techniques of in the 35 to 54 age group. In contrast, men have a
endoscopy, imaging, and biochemistry that can now somewhat older average age of death with 30.2 per-
be used to detect many asymptomatic cancers and cent in the 55 to 74 age group. Most of this difference
pathological techniques that facilitate the differen- is attributable to the difference in the age distribu-
tiation of neoplastic from inflammatory lesions, pri- tion of women with carcinoma of the breast and nu»n
mary from secondary neoplasms, and so forth. with carcinoma of the prostate. Survival has im-
The following interpretation of the most recent proved variably from the 1960s to the 1980s. Tho

Table II.6.4. Five-year survival rates by race in two race-related differences in survival of other rela-
time periods from principal malignant neoplasms in tively common carcinomas such as those of the lung,
the United States kidney, and stomach.
For the incidence of a disease to be considered
1960-5 1980-5 meaningfully, it must be presented in age-specific
Neoplasm White Black White Black terms. As the average age of a population increases
and the proportion of an age group in which various
Lung 8 5 13 12 cancers most commonly occur becomes larger, an
Breast (F) 63 46 76 64
increase in the number of cases is to be expected.
Prostate 50 35 73 63
This increase, however, can tend to blur the more
Colon 43 34 55 48
Bladder 53 24 78 56
important question of whether the incidence of that
Uterus 73 31 83 52
disease is increasing in a specific age group. The
Ovary 32 32 38 38 statistical analyst must also be cognizant of the im-
Cervix 58 47 67 59 pact of technological improvements on the finding of
Rectum 38 27 53 39 potential cases and the establishment of a diagnosis,
Non-Hodgkin's 31 ? 51 44 as well as changes in interest in the disease in ques-
lymphomas tion and changes in access to medical care.
Kidney 37 38 52 55 Moreover, the addition to or removal from the
Leukemias 14 ? 34 27 environment of a carcinogen is a convenient explana-
Stomach 11 8 16 19 tion for the waxing or waning of the occurrence of a
Pancreas 1 1 3 5
cancer. In this regard the long latent period of most
clinical cancers is often overlooked. For example, an
Note: Data are percentages.
Source: Data through 1986 from state records of Connecti-
argument used in the 1940s against the hypothesis
cut, Hawaii, Iowa, New Mexico, Utah, and Atlanta, De- that cigarette smoking was a major cause of lung
troit, Seattle—Puget Sound, San Francisco-Oakland. cancer was that many more women were smoking
than had previously been the case, yet no increase in
lung cancer among women had occurred. Conse-
greatest improvements have occurred in the treat- quently, the relationship between smoking and lung
ment of stomach cancer in both sexes and in uterine cancer in men was viewed by some to be coincidental
cancer. Of the more common neoplasms, only lung rather than causal. But of course, in retrospect we
cancer has increased in incidence in both sexes, as can see that most of the women in question had not
has carcinoma of the prostate in men. Survival was yet smoked for a sufficient length of time for the
below 20 percent for four of the more common neo- result to become evident in cancer statistics. Per-
plasms in the 1960s (leukemias, stomach, lung, pan- haps future analysis will clarify in a similar fashion
creas), and save for the leukemias, it remains below why gastric cancer is decreasing in the United
20 percent. The explanation for the decrease in States or why prostate cancer is increasing. Cer-
death from stomach cancer lies in a decline in its tainly one of the most difficult problems in identify-
occurrence, not by a great improvement in therapeu- ing causes of cancer is that of cocarcinogenesis. The
tic success. Survival generally has been and remains most flagrant example is the additive effect of the
poorer for black than for white patients. In 1960 inhalation of both cigarette smoke and asbestos par-
white patients had a 42 percent better chance than ticles on the occurrence of lung cancer. Both of these
their black counterparts of survival following treat- agents are independently carcinogenic, and their
ment of carcinoma of the uterus, a 29 percent better combined effect greatly increases the incidence of
chance with carcinoma of the bladder, and a 17 per- the disease.
cent better chance with carcinoma of the breast. In With regard to public health, the greatest problem
1980 the greatest race-related survival differences of exogenous carcinogenesis today is not exposure to
were such that whites had the following better industrial pollutants, as many believe, but rather
chances than blacks: carcinoma of the bladder, 22 the use of tobacco products. Whereas cigarette
percent; carcinoma of the uterus, 21 percent; and smoke appears to exert the most potent carcinogenic
carcinoma of the rectum, 14 percent. These differ- effect, cigar smoke and chewing tobacco are also
ences have often been attributed to the black popula- implicated. Historically, the possibility that an in-
tion's poorer access to medical care. However, this is crease in lung cancer was related to an increase in
obscured by the fact that there do not seem to be cigarette smoking was first raised in Germany in

the 1920s. In the United States interest in this ques- in comparison with nonsmokers ranging from 3.8 to
tion was stimulated in 1950 with the publication of 14.2 percent (mode 11 percent). In four studies of
three epidemiological studies, each of which showed women the excess was smaller, ranging from 2.0 to
that lung cancer patients were likely to be heavy 5.0 percent. Despite the fact that no specific suffi-
smokers. ciently potent pulmonary carcinogens have as yet
Although an epidemiological association cannot been identified in tobacco smoke, a 1970s finding
prove a causal relationship, the satisfaction of five appears to clinch the causal relationship between
criteria make such a connection highly probable: (1) smoking and the development of lung cancer. R. Doll
The association between the suspected pathogen and and R. Peto (1976), in a 20-year investigation of the
the disease is observed consistently. (2) In compari- mortality of British physicians in relation to smok-
son with suitable control groups, the association is ing, showed that the risk diminishes increasingly
strong. (3) The association is relatively specific with after smoking has been discontinued for several
the disease in question. (4) The temporal relation- years. This obviously cannot be ascribed to genetic
ship between exposure to the pathogen and the onset or psychological factors. However, even 15 years af-
of the clinical disease is appropriate and consistent. ter cessation the risk among former smokers re-
(5) The association is consistent with a known or mained twice that of men of similar age who had
plausible explanation of the natural history of the never smoked.
disease. Smoking has now been common among women
Resistance to the acceptance of a causal relation- long enough to be reflected in an alarming increase
ship between smoking and the development of lung in the incidence of lung cancer. This began in the
cancer was based initially on doubt that the inci- mid-1960s, and the incidence now is half that of men
dence of lung cancer was actually increasing and in the United States. As of 1986 the rate of death
then on a failure to appreciate the long preclinical from lung cancer for U.S. women equaled that for
phase of the disease. A massive prospective study of breast cancer, which has remained stable. In the
the effects of smoking on health published by E. C. case of the latter disease it appears that, of the half-
Hammond and D. Horn in 1958 purported to show million women worldwide in whom breast cancer
that smoking was not uniquely associated with lung develops annually, half reside in North America and
cancer. western Europe, which contain less than 20 percent
Similarly, the observation that cigarette smoking of the world's population. However, it is hazardous to
was associated with neoplasms of organs, such as the compare prevalence or even mortality statistics with-
bladder, which did not come into contact with smoke, out knowing critical local circumstances. For exam-
and with'cardiovascular diseases was used by propo- ple, why would the age-adjusted rate of death from
nents of tobacco interests and some biostatisticians breast cancer in Finland and Denmark be more than
to cast doubt on a causal relationship between the triple the rate in Sweden, and why would the rate in
inhalation of cigarette smoke and the development Scotland be quintuple that of England?
of lung cancer. This argument ignored the multiplic- A daughter or sister of a woman with breast cancer
ity of components of tobacco smoke, which could has a nearly three times greater risk of developing
easily act differently on different tissues, and the this disease than a woman without such an associa-
clearly quantitative relationship between smoking tion. The risk is greater if the relative's cancer was
and the increased probability of lung cancer develop- found at an early age, and a great deal more if both
ing. Nevertheless, lung cancer occurs in a small mi- mother and sister have been affected. This suggests a
nority of even heavy smokers. This has been taken genetically mediated predisposition, as does the in-
to indicate an intrinsic predisposition that, if identi- creased risk of a secondary primary breast cancer as
fied, could be used to warn persons at risk. But compared with the risk of a first occurrence. How-
investigations have thus far failed to yield useful ever, other observations indicate that environmental
results. Finally, there have been no reproducible ex- factors must also enter in. For example, the preva-
periments in which tobacco smoke has caused lung lence of breast cancer in Japan is about one-fourth
cancer in experimental animals. Although positive that in northern Europe or North America. Neverthe-
results would be convincing, negative results are less, among women of Japanese ancestry living in
attributable to species differences and, perhaps, in- North America, the incidence of breast cancer by the
sufficient duration of exposure. second generation matches that of white North
Eight prospective studies of male cigarette smok- American women. Whether dietary or other poten-
ers have shown an excess mortality from lung cancer tial cofactors are implicated remains unresolved.

Unfortunately, cancer statistics often reveal the in tropical countries such as Peru, Ecuador, or Pan-
complexities of the disease under investigation ama, but data from other countries conflict with
rather than causal explanations. Carcinoma of the these extreme examples.
prostate is the second most frequently occurring can- Certainly the Westernizing of the Japanese diet
cer among U.S. men; it is the fifth worldwide. This has provided persuasive evidence of the carcinogenic
disease is more prevalent among U.S. blacks, despite role of fat. Nutrition surveys of 1955 and 1984 indi-
their heterogeneity, than any other population that cate that the fat intake of Japanese women in-
has been studied. It is about 80 percent more com- creased by about 180 percent during these years and
mon in black than in white men in the United the mortality from colorectal cancer increased by
States. It is also common in black Caribbean popula- about 130 percent. There was a lag of about 15 years
tions, whereas sketchy information from Africa indi- between the beginning of the widespread dietary
cates much lower prevalences. Carcinoma of the pros- change and the beginning of the increase in death
tate is 28 times as common among blacks in Atlanta from this neoplasm. A recent U.S. study has also
as among Japanese in Osaka. Although the inci- demonstrated an association between a high level of
dence appears to be low throughout the Orient, it is animal fat consumption and the occurrence of this
much higher among men of Chinese and Japanese neoplasm. The predominant hypothesis for this asso-
extraction living in Hawaii. ciation is that, since a higher fat consumption in-
The incidence of clinically evident prostate cancer creases the excretion of bile acids and the growth of
is more highly correlated with increasing age above colonic bacteria, the opportunity to convert bile ac-
50 than is any other neoplasm. It is six to seven ids into carcinogenic substances by bacterial metabo-
times more prevalent in the 75 to 84 than the 55 to lism is facilitated. In the United States the incidence
64 age group, and the black-white difference in of colorectal cancer has remained stable in white
prevalence diminishes with increasing age. There is men and has decreased moderately in white women,
no convincing evidence of the pathogenicity of any but has increased in the black population. In addi-
industrial exposure for this neoplasm. However, an tion to changes in incidence, an unexplained patho-
increased risk is associated with chronic cigarette logical change has been occurring: In U.S. patients
smoking, and there appears to be a correlation be- the lesion is less commonly located in the rectum
tween an above-average sexual drive and susceptibil- and more commonly found in the colon. It would be
ity to prostatic carcinoma. This could mean that a satisfying to conclude that this is a reflection of the
subtle alteration in the metabolism of sexual hor- increasingly frequent removal of premalignant le-
mones has a predisposing role, but studies have sions from the rectum, but medical intervention is
yielded inconsistent results. Alternatively, men with an unlikely explanation.
a high sexual drive, particularly in a permissive One well-recognized environmental carcinogen is
culture, have an increased likelihood of exposure to the ultraviolet component of sunlight, which is a
multiple sexual partners. A correlation between pro- major cause of skin cancers. Susceptibility is related
miscuity and prostatic carcinoma, if substantiated, to paleness and a poor ability to tan, as well as to
would suggest an analogy to the better-documented chronic exposure to sunlight. The overall incidence
correlation between promiscuity and carcinoma of of nonmelanoma skin cancers in the white U.S. popu-
the cervix in women and the possibility that a sexu- lation is about 165 per 100,000. However, the preva-
ally transmitted virus is a pathogenetic agent. None lence in Texas is about three times that in Iowa. The
of these hypotheses, however, explains the increase incidence of melanoma is only about 4 per 100,000,
in the occurrence of this disease in the late 1900s. but 65 percent of the deaths attributed to skin can-
With regard to possible roles of diet in carcino- cers are caused by this disease. The lesion occurs
genesis there has been particular interest in twice as often on the legs of white women as on those
whether the presence or deficiency of certain compo- of white men. It occurs nearly twice as frequently on
nents of food influences the development of colo- the male trunk than the female trunk. This may
rectal cancer. Both diets low in fiber and high in fat reflect relative exposure to sunlight due to differ-
have been proposed to be pathogenetic. Investiga- ences in clothing. Not only is melanoma uncommon
tions have yielded conflicting results, but the best in blacks, but its location tends to be different: It is
evidence now points to a carcinogenic effect of in- more commonly found on palms or soles and within
creased fat consumption, particularly in women. the mouth - less heavily pigmented areas. The inci-
Colorectal cancer has been reported to be up to 10 dence of melanoma has been found to be increasing
times as common in central European countries as wherever statistics have been kept. The highest inci-

dence has been found in Arizona (16 per 100,000), crease has been worldwide and for unexplained rea-
where the disease has more than quadrupled in the sons. It remains the most prevalent carcinoma in
brief period from 1969 to 1978. It also quadrupled in East Asia, with the rate in Japan being more than
Connecticut from 1939 to 1972. The smallest in- seven times that in the United States, accounting for
crease has been observed in Sweden: 80 percent from one-third of all cancer deaths on those islands. The
1957 to 1971. Consistent with the increased inci- repetitive ingestion of high concentrations of salt
dence, mortality has nearly doubled. Whether the irritates the stomach lining, and this has been pro-
increase of this lethal disease is attributable to posed as a potential cause of gastric cancer. In fact,
changes in ultraviolet intensity due to atmospheric the decline in the incidence of this disease has been
pollution is as yet unknown. correlated with the decline in the salt preservation
Turning to human cancers definitely attributable of foods. In regions in which stomach cancer remains
to "civilization," X-rays and related ionizing radia- common, such as Japan, salted seafood has remained
tion are estimated to be the cause of no more than 3 a dietary staple. The incidence of gastric cancer
percent of cancers. Exposure to radon gas has been among first-generation immigrants from Japan to
clearly shown to be a cause of lung cancer in uranium the West is similar to that in their communities of
miners. Although this is a small group at risk, if it origin, but it declines to the incidence of the Western
were confirmed that the concentration of radon in community in which the next generation resides.
some homes was sufficient to be carcinogenic, pre- This suggests that the neoplastic process begins irre-
sumably the proportion of cases of cancer known to be versibly during childhood, regardless of relocation or
due to radiation exposure would increase substan- dietary changes after a certain age. Because this is
tially. Thyroid cancer results from a small to moder- not a genetically determined disease, a generation
ate radiation exposure to the neck with a latency that has not been exposed to the inducing irritant of
period of about a decade. A dose that is large enough salt at a critical age presumably will not suffer inor-
to destroy the gland leaves no tissue to undergo dinately from this neoplasm.
neoplastic transformation. Bone marrow is another Carcinoma of the cervix appears not to be related to
radiosensitive organ. The increased risk of develop- geography, but primarily to the sexual practices in a
ing leukemia, depending on dosage of radiation, be- given region or subculture. The commencement of
gins as early as 2 years after exposure, reaches a peak sexual intercourse during adolescence, multiple part-
probability after 6 to 8 years, and then diminishes. ners, or partners who have had numerous partners
Fetuses and infants are particularly sensitive. are all factors associated with an increased risk of
Suspicion of potential carcinogenesis has also developing the disease, as is a large number of preg-
fallen on synthetic food additives, such as dyes and nancies. Thus, carcinoma of the cervix is rare among
flavoring agents, and contaminants, such as pesti- nuns and common among prostitutes. A sexually
cides and fertilizers, either from direct spraying or transmitted virus is suspected to be a causative factor
from absorption of affected groundwater. Because of or cofactor. As with prostatic cancer, chronic cigarette
this suspicion, the Delaney amendment to the U.S. smoking appears to increase the risk of occurrence of
Food, Drug and Cosmetic Act was passed in 1958. this neoplasm. Another peculiar difference, at least
The amendment requires the banning of food addi- in the United States, is that carcinoma of the cervix
tives if they cause cancer in any species of experi- occurs about twice as frequently among black as
mental animal in any dosage. One result has been among white women, whereas carcinoma of the
the forced withdrawal of some products based on uterus occurs two to four times as often in white
quite dubious and unrealistic experiments. In view women.
of the huge number of compounds, both synthetic Cancer of the liver is much more prevalent in
and natural, to which people are exposed, usually in many of the developing countries than in the indus-
combinations having unknown interactions, decid- trialized world. Its incidence is highest in sub-
ing which ones to test and what tests are both rele- Saharan Africa, China, southern Asia, and Japan
vant and practical is an insoluble problem. (the exception among industrialized countries).
Worldwide, stomach cancer, which has become China alone accounts for about 45 percent of the
relatively uncommon in the United States, is the world's cases. The liver is subject to two principal
most prevalent visceral cancer (second for men, types of cancer. One originates in liver cells, and a
fourth for women). Nevertheless, death rates have history of infection with the hepatitis B virus predis-
been declining since the 1930s to become only about poses to this. The other originates in cells of the bile
35 percent of what they were at that time. The de- ducts. A predisposition to develop this form of cancer

is caused by infestation with the liver fluke exposure to known carcinogens, will exert by far the
Clonorchis sinensis and related parasites. The geo- greatest benefit to public health.
graphic distribution of these parasites is reflected in Thomas G. Benedek and Kenneth F. Kiple
the prevalence of this disease. Alcoholism has not
been shown to be a major predisposing factor. Bibliography
Other cancers in the developing world are associ- Ackerknecht, Erwin H. 1965. History and geography of the
ated with indigenous infectious agents and with cul- most important diseases. New York.
tural practices. Betel nut chewing, for example, is Austoker, Joan. 1988. A history of the Imperial Cancer
linked with high rates of oral cancer in central and Research Fund. Oxford.
southeast Asia and Kashmir; Bantu natives, who Boyle, P., C. S. Muir, and E. Grundmann, eds. 1989. Can-
cer mapping. New York.
hold warming pans of charcoal against their bodies,
Braun, Armin C. 1977. The story of cancer: On its nature,
are subject to cancers of the abdominal wall. The causes, and control. London.
frequent occurrence of esophageal cancer has been Burnet, Macfarlane, and David 0. White. 1972. Natural
related to the consumption of very hot beverages in history of infectious diseases, 4th edition. Cambridge.
some cultures. Burkitt's lymphoma, which occurs Cancer Research Campaign. 1988. Factsheet, Nos. 4-12.
almost exclusively in central Africa and New London.
Guinea, is probably caused by the Epstein-Barr vi- Davis, Devra Lee. 1989. Natural anticarcinogens, carcino-
rus in genetically predisposed individuals. Bladder gens, and changing patterns in cancer: Some specula-
cancer is a common problem in North Africa, and tion. Environmental Research 50: 322-40.
especially Egypt, because infestation with the para- Doll, R., and A. B. Hill. 1952. A study of the aetiology of
site Schistosoma haematobium induces the disease. carcinoma of the lung. British Medical Journal. 2:
In summary, the concept of cancer has evolved 1271-86.
1954. The mortality of doctors in relation to their smok-
through the ages from that of a single disease to one ing habits. British Medical Journal 1: 1451-5.
of many diseases with many causes. Most prevalent Doll, R., and R. Peto. 1976. Mortality in relation to smok-
are carcinomas of the stomach, lungs, breast, cervix, ing: 20 years' observations on male British doctors.
colon and rectum, prostate, and liver. Chief among British Medical Journal 2: 1525-30.
carcinogens are irritants such as fumes of tobacco 1981. The causes of cancer: Quantitative estimates of
and certain metals, ionizing and ultraviolet radia- avoidable risks of cancer in the United States today.
tion, specific chemical compounds, some helminthic Oxford.
parasites, and possibly viruses. Everyone is con- Elwood, J. M., and J. A. Lee. 1975. Recent data on the
stantly bombarded by carcinogens of various poten- epidemiology of malignant melanoma. Seminars in
cies, but cancer develops in a minority of people. A Oncology 2: 149-53.
few uncommon neoplasms clearly are genetically de- Ernster, V. L. 1988. Trends in smoking, cancer risk, and
termined, but the degree of resistance to carcinogens cigarette promotion. Cancer 62: 1702—12.
also appears to have a genetic basis. Greenberg, Michael. 1983. Urbanization and cancer mor-
tality: The United States experience, 1950-1975. New
Yet even if cancer is viewed as multiple diseases York.
with multiple causes, each disease involves the same Haenszel, W., and M. Kurihara. 1968. Studies of Japanese
phenomenon: an inadequately controlled division migrants. I. Mortality from cancer and other diseases
and multiplication of cells that can infiltrate adja- among Japanese in the United States. Journal of the
cent tissues and, in many types, form distant secon- National Cancer Institute 40: 43-68.
dary lesions. The factors that permit metastatic tu- Hammond, E. C , and D. Horn. 1958. Smoking and death
mor cells to survive and implant remain just as rates: Report on forty-four months of follow-up of
mysterious as the factors that initiate the loss of 187,783 men. Journal of the American Medical Asso-
control of cell division. ciation 166: 1159-72.
The available treatments are generally drastic Hirsch, August. 1886. Handbook of geographical and his-
torical pathology, Vol. 3, trans. Charles Creighton.
and poorly selective of the foci of disease and, in
London.
many circumstances, not curative. Earlier diagnosis Hippocrates. 1931. Aphorisms VI, trans, and ed. W. H. S.
improves the cure rate of many but not all cancers. Jones. Cambridge.
Therefore, public education about the signs of cancer Honda, G. D., L. Bernstein, R. K. Ross, et al. 1988. Va-
and further improvements in the sensitivity of diag- sectomy, cigarette smoking, and age at first sexual
nostic methods should be sought. However, until our intercourse as risk factors for prostate cancer in
understanding of the fundamental biology of cancer middle-aged men. British Journal of Cancer 46:
improves, preventive measures, such as minimizing 1307-18.

Howe, G. Melvyn. 1977. A world geography of human Reedy, J. 1975. Galen on cancer and related diseases. Clio
diseases. London. Medica 10: 227-38.
Jones, Lovell A., ed. 1989. Minorities and cancer. New Satariano, W. A., and M. Swanson. 1988. Racial differ-
York. ences in cancer incidence: The significance of age-
Luinsky, William. 1989. Environmental cancer risks — specific patterns. Cancer 62: 2640-53.
real and unreal. Environmental Research 50: 207-9. Silverberg, E., C. C. Boring, and T. S. Squires. 1990. Can-
McGrew, Roderick E. 1985. Encyclopedia of medical his- cer statistics, 1990. California Cancer Journal for Cli-
tory. New York. nicians 40: 9-25.
Miller, D. G. 1980. On the nature of susceptibility to can- Swanson, G. M. 1988. Cancer prevention in the workplace
cer. Cancer 46: 1307-18. and natural environment. Cancer 62: 1725-46.
Mills, P. K. et al. 1989. Cohort study of diet, lifestyle, and Whittemore, A. S., and A. McMillan. 1983. Lung cancer
prostate cancer in Adventist men. Cancer 63:598-604. mortality among U.S. uranium miners: A reappraisal.
Muir, C. S. 1990. Epidemiology, basic science, and the Journal of the National Cancer Institute 71: 489-505.
prevention of cancer: Implications for the future. Can- Willett, W. 1989. The search for the causes of breast and
cer Research 50:6441—8. colon cancer. Nature 338: 389-94.
Natarajan, N., G. P. Murphy, and C. Mettlin. 1989. Pros- Willett, W., et al. 1990. Relation of meat, fat, and fiber
tate cancer in blacks: An update from the American intake to the risk of colon cancer in a prospective
College of Surgeons' patterns of care studies. Journal study among women. New England Journal of Medi-
of Surgical Oncology 40: 232-6. cine 323: 1644-72.
Parkin, D. M., E. Laara, and C. S. Muir. 1988. Estimates of Wolff, Jacob. 1907. The science of cancerous disease from
the worldwide frequency of sixteen major cancers in earliest times to the present, trans. Barbara Ayoub,
1980. International Journal of Cancer 41: 184-97. 1989. Canton, Mass.
Patterson, James T. 1987. The dread disease: Cancer and United States General Accounting Office. 1987. Cancer
modern American culture. Cambridge, Mass. patient survival: What progress has been made? Wash-
Preston-Martin, S., et al. 1990. Increased cell division as a ington, D.C.
cause of human cancer. Cancer Research 50: 7415-21. Zarizde, S., and P. Boyle. 1987. Cancer of the prostate:
Rather, L. J. 1978. The genesis of cancer: A study in the Epidemiology and aetiology. British Journal of Urol-
history of ideas. Baltimore. ogy 59: 493-502.

PART III
Medical Specialties and Disease

Prevention

m.l. Genetic Disease 113
Some Operational Definitions
m.i More often than not, when the term hereditary is
applied to a particular trait, the natural inclination is
Genetic Disease to equate it with the term genetic. However, heredi-
tary refers only to the sustained passage of a trait
from generation to generation. Surnames, property,
and titles may be hereditary by law or custom, but
The idea that a particular physical feature, either they are not genetic. We may regard a hereditary
normal or abnormal, is hereditary is probably as trait as genetic only when the passage of that trait
old as our species itself. However, as has been noted from generation to generation is determined, at least
by many other writers, tracing the origins of an in part, by one or more genes. In much the same way,
idea is a formidable, if not impossible, task. Clearly, the term congenital has often been equated with ge-
the concept of "like begets like" found a practical netic when, in fact, this term signifies only that a trait
expression in the early domestication of animals; is present at birth. A congenital trait is not necessar-
breeding stock was chosen on the basis of favorable ily genetic or even hereditary. Thus, the purview of
traits. The first tangible evidence that human be- medical genetics may be said to include those traits,
ings had at least a glimmer of the notion of hered- both congenital and of delayed onset, whose origins
ity can be found in the domestication of the dog lie in defects in single genes, in groups of genes, or in
some 10,000 years ago. Yet it is only in the past 100 the size or number of the chromosomes.
years that we have begun to understand the work- A useful checklist for assessing whether a trait is
ings of heredity. genetically determined was provided by J. V. Neel
This essay traces the development of the concept and W. J. Schull (1954). A trait is genetically deter-
of heredity and, in particular, shows how that devel- mined by the following:
opment has shed light on the host of hereditary and 1. It occurs in definite proportions among persons
genetic diseases we have come to recognize in hu- related by descent, when environmental causes
mans. It begins with a brief discussion of some basic have been ruled out.
concepts and terms, which is followed by an outline 2. It fails to appear in unrelated lines such as those
of the heuristic model of genetic transmission that of in-laws.
has come to be the standard of modern medical genet- 3. It displays a characteristic age of onset and course
ics. Once this groundwork is in place, the history of of development, in the absence of other known
the study of human genetic disease is developed causes.
from the earliest records, through the birth of medi- 4. It shows greater concordance in monozygous (iden-
cal genetics, to the molecular era. Naturally, a de- tical) twins than in dizygous (fraternal) twins.
tailed narrative of this history would require several
volumes. Therefore, some events and ideas have When the role of chromosomal anomalies became
been omitted or treated only cursorily. fully appreciated in the 1960s, a fifth item was
The most recent development in the study of hu- added to the checklist:
man genetic diseases is traced through three specific 5. It consists of a characteristic suite of features
examples. Each of these represents a microcosm of (syndrome) coupled with a clearly demonstrated
the development of medical genetics. Our under- chromosomal abnormality (Thompson and Thomp-
standing of the first of them, sickle cell anemia, son 1980).
represents a triumph of the molecular model of hu-
man disease. The discovery of the second, Down syn- In the present era of molecular biology and recom-
drome, reveals the role in medical genetics of the binant DNA technology we must add yet another
cytogeneticist, who studies chromosomes. The third, item to the list:
kuru, exemplifies a case in which the expectations of 6. It is linked to a specific DNA sequence (probe)
modern medical genetics led initially to an errone- that has been mapped to a particular region of a
ous conclusion, although that failure led eventually chromosome.
to spectacular new knowledge. This essay closes
with a brief assessment of the future development of Throughout the following discussions, traits that
medical genetics in the molecular era. are regarded as genetic but not chromosomal, hav-
ing met criteria 1 through 4 and 6 but not 5, are
accompanied by a reference number. This number is

114 III. Medical Specialties and Disease Prevention
the entry number of a given disorder in the catalog Morton 1982). Second, it has become a heuristic de-
complied by V. A. McKusick (1986) of more than vice through which clinical variation in the presenta-
3,000 Mendelian phenotypes in human beings. For tion of a disease can be assessed. After spending
example, the entry number for sickle cell anemia is more than half a century studying the inheritance of
14190. An excellent reference for chromosomal condi- complex traits, Sewall Wright (1968) concluded that
tions is E. Thurman (1986). there is a network of effects leading from the gene to
the final outward manifestation, the phenotype, and
Models of Genetic Transmission that a number of basic generalizations can be made:
In recent years, medical geneticists have been sup-
plied with a battery of sophisticated analytic tools to 1. The variations of most characters are affected by a
great many loci (the multiple-factor hypothesis).
be used in conjunction with advanced laboratory
techniques for determining the transmission of vari- 2. In general, each gene replacement has effects
ous traits. These analytic methods have been de- on many characters (the principle of universal
rived from what is now called the multifactorial (or pleiotropy).
mixed) model (see Morton 1982). According to this 3. Each of the innumerable alleles at any locus has a
model the observed variation in a trait, such as the unique array of differential effects in taking ac-
clinical presentation of a genetic disease or the liabil- count of pleiotropy (uniqueness of alleles).
ity to develop a complex disorder like heart disease, 4. The dominance relation of two alleles is not an
is determined by the joint effects of major gene loci attribute of the alleles but of the whole genome
and a background composed of multiple minor loci (a and the environment. Dominance may differ for
polygenic effect) and a nongenetic component (an each pleiotropic effect and is in general easily
environmental effect). A graphic representation of modified (relativity of dominance).
the multifactorial model is shown in Figure III. 1.1. 5. The effects of multiple loci on a character in gen-
The most important difference between this model eral involve much nonadditive interaction (uni-
and earlier ones is that the nongenetic component is versality of interaction effects).
regarded as transmissible, as are genetic effects. 6. Both ontogenetic homology and phylogenetic
homology depend on calling into play similar
The impact of this model has been twofold. First, it
chains of gene-controlled reactions under similar
has provided a theoretical underpinning for the field
developmental conditions (homology).
of genetic epidemiology (Morton and Chung 1978;
7. The contributions of measurable characters to
overall selective value usually involve interaction
effects of the most extreme sort because of the
2q(l-q)
usually intermediate position of the optimum
(l-q2)
grade, a situation that implies the existence of
innumerable selective peaks (multiple selective
peaks).
From this perspective one must say that no gene
responsible for a human genetic disease exists in a
developmental vacuum. It exists in a milieu com-
Figure III. 1.1. Mixed model of liability for complex hu- posed of its own locus, its chromosomal position and
man disease. The abscissa reflects an arbitrary liability close neighbors, the various effects of other genes
scale in which the left-most point is low risk and the elsewhere in the genome, the inter- and intracellu-
right-most is high risk. Z is a threshold beyond which lar environment, and the external environment,
(shaded area) individuals will develop the disease in ques- both intra- and extrauterine, in which it ultimately
tion. The effects of a single major locus are indicated by finds expression. However, the mechanisms by
the frequency distributions of the alleles: AA = (1 — q2), which this multitude of effects operates are only just
Aa = 2q (1 - q), and aa = q2, where a is taken to be the being discovered. This phase of the history of genetic
disease gene. The presence of AA and Aa individuals be-
yond Z indicates the further effects of the multifactorial
disease has yet to be written.
background, including nongenetic effects. The value u is
the mean population liability, t the deviation in mean History of the Study of Genetic Disease:
genotype-specific liability, and d the degree of dominance From the Greeks to Garrod
at the locus. (From Comings et al. 1984, with permission As already stated, the idea that the features of par-
from the American Journal of Human Genetics.) ents could be transmitted to their offspring was ap-

III.l. Genetic Disease 115
plied very early in human history in the domestica- cussing heredity were usually abstract qualities
tion of animals. Some of the knowledge of "good such as good and evil or desirable normal character-
inheritance," the transmission of favorable features, istics such as eye color, strength, speed, and beauty.
undoubtedly came from observations of "bad inheri- Of course, they also took notice of the shocking and
tance." Thus, for some 10,000 years we have been fantastic, gross malformations, or severe illness. Em-
aware to a greater or lesser degree that certain mal- pedocles suggested in the fifth century B.C. that the
formations and diseases are hereditary, if not ge- cause of monsters, as grossly malformed infants
netic. However, only from the written records of an- came to be called, was an excess or deficit of semen.
cestors can we reliably assess the state of their Many other writers held similar views, which pre-
awareness regarding heredity. sumably became part of the hereditary theory of
Hippocrates. The treatment of infants with abnor-
Early History malities was roughly the same everywhere in the
By the time of the Greeks, ample evidence already ancient world. They either were left to die or were
existed that people were cognizant of heredity, both killed outright. Often, the mother suffered the same
good and bad. Moreover, many Greek scholars specu- fate as her offspring. The practice of destroying ab-
lated as to the mechanism of heredity. Nearly all of normal infants was advocated by Hippocrates, Plato,
them had a theory of vertical transmission, but the Aristotle, and virtually all others whose works on
theory promoted by Hippocrates survived until the the subject have survived. Yet the practice was not
Renaissance. Writing in the fourth century B.C., universal, as evidenced by the mummy of an
Hippocrates put forth the idea that each organ and anencephalic (20650) infant at Hermopolis. The ar-
tissue produced, in its turn, a specific component of chaeological evidence suggests that this baby, who
semen. This composite semen was then transmitted would have been stillborn or died shortly after birth,
to the woman through coitus, whereupon it incu- was an object of worship (Glenister 1964).
bated to become a human baby. This, of course, in- The physical, mechanistic interpretation of the
cluded the good and the bad: causes of birth defects was modified by the some-
what more mystical Roman frame of mind. In the
. . . of the semen, however, I assert that it is secreted by
the whole body - by the solid as well as by the smooth
first century A.D., Pliny the Elder wrote that mental
parts, and by the entire humid matters of the body. .. . The impressions resulting from gazing on likenesses of
semen is produced by the whole body, healthy by healthy the gods during pregnancy were sufficient to pro-
parts, sick by sick parts. Hence when as a rule, baldheaded duce monsters. Indeed, the root of the word monster
beget baldheaded, blue-eyed beget blue-eyed, and squint- is the Latin word monere, "to warn." Thus, such
ing, squinting; and when for other maladies, the same law children were regarded as warnings from the gods
prevails, what should hinder that longheaded are begotten transmitted to pregnant women. J. W. Ballantyne
by longheaded. (Hippocrates in Vogel and Motulsky 1979) (1902) related the circumstances of a black queen of
ancient Ethiopia who presented her husband, the
Note that in this single passage Hippocrates ac- black king, with a white child. It was concluded that
counts for the inheritance not only of desirable traits the queen had gazed on a white statue of the goddess
but of the abnormal and undesirable as well, and by Andromeda during the early stages of her preg-
the same mechanism. So powerful was the idea of nancy. The description of the white infant, however,
heredity among the Greeks that many scholars felt leads one to suspect that it was an albino (20310),
the need to warn against unfavorable unions. Thus particularly given the propensity for royalty to
did the sixth-century B.C. scholar Theognis lament: marry close relatives.
We seek well bred rams and sheep and horses and one The decline of reason that marked the Middle
wishes to breed from these. Yet a good man is willing to Ages was reflected in interpretations of the birth of
marry an evil wife, if she bring him wealth: nor does a malformed infants. T. W. Glenister (1964) notes that
woman refuse to marry an evil husband who is rich. For such children were called "Devil's brats" and were
men reverence money, and the good marry the evil, and
generally believed to have been conceived in a union
the evil the good. Wealth has confounded the race.
(Theognis in Roper 1913)
with Satan. As was the case with any perceived
deviation from piety, the fate of both infant and
Clearly, Theognis believed that marriage for the mother was quickly and ruthlessly determined. Late
sake of money would cause the race to sink into in the Middle Ages, however, the rise of astrology
mediocrity and greed. sometimes made for surprising outcomes. For exam-
The traits commented on by the Greeks when dis- ple, when in the beginning of the thirteenth century

a deformed calf said to be half human in its appear- not to set them aside with ideal thoughts and idle
ance was born, the cowherd was immediately ac- words about 'curiosities' or 'chances.' Not one of
cused of having committed an unnatural act, the them is without meaning; not one that might not
punishment for which was burning at the stake become the beginning of excellent knowledge." He
(Glenister 1964). Fortunately for the cowherd it was went on to speak of new diseases that "are due
pointed out that a particular conjunction of the plan- mainly to morbid conditions changing and combin-
ets had recently occurred, a conjunction that was ing in transmission from parents to offspring."
often the cause of oddities of nature. The cowherd's The debt owed to scholars such as Harvey was
life was spared. acknowledged in the twentieth century, when medi-
As the Renaissance dawned, reason returned to cal genetics was coming into full bloom. Archibald
the writing of discourses on heredity and failed he- Garrod, the father of human biochemical genetics, of
redity. Scholarly works of the classical era were re- whom we will hear more, paid homage to his intellec-
discovered, and the development of a science of he- tual ancestor: "It is rather, as Harvey saw so clearly,
redity was once again underway. A curious episode because we find in rare diseases the keys to note a
occurred a few years after the death of Leonardo da few dark places of physiology and pathology, that I
Vinci in 1519. A half-brother of Leonardo conducted recommend them to you as objects of study" (Garrod
an experiment in an attempt to produce a second 1928).
Leonardo. The half-brother, Bartolommeo, who was
45 years younger than the great artist and scholar,
tried to recreate the exact circumstances of Leo- The Forgotten Origins of Medical Genetics
nardo's birth. Leonardo was the illegitimate son of With the Enlightenment the floodgates to inquiry
Fiero, a notary of Vinci, and a peasant girl of the were opened for medical scientists and progress was
same city named Caterina. Bartolommeo, a notary made on nearly all fronts in understanding pathol-
by trade, moved to Vinci, whereupon he sought out a ogy. However, in spite of eloquent writings on hered-
peasant girl much like Caterina. He found one and ity in general and on rare cases in particular, few
married her, and she bore him a son, whom they references to specific genetic diseases were made
named Piero. One author notes the following: before the twentieth century. Yet among those few
instances are to be found brilliant insights.
Bartolommeo had scarcely known his brother whose spiri- Between 1745 and 1757 the French natural phi-
tual heir he had wanted thus to produce and, by all ac- losopher Pierre Louis Moreau de Maupertuis con-
counts, he almost did. The boy looked liked Leonardo, and
was brought up with all the encouragement to follow his
ducted studies on the heredity of polydactyly (the
footsteps. Pierino da Vinci, this experiment in heredity, condition of having more than the normal number of
became an artist and, especially, a sculptor of some talent. fingers and/or toes; 26345). Maupertuis published a
He died young. (Ritchie-Calder in Plomin et al. 1980) four-generation pedigree of polydactyly and com-
mented, "That peculiarity of the supernumerary dig-
As the foregoing passage indicates, the Rennaisance its is found in the human species, extends to the
saw a revival of the principles of heredity. The writ- entire breeds [races]; and there one sees that it is
ings of Hippocrates and Aristotle were translated equally transmitted by the fathers and by the moth-
and amplified by medical scholars such as Fabricius ers" (Glass 1947).
ab Aquapendente and his pupil William Harvey. In He based his theory of heredity on these studies
addition, there was a growing interest in rare and and suggested that particles of inheritance were
unusual medical cases. Weeks before his death in paired in the "semens" of the father and the mother
1657, William Harvey wrote a letter of reply to a and that "there could be . . . arrangements so tena-
Dutch physician's inquiry about an unusual case in cious that from the first generation they dominate"
which he counseled, "Nature is nowhere accustomed (Glass 1947). This led him to suggest that hereditary
more openly to display her secret mysteries than in pathologies were accidental products of the semen.
cases where she shows traces of her workings apart In other words, he correctly predicted genes, domi-
from the beaten path" (in Garrod 1928). nance, and mutation. In addition, he estimated the
For Harvey and others, rare pathology was not a probability of polydactyly at 1 per 20,000 by his own
source of revulsion or the workings of Satan but, survey and noted that the chance of a joint occur-
rather, a subject demanding study and understand- rence of an affected parent and an affected offspring
ing. In 1882, Sir James Paget made a similar appeal was 1 per 400,000,000 and that of an affected grand-
on behalf of the study of rare disorders: "We ought parent, parent, and offspring in sequence was 1 per

8,000,000,000,000 if the disorder was not hereditary. disease originated. Finally, he called for the estab-
This made the probability of his four-generation fam- lishment of hereditary disease registers that could
ily being chance so small as to be immediately dis- be used for the study of these diseases: "That to
missed. Here, then, was also the first use of statistics lessen anxiety, as well as from a regard to the moral
in a study of heredity. principle, family peculiarities, instead of being care-
Various sex-linked, or X-linked, disorders such as fully concealed, should be accurately traced and
color blindness (30370) and hemophilia (30670) were faithfully recorded" (Adams 1814, in Motulsky
accurately described in the late eighteenth and early 1959).
nineteenth centuries. A German physician and pro-
fessor of medicine, Christian F. Nasse, presented in The Impact of Mendelism
1820 a detailed pedigree of X-linked, recessive hemo- The story of the discovery of the basic hereditary
philia and noted: laws of segregation and independent assortment by
the Austrian monk Mendel and of their subsequent
All reports on families, in which a hereditary tendency independent rediscovery by Carl Correns, Hugo de
toward bleeding was found, are in agreement that bleed- Vries, and Erich von Tschermak some 35 years later
ers are persons of male sex only in every case... . The has been told many times (e.g., Olby 1966; Stern and
women from those families transmit this tendency from
their fathers to their children, even when they are mar-
Sherwood 1966). Mendel, conducting experiments in
ried to husbands from other families who are not afflicted
hybridization with the common garden pea, Pisum
with this tendency. This tendency never manifests itself in sativum, in his garden at the Augustinian monas-
women. (Vogel and Motulsky 1979) tery in Brno, Czechoslovakia, demonstrated that al-
ternative hereditary "characters" for a single trait
Perhaps the most remarkable instance before the segregated from one another each generation and
work of Gregor Johann Mendel (which although pub- that the characters for multiple traits assorted inde-
lished in 1866 had to await rediscovery until the pendently in each generation. Moreover, the ob-
beginning of the twentieth century) was an 1814 served distribution of characters for multiple traits
publication by British physician Joseph Adams followed a precise mathematical formulation - a bi-
(Motulsky 1959). In this study, the author drew a nomial series. Mendel reported his results to the
distinction between familial diseases, which he con- Natural Science Association of Brno in 1865. His
sidered to be confined to a single generation, and written report was published the following year, but
hereditary diseases, which he noted were passed on almost no attention was paid to it until 1899.
from generation to generation. Moreover, Adams de- By that time, however, numerous investigators
fined congenital disorders as ones appearing at birth were pursuing experiments in heredity, and many of
and regarded them to be more likely familial than them had chosen simple plants as their experimen-
hereditary. He observed that familial inherited distal systems. Professor Hugo de Vries, a Dutch bota-
eases were often very severe, so much so that subse- nist, studying hybridization, came upon a reprint of
quent transmission from the affected individual was Mendel's report, where he found the solution to the
ruled out by early death. These conditions increased problems he had been working on. Thus, while he
among the offspring because of mating between had independently derived his own formulation of
close relatives and were often to be seen in isolated the law of segregation, he reported the Mendelian
districts where inbreeding was common. Clearly, results as well and stressed their importance in a
from a modern perspective, Adams's familial dis- 1900 publication (Olby 1966). At the same time,
eases were what we term recessive and his heredi- both the German botanist Correns and the Austrian
tary diseases were what we term dominant. botanist von Tschermak independently discovered
Adams also concluded that hereditary diseases (in the Mendelian laws and recognized their signifi-
the modern sense) were not always to be found at cance. All three published translations of Mendel's
birth but might have later ages of onset, that correla- paper and commented on the laws therein. That
tions existed among family members with regard to these papers opened the newfieldof genetics and put
the clinical features of a hereditary disease, and that it on a sound analytic footing from the outset is
hereditary diseases might be treatable. Adams undeniable. However, as we will see, the translation
hinted at the phenomenon of mutation when he re- by de Vries had an almost immediate impact on the
marked that a severe disease would last only a sin- study of human genetic disease.
gle generation were it not for the fact that normal The English biologist William Bateson was also
parents occasionally produced offspring in whom the interested in plant hybridization. However, his inter-

est stemmed from the fact that, as an ardent advo- Adams, who, it should be remembered, had made a
cate of evolution, he was unable to reconcile his similar observation about inbreeding nearly 90
belief that hereditary variation was discontinuous years earlier. William Bateson read the paper and
with the Darwinian model of evolution through selec- discussed its conclusions with Garrod. Bateson recog-
tion on continuous variation. Bateson thus had nized that the pathology was discontinuous, all or
spent years searching for a mechanism for discontin- none, affected or normal. Moreover, the high inci-
uous traits (Carlson 1966). Then in 1900 he read de dence of consanguinity and the characteristic famil-
Vries's account of Mendel's experiments. As E. A. ial pattern of normal, consanguinous parents having
Carlson (1966) notes, Bateson called the moment affected offspring were precisely what would be ex-
when he recognized the importance of Mendel's work pected were the abnormality determined by a rare,
"one of the half dozen most emotional moments of recessive Mendelian character. Bateson commented
his life." In Mendel's work, Bateson believed he had on the case in a footnote in a 1902 report to the
found the mechanism for discontinuous variation for Evolution Committee of the Royal Society with E. R.
which he had searched. Shortly after this time, Bate- Saunders:
son mistakenly championed Mendelism as an alter-
native to Darwinism, a position that haunted him Now there may be other accounts possible, but we note
the rest of his life (Sturtevant 1966). In 1901, how- that the mating of first cousins gives exactly the condi-
tions most likely to enable a rare and usually unseen
ever, Bateson, as we shall see, made an almost off- recessive character to show itself. .. first cousins will
hand comment that turned out to be a fundamental frequently be bearers of similar gametes, which may in
contribution to the study of human genetic diseases. such unions meet each other, and thus lead to the mani-
In 1897 Sir Archibald E. Garrod, a member of the festation of the peculiar recessive characters in the
staff of London's St. Bartholemew's Hospital, came zygote.
upon and was intrigued by a case of alkaptonuria
In Bateson's interpretation of the situation, Gar-
(20350). Alkaptonuria is a nonfatal disorder, present
rod saw the solution to the problem of alkaptonuria.
at birth, that is characterized by the excretion of
Garrod published the landmark paper "The Inci-
homogentisic acid in the urine, which turns the
dence of Alkaptonuria: A Study in Chemical Indi-
urine dark upon standing. The disorder is often ac-
viduality" in 1902, adding further clinical data and
companied in later years by arthritis and a black
incorporating the hereditary mechanism proposed
pigmentation of cartilage and collagenous tissues.
by Bateson. Therein he reported on nine families of
At the time that Garrod was diagnosing his first
alkaptonuries and noted:
case of alkaptonuria it was believed that the condi-
tion was infectious and that the excretion of It will be noticed that among the families of parents who
homogentisic acid was the result of bacterial action do not themselves exhibit the anomaly a proportion corre-
in the intestine. Garrod, however, refused to accept sponding to 60 per cent are the offspring of marriages of
this view, believing instead that the condition was a first cousins.
form of abnormal metabolism (Harris 1963). He pub- However, he continued:
lished this theory in 1899 along with the contention
that the error of metabolism was congenital (Garrod There is no reason to suppose that mere consanguinity of
1899. parents can originate such a condition as alkaptonuria in
their offspring, and we must, rather seek an explanation
Less than a year later Garrod made what would
in some peculiarity of the parents, which may remain
prove to be his crucial observation. He noted that, latent for generations, but which has the best chance of
among four families in which all alkaptonuric off- asserting itself in the offspring of the union of two mem-
spring had two unaffected parents, three of the pa- bers of a family in which it is transmitted.
rental pairs were first cousins. In 1901 he wrote in
the Lancet: Garrod (1902) suggested that the laws of heredity
discovered by Mendel and relayed to him by Bateson
The children of first cousins form so small a section of the offered an explanation of the disorder as an example
community, and the number of alkaptonuric persons is so of a Mendelian recessive character and, thus,
very small, that the association in no less than three out of
four families can hardly be ascribed to chance, and further there seems to be little room for doubt that the peculiari-
evidence bearing upon this point would be of great interest. ties of the incidence of alkaptonuria and of conditions
which appear in a similar way are best explained by sup-
This circumstance would hardly have surprised posing that... a peculiarity of the gametes of both par-
Garrod's fellow countryman and physician Joseph ents is necessary.

3,4-DIHYDROPHENYLALANINE
Here Garrod had already gone beyond alkapton- MELANIN
uria to include the possibility of other disorders shar-

ing the same hereditary mechanism. Indeed, Garrod
did go on to study cystinuria (22010), albinism
DIETARY PROTEIN 4 TYROSINE-3-HYDROXYLASE
/ (A)
(A) \ / TYROSINE
TYI PEROXIDASE
(20310), and pentosuria (26080) and to put them all PHENYLALANINE ••TYROSINE 1 **THYROXINE
in the same class with alkaptonuria. PHENYLALANINE-4-HYDROXYIASE (0)
In 1908 Garrod delivered the Croonian Lectures to
T
(8) TYROSINE
TRANSAMINASE
the Royal College of Physicians. To these lectures,
and to the four disorders on which they were based, 4-HYDROXYPHENYLPYRUVIC ACID
Garrod gave the name "Inborn Errors of Metabo-
lism." The impact of Mendelism was fully felt by
then, and there were few who doubted that these and
other diseases were due to Mendelian characters.
t 4-HYDROXYPHENYLPYRUVIC
HOMOGENTISIC ACID
ACID HYOROXYLASE
Garrod then went on to the next stage of the study of

HOMOGENTISIC ACID
inborn errors, by noting in the case of alkaptonuria (C)
T
OXYGENASE
that
4-MALEYLACETOACETIC ACID
we may further conceive that the splitting of the benzene MAIEYLACETOACETIC ACID
ring in normal metabolism is the work of a special en-
zyme, that in congenital alkaptonuria this enzyme is want- T
FUMARYLACETOACETIC ACID
ISOMERASE
ing, whilst in disease its working may be partially or even

completely inhibited. Figure III. 1.2. A representation of metabolic pathways
involving the amino acid tyrosine. These pathways are
He was suggesting that the pathology of inborn er- linked to no fewer than six genetic diseases of the type
rors of metabolism consisted of a blockade at some envisioned by Garrod. (A) A defect in the gene coding
point in the normal pathway and that this blockade for phenylalanine-4-hydroxylase results in the recessive
was caused by the congenital deficiency or absence disorder phenylketonuria (26160). (B) A defect in the
of a specific enzyme (Harris 1963). The truth of his gene coding for tyrosine transaminase results in the
insight is evidenced by the metabolic pathways rare disease tyrosinosis (27680), whereas a defect at the
next step involving 4-hydroxyphenylpyruvic acid
shown in Figure III.1.2. Clearly, Garrod believed
hydroxylase leads to the much more serious disorder ty-
that these deficiencies were transmitted as Mende- rosinemia (27660). (C) The metabolic lesion suggested by
lian characters, or determinants, and that the study Garrod for alkaptonuria is in fact a defect in the gene
of the families, particularly those in which inbreed- coding for homogentisic acid oxygenase. (D) A form of
ing was known or suspected, was crucial to obtain- goitrous cretinism (27470) is caused when there is a le-
ing new insights into old disease entities. sion involving the enzyme tyrosine peroxidase. (E) An-
The principal tenet of inborn errors of metabolism, other of Garrod's original defects, albinism, arises when
that transmitted enzymic defects cause disease, even- the gene for tyrosine-3-hydroxylase is defective. To date,
tually led to the "one gene-one enzyme" hypothesis more than 500 such disorders are known to exist in hu-
(Beadle 1945) and to the theory of gene action. In mans. Some are vanishingly rare, but others, such as
1950 G. W. Beadle called Garrod the "father of chemi- phenylketonuria, are quite common (From McKusick
1986).
cal genetics" (Harris 1963).
The Modern Era of Medical Genetics: the time Garrod was writing for most geneticists to
Three Examples of "Excellent Knowledge" reduce Mendel's laws to purely chemical phenom-
From our contemporary perspective, the work and ena. Indeed, in the earliest days of the rediscovery of
insights of Garrod are landmarks. There can be no Mendel much of the effort being expended in formal
doubt that the incorporation of the Mendelian laws genetics was devoted to coming to terms with a grow-
of heredity into the study of human diseases was the ing list of exceptions to those laws (Carlson 1966).
turning point in the history of medical genetics. Sur- This is not to say that medical genetics had been
prisingly, however, Garrod's theories and sugges- put on hold until the middle of the twentieth cen-
tions went largely unnoticed for several decades. tury. In fact, progress in understanding the heredi-
One reason for this slow recognition, according to H. tary nature of numerous human diseases was being
Harris (1963), was that it was quite impossible at made, but it did not truly come together until the

middle of this century. Two disorders that contrib- showed traces of the sickling trait and three of the
uted greatly to this progress were sickle-cell anemia patient's siblings had died at an early age of severe
and Down syndrome. anemia, Emmel made no reference to a possible he-
reditary component in the disorder. The first such
The Triumph of the Molecular Model: Sickle- suggestion was offered six years later by J. G. Huck
Cell Anemia (1923). In addition to reporting the first large clini-
G. J. Brewer (1985) has commented that sickle cell cal sample, 17 patients, Huck displayed the pedi-
anemia (14190) is one of the most fascinating dis- grees of two sickle-cell families. In one of these fami-
eases in medicine. And this one disease may be cred- lies, both parents were affected but had produced one
ited with having ushered in the era of molecular normal offspring in addition to two affected off-
medicine. spring. The significance of these families was noted:
The first case of sickle-cell anemia was reported in "Apparently the 'sickle cell' condition in man is in-
1910 by a Chicago physician, J. B. Herrick. Upon his herited according to the Mendelian law for the in-
examination of a young black man from Grenada, heritance of a single factor." Moreover, "one interest-
West Indies, he found, among other features, "a sec- ing feature of this inheritance is the fact that the
ondary anemia not remarkable for the great reduc- sickle cell condition is dominant over the normal
tion in red corpuscles or hemoglobin, but strikingly condition" (Huck 1923). Over the course of 13 years,
atypical in the large number of nucleated red corpus- reports of a unique pathological finding had led to
cles of the normoblastic type and in the tendency of the recognition of a hereditary disease - sickle-cell
the erythrocytes to assume a slender sickle-like anemia.
shape" (Herrick 1910). Herrick had never before en- After this good start, the study of sickle-cell ane-
countered a similar abnormality and reported: mia slowed dramatically - partly because most in-
vestigators failed to recognize a fundamental differ-
Whether the blood picture represents merely a freakish ence between sickle-cell anemia and the nonanemic
poikilocytosis or is dependent on some peculiar physical or sickle-cell trait. Most believed that the latter was
chemical condition of the blood, or is characteristic of some merely the dormant stage of the former. In 1933 L.
particular disease, I cannot at present answer. I report W. Diggs and his colleagues suggested that this inter-
some details that may seem non-essential, thinking that if
a similar blood condition is found in some other case a
pretation was incorrect. They showed that the per-
comparison of clinical conditions may help in solving the centages of hemoglobin determinations among black
problem. (Herrick 1910) schoolchildren with the sickle-cell trait were not dif-
ferent from those of controls. In addition, no signifi-
Soon after, a similar case was reported, and within cant pathology appeared to be associated with the
a very few years, the first fully scientific investiga- sickle-cell trait. Clearly this meant that "the impor-
tion of the sickling phenomenon was described. That tance of the sickle cell trait appears to be limited to
study, published in 1917 by V. E. Emmel, was based the relatively small grooup who in addition to the
on the case of a young black woman in St. Louis. The trait have sickle cell anemia" (Diggs et al. 1933).
patient had an ulceration on her leg and severe As the distinction between the trait and the ane-
anemia, and "instead of the typical rounded disk mia became fully accepted, the pace of research on
form, about one-third of the corpuscles are greatly sickle-cell anemia quickened, and in 1949 two mile-
elongated in shape. A large percentage of the latter stones were reached almost simultaneously. First,
have a rounded, rod-like shape with more or less two investigators independently discovered the cor-
tapered ends, and as a rule present a curved or rect mechanism of inheritance of the trait and the ane-
crescentic form" (Emmel 1917). Emmel was the first mia. One of these, a medical officer serving in what
to show that the sickling of the red cells was develop- was then Rhodesia, compiled several large Bantu
mental, with seemingly normal, enucleate red cells pedigrees of the sickle-cell trait. In one he observed
undergoing the sickling change as they matured. He two affected parents having a child with sickle-cell
further showed that none of the red cells from con- anemia. From his studies he concluded that the
trols or from any other type of anemia or leukemia sickle-cell trait appears as a heterozygote with the
could be induced to sickle. However, Emmel did find normal allele, whereas sickle-cell anemia is the homo-
that a small proportion of the red cells from the zygous state of the sickle-cell gene, meaning that it
patient's father, who was not anemic, did undergo must be inherited from both parents (Beet 1949).
sickling in cell culture conditions. Second, J. V. Neel (1949) reported precisely the
Curiously, even though the father of the patient same conclusion based on a more statistical analy-

sis. These findings led to the recognition that the
vast majority of dominant genetic diseases are
heterozygous. The first report on the implications of
an altered molecule in the pathogenesis of a human
disease should probably be credited to M. Hoerlin
and G. Weber, a German physician and a medical
student, respectively, who wrote in 1947 that the
condition known as methemoglobinemia (14170)
was due to a "variant of the globin component of the
hemoglobin molecule" (Heller 1969). However, the
report that is celebrated is that of L. Pauling and
colleagues (1949). Through a set of meticulous ex-
periments they were able to show that the hemoglo-
bin molecules in individuals with sickle-cell anemia
and those in normal controls were fundamentally
different but, "having found that the electrophoretic
mobilities of sickle-cell hemoglobin and normal
hemoglobin differ, we are left with the considerable
problem of locating the cause of the difference" (Pau-
ling et al. 1949).
They predicted that the abnormality would be
found in the globin part of the molecule and not in
the heme groups, that the sickling process involved
abnormal interactions of altered molecules, and that
the alteration resulted in two to four more net posi-
tive charges per molecule. Their predictions, we
know, were all correct, as was shown by V. M. Ingram
Normal hemoglobin
in 1956. Denatured sickle-cell hemoglobin (HbS), di-
gested with trypsin, was compared with normal Figure III.1.3. The original two-dimensional chromato-
hemoglobin (HbA) after sequential electrophoresis graphic spreads of normal and sickle-cell hemoglobins.
and partition chromatography (Figure III.1.3). The The different "spot" having a net positive charge is seen
abnormal HbS differed in only one "spot" on the to have moved further left in the electrophoretic field,
filter, which had a net positive charge. Within three toward the negative pole. The alteration in the pattern
years it was demonstrated that the charge was represents the substitution of the amino acid valine for
caused by the alteration of a single amino acid glutamic acid. (From Ingram 19J)6, with permission;
through a mutation (Ingram 1959). copyright 1956 by Macmillan Journals Limited.)
Since the moment the puzzle of sickle-cell anemia
was solved, the study of mutant globins and their
associated disorders has signaled nearly every major diagnosis of genetic diseases was pioneered with
advance in molecular biology. In 1978 R. M. Lawn HbS by Kan and Dozy (1978) and is now being ap-
and colleagues and Y. W. Kan and A. M. Dozy inde- plied to a wide range of disorders, including cancer
pendently demonstrated the first human restriction and acquired infectious diseases (Caskey 1987).
fragment length polymorphisms (RFLPs) in the re-
gion of the beta-chain of the hemoglobin molecule. The Arrival of Cytogenetics: Down Syndrome
This led to the explosion of recombinant-DNA-based The chromosome theory of heredity, that the Mende-
studies on human genetic diseases as well as human lian characters were contained in the chromosomes,
gene mapping (Willard et al. 1985). The discovery of developed soon after the rediscovery of Mendel's
highly repetitive DNA sequences in globin genes laws and was in large measure a direct result of the
has resulted in the development of the hypervari- precision of Mendel's own experimental observa-
able "minisatellite" and VNTR (variable number of tions. W. S. Sutton had observed a very high degree
tandem repeat) DNA probes (Jeffreys et al. 1985, of organization of the chromosomes of the orthop-
1986; Nakamura et al. 1987). In addition, the use of teran genus Brachystola. He concluded that the par-
other recombinant DNA techniques in the molecular allels between the organization and behavior of the

chromosomes and the laws of segregation and inde- able with it. For the next 92 years repeated studies
pendent assortment could not be due to chance: "We of Down syndrome failed to produce a viable etio-
have reason to believe that there is a definite rela- logic hypothesis. L. S. Penrose (1939) summarized
tion between chromosomes and allelomorphs or unit the state of knowledge by noting that the disorder
characters" (Peters 1959). Sutton proposed that mul- had failed to meet Mendelian expectations, though
tiple characters would be found on a single chromosome had favored "irregular dominance" as an expla-
some and made a direct reference to genetic linkage: nation, and that the only clear and stable correlate
"If then, the chromosomes permanently retain their was late maternal age. Penrose (1939) ended his
individuality, it follows that all allelomorphs repre- paper by suggesting that "Mongolism and some
sented by any one chromosome must be inherited other malformations may have their origin in chro-
together" (Peters 1959). mosome anomalies." Two decades later the improve-
Spurred by the work of Sutton and others inter- ments in cytological techniques that allowed the cor-
ested in chromosomes, T. H. Morgan and a group of rect number of human diploid chromosomes to be
his students at Columbia University began to study determined also provided the solution to Down syn-
the inheritance of unit characters, the individual fac- drome. In 1959 three French cytologists, led by J.
tors of Mendelian transmission (Allen 1978; Carlson Lejeune (1959), announced that patients with Down
1981). Using the fruit fly Drosophila as their experi- syndrome had an extra chromosome, which was one
mental model, Morgan and his students made a series of the small telocentric chromosomes later desig-
of fundamental discoveries that led, by 1914, to their nated as chromosome 21 (Figure III. 1.4).
conclusion that the Mendelian factors, or genes, were This first example of a human disorder caused by
physical entities present in the chromosomes in a a specific chromosome anomaly in which there ex-
linear manner (Sturtevant 1913; Morgan 1914). isted at least one triploid chromosome in an other-
In 1923 T. S. Painter suggested that the number of wise diploid set (now called trisomy) led to a spate of
human chromosomes was 48, and this became the similar findings. These included Turner's syndrome
accepted number for the next 23 years. Improved (caused by the lack of one X-chromosome-XO), Klein-
cytological techniques eventually led to better reso- felter's syndrome (XXY), trisomy 13, and trisomy 18
lution of the chromosomes, with the result that J. H. (Thurman 1986). In 1960 the first international con-
Tjio and A. Levan (1956) established that the correct gress was called, in Denver, Colorado, to establish a
number of human diploid chromosomes was In = 46. standardized cytogenetic nomenclature. Much of the
So strong had been the belief in Painter's estimate impetus came from the discovery of chromosome
that, as Tjio and Levan themselves noted, a previous banding techniques by which each chromosome
study by another group had been abandoned because could be identified individually. Over time these
"the workers were unable to find all the 48 human techniques have been refined to the point where
chromosomes in their material; as a matter of fact, subbands and regions within them can be identified
the number 46 was repeatedly counted in their (Thurman 1986). However, even with these refine-
slides" (Tjio and Levan 1956). (Clearly, an open mind ments it has only recently been possible to study
is as important as good technique.) directly what specific regions of chromosome 21 are
It was not long after the number of human chromo- responsible for the Down syndrome phenotype.
somes was established that the solution to an old As has been the case with sickle-cell anemia and
and curious medical puzzle became apparent. A con- many other human diseases, recombinant DNA tech-
dition called furfuraceous idiocy had been described nology has enabled researchers to study Down syn-
in 1846 by the French physician E. Seguin. The drome with greater detail and precision. Chromo-
traits marking the syndrome included characteristic some 21 contains less than 2 percent of the DNA in
facial features, slow and incomplete growth, and the human genome, yet with an estimated 50,000
mental retardation. J. Langdon Down ascribed these genes in the genome (Shows, Sakaguchi, and Naylor
traits to the Mongol type in 1867: "A very large 1982), it probably houses 1,000 genes. By means of
number of congenital idiots are typical Mongols. So recombinant DNA and related techniques, more
marked is this, that when placed side by side, it is than 20 of those genes, along with nearly 50 anony-
difficult to believe that the specimens are not chil- mous sequences, have been mapped (see Figure
dren of the same parents" (Down 1867). III.1.4). Among the mapped genes is one that codes
From this publication the term Mongolian idiot for a ribosomal RNA (RNR-4, 18045). In addition,
replaced the previous name for the condition, and several genes of medical interest are known. These
later the term Down syndrome became interchange- include the gene for the enzyme cystathionine beta-

(McKusick 1986), and linked to this locus at 21q22 is
II U the locus for the enzyme superoxide dismutase

(SOD-1). Y. Groner and colleagues (1986) have re-
viewed molecular evidence that SOD-1 enhances
lipid peroxidation, which leads to toxic neurological
effects and to cataracts.
The Alzheimer's disease-like dementia of older
Down syndrome patients suggested that the q22 re-
gion of chromosome 21 might be the location of the
amyloid protein found in the senile plaques of
Alzheimer's patients. D. Goldgaber and colleagues
(1987) and R. E. Tanzi and colleagues (1987) indepen-
dently reported that the amyloid-B protein gene
mapped nearby at 21q21. The effect resulting from
the extra copy of the amyloid-B protein gene in
Down syndrome is an overproduction of amyloid and
presenile plaque formation. (
Finally, the advent of recombinant DNA tech-
niques and sophisticated analytic tools for estimat-
ing genetic linkage relationships have enabled one
group to focus on the cause of the trisomy. Using
several well-mapped anonymous DNA sequences
-, CBS from chromosome 21 as well as a probe for SOD-1, A.
C. Warren and colleagues (1987) have demonstrated
that recombination among DNA markers on chromo-
ETS2 somes 21 that have undergone nondisjunction, the
event leading to a trisomy, occurs to a significantly
lesser extent than it does in controls. Reduced recom-
Figure III. 1.4. Top: G-banded chromosome spread of a bination is indicative of asynapsis, or a failure of
man with Down syndrome (47, XY, +21). The individual normal chromosome pairing. This result will very
chromosome numbers are designated by convention. Bot- likely lead to the discovery of the molecular mecha-
tom: ideogram of human chromosome 21 indicating the nism of chromosome pairing.
subregional localization of several genes of interest (see
text). (From J. A. Fraser-Roberts and Marcus E. A Failure of Expectations: Kuru
Pembrey 1978, with permission.) In August 1953, an officer in an Australian govern-
ment patrol working in the South Fore region of the
highlands of Papua New Guinea noted a peculiar
synthase (CBS), which is implicated in the recessive condition:
metabolic disorder homocysteinuria (23620); the
gene for liver-type phosphofructokinase (PFKL), Nearing one of the dwellings [at Amusi], I observed a
which, in deficiency, leads to a type of hemolytic small girl sitting down beside a fire. She was shivering
violently and her head was jerking spasmodically from
anemia (17186); and two oncogenes, ETS-2 (16474)
side to side. I was told that she was a victim of sorcery and
and ERG (16508). The precise localization of ETS-2 would continue thus, shivering and unable to eat, until
to band 21q22 was a major indication that this re- death claimed her within a few weeks. (J. McArthur 1953,
gion of chromosome 21 is the one responsible for in Lindenbaum 1979)
many of the medical features of Down syndrome.
Individuals with Down syndrome have, in addi- The condition from which she was suffering was
tion to classical facial features and mental retarda- locally called kuru (trembling or fear), a progressive
tion, a greatly increased risk of developing myeloid neurological disorder peculiar to that region of
leukemia, a high incidence of cataract, and, in older Papua New Guinea.
patients, a neurological degeneration resembling Because the South Fore region was relatively iso-
Alzheimer's disease. The oncogene ETS-2 at 21q22 is lated and the villages interrelated through exten-
known to be rearranged in acute myeloid leukemia sive kinship ties, it was thought that kuru was a

genetic disease occurring in an isolated district the pace of discovery matched only by that seen when
where inbreeding was elevated. However, kuru re- Mendel's laws of heredity were revealed in 1900.
quired that the gene be dominant in women and The future of medical genetics is very bright in-
recessive in men for the epidemiology of the illness deed. Systematic screening of the human genome has
to be accounted for by a genetic factor (Bennett, revealed hundreds of inherited DNA sequence vari-
Rhodes, and Robson 1959). Thus, even as early as ants, or RFLPs (Willard et al. 1985; O'Brien 1987).
1963 the genetic etiology that seemed plausible was Exploitation of these markers has made it possible to
being discarded (Lindenbaum 1979). establish genetic linkage and chromosome map loca-
The case of kuru is mentioned here briefly because tions for a large number of hereditary human ill-
it is a good example of the sophistication achieved in nesses including Duchenne muscular dystrophy
medical genetics and the study of human diseases. In (Davies et al. 1983; 31020), Huntington's disease
the early part of the twentieth century, the power of (Gusella et al. 1983; 14310), cysticfibrosis(Tsui et al.
the Mendelian model was so great that the abandon- 1985; 21970), adult polycystic kidney disease (Reed-
ment of an unwieldy genetic hypothesis, which for ers etal. 1985; 17390), retinoblastoma (Cavenee et al.
kuru took only a couple of years, might have required 1985; 18020), familial polyposis (Bodmer et al. 1987;
decades. The true cause of kuru was a bizarre infec- 17510), manic-depressive or bipolar illness (Egeland
tious agent that S. B. Prusiner (1982) termed a priori, et al. 1987; 30920), and neurofibromatosis (Barker et
or proteinaceous infectious particle. In an odd twist, al. 1987; 16220). Moreover, the genes themselves
the infectious component in prions, a relatively small have been cloned for retinoblastoma (Friend et al.
protein called the prion protein, PrP 27-30 (Prusiner 1986) and Duchenne muscular dystrophy (Monaco et
et al. 1984), was found to have a normal homolog in al. 1986), as well as for chronic granulomatosus dis-
mammalian genomes, including human ones. PrP ease (Royer-Pokora et al. 1986; 30640). These suc-
produced its effect by forming rodlike structures recesses have made the production of a genetic map of
sembling amyloid, and it was thought that not only the entire human genome, first suggested by D.
was the PrP gene to be found on chromosome 21 but Botstein and colleagues (1980), not just a desirable
that Alzheimer's disease and even Down syndrome goal but a feasible imperative. Much of this work has
might be associated with prion infection (Prusiner already been accomplished (see Donis-Keller et al.
1982). However, Y.-C. J. Liao and colleagues (1986) 1987; White 1987), but much more must be done.
and R. S. Sparkes and colleagues (1986) indepen- Clearly, the day of an exact science of molecular medi-
dently reported cloning the human PrP gene and cal genetics has dawned and with it has come, after
mapping it to chromosome 20. The story of the prion 10,000 years, the potential for treating and even cur-
and of the PrP gene is still unfolding, and although it ing genetic diseases (Anderson 1984).
is not technically a genetic disease, kuru and neuro- Eric J. Deuor
logical disorders like it fit well within the multi-
factorial heuristic model that moved the study of This work was supported in part by Grants MH 31302 and AA
03539 from the National Institutes of Health. Jeanette A. Sharif
genetic diseases from one of recording oddities to a typed the manuscript and Roberta Rich provided the illustrations.
complex, interdisciplinary enterprise making use of
a full range of techniques and technologies. Bibliography
Allen, G. E. 1978. Thomas Hunt Morgan: The man and his
science. Princeton, N. J.
Summary and Prospects Anderson, W. F. 1984. Prospects for human gene therapy.
The history of the study of human genetic diseases is Science 226: 401-9.
not unlike that of any other area of medical science. It Ballantyne, J. W. 1902. Antenatal pathology and hygiene.
has been marked by periods of superstition and Edinburgh.
pseudoscience as well as byflashesof brilliant insight Barker, D., et al. 1987. Gene for von Recklinghausen
such as those of Maupertius, Adams, and Garrod. It neurofibromatosis is in the pericentromeric region of
chromosome 17. Science 236: 1100-2.
has also been characterized by an exponential in-
Bateson, William, and E. R. Saunders. 1902. Experimental
crease in fundamental understanding coupled with studies in the physiology of heredity: Report to Evolu-
technological and methodological breakthroughs, as tion Committee of the Royal Society, No. 1. London.
was clearly exemplified by sickle-cell anemia and Beadle, G. W. 1945. Biochemical genetics. Chemical Re-
Down syndrome. The recent development of recombi- view 37: 15-96.
nant DNA technology has ushered in a revolution in Beet, E. A. 1949. The genetics of the sickle-cell trait in a
the study of human genetic disease, a quickening of Bantu tribe. Annals of Eugenics 14: 279-84.

Bennett, J. H., F. A. Rhodes, and H. N. Robson 1959. A Glass, B. 1947. Maupertius and the beginnings of genetics.
possible genetic basis for kuru. American Journal of Quarterly Review of Biology 22: 196-210.
Human Genetics 11: 169-87. Glenister, T. W. 1964. Fantasies, facts, and foetuses. Medi-
Bodmer, W. E, et al. 1987. Localization of the gene for cal History 8: 15-30.
familial adenoma tous polyposis on chromosome 5. Goldgaber, D., et al. 1987. Characterization and chromo-
Nature 328: 614-16. somal localization of a cDNA encoding brain amyloid
Botstein, D., et al. 1980. Construction of a genetic linkage of Alzheimer's disease. Science 235: 877-80.
map in man using restriction fragment length poly- Groner, Y., et al. 1986. Molecular genetics of Down's syn-
morphism. American Journal of Human Genetics 32: drome: Overexpression of transfected human Cu/Zn-
314-31. superoxide dismutase gene and consequent physio-
Brewer, G. J. 1985. Detours on the road to successful treat- logical changes. Cold Spring Harbor Symposium on
ment of sickle cell anemia. In Genetic perspectives in Quantitative Biology 51: 381-93.
biology and medicine, ed. E. D. Garber. Chicago. Gusella, J. F., et al. 1983. A polymorphic DNA marker
Carlson, E. A. 1966. The gene: A critical history. genetically linked to Huntington's disease. Nature
Philadelphia. 306: 234-8.
1981. Genes, radiation, and society: The life and work of Harris, H. 1963. Introduction: Garrod's inborn errors of
H. J. Muller. Ithaca, N.Y. metabolism. London.
Caskey, C. T. 1987. Disease diagnosis by recombinant Heller, P. 1969. Hemoglobin M: An early chapter in the
DNA methods. Science 236: 1223-9. saga of molecular pathology. Annals of Internal Medi-
Cavenee W. K., et al. 1985. Genetic origin of muta- cine 70: 1038-41.
tions predisposing to retinoblas toma. Science 228: Herrick, J. B. 1910. Peculiar elongated and sickle-shaped
501-3. red blood corpuscles in a case of severe anemia. Ar-
Comings, D. E., et al. 1984. Detection of a major gene for chives of Internal Medicine 6: 517—21.
Gilles de la Tourette's syndrome. American Journal of Huck, J. G. 1923. Sickle cell anemia. Johns Hopkins Hospi-
Human Genetics 36: 586-600. tal Bulletin 34: 335-44.
Davies, K. E., et al. 1983. Linkage analysis of two cloned Ingram, V. M. 1956. A specific chemical difference be-
sequences flanking the Duchenne muscular dystro- tween the globins of normal human and sickle-cell
phy locus on the short arm of the human X chromo- anemia hemoglobin. Nature 178: 792—4.
some. Nucleic Acids Research 11: 2303-12. 1959. Abnormal human hemoglobins: III. The chemical
Donis-Keller, et al. 1987. A genetic linkage map of the difference between normal and sickle cell hemoglo-
human genome. Cell 51: 319-37. bins. Biochemical Biophysical Acta 36: 402—11.
Diggs, L. W., C. F. Ahmann, and J. Bibb. 1933. The inci- Jeffreys, A. J., V. Wilson, and S. L. Thein. 1985. Hyper-
dence and significance of the sickle cell trait. Annals variable "minisatellite" regions in human DNA. Na-
of Internal Medicine 7: 769-78. ture 314: 67-73.
Down, J. L. H. 1867. Observations on an ethnic classifica- Jeffreys, A. J., et al. 1986. DNA "fingerprints" and segrega-
tion of idiots. Journal of Mental Science 13: 121-3. tion analysis of multiple markers in human pedigrees.
Egeland, J. A., et al. 1987. Bipolar affective disorder American Journal of Human Genetics 39: 11—24.
linked to DNA markers on chromosome 11. Nature Kan, Y. W., and A. M. Dozy. 1978. Polymorphism of the
325: 783-7. DNA sequence adjacent to the beta globin structural
Emmel, V. E. 1917. A study of the erythrocytes in a case of gene: Relationship to sickle mutation. Proceedings of
severe anemia with elongated and sickle-shaped red the National Academy of Sciences 75: 5671—5.
blood corpuscles. Archives of Internal Medicine 20: Lawn, R. M., et al. 1978. The isolation and characteriza-
586-98. tion of linked delta and beta-globin genes from a
Fraser-Roberts, J. A., and M. E. Pembrey. 1978. An intro- cloned library of human DNA. Cell 15: 1157-74.
duction to medical genetics, 7th edition. Oxford. Lejeune, J., M. Gautier, and R. Turpin. 1959. Etude des
Friend, S. H., et al. 1986. A human DNA segment with chromosomes somatiques de neuf enfants mongoliens.
properties of the gene that predisposes to retinoblas- Comptes Rendus 248: 1721-2.
toma and osteosarcoma. Nature 323: 643-6. Liao, Y.-C. J., et al. 1986. Human prion protein cDNA:
Garrod, A. E. 1899. Contribution to the study of alkapto- Molecular cloning, chromosome mapping, and biologi-
nuria. Proceedings of the Royal Medical and Chirurgi- cal implications. Science 233: 364-7.
cal Society 11: 130-5. Lindenbaum, S. 1979. Kuru sorcery. Palo Alto, Calif.
1901. About alkaptonuria. Lancet 2: 1484-6. McKusick, V. A. 1986. Mendelian inheritance in man, 7th
1902. The incidence of alkaptonuria: A study in chemi- edition. Baltimore.
cal individuality. Lancet 2, 1616-20. Monaco A., et al. 1986. Isolation of the candidate cDNAs
1908. The Croonian Lectures on inborn errors of metabo- for portions of the Duchenne muscular dystrophy
lism. Lancet 2: 1-7, 73-9, 147-8, 214-20. gene. Nature 323: 646-50.
1928. The lessons of rare maladies. Lancet 1: 1055-9. Morgan, T. H. 1914. The mechanism of heredity as indi-

cated by the inheritance of linked characters. Popular linked factors in Drosophila, as shown by their mode
Science Monthly, January, 1—16. of association. Journal of Experimental Zoology 14:
Morton, N. E. 1982. Outline ofgenetic epidemiology. Basel. 43-59.
Morton, N. E., and C. S. Chung, eds. 1978. Genetic 1966. A history of genetics. New York.
epidemiology. New York. Tanzi, R. E., et al. 1987. Amyloid beta-protein gene:
Motulsky, A. E. 1959. Joseph Adams (1756-1818): A for- cDNA, mRNA distribution, and genetic linkage near
gotten founder of medical genetics. Archives of Inter- the Alzheimer locus. Science 235: 880—4.
nal Medicine 104: 490-6. Thurman, E. 1986. Human chromosomes: Structure, behav-
Nakamura, Y., et al. 1987. Variable number of tandem ior, effects, 2d edition. New York.
repeat (VNTR) markers for human gene mapping. Thompson, J. S., and M. W. Thompson. 1980. Genetics in
Science 235:1616-22. medicine, 3d edition. Philadelphia.
Neel, J. V. 1949. The inheritance of sickle cell anemia. Tjio, J. H., and A. Levan. 1956. The chromosome number
Science 110: 64-6. of man. Hereditas 42: 1-6.
Neel, J. V., and W. J. Schull. 1954. Human heredity. Chicago. Tsui, L.-C, et al. 1985. Cystic fibrosis locus defined by a
O'Brien, S. J., ed. 1987. Genetic maps, 1987: A compilation genetically linked polymorphic DNA marker. Science
of linkage and restriction maps of genetically studied 230: 1054-7.
organisms. Cold Spring Harbor, N.Y. Vogel, F., and A. G. Motulsky. 1979. Human genetics. New
Olby, R. C. 1966. Origins ofMendelism. New York. York.
Paget, J. 1882. The "Bradshawe" lecture on some rare and Warren, A. C, A. Chakravarti, and C. Wong, 1987. Evidence
new diseases. Lancet 2: 1017-21. for reduced recombination on the nondisjoined chromo-
Painter T. S. 1923. Studies in mammalian spermatogene- somes 21 in Down syndrome. Science 237: 652—4.
sis: II. The spermatogenesis of man. Journal Experi- White, R. L., ed. 1987. Linkage maps of human chromo-
mental Zoology 37: 291-336. somes. Salt Lake City, Utah.
Pauling, L., et al. 1949. Sickle cell anemia, a molecular Willard, H., et al. 1985. Report of the committee on human
disease. Science 110: 543-8. gene mapping by recombinant DNA techniques. Hu-
Penrose, L. S. 1939. Maternal age, order of birth and man Gene Mapping 8, Cytogenetic Cell Genetics 40:
developmental abnormalities. Journal of Mental Sci- 360-498.
ence 85: 1139-50. Wright, S. 1968. Evolution and the genetics ofpopulations,
Peters, J. A., ed. 1959. Classic papers in genetics. Engle- Vol. 1. Chicago.
wood Cliffs, N.J.
Plomin, R., J. C. DeFries, and G. E. McClearn. 1980. Behav-
ior genetics: A primer. San Francisco.
Prusiner, S. B. 1982. Novel proteinaceous infectious parti-
cles cause scrapie. Science 216: 136—44.
Prusiner, S. B., et al. 1984. Purification and structural III.2
studies of a major scrapie prion protein. Cell 38:
127-34. Immunology
Reeders, S. T., et al. 1985. A highly polymorphic DNA
marker linked to adult polycystic kidney disease on
chromosome 16. Nature 317: 542-44. The knowledge of acquired resistance to disease and
Roper, A. G. 1913. Ancient eugenics. Oxford. the practices connected with it are very old. Ancient
Royer-Pokora, B., et al. 1986. Cloning the gene for an medical systems of both East and West offered expla-
inherited human disorder: Chronic granulomatous dis- nations of why no one got smallpox twice and how
ease on the basis of its chromosomal location. Nature one might be protected from getting it at all. But the
322: 32-8. history of immunology as a science began only 100
Shows, T., A. Y. Sakaguchi, and S. L. Naylor. 1982. Map- years ago with the experiments of Louis Pasteur.
ping the human genome, cloned genes, DNA poly-
This history falls into two distinct periods, roughly
morphisms, and inherited diseases. In Advances in
human genetics, Vol. 12, ed. H. Harris and K. before and after World War II. It begins with a fan-
Hirschern. New York. fare, with the production of protective vaccines and
Sparkes, R. S., et al. 1986. Assignment of the human and antisera, probably the earliest example of truly effec-
mouse prion protein genes to homologous chromo- tive medical treatment. The great theoreticians of
somes. Proceedings of the National Academy of Sci- the period were biochemists, investigating the chem-
ences 83: 7358-62. istry of antigen and antibody and the nature of the
Stern, C, and E. R. Sherwood, eds. 1966. The origin of antigen-antibody reaction. The part played by blood
genetics: A Mendel source book. San Francisco. cells in the body's defenses had been in the fore-
Sturtevant, A. H. 1913. The linear arrangement of six sex- ground of discussions before the turn of the century,

III.2. Immunology 127
but it was pushed into the shade by the discovery of tality (Behring 1895). Meanwhile in Paris, Emile
the striking therapeutic effects of immune sera. Roux and Alexandre Yersin made the large-scale
After World War II, when it became clear that anti- production of the serum possible by using horses as a
biotics could control infections for which there was no source of antitoxin. In their first 300 cases, mortality
serological treatment, interest in immunological fell from 50 to 25 percent. In 1894 the Pasteur serum
methods of treatment waned and focused instead on was taken to England by Joseph Lister, and it was
the cellular biology of the immune process as a part of equally successful there (Parish 1965).
general biology. A single theory came to unite all of In England, cells and serum came together in the
immunology, making possible the striking expansion work of the clinical bacteriologist Almroth Wright.
of the field that took place in the 1970s. Wright demonstrated that phagocytes could not en-
gulf their victims without the help of a serum factor
Cells and Serum that he called an opsonin. The level of opsonic activity
The idea of cells defending the body against invaders showed the state of his patients' defenses against
was proposed by the Russian zoologist I. I. Mechni- bacterial infection and their response to the vaccines
kov. He saw that a yeast infecting a transparent he prepared for them. Local infections, such as boils,
water flea was surrounded by white blood cells that acne, appendicitis, and tuberculosis, were treated
stuck to the yeast and killed it. Mechnikov called the with autovaccines made from the patient's own or-
cells phagocytes (Mechnikov 1884; Besredka 1921). ganisms and calculated, in Bernard Shaw's phrase, to
As Arthur Silverstein has pointed out, phagocytosis stimulate the phagocytes. At the Department for
at this time was associated with the pathology of Therapeutic Immunization at St. Mary's Hospital in
inflammation rather than immunity. The first ex- London, he and a devoted group worked night and
perimental work on immunity, Pasteur's early ex- day at stimulating the phagocytes and determining
periments on chicken cholera, was only four years opsonic indices. Autovaccination and injections were
old in 1884 when Mechnikov's work appeared, and the treatment of the moment, especially, it seems, in
the germ theory of disease itself was hardly any the English-speaking world. From about 1945 on-
older (Silverstein 1979). Mechnikov's idea attracted ward, however, autovaccines were superseded by an-
Pasteur's interest, and Mechnikov was invited to tibiotics. Among the young bacteriologists who were
Paris in 1888. Wright's colleagues was Alexander Fleming, who la-
In Germany, especially among the Berlin bacteri- ter discovered penicillin. The department Wright
ologists around Robert Koch, the chief role in defense founded is now the Wright-Fleming Institute.
appeared more and more clearly to belong to the
blood serum rather than the cells. This group of The Age of International Serology, 1900-50
workers had earlier mounted an all-out attack on In spite of the popular appeal of the struggle of
Pasteur and the French workers, including Mechni- phagocytes, it was not cells but serum that set the
kov. This was a transposition into scientific terms of style. The key event of this period is the discovery of
the old nationalistic hatred between France and Ger- the striking clinical effectiveness of diphtheria anti-
many that had resulted in the Franco-Prussian War toxin. The production and control of this serum and
of 1870 (Foster 1970). In this case, the Germans had others like it pointed the direction for research in
some very telling ammunition. In 1890, Emil von theory and in practice.
Behring and his Japanese colleague Shibasaburo Although it was the diphtheria serum and its prob-
Kitasato, working at Koch's institute, diverted atten- lems that lent them much of their significance, the
tion from cellular to so-called humoral immunity first of the national serum institutes was established
when they showed that animals could be made im- just before the appearance of the serum. The Institut
mune to the effects of the toxins produced by both the Pasteur was set up in 1888, following the national
tetanus and diphtheria bacilli. Immunity could be enthusiasm in France created by Pasteur's success
transferred by an injection of immune serum, a find- with rabies immunization (Delaunay 1962). The in-
ing that was quickly applied outside the laboratory. stitute was not, strictly speaking, a state concern,
Within a year, on Christmas Eve of 1891, the serum because it was independently funded, but it had na-
was tried out on a child acutely ill with diphtheria. tional status. Its opening marked the end of Pasteur's
The results were sensational (Behring 1895). The active life; he had had a stroke the previous year, and
production of sheep and goat serum began in 1892, the new institute was to be run not by Pasteur him-
and in 1894 it was introduced into the Berlin hospi- self, but by his successors, the Pastoriens.
tals. There was an immediate fall in diphtheria mor- From its beginning, the institute offered courses on

bacteriological technique. Among the students were guinea pig against 100 fatal doses of toxin. The
young bacteriologists from all over the world; many method seemed logical, but in practice the results
were medical officers of the French colonies, which were unreliable.
led to the establishment of the Instituts Pasteur The problem was taken up by Paul Ehrlich, head
d'Outre-Mer. The first four of these, in Saigon, of the newly established Institut fur Serumprufung
Nhatrang, Algeria, and Tunis, were founded be- und Serumforschung in Berlin. Ehrlich's assay proce-
tween 1891 and 1894. Among them may also be men- dure followed Behring's quite closely, but he defined
tioned the Haffkine Institute in Bombay, founded in his units using a standard toxin and a standard
1899 and led by a Pastorien, Waldemar Haffkine. As antiserum, and new batches of either were assayed
Noel Bernard points out, the vulnerability of the by comparison with these. The Lo dose of a new toxin
whites in these new areas of colonization stimulated was the number of lethal doses (L.D.'s) neutralized
interest in the diseases endemic in them; the In- by one unit of the original antiserum, and the L+
stituts Pasteur d'Outre-Mer concentrated on plague, dose was the number of lethal doses just not neutral-
cholera, and malaria - and snake bite (Bernard ized. Theoretically, as Behring had expected, L+ —
1960). In Europe, needs were different: Centers that Lo = 1 L.D. But in practice, as the toxin aged, the
had begun by working on vaccines turned their atten- difference increased. The toxin's capacity to neutral-
tion to the large-scale production of diphtheria anti- ize antitoxin remained constant, but the toxicity of
serum. Thus, Institut Pasteur set up a special center the solution gradually declined.
for making horse serum at Garches, outside Paris. Ehrlich interpreted this in terms of his side-chain
A similar evolution took place in London, leading theory as meaning that there were two different side
to the foundation of the British Institute of Preven- chains on the toxin molecule, which he called the
tive Medicine, renamed the Lister Institute in 1891 toxophore and the haptophore groups, responsible
(Chick, Hume, and Macfarlane 1971). Rabies at that for the toxic property and the property of neutraliz-
time was an uncommon, but fatal result of animal ing antitoxin, respectively. The toxophore group, he
bites in England, as on the Continent; no one could thought, was labile, so that toxicity declined over
predict which bite might be fatal. Pasteur himself time. A further difficulty lay in the fact that succes-
suggested a Pastorien, Marc-Armand Ruffer, who sive additions of antiserum had unequal effects on
had connections in England and Germany, as well as the toxicity: The first few additions might not dimin-
Paris, to head it. In 1893 Ruffer reported on the ish the toxicity at all, though antibody was being
astonishing effectiveness of Behring's diphtheria se- absorbed. Ehrlich thought this meant that the toxin
rum, and in 1894 a serum department was created at consisted of a mixture of different components, each
the Lister. Soon after, the Wellcome Laboratories giving a different ratio of antigen to antibody.
were founded to make the serum commercially. The most "avid" components took up the highest
In the same year Carl Salomonsen, director of the proportion of antibody and took it first; the less avid,
University Bacteriology Laboratory in Copenhagen, later. He illustrated this by a stepped diagram, the
went to Paris to learn the techniques. On Salomon- profile of which represented the relationship between
sen's return, he applied to his government for funding toxicity and avidity for antiserum at each stage of
for a laboratory for serotherapeutic experiments and neutralization. Each step represented a separate,
undertook at the same time to produce diphtheria named component, which he called toxin, toxone, and
serum in quantity for free distribution. The Statens toxoid, each with named subdivisions (Ehrlich 1887-
Serum Institutet under Thorwald Madsen became 8). The development of a clearly visualized, but quite
independent of the University in 1901 (Salomonsen speculative chemistry, along with a new vocabulary
1902). Elsewhere too, rabies vaccination led the way to describe the visualized substances, was very typi-
to the manufacture of diphtheria serum, which was cal of Ehrlich's thinking (Mazumdar 1976). It was the
not only a tremendous therapeutic success, but a com- first statement of his side-chain theory, the theory of
mercial success as well (Defries 1968). immunity around which argument raged for the next
The most important of the problems raised by the 20 years and which has never quite disappeared from
clinical use of the serum was that of standardization. immunology.
The first attempt at a biological assay was made by The feature of Ehrlich's assay procedure that
Behring. His method was to standardize the anti- made it so successful was his insistence on measur-
serum against the toxin. The minimum fatal dose of ing all new serum samples against a standard se-
toxin was first established, and one unit of antitoxin rum. The standard was preserved desiccated, frozen,
was defined as the amount necessary to protect a and under vacuum, at Ehrlich's own new specialized

laboratory in Frankfurt, which continued to provide also been in contact with Jules Bordet at the Institut
for international standardization up to World War I. Pasteur, was the first to develop an alternative inter-
During the war, communications with Frankfurt pretation of Ehrlich's stepped diagram. Working
were cut off, and standards began to drift. with the physical chemist Svante Arrhenius, he sug-
The decision to take over the regulation of serum gested that the antigen—antibody reaction was a
standards was made by the League of Nations reversible equilibrium like the neutralization of acid
Health Committee in 1921. A series of International by base, a type of reaction that gave a smooth expo-
Conferences on the Standardization of Sera and Sero- nential curve rather than a series of steps. There
logical Tests was held; it was decided to keep the was no need to postulate a whole series of different
Ehrlich unit as the international standard, but since substances (Arrhenius and Madsen 1902; Rubin
Germany was excluded from the League of Nations, 1980). The theory had an indifferent reception, but
the standard serum was to be in Copenhagen. Ehrlich's enemies, led by Max von Gruber in Vi-
Madsen suggested that similar agreements could be enna, hoped that what they saw as a splendid refuta-
reached for other biologicals, such as hormone prepa- tion meant the end of Ehrlich's ascendancy.
rations and plant extracts. In 1924, the Permanent For Bordet, however, the outstanding fact was
Commission on Biological Standardization was set that an agglutinable substance absorbed different
up with Madsen as its chairman (Hartley 1945). amounts of its agglutinin according to the relative
Copenhagen became the center of coordination for proportions of the reacting substances: The reaction
all work on serum standards, with individual sam- was not chemical at all, but physical. He compared
ples of diphtheria antitoxin and other antibacterial the phenomenon to that of dyeing: If one dipped a
sera kept at Cophenhagen, Frankfurt, Hampstead, series of pieces of paper in a dye solution, the first
and Toronto, and at Paris at the Institut Pasteur few would be strongly colored, and the later ones
(Jensen 1936). paler and paler as the dye was exhausted. As early
as 1896, he had suggested that "serum acts on bacte-
The Nature of Specificity, 1900-50 ria by changing the relations of molecular attraction
In the nineteenth century, the startling success of between bacteria and the surrounding fluid" (Bordet
the serum treatment of diphtheria had given rise not 1896).
only to the practical problems of standardization and Bordet's physical point of view was taken up by
their solution, and to the international organization Karl Landsteiner in Vienna, who had been trained
to coordinate the work, but also to a theoretical in both medicine and structural organic chemistry.
interest in the antigen-antibody reaction and the He had joined Gruber's serological laboratory in
nature of specificity. The earliest formulation of 1896 and, like other Gruber students, followed the
these problems came with Ehrlich's side-chain Gruber line of anti-Ehrlich argument. Landsteiner
theory. According to the theory, the antibody had a proposed a physicochemical model for the antigen-
unique chemical affinity for the haptophore on the antibody reaction: the precipitation of inorganic col-
toxin. Ehrlich suggested that the union of antitoxin loids. The model was particularly apt because the
with its toxin tore the antibody molecule free of the form of antigen-antibody reaction that Landsteiner
cell that carried it on its surface. This trauma caused usually worked with was a precipitin reaction, in
an overproduction of identical replacement mole- which a soluble antigen was precipitated out of solu-
cules, rather as healing of an injury caused overpro- tion by an antibody.
duction of new tissue (Ehrlich 1887-8; Mazumdar Colloid chemistry dealt with the behavior of mate-
1976; Silverstein 1982). rials that formed very large particles, so large that
The side-chain theory had two implications that their reactions depended on the physical properties of
drew criticism. First, the side chains were supposed their surfaces rather than on their chemical nature.
to bind to their receptors firmly and irreversibly In the early part of the twentieth century, the physi-
according to the law of definite proportions, by the cal chemistry of colloids seemed to hold great promise
type of linkage now called covalent. Second, the for explaining the reactions of living tissue and its
theory required that the body be provided with pre- major constituent, protein. It seemed particularly ap-
existing antibodies to match every conceivable anti- propriate for the antigen-antibody reaction, because
gen, even those artificial molecules that could have it was thought that only proteins were antigenic.
had no possible role in the evolution of the species. Working with the Viennese colloid chemist Wolfgang
Madsen, who had learned the technique of diphthe- Pauli, who was one of the most enthusiastic propo-
ria serum assay from Ehrlich himself, but who had nents of the "chemistry of life," Landsteiner pointed

out that it was colloids with opposite charges that thinking in both immunology and chemistry (Ma-
precipitated each other. The antigen-antibody reac- zumdar 1989). In English, it became known as the
tion might be an electrochemical surface adsorption: template theory, and in one form or another, it was
Subtle surface charge effects might account for anti- generally accepted for the next 20 years or more.
body specificity (Landsteiner 1909). He and Pauli Landsteiner had been a rather isolated theoretical
developed an apparatus for comparing the charge on thinker at a time when theory was of little interest
proteins by following their movements in an electric to the practical serologist. In addition, criticism of
field. Their apparatus was adopted by Leonor Michae- Ehrlich was not popular in Vienna. Thus, after the
lis and his group in Berlin, who thought the same political and economic collapse of Austria at the end
features might account for the activities of enzymes. of World War I, Landsteiner was eager to leave, and
Landsteiner then entered into a long program of re- in 1922 was invited to joing the Rockefeller Institute
search, aiming to define the antigenic specificity of in New York. There, in a sympathetic environment,
proteins carrying known substituent groups, a proj- he was able to continue his work on artificial anti-
ect that made use of his skill in structural chemistry. gens. He also turned again to the blood groups,
The final proof of his position came in 1918, when he which he had not worked on since 1901-9, when he
demonstrated that antigenic specificity was deter- discovered them (Landsteiner 1901). It was for this
mined mainly by the charge outline of the antigen discovery, and not the work on artificial antigens,
(Landsteiner and Lampl 1918). This conclusion that he was given the Nobel Prize in 1932.
united the colloid or physical concept of charge with Landsteiner's interest in the blood groups began
the structural concept of the chemical nature of the in 1900, when he and many others tried to explain
molecule (Mazumdar 1976; Silverstein 1982). the presence of antibodies in human blood that ag-
Landsteiner's demonstration of the importance of glutinated the red cells of other human bloods. Most
charge outline had several implications. The first proposals linked them to some common disease, such
was that specificity need not be absolute, as Ehr- as tuberculosis and malaria. It was Landsteiner's
lich's theory would have it. Cross-reactions could suggestion that these were "natural antibodies"
take place between similarly charged groups simi- whose presence was independent of infection. Land-
larly placed on the antigens. A huge number of differ- steiner himself showed curiously little interest in
ent specific antibodies was not, therefore, necessary. this pregnant finding, perhaps because the "natural
The second was that the antigen-antibody reaction antibodies" and the sharply defined specificity of the
was not a firm chemical binding; the two were different groups seemed to support Ehrlich's theory.
linked not by valency bonds, but by the so-called Although Landsteiner had suggested in 1901 that a
short-range forces that surrounded a molecule, as in knowledge of blood groups would be useful in blood
the model of a crystal lattice (Marrack 1934). The transfusion, transfusion was used very little for
third implication, that of the generation of antibody many years afterward. It was reported on occasion-
diversity, was not made until 1930, by the Prague ally during World War I, and although a large litera-
biochemist Felix Haurowitz. ture accumulated, it did not become a routine hospi-
Haurowitz's training, like that of Landsteiner, tal procedure until the establishment of blood banks
had included both colloid chemistry and structural shortly before World War II. In Britain, fear of civil-
chemistry. He spent some time with Michaelis work- ian casualties on a large scale stimulated the organi-
ing on the physical chemistry of charge in relation to zation of a blood collection and distribution system.
enzyme activity. But after the war Prague had lost Landsteiner and his colleagues at the Rockefeller
its links with Vienna; Haurowitz heard nothing Institute discovered several more sets of inherited
about the work of Landsteiner until 1929, when the antigens on red cells, the MN and P systems, and in
serologist Fritz Breinl told him about it. Breinl and 1940 the rhesus, or Rh, system. These workers found
Haurowitz, then working together, suggested that rhesus incompatibility between mother and fetus to
antibody might be assembled on the charge outline be the cause of hemolytic disease of the newborn, a
of its antigen, appropriately charged amino acids discovery that led in the 1960s to an immunologic
lining up by adsorption onto the antigen to form a method of specifically suppressing antibody forma-
specific antibody globulin. There was no need for tion in the mother and so preventing the disease.
Ehrlich's innumerable preformed specificities. The In an era when human genetics was represented
organism made its antibody as required. It was a by the eugenics movement, blood groups were the
simple and economical solution to the problem of only normal human trait that was clearly inherited
antibody diversity; it made use of the most advanced according to Mendelian laws. They seemed to be

direct products of the genes, untouched by any envi- tation coefficient of 7 S, corresponding to a molecu-
ronmental effect. They could be analyzed mathemati- lar weight of about 15,000, but there was a small
cally as the Gottingen statistician Felix Bernstein amount of heavier 18 S globulin. As in the salting-
had shown (Bernstein 1924; Mazumdar 1992), and out technique, antibody activity went along with the
as a model genetic system, they might come to do for globulin fraction. Svedberg saw ultracentrifugal
human genetics what the fruit fly Drosophila had analysis as a contribution to classical colloid chemis-
done for genetic theory in the 1920s. To critics of the try: Particle size and dispersal of proteins in solution
eugenist's social biases, such as the left-wing scien- were central to the colloid tradition.
tists of the 1930s, blood groups represented a means In 1930 Svedberg's younger colleague Tiselius de-
of making human genetics the genuinely "value-free veloped an apparatus for the separation of protein
science" that it had so far grotesquely failed to be molecules in terms of their charge, based on the
(Hogben 1931). In practice, the complex genetics of work of Landsteiner and Pauli. Tiselius, too, felt
blood group antigens was to provide a model for the that the study of electrokinetic phenomena was
genetics of tissue types, essential in the choice of among the most important of the tasks of colloid
organs for grafting and for the genetics of proteins chemistry (Tiselius 1938).
(Grubb 1989). Svedberg's and Tiselius's earlier methods had
been useful for the analysis of protein mixtures,
The Chemistry of Antibody Globulins, whereas the new techniques of the 1940s made it
1930-60 possible to prepare the products on a large scale. The
The history of protein chemistry is the history of a name chromatography was coined by the Russian
sequence of innovations in instrumentation and tech- botanist M. Tswett in 1910 to describe his method of
nique, each of them pointing to a new vein of knowl- separating colored plant materials. The first good
edge to be worked. Most of these were fractionation chromatographic method for proteins was introduced
methods; proteins could be separated in terms of in 1944 by A. J. P. Martin and his colleagues at St.
charge or particle size, and biological activity corre- George's Hospital in London. Martin's method was to
lated with the resulting serum fractions or protein use a filter-paper sheet as the adsorbent, with the
fragments. For most of the period, efforts in this area solvent containing the test material flowing slowly
were more or less independent of the work on immune up a vertical sheet by capillary action. It also incorpo-
specificity, but they too had their roots in colloid rated the novel idea of two-dimensional separation.
chemistry. Not until after World War II did protein When separation with one solvent was complete, the
chemists begin to feel that the high aspirations of paper was turned 90 degrees and another separation
colloid chemistry were an absurdity better forgotten. with another solvent, or with an electric current, was
The earliest and simplest preparative separa- performed. This method, called "fingerprinting,"
tion method for serum proteins was "salting-out," was good for identifying differently charged amino
achieved by adding neutral salts to the protein solu- acids in a mixture of peptide fragments of proteins,
tion, a technique introduced in the mid-nineteenth and it became a favorite with protein geneticists.
century. By 1930 there were still some chemists After the war ended, a new group of methods for
who were not convinced that the serum antibodies the separation of charged molecules appeared. Ion
were actually globulins, and not some other mate- exchangers are essentially insoluble acids or bases
rial (Spiegel-Adolf 1930). in the form of a highly cross-linked matrix, usually a
With their sophisticated techniques and mathe- resin, through which a solvent carrying the material
matical approach, the physical chemists working at to be analyzed can percolate. Molecules with the
Uppsala in Sweden transformed colloid chemistry. same charge as the solid are repelled by it to various
The vitalistic enthusiasm of Pauli faded into a hard- degrees and pass more or less quickly through,
line physical science. However, both The Svedberg whereas those with the opposite charge are entan-
and Arne Tiselius thought of themselves as colloid gled and delayed. In 1951 an ion-exchange resin was
chemists. brilliantly applied to the separation of amino acids
Svedberg's work on protein separation began to by Stanford Moore and William H. Stein at the
appear in 1925. Using a high-speed centrifuge, he Rockefeller Institute in New York (Moore and Stein
found that proteins were forced to the bottom of a 1951). They not only obtained a quantitative separa-
tube in order of their size. He assigned to each a tion of mixtures containing an astonishing number
sedimentation coefficient S that indicated molecular of different substances, up to 50 in some cases, but
weight. The serum globulin mainly had a sedimen- also automated the procedure so that it could be run

unattended overnight. In the morning, the research- supporting Linus Pauling's suggestion in 1940 of a
ers would find a series of tubes filled by an auto- long antibody molecule with a rigid centerpiece and
matic fraction collector, ready for them to analyze. two flexible ends, which folded, or molded, them-
This type of method with its greatly increased pro- selves on the antigen as a template to effect a spe-
ductivity made possible the rapid accumulation of cific match (Porter 1959). For Porter in 1959, a tem-
information on amino acids and their sequence in plate theory of the generation of antibody diversity
many different proteins. was still the most likely possibility.
Protein molecules, however, easily lost their bio- In 1962 Porter tried a different dissection of the
logical activity with the rough handling that resins antibody globulin by opening its disulfide bonds.
gave them. Investigators might succeed in isolating Separation of the result on a Sephadex column pro-
a protein peak by a preparative method, only to find duced two peaks, one heavy and one light. He
that all the antibody activity had disappeared, "lost thought that these must be two chains of the
on the column." It was not long before a better way globulin molecule, normally joined together by
was found. Cellulose-based ion exchangers were in- disulfide bonds. Amino acid analysis showed that
troduced by Herbert A. Sober and Elbert A. Peterson there must be two of each chain. The relation of the
and by Jerker Porath at Uppsala (Sober et al. 1956). chains to the papain pieces was determined immuno-
The anion exchanger was diethylaminoethyl cellu- logically, using goat antisera to the rabbit frag-
lose, or DEAE, and the cation, carboxymethyl (or ments. Porter then proposed a second model of the 7
CM) cellulose. These materials turned out to be far S globulin molecule, with a pair of heavy chains
less destructive to the protein molecule. A second joined by disulfide bonds and a light chain attached
type of material developed by Porath was a dextran to each one, with the antibody site in fraction I,
gel called Sephadex by its manufacturer. It was not probably on the heavy chain. This model stood up
an ion exchanger; it acted, to use Porath's (1960) satisfactorily to additional evidence, to the discovery
expression, as a kind of molecular sieve. Large mole- of different types of heavy chain in different classes
cules, such as the 18 S globulin, passed almost unhin- of immunoglobulin, and to the discovery of individ-
dered through it, excluded from the finer pores of the ual genetically determined polymorphisms of both
gel; smaller ones, such as albumin and 7 S globulin, chains (Porter 1973).
wandered more slowly, exploring the labyrinth Using the fingerprinting technique, several labo-
within. All these materials were soon available com- ratories in Britain and the United States, and Mi-
mercially, many from firms centered in Uppsala. As chael Sela and his group in Israel, found that the
the techniques and the rather expensive equipment peptide maps of I and II from different antisera were
for column chromatography and automatic fraction very slightly different from each other. The chemists
collecting spread through laboratories, protein chem- were getting nearer to finding out the amino acid
istry, particularly the chemistry of antibody globu- sequence of an individual antibody; there was, how-
lins, moved very rapidly (Morris and Morris 1964). ever, still too much heterogeneity in normal anti-
The range of separation methods now available body to make such detail possible.
made possible an attack on the structure of the The problem was solved by an accident of nature.
immunoglobulin molecule. Rodney Porter, working To everyone's surprise, the fingerprints of normal
at St. Mary's Hospital Medical School in London, light chains and the so-called Bence-Jones protein
separated out a rabbit immunoglobulin by chroma- turned out to be almost identical. This material,
tography on DEAE, and then digested it with the named for its nineteenth-century discoverer, is
proteolytic enzyme papain to break it into sections found in the urine of patients with myeloma, a lym-
small enough to be understood. The digest was first phoid tumor of the bone marrow. The only difference
put into the ultracentrifuge. There was only one seemed to be that normal light chains were a mix-
peak, at 3.5 S, showing that the 7 S globulin had ture of two types, whereas the Bence-Jones chains
broken into smaller fragments of roughly equal size. were homogeneous, and therefore an ideal material
On CM cellulose, there were three peaks. Amino available in large quantities for sequence studies on
acid analysis by the Moore and Stein method on an the amino acid analyzer. It appeared that each pa-
ion-exchange resin showed that peaks I and II were tient produced a different chain; each chain con-
almost identical, and III, very different from them; sisted of two sections, a variable region and a con-
antibody activity was present in peaks I and II. Por- stant region. Of the 105 amino acids of the variable
ter's first interpretation of his results was that the region, about 30 varied from case to case. In this
molecule was a long single chain with three sections, variation lay the essence of antibody specificity.

Parallel with the detailed information that built Australia, together with Frank Fenner of the Austra-
up throughout the 1950s on amino acid sequences, lian National University, suggested that an animal
evidence began to accumulate that these sequences body had some mechanism for distinguishing "self"
were under genetic control. Information that speci- from "not-self." Antigens that were present before
fied each amino acid was found to be encoded in birth were accepted as "self," and an animal made no
deoxynucleic acid, or DNA, transferred to a messen- antibody to them (Burnet and Fenner 1949). Burnet's
ger ribonucleic acid, or RNA, and transcribed as an experiment failed, but a similar one that produced a
amino acid to be added to the growing peptide chain. tolerance to foreign skin grafts succeeded at the
The system appeared to be strictly directional. Fran- hands of a British group led by Peter Medawar. Dur-
cis Crick of Cambridge University stated what he ing the war, Medawar had served in a London hospi-
called the "central dogma" of protein synthesis: tal, treating the wounded and burned of the London
Once genetic information has passed into protein, it blitz. He had tried to use grafts of donor skin in the
cannot get out again. No protein could be formed by same way he had used donor blood, which was then
copying another protein (Crick 1957). saving so many lives. Bat donor skin did not "take."
If this were so, it would make the template theory It was Medawar's idea that graft rejection was an
of antibody formation impossible. But the template immunogenetic phenomenon, as it was Burnet's idea
theory had deep roots, and distinguished supporters, that self-tolerance was established in fetal life. In
such as the U.S. immunochemists Pauling and Mi- 1960 Burnet and Medawar shared a Nobel Prize.
chael Heidelberger. Haurowitz, now at Indiana Uni- From the early 1950s, attention focused on toler-
versity, continued to hold that antigen could inter- ance. Burnet, speaking a t a conference at the Royal
fere, if not with the primary amino acid sequence of Society of London in 1956, saw the interest in this
the protein, at least with its folding. In 1963 he was "vital" phenomenon as one of the ways in which
arguing that antibodies were normal globulins and immunology was becoming more and more biologi-
that their amino acid sequences were shown by fin- cally oriented (Burnet 1957). There was also the
gerprinting to be almost identical with one another, discovery by the U.S. investigators William Talia-
leaving only the folding to account for antibody speci- ferro and David Talmage that a very few cells, con-
ficity. By then, he knew that his theory was becom- taining no detectable antigen, could transfer the full
ing less and less likely to be validated, and he often antibody-forming capacity of an immune animal to a
appeared to accept that its time had passed. But new host. These findings could not be explained by
Haurowitz never laid down his arms. As he had said the template theory. Alternative explanations began
in 1960, he could not imagine the formation of a to appear.
mold without a cast, or antibody without antigen. Among the most important alternatives was the
natural selection theory of the Danish immunologist
Cellular Immunology and the Selection Niels Kaj Jerne, which appeared in 1955. It was a
Theories theory that would have appealed to Paul Ehrlich: It
It was not, however, the argument from the central proposed that "natural" antibodies were continu-
dogma that turned immunologists away from the ously being formed, before any antigen was pre-
template theory. In spite of the growth of molecular sented. A given antigen would select its match from
biology in the postwar period, it was the complex among this population of miscellaneous antibodies
phenomena of immune cells and immunized ani- and would form an antigen-antibody complex. The
mals that provided the impetus for building the complex would then be taken up by a phagocyte,
new theory. The theoreticians, especially Frank which would trigger further production of the same
Macfarlane Burnet, considered themselves biolo- antibody specificity (Jerne 1955). The theory fitted
gists and drew their ideas from contemporary think- Burnet's concept of self-tolerance: There should be
ing in biology. no antiself antibodies. Ehrlich had called this the
During the 1940s, a number of pieces of evidence horror autotoxicus.
accumulated that were to throw doubt on the tem- Both Talmage and Burnet offered improvements
plate theory. One was the phenomenon of tolerance: on Jerne's idea. Talmage suggested that attention
Ray Owen in California had found that cattle twins should focus on antibody-producing cells rather than
that shared intrauterine circulation before birth on serum antibody: Certain cells might be selected
each contained some of the other's blood cells and for multiplication when their produce reacted with
made no antibody to them as adults. In 1949 Burnet the antigen. Talmage's suggestion, however, was
of the Walter and Eliza Hall Institute in Melbourne, overshadowed by that of Burnet, which was similar

in many ways but much more fully worked out. The clonal selection theory appeared in 1957. Al-
Burnet called his version the clonal selection theory, most a t once, evidence strongly supporting the
and it was this version that eventually obtained theory was produced by Gustav Nossal and Joshua
general acceptance. Lederberg. Using the most direct means of testing
Burnet was born and educated in Australia, where clonal selection, they isolated single lymphocytes
he took his medical degree in 1922. His postgraduate from rabbits immunized with two antigens and
tour, however, took him to London's Lister Institute, found that each cell produced only one specificity of
where he worked on bacteriophage viruses and their antibody. It was technically a difficult feat and not
serological classification. After getting his doctor- easy to reproduce (Nossal and Lederberg 1959).
ate, Burnet joined the National Institute for Medical Although Burnet himself had not insisted on the
Research. Here he learned the practical techniques capacity of each cell to make only one antibody, it
of limit dilution and cloning used to grow a virus in seems to have been this finding that provided the
pure culture. According to his colleague Gordon Ada strongest support for his theory. One cell, one anti-
(1989), this work at the bench may have provided body: By 1967 Jerne could call that slogan "Burnet's
him with models for his later immunologic theories. dogma in its uncompromising form" (Jerne 1967),
Burnet was always careful to give Jerne full credit thus giving it equal status with Crick's "central
as the "onlie begetter" of the selection theory (Burnet dogma," mentioned earlier. At the Cold Spring Har-
1967). But he did not like the idea that phagocytosing bor Symposium that year, it began to seem as if the
an antigen-antibody complex caused a cell to pro- clonal selection theory had been accepted by the
duce antibody. He suggested instead that the natural leaders i n thefield.In the 10 years since it had been
antibody was not free in the serum but attached to the proposed, a plethora of experiments on lymphocytes
cell surface as a receptor, rather as Ehrlich had sup- had demonstrated that antigen turned a small
posed 50 years before. Antigen then selected the cell subpopulation on to clonal expansion and that anti-
that carried a suitable antibody, and that was the gen was not present in all the antibody-producing
stimulus for the cell to start proliferating. Somatic cells. As Burnet had said, the way the theory was
cells do not mate; apart from mutations, their prog- stated made it easy to think of ways to test it.
eny are identical, a clone of genetically identical
cells, all producing identical antibodies. Burnet sug- Immune System
gested that each cell probably produced only one or The growing power of the clonal selection theory
two antibodies, because that gave a reasonable num- during the late 1960s created a magnetic storm in
ber of cell types to deal with the number of different the minds of immunologists. The disturbance was
possible antigens (Burnet and Fenner 1962). worldwide, but the epicenter was at the Hall Insti-
This theory explained two biological phenomena tute in Melbourne, where Burnet and his students
of immunity that had not gone well with the tem- Ada, Nossal, and Jacques Miller, all biologists, disen-
plate theory. It explained tolerance of self as the tangled the life and work of lymphocytes. The Soviet
absence of "forbidden clones" of cells that would immunologist R. V. Petrov (1987) has called this the
have made antiself antibody. And it matched the period of the dictatorship of the lymphocyte. The
kinetics of antibody production: the delay following consequence of the acceptance and pervasiveness of
inoculation of the antigen while the first few genera- the clonal selection theory was a general reorienta-
tions of cells were produced and then the exponen- tion of the field toward the study of cells.
tial rise in titer as the doubling numbers of each new The thymus was an organ whose histology was
generation came into being. It explained why a sec- described i n great detail in all the elementary text-
ond exposure to antigen had a more immediate and books, but it had never been found to have any
more marked effect: A substantial number of cells of function. Thymectomy seemed to have no effect on a
the right clones already existed, ready to begin their normal adult. In 1961 Burnet suggested to Miller
proliferation. that he try to discover the effect of thymectomy not
Burnet did not waste much time on the central on adults, but on newborns in whom, according to
dogma, but it supported his position, and as a biolo- his theory, self-tolerance was still being established.
gist, he very soon accepted it as a matter of course. It Experiments on mice produced a striking effect: The
had become a kind of Lamarckian heresy, he said, to thymectomized mice looked ill; they had constant
believe that the environment could produce herita- diarrhea and infections; foreign skin grafts, even
ble changes in protein structure (Burnet and Fenner skin grafts from rats, flourished on them, and they
1962). could hardly produce any antibody (Miller 1962).

In 1963 Australian and U.S. investigators met for tion against infection, something that had nothing to
a conference on the thymus. It was arranged by the do with serum and seemed to be destructive rather
U.S. pediatrician Robert Good, who had been treat- than protective did not attract much interest. It was
ing children with immune deficiencies, most of not until 1939 that Landsteiner and his colleague
whom had congenital absence of the thymus. Like Merrill Chase at the Rockefeller Institute made the
Miller's mice, they suffered from endless infections, connection between delayed hypersensitivity and con-
and they neither rejected grafts nor produced anti- tact hypersensitivity to such things as poison ivy and
bodies. In some of them, the thymus looked normal to the artificial antigens that Landsteiner had been
and graft rejection was normal, but no antibodies working on for the past half-century (Landsteiner
were produced. The only known experimental model and Chase 1939). In the following year, Landsteiner
of this type of deficiency was the chick from which and Chase managed to transfer contact sensitivity by
the bursa of Fabricius, an organ rather like the mam- means of live cells. In addition, Jules Freund (1956),
malian appendix, had been removed. The bursa working at the New York Public Health Research
seemed to be responsible for producing the cells that Institute, found that lesions could be made much
made antibody, suggesting that there were two differ- bigger by injecting antigen in an oily mixture that
ent types of lymphocyte, one mediating graft rejec- contained a trace of tuberculin. Because there were
tion and the other making antibody. During the now techniques that could be used, research could
1960s, details accumulated on the powers of differ- begin.
ent types of cell cultured in isolation. It was left to It soon became clear that delayed hypersensitivity
Miller and Graham Mitchell at the Hall Institute in could take the form of autoimmune disease, and that
1968 to add one more parameter, the behavior of this kind of disease could often be reproduced by
thymus and bone marrow cells mixed together. The injecting material from the target organ in Freund's
mixed culture generated 20 times more antibody- adjuvant. During the 1950s, laboratories in Britain
producing cells than either cell type alone: The anti- and the United States worked on the problem using
body response must depend on cellular cooperation. experimental allergic encephalitis as a model. Un-
Their next paper made the roles clear. The bone der the microscope, all the lesions looked very much
marrow, or B, cells produced antibody, but the thy- the same: There was always a cuff of cells surround-
mus, or T, cells were needed as "helpers" (Petrov ing the small blood vessels. Most of the cells were
1987). It was soon found that T cells were composed lymphocytes, with some phagocytic cells, the macro-
of helpers, suppressors, and cytotoxic cells. phages. The New York immunologist Sherwood Law-
Back in 1890, Robert Koch announced that he had rence insisted that he was able to transfer specific
found a cure for tuberculosis. He was injecting a sensitization with a cell-free extract from sensitized
secret substance, later admitted to be an extract of cells; he called his putative agent "transfer factor."
tubercle bacilli, which he called tuberculin. It pro- Other immunologists thought that there was some-
duced a striking flare-up of skin lesions in an in- thing wrong with his experiments. There were no
fected patient. But disappointingly, it was not a cure known soluble factors, other than antibody, or per-
(Koch 1891). The Viennese pediatrician Clemens haps antigen - Burnet thought it must be antigen -
von Pirquet, working on the "serum sickness" that that could transfer a specific sensitivity.
often followed the injection of diphtheria serum, rec- Throughout the 1960s, under the influence of the
ognized that the tuberculin reaction had some rela- clonal selection theory, more and more attention
tion to his concept of "allergy," or altered reactivity, came to be focused on lymphocytes. Byron Waksman
but it was independent of antibody and could not be and his group at Yale University found that they
transferred by serum. Others saw the same kind of could wipe out delayed hypersensitivity with anti-
lesion in chronic bacterial infections, and it came to lymphocyte serum, an experimental finding that
be called "infectious allergy" (Schadewaldt 1979). could be used clinically to prolong the life of trans-
The lesions were very characteristic: a hard red plants as well as to dampen autoimmune disease
lump that often had a black, necrotic center, which (Waksman, Arbouys, and Arnason 1961). Tissue cul-
developed slowly over a few days and took weeks to ture techniques improved, so that immune lympho-
heal. The reaction was thought perhaps to be respon- cytes could be watched as they responded to antigen
sible for the tissue destruction in tuberculous lungs, by beginning to proliferate. The relation of the two
and as "delayed hypersensitivity," to be quite sepa- types of cell in the lesions could be disentangled;
rate from protective immunity. antigen stopped the migration of macrophages away
In an era that concentrated on serology and protec- from a site, but it worked through the lymphocyte,

which produced a soluble "migration inhibition fac- tical medicine was marked by the appearance of
tor," the first of many such factors to be described. A more than one textbook of clinical immunology.
different group of T cells could be seen to kill the Waksman has called the decade beginning in
cells of foreign grafts or tumor cells. Activated 1980 the "holocene era," the era when everything is
macrophages, too, could kill normal cells, especially connected to everything else. That era had already
if the cells were coated with antibody. It was begun in the 1970s, with the work on cell-cell inter-
Wright's opsonic effect brought back to life. At- actions. The end of the decade saw interaction be-
tempts were made to apply this new knowledge to ginning between cell biologists with their culture
human pathology. Patients' lymphocytes were tested techniques and immunochemists and their se-
for their behavior with suspected antigens in some quence studies. The common meeting ground was
diseases thought to be autoimmune. now to involve not only cells and serum, but also
As Anne-Marie Moulin (1989) has pointed out, the genetics and molecular biology. The raw material
Cold Spring Harbor Symposium of 1967 marked the was provided by the myeloma proteins, each repre-
moment at which immunologists seem to have agreed senting a different immunoglobulin that could be
to accept the clonal selection theory. During the studied in isolation. By 1970 it was fully accepted
1960s, different domains of immunology had evolved that antibody diversity was genetically determined.
under the guidance of its heuristic influence. The The question was still, as it had been for half a
theory suggested new questions and demanded new century, how such tremendous diversity could be
techniques, particularly techniques for growing and genetically controlled.
manipulating cell cultures on the microscopic scale. Sequence studies had shown that the variable re-
These new techniques in turn laid bare dozens of new gion on the globulin was confined to one end of each
phenomena and relationships. An early indicator of chain and that these sites were separately coded in
the crossing over between the separate areas of immu- the genome. The number of genes for the variable
nology was the change of name around 1970 of de- regions was estimated to be perhaps no more than a
layed hypersensitivity, first to delayed (cellular) hy- thousand. Were all these genes to be found in the
persensitivity, then to cell-mediated immunity, as the germ line of every cell? Some immunologists, such
barriers disappeared between the work on antibody- as Jerne, argued that a small number of them were
producing clones of lymphocytes and the work on the but that this number was expanded by somatic muta-
lymphocytes of delayed hypersensitivity. tion in the individual after conception (Jerne 1971).
Cell-mediated immunity in the 1970s was, as The argument against this view was that the se-
Waksman has noted, completely redefined. More quences within variable regions fell into distinct
than 100 descriptions of new cellular phenomena groups, identical in all members of a species, and
were published over the 10 years (Waksman 1989). these appeared to be inherited in the regular Mende-
Many experiments showed that relationships be- lian fashion, making somatic mutation unlikely.
tween cells were mediated by soluble factors. Some Yet many workers had found that the 18 S
of these turned out to be capable of performing in globulin formed just after immunization seemed to
more than one experimental scenario. The first of show less variety of variable regions than the 7 S
them was the lymphocyte-stimulating factor re- that came later, suggesting that somatic mutation
leased by T cells that turned the B cells on to clonal could have occurred during clonal expansion. Evi-
proliferation. There was also a suppressor factor and dence for somatic mutation came in 1981 from Lou
a macrophage inhibitory factor, which kept the Hood and his group at the California Institute of
macrophage close to the active focus, and there were Technology. They used the hybridoma technique, de-
lymphotoxins, which were released by the "killer T veloped in the mid-1970s, to make a myeloma that
cells," or "K cells," that worked directly on a foreign produced antibody of a predetermined specificity.
target cell. It became possible to define the compli- Cells from a mouse myeloma were hybridized with
cated relationships that could exist among the tar- spleen cells from 19 different immunized mice. The
get cell, the immunoglobulin, and the macrophage variable-region sequences of the antibody globulins
or K cell, or between antigen—antibody complexes were compared with the germ-line sequence of
and effector cells. Transfer factor was now in good mouse DNA related to the antibody binding site. Not
company. As Sherwood Lawrence (1970) wrote, the all of the antibody sequences were identical: Half of
spell was broken, and the ambiguity that had so long them reflected the exact sequence as coded for in the
surrounded this branch of immunology was being germ line, but the others differed from one another
cleared up. The diffusion of this knowledge into prac- by one to eight amino acids. The germ-line sequence

was found in the 18 S globulin and the variants in ing programs (Cinader 1975). The first congress in
the 7 S (Crews et al. 1981; Clark 1983). It appears 1971 attracted about 4,000 participants, the sixth,
that the variable region is encoded by the germ-line held in Toronto in 1986, about 12,000. An expansion
genes but that further variants can arise after birth was clearly taking place.
and perhaps after stimulation by antigen. Clonal
expansion seems to generate new mutants, some of Conclusion
which respond to the antigenic stimulus by produc- A historian of science brought up on Thomas Kuhn's
ing a shower of new clones. Some of these clones may concepts of paradigm change and discontinuity in
produce an ever closer antigen-antibody match, science would probably want to ask whether the
rather as an animal species evolves to fill an ecologi- clonal selection theory and the massive expansion of
cal niche by natural selection. thefieldthat followed its acceptance could qualify as
the kind of gestalt shift that Kuhn had in mind. Was
The Clonal Selection Theory and the Field there a profound discontinuity between the thinking
As already mentioned, the Cold Spring Harbor Sym- of prewar serologists and that of cellular immunolo-
posium of 1967 was a marker for the point at which gists after 1957? In the author's opinion, there was
immunologists accepted the clonal selection theory. not. The new theory had the effect of enormously
It also marked the point at which the volume of enlarging thefield,uniting its domains, and linking
immunology research began to expand enormously. immunology to the broader biological sciences. But a
As Moulin has pointed out, the conception of the large part of the practice and theory of the prewar
immune apparatus as a system began to appear soon years was carried over, intact, to the synthesis of the
after 1967. A system implied a unified body of knowl- 1960s and 1970s.
edge as well as a complex mechanism with interact- The work on vaccines lost nothing in the transi-
ing parts. Significantly, it also provided a means of tion, although some of it has been less generally
formulating problems in a way that attracted grants useful since the coming of antibiotics. In some cases,
to solve them. It provided a framework for experi- it was the very success of the vaccination program
ment, if not a guarantee of experimental success that made its continuation unnecessary. In others,
(Moulin 1989). With the acceptance of the clonal such as that of diphtheria, the rarity of the disease
selection theory as a basis for research programs, in the West has made the serum treatment a thing of
the sudden expansion of immunology as a research the past, though diphtheria is still an important
field gave birth to a large number of specialist re- concern of the Haffkine Institute in India. Serologi-
search journals. Between 1970 and the date of writ- cal tests for disease are as important as they ever
ing in 1988, 47 new immunological journals came were.
into being. One of the most significant continuities has been
As part of the same surge of growth, immunolo- in blood grouping. As well as being directly utilized
gists began to create a formal international organiza- in hospital blood banking, the thinking about and
tion for themselves. Conferences on particular prob- techniques of blood group serology laid the concep-
lems, such as the one on tolerance in London in tual foundation for human genetics in general.
1957, the Antibody Workshop, which met irregu- Blood group genetics with its complex antigens and
larly between 1958 and 1965, and the Cold Spring its mathematical Mendelism provided a model on
Harbor Symposium of 1967, had always been of which human genetics, and the genetics of proteins
great importance to the workers in this very interna- and cells, could be patterned.
tional field (Porter 1986). But from 1968, with the On the theoretical side, Landsteiner's work on the
formation of the International Union of Immunologi- nature of specificity is probably more significant
cal Societies, the connections became structured and now than it was to most of his contemporaries, who
permanent. The First International Congress of Im- were more interested in the control of infectious
munology was held in Washington, D.C., in 1971. disease. The new findings extended rather than re-
One of the goals of the International Union was to interpreted his work, and immunologists continue to
demonstrate the range and power of the new immu- use his techniques. Of the ideas based on Land-
nology, as well as its applicability in medicine and steiner's template theory, only Haurowitz's was to-
industry, so as to promote the creation of indepen- tally discarded by clonal selectionists. Its destruc-
dent departments of immunology in universities and tion, in fact, had been essential to their program.
medical schools (as opposed to research institutes) Even if it had not been, it would have been run
and to encourage the expansion and funding of teach- aground sooner or later on the changes in protein

genetics and the central dogma. It was embedded in butions from the University Laboratory for Medical
the chemistry of the 1920s and 1930s, and there it Bacteriology to celebrate the inauguration of the State
had to stay. Colloid chemistry itself evolved away Serum Institute, ed. Carl J. Salomonsen. Copenhagen.
from the vitalism of its original exponents, but it Behring, Emil von. 1895. Leistungen und Ziele der Se-
was the source of the physical chemistry that devel- rumtherapie. Deutsche medizinische Wochenschrift
oped in Uppsala and of the work on the antigen- 21: 623-34.
antibody reaction. Bernard, Noel. 1960. Les Instituts Pasteur d'Outre-Mer.
L'Opinion Economique et Financiere 35: 86-92.
The elevated position of Ehrlich's theory in con- Bernstein, Felix. 1924. Ergebnisse einer biostatistischen
temporary immunology is rather paradoxical. On zusammenfassenden Betrachtung uber die erblichen
the one hand, its basic premises of perfect one-to-one Blutstrukturen des Menschen. Klinische Wochen-
specificity of antigen and antibody and firm chemi- schrift 3: 1495-7.
cal union of the covalent type had already been out- Besredka, Alexandre. 1921. Histoire d'une idie: L'oeuvre
grown by his contemporaries. His diagrams, like his deE. Metchnikoff: Embryogene, inflammation, immu-
terminology, seemed to pretend to a concrete knowl- nity, senescence, pathologie, philosophie. Paris.
edge that he did not really possess. In addition, the Bordet, Jules. 1896. Sur le mode d'action des serums pre-
side-chain theory needed a huge diversity of pre- ventifs. Annales de I'Institut Pasteur 10: 193-219.
formed antibody specificities. It was this weakness Breinl, Friedrich, and Felix Haurowitz. 1929. Chemische
that Haurowitz's instruction theory of antibody for- Untersuchungen des Prazipitates aus Hamoglobin
mation was meant to correct. But to our contempo- und anti-Hamoglobin-Serum und Bemerkungen iiber
die Natur der Antikorper. Hoppe Seylers Zeitschrift
raries, that was just the feature that gave Ehrlich's
fiirphysiologische Chemie 192: 45-57.
theory its lasting value: It was a selection theory, Burnet, Sir Frank Macfarlane. 1957. A discussion of im-
like the theories of the 1950s. Finally, Ehrlich's munological tolerance under the leadership of Sir
drawings of the side-chain theory are a visual meta- Frank Macfarlane Burnet, 8 March 1956. Proceed-
phor; they can represent a modern receptor as well ings of the Royal Society of London (Series B) 146:
as they did the receptor of 1900. Thus, Ehrlich has 1-92.
been given the role of an inspired precursor by his- 1967. The impact of ideas on immunology. Cold Spring
torically conscious immunologists of the 1980s (Ada Harbor Symposium on Quantitative Biology 32: 1-8.
and Nossal 1987). Burnet, Sir Frank Macfarlane, and Frank Fenner. 1949.
Finally, as Burnet himself saw, the conception of The production of antibodies. Melbourne.
the clone originates in bacteriology, and that of selec- 1962. The integrity of the body. Cambridge, Mass.
Chick, Harriette, Margaret Hume, and Marjorie Macfar-
tion, in a Darwinistic population genetics. The theory
lane. 1971. War on disease: A history of the Lister
was not a new one. Instead, it was an old one trans- Institute. London.
posed to a new and fertile setting, where it developed Cinader, Bernhard. 1975. Six years of the International
a truly explosive heuristic power. Rather than being Union of Immunological Societies: Presidential Re-
revolutionary, it placed immunology among the bio- port, Brighton, 1974. International Archives of Allergy
logical sciences of the twentieth century, sharing & Applied Immunology 48: 1-10.
with them their most fundamental assumptions. Clark, William R. 1983. The experimental foundations of
The history of immunology, in spite of its seeming modern immunology, 2d edition. New York.
discontinuities, is one of the evolution of a single Crews, S., et al. 1981. A single VH gene segment encodes
species: There are few extinctions in the fossil record the immune response to phosphoryl choline: Somatic
of this science. But then, it is only 100 years old. mutation is correlated with the class of the antibody.
Cell 25: 59-66.
Pauline M. H. Mazumdar
Crick, Francis H. 1957. On protein synthesis. Symposium
of the Society for Experimental Biology 12: 138-67.
Defines, R. D. 1968. The first forty years, 1914-1955:
Bibliography Connaught Medical Research Laboratories, University
Ada, Gordon L. 1989. Conception and birth of the clonal of Toronto. Toronto.
selection theory. In Immunology 1930-1980: Essays Delaunay, Albert. 1962. L'Institut Pasteur des origines a
on the history of immunology, ed. Pauline M. H. aujourd'hui. Paris.
Mazumdar, 33—40. Toronto. Ehrlich, Paul. 1887-8. Die Wertbemessung des Diphtherie-
Adan, Gordon L., and Sir Gustav Nossal. 1987. The clonal- heilserums. Klinisches Jahrbuch 6: 299-324.
selection theory. Scientific American 257: 62-9. Foster, W. D. 1970. A history of medical bacteriology &
Arrhenius, Svante, and Thorvald Madsen. 1902. Physical immunology. London.
chemistry applied to toxins and antitoxins. In Contri- Freund, Jules. 1956. The mode of action of immunological

adjuvants. Advances in Tuberculosis Research 7: Mazumdar, Pauline M. H. 1974. The antigen-antibody
130-48. reaction and the physics and chemistry of life. Bulle-
Geison, G. J. 1974. Pasteur. In Dictionary of scientific tin of the History of Medicine 48: 1-21.
biography, Vol. 10, ed. C. C. Gillispie, 350-416. New 1975. The purpose of immunity: Landsteiner's interpre-
York. tation of the human isoantibodies. Journal of the His-
Grubb, Rune. 1989. Interaction between immunology and tory ofBiology 8: 115-33.
genetics: Blood group systems as important early mod- 1989. The template theory of antibody formation. In
els and as tools. In Immunology, 1930-1980, ed. P. M. Immunology, 1930-1980, ed. P. M. H. Mazumdar, 1 3 -
H. Mazumdar, 131-42. Toronto. 32. Toronto.
Hartley, Sir Percival. 1945. International biological stan- 1990. The eugenists and the pauper class: The genetics of
dards: Prospect and retrospect. Proceedings of the human inferiority. London.
Royal Society of Medicine 39: 45-58. 1992. Eugenics, human genetics, and human failings:
Haurowitz, Felix. 1960. Immunochemistry. Annual Re- The eugenic society, its sources and its critics. London.
view of Biochemistry 29: 609-34. In press. Species and specificity: An interpretation of the
1963. The chemistry and functions of proteins. New history of immunology.
York. Mazumdar, Pauline M. H. ed. 1989. Immunology 1930-
Hogben, Lancelot. 1931. Genetic principles in medicine 1980: Essays on the history of immunology. Toronto.
and social science. London. Mechnikov, Ilya Ilyich. 1884. Ueber eine Sprosspilzkrank-
Jensen, Klaus. 1936. Report on international standards heit der Daphnien: Beitrag zur Lehre iiber den Kampf
maintained at the Statens Serum Institutet, Copenha- der Phagocyten gegen Krankheitserreger. Archiv fur
gen, Denmark, on behalf of the Health Organisation pathologische Anatomie und Physiologie und fiir
of the League of Nations. League of Nations, Quarterly klinische Medizin (Virchow) 96: 177-95, 2 plates.
Bulletin of the Health Organisation. Special number Miller, J. F. A. P. 1962. Effect of thymectomy on the immu-
on biological standardisation, II. November 1936, nological responsiveness of the mouse. Proceedings of
728-34. the Royal Society of London, Ser. B, 156: 415-28.
Jerne, Nils Kaj. 1955. The natural selection theory of Moore, Stanford, and William H. Stein. 1951. Chromatog-
antibody formation. Proceedings of the National Acad- raphy of amino acids on sulfonated polystyrene resins.
emy of Sciences of the U.SA. 41: 849-57. Journal of Biological Chemistry 192: 663-81.
1967. Summary: Waiting for the end. Cold Spring Har- Morris, C. J. O. R., and P. Morris. 1964. Separation meth-
bor Symposium on Quantitative Biology 32: 591-603. ods in biochemistry. London.
1971. The somatic generation of immune recognition. Moulin, Anne-Marie. 1989. Immunology old and new: The
European Journal of Immunology 1: 1-9. beginning and the end. In Immunology, 1930—1980,
Judson, Horace. 1979. The eighth day of creation: Makers ed. P. M. H. Mazumdar, 241-8. Toronto.
of the revolution in biology. New York. 1991. Le dernier langage de midecine: Histoire de
Koch, Robert. 1891. Weitere Mittheilung iiber das Tubercu- I'immunologie de Pasteur au SIDA. Paris.
lin. Deutsche medizinische Wochenschrift 17:1189-92. Nossal, G. J. V., and J. Lederberg. 1959. Antibody produc-
Landsteiner, K. L. 1901. Ueber Agglutinationserschein- tion by single cells. Nature 181: 1419-20.
ungen normalen menschlichen Blutes. Wiener klin- Parish, H. J. 1965. A history of immunisation. Edinburgh.
ische Wochenschrift 37: 1132-4. Petrov, R. V. 1987. Me or not-me: Immunological mobiles.
1909. Die Theorien der Antikorperbildung. Wiener klin- Moscow.
ische Wochenschrift 22: 1623-31. Porath, Jerker. 1960. Gel filtration of proteins, peptides
Landsteiner, K. L., and Merrill W. Chase. 1939. Studies on and amino acids. Biochimica et Biophysica Ada 39:
the sensitisation of animals with simple chemical com- 193-207.
pounds: VI. Experiments on the sensitisation of Porter, R. R. 1959. The hydrolysis of rabbit gamma-
guinea pigs to poison ivy. Journal of Experimental globulin and antibodies with crystalline papain.
Medicine 69: 767-84. Biochemical Journal 73:119-27.
Landsteiner, K. L., and H. Lampl. 1918. Ueber die 1973. Structural studies of immunoglobulins. Science
Abhangigkeit der serologischen Spezifizitat von der 180: 713-16.
chemischen Struktur (Darstellung von Antigenen mit 1986. Antibody structure and the Antibody Workshop.
bekannter chemischer Konstitution der spezifischen Perspectives inBiology & Medicine 29(3, pt. 2): S161-5.
Gruppen) XII Mitteilung uber Antigene. Biochem- Rubin, Lewis P. 1980. Styles in scientific explanation: Paul
ische Zeitung 86: 343-94. Ehrlich and Svante Arrhenius on immunochemistry.
Lawrence, Sherwood H. 1970. Editorial: Cellular immunol- Journal of the History of Medicine 35: 397-425.
ogy. Cellular Immunology 1: 1-2. Salomonsen, Carl Julius. 1902. The rise and growth of the
Marrack, John R. 1934. The chemistry of antigens and serum institute. In Contributions from the University
antibodies. Privy Council: Medical Research Council for Medical Bacteriology to celebrate the inauguration
Special Report Series No. 194, 82-7. London. of the State Serum Institute, 3-20. Copenhagen.

Schadewaldt, Hans. 1979. Geschichte der Allergie, Vol. 1. until the floury starch had been washed out, the
Munich. residual gluten had all the properties of animal tis-
Silverstein, Arthur M. 1979. Cellular versus humoral im- sues. Similar fractions were found in other plant
munity: Determinants and consequences of an epic foods. It was thought that these were the essential
19th century battle. Cellular Immunology 48: 208-21. nutrients, and it was the job of the digestive system
1982. Development of the concept of specificity, I and II.
to winnow away the unwanted starch, fiber, and so
Cellular Immunology 67: 396-409; 71: 183-95.
forth and leave the glutenlike material to be circu-
Sober, Herbert A., F. J. Gutter, Mary M. Wyckoff, et al.
1956. Chromatography of proteins: II. Fractionation lated in the blood, for patching and filling.
of serum protein on anion-exchange cellulose. Journal
of the American Chemical Society 78: 756-63. Protein
Spiegel-Adolf, Mona. 1930. Die Globuline. Leipzig. With the discovery of nitrogen as an element toward
Svedberg, The. 1938. Ueber die Ergebnisse der Ultracen- the end of the eighteenth century, and the develop-
trifugierung und Diffusion fur die Eiweisschemie. ment in France of methods for analyzing the amount
Kolloid Zeitschrift 85: 119-28. of nitrogen in different materials, came the discov-
Tiselius, Arne. 1938. Electrophoretische Messungen am ery that both animal tissues and the "animal-like"
Eiweiss. Kolloid Zeitschrift 85: 129-36. fractions in vegetables contained nitrogen, whereas
Waksman, Byron H. 1989. Cell-mediated immunity. In starch, sugar, fats, and vegetable fibers contained
Immunity, 1930-1980, ed. P. M. H. Mazumdar, 143- only carbon, hydrogen, and oxygen.
66. Toronto.
Waksman, Byron H., S. Arbouys, and B. G. Arnason. 1961.
After more work, mostly in Germany, it was con-
The use of specific lymphocyte sera to inhibit hyper- cluded that these nitrogenous compounds were
sensitive reactions of the delayed type. Journal of really all of one class, the proteins, and that they
Experimental Medicine 114: 997-1022. could be converted one to another by animals, but
that as a class they had to come from the vegetable
kingdom. Because they were considered the true nu-
trients, the value of a food or animal feedstuff could
be judged by its nitrogen content. It was also
thought that the force exerted in the contraction of
III.3 muscles came from the "explosion" and destruction
Nutritional Chemistry of some of their protein, with the subsequent break-
down of the residue to urea, a simple nitrogen com-
pound that the kidneys diverted into the urine. It
The idea that diet is an important factor in health is was therefore particularly important for those en-
a very old one and, if anything, had greater promi- gaged in hard physical work to have a high-protein
nence in the time of Hippocrates than it does now. diet, and on a dry matter basis, the foods highest in
However, the development of a workable system or protein were meat, cheese, and eggs.
science of nutrition had to await the development of As a corollary to this idea, carbohydrates (i.e.,
modern chemistry with its significant advances at starch and sugars) and fats were considered "respira-
the end of the eighteenth century. tory" foods. These were combusted in the body (i.e.,
Before that time, the purpose of nutrition in they reacted with oxygen) and this produced heat;
adults was assumed to be the replacement of this reaction, by "mopping up" oxygen in the tissues,
abraded (or worn-out) tissues. Meat, the tissues of was thought to protect the valuable protein from
other animals, seemed an effective food for this pur- oxidation.
pose, because it provided essentially like-for-like, Because people in affluent countries tended to eat
but vegetable foods seemed to be made of quite differ- more animal foods, and therefore more protein, it
ent "stuff." Animal tissues allowed to decompose was concluded that the extra protein gave them ex-
became putrid and alkaline, whereas most vegeta- tra energy, which, in turn, made them prosperous.
bles became acid and did not become putrid. When The diet chosen by healthy, hard workers in the
heated and dried, animal tissues became hornlike, United States was found to contain, typically, some
whereas vegetables became powdery. However, 120 grams of protein per day, and this was adopted
Iacopo Bartolomeo Beccari of the University of Bolo- generally as a recommended standard at the end of
gna pointed out in 1728 that, when sieved (i.e., the nineteenth century.
debranned) wheat flour was wetted and pummeled Once set, however, the whole pyramid of ideas
into a dough and then kept under running water collapsed with the discovery that physical labor did

III.3. Nutritional Chemistry 141
not cause a significant breakdown of muscle protein. 1830, attempts were made in England to assess what
Fats and carbohydrates were the main energy quantities of carbon and nitrogen were required for
sources for all forms of activity. Tests showed that 60 an adequate diet. (Hydrogen and oxygen could be
grams of protein per day could support health and supplied in the form of water.) There was a demand
vigor in an active man. However, in the early years at this time for objective, scientific answers to the
of the twentieth century, it was also discovered that problem of providing food for prisoners and inmates
all proteins were not nutritionally equal. Whereas of poorhouses that would support health without
protein molecules themselves were very large, typi- being superior to what was within reach of honest,
cally containing more than 10,000 atoms, boiling working laborers. The first estimate was that the
them in a solution of strong acid resulted in the average man required at least 300 grams of carbon
production of 20 or so fairly simple crystalline com- and 15 grams of nitrogen per day.
pounds, all of the same chemical class - the amino It had been demonstrated as early as the 1780s, by
acids. Later work showed that proteins had to be Antoine Laurent Lavoisier and others, that respira-
broken down to these constituent units in the digestion and combustion were similar processes, with
tive tract before absorption could take place. The carbon dioxide being an end product of each. By 1870
body proteins were then built up anew from these it had been shown that the heat produced by the
units, or building blocks, with each protein having a metabolism of food in the body was the same as that
fixed composition. produced by the combustion of food in the laboratory.
The practical significance of this is that humans, This made it possible to transfer the physicists' new
and other members of the animal kingdom, have thinking about the conservation of energy and the
the ability to convert some amino acids to others, mechanical equivalent of heat to nutrition. The con-
but about half of the amino acids must be provided tribution of carbohydrates and fats to the diet was
by the diet. These are called the essential amino then expressed not as so many grams of carbon, but
acids. In general, the mix of individual proteins as so many kilocalories of energy that would be
contained in foods, even those of plants, includes all released if they were metabolized to carbon dioxide
the amino acids, but the proportions differ. It was and water in the body. (The amount of heat required
demonstrated in 1915 that growth stopped in young to raise the temperature of 1 kilogram of water by
rats when the only protein they received was zein, a 1°C is 1 kilocalorie. This is the unit used in nutri-
particular protein fraction from maize containing tional literature, but commonly written as Kcal, the
none of the amino acids lysine and tryptophan. Ordi- K indicating that the unit is the kilogram rather
nary growth was restored by supplementing the than the gram unit.)
diet with both of these chemicals, proving that they It was possible to estimate the energy value of
were dietary essentials. In later experiments with foods by burning them in an atmosphere of pure
bean proteins, methionine (present in beans at a oxygen (to make complete combustion more rapid),
low level in relation to the requirements of ani- using a submerged metal casket (usually called a
mals) was determined to be the limiting factor for "bomb"), and measuring the heat released from the
growth. increase in temperature of the surrounding water.
For productive farm animals, with their high rates This "gross" figure needed correction for the propor-
of growth and reproduction, it has proved economic tion of the food that was indigestible. With ordinary
in some circumstances to supplement commercial human foods, this was only a small correction, and
diets with synthetic lysine or methionine. However, for practical purposes values of 4 Kcal per gram for
in practical human diets based on mixtures of foods, carbohydrates and 9 Kcal per gram for fats have
there is little evidence of a single amino acid being been found adequate. Protein not needed for new
limiting. An exception are the amino acid-deficient tissue synthesis and broken down also yields approxi-
diets of infants given some all-vegetable-protein for- mately 4 Kcal per gram. Energy requirements were
mulas as substitutes for milk. found to vary from as few as 2,000 Kcal per day in
sedentary men to as many as 4,000 Kcal in someone
Energy doing long hours of physical work. Women, in gen-
We return now to the role of carbohydrates and fats. eral, had lower requirements in proportion to their
After the realization that carbon, hydrogen, oxygen, smaller muscular frame. In practice, more than 90
and nitrogen together make up the great bulk of food percent of the food we eat is needed as fuel, that is,
materials, and the development of reasonably good as a source of energy, rather than for the replace-
analytic methods for their determination by about ment of worn-out tissue.

Vitamins that can be provided by an ordinary mixed diet.
Although the scientific evaluation of diets at the end Others, however, have recommended megadoses of
of the nineteenth century focused on protein and up to 1,000 milligrams per day, or even more, on the
energy, some realized that there were other require- principle that "if a little is good, more must be bet-
ments for a healthy diet. In particular, it was known ter," especially in resisting disease. In practice, such
that sailors on long voyages developed scurvy unless quantities can be obtained only by consuming the
they periodically ate fresh green vegetables or fruit. synthetic chemical.
Citrus fruit juice was particularly valued. James A continuing role of nutritional chemistry is that
Lind, a British naval surgeon, carried out a famous of determining whether new kinds of food processing
controlled trial on a group of scorbutic sailors in result in the destruction of vitamin C. For example,
1747. He found that a combination of oranges and potatoes have been important in protecting northern
lemons produced a rapid cure, whereas neither sulfu- Europeans from scurvy since their adoption as a
ric acid nor vinegar had any value. major food staple in the eighteenth century. How-
Lind believed that scurvy resulted from the debili- ever, the process whereby they are converted to "in-
tating effect of the moist air in ships at sea and that stant" mashed potato powder destroys most of their
the antiscorbutic factor in citrus fruits was not nor- vitamin C. Manufacturers therefore add synthetic
mally needed by people living on land. Nineteenth- ascorbic acid, so that the consumer receives the
century experience showed that this was not so. same benefit as that obtained from traditionally
Scurvy was a serious disease among those rushing to cooked potatoes.
the California gold fields in 1849, both when they Another disease that was associated with faulty
were en route by ox wagon and after they had ar- diet by the end of the nineteenth century was
rived. It caused thousands of deaths in the Allied beriberi, a potentially fatal condition first encoun-
armies during the Crimean War, and even broke out tered by Europeans in the Dutch East Indies and
during the relatively short siege of Paris in 1870-1. Malaysia. Statistics from prisons and elsewhere indi-
A lecturer at a London medical school had said in cated that it was associated with the use of white
1830: "Scurvy is a purely chemical disease . . . each (i.e., highly milled) rice, rather than the cruder
part of the body is ready to perform all its functions, brown rice. The initial explanation was that, with
but one of the external things necessary for its doing the outer protective layers removed, white rice
so is taken away." He compared the condition to the grains became contaminated by the penetration of
suffocation of someone deprived of fresh air. The toxic microorganisms through their porous surface.
"necessary thing" for preventing scurvy, he said, was In a period when microorganisms were found to be
contained in fresh animal and vegetable food. By responsible for so many diseases, the explanation
contrast, the diet of sailors and soldiers on active seemed plausible. However, when it was discovered
duty was normally restricted to dried and preserved that chickens that had developed the same disease
foods. His views were finally to be proved correct 100 when fed white rice could be cured by the addition of
years later. After a series of erroneous guesses as to the "branny layer" or "rice millings" to the white
the nature of the antiscorbutic factor, real progress rice diet, the explanation seemed less satisfactory.
was made when a report from Norway in 1907 indi- Next it was realized that, if other starchy foods were
cated that the disease could be reproduced in guinea substituted for white rice, the disease could still
pigs. This made it practicable to test different frac- occur. Finally, it was accepted that this disease, and
tions of lemon juice and other foods, to concentrate presumably others, could be explained by a lack of
the active factor, and finally to isolate it. This work something, rather by positive toxicity. This became a
was completed in 1932, and the chemical, called central concept in the development of nutritional
ascorbic acid (or vitamin C), was synthesized in views.
1933. Ascorbic acid proved similar to a sugar in its The first attempts to isolate and identify the
structure, and a daily intake of only 10 milligrams antiberiberi factor, using animals to test the activity
per day was sufficient to prevent scurvy. (This corre- of different materials, actually came before the corre-
sponds to approximately one-eighth of an ounce over sponding work on the antiscorbutic factor. In 1912
an entire year.) Casimir Funk suggested that the factor in rice bran
Since the discovery of vitamin C, there has been was a "vital amine," or "vitamine," and that a num-
some controversy as to how much is required for ber of diseases were caused by a dietary lack of min-
optimal health. The official recommendation in most ute amounts of this or similar organic compounds.
countries is from 30 to 75 milligrams per day, levels This proved to be true except that the compounds

III.3. Nutritional Chemistry 143
were not all of the chemical group called amines, and The function of vitamin D was next related to the
the term was reduced to vitamin. At least until the absorption of calcium and its deposition in bones.
chemical structures of the factors became known, Rickets, which characteristically results in bent legs,
they were listed as vitamins A, B, C, and so forth. And occurs when bones are soft and undermineralized.
when vitamin B, the water-soluble factor in yeast, The condition so prevalent in young children in Vic-
was realized to be itself a complex of factors, these torian cities was caused by inadequate irradiation of
factors were called Blf B2, B6, and so on. These code the skin, because of the pall of smoke from coal-
names have now been largely replaced by the corre- burning homes and industries and the use of starch-
sponding chemical names, which in this case are thia- based weaning formulas that lacked the vitamin.
mine, riboflavin, and pyridoxine for Bu B2, and B6. For a given amount of irradiation, less vitamin D is
Altogether 13 vitamins have been discovered. synthesized in people with pigmented skins than in
Some species need other organic compounds in people with less pigmentation. At the beginning of
addition to the vitamins required by humans; others the twentieth century, a mild case of rickets was
can synthesize vitamins. Dogs, pigs, and many other considered almost normal in the young children of
animals, for example, make their own vitamin C and black families who had migrated to northern indus-
thus thrive on a diet that would be scorbutic for trial cities in the United States. It is still a problem
human beings. among children of Asian immigrants in the United
Because the animal kingdom, as a whole, lives on Kingdom.
the vegetable kingdom, one would expect that all of Cobalamin (or vitamin B12), the last vitamin to
the vitamins we in the animal kingdom require date to be discovered (in 1948), is synthesized only
would be synthesized by plants. However, there were by microorganisms. Ruminant animals obtain it
some puzzling exceptions for investigators to un- from the bacteria living in their rumen (i.e., fore-
ravel. The first was vitamin A (or retinol), the fat- stomach), and others from food with adhering soil
soluble factor, the lack of which resulted first in an bacteria. Omnivores, humans among them, obtain
inability to see in dim light and then in ulceration of the vitamin from meat, fish, eggs, and milk.
the cornea of the eye and permanent blindness. The As with ascorbic acid, the development of chemi-
richest sources of the factor were fish liver oils; it cal analytic methods for determining the levels of
was colorless and had characteristic chemical proper- each vitamin in foods and the inexpensive produc-
ties. Yet green leafy foods also prevented the defi- tion of vitamins have enabled food manufacturers to
ciency, but apparently did not contain the same fortify processed foods with them - without unduly
chemical. Finally it was discovered that green leafy raising their prices. Thus, margarine has vitamins
foods contained a group of chemicals, the carote- A and D added at levels at least as high as those in
noids, yellow, orange or red in color, which acted as butter, for which it is a substitute. White rice is
provitamins - and were converted to the actual vita- fortified with thiamine, milk with vitamin D, and so
min in the body. on. In addition, many people in the more affluent
Another disease to be associated with the lack of a countries take vitamin pills, or capsules, to ensure
fat-soluble vitamin was rickets, and again workers that they are receiving a sufficient dosage or in the
engaged in studying the cause of the disease ob- hope of "superhealth," although there is no conclu-
tained apparently contradictory results. Some re- sive evidence that there is such a thing.
ported that they could cure rachitic puppies by giv-
ing them exercise, that is, taking them for walks, Minerals
without changing their diet. Others reported that The last class of long-recognized nutrients comprises
they could cure the condition not by giving the pup- minerals. Dried bones were known to consist mainly
pies exercise but by supplementing their diet with of calcium phosphate, and when other tissues were
fish liver oil - even if the oil had been oxidized so brought to red heat in a furnace, there was always a
that it had lost its vitamin A activity. This paradox small residue of incombustible ash, or mineral salts.
was resolved by a long series of studies showing that Up to about 1850 it was apparently assumed that a
an active factor (to be named vitamin D) was pro- practical diet would always supply a sufficient quan-
duced by the action of the sun's ultraviolet rays on tity of these minerals in humans, and even in fast-
sterols, such as cholesterol, which animals synthe- growing farm animals. Yet deficiencies can and do
sized for themselves. Vitamin D is synthesized in occur, as can be seen from a discussion of three
animal or human skin exposed to sunlight, after elements.
which it is stored in the liver. The fact that iron salts were an effective treat-

ment for chlorosis ("green sickness") in young Animals grazing in fields where the soil is low in
women was not at first regarded as the correction of particular elements are unproductive because the
a nutritional deficiency. Thomas Sydenham, for ex- plants they eat are also low in such elements as
ample, wrote in 1670 that a medicine made from copper, cobalt, and phosphorus. This problem is virtu-
steeping iron filings in wine and boiling the liquid ally unknown in human nutrition because of the
down to a syrup had the effect in cases of chlorosis of greater variety of our diets. However, iodine is one
"returning the pale and death-like face to a ruddy exception. This element was discovered in 1811, and
color and giving the pulse strength." But there was by 1820 its salts were already being used in the
no more suggestion of this being a nutritional use of treatment of goiter. This is a condition of gross swell-
iron than there was of mercury being a nutritional ing of the thyroid gland at the front of the neck. It
factor in the treatment of syphilis. had always been common in particular areas of the
By 1800, however, it was understood that blood world, usually those well away from the ocean. Tradi-
contained iron, and then that the level of iron was tional treatments with seaweed and the ash of
reduced in the paler blood of chlorotics. From 1830 sponges were explained by their high content of io-
pills containing ferrous sulfate were in standard use dine, and by the 1830s it was proposed that goiter,
for the treatment of chlorosis, or anemia as it came and the associated condition of cretinism in children,
to be known, and were considered to be generally was due to a deficient iodine intake. This was fol-
effective. lowed by the widespread use of iodine compounds,
German workers, however, who were in the lead often with bad effects, so that the theory became
from 1850 in carrying out quantitative balance stud- discredited. August Hirsch, in the English edition of
ies in model animals, became skeptical as to whether his Handbook of Geographical and Historical Pathol-
these pills actually contributed iron to the blood. ogy, published in the 1880s, referred to the "short-
When large doses of ferrous sulfate were given orally lived opinion" that iodine deficiency explained the
to dogs, the iron was recovered almost completely in problem and said that the evidence compelled one to
their feces, with little or none appearing in the urine. conclude that goiter and cretinism should be classed
This result contrasted with the results of the Ger- among the infective diseases.
mans' previous work on protein nutrition in dogs. Gradually, however, it came to be understood that
Proteins were absorbed almost entirely from the gut, relatively small excesses of iodine could be toxic, but
and those not immediately required were broken that a minimal average intake of 50 millionths of a
down, with the surplus nitrogen appearing in the gram per day was needed to avoid goiter. Indeed, the
form of urea in the urine. The scientists' first conclu- swelling of the thyroid produced by iodine deficiency
sion, therefore, was that inorganic iron salts were is apparently a feedback reaction whereby the body
indigestible and therefore useless in the treatment of attempts to capture more of the element in order to
anemia. But realizing that this was contrary to the use it for the synthesis of hormones. The prevention
clinical evidence, they hypothesized that the iron in of goiter is the only known role of iodine in animal
some way neutralized the harmful effects of bacteria organisms, but the stimulatory effect of hormones
in the gut, leading to better absorption of the natural extends to all tissues. Children born as cretins, be-
components of the food. cause of a lack of iodine, have irreversible brain
Further work showed that even iron salts injected damage.
into a dog's tissues failed to appear in the urine. In Extensive chemical analysis of foods and water
fact, it appears that animals and humans have essen- supplies have failed to explain the existence of goiter
tially no means of excreting surplus iron from tis- in a few areas of the world, and it is believed that
sues. The balance is maintained by carefully con- other factors may reduce either the bioavailability of
trolled absorption mechanisms that normally admit the iodine consumed or the effectiveness of the thy-
only as much iron through the gut wall as is re- roid hormone produced from it. Some such factors, in
quired by the tissues. However, even under condi- cabbage family plants, for example, are already
tions of acute deficiency, no more than 20 percent of known. However, even in these areas an increase in
iron in foodstuffs can be absorbed, and normally it the iodine supply has greatly reduced the incidence
may be only 1 to 2 percent. Mild anemia remains a of goiter and also of cretinism.
problem in many parts of the world, particularly for In most countries where the production of domes-
women on mainly vegetarian diets. They generally tic salt is organized in fairly large-scale units, it has
eat less than men but have a greater need for iron been found practicable to fortify it with up to 1 part
because of their loss of menstrual blood. in 10,000 of potassium iodide or iodate. This has

HL3. Nutritional Chemistry 145
proved an effective public means of preventing the much greater average income per head and far
disease. In areas where salt is not refined, those at more sophisticated sanitary and medical re-
risk are sometimes given an injection of iodized oil, sources. The major cause of the shorter life expec-
which can remain effective for as long as two years. tancy in the richer countries was the greater risk
In many affluent countries, chemists must ascertain of cardiovascular heart disease resulting in a
whether the consumption of iodine is excessive be- "heart attack." It also appeared that individuals in
cause of the increasing use of iodine-containing affluent communities were more subject to certain
chemicals for the disinfection of food-processing types of cancer.
equipment.
Another chemical element discovered in the same Rich Diets
decade as iodine is selenium. In the 1930s it was Among the factors considered to be potential con-
found to be present at toxic levels in plants grown on tributors to this condition was the "affluent diet."
soils rich in selenium in Wyoming and the Dakotas, Obviously, individuals' diets differed, but typical pat-
and responsible for disease among grazing sheep. But terns in the more prosperous Western countries re-
not until 1957 was it recognized as an essential nutri- vealed considerably higher levels of sugar, salt, and
ent. Farm animals have been found to be deficient in fat than existed in diets elsewhere. Almost all recom-
places as far apart as Sweden and New Zealand; these mendations up to that point had consisted of "at
animals have characteristic lesions in their muscles, least so much of this" and "don't risk being short of
including heart muscle. The major cause of keshan that," particularly to encourage maximum growth
disease in parts of China, in which children die with in the young.
characteristic changes in their heart muscle, is now But now there is an entirely new type of research
suspected to be selenium deficiency. on dietary factors that could have adverse long-term
effects when nutrients are consumed at high levels
Reassessments for long periods. One factor is total energy intake.
By the 1960s the status of nutrition could be summa- People whose intake is not limited by a shortage of
rized as follows: money and who burn fewer calories because they do
not engage in much physical work or exercise tend to
1. Apparently all of the chemical nutrients had been gain weight. Grossly obese people are, in general,
identified, so that it was possible to define an poor health risks - for diabetes, for example, as well
adequate diet in completely chemical terms. as for cardiovascular heart disease. One can calcu-
2. There was still a great deal of malnutrition late the number of calories a person needs to con-
among the poorest people on the earth, mainly sume to maintain an ideal weight, but appetite can
because of a lack of quantity of food. And the be compelling, and obesity is a problem for millions
coarsest foods were too bulky for the small stom- of people, in terms of both physical health and self-
ach capacities of newly weaned infants. The main esteem. Nutritional science has not been able to
problem was therefore one of economic distribu- provide a simple solution, though the dietary
tion of purchasing power and of the organization changes to be discussed next have been of some help
of food production rather than programs aimed at in this regard. (It should be noted that health risks
supplying specific nutrients. increase only with severe obesity. Many people feel
3. The main exceptions to this were the deficiency of compelled to become abnormally thin, and young
vitamin A in children in developing countries and women in particular may become seriously ill from
the large pockets of goiter and cretinism, also anorexia, that is, "failure to eat.")
mainly in developing countries. Again, there
were scientifically tested procedures for dealing Cholesterol and Fat
with these deficiencies, and their execution was a Cardiovascular disease involves the blockage of ar-
matter for government programs of education and teries that provide oxygen within the muscular
public health, with technical support. walls of the heart. The death of even a small portion
4. The populations of the most affluent countries had of this muscle from lack of oxygen can result in the
diets that in general provided most of the recom- disorganization of the heartbeat and thus a failure of
mended levels of nutrients. Yet life expectancy at the heart to meet the body's oxygen needs. The
age 5 in a country such as Cuba or Panama was plaques that build up in blood vessels and that nar-
greater than that for corresponding children in a row the flow of blood contain a high proportion of
country like the United States or Sweden, with a cholesterol. The typical diet of affluent Westerners

with their high intake of animal foods (i.e., meat, years, a lower incidence of cancer of the colon among
eggs, and dairy products) is rich in cholesterol. One communities isolated from sophisticated Western
recommendation, therefore, has been to lower choles- food products has prompted the suggestion that
terol intake, in particular the intake of egg yolks these people are protected by the higher fiber con-
(even though in the past eggs were regarded as the tent of their diets. Perhaps the greater volume of
perfect food because they contained everything the material in the colon dilutes any carcinogenic com-
rapidly growing embryonic chicks needed). pounds present. It is thought that gut bacteria may
Cholesterol, however, is a vital constituent of cell produce such carcinogens by acting on bile acids.
walls, and we, like other animals, synthesize it con- Of course, differences among communities in the
tinuously, regulating that synthesis (at least to some incidence of colon cancer can be explained by things
extent) according to dietary intake. Some studies other than diet. However, genetics does not appear
indicated that people with high blood levels of choles- to be one of them, because, in general, after two
terol were at greater risk from cardiovascular heart generations, emigrant groups seem to have a disease
disease. But evidence mounted that cholesterol lev- pattern similar to that of their hosts. Moreover,
els in the blood were affected more by the dietary some studies have confirmed the importance of diet
intake of saturated fat than by simple cholesterol in colon cancer; there tend to be fewer cases among
intake. "Saturated," in this context, means satu- vegetarians than among other groups. Vegetarians
rated with hydrogen. In practice, saturated fats are obviously have a lower intake of fat and animal
those, like beef or mutton fat, butter, and some types protein than do others, and they consume more vege-
of margarine, that are solid at room temperature. tables and more fiber.
In contrast, most vegetable fats, which are called Vegetables are extremely complex mixtures of
"oils" because they are normally in the liquid state - natural, "organic" chemicals. Some believe that,
for example, corn oil and olive oil - are more unsatu- rather than fiber, the green and yellow vegetables
rated. Margarines are made from vegetable oils that that are the principal sources of carotenoids in our
are saturated by hydrogen to various extents. Soft, diet may provide protection against colon cancer. The
or "tub," margarines are the least saturated. Of cur- protective factors could also be other chemicals found
rent interest is whether the fat content of the "afflu- in some vegetables more than others. For example,
ent diet," in which fats typically provide 40 percent there is a class of compounds, including pectins and
of the calories, should be reduced or whether there is gums, that are not digested in the small intestine
something about unsaturated fat that counteracts along with starch, but are rapidly fermented by bac-
the adverse effects of animal fats. In particular, the teria when they reach the colon. They are now sub-
"omega-threes" found in fish oils are under intensive sumed within the overall term dietary fiber, though
study. Also, strong evidence exists that people with they may in some respects produce effects that differ
high blood pressure (hypertension) are at increased from those of the largely unfermented cellulose.
risk from cardiovascular heart disease, and that a Research in thefieldof nutrition is inevitably slow.
high salt intake promotes this condition. Diseases appearing mainly in middle-aged humans
cannot be modeled with certainty in short-term ani-
mal trials. In the meantime, nutritionists' most com-
Dietary Fiber mon advice, after the admonition to get more exer-
Modern food industries have been able to process cise and stop smoking, is to consume a "prudent" diet
seeds and vegetables so as to extract the fat and sugar modeled on the traditional Mediterranean peasant
or, in the case of grains, to mill off the outer branny diet, with a predominance of cereals, vegetables, and
layers to yield white rice or white wheatflour.The fruit, a sparing amount of meat, preference being
public, in general, prefers sweet foods that "slip given tofishand chicken, and a moderate amount of
down" easily because of their fat content and contain dairy products that are low in fat.
nothing "scratchy in the mouth." The fibrous resi-
dues from the processing of foods of this type have
been used to feed farm animals. Ruminants, in par- Summary
ticular, are able to ferment and utilize cellulose. The first problem for nutritional science, to identify
In the past it was thought that, because "rough- the chemicals required in a diet to support growth
age" apparently passed through the gut unchanged, and maintenance, has been solved. The deficiencies
the fiber had no significance as long as people had involved in diseases such as scurvy and beriberi
just enough not to become constipated. But in recent have been identified. The adequacy of diets can be

III.4. Diseases of Infancy and Early Childhood 147
determined and the deficient nutrients supplied.
The problems of malnutrition are now largely politi- m.4
cal and economic. Another problem for nutritional
science is to ascertain which components of our foods Diseases of Infancy and Early
either enhance or reduce our resistance to chronic Childhood
disease. This work is still at an early stage.
Kenneth J. Carpenter
In ancient times physicians wrote primarily on the
Bibliography care of infants, and only incidentally about chil-
Beccari, I. B. 1728. Defrumento. (English translation in C. dren's diseases, because their concept of medicine
H. Bailey [1941], A translation of Beccari's lecture stressed the maintenance of health rather than the
"Concerning grain," Cereal Chemistry 18: 555-61.) diagnosis of specific disease entities (for medical
Carpenter, K. J. 1986. The history of scurvy and vitamin C. perspectives on children during antiquity, see
New York. Etienne 1973). The earliest of these "pediatric"
Goodman, D. C. 1971. The application of chemical criteria texts known to us was that of Soranus of Ephesus
to biological classification in the eighteenth century. (active around A.D. 100), On Gynecology, which in-
Medical History 15: 23-44. cluded 23 chapters on infant care (see Soranus
Greenwald, P., E. Lanza, and G. A. Eddy, 1987. Dietary 1956; also Ruhrah 1925; Still 1931; Garrison 1965;
fiber in the reduction of colon cancer risk. Journal of Peiper 1966). First, Soranus gave instructions on
the American Dietetics Association 87: 1178—88. sectioning the umbilical cord, feeding, swaddling,
Guggenheim, K. Y. 1981. Nutrition and nutritional dis-
choosing a wet nurse (if necessary), bathing the
eases: The evolution of concepts. Lexington, Mass.
Holmes, F. L. 1964. Introduction to "Animal Chemistry by
baby, and other activities essential to infant care.
Justus Liebig." Sources of Science No. 4: vii-cxvi. Then he discussed the treatment of common disor-
1975. The transformation of the science of nutrition. ders of infancy, including teething, rashes, and
Journal of the History of Biology 8: 137-44. "flux of the belly," or diarrhea.
Ihde, A. J., and S. L. Becker. 1971. Conflict of concepts in Soranus was a leader of the Methodist sect at a
early vitamin studies. Journal of the History of Biol- time when Greek medicine was enlivened by various
ogy 4: 1-33. contending schools of thought. Methodism taught
McCollum, E. V. 1957. A history of nutrition. Boston. that disease was due to excessive relaxation or con-
National Research Council. 1980. Recommended dietary traction of internal pores of the body, leading to
allowances. Washington, D.C. immoderate secretion and moisture in the first in-
Stockman, R. 1895. Observations on the causes and treat-
stance and to diminished secretion and dryness in
ment of chlorosis. British Medical Journal 2: 1473-6.
Yetiv, J. Z. 1986. Popular nutritional practices: A scientific
the second. The cause of disease was considered un-
appraisal. Toledo, Ohio. important, stress being laid instead on treatment
that, crudely put, consisted of inducing the contrary
state, drying the moist or humidifying the dry. In his
section on infant management, Soranus concen-
trated on the practicalities of care and treatment
without slavish adherence to the tenets of Method-
ism. The result was a pragmatic guide uncompli-
cated by theoretical or speculative overtones.
During the second century, Claudius Galen inau-
gurated a radical change in perspective by setting
out his own complex theoretical synthesis. In so do-
ing he established humoral theory, already several
hundred years old, as the main guide to understand-
ing health and disease. He was so successful that for
the next 1,500 years humoral doctrine permeated
most medical writings, including those on children
and their diseases (for a guide to humoral theory, see
Ackerknecht 1968).
According to this doctrine, the four elements,
earth, fire, air, and water, were related to four quali-

ties, hot, dry, cold, and wet. These qualities in turn cal conceptions of disease and its relation to health,
interacted with the four humors of the body, blood, see Riese 1953; Temkin 1977.)
phlegm, yellow bile, and black bile. Well-being de- The interplay between the humoral and ontologi-
pended on the humors being in balance. Illness came cal interpretation of disease can be illustrated by an
about when one or more humors became predomi- examination of medieval and early modern descrip-
nant either for internal, constitutional reasons or tions of measles and smallpox. Rhazes, an Arab phi-
because of external strains, usually dietetic or clima- losopher and physician at the turn of the tenth cen-
tic. To restore health required ridding the body of tury, wrote a text on children, Practica puerorum,
excess humors either actively, through drugs, purg- unusual for the times in that it dealt only with
ing, vomiting, or bloodletting, or passively, by main- diseases and ignored infant management (for an En-
taining the patient's strength while trusting nature glish translation and analysis, see Radbill 1971).
to restore the natural humoral state. Hippocratic Rhazes also penned a treatise on smallpox and mea-
physicians had favored the latter, expectant method, sles, which he distinguished between but considered
whereas Galen advocated the former, more energetic to have the same cause: putrefaction and fermenta-
course of action. tion of the blood. Whether a person exhibited the
Book 1 of Galen's Hygiene, entitled "The Art of symptoms of smallpox or those of measles depended
Preserving Health," contains five chapters on the on humoral constitutions (see Rhazes 1939).
care of the newborn and young child. Milk, accord- Until about the seventeenth century, physicians
ing to Galen, was the ideal food for infants "since followed Rhazes' example in describing the two dis-
they have a moister constitution than those of other eases under the same heading. Thomas Phaire, a
ages" (Galen 1951). Infants were also warm by na- Welsh physician whose pediatric text, published in
ture, and "in the best constituted bodies," this qual- 1545, was the first to appear in the English lan-
ity would remain constant until adolescence, when it guage, began his chapter on smallpox and measles
would increase in intensity. In contrast, the normal thus: "This disease is common and familiar . . . it
body would steadily dry out from infancy onward to hath obtained a distinction into two kinds: that is to
reach desiccation in old age. In addition, there were say, varioli the measles, and morbilli, called of us the
individual differences, inborn divergences from the smallpox. They be both of one nature, and proceed of
ideal constitution, that would require special man- one cause, saving that the measles are engendered of
agement, but these were not specifically discussed in the inflammation of blood, and the smallpox of the
Galen's Hygiene. inflammation of blood mingled with choler [yellow
However, the concept of constitutional change dur- bile]" (Phaire 1965).
ing growth and development, associated with that of In the following century an English physician,
innate differences in temperament or constitution, Thomas Sydenham, provided the first description of
gave great flexibility to humoral theory and an al- measles per se, as well as of scarlet fever and
most limitless explanatory power. In part because "chorea" (St. Vitus dance, Sydenham's chorea). He
the theory was so intellectually satisfying, its valid- did so on the basis of clinical observation while re-
ity was not seriously questioned until about the six- taining a humoral interpretation of cause and treat-
teenth century. Even after the surfacing of doubts, ment. That Sydenham could be innovative while
humoralism survived, in various eroded forms, into still adhering to humoral theory was due in part to
the nineteenth century. In contrast to the modern his conviction that diseases could be classified into
ontological concept of diseases as specific entities species, as were plants and animals. In giving advice
(each with its own cause, natural history, and cure), on medical reform, he stated: "It is necessary that all
under humoral doctrine illness was considered a per- diseases be reduced to definite and certain species,
sonal manifestation of humoral imbalance due to and that, with the same care which we see exhibited
environmental stress interacting with the individ- by botanists in their phytologies" (Sydenham 1848;
ual's own special constitution. However, the dichot- Yost 1950). Sydenham himself never published a
omy was not absolute, because ancient physicians nosology, but his advice was repeatedly heeded in
recognized some diseases as specific entities and the eighteenth century, Carl von Linn6 (Linnaeus),
named them according to presumed anatomic site or the great plant and animal taxonomist, being one of
to cause. Thus, the Hippocratic writings described the first to produce a classification of diseases.
phthisis (tuberculosis), pneumonia, and pleurisy, Nosology did not prosper in pediatrics, where
and in succeeding centuries such distinctions be- eighteenth-century physicians continued to list
came more common. (For fuller discussions of histori- symptoms and diseases unsystematically. Yet it was

one of Sydenham's pupils, Walter Harris, who first hydrocephalus (reprinted and discussed in Ruhrah
diverged from classical humoral theroy. In his Trea- 1925). Whytt gave an excellent clinical account of
tise of the Acute Diseases of Infants (published in this condition, which, however, would not be recog-
1698 in Latin) Harris insisted that the prevailing nized as meningitis due to tuberculosis until the
cause of illness in infancy was excess acidity. Cure early nineteenth century. The regular practice of
involved neutralizing and absorbing the acid with performing autopsies began with the advent of chil-
"testaceous powders" such as powdered oyster shell, dren's hospitals, which were introduced in Paris af-
crab's claws, egg shell, chalk, coral, mother of pearl, ter the French Revolution. The Enfants Malades
and burned ivory. The residue was then removed by was established in 1802 for sick children over the
purgation. Harris recommended rhubarb, a mild age of 2 years and the ancient foundling hospital,
laxative by the standards of the time. the Enfants Trouves, was reorganized to accommo-
For the next 100 years, until the early nineteenth date ailing babies as well as unwanted ones.
century, Harris's acid theory was predominant. From contemporary reports one gathers that physi-
George Still (1931) has suggested that its popularity cians were rarely refused permission to perform au-
was due to its simplicity. The old humoral pathology topsies (Crosse 1815). With a relatively large num-
no longer seemed a reliable guide: it had become ber of children under their care, hospital doctors
very complex because commentators felt free to could also apply the so-called numerical method, a
amend it to suit themselves. In contrast, Harris sup- rudimentary statistical analysis by which mortality
plied his readers with a simple cause and remedy for as well as complication and recovery rates could be
most early childhood ailments. assessed (Ackerknecht 1967). Under this system cer-
The late eighteenth century witnessed a revolu- tain diseases, such as early childhood tuberculosis,
tion in chemistry. Owing to experimental input from could now be recognized and reported. Whytt's
many natural scientists and to Antoine Lavoisier's "dropsy of the brain" was classified as a manifesta-
deductive genius, much time-honored knowledge tion of tuberculosis when it was discovered that the
was discarded. This included the Aristotelean doc- disease was associated with granular tubercular de-
trine of the four elements so intimately related to posits on the membranes covering the brain (Papa-
humoral theory, which was replaced by propositions voine 1830).
that became foundational to modern chemistry. The French pediatricians attempted to classify chil-
revised science had swift repercussions in medicine, dren's diseases, whereas, as already mentioned, ear-
including pediatrics. Previously, physicians and oth- lier authors had dedicated chapters with complete
ers had evaluated the quality of milk on sight, by impartiality to symptoms (e.g., nightmares, sneez-
tasting, or through a nail test originally credited to ing, hiccoughs) and to specific morbid conditions
Soranus that involved assessing the consistency of (e.g., mumps, measles, smallpox). In 1828 Charles
milk by pouring a drop on the fingernail and watch- M. Billard published a text exclusively on infant
ing the rate of spread (Soranus 1895; Still 1931). diseases, which he classified according to the site of
Now, both human and animal milk could be sub- the main lesion: skin infections, those of cellular
jected to chemical analysis. In the 1799 edition of his tissue, of the digestive tract, of the respiratory and
pediatric text, the English surgeon-midwife Michael cardiac systems, of nervous or cerebrospinal origin,
Underwood (1806) discussed and tabulated the com- of the locomotor and generative systems, and finally
parative properties of human and animal milk. congenital disorders. Frederic Rilliet and Antoine
Early in the nineteenth century, chemists were sup- Barthez, authors of a general pediatric treatise first
plying information on the nitrogenous (protein), fat, published in 1843, used a different method. Diseases
carbohydrate, and mineral content of common food- were classified primarily according to underlying
stuffs. However, vitamin detection was delayed until pathology: phlegmasias (inflammations), hydropsies
the twentieth century with consequences that will (accumulation of watery fluid), hemorrhages, gan-
be discussed in the section on deficiency diseases. grenes, neuroses, acute specific diseases, the various
In the second half of the eighteenth century some kinds of tuberculosis, and finally entozoan (para-
medical men, notably Giovanni Morgagni and John sitic, caused by various worms) diseases. Under
Hunter, stressed the need to correlate clinical signs these headings, further subdivisions were made ac-
during life with later autopsy findings. This ap- cording to the site affected (Barthez and Rilliet
proach was occasionally used in the eighteenth- 1853).
century pediatrics, by Robert Whytt, for example, in In early-nineteenth-century Paris, with children's
his observations on dropsy in the brain or acute hospitals growing in number and size, pediatrics

emerged as a specialty inasmuch as physicians there Cross-infection had frequently ravaged pediatric
could engage full time in the care of children. They wards in the early nineteenth century; hence, with
published extensively, stimulating interest in pediat- the discovery that microorganisms caused conta-
ric research abroad, although in the United States gious diseases, the isolation of potentially infective
and in Britain physicians continued throughout the patients seemed an obvious solution. As Harry Dowl-
nineteenth century to be generalists rather than ing (1977) points out, between 1880 and 1900, 21
specialists (for the history of pediatrics in the United microorganisms were identified as the causes of spe-
States, see Cone 1979). At first, the concept of pediat- cific diseases, including the bacilii responsible for
ric hospitals did not gain approval in English- tuberculosis, typhoid fever, and diphtheria. Also dis-
speaking countries for a variety of reasons, some of covered were the pneumococcus and meningococcus
which are remarkably consonant with modern opin- associated with the common forms of pneumonia and
ion. It was said that children, especially babies, meningitis, and the streptococcus whose hemolytic
should not be separated from their parents and form produced scarlet fever and rheumatic fever. Yet
would have a better chance of recovering at home knowing the causes of these illnesses was not imme-
than in hospitals, where, as evident from the Pari- diately helpful. More obvious benefits would have to
sian reports, cross-infection was rife (Anon. 1843). await specific vaccines and antibiotics.
On Malthusian and moral grounds, Henry Broug- Babies continued to die at a steady rate. As histori-
ham held that "the gratuitous maintenance of poor ans have frequently indicated, in England the infant
children, may safely be pronounced dangerous to mortality rate did not decline during the nineteenth
society, in proportion as it directly relieves the par- century, hovering between about 140 and 160 per
ent from his burthen. It removes the only check upon 1,000 from 1839, when national vital statistics were
improvident marriages, and one of the principal first recorded, until 1900, even though all other age
guards of chastity" (Brougham 1823). With Broug- groups exhibited a falling death rate from midcen-
ham, foundling hospitals were the prime but not the tury onward (Logan 1950; McKeown 1976; F. B.
exclusive subject of contention. Nevertheless, by the Smith 1979; Winter 1982; Wohl 1983; Dwork 1987).
1850s opinion had changed sufficiently to allow for Most other countries that kept vital statistics
the establishment of pediatric hospitals, albeit small were looking at similar trends. In Massachusetts,
ones initially, in the United States and Britain. One the earliest state to keep continuous records, the
reason for the change was pressure from physicians infant mortality rate was similar to that of England.
who argued that the intensive investigation of pedi- During the second half of the nineteenth century,
atric disease required a hospital base (Anon. 1849). Massachusetts reported the highest infant mortality
For the next hundred years, pediatric hospitals and rate of 170 for the years 1870 to 1874 and the lowest
clinics served as sites of further investigation and of 123 for the years 1855 to 1859; for 1895 to 1899
treatment of disease. After World War II, however, the rate was 153 (U.S. Bureau of the Census 1960).
the earlier concept that babies and small children The French and Germans reported even higher in-
should not be separated from their mothers surfaced fant death rates; in 1895 the French infant mortality
again with renewed intensity. Psychoanalysts in par- rate was 177, the German one 230 (Mitchell 1975).
ticular drew attention to the long-term emotional However, the Scandinavian countries and Ireland
effects of maternal deprivation, most evident in chil- were doing much better, with lower and falling in-
dren reared in orphanages but also demonstrable in fant death rates during the second half of the cen-
babies hospitalized for acute disease or for surgery. tury, demonstrating that much loss of life elsewhere
Most influential perhaps was the 1951 report pre- was unnecessary. In 1895 the infant mortality rate
pared by John Bowlby (1951) for the United Nations in Norway was 96, in Sweden 95, in Denmark 137,
program on the welfare of homeless children, but as and in Ireland 104 (Mitchell 1975). In England, re-
early as 1942 Harry Bakwin, a pediatrician, had gional statistics showed that infant mortality was
drawn attention to apathy in babies confined to hospi- often twice as high in industrial areas as in rural
tals. Indeed, from the mid-nineteenth century on- ones, which, together with the Scandinavian experi-
ward some physicians had opposed the isolation of ence, suggested that predominantly agricultural so-
infants, but the dictates of hospital organization and cieties exhibited conditions most favorable to infant
fears of cross-infection severely restricted parental survival (for contemporary discussions, see Jones
access to their children until the psychoanalytic con- 1894; Newman 1907). Industrial areas were more
cept of maternal deprivation was elaborated in the lethal, it was often concluded, because so many moth-
1950s. ers went out to work, abandoning their babies to

casual care and bottle feeding. Dirt and environmen- probably contributed significantly to the high infant
tal pollution, including food contamination, were mortality. Chronically undernourished women gave
seen as secondary to the damage caused primarily birth to puny, sickly babies ill-equipped to withstand
by a lack of breast feeding. exposure to infection and the other hazards prevail-
According to English vital statistics, the main killing in a working-class environment, such as cold and
ers of infants were "atrophy" and debility, pulmonary damp housing and an inadequate diet. On the whole,
diseases (bronchitis and pneumonia), convulsions however, Victorian physicians did not consider pov-
and meningitis, diarrheal diseases, and tuberculosis erty and its consequences to be responsible for the
(Newman 1907). In the United States the picture was unacceptably high infant mortality rate. Instead,
similar, except that diarrheal diseases accounted for they focused on the dangers of artificial feeding;
a larger porportion of deaths, while pulmonary dis- influenced by middle-class expectations and stan-
eases were less prominent than in England (Cone dards, they berated women for going out to work,
1976). By the last third of the nineteenth century, leaving their infants to be bottle-fed and possibly
smallpox, which formerly had been particularly haz- drugged by ignorant baby minders. It apparently did
ardous to babies, no longer accounted for many not occur to them that a mother's earnings might be
deaths, probably owing to widespread vaccination in essential for family survival, probably because a
the first months of life. But otherwise, medical prog- working mother was so contrary to the general Victo-
ress, including the recognition of microorganisms as rian image of womanhood.
the cause of infectious diseases, seems to have had By the onset of the First World War, infant mortal-
little relevance to the plight of infants. The diarrheal ity had fallen significantly in most European coun-
diseases, for example, included a variety of conditions tries and in the United States. The infant mortality
that defied simple classification. Job Lewis Smith, a rate for Massachusetts dropped from 141 in 1900 to
noted New York pediatrician, discussed simple diar- 116 in 1914 (Woodbury 1926). In England and Wales
rhea, intestinal catarrh or enterocolitis, the dreaded the reduction was from 154 in 1900 to 105 in 1914.
cholera infantum, enteritis, and colitis in the 1890 Some of this abrupt change must be attributed to
edition of his Treatise on the Diseases of Infancy and factors that had emerged in the nineteenth century
Childhood. Infantile cholera, the most acute and se- but had taken time to prove beneficial, for example,
vere type, was so called because its symptoms were so better nutrition for the population at large leading
similar to those of epidemic cholera. Diarrheal dis- to the birth of healthier babies (for discussions of the
eases were more common and fatal in the hot summer reasons for the decline of mortality at the turn of the
months, but the hot weather alone could not be re- century, see Woodbury 1926; McKeown 1976; Dy-
sponsible because summer diarrhea caused less harm house 1978; F. B. Smith 1979; Dwork 1987). The
in rural areas. Smith therefore subscribed to the contribution of direct medical intervention to the
time-honored view that the cause was related "to the initial decline in mortality remains debatable, but
state of the atmosphere engendered by heat where progress in the understanding of disease began to
unsanitary conditions exist, as in large cities." Once, exert observable effects on infant survival after
out of deference to germ theorists, he sent intestines World War I.
from a child who had died of cholera infantum for So numerous were the twentieth-century break-
examination by William H. Welch. The report was throughs in understanding pediatric disease that
inconclusive because all kinds of bacteria were found only a brief summary can be attempted here. A list-
on the surface of the intestines. Still, Victor C. ing of important disease categories is accompanied
Vaughan, professor of hygiene and physiological by a short discussion of how changes in traditional
chemistry at the University of Michigan, was confi- thinking gradually provided a new basis for reme-
dent that the diarrheas were caused by toxin- dial action.
producing bacteria. In his opinion, "there is not a
specific micro-organism, as there is in tuberculosis, Diseases Related to Infant Feeding
but any one or more of a large class of germs, the Infant nutrition is intimately connected with health.
individual members of which differ from one another Breast feeding was always recognized as the ideal
sufficiently morphologically to be regarded as dis- method of nourishing infants but was not always
tinct species, may be present and may produce the practicable. If a mother was unable or unwilling to
symptoms" (Vaughan 1897). suckle her baby, wet nursing was a socially accept-
Recent historians, particularly Anthony S. Wohl able alternative until the beginning of this century.
(1983), have pointed out that maternal malnutrition In poorer families, however, nursing could be re-

placed only by artificial feeding. A fourth option, Lait, rapidly being established all over France, en-
direct suckling from an animal, commonly the goat, couraged artificial feeding. But soon the two men
was sometimes adopted on the European continent. compromised and together organized the first inter-
The literature on infant feeding is enormous (for national conference on infant welfare (Congres Inter-
comprehensive historical studies, see Wickes 1953; national des Gouttes de Lait, 1905) held in Paris.
Cone 1976; Fildes 1986). By the nineteenth century, Similar movements were developing in other coun-
physicians in the United States and Britain tended tries. As early as 1893, the philanthropist Nathan
to discourage wet nursing because of the adverse Straus began organizing the distribution of pasteur-
effects on the nurse's own infant, who was usually ized milk for children under 5 years of age in New
abandoned to foster care and the bottle. Efforts were York City (Straus 1917). At about the same time,
directed toward increasing the safety of bottle feed- Henry L. Coit arranged for the production of certi-
ing, perceived as the most important cause of high fied milk in Newark, New Jersey (Blake 1953).
infant mortality. In 1867 Justus von Liebig, the re- These pilot schemes demonstrated the possibility of
nowned German chemist, marketed an infant food ensuring a clean milk supply, although because of
prepared on scientific principles (Drummond and the expense involved city authorities only gradually
Wilbraham 1958). It was not as perfect as he as- adopted similar methods to ensure safe milk for all
sumed (vitamins were then undreamed of), but it inhabitants. Rapidly disappearing, however, was
was the forerunner of an endless variety of propri- the nineteenth-century conviction that breast feed-
etary infant foods. Many contained only powdered ing was the only safe way of nourishing infants. The
carbohydrates and thus, if not made up with milk new century ushered in greater professional accep-
and supplemented with other foods, could not begin tance of bottle feeding, spurred on by the availabil-
to nourish an infant (for a discussion of interactions ity of methods of checking the purity of milk and its
between physicians, infant food companies, and bacterial content and of sterilization and pasteuriza-
mothers, see Apple 1981). tion. Also novel was the awareness that incipient
A somewhat different situation prevailed in illness was often indicated by the failure of a baby's
France, where it had become common practice by the height and weight to increase, measures that were
eighteenth century for infants to be sent into the easy to monitor on a regular basis.
countryside to be wet-nursed together with the foster However, as will be discussed in the next section,
mother's own baby (Sussman 1982). Infant mortality not until the 1920s was it understood why infants
was even higher than in English-speaking countries, fed sterilized milk, or proprietary foods, might not
the fertility rate was lower, and in part because of the thrive unless also given supplements such as orange
threat of depopulation, concerned French physicians juice.
finally introduced novel methods for improving in-
fant survival. In 1892 Pierre Budin, professor of ob- Deficiency Diseases
stetrics, organized a "Consultation de Nourrisons" at According to J. C. Drummond and Anne Wilbraham
the Charite Hospital in Paris. Women who had been (1958), the earliest mention of rickets as a disease
delivered at the hospital were advised on breast feed- entity was made in a 1634 Bill of Mortality for the
ing and infant care; after discharge, the babies were city of London. Between 1645 and 1650, at least
examined and weighed weekly until weaned, then three physicians, including Francis Glisson, gave
less frequently until they were 2 years of age. Great accounts of the disease. Glisson's work, De rachitide,
emphasis was placed on breast feeding, as well as on published in 1650, not only was the most extensive
weight and height. Also in 1892 Gaston Variot, a but also made reference to scurvy as a disease that
pediatrician, organized the distribution of sterilized could be associated with rickets in infants. Subse-
milk, at reduced prices, at the Belleville dispensary. quently, most European pediatric texts discussed
Two years later, Leon Dufour, a medical practitioner rickets, but no clear reference to infantile scurvy
in Normandy, opened a milk station, called the reappeared until the late nineteenth century. It
"Goutte de Lait," at Fecamp. Here also babies' growth would seem that rickets was commonplace in north-
was carefully supervised, and when breast feeding ern Europe, particularly in England, whereas infan-
proved impracticable, sterilized milk was provided tile scurvy was rare until the advent of proprietary
free or at reduced prices (McCleary 1935; Blake foods and the use of boiled or sterilized milk. In the
1953). United States, however, rickets was either unrecog-
At first there was friction between Budin and nized or had a low incidence until the late nine-
Dufour because the former felt that the Gouttes de teenth century, for it was rarely discussed in the

earlier pediatric textbooks or, if mentioned, was dis- Since then, physicians and nutritionists have sought
missed as of rare occurrence (for the first North to understand, prevent, and cure this and similar
American monograph on rickets, see Parry 1872). disorders and syndromes, collectively known as
Thomas Cone and others have pointed out the lack protein-energy malnutrition (PEM) and most com-
of consensus on the cause of rickets by the end of the monly found in developing countries. (The research
nineteenth century (Hess 1929; Cone 1979). Some literature is very large; see, e.g., Trowell, Davies, and
believed it was due to an improper diet, others to a Dean 1954; Jellife 1969; Olson 1975.) At one extreme
lack of sunshine or exposure to polluted air. Yet are marasmic infants, in whom growth failure is com-
others regarded it as a degenerative disease. In this bined with wasting from starvation, as a result of a
view, fortified by perceived similarities in the micro- diet deficient in both calories and protein. At the
scopic bony lesions of syphilis and rickets, parental other extreme is kwashiorkor, thought to be due to a
syphilis could be expressed in offspring as rickets or diet with an adequate caloric content but deficient in
as an increased liability to rickets (for a discussion of usable protein. In between are less obvious forms of
"hereditary" syphilis as the cause of other diseases PEM, characterized by growth retardation and asso-
in the offspring of syphilitics, see Lomax 1979). ciated with a greater liability to infection than is
As indicated by Kenneth Carpenter (1986) ideas found in well-nourished children. Infectious disease
about the cause of scurvy were just as confused. In interferes with a child's appetite, thereby provoking
1883 Thomas Barlow described the clinical and or worsening malnutrition, and the latter state de-
pathological signs of infantile scurvy, a disease en- creases resistance to infection. In former centuries,
tity rarely recognized in babies. He also indicated protein-calorie deficiency syndromes were probably
that the best remedy was orange juice. Soon physi- responsible for much wasting, infection, and diarrhea
cians in other countries were recognizing "Barlow's in American and European babies, but the incidence
disease," but they could not agree as to the cause or would be difficult to estimate retrospectively because
even the cure. In 1898 the American Pediatric Soci- illness was perceived and described so differently at
ety reported an investigation of infantile scurvy. that time.
Most physicians who had been consulted thought
that proprietary foods, and perhaps sterilized milk, Congenital Abnormalities
were responsible for the condition. One dissenter, In the past, a great deal of ingenuity was applied to
August Caille, considered the illness to be a form of explaining the occurrence of birth defects. In the
ptomaine poisoning caused by the absorption of tox- sixteenth century the French surgeon Ambroise
ins (Cone 1979; Carpenter 1986). Epidemiology and Pare suggested no fewer than 13 possible causes,
clinical medicine could not produce decisive evi- including the wrath of God, imperfections in "the
dence in favor of any particular theory (see Wilson seed," the imagination of the pregnant mother, and
1975). injuries to the uterus during gestation (Pare 1982).
Early in the twentieth century, researchers using The notion that maternal impressions during preg-
animal models to establish dietary requirements nancy could influence the developing fetus was very
came to the rescue. Administering modified diets to persistent. As indicated by Joseph Warkany (1977),
animals was not a new technique, but with improve- a chapter entitled "Maternal Impressions" in J. M.
ments in chemical analysis it was becoming more Keating's 1889 Cyclopedia of the Diseases of Chil-
precise. In 1907 scurvy was produced experimen- dren recorded 90 cases of congenital defects, blaming
tally in guinea pigs, and further experiments led mental trauma suffered by the mother during preg-
Casimir Funk to propose, in 1912, that scurvy, pella- nancy for the abnormalities. Explanations of this
gra, rickets, and beriberi were caused by a dietary sort were advanced in the late nineteenth century
lack of essential factors, which he called "vita- because the mechanism of inheritance remained a
mines." The hypothesis was received with enthusi- mystery. Most physicians and biologists, such as
asm, deficiency diseases were induced in animals, Charles Darwin, continued to believe that acquired
and between 1928 and 1938, vitamins A, B,, C, D, parental characteristics could be transmitted to off-
and E were isolated and chemically defined (Harris spring under appropriate circumstances. This age-
1970). old concept was the basis not only of Jean Baptiste
Another type of deficiency was recognized when de Lamarck's theory of evolution but also of Dar-
Cicely Williams (1933) drew attention to kwashior- win's theory of pangenesis (Zirkle 1946; Churchill
kor, a disorder brought on by malnutrition in previ- 1976).
ously healthy West African toddlers after weaning. Change came in 1900 with the dramatic rediscov-

ery of Gregor Mendel's work on the laws of inheri- Infectious Diseases
tance in peas. In 1902 an English physician, Archi- Although their cause was uncertain until the last
bald Garrod, voiced his suspicion that a rare disease third of the nineteenth century, childhood exanthe-
in babies called alkaptonuria was hereditary and mata and whooping cough were recognized by a ma-
surmised that this "inborn error of metabolism" jority of physicians as contagious. The responsible
(Garrod's term) was due to the lack of a necessary agent was thought to be a specific virus, or morbid
enzyme and that genes (the Mendelian hereditary poison, often undetectable by the senses. However,
factors) produced enzymes (Garrod 1908). However, physicians who subscribed wholeheartedly to the mi-
his hypothesis was not taken seriously until it was asmic theory of transmission did not accept the no-
confirmed in 1941 by George Beadle and E. L. Ta- tion of a causal virus or physicochemical agent of
tum, who had investigated the genetic control of infection. Instead, they believed that polluted air, or
biochemical reactions in a mold — neurospora. miasma, could excite a variety of fevers, the specific
Apart from genetic anomalies, birth defects can be nature of any epidemic being determined by the
caused by chromosomal abnormalities, by a deleteri- geography of the locality, the season of the year, or
ous environment, or by a multiplicity of factors the personal constitution. For example, William P.
(Chudley 1985). Definite evidence of environmental Dewees, author of the first U.S. pediatric textbook
action was not adduced until 1941, when N. M. (1826), doubted that whooping cough, mumps, and
Gregg reviewed 78 cases of congenital cataract, find- measles were contagious. In his view they were epi-
ing a history of maternal rubella infection during demic diseases, that is, dependent on some condition
pregnancy in all but 10 cases. Twenty years later the of the atmosphere. In his words: "It is a rule, with
"thalidomide scandal" concentrated attention on the few or no exceptions, that, where a disease can be
teratogenic risk associated with drugs taken during traced to atmospherical influence, it does not prove
pregnancy. This was followed by the equally dra- contagious. Nature indeed can hardly employ two
matic recognition that specific congenital malforma- such opposite causes to produce the same effect"
tions, Kenneth Jones's "fetal alcohol syndrome," (Dewees 1829).
could result from maternal alcoholism during preg- In 1798 Edward Jenner had advocated the use of
nancy (Jones and Smith 1973). cowpox (vaccination) as protection against smallpox,
Since antiquity, maternal alcoholism had been as- a disease particularly fatal to infants. In a remark-
sociated with injury to offspring. But as indicated by ably short time, vaccination replaced inoculation as
Rebecca Warner and Henry Rosett (1975), concern the means of providing immunity to smallpox (Ed-
about and research into the potential hazards of wardes 1902; Hopkins 1983). However, because the
maternal alcoholism "virtually disappeared" be- mechanism of protection was not understood, con-
tween about 1920 and 1940. Many reasons can be firmed miasmatists continued until the end of the
adduced for this rather sudden change, including the nineteenth century to protest vaccination, which con-
effects of prohibition in the United States and the tradicted their epidemic, nonspecific theory of dis-
discrediting of the ancient belief in the inheritance ease (for antivaccinationist views, see Crookshank
of acquired characteristics. Especially in the nine- 1889; Creighton 1894; Tebb 1898). In their opinion,
teenth century, the latter concept was exploited to the decreased incidence of smallpox after mass vacci-
explain the appearance of many congenital diseases, nation was due not to protection afforded by vaccina-
including damage to an infant born to an inebriate tion, but to a natural decline in smallpox epidemics
woman. Alcohol was presumed to damage the germ counterbalanced by an increase in other diseases
cells, male or female, and hence to have an adverse such as measles and whooping cough.
effect on the offspring. To the nineteenth-century Immunity began to be understood when Louis Pas-
mind, this was an example of the hereditary trans- teur discovered that the injection of an attenuated
mission of disease leading to familial degeneration. culture of chicken cholera protected laboratory birds
By the 1920s such Lamarckian-type hereditary from the effects of a subsequent inoculation of viru-
transmission had been largely discredited, and the lent culture (for a discussion of Pasteur's work on
phenomena it had allegedly explained were now usu- attenuation, see Bulloch 1938). Strategies of attenua-
ally ascribed to social and economic disadvantage. tion were enlarged to include dead organisms and
Furthermore, the uterine environment was not per- prepared extracts; at the same time immunity began
ceived to be a potential site of teratogenic action to be explained by the production of specific serum
until the maternal rubella findings were published antibodies to bacterial antigens and of antitoxins
in the early 1940s. that neutralized toxins. Scientists undertook the

preparation of specific protective sera with striking infant mortality rate is usually much lower than
success in 1894, when Pierre P. E. Roux demon- that which prevailed in western Europe and the
strated the value of diphtheria antitoxin, which had United States at the turn of the century.
been discovered earlier by Emil von Behring and Elizabeth Lomax
Shibasaburo Kitasato.
Diphtheria antitoxin, although frequently life- Bibliography
saving, conferred only passive, temporary immunity Ackerknecht, Erwin H. 1967. Medicine at the Paris hospi-
and could not prevent the spread of disease. Gradu- tal, 1794-1848. Baltimore.
ally a safe attenuated toxin (toxoid) was developed so 1968. A short history of medicine. New York.
that by the 1930s children could be actively immu- Anon. 1843. On the diseases of children. British and For-
nized against diphtheria. By this time, a vaccine eign Medical Review 15: 320—8.
1849. On the diseases of children. British and Foreign
against pertussis had also been discovered, and pas- Medico-Chirurgical Review 3: 406-32.
sive immunization against tetanus, as well as certain Apple, Rima. 1981. "How shall I feed my baby?" Infant
types of pneumococci and meningococci, was possible. feeding in the United States, 1870-1940. Ph.D. disser-
Research continued apace during the Second World tation, University of Wisconsin.
War, when a safe tetanus toxoid was discovered Bakwin, Harry. 1942. Loneliness in infants. American
(Dowling 1977). This was followed by the discovery of Journal of Diseases of Childhood 63: 30—40.
poliomyelitis vaccine in 1956 and, more recently, of Barthez, A.-C.-E., and F. Rilliet. 1853. Traite clinique et
vaccines for rubella, measles, and mumps. Today, a pratique des maladies des enfants, 3 vols. Paris.
full immunization program during infancy elimi- Billard, Charles M. 1835. Traite des maladies des enfants
nates, in large measure, the ill health, chronic disabil- nouveau-nes et a la mamelle, 3d edition. Brussels.
ity, and mortality that were once associated with the Blake, John B. 1953. Origins of maternal and child health
common infectious diseases of childhood. programs. New Haven, Conn.
Bowlby, John. 1951. Maternal care and mental health.
World Health Organization Monograph No. 2. Geneva.
Conclusion Brougham, Henry. 1823. Early moral education. Edin-
Unfortunately, it is impossible in the space allotted burgh Review 38: 437-53.
to discuss all of the novel concepts of early child- Bulloch, William. 1938. The history of bacteriology. London.
hood illness that evolved during the twentieth cen- Carpenter, Kenneth J. 1986. The history of scurvy and
tury. Among these was an appreciation of the rapid vitamin C. Cambridge.
debility and death that result whenever fluid is Chudley, A. E. 1985. Genetic contributions to human mal-
quickly lost and not replaced; this led to the devel- formations. In Basic concepts in teratology, ed. T. V. N.
opment of methods for maintaining or restoring Persaud, A. E. Chudley, and R. G. Shalko, 31-66. New
acid-base balance during rehydration. Also in the York.
twentieth century were the recognition and treat- Churchill, Frederick B. 1976. Rudolf Virchow and the
ment of hormonal disorders, of hemolytic disease of pathologist's criteria for the inheritance of acquired
characteristics. Journal of the History of Medicine 31:
the newborn, and of numerous neurological and vi- 115-48.
ral disorders. Cone, Thomas E. 1976. 200 years of feeding infants in
In 1906 George Newman had already indicated America. Columbus, Ohio.
that prematurity and immaturity at birth were 1979. History ofAmerican pediatrics. Boston.
among the largest contributors to infant mortality Creighton, Charles. 1894. History of epidemics in Britain,
and were on the increase (Newman 1907). Today Vol. 2. Cambridge.
infection and malnutrition, the chief causes of infant Crookshank, Edgar M. 1889. History and pathology of
death between the ages of 1 month and 1 year in vaccination, 2 vols. London.
Newman's time, are well understood and are rarely Crosse, John. 1815. Sketches of the medical schools of
fatal, thus allowing pediatric medicine and research Paris. London.
to concentrate on improving the premature infant's Dewees, William P. 1829. Treatise on the physical and medi-
chance of survival during the neonatal period. New- cal treatment of children, 3d edition. Philadelphia.
Dowling, Harry F. 1977. Fighting infection: Conquests of
man and his contemporaries would be gratified, per-
the twentieth century. Cambridge, Mass.
haps amazed, that the current infant mortality rate Drummond, J. C, and Anne Wilbraham. 1958. The En-
in developed countries is one-fifteenth to one- glishman's food: A history of five centuries of English
twentieth the rate in their time. Even in Third diet. London.
World countries, where many more babies are sub- Dwork, Deborah. 1987. War is good for babies and other
ject to malnutrition and vulnerable to infection, the young children. London.

Dyhouse, Carol. 1978. Working class mothers and infant clinical experience. American Journal of the Medical
mortality in England, 1895-1914. Journal of Social Sciences 63: 17-52, 305-29.
History 12: 248-62. Peiper, Albrecht. 1966. Chronik der Kinderheilkunde.
Edwardes, Edward J. 1902. A concise history of small-pox Leipzig.
and vaccination in Europe. London. Phaire, Thomas. 1965. The boke of children. Reprint.
Etienne, R. 1973. La conscience m6dicale antique et la vie London.
des enfants. In Annales de d&mographie historique, Radbill, Samuel X. 1971. The first treatise on pediatrics.
ed. J. Dupaquier, 15—46. Paris. American Journal ofDiseases of Children 122:369-76.
Fildes, Valerie. 1986. Breasts, bottles and babies. Edin- Rhazes. 1939. Rhazes' treatise on the small-pox and mea-
burgh. sles, trans. Williams A. Greenhill; reprinted in Medi-
Galen, 1951. Galen's hygiene (De sanitate tuenda), trans. cal Classics 4: 19-84.
Robert Montraville Green. Springfield, 111. Riese, Walther. 1953. The conception of disease. New York.
Garrison, Fielding H. 1965. In Abt-Garrison history of Ruhrah, John. 1925. Pediatrics of the past. New York.
pediatrics, 1-170. Philadelphia. Smith, F. B. 1979. The people's health, 1830-1910. London.
Garrod, A. E. 1908. Inborn errors of metabolism. Lancet 2: Smith, Job Lewis. 1890. Treatise on the diseases of infancy
107, 73-9, 142-8, 214-20. and childhood, 7th edition. Philadelphia.
Gregg, N. McAlister. 1941. Congenital cataract following Soranus. 1895. Soranus d'Ephese, "Traiti des maladies des
German measles in the mother. Transactions of the femmes," trans, into Franch by F.-J. Herrgott. Nancy.
Ophthalmological Society of Australia 3: 35-46. 1956. On gynecology, trans. Owswi Temkin. Baltimore.
Harris, Leslie J. 1970. The discovery of vitamins. In Still, George F. 1931. The history of paediatrics. London.
The chemistry of life, ed. Joseph Needham, 156-70. Straus, Lina Gutherz. 1917. Disease in milk, the remedy
Cambridge. pasteurization: The life work of Nathan Straus. New
Hess, Alfred F. 1929. Rickets including osteomalacia and York.
tetany. Philadelphia. Sussman, George D. 1982. Selling mother's milk: The wet-
Hopkins, Donald R. 1983. Princes and peasants: Smallpox nursing business in France, 1715—1914. Urbana, 111.
in history. Chicago. Sydenham, Thomas. 1848. The works of Thomas Syden-
Jelliffe, Derrick B. 1969. Child nutrition in developing ham, M.D., Vol. 1, trans, from the Latin by R. G.
countries. Washington, D.C. Latham. London.
Jenner, Edward. 1798. An inquiry into the causes and Tebb, William S. 1898. A century of vaccination and what
effects of the variolae vaccinae. London. it teaches. London.
Jones, Hugh R. 1894. The perils and protection of infant Temkin, Owsei. 1977. The double face ofJanus. Baltimore.
life. Journal of the Royal Statistical Society 58: 1-98.
Trowell, H. C, J. P. N. Davies, and R. F. A. Dean. 1954.
Jones, Kenneth L., and David W. Smith. 1973. Recognition Kwashiorkor. London.
of the fetal alcohol syndrome in early infancy. Lancet
Underwood, Michael. 1806. Treatise on the diseases of chil-
2: 999-1001. dren. Boston.
Logan, W. P. D. 1950. Mortality in England and Wales U. S. Bureau of the Census. 1960. Historical statistics of
from 1848 to 1947. Population Studies 4: 132-78. the United States: Colonial times to 1957. Washington,
Lomax, Elizabeth. 1979. Infantile syphilis as an example D.C.
Vaughan, Victor. 1897. Diarrheal diseases. In An Ameri-
of nineteenth century belief in the inheritance of ac-
quired characteristics. Journal of the History of Medi- can textbook of the diseases of children, ed. Louis Starr,
cine 34: 23-39. 479-500. Philadelphia.
McCleary, G. F. 1935. The maternity and child welfare Warkany, Joseph. 1977. Congenital malformations of the
movement. London. past. In Problems of birth defects, ed. T. V. N. Persaud,
McKeown, Thomas. 1976. The modern rise of population. 5-17. Baltimore.
London. Warner, Rebecca H., and Henry Rosett. 1975. The effects of
Mitchell, B. R. 1965. European historical statistics. New drinking on offspring: An historical survey of the
York. American and British literature. Journal of the Stud-
Newman, George. 1907. Infant mortality: A social prob- ies of Alcohol 36: 1395-420.
lem. New York. Wickes, I. G. 1953. A history of infant feeding. Archives of
Olson, R. E., ed. 1975. Protein calorie malnutrition. New Diseases of Childhood 28: 151-8, 232-40, 416-22,
York. 495-502.
Papavoine, Jean Nicholas. 1830. Arachnitis tubercu- Williams, Cicely D. 1933. A nutritional disease of child-
leuses. Journal Hebdomadaire 4: 113. hood associated with a maize diet. Archives of Dis-
Pare, Ambroise. 1982. Ambroise Pare, on monsters and eases of Childhood 8: 423-33.
marvels, trans, and ed. Janis L. Pallister. Chicago. Wilson, Leonard G. 1975. The clinical description of
Parry, John S. 1872. Observations on the frequency and scurvy and the discovery of vitamin C. Journal of the
symptoms of rachitis with the results of the author's History of Medicine 30: 40-60.

III.5. Famine and Disease 157
Winter, J. M. 1982. The decline of mortality in Britain, Ordinary starvation may be said to begin some 4
1870-1950. In Population and society in Britain, or 5 hours after a meal. It is then that the liver
1850-1980, ed. Theo Baker and Michael Drake, 100- begins to release as glucose its store of glycogen. As
20. London. this process continues, muscle and adipose (fatty)
Wohl, Anthony S. 1983. Endangered lives: Public health in tissue, which otherwise rely on free glucose for fuel,
Victorian Britain. London. gradually revert to the oxidation of fatty acids. This
Woodbury, Robert M. 1926. Infant mortality and its causes.
allows circulating glucose to be consumed primarily
Baltimore.
Yost, R. M. 1950. Sydenham's philosophy of science. Osiris
by the brain.
9: 84-105. Liver glycogen alone in the absence of any food
Zirkle, Conway. 1946. The early history of the idea of the intake supplies glucose to the blood for roughly 12 to
inheritance of acquired characters and of pangenesis. 16 hours before a number of metabolic changes be-
Transactions of the American Philosophical Society, gin shifting liver activity to gluconeogenesis, the
2d Ser., 35: 91-151. conversion of muscle protein into glucose. Within 24
hours or longer, depending on the level of food in-
take, liver glucose output is fully dependent on im-
ported protein. With the onset of gluconeogenesis,
the liver itself burns fatty acids delivered from adi-
III.5 pose tissue. As these arrive in increasing amounts,
only partial oxidation occurs. This results in the
Famine and Disease liver sending ketones (incompletely burned fatty ac-
ids) into circulation. These become fuel for both mus-
cle and brain as their level in the blood increases. In
Famine can be denned as a failure of food production the case of rapidly induced starvation, keto acid con-
or distribution resulting in dramatically increased centrations can reach dangerous levels, resulting in
mortality. This increase is attributable to two, and dehydration and, eventually, in coma. This, how-
very often three, orders of disease. First, there is the ever, can be avoided by the intake of small amounts
disease of general starvation characterized by wast- of carbohydrate.
ing and inanition. Second, there are behavioral dis- Gluconeogenesis continues for about a week be-
orders and social disruptions, some a direct conse- fore ketone production levels off. Muscle gradually
quence of energy deficiency, others linked to mental ceases to be reliant on keto acids, making ever
disturbance. These can be lethal in their own right greater use of free fatty acids liberated from adipose
while at the same time contributing to the general tissue. The brain now takes ketone bodies over glu-
starvation and to the spread of contagious illness. cose for nourishment. This allows gluconeogenesis to
Third, there is epidemic infection, which is not al- shut down, eliminating the demands of this process
ways seen in mass starvation but which is frequent on muscle protein. At this point, the body's metabo-
enough to be considered a classic concomitant. Facili- lism is fully adjusted to draw on fat for almost all of
tated by impaired individual and community resis- its energy needs.
tance to pathogenic agents, contagions tend to run Protein catabolism and the destruction of active
an exceedingly rapid course through famished popu- tissue is never totally eliminated, however. Wasting,
lations, contributing in large measure to overall loss of weight or body mass, the most obvious exter-
mortality. nal manifestation of general starvation, is most pre-
cipitous during the first few days. It becomes less so
General Starvation over a longer period. If semistarvation extends over
Starvation, a condition in which the body draws on its weeks or months, the rate of wasting will continue to
own internal reserves for energy, arises from normal decline. Fat accounts for the greatest portion of wast-
processes essential to survival. These processes lead age after the first several days, but to the end there
to the disease of general starvation, or undernutri- is a relatively slight but slowly increasing usage of
tion, only after progressing beyond a threshold where protein.
damage resulting in functional incompetencies is This continuing attrition of protein, even as fat
done to active tissue. If starvation is not acute, that is, remains available, is not borne equally by all organs
not rapidly induced, dysfunctions incompatible with of the body. Heart and kidney tissue sustain slightly
heavy work are not apparent in nonobese people be- less loss than would be expected given their propor-
fore the loss of 10 percent of prestarvation weight. tion of total body mass. The liver, intestines, and

skin incur more than their share of the loss. Postmor- percent weight loss is incurred, however, the chances
tem examinations of starvation victims reveal no of survival are virtually nil without medical interven-
part of the body immune to atrophy except the brain. tion. A 40 percent wastage during famine is almost
During famine, starvation initially affects those certainly fatal.
who are physiologically the most vulnerable. Differ- Individuals suffering from advanced undernutri-
ent forms of protein-energy malnutrition, kwashior- tion can survive for prolonged periods owing to two
kor and marasmus, show up early in young children. remarkable means of accommodation that allow the
Before gross weight loss is seen in older children and energy budget to reach near equilibrium and permit
adults, there is a loss of endurance. Those who are weight loss to slow dramatically despite a very low
afflicted require frequent rests from work. As gen- level of caloric intake. The first is a decline in basal
eral starvation becomes more advanced, there are metabolism, which occurs because wasting reduces
complaints of weakness and muscle pains. Move- the number of metabolically active cells, accompa-
ment becomes sluggish. Individuals sit or lie down nied by a decrease in the metabolic rate of the sur-
whenever possible. A slow, shuffling gait develops. viving biomass. The second is a decline in spontane-
Nocturnal sleep is interrupted, but total sleep pro- ous movements and a decreased cost of movement.
gressively increases. An acute sensitivity to noise In other words, starving people reduce their actions
develops; the skin becomes extremely sensitive and to a minimum. Moreover, any activity that cannot
bruises easily. There are complaints about feeling be avoided becomes less expensive energywise be-
cold. Blood pressure and heart rate decline. A diar- cause of reduced weight. Of these two factors, cur-
rhea attributed to visceral atrophy and malfunction tailed activity accounts for the greatest savings. In
occurs in individuals who are free of intestinal infec- experiments conducted during World War II, volun-
tion. Edema often appears, first in the face, then in teers restricted to a semistarvation diet for 6
the extremities, later in the abdominal and thoracic months were observed to reduce movement-related
cavities. energy expenditures by 71 percent. Approximately
Whereas the intellect remains largely unimpaired, 60 percent of this was achieved by elective curtail-
the emotions are greatly affected. Victims' moods ment of activity. A reduction of anywhere near this
alternate between apathy and extreme irritability. magnitude during a famine is bound to have pro-
The starving become discouraged and depressed but found social implications.
also display an exaggerated ill temper. Critical abil-
ity seems to fail. There is lack of concentration and Behavioral Disturbances and Social
lapse of memory. Speech becomes slow. Appearance Disorders
and manners become matters of indifference. Inter- People suffering inanition obviously find it impossi-
est in sex disappears. Women experience amenor- ble to maintain normal social relations. No matter
reah; spermatogenesis declines in men. An inversion what their cultural definition, ordinary interactions
takes place: Light hair appears on women's faces, are also affected by the emotional correlates of starva-
whereas men's beards stop growing. Both sexes lose tion and by individual and collective efforts to sur-
hair from the top of the head and around the genitals. vive under extreme conditions. Famine, as a net re-
Victims think only of their diseased condition and sult, gives rise to a series of social transformations.
food. But when starvation becomes acute, even appe- Seen as variously altered patterns of interaction,
tite disappears. these transformations progressively unfold under de-
The length of time a starving individual can sur- teriorating conditions. For this reason, they have
vive on endogenous sources of energy varies, depend- been viewed as broadly diagnostic of the prevailing
ing on fat reserves, the magnitude of caloric deficit level of want. This view is most certainly justified
(determined by energy intake and level of physical with respect to two dimensions of interaction, its fre-
activity), and ambient temperature. Inactive indi- quency and the extent to which it involves positive
viduals with normal weight for height can endure reciprocities. Both of these indicators disclose the
nearly total starvation for about 2 months. Semistar- characteristic rise and fall of a stress-response curve
vation in active subjects consuming between 1,300 as famine progresses from threat to full-fledged real-
and 1,600 kilocalories per day has been studied unity. Figure III.5.1 illustrates this in terms of the rela-
der controlled conditions for up to six months. Dur- tionship between food supply and generosity.
ing a famine food intake may fall below this level Social responses to famine develop through three
but often for only brief periods of time at first. phases. The first, the alarm phase, marked by gen-
Hence, victims can endure for months. Once a 30 eral hyperactivity and intensified feelings of attach-

c High Average merely to assuage hunger. To conserve supplies, ex-
o Availability of Depletion
Basic Resources of Surplus penditures other than those immediately related to
obtaining food are pared to a minimum. The extent
o
of active social relations as indexed by food sharing
s Resistance
shrinks considerably as a result.
o
CO
This "social atomization" is the hallmark of the
resistance phase. Essentially, it entails the closure of
Exhaustion
the household as a food-sharing unit. Generosity
Low disappears; supplies are hidden; food preparation
Low Ecological Stress High and consumption take place in secret. Visits from
Figure III.5.1. Relation of social cooperation to ecological relatives and friends arouse suspicion and may be
stress in a social action system. (AdaptedfromLaughlin regarded as unfriendly acts.
and Brady 1978.) Lawlessness, including physical aggression, con-
tinues to increase, but during the resistance phase of
famine there tends to be less concerted and sustained
ment, is triggered by the onset of an emergency. This violence, particularly after the average level of
reaction, also reported in the wake of sudden catas- weight loss in a community begins to exceed 20 per-
trophes such as floods and tornadoes, can create on cent. The physical wherewithal for rioting or other
the community level what has been called a "disas- active expressions of political unrest becomes practi-
ter utopia," a social environment of extraordinarily cally nil beyond this point. Active expressions of any
intense mutual care and assistance. Thus, the shar- sort gradually disappear. Ritual observances are put
ing of food and other resources among friends and off; religious attendance declines. People congregate
neighbors actually increases, apparently irrespec- only where there is promise of receiving food.
tive of whether there is any prospect of outside assis- Exhaustion, the final phase of famine, comes with
tance. Although accounts of local-level responses to the disintegration of the household, the social bul-
this earliest phase of famine are relatively few, this wark of resistance. Its collapse is foreshadowed as
phenomenon has been documented in a variety of food sharing within the household becomes increas-
cultural settings, including diverse urban and rural ingly discriminatory during the resistance phase.
locations in Africa, western Europe (Ireland and the There is a distinct tendency to see the elderly as a
Netherlands), South Asia (India and Nepal), and drain on provisions. Tolerance toward younger de-
Oceania (Yap and Tikopia). Hoarding at this stage pendents does not erode as quickly, but generally
does occur, but it appears to be limited to market there comes a point when children too receive dispro-
economies and, more particularly, to those individu- portionately small amounts of food. These types of
als least threatened by starvation. discrimination - arguably adaptive insofar as they
Intensification affects virtually every sphere of favor principal providers, those on whom eventual
life during the alarm stage. Market activity in- recovery will depend - show up in age-specific mor-
creases and, under certain conditions, may become tality rates. In the Punjab, for example, where in
chaotic. Food prices soar. Population movement in- 1939 famine resulted in an overall increase in mor-
creases, as individuals and families seek to relieve tality of more than 52 percent, the elderly sustained
their mounting plight. Mystical efforts to find relief a 288 percent increase in their rate of death and
intensify; religious congregations swell. Political ac- mortality among children under 10 rose by 192 per-
tivity increases. Violence erupts, both spontaneous cent. By contrast, among individuals between 10
and concerted, frequently at sites where food and and 60 years of age, mortality actually declined to a
other commodities are in storage or transit. level 14 percent less than the average for the preced-
As starvation begins to exact a physical toll and ing 4 years.
individuals become weaker and more easily fa- Although exhaustion does not sweep over a fam-
tigued, famine progresses beyond the stage of alarm ished population all at once, the appearance of ne-
and into a protracted phase of resistance. The ques- glected, wandering children is a certain sign that
tion of available energy becomes paramount at this pockets of it exist within a region. The same holds
point. People turn to unusual sources, including for the abandonment and sale of children. Parents
foods known to be edible but normally ignored and may take such drastic steps out of concern for their
species ordinarily regarded as inedible or abhorrent. own survival or out of the hope that being in some
Items of no nutritional value may be consumed other individual's or agency's custody will save their

offsprings' lives. But in either instance, as well as in large number of food producers. This is most liable to
the case of infanticide or parental suicide, an under- occur when a new disease is introduced into a region
lying cause is almost certainly the mental fatigue whose inhabitants have no acquired immunity.
that comes from hearing ceaseless cries for food that Many native American populations suffered severe
cannot be stilled. famine upon first exposure to such commonplace Old
The final vestiges of cooperation in the worst fam- World illnesses as measles and smallpox. Generally
ines are found only in the most instrumental rela- speaking, however, it is more often the case that
tionships. Anyone promising to put a bite of food in infectious epidemics follow in the wake of starvation.
one's mouth is a friend. The fact that people some- The diseases that become epidemic tend to be famil-
times kill ruthlessly to acquire scraps of food sug- iar ones, long endemic to a region. Virtually any
gests that anyone standing in the way of eating is an endemic illness has epidemic potential during fam-
enemy. Cannibalism may occur during extreme famine, but certain of them have become notorious.
ine, though its extent is impossible to gauge. Sui- In the Western world, those diseases most disposed
cide, even in cultures where it is otherwise unheard to reach epidemic proportions have been typhus, re-
of, becomes very common. lapsing fever, smallpox, dysentery, tuberculosis, bu-
Exhaustion leaves an indelible mark on survivors. bonic plague, influenza, and pneumonia. Changes
A significant incidence of gross stress reaction affecting public health have altered the epidemic
(acute situational maladjustment), a disease cate- potential of these diseases at various points in his-
gory that originally comprised the mental depres- tory. Thus, typhus (famine fever, spotted fever), a
sions of combat personnel whose disturbances could louseborne infection that for centuries had been Eu-
not be described accurately by existing psychiatric rope's most dreaded famine disease, ceased to be a
labels, has been documented among both European concern among most undernourished groups during
famine victims and Australian aborigines. Gross World War II owing to the widespread use of DDT.
stress reaction is thought to arise from a severely However, with the disappearance of typhus, epi-
disturbed interpersonal environment. demic tuberculosis, which almost certainly had been
Relief-induced agonism is another postfamine syn- present but undetected in previous famines, became
drome worthy of note. It consists of a varied pattern a major problem.
of aggressive, exigent, and quarrelsome behavior, As for the East, experience with famine-related
both verbal and nonverbal. It is seen during the epidemics has been much the same as that of Eu-
course of relief operations, particularly after the rope, with some exceptions. Typhus has not been
refeeding of victims. Relief-induced agonism ap- seen in well-watered tropical and semitropical re-
pears to be nonspecific in the sense that it is not gions where people are accustomed to bathing daily.
directed at any particular target. The agonism ex- In contrast, waterborne disease such as dysentery
presses itself as a general irritability and a remon- and cholera have become virtually synonymous with
strative or combative attitude toward anyone at mass starvation in such climates. Typhoid epidemics
hand, including relief personnel. What sometimes have been associated with famines in China. Acute
causes people who were heretofore wasted, inactive, malaria and heavy hookworm infestations have
and emotionally apathetic to become suddenly quite been observed in famished populations of India.
animated, clamorous, and contentious upon receiv- In Africa the effects of malaria do not appear to be
ing ample nourishment is not known. aggravated by general starvation. However, con-
trary to experience in the rest of the Old World,
Famine and Infectious Disease including India, recent episodes of general starva-
General starvation increases susceptibility to numer- tion in Ethiopia, Nigeria, and the Sahel have been
ous pathogens. Conversely, infection accelerates the accompanied by epidemics of measles extremely le-
course of general starvation. This process is en- thal to children. Yet judging from records of the
hanced as declining health and increased mortality Great Ethiopian Famine of 1888-92, the greatest of
add to social disorder, creating greater impediments all African famines, epidemic measles has not al-
to the acquisition of food, increased undernutrition, ways been a problem in Africa in times of dearth.
and conditions ripe for the spread of disease. More common have been epidemics of cholera, small-
This vicious circle can originate on the side of ei- pox, meningitis, dysentery, and pneumonia, and ty-
ther pathogenic illness or undernutrition. Epidemic phus outbreaks have also been reported in Ethiopia.
disease has the potential for ushering in general Two factors, often working together, facilitate the
starvation, especially if infections debilitate or kill a occurrence of epidemics under famine conditions.

EII.5. Famine and Disease 161
The first is loss of community resistance to the nourished populations. Reflecting the high incidence
spread of infection, and the second is loss of individ- of infection that such populations experience even in
ual immune competence. the best of times, the buildup of immunoglobulin
Loss of community resistance can be accounted for levels in children is especially rapid. Despite this,
by a number of phenomena. These include popula- when confronted with certain antigens, including
tion dislocations and the overcrowding of public fa- the pathogens of typhoid, influenza, mumps, diphthe-
cilities, both of which destroy barriers to the spread ria, and yellow fever, the immunoglobulins appear
of infections. Transmission is further abetted by the hypoactive. Secretory immunoglobulin A (IgA),
behavioral economies that accompany inanition and which prevents bacteria from adhering to mucosal
undermine domestic hygiene and public sanitation. surfaces, is found at abnormally low levels in the
Loss of community resistance is clearly illustrated undernourished, which helps to explain why starva-
in the case of typhus. Normally confined to isolated tion is generally associated with high rates of respi-
pockets of stark poverty, typhus often broke out over ratory and gastrointestinal infection. What remains
vast areas of Europe during starvation winters when unknown, and this applies to all of the foregoing
a massive number of people, lacking energy and functional impairments, is the degree of depression
wrapped in thick layers of clothing to combat of immunoglobulin levels that can be withstood be-
hypothermia, found it increasingly difficult to bathe fore the onset of clinical disease.
or wash their clothes. This lapse opened the way to Nutritional balance is adversely affected by a num-
heavy louse infestations. Since dessicated louse feces ber of reactions to infection. These include higher
clinging to unwashed garments were readily inhaled caloric expenditure resulting from greater mobiliza-
or rubbed into the eyes, the disease spread rapidly tion of protein due to increased stress and adrenocor-
by casual contact wherever famished wanderers tical activity; decreased food intake owing to general
passed through a region or clustered to find relief malaise, increased secretion of mucus, and appetite
from cold and hunger. During the Russian famine of loss; and intestinal changes leading to reduced ab-
1919-22, the incidence of typhus in Leningrad sorption of ingested foods. With regard to energy
showed a negative relationship not only with energy expenditure, relatively little is known beyond the
intake but with frequency of bathing. The death of fact that, if infection involves fever, basal metabo-
nearly 193,000 people was attributed to typhus and lism increases. Nevertheless, it is suspected that
relapsing fever, also louseborne, during Ireland's even in the absence of fever virtually all infections
Great Hunger (1845-52). By comparison, approxi- increase the demand on energy sources. The effects
mately 20,000 died of starvation. of illness on protein nutrition have received a great
Starvation can undermine individual resistance deal of attention. Protozoal and helminthic diseases
at virtually every line of bodily defense. As protein such as malaria and hookworm have adverse affects
is lost, protective anatomic surfaces such as skin on nitrogen balance proportional to parasitic load.
and mucous membranes lose integrity as barriers Most bacterial and viral infections have negative
against the invasion of pathogens. Flaky skin le- effects on nitrogen balance. Bacterial and viral infec-
sions, intestinal atrophy, and a reduction in tissue- tions of the intestinal tract are of major significance
healing capacity, frequently observed in children in most developing countries where diarrhea consti-
suffering from chronic protein-energy malnutri- tutes a major disease, particularly in infants and
tion, facilitate infection. young children. Intestinal infections impair the ab-
Once inside the body, infective agents encounter sorption of nitrogen, but more significant in creating
an impaired immune system. On the cellular side of a nitrogen imbalance is an abnormally high excre-
this system, starvation has ill effects on both tion of that element in urine, much of this coming
phagocytes and T-lymphocytes as the former lose from an increased breakdown of muscle tissue. Con-
efficiency as bacteria killers and the formation of the siderable nitrogen is also lost through fever-induced
latter is depressed. On the humoral side, the comple- sweating. Making up for nitrogen loss is difficult
ment system, a group of proteins that interact to given the decline in appetite that typically accompa-
form substances for the destruction of bacteria and nies intestinal illness.
viruses, functions poorly in undernourished chil-
dren. Immunoglobulins, protein molecules secreted History and Geography
by B-lymphocyte-derived plasma cells and a princi- Food production and distribution in every society are
pal element of the humoral immune system, are enmeshed in human ecologies of great complexity.
often found in serum at high levels among mal- Because of this, untoward conditions and events of

many sorts can lead to famine. These include natural the Standard Cross-Cultural Sample (SCCS), a repre-
disasters such as drought, flood, volcanic eruption, sentative, worldwide sample of the world's known
frost, and pestilence. In addition, there are social and well-described societies. The SCCS, developed
factors such as war, revolution, political policy, gen- by George P. Murdock and Douglas R. White, in-
eral economic collapse, speculation in food commodi- cludes 186 communities dependent on a wide variety
ties, administrative decision or indecision, inade- of subsistence systems. Each community is precisely
quate transportation, runaway population growth, located at a point in time, the sample as a whole
and gross social inequality. Despite the popular incli- spanning history from ancient civilization to the
nation throughout history to blame food disasters on twentieth century. The incidence of famine recorded
one or another of these phenomena, close analysis of in SCCS bibliographic sources reveals no remark-
specific cases invariably reveals multiple causes. Ef- able differences in the frequency of unexpected food
forts to untangle general factors have led to the cre- shortages among the world's major geographic re-
ation of various classification schemes and models of gions. Climatically, data show no more than a mildly
famine development. They have also resulted in re- positive relationship between the incidence of starva-
gional studies of outstanding quality. To date, how- tion and aridity. With respect to persistent famine
ever, little headway has been made in explaining (i.e., its occurrence more than once per generation)
famine in a way that would account for its historical the sample does show, as many would predict, a
and geographic incidence on a global scale. rather strong association with endemic hunger. Fi-
One large-scale pattern awaiting explanation is nally, statistics indicate a global tendency for the
seen in the proportional number of famines suffered severity of food shortages to increase with both in-
in regions of the Old World over the past 6,000 years. creased societal complexity and dependence on food
Beginning about 4000 B.C. and until 500 B.C., exist- importation.
ing records point to the Middle East and northeast
Africa, especially the valleys of the Tigris and Eu- Detection of Famine
phrates rivers and the Nile, as extraordinarily fam- Possibly throughout history, most certainly in the
ine prone. Over the next 1,000 years, the region of nineteenth and twentieth centuries, the term famine
disproportional incidence shifted to Rome and the has been used loosely. Hungry seasons, annual peri-
eastern parts of its empire, including Greece, Asia ods of dearth afflicting societies just before harvest,
Minor, Syria, and Judea. Western Europe became have been called famines. To add to the semantic
the major locus about A.D. 500. Eastern Europe as- confusion, there have been allegedly deliberate mis-
sumed this grim distinction after 1500, but about applications of the term by some governments in
1700 the high frequency of famine moved further order to elicit aid when it was not warranted. More-
eastward. From that year until 1974, periods of over, some governments have avoided using the
dearth occurred with greatest frequency among peo- term when it ought to have been used. The concept of
ples residing within a huge belt extending from re- famine has clearly been politicized. Nevertheless,
gions of Russia south of Moscow, across the southern one must admit that famines, unlike sudden physi-
Asian steppes, into India and China. More recently, cal catastrophes such as earthquakes and hurri-
African regions, especially the East and the Sahel, canes, are not always easy to detect. Often unan-
have been the scene of a disproportionate share of nounced by any violent event, famine can develop
food emergencies. insidiously, remaining invisible for a protracted pe-
The several published lists of the world's major riod to members of the privileged classes, especially
famines, all compiled before the 1970s, contain little if they are inured to the sight of poverty, endemic
mention of catastrophic food shortages among the undernutrition, and disease. One can perhaps better
peoples of sub-Saharan Africa, Oceania, and the comprehend the tendency for famine to escape notice
New World. These omissions grossly underrepresent by reflecting on the fact that during the Ethiopian
the experiences of "peoples without history," leaving famine of 1973-5 it was estimated that at any one
vast sectors of the world a blank map and much of time not more than 8 percent of that country's popu-
the information required to chart the occurrence of lation was starving to death. In a nation where as
famine beyond Eurasia unassembled. What truly many as 20 million people are perpetually hungry,
universal patterns might be discovered once the tem- the threshold at which suffering becomes perceived
poral and spatial distribution of famine has been as an emergency stands relatively high.
more broadly mapped can be glimpsed from a pre- For this reason, historical sources bearing on the
liminary analysis of unpublished data drawn from study of famine, whether official, academic, or popu-

lar, must be read with caution. A rigorous historical Helwig-Larsen, Per, et al. 1952. Famine disease in Ger-
detection of famine should include the following: man concentration camps, complications and sequels.
Copenhagen.
1. evidence of a dramatic increase in mortality; Hocking, Frederick. 1969. Starvation. Melbourne.
2. evidence that such an increase occurred in several Keys, Ancel. et al. 1950. The biology of human starvation,
adjacent communities at once; 2 vols. Minneapolis.
3. consideration of the possibility that lethal disease Laughlin, Charles D., Jr., and Ivan A. Brady. 1978. Intro-
unrelated to general starvation bears responsibil- duction: Diaphasis and change in human populations.
ity for increased mortality; In Extinction and survival in human populations, ed.
4. data showing a correlation between mortality Charles D. Laughlin, Jr., and Ivan A. Brady, 1—48.
New York.
curves and the price of food;
MacArthur, Sir William P. 1957. Medical history of the
5. information indicating disproportional mortality famine. In The great famine, ed. Edward R. Dudley
among the economically marginal; and T. Desmond Williams, 263-316. New York.
6. evidence of a depression in live births; and Murdock, G. P., and D. R. White. 1969. Standard cross-
7. statements contained in contemporary accounts cultural sample. Ethnology 8: 329-69.
referring to dearth, misery, or death owing to Pankhurst, Richard. 1966. The great Ethiopian famine of
want. 1888-1892: A new assessment. Journal of the History
Robert Dirks of Medicine and Allied Sciences 21(2, 3): 95-124,
271-94.
Bibliography Post, John D. 1976. Famine, mortality and epidemic dis-
Appleby, Andrew. 1973. Disease or famine? Mortality in ease in the process of modernization. Economic His-
Cumberland and Westmoreland, 1580-1640. Eco- tory Review 29: 14-37.
nomic History Review, 2d Sen, 26: 403-31. Robson, John R. K., ed. 1981. Famine: Its causes, effects
Blix, Gunnar, et al., eds. 1971. Famine: A symposium and management. New York.
dealing with nutrition and relief operations in time of Scrimshaw, N. S., et al. 1968. Interactions of nutrition and
disaster. Upsala. infection. World Health Organization Monograph Se-
Burger, G. C. E., et al. 1948. Malnutrition and starvation ries No. 57. Geneva.
in western Netherlands, September 1944-July 1945, 2 Smith, Dean A., and Michael F. A. Woodruff. 1951. Defi-
parts. The Hague. ciency diseases in Japanese prison camps. Medical Re-
Cawte, John. 1978. Gross stress in small islands: A study search Council Special Report Series No. 274. London.
in macro-psychiatry. In Extinction and survival in hu- Taylor, C. E., and Cecile DeSweemer. 1973. Nutrition and
man populations, ed. Charles Laughlin, Jr., and Ivan infection. World Review of Nutrition and Dietetics 16:
Brady, 95-121. New York. 204-26.
Cepede, M., and M. Lengelle. 1953. Economique ali- Turnbull, Colin. 1972. The mountain people. New York.
mentaire du globe. Paris. Tushnet, L. 1966. The uses of adversity. New York.
Chandra, R. K. 1976. Nutrition as a critical determinant Woodham-Smith, Cecil. 1962. The great hunger, Ireland,
in susceptibility to infection. World Review of Nutri- 1845-1849. New York.
tion and Dietetics 25: 167-89.
Colson, Elizabeth. 1979. In good years and bad: Food
strategies of self-reliant societies. Journal of Anthropo-
logical Research 35: 18-29.
Dando, William A. 1980. The geography of famine. New
York.
Dirks, Robert. 1979. Relief induced agonism. Disasters 3:
195-8.
1980. Social responses during severe food shortages and
famine. Current Anthropology 21: 21-44.
Gopalan, C , and S. G. Srikantia. 1973. Nutrition and
disease. World Review of Nutrition and Dietetics 16:
98-141.
Goure, L. 1962. The siege of Leningrad. Stanford, Calif.
Grande, Francisco. 1964. Man under caloric deficiency. In
Handbook ofphysiology, Sec. 4, ed. D. B. Dill, 911-38.
Washington, D.C.
Greenough, Paul R. 1982. Prosperity and misery in mod-
ern Bengal: The famine of 1943-1944. New York.

tice and offered effective treatments. Proponents of
III.6 this model point to the establishment of the germ
A History of Chiropractic theory of disease, the development of diphtheria anti-
toxin, the creation of salvarsan (for use against
syphilis) and the discovery of insulin as evidence of
how scientific progress fueled medicine's expansion.
Chiropractic is a system of healing that holds that According to the second model, political organiza-
disease results from a lack of normal nervous function and lobbying were the critical factors behind
tion caused by a disordered relationship between the medicine's new strength. Proponents of this model
musculoskeletal and nervous systems. Controversial point to demographic data suggesting that medical
from its inception, chiropractic has grown into the practice had little impact on morbidity and mortal-
largest nonallopathic healing profession in the ity and to the aggressive political maneuvering of
United States, with nearly 35,000 active practitio- the AMA to support their argument.
ners. Although considered by many a "marginal" Despite their differences, these two schools share
group, chiropractors are licensed in all 50 states, are the assumption that allopathic medicine established
reimbursed by Medicare, Medicaid, and many third- hegemony over health care during the early twenti-
party payers, and in 1984 earned an average yearly eth century. Neither approach provides a particu-
net income of $55,000. The recent defeat of the larly useful framework for discussing chiropractic,
American Medical Association (AMA) by chiroprac- because each virtually ignores unorthodox medicine.
tors in a major lawsuit dramatically emphasizes chi- Although medicine clearly wielded the greatest in-
ropractic's current strength. The public image of chi- fluence on the U.S. health care system, the success of
ropractic has significantly improved, and opposition chiropractic demonstrates that there are important
from medical organizations has abated. Chiropractic limits to medicine's authority. A close examination
has successfully established itself as an alternative of chiropractic history helps identify those limits
healing profession. and the forces that define them.
At first glance, it seems an unlikely system to
have achieved such success. Chiropractic was founded The Critical Early Years, 1895-1924
in 1895, just as medicine was being transformed into In 1895 Harvey Lillard visited the offices of Daniel
a dominant profession. Successfully uniting dispa- David Palmer. "D.D.," as he is nearly always re-
rate elements of the medical community, the AMA ferred to, had recently opened his practice in Daven-
reorganized in the early 1900s and developed into a port, Iowa, after a varied career that included stints
powerful force, influencing nearly every aspect of as a schoolmaster and grocery clerk. Lillard, a jani-
the U.S. health care system. The homeopathic and tor, complained that ever since he had received a
eclectic sects, important mid-nineteenth-century blow to his neck 17 years ago he had been deaf.
competitors, virtually disappeared during the first Palmer examined the patient and noted a lump in
decades of the twentieth century. Physicians ac- the cervical region. He manipulated Lillard's spine
tively and effectively suppressed competition from and, much to the delight of both patient and practi-
patent medicine vendors with pure food and drug leg- tioner, restored his hearing. Chiropractic was born.
islation. Yet despite the impressive strength of the Therapeutic manipulation was not unknown to
medical profession, chiropractic thrived. Whereas late-nineteenth-century North Americans. They
nearly every other form of unorthodox healing was were aware of the long tradition of massage as a
being suppressed, banned, or co-opted, this system of healing modality. Bohemian immigrants to the Mid-
healing established itself as an independent profes- west practiced a special form of massage, napravit.
sion. By 1930 it was already the largest nonallo- Bonesetting, a form of manipulation involved primar-
pathic sect in the United States, with nearly 16,000 ily in treating orthopedic problems, hadflourishedin
practitioners. some areas. Finally, in Kirksville, Missouri, in 1874,
This extraordinary development does not fit easily Andrew Taylor Still had founded osteopathy, a school
into current historiographic models. Broadly speak- of healing that utilized spinal manipulation.
ing, two models have been offered to explain medi- These diverse healing techniques shared more
cine's enormous growth during the late nineteenth than their emphasis on manual manipulation.
and early twentieth centuries. According to the first, Drugless healing was an important theme in many
medicine benefited from scientific developments, nonallopathic systems in the mid-nineteenth cen-
which provided a new rational basis for medical prac- tury. It was part of a larger response to the excesses

III.6. A History of Chiropractic 165
of "heroic" therapies (i.e., vigorous cathartics, emet- chiropractic and contrasted sharply with the view of
ics, and bloodletting) and in fact, mid- and late- medicine's new research elite. Increasingly secular,
nineteenth-century healers, both inside and outside the science of medicine was located in university
the medical profession, increasingly began to empha- laboratories, required special training, and was
size milder interventions. They shared a growing based on a reductionist philosophy. Deductive reason-
recognition that the worth of many conventional ing and the manipulation of nature in an experimen-
remedies had never been scientifically proved and tal setting were its hallmarks. In contrast, chiroprac-
placed a new emphasis on the healing power of na- tors emphasized a different scientific approach. A
ture. Their skepticism about heroic medicine was scientist observed nature, collected facts, classified
epitomized by the words of Oliver Wendell Holmes these facts, and thereby gained insights into the
when he proclaimed in 1860 that, with the exception laws of nature. Furthermore, science linked the
of a few specific remedies, "if the whole materia physical and spiritual worlds and reemphasized the
medica, as now used, could be sunk to the bottom of perfection of the Creator. In his seminal 1910 work,
the sea, it would be all the better for mankind and Textbook of the Science, Art and Philosophy of Chiro-
all the worse for the fishes." practic, Palmer explained:
Nonallopathic healers took advantage of this cli-
Chiropractic is the name of a systematized knowledge of
mate arguing against any pharmacological therapy,
the science of life . . . an explanation of the methods used
and host of drugless alternatives developed, among to relieve humanity of suffering and the prolonging of life,
them hydropathy, osteopathy, and magnetic healing. thereby making this stage of existence much more effi-
As a drugless system that emphasized the body's cient in its preparation for the next step, a life beyond.
natural healing powers, chiropractic fit easily into
this important nineteenth-century trend. Palmer believed that science ought to serve a subordi-
Briefly stated, Palmer's chiropractic fused mag- nate and supportive role in relation to religion. A
netic healing with therapeutic manipulation. Palmer significant portion of U.S. society shared that view as
believed that subluxations of the spinal column the popularity of fundamentalism in the 1920s and
caused disease by impinging on the nervous system the Scopes monkey trial dramatically demonstrated.
and inhibiting the flow of the body's vital "fluid," Thus, the chiropractic approach to science remained
which Palmer called "innate intelligence"; disease a powerful model well into the twentieth century,
resulted from either a deficiency or an excess of this with its legitimacy resting heavily on the assumption
fluid. By examining the patient's spine, a chiroprac- that science should reflect God's grandeur.
tic could detect the malalignment responsible for the Ironically, chiropractors also sought to benefit
patient's ailment, manually manipulate the verte- from the growing prestige of science. They deflected
brae, and restore normal alignment, allowing the allopathic attacks on chiropractic as quackery by
return of proper nervous function. Once the normal arguing that their system of healing was a truly
flow of "innate intelligence" resumed, the body's in- scientific way of dealing with disease. In fact, they
ner healing powers ensured a return to health. even launched their own offensive by ridiculing phy-
Palmer argued that his chiropractic approach of- sicians for adopting a scientific approach that epito-
fered the world an important new philosophy. He mized the corrupt "atheistic materialism" that was
believed that God had created a balanced, ordered destroying the United States.
universe and that equilibrium was the fundamental Their efforts to reconcile science and religion by
organizing principle of life. "Innate intelligence" rep- emphasizing the primacy of God attracted support at
resented God's presence in human beings. Subluxa- a time when the appropriate relationship between
tions created disequilibrium, and the inevitable se- science and religion was hotly contested. They ar-
quela of this violation of natural law was disease. gued that by using drugs and surgery as therapies,
Palmer's vision was consonant with cultural and and by failing to appreciate the importance of the
intellectual assumptions that were prevalent in the spiritual in health and disease, physicians rejected
United States at the turn of the century. It linked the healing power of nature, and implicitly rejected
health care to a worldview in which God was benevo- the beneficence and wisdom of God Himself. When
lent and ruled the universe through natural laws. It surgeons began to perform an increasing number of
emphasized that there should be no conflict between appendectomies in the early twentieth century, chiro-
religion and science; science served religion by dem- practors sarcastically noted that it seemed odd that
onstrating the Creator's natural laws. the creator of the universe had made the mistake of
This view of science was a critical component of giving humans a useless appendix. By focusing on

the appendix, an organ presumed to be a vestigial patient. In contrast, chiropractic colleges required
remnant of the evolutionary process, chiropractors no formal educational background and no foreign
highlighted their allegiance with antievolutionists. languages. Anyone with common sense who was
Chiropractic's appeal extended beyond the scien- willing to apply himself or herself could become a
tific and philosophical. Important turn-of-the-cen- chiropractor.
tury social and political themes also reverberated in Although necessary, the congruence of chiroprac-
the chiropractic literature. Chiropractors repeatedly tic's social, political, cultural, and scientific appeals
characterized the AMA as a trust, invoking a famil- with early-twentieth-century beliefs was not suffi-
iar and powerful image central to this era of reform. cient to ensure the system's survival. To be success-
They pointed to the growing public health movement ful, chiropractic needed more than a coherent mes-
as an indication that medicine, like all trusts, ma- sage; it needed a leader. The man who responded to
nipulated government to its own profit. Compulsory this need was Bartlett Joshua Palmer.
allopathic examination of schoolchildren and the B.J., as he is invariably referred to, was D. D.
armed forces' refusal to use nonallopathic healers, Palmer's son. When the elder Palmer was jailed in
they contended, demonstrated the power of medicine 1906 for violating the medical practice law, B.J. took
over government. over the reigns of the Palmer School of Chiropractic
Like all trusts, medicine was ruled by a narrow (P.S.C.). Under his charismatic leadership both the
circle of conspirators. It was not the trustworthy, school in Davenport, Iowa, and the general focus of
rural general practitioners who were responsible for chiropractic expanded enormously. B.J. began to
medicine's monopolistic excesses; they too were be- market this system of healing aggressively, and en-
ing duped by a small group of eastern, elite intellec- rollment at the P.S.C. increased from a trickle, to a
tuals. This argument sought to capitalize on the stream, to a flood. There had been a total of 15
disgruntlement of those physicians who resented the graduates in the decade before B.J. inherited the
AMA's increasing emphasis on research science. Fur- school. Starting in 1921 the P.S.C. graduated more
thermore, it allowed individuals to condemn the than 1,000 students per year. Although the number
medical profession but to retain confidence in their of graduates soon declined into the hundreds, the
personal physician. Palmer School remained a major chiropractic institu-
Chiropractors accused medicine of dominating tion throughout B.J.'s career.
the media, another characteristic of monopolies. B.J. did not limit his efforts to the development of
They cited AMA boycotts of newspapers that con- the P.S.C. He tirelessly proselytized for all of chiro-
tained "quack" advertisements and the explosive practic. Establishing a printing office at the Palmer
increase in the number of press releases by physi- School, he turned out a flood of chiropractic litera-
cians' organizations. ture. He opened one of the first radio stations in Iowa,
The chiropractic solution to the problem of the over whose powerful airways he proclaimed the bene-
medical trust was simple: open competition. The fits of chiropractic healing. B.J. went on lecture tours,
United States was built on rugged individualism. organized the Universal Chiropractors Association,
The merit of each practitioner and each healing lobbied legislators, and appeared at trials. A nearly
profession should be established solely by a jury of cultlike atmosphere developed around him and few
patients. Individuals should determine whether could be neutral about the man. Nonetheless, B.J.'s
their health care was adequate; government regula- forceful advocacy of chiropractic created more public-
tion was unnecessary and demeaned the "common ity, which was necessary to the development of the
man" by suggesting that he was incapable of assess- field. Indeed, it began to flourish as his efforts com-
ing the quality of his health care. Physicians had bined this system of healing with a philosophy of
no right to expect governmental protection or to health and disease that resonated with important
hold themselves up as elite members of the healing concerns for many North Americans. The growing
profession. Rather, they were a wealthy aristocracy influence of chiropractic arguments and chiroprac-
attempting selfishly to protect their interests. AMA tors is suggested by their ability to convince legisla-
efforts at educational and licensing reform were tors that chiropractors deserved licensure. In 1913
guaranteed to exclude the honest poor from the Kansas passed the first law recognizing chiroprac-
medical profession. By requiring collegiate training tors, and several other states in the Midwest soon did
before medical school and the use of Latin prescrip- the same. By the 1930s, despite vigorous medical
tions, the AMA had erected artificial barriers de- opposition, chiropractors had obtained some form of
signed to elevate the physician and intimidate the legal recognition in 32 states. Despite the skepticism

and outright hostility of physicians, millions of North machines. Machines created change, and although
Americans were consulting chiropractors. change could be positive, it also caused uncertainty
and upheaval. As industrialization proceeded during
Parallel Evolution, 1920-60 the late nineteenth and early twentieth centuries,
The rapidly changing medical, social, and political many were uncertain whether the changes induced
landscape of the 1920s to the 1960s challenged chiro- by modern technology were improvements, and
practic's ability to adapt and thus to survive. On the straight chiropractors were able to tap into this well-
one hand, an excessive reliance on beliefs and theo- spring of concern.
ries developed in the 1890s might render this system Conversely, the "mixers" utilized the positive im-
anachronistic. On the other, chiropractic risked los- age of technology to foster their growth. Machines
ing its distinctive character if it underwent radical were new and exciting, the wave of the future, and
reform and became "medicalized." An examination chiropractic needed to take advantage of modern
of the changing role of technology in chiropractic, technology in order to see that future. Many mixer
the modification of its criticisms of the germ theory, schools, led by the National School of Chiropractic of
and the stiffening of chiropractic educational stan- Chicago, advocated using diagnostic and therapeutic
dards will demonstrate how it successfully re- adjuncts. As if to emphasize its differences with the
sponded to the challenge. straight chiropractors, the National School of Chiro-
practic had several physician-chiropractors on its
Mixers versus Straights: Technology in faculty by 1916.
Chiropractic As the leader of straight chiropractic, B. J. Palmer
At the 1924 annual homecoming of the P.S.C, B. J. had rarely declined an opportunity to ridicule the
Palmer made a startling announcement: Henceforth mixers. When he suddenly declared that the neuro-
the "neurocalometer" would be a vital component of calometer was not only acceptable but central to
the chiropractic system. Touted as a breakthrough chiropractic practice, many ardent supporters were
for scientific chiropractic, the neurocalometer was a outraged. Four key members of the Palmer School
machine designed to help diagnose subluxations by faculty resigned. Palmer was accused of betraying
registering differences in heat alongside the spinal his colleagues, and because the neurocalometer
column. It could be obtained only from the Palmer could be obtained only from Palmer, many thought
School for $500 and a $1.00 per month service he had been motivated by greed. The neurocalom-
charge. eter debate signaled an important change in chiro-
Chiropractors were stunned, and with good rea- practic. Although advocates of straight practice con-
son. Since chiropractic's earliest years, the use of tinued to play an important role, their strength
technology had engendered enormous controversy. waned and gradually most chiropractors incorpo-
B. J. Palmer himself had argued strenuously that rated adjuncts into their practice. The introduction
diagnosis and treatment should be performed only of the neurocalometer in 1924 reflected a shift in
by manual manipulation. In fact, he claimed that U.S. attitudes toward technology, for the prosperity
the Palmer School taught chiropractic "P, S, and of the 1920s had eased earlier fears about it while
U" - pure, straight, and unadulterated - and scorn- highlighting its economic benefits. B. J. Palmer's
fully labeled any practitioners who utilized other acceptance of machines is best seen in this light. As
modalities as "mixers." machines became firmly enmeshed in the fabric of
For "straight" practitioners, chiropractic was a U.S. life, it became untenable for this system of
natural system of healing that allowed the body to healing to reject them, although the distinction be-
manifest its intrinsic restorative powers. The use of tween straights and mixers, while increasingly
machines implied that natural methods of diagnosis blurred, would endure for some time.
and treatment were inadequate. By avoiding the use
of machines, chiropractic buttressed its argument The Germ Theory and Chiropractic
that it was fundamentally different from medicine, Another milestone in the evolution of chiropractic
which relied increasingly on new technologies dur- was an increasing acceptance of the germ theory of
ing the early years of the twentieth century. By disease. At first many chiropractors had rejected the
rejecting technology, chiropractic also avoided regu- notion that bacteria could cause disease. However,
lation under medical practice laws. as germ theory achieved widespread acceptance,
On a deeper level, the rejection of technology re- they realized that rejection of the association be-
flected the ambivalence of many Americans toward tween bacteria and disease would make chiropractic

seem retrogressive. Accordingly, chiropractors no schools, many of which had curricula that required
longer insisted that bacteria could not cause disease only 18 months of schooling.
but instead argued that bacterial infection was a Chiropractors responded by gradually embracing a
secondary phenomenon that occurred only in per- professional model of training and reducing 79
sons whose ability to resist disease had been vitiated schools in 1920 to only 21 by 1932. Those that re-
by a spinal subluxation. This stance allowed chiro- mained increased the period of training and strength-
practors to highlight a major problem with germ ened their faculties, and schools that had previously
theory: If the key to disease was simply infection emphasized how rapidly one could become a chiro-
with pathogenic organisms, why didn't everyone ex- practor increasingly stressed the advantages of their
posed to a germ become ill? Or why did some people clinical facilities, eminent faculty, and comprehen-
infected with the same organism die and others expe- sive curricula. In 1935 the National Chiropractic
rience only a mild illness? By emphasizing resis- Association (NCA), the mixers' professional organi-
tance as the key to health and disease, chiropractors zation, established a Commission on Educational
retained their explanatory model while continuing Standards. This led to the adoption of formal accredit-
to challenge formal medicine. ing procedures, and the International Chiropractors
Association, the straight chiropractics' representa-
Educational Reform in Chiropractic tive, followed suit. Spurred by the tireless efforts of
Education provides another window on the develop- John Nugent, director of education of the NCA, a
ment of this system of healing. During the earliest continual strengthening of educational standards oc-
years of chiropractic, disagreements developed over curred in the 1940s and 1950s.
what, if any, formal education should be required. The adoption of technology, reconceptualization of
One group of practitioners, commonly referred to as the relationship between bacteria and disease, and
"field-men," opposed any formal training, arguing educational reform were all ways in which chiroprac-
that it was elitist. They felt that chiropractors should tors responded to a changing environment. Chiro-
reject the medical model of education with its empha- practic's ability to retain its distinct identity while
sis on "book-learning" and instead rely on the practi- undergoing this evolution helps explain how it has
cal training that an apprenticeship provided. Al- avoided the fate of other alternative healing sects.
though the field-men's arguments were heavily The evolutionary trajectories of medicine and chiro-
influenced by their concern that licensing legislation practic can be conceived of as two parallel lines, and
would exclude practitioners who lacked a chiroprac- the ability of the latter to maintain a constant dis-
tic diploma, their stance also highlighted the ideo- tance from medicine is perhaps the most remarkable
logical commitment to egalitarianism that many chi- quality in its historical development. If the distance
ropractors felt their field should embody. between the two professions had narrowed, as in
Competition among chiropractic colleges also in- the case of homeopathy and osteopathy, chiroprac-
hibited the adoption of educational standards. Each tic would have risked losing its identity. If the dis-
institution vied for students and wanted to be recog- tance had widened, chiropractic would have risked
nized as the "true" standard bearer of the profession. becoming anachronistic. Instead, it flourished as it
Each had a slightly different definition of chiroprac- adroitly maneuvered between the Scylla of conver-
tic, typically dividing along the "mixer-straight" gence and the Charybdis of divergence.
axis. Each wanted its own diploma to be the exclu-
sive prerequisite for a chiropractic license. Attempts From Marginally Acceptable to the
to block the legislative recognition of rivals occasion- Acceptable Margin: The 1960s through the
ally resulted in open warfare among the schools. 1980s
Despite this contentious beginning, the conviction The 1950s and 1960s were a golden age for med-
that there was a need for minimal educational stan- icine. Federal support for biomedical science ex-
dards gradually gained wider acceptance. Exposes of panded enormously after World War II, and im-
mail-order chiropractic "colleges" had tarnished the pressive diagnostic and therapeutic advances aided
reputation of the entire profession, and the dramatic medicine's emergence as the most highly regarded
reform of medical education in the early twentieth profession in the United States. Federal subsidies
century had opened a wide gap between the training for hospital construction helped create an enormous
standards of regular physicians and those of chiro- health care industry.
practors. Physicians exploited this difference by fre- Simultaneously, chiropractic seemed to stagnate.
quently ridiculing the standards of chiropractic It received no significant federal support, and indi-

rect subsidies, in the form of support to veterans again became controversial in chiropractic, and a
under the G.I. bill tofinancetheir chiropractic educa- new "superstraight" faction emerged that eschewed
tion, were small indeed in comparison with the mas- nearly all machinery.) The AMA's antichiropractic
sive investment in orthodox medicine. Perhaps more efforts may have paradoxically created new support
than ever before, medicine dwarfed chiropractic, and for this system of healing.
in the early 1960s the AMA set out to destroy it. The Chiropractic witnessed much more cohesion among
motives for its assault ranged from concern that its practitioners, for efforts by the medical profes-
chiropractic was gradually achieving acceptance to sion to eradicate it had the effect, despite the persis-
the conviction that chiropractors were unscientific tent argument between mixers and straights, of
cultists who were detrimental to the public health. unifying chiropractors. Certainly, the tangible mani-
The assault was launched by the AMA Committee festation of chiropractic unity was adept political
on Quackery, created in 1963. maneuvering. From their earliest struggles to ob-
The committee mounted an intensive campaign. tain state licensure at the beginning of the twenti-
Under its direction, the AMA adopted a resolution eth century, chiropractors have demonstrated a con-
calling chiropractic an unscientific cult, distributed siderable mastery of the U.S. political process and
publications critical of its practice, and discouraged thus, despite opposition from the vaunted AMA
medical organizations from condoning interactions lobby, they have shrewdly combined personal ap-
between physicians and chiropractors, even declar- peals, mass mailings, and the efforts of paid lobby-
ing consultation with chiropractors unethical. ists to promote their goals.
Despite this remarkable onslaught, chiropractic Finally, chiropractic began explicitly to limit its
not only survived but thrived. During the tenure of claim of effectiveness and increasingly emphasized
the committee (1963-74), chiropractic greatly ex- its role in the management of musculoskeletal disor-
panded as schools opened, the number of chiroprac- ders. In 1969 both major chiropractic associations
tors grew, and licensing was granted in the few rejected the "one cause-one cure" tenet of chiroprac-
states that had withheld it. Chiropractic achieved tic. This freed chiropractors from having to respond
federal recognition when it became incorporated to medical hecklers who ridiculed them for believing
into the Medicare and Medicaid programs. that cancer, diabetes, and other ills were caused by
The ability of chiropractic to resist AMA's assault spinal subluxations. Growing evidence supported
rested on four important developments: (1) a new chiropractic's contention that it was an effective
social climate, (2) improved intraprofessional cohe- therapeutic modality for low back pain. The preva-
sion, (3) shrewd political maneuvering, and (4) jetti- lence of this condition combined with orthodox medi-
soning of its one cause-one cure hypothesis. A new cine's paucity of effective treatments for back
social climate had come about with the extraordi- problems helped chiropractors define a niche for
nary upheavals of the 1960s. The civil rights move- themselves in the U.S. health care system.
ment, the women's movement, the antiwar move- By the mid-1970s chiropractic occupied a new and
ment, and the environment movement, among greatly strengthened position. In the face of a chang-
others, rejected the status quo. What had previously ing social climate and numerous antitrust lawsuits
been held to be authoritative was now condemned as instituted by chiropractors, opposition from orga-
authoritarian. Science and technology were no nized medicine began to abate. The AMA and other
longer accepted as unalloyed good, critics argued medical organizations grudgingly recognized that
that physicians had lost touch with the art of medi- there might be some benefits from spinal manipula-
cine, and conventional health care came to be tion, and of course the inclusion of chiropractic in
viewed as impersonal, costly, and inefficient. Long the Medicare and Medicaid programs helped legiti-
critical of organized medicine, chiropractors began mize the profession. In 1979 a conference sponsored
to find an increasingly receptive audience as toler- by the National Institute of Neurological and Com-
ance for, and interest in, alternative medicine ex- municative Disorders and Stroke of the National
panded enormously. Chiropractic benefited greatly Institutes of Health addressed the research status of
from this new openness and yet, as a well- spinal manipulative therapy. At this meeting, medi-
established profession, simultaneously avoided the cal doctors, osteopaths, scientists, and chiropractors
appearance of being a fad. The criticism that medi- exchanged information. Although the scientific ba-
cine was too reliant on technology led chiropractors sis for manipulative therapy remained a subject of
to reemphasize their reliance on "natural" healing. debate, a consensus emerged that this therapy was
(Ironically, the use of technologies like diathermy of clinical value in the treatment of back pain. The

fact that chiropractic was seriously discussed by a
branch of the National Institutes of Health - one of III.7
the cathedrals of scientific medicine - symbolizes Concepts of Addiction: The
how far chiropractic had traveled.
Although, as this essay has shown, chiropractic U.S. Experience
has become more acceptable to the mainstream of
U.S. society, it has not become widely accepted as a
conventional therapy. The majority of Americans Addiction has remained a vague concept in spite of
have never visited a chiropractor, and considerable efforts to define it with physiological and psychologi-
confusion exists about what chiropractors do. How- cal precision. The word's Latin root refers to a legal
ever, the number of people who have been treated by judgment whereby a person is given over to the
a chiropractor is gradually increasing, and chiroprac- control of another. In recent centuries the meaning
tic's public image is improving. The periphery of the has ranged from a simple inclination toward an ac-
U.S. health care system is perhaps the ideal position tivity or interest to an uncontrollable desire to take
for chiropractic. It provides legitimacy while allow- opium, which historically was viewed as the most
ing for the distance from conventional medicine that addictive of drugs. Opiate addiction is characterized
is fundamental to chiropractic's identity. chiefly by the repeated use of the drug to prevent
withdrawal symptoms, which include muscle and
Steven C. Martin
joint pains, sweating, and nausea. The extreme dis-
comfort of withdrawal passes away after one to three
Bibliography days, although a yearning for the drug may last for a
Baer, Hans A. 1987. Divergence and convergence in two very long time. Some attempts to define addiction in
systems of manual medicine: Osteopathy and chiro- medical terms (e.g., restricting it to opiate with-
practic in the United States. Medical Anthropology drawal phenomena) have led to confusion among
Quarterly 1: 176-93. members of the public because cocaine, according to
Brennan, Matthew J. 1987. Demographic and professional
that restricted definition, would be considered nonad-
characteristics of ACA membership: 1987 annual sur-
vey and statistical study. Arlington, Va. dictive and, by implication, safer than the opiates.
Cooper, Gregory S. 1985. The attitude of organized medi- For the sake of brevity, this essay considers chiefly
cine toward chiropractic: A sociohistorical perspec- opium and coca and their constituents and deriva-
tive. Chiropractic History 5: 19—25. tives. The chemicals that could be discussed range
Dye, A. Augustus. 1939. The evolution of chiropractic: Its from the barbiturates to lysergic acid diethylamide
discovery and development. Philadelphia. (LSD), but the models of control and therapy com-
Gibbons, Russell W. 1980. The evolution of chiropractic: monly applied to these other substances evolved in
Medical and social protest in America. In Modern the past two centuries from experience with the coca
development in the principles and practice ofchiroprac- bush, opium poppies, and their powerful alkaloids.
tic, ed. Scott Haldemann, 3-24. New York.
1985. Chiropractic's Abraham Flexner: The lonely jour-
ney of John J. Nugent, 1935-1963. Chiropractic His- Opium
tory 5: 44-51. The opium poppy appears to be indigenous to the
Palmer, Bartlett J. 1917. The science of chiropractic, 3d eastern Mediterranean area. The manner of produc-
edition. Davenport, Iowa. ing crude opium is to scratch the surface of the poppy
Palmer, Daniel D. 1910. Textbook of the science, art, and pod and scrape off the juice that exudes, collecting
philosophy of chiropractic. Portland, Ore. and drying the material until it is solid. This crude
Reed, Louis. 1932. The healing cults. Chicago. opium can be taken alone or in combination with
Turner, Chittendon. 1931. The rise of chiropractic. Los other substances. Mithradatum, theriac, and philon-
Angeles. ium are three ancient and renowned medicines that
Wardwell, Walter I. 1972. Limited, marginal, and quasi- contained opium, among other substances, when
practitioners. In Handbook of medical sociology, 2d compounded during the early centuries of the Ro-
edition, ed. Howard E. Freeman, Sol Levine, and Les man Empire, although in subsequent eras opium
G. Reeder, 250-73. Englewood Cliffs, N.J.
1988. Chiropractors: Evolution to acceptance. In Other
was not invariably a constituent.
healers: Unorthodox medicine in America, ed. Norman The smoking of opium, so closely associated with
Gevitz, 157-91. Baltimore. China in the nineteenth and early twentieth centu-
Wilk v. American Medical Association. 1987. 671 F. Supp. ries, appears to have been introduced to the Chinese
1465 (N.D. 111.). in the seventeenth century by Dutch traders who had

EII.7. Concepts of Addiction 171
earlier supplied tobacco for smoking. The Chinese mouth, clysis, or absorption through denuded skin, as
government attempted to outlaw the practice as early after blistering. The refinement of the hypodermic
as 1729, but through much of the nineteenth century, syringe and needle at midcentury created a mode of
as supplies came from the region of Turkey and Per- delivery as revolutionary in the history of addiction
sia and later mostly from India, the attraction of as had been the isolation of morphine.
smoking opium grew. The attempts of some Chinese Hollow needles and syringes had been employed
administrators to cut off foreign opium importation long before the appearance of the familiar syringe
were frustrated by the defeat of China in the so-called and needle in the nineteenth century, but the grow-
Opium War of 1839-42. Near the close of the century, ing number of purified chemicals, such as mor-
young reformers blamed widespread addiction to phine, that could be directly injected into the body
opium and consequent lethargy and inefficiency for stimulated the pace of development and production.
China's defeat by Japan in 1895. In response to a At first, injected morphine was considered less
growing antagonism to opium use, the dowager em- likely to be addictive than oral morphine because a
press Tzu Hsi instituted a program to eliminate do- smaller amount was required for equivalent pain
mestic opium production and to seek a reduction in relief. But by the 1870s this assumption was found
the importation of opium from India. This action was to be erroneous, although many physicians contin-
one of three crucial events in 1906 that led to a world- ued to use injected morphine for chronic ailments,
wide effort to control the production and distribution such as arthritis.
of opium and the opiates.
The second event was the Liberal Party's victory in Restrictions
the British parliamentary elections. The Liberal In most European nations, the central government
Party had long taken a stand against sending opium controlled the practice of medicine and the availabil-
from India to China against the will of the Chinese ity of dangerous drugs through legislation. In addi-
people and government, although treaty rights to do tion, by the mid-nineteenth century, European phy-
so had been established by the British military. Com- sicians and pharmacists had organized themselves
plicity in facilitating Chinese addiction to opium on a national level. By contrast, in the United
deeply offended many Britons, especially those who States the federal government relegated to the indi-
promoted Christian missionary efforts in China. Pre- vidual states control over the health professions,
vious British governments had argued that opium and the professions themselves were poorly orga-
was not particularly harmful, being the equivalent of nized nationally. No laws controlled the sale of,
distilled spirits among Westerners, and that the contents of, or claims for "patent medicines," and
opium trade was needed to pay for the British admin- there were few local laws restricting the availabil-
istration in India. After 1906, however, cooperation ity of opium, morphine, and, later, cocaine. The
between the British and Chinese governments in result was a thriving and open market in these
curbing opium production was theoretically possible. substances until late in the century, when some
The third major antiopium event of 1906 was the states began to enact laws preventing the acquisi-
U.S. decision to convene the Shanghai Opium Com- tion of opiates and cocaine except with a physician's
mission, a decision that reached fruition in.1909, as prescription. The U.S. Constitution grants the regu-
is discussed in the section on the origin of interna- lation of commerce among the states to the federal
tional control. government, so no state law could affect the sale of
drugs or products across state lines. The conse-
quence was a higher per capita consumption of
Morphine and the Hypodermic Syringe opium and opiates in the United States than in
The isolation of morphine from opium by F. W. A. other Western nations and even, a government offi-
Sertuener in 1805 marked the beginning of a new era cial claimed in 1910, more than the legendary con-
in opium use. Physicians now had access to a purified sumption of opium in China.
active ingredient; hence, they were no longer un-
certain of the strength of a dose and could investigate
the effect of a specific amount. Commercial produc- Addiction and Its Treatment
tion followed the isolation of morphine and by the The model of addiction to opium and opiates is the
1830s morphine was commonly available in any area one to which addiction to other substances has been
touched by pharmaceutical trade with Europe and compared. Such addiction has long been viewed in
the United States. Morphine was administered by moral terms, with the addict seen as "vicious" or

"degenerate," driven by a "sinful" desire for plea- ual withdrawal was a technique that favored outpa-
sure. But as drugs were increasingly used to treat tient care and self-treatment by over-the-counter ad-
illnesses it was also understood that an individual diction "cures." Critics of this method argued that
could inadvertently become addicted to them - an many addicts could lower their opiate intake only to
understanding that has helped to give rise to the a certain level below which they could not comfort-
biological concept of addiction as an illness. ably descend. An example of this threshold is the
The investigation of addiction has experienced a case of William Steward Halsted, a physician at
decided shift over the past two centuries or so from Johns Hopkins Medical School who had to take a
the moral view of addiction as "sin" to the biological daily amount of morphine, about two to three grains,
concept of addiction as disease, prompting some to for the last 30 years of his life.
argue that the "disease" in question was invented Halsted's experience suggests the third option, in-
rather than discovered. Yet as more and more have definite opiate maintenance. Of course, the strong,
adopted the view of addiction as a disease, the ques- and for some the invincible, hold that opiates had
tion of susceptibility has arisen, with biologists oscil- over a user is what led to popular and professional
lating between the conviction that everyone is fear of narcotics. Perpetuating addiction was the
equally susceptible and the belief that only some are opposite of curing it, and initially the reason for
susceptible for psychological as well as physiological doing it was simply the difficulty of stopping. Early
reasons. in the twentieth century, however, scientific reasons
Such ambivalence can also be found in legal sys- for maintenance were advanced. Influenced by the
tems that attempt to distinguish between morally rise of immunology, some researchers theorized that
"superior" and morally "inferior" addicts and in the the body produced antibodies to morphine. If the
medical profession, where physicians for a century level of morphine dropped below that required to
have tried to find among their patients signs that "balance" the antibodies, the antibodies would pro-
would warn of addictive liability. These questions are duce withdrawal symptoms. Thus, unless the anti-
still relevant to contemporary addiction research. bodies and every vestige of morphine could be re-
During the nineteenth century, once opiate addic- moved from the individual, maintenance would be
tion became familiar to physicians, a debate ensued required to create a normal physiological balance.
over whether the continuous use of opium was a Research produced no evidence of antibodies to
habit or a disease over which the patient had little morphine, but a less specific claim found adherents
control. The debate was complicated by a belief that around the time of World War I. The hypothesis was
abrupt withdrawal from opium could cause death. that continued exposure to a substance like mor-
Three options were proposed and vigorously de- phine caused a pathological change in the body's
fended. The first was abrupt withdrawal, recom- physiology that could not be altered by any known
mended almost exclusively as a hospital procedure. treatment, but required indefinite maintenance for
The addict was considered to be ingenious in obtain- normal functioning. This hypothesis was rejected in
ing drugs and to have a will so weakened by addic- the antiaddiction fervor just after World War I in the
tion and craving for opium that, unless he or she was United States, although it was revived by Vincent
securely confined, withdrawal would not be success- Dole and Marie Nyswander in the 1960s as a justifi-
ful. It could be assisted by the administration of cation for maintenance by methadone, a synthetic,
belladonna-like drugs that counteracted withdrawal long-acting opiate.
symptoms such as sweating. These drugs also caused A treatment for addiction that found wide accep-
delirium, which, it was hoped, would have the effect tance in the first two decades of the twentieth cen-
of erasing the addict's memory of the withdrawal. tury, especially in the United States, was described
(Scopalamine is given today just before general anes- by Charles B. Towns, the lay proprietor of a hospital
thesia for a similar reason.) The high rate of relapse for drug and alcohol abusers, and Alexander Lam-
in the weeks after treatment brought into question bert, a respected professor of medicine at Cornell
the value of detoxification. Medical School and later president of the American
The second option was gradual withdrawal, recom- Medical Association. An insurance salesman and
mended because of the presumed ease of the treat- stockbroker, Towns purchased from an anonymous
ment as well as the fear that sudden termination of person a general treatment for addictions. Lambert
the opiate would result in death. The idea that became convinced of the treatment's efficacy, and he
abrupt withdrawal could cause death was not widely and Towns published it jointly in the Journal of the
refuted in the United States until about 1920. Grad- American Medical Association in 1909. The reputa-

III.7. Concepts of Addiction 173
tion of the Towns-Lambert treatment can be gauged Cocaine
by the fact that the U.S. delegation attempted to Cocaine, a central nervous system stimulant, offers
persuade the Shanghai Opium Commission to ap- a contrast to the opiates, although both have been
prove the treatment formally. The commission de- subject to extreme praise and condemnation. Coca
clined to do so. bushes are native to South America, and the leaves
The treatment, which combined various medical have been chewed there for millennia. The amount of
theories of the time, was based on the belief that cocaine extracted by chewing was increased by the
morphine or other addicting substances had to be addition of an alkaline substance to the wad of leaves,
eradicated from the body. Therefore, a powerful but the tissue level of cocaine obtained in this way
mercury-containing laxative, called "blue mass," was small compared with that obtained from the puri-
was administered several times, culminating in the fied alkaloid cocaine, identified and named by Albert
passing of a characteristic stool that brought a pro- Niemann in 1860. Cocaine was not commercially
found sense of comfort. During the latter part of the available until the early 1880s. Before it was intro-
therapy a formula, chiefly belladonna and hyoscine, duced to the market, extracts of coca leaves, often in a
which presumably counteracted the symptoms of wine solution such as Vin Marianni, found favor as a
withdrawal, was given at half-hour intervals. In the tonic both with physicians and with the public.
early years of this treatment, prominent physicians Pure cocaine proved extraordinarily popular.
such as Richard C. Cabot of Boston allowed their Within a year of its introduction in the United
names to be closely associated with that of Towns. In States in 1884, Parke, Davis & Co. offered cocaine
the years immediately after World War I, however, and coca in 14 forms. Cocaine was expensive, but
Lambert rejected the treatment as worthless and soon became an ingredient in the new drink Coca-
adopted the position then becoming popular that Cola and was found to be a specific remedy for hay
there was no specific treatment for addiction. Towns, fever and sinusitis. Within a few years, reports ap-
by contrast, continued to operate his hospital in New peared in medical journals and the popular press
York, applying the same treatment to alcohol addic- telling of ruined careers and bizarre behavior among
tion. "Bill W." received the inspiration to found Alco- some users, but eminent experts such as William A.
holics Anonymous while undergoing treatment at Hammond, a professor of neurology in New York
the Towns Hospital in 1934. medical schools and a former surgeon-general of the
In subsequent years, the treatment of opiate addic- U.S. army, reassured the profession and the public
tion has focused on achieving abstinence following that cocaine was harmless and the habit no more
detoxification, or maintenance using heroin, mor- severe than that of drinking coffee.
phine, or methadone. Even when abstinence is Within 10 years, however, observers raised serious
achieved, however, relapses are common. In the doubts that cocaine was as safe as had been asserted
1970s pharmacological research led to the develop- by Hammond and by cocaine's chief advocate in Eu-
ment of naltrexone, which blocks the effects of opi- rope, Sigmund Freud. By the first decade of the twen-
ates, and several new drugs, most prominently tieth century, cocaine was no longer considered an
clonidine, that lessen the discomfort of withdrawal. ideal tonic but an extremely dangerous substance. In
The popularity of treatment and the growing em- the United States, this new image, now associated
phasis on law enforcement to curb supply and pun- with uncontrolled consumption, violence, and dis-
ish users reflect social attitudes toward drug use. torted thinking, provided powerful impetus to estab-
These attitudes have, in the course of a long span of lish a national antinarcotic law, despite constitu-
drug consumption, evolved from toleration of use tional restrictions. In most other nations cocaine
during the decades immediately following the intro- production and distribution was already regulated
duction of new substances, such as cocaine, to ex- by national pharmacy laws. Through a complex se-
treme hostility toward drugs and drug users as the ries of events, the United States placed a national
"epidemic" wears on. In the United States, medical prohibition on narcotics use except for medical pur-
and therapeutic approaches initially found favor but poses and initiated an international campaign to con-
have since given way to law enforcement in response trol the production and distribution of opiates and
to the public's belated fearful reaction to the effect of cocaine.
drugs on individuals and society. Some countries,
such as Indonesia, employ the death penalty against The U.S. Response to Addiction
drug suppliers, whereas others rely on less stringent The per capita consumption of narcotics in the
controls. United States was officially described in the late

nineteenth century as much higher than that of any Philippine Islands. The U.S. Congress took a more
comparable Western nation, perhaps even that of severe stance, mandating total prohibition of opium
China. This may well have been the case, but reli- and derivatives, except for medical purposes, for Fili-
able comparisons are often difficult to make, partly pinos in 1905 and all other groups (mainly Chinese)
because drug use and addiction have been topics in the Islands in 1908.
relatively neglected by historians. It was obvious to the U.S. government that its
Concern in the United States over opiate addiction meager enforcement could not prevent the smug-
and the rise in consumption, which reached a peak gling of opium into the Philippines. Conflict with
in the 1890s, led to state laws that in most instances China over the treatment of Chinese aliens in the
made morphine available only by a physician's pre- United States along with the crucial events of 1906
scription, although there was no restriction on inter- in China and the United Kingdom provided Bishop
state commerce. Cocaine use increasingly worried Brent with a rare opportunity. He wrote President
the public, who associated it with the underworld Theodore Roosevelt urging that the United States
and assumed that its use by blacks was a cause of convene a meeting of relevant nations to assist
unrest among them in the South. The latter associa- China with its antiopium crusade. Successful control
tion exemplifies the linkages so easily made by the of narcotics traffic would aid the Philippines and the
public between drugs and social problems. United States, and might also placate China. The
Some of the unusual factors associated with exten- acceptance of Brent's idea resulted in a survey of the
sive narcotics use in the United States (i.e., late U.S. domestic drug problem and the convening of the
professionalization of medicine, an open drug mar- International Opium Commission at Shanghai in
ket, and constitutional restrictions on national legis- February 1909. Brent was chosen to preside over the
lation) began to change in the late nineteenth cen- 13 nations that gathered there. The commission's
tury. A domestic movement to control dangerous rather noncontroversial resolutions were used by
drugs, especially patent medicines, led to passage of the United States to convene the International
the Pure Food and Drug Act of 1906, which required Opium Conference, a treaty-making body, at the
accurate labeling of the narcotic contents of products Hague in December 1911. The dozen nations repre-
sold in interstate commerce. The acquisition of the sented at the conference, again chaired by Brent,
Philippine Islands in 1898 and the necessity of deal- adopted an International Opium Convention in Janu-
ing with the opium problem there spurred the most ary 1912. This treaty also included provisions for the
important decision making on narcotics by the fed- control of cocaine. Control would be enforced primar-
eral government. The Philippine experience not only ily through the domestic legislation of several na-
accelerated the passage of national laws but, of tions: However, the treaty would not come into force
broader significance, led directly to a U.S.-inspired until every nation on earth had ratified. This diffi-
treaty to control narcotics worldwide, as well as to cult requirement arose out of the fear of some produc-
the international antiaddiction effort that persists to ing and manufacturing nations that, without univer-
this day. sal adoption, the nonadhering nations would be able
to dominate a lucrative market.
Origin of International Control At a conference in June 1914, it was decided that
Under Spanish rule, there had been an opium mo- any nation ratifying the treaty could put it into effect
nopoly in the Philippines from which opium smokers without waiting for unanimity. The United States
could obtain supplies. The newly arrived U.S. govern- chose to do so, and enacted the Harrison Narcotic Act
ment decided to reinstitute the monopoly and use in December 1914. World War I slowed ratification,
the profits to help support universal education there. but when the fighting ended, several of the victorious
However, U.S. missionary and political leaders nations, including the United Kingdom and the
strongly rejected the proposal. The impasse led to United States, added the Hague Convention to the
the creation of an investigating committee ap- Versailles Treaty, mandating that ratification of the
pointed by the Philippine government that included Peace Treaty include the Opium Convention. It was
Charles Henry Brent, Protestant Episcopal bishop of as a result of this requirement, and not of any domes-
the Philippines, who would become the key figure in tic drug crisis, that the United Kingdom enacted the
establishing an international campaign against nar- Dangerous Drugs Act of 1920. In later decades, espe-
cotics. The committee examined control measures cially in the United States, the origins of this act were
used in other areas of the Orient and recommended a forgotten, and the provision of opiates to some addicts
gradual reduction approach for opium users in the allowed under the act was claimed to have solved a

III.7. Concepts of Addiction 175
serious addiction problem in the United Kingdom. Board (INCB), which oversees the ongoing function-
This is an example, common in the area of drug pol- ing of treaty obligations and provides technical assis-
icy, of trying to base solutions to an addiction problemtance in the form of statistics and chemical analyses.
on the laws or practices of another nation without INCB, established by the Single Convention, suc-
taking into consideration differences in history and ceeds the League's PCOB (1929-67) and the Drug
culture. Supervisory Board (1933-67).
The appearance in the 1960s of problems with
The Establishment of an International newer drugs, such as LSD, barbiturates, amphet-
Bureaucracy amines, and tranquilizers, prompted a new treaty,
The League of Nations assumed responsibility for the Convention on Psychotropic Drugs (1971), which
the Hague Convention in 1920. In 1924 the First aims to expand international supervision beyond the
Geneva Opium Conference addressed the gradual traditional substances linked to opium, coca, and
suppression of opium smoking. This was soon fol- cannabis. In 1988 a convention intended to improve
lowed by the Second Geneva Opium Conference, criminal sanctions against international traffickers
which expanded international control over drugs by was submitted to members of the United Nations for
establishing a system of import and export certifi- ratification.
cates, creating the Permanent Central Opium Board
(PCOB) to oversee the new provisions, and adding Recent Responses to Drug Use
coca leaves and cannabis to the list of controlled Research into the mechanisms of drug addiction and
substances. The United States, because it did not dependence has greatly increased in the past
recognize the League, relinquished leadership of the quarter-century. In the nineteenth century, research
international movement, and went so far as to walk centered on modes of delivery, the development of
out of the Second Geneva Opium Conference be- the hypodermic syringe, and the nature of opiate
cause, in its view, the other nations were unwilling addiction. The pattern of withdrawal was described
to take meaningful steps to curb opium production and treatment for opiate addiction sought. Cocaine
and refused to ban the manufacture of diacetyl- was offered, for example, as a cure for morphinism
morphine, more commonly known by its generic and alcoholism. Other cures were drawn from popu-
name, heroin. Heroin had been introduced by the lar medical theories of the time, autointoxication,
Bayer Company in 1898 as a cough suppressant and and other aspects of immunological response.
within two decades had replaced morphine as the Confidence in treatment was equaled only by en-
drug of choice among youth gangs in New York City. thusiasm for research, until after World War I
Heroin had an advantage over morphine in that it when, especially in the United States, a powerful
could be sniffed as well as injected and became the reaction against drug use caused both professionals
most feared of the opiates in the United States. In and the public to reject current treatments — which,
1924 the United States banned domestic production in fact, were of little value - and to lose interest in
of heroin. research. The battle against drug abuse came to
In 1931 a conference was held in Geneva on limit- rely primarily on law enforcement. Research again
ing the manufacture of narcotic drugs, and in 1936 found support in the late 1960s and the 1970s when
another Geneva conference dealt with suppressing consumption rose and there was a certain toleration
the illicit traffic in dangerous drugs. After World of "recreational" or "experimental" drug use among
War II the United Nations accepted responsibility youth. However, as fear of drugs and drug users
for narcotics control, and in 1961 the various trea- increased, the public grew impatient with treat-
ties were combined into the Single Convention on ment and toleration of any drug use and, again,
Narcotics. A significant addition to the older treaties funding for research fell. In recent decades, signifi-
was the prohibition of cannabis production. cant advances have included the discovery of opiate
The United Nations placed drug control under the receptor sites in the brain, of the existence of natu-
Economic and Social Council (ECOSOC). The UN rally produced opiates, endorphins, and of the exis-
Commission on Narcotic Drugs meets annually to tence of chemicals that block opiate receptor sites.
review the drug problem and make recommendations Specific treatment for cocaine dependence has
on policy to ECOSOC. The commission is the succes- eluded investigators.
sor to the League's Advisory Committee on Traffic in On an international level, attempts have been
Opium and Other Dangerous Drugs (1921-40). Also made to interdict drugs coming from producing ar-
under ECOSOC is the International Narcotic Control eas; persuade local growers of poppies, coca bushes,

and marijuana to grow other crops; arrest local deal- Taylor, Arnold H. 1969. American diplomacy and the nar-
ers; and spray illicit crops with herbicides. Crop sub- cotics traffic, 1900-1939. Durham, N.C.
stitution as an international policy dates to the Terry, Charles E., and Mildred Pellens. 1928. The opium
1920s, when the League of Nations sought to per- problem. New York.
suade opium growers in Persia to grow other crops,
and continues today in major opium-producing ar-
eas, such as the "Golden Triangle" in northern
Burma. This scheme has not yet cut into the world
supply of opium and coca and, of course, is irrelevant
to the control of manufactured drugs such as syn- III.8
thetic opiates and stimulants like amphetamine. Tobaccosis
Spraying the crops of producing nations and other
policies advocated by consuming nations raise sensi-
tive questions of sovereignty. Furthermore, produc- The term tobaccosis in this essay denotes, collec-
ing nations claim, as they did during the first U.S. tively, all diseases resulting from the smoking,
campaign to control production before World War I, chewing, and snuffing of tobacco and from the
that the problem is not production but the consum- breathing of tobacco smoke. They include cancers of
ing nations' demand for drugs. the mouth, nasopharynx, larynx, trachea, bronchi,
In its worldwide campaign against addiction, the lungs, esophagus, stomach, liver, pancreas, kidney,
United States early in this century asserted that the bladder, prostate, and cervix, as well as leukemia.
use of narcotics for anything other than strictly medi- They also include atherosclerosis of the cardiovascu-
cal treatment was dangerous and morally wrong. lar system - coronary heart disease (with ischemia
This attitude represented the thinking of most and infarction), cardiomyopathy, aortic and other
North Americans at the time, but it was not a univer- aneurysms, cerebrovascular hemorrhages and block-
sal view and is not a view always held by the United ages; renal failure and peripheral vascular disease;
States. The vicissitudes of moral attitude toward emphysema and chronic obstructive pulmonary dis-
addiction over the past two centuries illustrate that eases; peptic ulcer disease and regional ileitis; cir-
the response to addiction is intimately bound to the rhosis of the liver; immunological deficiencies and
social history and mores of a nation or region at any failures of endocrine and metabolic functions; and
given time. The history of addiction has a medical fetal diseases and perinatal disabilities.
element, but it is also a reflection of nations' charac- Tobaccosis is the foremost plague of the twentieth
teristic approaches to individual and social prob- century and thus joins the most fearsome plagues
lems. Integration of the history of addictive sub- that devastated humanity during this millennium
stances with the social history of nations and regions such as the Black Death, smallpox, malaria, yellow
remains a fertile area for research. fever, Asiatic cholera, and tuberculosis. But unlike
David F. Musto microparasitic plagues, whose victims experienced
pathognomonic disease manifestations within days
Bibliography or weeks of exposure, tobaccosis is an extraordinarily
Bonnie, Richard J., and Charles H. Whitebread II. 1974. insidious disease entity of long latency resulting from
The marihuana conviction: A history of marihuana exposure to tobacco for many years or decades and
prohibition in the United States. Charlottesville, Va. manifested by increased occurrence of any of a broad
Clark, Norman H. 1976. Deliver us from evil: An interpreta- spectrum of neoplastic and degenerative diseases or-
tion of American prohibition. New York. dinarily associated with advanced age. Thus, the pow-
Courtwright, David T. 1982. Dark paradise: Opiate addic- erfully malignant nature and magnitude of the tobac-
tion in America before 1940. Cambridge, Mass. cosis pandemic went largely undetected during the
Lowes, Peter D. 1966. The genesis of international narcot- first four centuries of its global march; and it is only
ics control. Geneva. late in thefifthcentury of the post-Columbian world's
Morgan, H. Wayne. 1981. Drugs in America: A social his- exposure to tobacco that the extent of tobacco's depre-
tory, 1800-1980. Syracuse, N.Y. dations is being fully revealed. Because of its leader-
Musto, David F. 1987. The American disease: Origins of
ship in the production, marketing, and use of tobacco,
narcotic control. New York.
Parssinen, Terry M., and Karen Kerner. 1980. Develop- the United States has borne much of the brunt of the
ment of the disease model of drug addiction in Britain, tobaccosis pandemic. Hence, this historical account
1870-1926. Medical History 24: 275-96. deals mainly with the U.S. experience.

III.8. Tobaccosis 177
Origin and Peregrinations of Tobacco Yet the popularity of tobacco in England was chal-
Tobacco is native to the Americas and was exten- lenged by James I, who became monarch of the Brit-
sively cultivated and smoked by the aborigines there. ish Isles after the death of Queen Elizabeth in 1603.
The addictive weed was first encountered by Christo- His "Counterblaste to Tobacco," published anony-
pher Columbus and crew on the island of Cuba in mously in 1604 and considered extreme and rather
November 1492. For some years it was known as quaint during intervening centuries, can now be ap-
paetun and by other names before it was given its preciated as somewhat prescient:
common name, tobacco, from the pipes in which it was
smoked on the island of Santo Domingo. And now good countrey men let us (I pray you) consider,
what honour or policie can move us to imitate the barba-
Increasingly cultivated and used by Spaniards and
rous and beastly manners of the wild, godlesse, and slavish
blacks in the West Indies and by Portuguese and Indians, especially in so vile and stinking a coustome? . ..
blacks in Brazil during the early decades of the six- A custome lothesome to the eye, hateful to the nose, harm-
teenth century, tobacco was introduced to many Euro- full to the braine, dangerous to the lungs, and in the black
pean countries during the latter decades of that cen- stinking fume thereof neerest resembling the horrible
tury. In 1559 tobacco seeds obtained in Lisbon by Jean stigian smoke of the pit that is bottomless. (Quoted in
Nicot, the French ambassador, from a Dutch trader Austin 1978)
just returned from the New World were sent as a me-
dicinal to Queen Catherine de Medici and the House The following year he organized, at Oxford, the
of Lorraine, thereby initiating tobacco cultivation first public debate on the effects of tobacco, at
and use in France and gaining lasting fame for Nicot. which - to get his point across - he displayed black
Tobacco was brought to England in 1565 by John brains and black viscera allegedly obtained from the
Hawkins, returning from a second voyage to Florida, bodies of smokers. To discourage tobacco sales and
but it did not gain immediate popular use. Two de- use, James I increased the tax thereupon 40-fold; but
cades later, Walter Raleigh established a colony on when use and smuggling increased, he reduced the
Roanoke Island in Virginia. When Francis Drake tax in 1608 to one shilling per pound of tobacco and
visited the ill-fated colony in June 1586, the gover- sold the monopoly right to collect it. With the estab-
nor and others returned with him to England, bring- lishment in 1607 of his namesake colony on the
ing with them the tobacco and pipe-smoking prac- James River in Virginia and on the initiative of John
tices soon popularized by Raleigh and others at Rolfe, tobacco quickly became its principal crop and
Queen Elizabeth's court. By 1600 tobacco was widely export. In 1615, 2,300 pounds were exported, in
used in all the maritime nations of Europe. 1618, 20,000 pounds, and by 1620, 40,000 pounds.
x
Meanwhile Portuguese traders carried tobacco in An outbreak of plague in London in 1614 gave
the latter 1500s to African ports and to India, the further impetus to smoking, in that doctors declared
Spice Islands, Japan, Macao, China, and elsewhere that steady smokers were not as subject to infection
in the Orient; and Spanish traders carried it to the as others and recommended tobacco as a disinfec-
Philippines. Other European merchants trading in tant. At that time, 7,000 shops were selling tobacco
the Levant took the weed with them throughout the in London, with use spreading among the poor de-
East. Thus, by the end of the seventeenth century, spite high prices. By 1615 tobacco imports had risen
tobacco was widely available and used in virtually to such an extent that James revoked his 1608 mo-
all trading nations of the world. nopoly grant and reassigned it at a higher price. In
1620 he ordered that all tobacco bear the govern-
ment seal, and in 1624 he decreed that only Virginia
Tobacco in Europe
tobacco be imported. Thus, despite the high costs
Among American Indians, from Canada to Brazil,
and discomfort of smoking, chewing, and snuffing
tobacco was widely smoked for its intoxicating ef- and despite intense repressive actions of such sover-
fects, as a medicinal, and for ceremonial purposes. eigns as King James I of England, King Christian IV
The spread of tobacco use from the New World gave of Denmark, Tsar Michael Romanov of Russia, and
rise to the first great drug controversy of global Sultan Murad of Turkey, tobacco continued to in-
dimensions. From the onset, opinions regarding to- crease in popularity.
bacco differed radically. Used by Indians as a remedy
for aches and pains, snake bite, abdominal and chest
pains, chills, fatigue, hunger and thirst, tobacco was Snuffing Cancer
extolled by European purveyors for its miraculous Among the lower classes, pipe smoking was the com-
curative powers. mon method of tobacco consumption; among the Eu-

ropean upper classes during the 1700s, pipe smoking creased, and after the war tobacco factories mush-
was largely supplanted by snuffing (the practice of roomed. By 1880, with a population of 50 million
sniffing tobacco dust). Within a few decades the wide- people, the United States consumed 1.3 billion ciga-
spread practice of snuffing generated the first clini- rettes annually, 500 million made locally and the
cal reports of cancer caused by tobacco - cancer of rest imported. Nonetheless, chewing tobacco — a U.S.
the nasal passages, as described by an English physi- concoction of tobacco and molasses - remained the
cian, John Hill, in 1761: leading form of tobacco in the United States through-
out the nineteenth century. Along with a great in-
This unfortunate gentleman, after a long and immoderate
use of snuff, perceived that he breathed with difficulty
crease in tobacco consumption during the nineteenth
through one of his nostrils; the complaint gradually century came increasing reports of tobaccosis, espe-
encreased 'till he perceived a swelling within. . . . It grew cially cancers of directly exposed tissues. Although
slowly, till in the end, it filled up the whole nostril, and medical science was still in its infancy in the nine-
swelled the nose so as to obstruct the breathing... he teenth century, occasional astute clinical observa-
found it necessary to then apply for assistance. The swell- tions gradually increased people's awareness of the
ing was quite black and it adhered by a broad base, so that pathogenicity of tobacco.
it was impossible to attempt to the getting it away . .. and In 1851, for example, James Paget saw a patient
the consequences was the discharge of a thick sharp hu- with leukoplakia ("smoker's patch") on the tongue
mor with dreadful pain, and all the frightful symptoms of
where he always rested the end of his pipe, and "told
cancer . . . and he seemed without hope when I last saw
him. (Quoted in Whelan 1984)
him he certainly would have cancer of the tongue if
he went on smoking" (quoted in Whelan 1984). And
Also in 1761, the Italian anatomist Giovanni in 1857 Lancet commented:
Battista Morgagni described lung cancer at postmor- Tobacco . . . acts by causing consumption, haemoptysis
tem without identifying its cause. A few years later, and inflammatory condition of the mucous membrane of
in 1775, Percival Pott described a scrotal cancer epi- the larynx, trachea and branchae, ulceration of the lar-
demic among London chimney sweeps, documenting ynx; short, irritable cough, hurried breathing. The circu-
the carcinogenicity of chimney smoke, which should lating organs are affected by irritable heart circulation.
have alerted many to the pathogenic implications of (Quoted in Whelan 1984)
chronic exposure of respiratory tissues to tobacco
smoke. In 1859 a French physician reported a remarkably
thorough study of 68 cases of cancer of the oral
Although tobacco-induced lung cancer must have cavity in a French hospital. Ascertaining the habits
produced many thousands of deaths from the six- of 67 of these patients, he found that 66 smoked
teenth to the nineteenth century, all such progres- tobacco and the other chewed tobacco. He also noted
sive chest diseases were lumped under the rubric of that cancer of the lip ordinarily occurred at the spot
phthisis or consumption until the late-nineteenth- where the pipe or cigar was held.
century scientific advances of histology, bacteriol-
ogy, and X-ray. At that time, because of the often In 1882 the Boston Medical and Surgical Journal
obvious relationships between snuffing and nasal offered this prescient view of cigarettes:
cancer, pipe smoking and lip cancer, tobacco chewing The dangers, then, which are incident to cigarette smok-
and cancer of the mouth, cigar smoking and cancer ing are, first, the early age at which it is taken up; second,
of the mouth and larynx, there was a growing real- the liability to excess; and, third, the bad custom of inhal-
ization that tobacco use produced cancers of directly ing the smoke. These are dangers super-added to those
exposed topical tissues. attendant upon the ordinary use of tobacco, and should be
considered by all medical men.
Nineteenth-Century Wars and Tobaccosis Despite such examples, however, leading physi-
British soldiers returning from campaigns on the Ibe- cians of the late nineteenth century were generally
rian Peninsula during the years 1808-14 introduced oblivious to the hazards of tobacco. In the monumen-
cigarettes to England. Likewise, veterans returning tally detailed Medical and Surgical History of the
from the Crimean War (1853-6) increased cigarette War of the Rebellion, prepared under the direction of
smoking in Britain — a practice soon brought to the Surgeon General of the Army Joseph K. Barnes by
United States by returning tourists, including New J. J. Woodward and colleagues and published in six
York society women. huge volumes from 1875 to 1888 under the author-
During the U.S. Civil War (1861-5) the use of all ity of the U.S. Congress, there are only two com-
kinds of tobacco, including that of cigarettes, in- ments about tobacco: that tobacco clyster may be

used for the treatment of zymotic disease and that 1964
5,000
abuse of tobacco may cause "irritable heart." Nor Surgeon
General's
was tobaccosis frequently mentioned by John Shaw Report
Billings, founder of the Index Medicus, the National
Library of Medicine, and author of voluminous
analyses of late-nineteenth-century U.S. mortality.
William Osier in his classic 1892 text, The Princi-
ples and Practice of Medicine, devoted only three
sentences in 1,000 pages to the effects of tobacco.
With the advent of cigarette-making machines,
which made possible the nearly unlimited produc- Tobacco,
Advertising,
tion of cigarettes, and portable "safety" matches (in- Cinema,
troduced at the turn of the century), which enabled Radio .
Great
smokers to light up whenever and wherever they WWI / Depression
wished, the stage was set for a vast increase in
cigarette consumption. However, as tobacco compa-
nies intensified promotional activities, a powerful 1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000
antitobacco movement developed, led by Lucy Page Figure III.8.1. Annual consumption of cigarettes by
Gaston and the Women's Christian Temperance U.S. adults (18 years of age and older), 1900-88. (Data
Movement, which substantially curbed cigarette from the Economic Research Service, U.S. Department
sales during the 1890s and early 1900s. of Agriculture.)
Twentieth-Century Cigarette Tobaccosis of the depression of the 1930s, only to increase dur-
A comprehensive view of evolving tobacco use pat- ing the latter part of the decade, presumably in
terns in the United States during this century is response to intensified advertising in magazines, on
presented in Table III.8.1, which documents the pro- billboards, and on radio as well as in response to the
gressive trend from cigar smoking and the use of incessant smoking of popular film stars and other
"manufactured tobacco" (pipe tobacco, chewing to- famous personalities.
bacco, and snuff) to cigarette smoking. Annual pro- During World War II, when cigarettes were made
duction of manufactured tobacco increased from 301 freely available to many military and some civilian
million pounds in 1900 to a peak of 497 million groups, consumption almost doubled again - from
pounds in 1918 and subsequently decreased to 142 1,976 cigarettes per adult in 1940 to 3,449 in 1945.
million pounds (1988). During the twentieth cen- After the war, cigarette consumption continued up-
tury, cigar production oscillated between 4 and 10 ward until 1950, when scientific findings showed
billion annually, with more cigars produced in 1900 smoking to be the principal cause of a rapidly in-
(5.6 billion) than in 1988 (3.2 billion). creasing epidemic of lung cancer. However, tobacco
Meanwhile, cigarette production and consumption sales soon recovered.
increased more than 100-fold, with consumption in- Intense wrangling over the validity of research
creasing from 2.5 billion cigarettes in 1900 to 640 findings on the harmful effects of tobacco generated
billion in 1981, then decreasing to 562 billion in so much confusion that in 1962 Surgeon General
1988. On a per capita basis in the United States, Luther Terry established the Advisory Committee of
annual cigarette consumption increased from 54 per Experts, whose landmark report on 11 January 1964
adult in 1900 to a peak of 4,345 per adult in 1963. rendered an authoritative verdict: "Cigarette smok-
Since then it has decreased to 3,096 cigarettes per ing is causally related to lung cancer in men; the
adult in 1988. magnitude of the effect of cigarette smoking far out-
The foremost determinants of national cigarette weighs all other factors. The data for women, though
consumption can be inferred from the trend changes less extensive, point in the same direction."
seen in Figure III.8.1. Cigarette consumption dou- Again the tobacco industry took vigorous defen-
bled during World War I, when cigarettes were in- sive action with intensified advertising; but when a
cluded in soldiers' rations sent to France. It doubled fairness doctrine required that advertising messages
again during the 1920s, propelled by innovative ad- on radio and television be balanced by antismoking
vertising campaigns and augmented by radio and messages, tobacco advertising was discontinued in
cinema. But then it decreased during the early years the broadcast media.

Table III.8.1. U.S. tobacco production and 1947 242 5.5 369.8 345.4 3,416
consumption, 1900—88 1948 245 5.6 386.9 358.9 3,505
1949 239 5.4 385.0 360.9 3,480
Tobacco products produced Cigarette 1950 235 5.5 392.0 369.8 3,522
consumption 1951 227 5.7 418.8 397.1 3,744
Mfg.
tobacco Per adult 1952 220 5.9 435.5 416.0 3,886
Total in billions 1953 209 6.0 423.1 408.2 3,778
(lbs. Total in (18+
Year x 106) Cigars Cigarettes billions years)
1954 204 5.9 401.8 387.0 3,546
1955 199 5.8 412.3 396.4 3,597
1900 301 5.6 3.9 2.5 54 1956 185 5.8 424.2 406.5 3,650
1901 314 6.1 3.5 2.5 53 1957 179 5.9 442.3 422.5 3,755
1902 348 6.3 3.6 2.8 60 1958 180 6.4 470.1 448.9 3,953
1903 351 6.8 4.0 3.1 64 1959 176 7.3 489.9 467.5 4,037
1904 354 6.6 4.2 3.3 66
1960 173 6.9 506.1 484.4 4,174
1905 368 6.7 4.5 3.6 70
1961 173 6.6 518.0 502.5 4,266
1906 391 7.1 5.5 4.5 86
1962 169 6.8 529.9 508.4 4,265
1907 388 7.3 6.3 5.3 99
1963 168 6.6 543.7 523.9 4,345
1908 408 6.5 6.8 5.7 108
1964 180 8.6 535.0 511.3 4,195
1909 431 6.7 7.9 7.0 125
1965 167 8.9 562.4 528.8 4,259
1910 447 6.8 9.8 8.6 151 1966 162 8.0 562.7 541.3 4,287
1911 424 7.0 11.7 10.1 173 1967 158 7.3 572.8 549.3 4,280
1912 435 7.0 14.2 13.2 223 1968 159 7.7 570.7 545.6 4,186
1913 444 7.6 16.5 15.8 260 1969 161 7.5 573.0 528.9 3,993
1914 441 7.2 17.9 16.5 267 1970 165 8.0 562.2 536.5 3,985
1915 442 6.6 18.9 17.9 285 1971 158 7.8 576.4 555.1 4,037
1916 466 7.0 26.2 25.2 395 1972 154 10.0 599.1 566.8 4,043
1917 483 7.6 36.3 35.7 551 1973 152 8.8 644.2 589.7 4,148
1918 497 7.6 47.5 45.6 697 1974 153 813 635.0 599.0 4,141
1919 424 7.1 53.9 48.0 727 1975 155 7.4 625.0 607.2 4,123
1920 413 8.1 48.1 44.6 665 1976 153 6.7 688.0 613.5 4,092
1921 387 6.7 52.8 50.7 742 1977 155 5.8 673.0 617.0 4,051
1922 420 6.7 56.4 53.4 770 1978 156 5.6 688.0 616.0 3,967
1923 413 7.0 67.2 64.4 911 1979 156 5.1 707.0 621.5 3,861
1924 414 6.6 73.2 71.0 982 4.9 702.0 3,851
1980 163 631.5
1925 414 6.5 82.7 79.8 1,085 5.0 744.0 3,840
1981 162 640.0
1926 411 6.5 92.5 89.1 1,191 4.5 711.0 3,753
1982 160 634.0
1927 396 6.5 100.2 97.5 1,279 4.3 668.0 3,502
1983 159 600.0
1928 386 6.4 109.1 106.0 1,366 4.5 657.0 3,446
1984 159 600.4
1929 381 6.5 122.8 118.6 1,504 4.0 665.3 3,370
1985 158 594.0
1930 372 5.9 124.2 119.3 1,485 1986 148 3.9 658.0 583.8 3,274
1931 371 5.3 117.4 114.0 1,399 1987 143 3.2 689.4 575.0 3,197
1932 347 4.4 106.9 102.8 1,245 1988 142 3.2 694.5 562.5 3,096
1933 342 4.3 115.1 111.6 1,334 Total 25,285 555.9 28,004.7 26,366.1 2,387 av.
1934 346 4.5 130.3 125.7 1,483
1935 343 4.7 140.1 134.4 1,564 Source: Economic Research Services, U.S. Department of
1936 348 5.2 159.1 152.7 1,754 Agriculture.
1937 341 5.3 170.2 162.8 1,847
1938 345 5.0 171.8 163.4 1,830
1939 343 5.2 180.8 172.1 1,900
5.4 189.4 181.9 1,976
Despite these setbacks for the tobacco industry,
1940 344
1941 342 5.6 218.1 208.9 2,236
sales ascended during the early 1970s. During the
1942 330 5.8 257.7 245.0 2,585 late 1970s, however, consumption began to decline
1943 327 5.9 296.3 284.3 2,956 under Joseph Califano as Secretary of Health, Educa-
1944 307 5.2 323.7 296.3 3,030 tion, and Welfare, a trend that fortunately has contin-
1945 331 5.3 332.3 340.6 3,449 ued, for several reasons. Among these are increasing
1946 253 5.6 350.1 344.3 3,446 evidence of the harm to persons who are chronically

Table III.8.2. Per capita adult consumption of
Mozambique 430 Cape Verde 210
manufactured cigarettes by country, 1985 Zambia 400 Zaire 210
Malawi 390 India 160
Cyprus 4,050 Netherlands 1,690 Ghana 380 Chad 150
Cuba 3,920 Sweden 1,660 Nigeria 370 Burma 150
Greece 3,640 Suriname 1,660 Peru 350 Nepal 150
Poland 3,300 Trinidad and Bolivia 330 Sudan 130
United States 3,270 Tobago 1,600 United Republic Niger 100
Japan 3,270 Algeria 1,590 of Tanzania 330 Ethiopia 60
Hungary 3,260 China 1,590 Central African Afghanistan 50
Canada 3,180 Hong Kong 1,580 Republic 280 Papua New
Iceland 3,100 South Africa 1,550 Bangladesh 270 Guinea 30
Yugoslavia 3,000 Tunisia 1,470 Uganda 260 Guinea 30
Switzerland 2,960 Barbados 1,380 Haiti 240 Burkina Faso 30
Lebanon 2,880 Nicaragua 1,380
Libyan Arab Costa Rica 1,340
Jamahiriya 2,850 Fiji 1,320 Note: An adult is denned as someone 15 years of age and
Kuwait 2,760 Mexico 1,190 over.
Spain 2,740 Democratic Peo- Source: WHO Program on Smoking and Health.
Australia 2,720 ple's Republic
Republic of of Korea 1,180
Korea 2,660 Guadeloupe 1,080
exposed to smoke generated by others and stronger
Austria 2,560 Morocco 1,070 antitobacco activities by official and voluntary agen-
Ireland 2,560 Indonesia 1,050 cies at national, state, and local levels, as well as the
Czechoslovakia 2,550 Honduras 1,010 vigorous campaign mounted by Surgeon General C.
New Zealand 2,510 Chile 1,000 Everett Koop.
Italy 2,460 Paraguay 1,000
Bulgaria 2,410 Guyana 1,000 World Tobacco Trends
France 2,400 Iraq 980 During recent decades, as antitobacco movements
Germany, Fed- Dominican have hobbled tobacco promotion and sales in some of
eral Republic 2,380 Republic 980 the affluent countries and as income levels have
Germany, Demo- Reunion 940 risen in many less developed countries, the multi-
cratic Republic 2,340 Congo 920 national tobacco companies have intensified their
Israel 2,310 Thailand 900
advertising efforts in the less developed world, re-
Singapore 2,280 Ecuador 880
USSR 2,120 Panama 850
sulting in the global tobacco consumption pattern
United Kingdom 2,120 Sierra Leone 830
seen in Table III.8.2.
Denmark 2,110 Jamaica 820 The leading countries in the production and con-
Saudi Arabia 2,110 El Salvador 750 sumption of tobacco are China, the United States, the
Romania 2,110 Benin 740 Soviet Union, Japan, the Federal Republic of Ger-
Syrian Arab Cote d'lvoire 710 many, the United Kingdom, Brazil, India, Spain,
Republic 2,050 Vietnam 670 France, and Italy. World production and consumption
Belgium 1,990 Pakistan 660 of cigarettes now exceed 5 trillion annually — more
Turkey 1,970 Iran 620 than enough to raise the world tobaccosis death toll
Norway 1,920 Senegal 610 substantially above the current level of about 3 mil-
Colombia 1,920 Cameroon 610 lion annually. Fortunately, during the 1980s the
Philippines 1,910 Guatemala 550 World Health Organization began to exercise forth-
Venezuela 1,890 Kenya 550
right leadership in supplying information on this dif-
Egypt 1,860 Angola 530
Malaysia 1,840 Zimbabwe 500
ficult issue, though it had not yet applied financial
Argentina 1,780 Sri Lanka 500 and personal resources commensurate with the na-
Uruguay 1,760 Lao People's ture and magnitude of the tobaccosis pandemic.
Portugal 1,730 Democratic
Finland 1,720 Republic 490 Nature of the Tobacco Hazard
Jordan 1,700 Togo 460
Brazil 1,700 Madagascar 450 Addictive Pleasures
Mauritius 1,700 Liberia 450 Although it has always been obvious that tobacco
contains a substance (nicotine) that yields psychic

Table III.8.3. Percentage of U.S. adults who smoked tured and retained by the respiratory mucous blan-
regularly, 1945-85 ket. Soluble components are then promptly absorbed
into the pulmonary circulation and conveyed by the
Men Women Combined systemic circulation throughout the body. Less sol-
Year (%) (%) (%) uble tars trapped by the mucous blanket are raised
1945 48 36 42 by ciliary action and coughing to the pharynx, then
1950 54 33 44 swallowed; thereafter, they pass to the esophagus,
1955 54 25 40 stomach, small intestine, portal circulation, and
1960 52 34 42 liver. Hence, chronic inhalation of tobacco smoke
1965 52 34 42 exposes the entire body - every tissue and cell - to
1970 44 31 38 powerful mutagens and carcinogens, thus hastening
1975 42 32 37 the malignant cellular evolutionary process and ac-
1980 38 30 34 celerating the development of the broad spectrum of
1985 33 28 30 neoplastic and degenerative diseases constituting to-
40-year 46 31 39 baccosis (Table III.8.4).
average
The differences in mortality among smoking and
Source: Estimated from survey data by Gallup Poll, Na- nonsmoking U.S. veterans amply confirm the pio-
tional Center for Health Statistics, and Centers for Dis- neering findings of Raymond Pearl, published in
ease Control. 1938, showing a great decrease in the longevity of
smokers. In fact, the life-shortening effects of smok-
ing are now so obvious that it seems incredible that
pleasures not obtained by the smoking of other plant they were generally overlooked for four centuries.
leaves, only during the 1980s did a strong scientific Among persons who start smoking in adolescence
and societal consensus emerge that nicotine is truly and continue to smoke a pack of cigarettes daily, the
addictive -just as addictive as heroin or cocaine and average loss of life is roughly 8 years - approximately
much more addictive than alcohol. equal to the cumulative time actually spent smoking.
Indeed, cigarette smoking is now the most serious
The most surprising finding of prospective and
and widespread form of addiction in the world. The
pathological studies - that the majority of tobaccosis
proportion of adult men and women who have smoked
deaths are caused by diseases of the cardiovascular
cigarettes in the United States during the past half-
system - initially generated incredulity, and indeed
century is indicated in Table III.8.3. Half of adult men
the phenomenon is still not well understood or fully
smoked at midcentury, this proportion decreasing to
believed by many. It nonetheless deserves full cre-
33 percent in 1985 and 30 percent in 1987. Likewise,
dence and is central to understanding the nature
smoking by adult women decreased from 34 percent
and magnitude of tobaccosis.
in 1965 to 28 percent in 1985 and 27 percent in 1987.
The fabric of evidence that cigarette smoking is a
major cause of atherosclerosis is woven of these evi-
Lethal Poisons dential threads:
The smoke of burning tobacco contains several thou-
sand chemicals and a number of radioisotopes, in- 1. The epidemic increase in ischemic heart disease
cluding hydrogen cyanide, nitriles, aldehydes, ke- in the United States during the twentieth century
tones, nicotine, carbon monoxide, benzopyrenes, followed the rise in cigarette smoking and oc-
aza-arenes, and polonium 210, an alpha-particle curred particularly among those age-sex sub-
emitter and therefore the most powerful contact groups most exposed.
mutagen, more than 100 times more mutagenic than 2. Individual studies document a close relationship
equivalent RADs of gamma radiation. The combina- between heavy cigarette smoking and early coro-
tion of an addictive substance (nicotine) and more nary disease.
than 50 potent mutagens (especially polonium 210) 3. There is a plausible pathogenic mechanism by
has made tobacco the foremost human poison of the which tobacco smoke could damage vascular tis-
twentieth century. sue: The absorption of inhaled tobacco smoke re-
sults in the circulation of polonium 210 and other
Pathogenic Mechanisms toxins, with injury to endothelial and other cells,
When tobacco smoke is inhaled deeply into the causing cellular damage, clonal proliferation, in-
lungs, most of the tars contained therein are cap- tramural hemorrhage, lipid deposition, fibrosis,

Table III.8.4 Deaths and mortality ratios among Cirrhosis of the liver 404 150 2.69
smoking U.S. veterans, 1980 Nephritis, nephrosis, 349 261 1.34
other kidney disease
Mortality Diabetes 315 221 .97
Observed Expected ratio All other diseases 2,801 2,100 1.33
Cause of death deaths deaths (O H-E)
No death certificate 849 390 2.18
All causes 36,143 20,857 1.73 found
Respiratory diseases 2,139 483 4.43
Emphysema and 1,364 113 12.07 Source: DatafromRogot and Murray (1980).
bronchitis
Influenza and 460 259 1.78
pneumonia and calcification. Though often overlooked, ioniz-
Pulmonary fibrosis 144 48 3.02 ing radiation is a powerful cause of atherosclerosis
and bronchiectasis and premature death from cardiovascular disease.
Pulmonary 81 36 2.27 4. Prospective studies of heavy smokers matched
tuberculosis with nonsmokers for numerous confounding vari-
Asthma 90 27 3.28 ables have consistently shown the relative risk of
Cancer of directly ex- 3,061 296 10.34 death from atherosclerosis to be much higher for
posed tissue smokers and directly related to the number of
Buccal cavity, pharynx 202 33 6.12 cigarettes smoked.
Larynx 94 8 11.75 5. Members of certain religious groups that eschew
Lung and bronchus 2,609 231 11.29 the use of tobacco, such as Seventh-Day Advent-
Esophagus 156 24 6.50 ists and Latter-Day Saints, have markedly lower
Cancer of indirectly ex- 4,547 3,292 1.38 morbidity and mortality rates from atheroscle-
posed tissue rotic disease.
Stomach 390 257 1.53 6. Quitting smoking is ordinarily followed by a re-
Intestines 662 597 1.11 duced incidence of coronary heart disease, among
Rectum 239 215 1.11 specific groups and for the entire population.
Liver and biliary 176 75 2.35 7. Experimental studies in animals have demon-
passages strated that tobacco constituents are potent
Pancreas 459 256 1.79 causes of atherosclerotic disease.
Kidney 175 124 1.41
Bladder 326 151 2.16 The evidence is clear, consistent, and compelling
Prostate 660 504 1.31 that tobacco smoke is a major cause of athero-
Brain 160 152 1.05 sclerotic disease and death.
Malignant lymphomas 370 347 1.07
Leukemias 333 207 1.61 Epidemic Curves
All other cancers 597 407 1.47
Temporal relationships between twentieth-century
All cardiovascular 21,413 13,572 1.58 epidemic curves for cigarette smoking and death
diseases from coronary heart disease, lung cancer, and
Coronary heart disease 13,845 8,787 1.58 emphysema/COPD (chronic obstructive pulmonary
Aortic aneurysm 900 172 5.23 disease) are presented in Figure III.8.2. The figure
Cor pulmonale 44 8 5.57 shows the massive epidemic of coronary heart dis-
Hypertensive disease 1,107 724 1.53 ease beginning in the 1920s - a few years after the
Cerebral vascular 2,728 2,075 1.32 World War I doubling of cigarette smoking; followed
disease by epidemic lung cancer beginning in the 1930s - 20
Peripheral vascular 20 6 3.52 "pack years" or 150,000 cigarettes after World War I;
disease followed by epidemic emphysema/COPD beginning
Phlebitis and pulmo- 214 175 1.22 in the 1940s - the third decade after World War I.
nary embolism
Furthermore, as tar content and per capita cigarette
Other diseases 1,333 724 1.84 smoking decreased during the last 2.5 years, mortal-
Ulcer of stomach, duo- 365 92 3.97 ity from coronary heart disease and cerebrovascular
denum, jejunum disease decreased.

5.000 5,000 §
Furthermore, a matched-pair analysis of Ameri-
can Cancer Society prospective data by E. C. Ham-
o
1,000|: 1,000 a.
o
mond (1964) enabled this author to construct a Lung
8 Cancer Index to total tobaccosis mortality and the
8 estimate of a quarter million U.S. tobaccosis deaths in
_.}•""'" I Coronary | 1962 - equal to the sum of all deaths from accidents,
2 100 100
~^~ 1 Heart DiseaseE infection, suicide, homicide, and alcohol. Truly, for
those who smoke a pack or more of cigarettes daily,
tobacco is an environmental hazard equal to all other
10 hazards to life combined. In 1967 this estimate was
updated to 300,000 deaths for 1966.
During two ensuing decades, U.S. lung cancer
deaths alone more than doubled from 48,483 in
_ 1965 to 137,000 in 1987. In 1984, with the help of
190019101920 1930194019501960197019801990 2000 the Multi-Agency Working Group at the National
Figure III.8.2. Cigarette consumption and tobaccosis
mortality in the United States, 1900-87. The asterisk
Institute on Drug Abuse, seeking to achieve an up-
indicates that the population exposure to tobacco tars is dated, realistic estimate of U.S. tobaccosis mortality
decreasing faster than the cigarette curve. (From Eco- during the 1980s, this author applied proportionate
nomic Research Service, U.S. Department of Agricul- analytic methods to 1980 U.S. mortality data;
ture; Vital Statistics of the United States; WCHSA Ar- 485,000 tobaccosis deaths from cigarette smoking
chives [personal communication]; Ravenholt 1962; were estimated that year (Table III.8.5), as were
Walker and Brin 1988; U.S. Department of Health and
Human Services.)
Table III.8.5 Estimated number of deaths caused by
Magnitude of the Hazard
cigarette smoking in the United States, 1980
Although some astute observers attributed lung can- Anatomic site or nature of disease or injury No. of
cer to smoking during the 1920s, 1930s, and 1940s,
there was little general awareness of this relation- (ICD number) deaths
ship until the publication of case-control studies in Malignant neoplasms (140-209, 230-9) 147,000
1950 showing that almost all (more than 90 percent)
Diseases of the circulatory system (390-459) 240,000
of lung cancer patients were smokers. The associa-
Ischemic heart disease (410-14) 170,000
tion of smoking with cancer of the lung was so obvi- Other vascular diseases 70,000
ous, consistent, and understandable that many scien- Diseases of the respiratory system other than 61,000
tists were readily convinced that smoking was the cancer (460-519)
main cause of that disease. But when a number of Emphysema (492) 13,000
prominent statisticians (who were themselves smok- Chronic bronchitis and other respiratory 48,000
ers) criticized these studies because of possible biases diseases
inherent in retrospective studies, massive prospec-
Diseases of the digestive system (520-79) 14,000
tive studies of morbidity and mortality differentials
Diseases of the esophagus, stomach, and duode- 2,000
among smokers and nonsmokers were launched num (530-7)
about the same time by the British Medical Associa- Cirrhosis and other diseases of digestive system 12,000
tion, the American Cancer Society, and the American
Veterans Administration. (Among the many publica- Certain conditions originating in perinatal pe- 4,000
tions resulting from these studies were those by Doll riod (760-79) (caused by maternal smoking,
and Hill [1952], Hammond and Horn [1958], Dorn low birth weight, and other congenital
disabilities)
[1959], and Rogot and Murray [1980].) The studies
showed that smokers not only died from cancers of External causes of injury (E800-E999) 4,000
directly exposed tissues of the mouth, larynx, and Injuries caused by fire andflames(E890-E899) 2,500
lungs, but also died at a greatly accelerated rate from Other accidental injuries 1,500
a bodywide spectrum of diseases, especially cardio- Miscellaneous and ill-defined diseases 15,000
vascular diseases (Table III.8.4) - thus confirming Total 485,000
the finding of Raymond Pearl in 1938 that smoking
exerted a profound life-shortening effect. Source: Ravenholt (1984).

5 Million Deaths from Tobacco
more than 2.9 million deaths from lung cancer,
Tobacco |
more than 7 million deaths from cardiovascular dis-
Alcohol ^ ^ ^ ^ H 1 Million Deaths from Alcohol
ease, and
more than 14 million deaths from all forms of
Other H 300,000 Deaths from Other Addictions tobaccosis.
AIDS I 70.000 Deaths from AIDS
During the 1980s, the U.S. tobaccosis death toll
was roughly 500,000 annually, for a total of 5 million
Figure III.8.3. The price of pleasure: deaths from addic-
tive substances and AIDS in the United States, 1980s.
deaths in the decade. Moreover, even if all tobacco
(From Ravenholt 1984 and Centers for Disease Control.) use ceased immediately, many millions would still
die of tobaccosis in ensuing decades.
In 1989 the world's inhabitants were smoking 5
trillion cigarettes annually and consuming millions
more than 500,000 tobaccosis deaths from all forms
of tons of tobacco as cigars, bidis, chewing tobacco,
of tobacco use.
and snuff, as well as in pipes and hookas. The tobac-
This estimate was accepted and used by the Ameri-
cosis death toll was more than 2.5 million, and that
can Council on Science and Health and the World
Health Organization, but not by the U.S. Office of in the twentieth century more than 50 million.
Smoking and Health (OSH), which preferred a more Considered a global entity with an extraordi-
"conservative" estimate of 320,000 tobacco deaths in narily diffuse, subtle nature and with lifetime laten-
1987, raised to 390,000 in 1988. cies, tobaccosis poses the ultimate challenge to epi-
demiology and to world public health and political
Suffice it to say that the annual tobaccosis death
leadership.
toll - whether the OSH "conservative" estimate of
390,000 or the more complete estimate of 500,000 R. T. Ravenholt
tobaccosis deaths - is far greater than mortality Excerpted and reprinted with the permission of the Population
from any other preventable cause of death in our Council from R.T. Ravenholt. 1990. Tobacco's global death march.
time and more than 25 times greater than current Population and Development Review 16(2):213-40.
mortality from the acquired immune deficiency syn-
drome (AIDS), which emerged during the 1980s as
a newly recognized and formidable disease entity Bibliography
Anon. 1882. Editorial. Boston Medical and Surgical Jour-
(Figure III.8.3). nal 107: 501.
Auerback, O., et al. 1957. Changes in the bronchial epithe-
Conclusion lium in relation to smoking and cancer of the lung.
Tobacco owes much of its destructive power to the New England Journal of Medicine 256: 97-104.
Austin, G. A. 1978. Perspectives on the history ofpsychoac-
fact that its lethal effects are not immediately dis- tive substance abuse. Rockville, Md.
cernible. Initial reactions to smoking like nausea Berkson, J. 1959. The statistical investigation of smoking
and respiratory distress usually subside, and many and cancer of the lung. Proceedings of the Mayo Clinic
persons continue smoking, chewing, or snuffing to- 34: 206-24.
bacco for several decades without apparent serious Billings, J. S. 1885-6. Report on the mortality and vital
injury or death. When serious illness does occur, it statistics of the United States as returned at the tenth
assumes such diverse forms that few comprehend census (June 1,1880), 3 vols. Washington, D.C.
the common cause. Chandler, W. U. 1986. Banishing tobacco. World Watch
Only recently, during the fifth century of post- Paper 68. Washington, D.C.
Columbian tobacco experience, has medical and Coleman S., P. T. Piotrow, and W. Rinehart. 1979. Tobacco:
epidemiological science advanced sufficiently that Hazards to health and human reproduction. Popula-
the diffuse nature and great magnitude of tobacco's tion Reports, Ser. L, No. 1. Baltimore.
depredations have become fully evident. In the twen- Diehl, H. L. 1969. Tobacco and your health: The smoking
controversy. New York.
tieth century alone, we tally these numbers: Doll, R., and A. B. Hill. 1952. A study of the aetiology of
In the United States the smoking of 26 trillion carcinoma of the lung. British Medical Journal 2:
cigarettes and 556 billion cigars and the consump- 1271-86.
tion of 25 billion pounds of "manufactured to- Dorn, H. F. 1959. Tobacco consumption and mortality from
bacco" (pipe tobacco, chewing tobacco, and snuff) cancer and other disease. Public Health Reports 74:
have produced: 581-8.

Fisher, R. A. 1957. Smoking: The cancer controversy, some Ravenholt, R. T., and W. Pollin. 1983. Tobacco addiction
attempts to assess the evidence. Edinburgh. and other drug abuse among American youth. Proceed-
Hammond, E. C. 1964. Smoking in relation to mortality ings of the 5th World Conference on Smoking and
and morbidity: Findings in first 34 months of follow- Health. Winnipeg.
up in a prospective study started in 1959. Journal of Reducing the health consequences of smoking — 25 years of
National Cancer Institute 32: 115-24. progress: A report of the Surgeon General. 1989. Rock-
Hammond, E. C, and D. Horn. 1958. Smoking and death ville, Md.
rates: Report on forty-four months of follow-up of Report of the Surgeon General: The health consequences of
187,783 men. Journal of the American Medical Asso- smoking. 1964. Washington, D.C.
ciation 166: 1194-308. Rogot, E., and J. L. Murray. 1980. Smoking and causes of
Harris, J. E. 1983. Cigarette smoking among successive death among American veterans: 16 years of observa-
birth cohorts of men and women in the United States tion. Public Health Reports 95: 213-22.
during 1900-80. JNCI 71: 473-9. Smoking and health: A report of the Surgeon General.
Hiryama, T. 1983. Passive smoking and lung cancer: Con- 1979. Washington, D.C.
sistency of the association. Lancet 2:1425-6. Tabor, S. J. W. 1843. A series of nine historical sketches of
Klebba, A. J. 1982. Mortality from diseases associated tobacco from 1492 to 1800. Boston Medical and Surgi-
with smoking. Vital and Health Statistics, Ser. 20, No. cal Journal 27: 396-9.
17. Hyattsville, Mo. Walker, W. J., and B. N. Brin. 1988. U.S. lung cancer
National Center of Health Statistics. 1950-86. Vital Statis- mortality and declining cigarette tobacco consump-
tics of the United States. Annual volumes. Washing- tion. Journal of Clinical Epidemiology 41: 179-85.
ton, D.C. Warren, S. 1942. Effects of radiation on the cardiovascular
Ochsner, A. 1941. Carcinoma of the lung. Archives of Sur- system. Archives of Pathology 34: 1070-9.
gery 42: 209. Whelan, E.M. 1984. A smoking gun: How the tobacco in-
Osier, W. 1892. The principles and practice of medicine. dustry gets away with murder. Philadelphia.
New York. WHO programme on tobacco or health, 15 November 1985.
Pearl, R. 1938. Tobacco smoking and longevity. Science 87: Report by the Director-General, World Health Organi-
216-17. zation, to the Executive Board, 77th Session.
Plenge, K. 1930. Tabakabusus und Koronarsklerose. Woodward, J. J., et al. 1875-88. The medical and surgical
Deutsche medizinische Wochenschrift 56: 1947. history of the War of the Rebellion, 6 vols. Washington,
Pollin, W., and R. T. Ravenholt. 1984. Tobacco addiction D.C.
and tobacco mortality: Implications for death certifica- Wynder, E. L., and E. A. Graham. 1950. Tobacco smoking
tion. Journal of the American Medical Association as a possible etiologic factor in bronchogenic carci-
252: 2849-54. noma: A study of six hundred and eighty-four proved
Radford, E. P., and V. R. Hunt. 1964. Polonium 210: A cases. Journal of the American Medical Association
volatile radioelement in cigarettes. Science 143: 143: 329-36.
• 247-9.
Ravenholt, R. T. 1962. Historical epidemiology and grid
analysis of epidemiological data. American Journal of
Public Health 52: 776-90.
1964. Cigarette smoking: Magnitude of the hazard.
American Journal of Public Health 54: 1923-5.
1966. Malignant cellular evolution: An analysis of the
causation and prevention of cancer. Lancet 1: 523—6.
1982. Circulating mutagens from smoking. New En-
gland Journal of Medicine 307: 312.
1984. Addiction mortality in the United States, 1980:
Tobacco, alcohol, and other substances. Population
and Development Review 10: 697-724.
1985. Tobacco's impact on twentieth-century US mortal-
ity patterns. American Journal of Preventive Medicine
1: 4-17.
Ravenholt, R. T, and W. H. Foege. 1963. Epidemiology and
treatment of lung cancer in Seattle. Journal of Dis-
eases of the Chest 44: 174-85.
Ravenholt, R. T, et al. 1966. Effects of smoking upon
reproduction. American Journal of Obstetrics and Gy-
necology 96: 267-81.

III.9. Occupational Diseases 187
workplace and the occurrence of disease. Ramazzini
III.9 wrote of the health problems of common laborers
Occupational Diseases and skilled artisans as well as of scribes, scholars,
tradesmen, and others in the growing commercial
classes. He alerted physicians to the significance of
In recent years, occupational diseases have become the workplace in identifying the sources of a pa-
an area of intense interest to medicine, public tient's illness.
health, industry, and labor. Whole new areas of medi- The Industrial Revolution fundamentally changed
cal and public health specialization have developed the methods of production and work relationships
since the end of World War II, partly in response to throughout the world. The factory system, which
the detection of carcinogens in the workplace, dust displaced workers from their land and homes, cre-
in the air that workers breathe, and human-made ated new dangers. In addition to accidents caused by
chemicals that workers touch, taste, or inhale. Black machinery, a faster pace of production, and long
lung (coal workers' pneumoconiosis), brown lung hours, new diseases plagued the working classes.
(byssinosis), and white lung (asbestosis) are three Because England was the first industrial nation,
industry-specific diseases that have gained interna- English reformers and physicians quantified, mea-
tional attention and highlighted the role of occupa- sured, and documented the effects of industrialism
tion in the creation of illness. Laborers as well as and urbanization on the lives of the English working
physicians have become acutely aware of the dan- classes. Edwin Chadwick, Thomas Percival, and Wil-
gers posed by substances and materials at work in a liam Fair were among a group of Benthamites, To-
host of industries from steel to petrochemicals. ries, and social reformers who sought to use statisti-
The growing attention to the hazards of the indus- cal and quantitative analyses to impose order and
trial workplace has alerted workers even in "clean" expose the horrible working and living conditions
worksites to occupational disease. Physical dangers that were closely linked to the development of the
are posed to office workers by video display termi- factory system. Charles Turner Thackrah, a physi-
nals, poorly designed furniture, noise, and vibra- cian in Leeds, paid particular attention to the dis-
tions. Stress at the workplace is now seen as impor- eases of various trades and, in 1832, wrote The Ef-
tant in the creation of the modern epidemics of high fects of Arts, Trades, and Professions on Health and
blood pressure, heart disease, and stroke. The very Longevity. Thackrah organized his text by occupa-
definition of disease has been altered by a rising tion, listing the diseases and disabilities associated
popular and professional consciousness of the impor- with each trade. Diseases of operatives, dealers, mer-
tance of occupation as a source of illness. chants and master manufacturers, and professional
men were itemized. Among the operatives who were
exposed to harmful substances at work were corn-
Occupational Diseases through the sillers, maltsters, coffee roasters, snuff makers, rag
Industrial Revolution sorters, papermakers, flock dressers, and feather
Despite the recent concern, however, attention to the dressers. Dangers listed in the section on merchants
worksite as a source of disease is not new. Even the and manufacturers were "anxiety of mind" and "lack
ancients recognized that certain occupations pre- of exercise." Despite the obvious impact of new indus-
sented special risks of disease and injury. Hippoc- trial and urban conditions on the life of the workers
rates described lead poisoning among metal miners. and their families, much of this early work is re-
Pliny the Elder was the first to describe the dangers markable for its emphasis on the responsibility of
that dust posed to tradesmen. Decimus Junius Juve- individual workers to both remedy and control those
nalis (Juvenal) wrote of the dangers that black- forces destroying their lives.
smiths faced from the soot of "glowing ore." Over the The growing European socialist movements inter-
course of the next two millennia a variety of observ- preted the disintegration of workers' health as confir-
ers remarked on the health hazards faced by specific mation of the unacceptable social costs of industrial
tradesmen, artisans, and common laborers. But it capitalism. In the mid-nineteenth century, Freder-
was not until 1700 that Bernardino Ramazzini wrote ick Engels wrote his classic treatise, The Condition
his classic text, De Morbus Artificum Diatriba (Dis- of the Working-Class in England. In this work he
eases of workers). This manuscript, the result of a devoted two chapters to the conditions of work in a
lifetime of study and observation, was the first sys- variety of industries, specifically noting the effects
tematic treatment of the relationship between the of these conditions on the health of workers. He was

especially concerned with the impact of child labor the medical and public health communities away
on the health of children pointing to its relationship from this social explanation of disease. This was
with child mortality and disablement: illustrated most directly by the effect of Robert
In the manufacture of glass, too, work occurs which seems Koch's discovery of the tubercle bacillus on the his-
little injurious to men but cannot be endured by children. tory of industrial lung disease. By the time of Koch's
The hard labor, the irregularity of the hours, the frequent discovery in 1882 an enormous literature about the
night-work, and especially the great heat of the working effect of dust on the health of workers had developed,
place (100 to 190 Fahrenheit), engender in children gen- especially in Europe. But with the discovery of the
eral debility and disease, stunted growth, and especially bacillus, the study of its relation to industry ceased,
affections of the eye, bowel complaint, and rheumatic and according to Ludwig Teleky (1948), a noted indus-
bronchial affections. Many of the children are pale, have trial physician and author of the first modern his-
red eyes, often blind for weeks at a time, suffer from tory of industrial hygiene. In Europe, researchers
violent nausea, vomiting, coughs, colds, and rheuma- "mocked at all those 'curiosities' of quartz lungs, coal
tism. . . . The glass-blowers usually die young of debility of lungs, and iron lungs, 'all of which belong in a cabi-
chest infections. (Engels 1980, reprint 1892 publication) net of curiosities.' " Until the beginning of the twenti-
By the mid-nineteenth century, physicians, sani- eth century all consumption or phthisis came to be
tary and social reformers, and radicals recognized a understood as tuberculosis, caused by a specific or-
wide variety of occupational diseases that afflicted ganism and spread like other infectious diseases.
industrial populations. The medical literature was
filled with articles about dust diseases and heavy- The United States in the Early Twentieth
metal poisonings closely linked to the high tempera- Century
ture, poor ventilation, and bad lighting of the early In the United States the medical community also
factories. Consonant with much medical theory that narrowed its focus, which set back the study of occu-
associated disease with the social and moral environ- pational disease for a generation. Others outside of
ment of different populations, the medical literature the medical community developed a broader concep-
noted the explicit relationship between disease and tion of the relationship between the work environ-
the work environment. Health was understood to be a ment and health. In the late nineteenth and early
reflection of the balance between people and nature. twentieth centuries, reformers concerned with the
Disease was seen as a reflection of the imbalance plight of the urban poor saw that the terrible condi-
between humans and the unnatural environments tions of their lives and their work could not be sepa-
that they created for themselves. Cities, factories, rated. Charity and settlement-house workers, for ex-
slums, and other manifestations of industrialism ample, documented that in nearly one of every four
were creating this imbalance. Hence, physicians and dwellings in New York City in 1890 there was a
public health workers writing about treatments, death from consumption. In the poorer neighbor-
diagnoses, and cures for disease often framed their hoods, it was clear, the toll was much higher, leaving
arguments in the personal, moral, and social terms those communities devastated by the disease. The
that infused medical theory. For example, throughout Progressive Era (1890-1920) analysis that inti-
most of the nineteenth century, impure air, "mias- mately linked social conditions and disease led re-
mas," and dust were considered sources of disease; formers and public health workers to emphasize the
industrial dust was seen as the source of one form of connection between work and disease as well.
"phthisis" or consumption, a chronic condition that In industrial sections of the United States, individ-
affected broad cross sections of western European and ual physicians and state public health officials par-
U.S. populations. Popular and medical opinion coin- ticipated in reform movements for workmen's com-
cided in that both used the terms phthisis and con- pensation legislation, and John B. Andrews and the
sumption to denote a set of symptoms of diverse social American Association for Labor Legislation led cam-
origins. The symptoms of wasting away, coughing, paigns against such problems as lead poisoning and
spitting, and weakening appeared in victims from "phossy jaw" (necrosis of the jaw caused by exposure
various classes and social strata. The root of a to phosphorus, as in the making of matches). But
worker's disease could be found by looking at a host of occupational disease was not yet seen as an intrinsic
variables including race, ethnicity, personal charac- part of the mandate of public health.
teristics, home life, and work. It was only in 1915 that the U.S. Public Health
By the last third of the nineteenth century, how- Service was granted authority to investigate "occu-
ever, the growing acceptance of germ theory moved pational diseases and the relation of occupations to

III.9. Occupational Diseases 189
disease." It organized an Industrial Hygiene and the U.S. government to act on their warnings about
Sanitation section, and shortly thereafter the Ameri- the deleterious effects of radiation.
can Public Health Association also formed its own Medical and public health interest in occupational
Industrial Hygiene section. In addition, a few of diseases gave rise to new professions, such as that of
the state departments of health took an active and industrial hygienist, and new specialties, such as
sustained interest in occupational diseases, most occupational medicine. They were dominated in the
notably in Ohio under the leadership of Emery R. 1920s by private companies, which supplied finan-
Hayhurst. cial support, research facilities, and even patients.
Even those reformers and physicians who were Indeed, in the United States hundreds of corpora-
concerned with diseases of occupation focused tions hired their own physicians, nurses, and engi-
mostly on acute poisonings, especially heavy-metal neering and medical personnel as part of company
and phosphorus exposure. In the early years of the welfare and health plans. But there were very few
twentieth century, such investigators as Alice Hamil- industrial agencies that were concerned with indus-
ton, Florence Kelley, Andrews, and Hayhurst car- trial health and only a few universities, such as
ried out detailed studies of lead, phosphorus, and Harvard, Yale, and New York University, organized
mercury in such states as New York, Illinois, and departments that addressed industrial hygiene spe-
Ohio. In 1911, following the tragic Triangle Shirt- cifically. Thus, the control of workplace hazards was
waist fire in New York, in which scores of immigrant in the hands of professionals associated largely with
women were killed, the state sponsored a massive private industry and therefore was not really associ-
study of factory conditions led by Robert Wagner and ated with the broader perspectives of the Progres-
Frances Perkins, among others. In the 1920s and sives and labor reformers.
after, industrial hygienists and occupational physi-
cians investigated chronic diseases in workers in a The Problem of Dust and the Emergence
number of occupations, especially painters and bat- of Chronic Disease
tery workers exposed to lead, watch-dial makers ex- While a host of investigators began to study particu-
posed to radium, and miners exposed to coal, silica, lar acute diseases caused by specific industrial tox-
asbestos, and other dusts. The problem of lead had ins, the problem of dust in the closed environments
been known since antiquity, but the widespread in- of factories and mines galvanized the attention of
troduction of lead into paint and gasoline and the the health community and work force. Dust was a
increased smelting of ores associated with the Indus- potential problem in virtually every industrial set-
trial Revolution heightened the awareness of the ting. There were mineral and metal dusts in coal
danger of lead to workers and the public alike. and metal mines, foundries, steel mills, and rubber
During the early 1920s, workers in various petro- factories, and vegetable and animal dusts in grana-
chemical plants and research centers developed ries, bakeries, textile mills, and boot and shoe facto-
signs of acute lead poisoning. This alerted the public ries. In the early twentieth century, the work of
health community to the potential environmental Thomas Oliver and a series of British governmental
damage that the recently introduced leaded gasoline studies were instrumental in revitalizing interest in
posed. The Workers' Health Bureau argued that oil the industrial etiology of lung disease and the prob-
refinery workers were being "used like canaries in lem of chronic occupational diseases in general. In
the coal mines" to test for the presence of poisonous 1902, in his famous treatise Dangerous Trades, Oli-
substances. A major national conference was conver cited four specific dust diseases: chalicosis or
vened by the U.S. Public Health Service to discuss silicosis, siderosis, anthracosis, and byssinosis.
public policy regarding the use of organic lead in In the first half of the twentieth century, labor and
gasolines. However, it was not until the late 1960s business focused mostly on silica dust, and though
and early 1970s that systematic efforts were made to this diverted attention from the other dust diseases,
eliminate lead from both indoor paint and gasoline. it did lead to the formulation of general public poli-
It was also in the 1920s that women who worked cies that were applicable to other chronic industrial
in factories producing luminous watch dials in New diseases. Politicians, labor, management, insurance
Jersey were found to have symptoms of chronic radia- company representatives, physicians, and lawyers
tion poisoning. This prompted occupational disease all raised questions of responsibility for risk in the
researchers and local physicians to undertake one of new industrial workplaces.
the first studies on the dangers of radium exposure. The central questions of the debate were: What
But again, it took until well after World War II for was an industrial disease? How could occupational

and environmental diseases be distinguished? How the statistical materials for their implications about
should responsibility for risk be assigned? Should a the work environment. Although the case for the
worker be compensated for impairments or for loss of significance of dust as a cause of pneumoconiosis was
wages due to occupational diseases and disabilities? building, Hoffman's focus in this 1908 report re-
Should industry be held accountable for chronic ill- mained on industrial dusts and tuberculosis.
nesses whose symptoms appeared years and some- The dust hazards for metal miners and other work-
times decades after exposure? At what point in the ers had become sufficiently apparent that, in 1911,
progress of a disease should compensation be paid? the U.S. Public Health Service and the Bureau of
Was diagnosis sufficient for compensation claims, or Mines were asked by the National Association for
was inability to work the criterion? Who was to the Study of Tuberculosis to conduct a thorough in-
define inability to work - the employee, the govern- vestigation of lung diseases of metal miners. In 1914
ment, the physician, or the company? In short, the the two federal agencies initiated the first such
questions and arguments addressed the problem of epidemiological study in the tristate lead- and zinc-
who defined what today we would call latency, time mining region of Missouri, Kansas, and Oklahoma.
of onset, and the very process of disease. The study exposed the horrendous toll that metal
Shortly after the Boer War, silicosis gained wider dusts were taking on miners in the area and graphi-
public notice, as English miners who had worked in cally described the suffering that many of the min-
the South African gold mines returned to Great Brit- ers experienced as the disease progressed: "If we can
ain. Oliver described the fate of "young miners in imagine a man with his chest bound with transpar-
the bloom of health" who, after working in the gold ent adhesive plaster, we can form a mental picture of
fields for only a few years, "returned to Northumber- how useless were the efforts at deep inhalation made
land and elsewhere broken in health." Because of by these patients" (Lanza 1917a).
the hardness of the rock from which gold was ex-
tracted, dry drilling and blasting created special haz- In Europe, as well as in the United States, the intro-
ards both for native workers and for their English duction of power hammers, grinders, cutting instru-
overseers. In 1902 a British governmental commis- ments, and sand blasters at the turn of the century
sion was appointed to study the nature and preva- had exposed large numbers of industrial workers to
lence of lung diseases in these mines. Investigators massive quantities of fine silica dust, which could
such as Edgar Collis, H. S. Haldane, and the Miners' penetrate deeply into their lungs. By the time of the
Phthisis Commission demonstrated clearly that vic- Great Depression, many of these workers had devel-
tims of "Rand Miners' phthisis" were primarily suf- oped symptoms of silicosis and, under the financial
fering not from tuberculosis, but from silicosis. This strains created by massive unemployment, began to
was the first systematic study of the hazard of expo- bring their claims for disability benefits into the
sure to silica dust. workers' compensation and court systems of the in-
In the United States, the British findings were dustrialized nations. Thus, silicosis emerged as a
employed by Frederick L. Hoffman in his study The major political, social, and economic issue in the
Mortality from Consumption in Dusty Trades (1908). mid-1980s.
It began with the observation that "no extended In the United States this produced a massive num-
consideration [was required] to prove that human ber of lawsuits which ultimately led to the conven-
health was much influenced by the character of the ing of national conferences and the revision of work-
air breathed and that its purity is a matter of very ers' compensation systems. In this process, the issue
considerable sanitary and economic importance." of chronic industrial disease was forced onto the
The study built on the clinical evidence presented agendas of the medical and public health communi-
in the British material as well as on progressive so- ties, and the debate began over responsibility for
cial analysis. But it was also significant because Hoff- risk as well as over definitions of the technical and
man used statistical data drawn from insurance com- medical means of distinguishing and diagnosing
pany records and census materials from both Great chronic conditions. In the ensuing years the problem
Britain and the United States. Although the British of noninfectious chronic diseases created by indus-
(especially Thomas Oliver) had also used statistical trial work processes would become the centerpiece of
and epidemiological data in their investigations, industrial medicine.
Hoffman was the first American to use such methods. Although the relationship of dust exposure to can-
In so doing he documented the prevalence and scope cer was noted by the 1930s, it was only during the
of industrially created lung diseases and also used 1950s and 1960s that the medical and public health

EII.9. Occupational Diseases 191
communities acknowledged its significance and such With the decline of heavy industry after 1960 and
investigators as Wilhelm Heuper, Harriet Hardy, Ir- the rise of white collar and service industries, many
ving Selikoff, and Lorin Kerr began to link exposure people argued that occupational disease was a leg-
to dusts and toxins at the workplace to a variety of acy of the industrial era. Yet the problem of occupa-
cancers. The investigations by Irving Selikoff of as- tional diseases has merely taken on a new form. The
bestosis, mesothelioma, and lung cancer were par- emergence of a strong environmental movement has
ticularly effective in galvanizing popular and profes- once again focused attention on the dangers of indus-
sional attention; the widespread dispersal of asbestos trial production at the same time that it has broad-
throughout the general environment caused pro- ened the scope of what was once seen as a problem
found awareness of the dangers of industrial produc- for the industrial work force alone. The emergence,
tion to the nation's health. for example, of a nuclear power industry — whose
Occupational health was also a matter of concern domain ranges from the production of atomic weap-
for many social, labor, and political movements and ons to nuclear medicine — has heightened awareness
this concern focused on industrial hazards. During about the danger that radiation poses for workers
the Progressive Era, for example, such unions as the even in the most highly technical professions. Fur-
Bakers' and Confectioners' Union, the International thermore, the problems of industrial and atomic
Ladies Garment Workers Union, and the Amalga- waste disposal have forged a link between those who
mated Clothing Workers joined middle-class reform are concerned primarily about protecting workers
groups such as the National Consumers' League to and environmentalists.
press for reform of working conditions. During the Moreover, as international economic competition
1920s, activist organizations like the Workers' intensifies and workers and professionals alike expe-
Health Bureau of America sought to aid labor rience intense pressure to increase the speed of pro-
unions in investigations of workplace hazards and duction and improve the quality of products, the
joined painters, hatters, and petrochemical workers scope of the definition of occupational disease contin-
to demand reform of factory conditions. During the ues to broaden. Stress, for example, which was once
1930s various unions within the Congress of Indus- considered a problem of executives, is now a major
trial Organizations used deplorable health and reason for compensating claims in California. And
safety conditions as a focal point for organizing work- some miscarriages have been linked with exposure
ers in heavy industry. In the next two decades, other to low-level radiation from video display terminals.
unions, such as, the International Union of Mine,
Mill and Smelter Workers, pressed for national legis- In conclusion, the history of occupational diseases
lation to protect their members from dust hazards. reflects the broad history of industrial production
In the 1960s safety and health became major activi- and changing relationships between capital, labor,
ties for such unions as the Oil, Chemical and Atomic and the state. Professionals such as physicians, in-
Workers' Union (OCAW) and the United Mine Work- dustrial hygienists, and engineers, who have ad-
ers (UMW). Leaders like Lorin Kerr of the UMW dressed the problem of industrial disease, have often
and Anthony Mazzochi of the OCAW were involved also played auxiliary roles in the political and social
in lobbying for national legislation to protect miners conflict over the value of workers' lives. But control
and other workers, and the UMW was also active in of industrial diseases has been accomplished largely
urging special legislation to compensate victims of through political activities and changing economic
coal workers' pneumoconiosis. conditions rather than through medical or engineer-
All of these activities culminated in the Coal Mine ing interventions. Professionals have usually played
Health and Safety Act of 1969 and the Occupational an important technical role after an issue has been
Safety and Health Act of 1970. The latter act man- forced upon the public's agenda because of an indus-
dated the creation of both the Occupational Safety trial or environmental catastrophe or because of con-
and Health Administration (OSHA) in the U.S. De- certed political activity.
partment of Labor and the National Institute of Oc- Until the 1950s, the history of medicine was often
cupational Safety and Health (NIOSH) in the De- understood to be the history of infectious disease.
partment of Health and Human Services (previously However, with the evolution of chronic, noninfec-
Health, Education and Welfare). OSHA was to set tious disease as a major public health problem, indus-
and enforce national standards of safety and health trial illnesses have taken on a new importance and
on the job, and NIOSH, the research arm, was to are no longer mere oddities in a "cabinet of curiosi-
determine safe levels of industrial pollutants. ties." Indeed, industrial disease may prove to be a

model for understanding all noninfectious illness,
for those physicians, government agencies, and pro- in. io
fessionals who study it will be forced to address a History of Public Health and
host of questions regarding social and political re-
sponsibility for society's health. In fact, ultimately, Sanitation in the West before
industrialized countries will be forced to ask what 1700
level of risk is acceptable for industrial progress and
who should bear the cost.
Gerald Markowitz and David Rosner Throughout most of the past, ideas about the means
and necessity of providing for the health of the gen-
Bibliography eral community were based on notions of what en-
Chernick, Martin. 1986. The hawk's nest incident. New sured an individual's well-being. At this personal
Haven, Conn. level, measures that we might consider motivated by
Derickson, Alan. 1988. Workers' health, workers' democ- aesthetic choices (rather than fully developed ideals
racy. Ithaca, N.Y. of cleanliness and the health necessities of personal
Engels, Frederick. 1980. The condition of the working-class hygiene) were interwoven with practices designed to
in England. Moscow. (Reprint of 1892 ed. London.) minimize exposure to disease and injury. In a narrow
Hoffman, Frederick L. 1908. The mortality from consump-
tion in dusty trades. U.S. Bureau of Labor Bulletin No.
sense, public health practices refer only to the orga-
79. Washington, D.C. nization of care for the sick of a community and the
Lanza, Anthony. 1917a. Miners' consumption. Public implementation of epidemic controls. Public sanita-
Health Bulletin No. 85. Washington, D.C. tion includes all collective measures taken to protect
1917b. Physiological effects of siliceous dust on the min- the healthy from disease. Yet even today many be-
ers of the Joplin district. U.S. Bureau of Mines Bulle- lieve that what ensures the health of an individual
tin No. 132. Washington, D.C. should be reflected in the rules for maintaining the
Markowitz, Gerald, and David Rosner. 1987. Slaves of the public's health.
depression: Workers' letters about life on the job. Ith- Through much of the past and present, the view
aca, N.Y. of "public" health has involved a compromise be-
Oliver, Thomas. 1908. Diseases of occupation. London. tween available community resources and the ide-
Rosner, David, and Gerald Markowitz. 1987. Dying for
work: Occupational safety and health in twentieth cen-
als of health maintenance at the individual level.
tury America. Bloomington, Ind. Thus, in order to examine the history of public
1991. Dusted: Silicosis and the politics of industrial dis- health and sanitation before the 1700s, it is neces-
ease. Princeton, N.J. sary to include some discussion of the ideas and
Stellman, Jeanne, and Susan Daum. 1973. Work is danger- ideals of personal hygiene along with the develop-
ous to your health. New York. ment of concepts that led to genuine public health
Stern, Bernhard J. 1946. Medicine in industry. New York. practices. "Basic" sanitary organization largely com-
Teleky, Ludwig. 1948. History of factory and mine hygiene. prised rudimentary sanitation and sanitary law,
New York. care of the sick poor, provision for public physicians,
Thackrah, Charles Turner. 1985. The effects of arts, trades and epidemic controls.
and professions on health and longevity (1832), ed.
Saul Benison. Canton, Mass. Sanitation
Weindling, Paul. 1985. The social history of occupational Archaeological records testify to the antiquity of
health. London.
communal efforts to provide clean water and dispose
of human and animal wastes. The engineering
achievements of some peoples, such as the ancient
Peruvians in the Western Hemisphere and the Etrus-
cans in Europe, were most impressive. They man-
aged extensive systems for refuse drainage and clear
water conveyance. However sophisticated the out-
come, the motivation for these projects probably lay
in fears common among tribal societies - for exam-
ple, the fear of pollution offending a god or gods, who
in turn could send disease and disorder. Reflecting
these aboriginal values, natural springs and wells

m.10. Public Health and Sanitation in the West before 1700 193
were sites of religious activity for millennia. But cleansing agents for the skin, and oils, soaps, un-
independently of the health benefits, the mainte- guents, and other cosmetics used to maintain a good
nance of a reliable water supply and efficient drain- personal appearance and skin tone. Moreover, con-
age of agricultural lands permitted larger human cern for personal hygiene went far beyond the realm
settlements, and thus, whether or not the health of attracting sexual partners or performing religious
benefits were perceived, these practices were copied cleansing rituals. Greeks and Romans worshiped
or reinvented in all the early civilizations of the health and consequently elevated in importance to
Mediterranean, in the valleys of the Yellow, Indus, their life-style the technical knowledge they believed
Tigris, Euphrates, and Nile rivers, and in the Incan would promote individual health and longevity.
and Mayan civilizations. Galen's Hygiene, written shortly after the death
The most celebrated early sanitary engineering of Emperor Marcus Aurelius in A.D. 180, repre-
achievements were those of republican and imperial sents the acme of professional health theory and
Rome, c. 300 B.C. to A.D. 200. In fact, many of the advice through which Greek medical thought and
conduits built by the Romans remained in use until pragmatic Roman farm hygiene were united in late
the twentieth century. Basing drainage projects on Mediterranean antiquity (Sigerist 1956). The Hippo-
the successes of Etruscan predecessors, who were cratic theory of the four humors, describing health
able to construct extensive underground drainage as a balance of the humors, which in turn repre-
channels because the loose, volcanic soil of southern sented the four elements of all material substance,
Italy was easily worked, early Romans developed dictated the fundamental ways of preserving equi-
systems of wells, rainwater cisterns, and irrigation librium through an individual's natural changes in
ditches that promoted rural, agricultural develop- age, diet, season, and exposure to noxious influ-
ment. Before 300 B.C., the Romans seem to have ences. The emphasis was on prevention, and the
associated the assurance of clean and abundant wa- health seeker needed to learn which foods were
ter with ordinary life, an ideal never specifically right for his or her constitution, when baths pro-
related to the maintenance of health, public or pri- moted or jeopardized health, what exercise was ap-
vate. But when they began to build cities, aqueducts propriate, when purgation was needed, and what
became a public symbol of the Roman way of life, as substances and influences were lethal. Attention
well as a symbol of Roman power and sensitivity to was to be focused on the fine details and manage-
the general welfare. Frontinus, in On Aqueducts (c. ment of the individual's environment.
A.D. 100), says that the first one was constructed in Nonetheless, despite the foregoing, which seems an
Rome in 312 B.C. idealistic portrayal of health practices in antiquity,
In rural areas, the prosperity of the "farm" or villa the stark reality is that 25 years was the average life
seems to have been the inspiration for securing a expectation for most Greeks, Romans, Egyptians,
reliable water supply, a favorite topic for the prag- and others in the vast ancient Greco-Roman Empire.
matic and aristocratic authors of treatises on Roman Roman elites recognized the importance of effective
agriculture and medicine (Scarborough 1981). These disposal of human wastes and so constructed miles of
authors fastidiously detailed the benefits and draw- sewers and cloacae, as well as public and private
backs of using plants and drugs, differentiated harm- latrines, and collected the waste for use as fertilizer
ful from benign bugs, and analyzed myriad sub- in rural areas (Scarborough 1981). However, an enor-
stances that promoted or undermined the well-being mous gulf separated the privileged and the poor. The
of the farm and the farmer. For Cato, Columella, hovels and lean-to shacks of the destitute, home-
Frontinus, Vitruvius, Varro, and Celsus, health lessness, and severe crowding (all of which mimic life
benefits were the natural harvest of the well- in modern Western and Third World slums) domi-
managed farm, a pastoral ideal of Roman life that nated Roman life (Scobie 1986). The ideals promoted
survived through the urban, imperial centuries. by the wealthiest citizens apparently had little im-
Although Romans generally welcomed practical pact on the public's health. De facto, the drainage
advice, the adoption of the Greek ideals of personal systems installed in individual homes were seldom
hygiene was delayed until after the period of early connected to street drains and sewers, as archeology
republican growth - a time of rapid development of at Pompeii has shown, and latrines were not provided
architectural and administrative models for aque- with running water. Alex Scobie (1986) has detailed
ducts, cisterns, cloacae, drains, and wells. Greeks and the multiple health problems attending the practical
Romans, however, shared a passion for the details of aspects of Roman public hygiene, observing that a
personal hygiene, including a fondness for baths, city the size of Rome with a population of approxi-

mately 8 to 10 million in early imperial times would practices were adopted and gradually transformed
have produced about 40,000 to 50,000 kilograms of only as Christian Mediterranean cities began to
body waste per day. Arguing that only a fraction of grow again in the eleventh and twelfth centuries.
that output reached the "public" collection sites, he In the European Middle Ages, cities grew to a
shows that the emphasis in Roman public hygiene maximum of 100,000 to 150,000 individuals by the
was the maintenance of the farm and an aristocratic early fourteenth century, only one-tenth the size of
life-style, whatever the adverse health costs to the ancient Rome. The Roman legal principles holding
general population. The emptying of public and pri- individual property owners responsible for cleaning
vate facilities enhanced agricultural productivity the streets in front of their homes dominated "pub-
and provided a livelihood for armies of unskilled lic" sanitary intervention. Medieval Italians were
workers. The collection of urine aided the cloth indus- far more willing than the Romans to specify what
try, because fullers used urine as a mordant for cer- individual behaviors put others at risk and therefore
tain dyestuffs. Roman literature does not adequately to write new legislation prohibiting the pollution of
testify to the horrors of Roman cesspits "nauseating public streets with animal carcasses, human refuse,
mixture(s) of the corpses of the poor, animal car- and other noisome substances. Yet we do not know to
casses, sewage, and other garbage" (Scobie 1986). what extent laws were actually enforced, and it is
Nor have the marvels of the aqueducts fared well probable that medieval cities were even more
under recent historical scrutiny. Frontinus sang the squalid than those of antiquity. Nonetheless, there
praises of the nine aqueducts that daily supplied the seems to have been a new ethic of communal, collec-
city of Rome (scholars have calculated that they tive responsibility for public health. Some of the
provided about 992,000 cubic meters of water each change may have come about with the Christianiza-
day), but he tells us little about the distribution of tion of Europe, which among other things empha-
water and whether there were any mechanisms to sized the physical and spiritual dangers of evil. Ro-
stem the flow of water into basins and tanks. Be- man baths were used in common by the wealthier
cause of their malleability, lead pipes were com- classes, but medieval laws dictated strict segrega-
monly used in the plumbing of aristocratic homes, tion of the sexes, treating as prostitutes, for exam-
but we do not know whether the water they carried ple, women who strayed near the baths on a day
was soft or hard. (Hard water would have prevented when only men could use the facilities.
much of the lead from seeping into the drinking During the Middle Ages, urban dwellers could
water.) Ancient pastoral fondness for rainwater empty chamber pots into the streets as liberally as
probably protected many Romans outside the great aristocratic Romans might have done, but medieval
city from the multiple health hazards attending ad- lawmakers often prescribed the times at which such
vanced urban sanitary technology. wastes could or could not be evacuated or ordered
The best and worst features of Roman public that words of warning be shouted to passersby below.
health, and of the Greek traditions and theories of For example, thirteenth-century residents of Siena
personal hygiene, were passed along in the books were enjoined to cry "Look out!" three times before
and physical artifacts that survived the piecemeal tossing the contents of a pot onto the street, and
dismantling of the Roman Empire. Thus, the strong fines were specified for those who were found non-
aristocratic voice that determined the ideals of pub- compliant. Medieval city governments, like their Ro-
lic and private health and their implementation re- man predecessors, hired laborers to clean streets,
mained relatively unchanged in the societies that cisterns, and sewers and to evacuate garbage. But
inherited Roman custom, such as the Byzantine and unlike Roman officials, who appear to have adopted
Islamic empires. But in western Europe, retreat to a a laissez-faire attitude toward enforcement, they
rural economic base, the effective disappearance of elected or appointed district supervisors to patrol
cities and market economies, and the introduction of both these employees and citizen behavior, and to
Germanic customs interrupted the Greco-Roman report infractions to judicial authorities. The medi-
public health tradition. It is true that in Benedictine eval belief that humans were sources of pollution (by
monasteries upper-class monks constructed infirma- the fourteenth century, lepers were forced to wear
ries, baths, latrines, caldaria, or steam rooms, and yellow to symbolize their danger to the community)
cold rooms in the best of Roman aristocratic tradi- had profound consequences for the development of
tion. (St. Gallen monastery in Switzerland, built in epidemic controls, as will be discussed in a later
the eighth century, is one of the best surviving exam- section.
ples of this tradition.) But most Roman sanitary Leading the way for the rest of Europe, Italian and

III.10. Public Health and Sanitation in the West before 1700 195
probably Spanish cities appropriated detailed Roman tient at their doorway or in the marketplace, giving
law and customs regulating the trappings of public passersby the opportunity to make a diagnosis or
sanitation - baths, sewers, fountains-as well as offer therapeutic suggestions.
sanitary personnel and marketplace regulations, In Egypt, India, and China where political up-
leaving most of these features unchanged, at least on heaval was not as common as in Mesopotamia and
paper, for hundreds of years. Public hygiene laws in Greece, highly individualized solutions to the com-
1700 strongly resembled those of 1300, with even the munal responsibility for providing physicians were
fines little changed. Those who could afford to follow devised. Thus, Egypt may have developed a state
all the recommendations of Galenic personal hygiene system for the use of doctors as expert witnesses and
did so without questioning the basic premises of provided a living allowance to all physicians, and by
health maintenance, public or private. Only the cre- the period of the New Kingdom had established a
ation of boards of public health, a very important formal hierarchy of doctors, the chief palace physi-
late-medieval contribution to public health, and, late cian at its pinnacle. Similarly, in ancient India the
in the seventeenth century, medical attention to occu- king and other extremely wealthy individuals were
pational disease represented significant advances in obliged to provide medical care for their people by
modern public health philosophy and practice. underwriting the services of priestlike Ayurvedic
physicians (Basham 1976).
Care of the Indigent and Public Physicians It was the Greek tradition that was ultimately
The organization of basic health services within a transmitted to western Europe. From as early as the
community involves the provision of medical care to fourth century B.C., the Greeks had established a
all members of that community and a conscious at- network of salaried physicians throughout the Helle-
tempt to prevent or minimize disease. A relatively nistic world. The terms of their contracts to individ-
recent innovation is the appropriation of communal ual communities varied widely, but the arrangement
resources for hospitals devoted principally to medi- assured healers of some measure of personal stabil-
cal intervention, that is, to hospitals that are some- ity. Unlike physicians in the more monolithic Egyp-
thing other than a refuge for the sick, the poor, or tian society, who were natives subject to the same
pilgrims. The earliest hospital in the modern West- legal privileges and restrictions as their patients,
ern sense was probably the Ospedale Maggiore of physicians in the mobile Greek world were often
Milan. It was built in the mid-fifteenth century, foreigners who received salaries as well as tax immu-
funded by church properties, and managed by a lay nities and special privileges (e.g., citizenship, the
board of governors, who in turn were appointed by right to own land, rent-free housing, or even choice
state officials. Most medieval cities acknowledged theater tickets) in return for contractual service to a
the need for city hospitals, symbols of good Christian community. This "system" - if indeed one can so call
governance, and thus hospitals became as character- a functional solution to the provision of medical
istic of this society as the aqueducts had been of care - was adopted by the Romans in the designa-
Rome. tion of archiatri, or public physicians, whose duties
The public employment of physicians was another were extended and to some extent redefined over the
significant development in the history of public centuries. Later Renaissance European elaborations
health before 1700. Even ancient Greece, where of the concept of public health mediated by public
many physicians were itinerant healers forced to wan- physicians was a rediscovery of ancient practices
der in search of patients, established political and lost during the Middle Ages.
economic centers and provided salaries and other By the second century of the common era, large
privileges to individuals who would agree to minister Roman cities designated up to 10 archiatri, their
to their populations (Nutton 1981). Yet wherever a salaries set by municipal councilors, to minister to
settlement grew large enough to support ethnic, lin- the poor. Physicians often competed for these commu-
guistic, or even economic diversity, it was more diffi- nal posts, suggesting that there were financial re-
cult to ensure a sufficient number of healers. wards beyond the salary itself- most likely access to
In some places, such as Mesopotamia, the provi- a wealthy patient population. Public physicians
sion of physicians could extend the power of rulers or seem to have been selected by laymen. Sources are
of a religion if people were assured that the proper largely silent on how their performance was as-
gods would be summoned when intervention was sessed or how they typically sought access to their
necessary. With politically or religiously less impor- clientele. It is unlikely that they had any responsibil-
tant illnesses, a patient's family could post the pa- ity for the maintenance of public health in other

respects, such as epidemic control or sanitation. tion to ensure medical care. Yet public physicians
Other salaried physicians in the Roman Empire in- were not true public health physicians or medical
cluded physicians to gladiators (Galen began his pro- officers of health, positions that Renaissance Italians
fessional career in such an assignment), to baths, seem to have invented. The institutions addressing
and to courts or large households. communal medical responsibility for health surveil-
The financial privileges and immunities granted lance arose instead from epidemic controls.
to public physicians may have ensured the survival Richard Palmer (1981) has demonstrated that in
of the office well into the early Middle Ages, for with large metropolitan areas the system of medici
inflation and the heavy fiscal demands on Roman condotti, the Italian medieval name for archiatri, fell
citizens around A.D. 200, these inducements were into disuse by the sixteenth century. But in small
considerable. In the early fourth century, the em- towns the system continued or even increased in
peror Constantine the Great extended state salaries popularity because it was a means of securing qual-
to teaching doctors irrespective of their medical ser- ity medical care without being at the mercy of itiner-
vices to the community, thus linking the interests of ant quacks or "specialists."
public physicians to those of local medical personnel. The system of rural public physicians was able to
That association would become paramount in the absorb the late medieval expansion in the number of
later Middle Ages, leading to the monitoring and medical professionals, which brought about a more
licensing of medical practice, ostensibly for the pub- equal distribution of medical goods and services. Cit-
lic good but equally obviously for the financial bene- ies no longer needed to import physicians. The finan-
fit of particular groups of healers. Under Emperor cial benefits they offered, the opportunities they pro-
Theodoric, in the early sixth century, Roman doctors vided for other, similarly trained practitioners, and
were given an overseer, an imperial physician called often the presence of a university provided ample
"count of the archiatri," who may have formed the inducements for urban medical practice.
first formal link between lay interests and medical The major cities of Italy and Spain provided the
elites because he could nominate and appoint physi- prototype in medicine for the northern European
cians to a college of medicine. Specialized medical cities of the seventeenth and eighteenth centuries:
services, such as those of official public midwives, They developed local medical colleges dedicated to
may also date from this period. The Islamic state, defending professional standards, restricting prac-
which replaced most of the Roman Empire in the tice to the "qualified," regulating pharmacies, and
Middle East, brought regulatory power over physi- mediating the state's charitable obligations to the
cians under the control of the state, which paid the poor in areas the church had abandoned (Lopez
salaries of physicians appointed to hospitals and Pinero 1981; Palmer 1981). Tightening the restric-
even administered licensing examinations (Karmi tions on membership became common in Italy, fore-
1981). shadowing the mercantilistic objectives of state
The medical institutions of late Rome did not per- medicine.
sist through the early Middle Ages, even in rela-
tively urbanized Italy and Spain. The practice of Epidemic Controls
community hiring of salaried physicians was not re- Refuse disposal and the provision of clean water
established until the twelfth and thirteenth centu- were regarded as aesthetic problems for growing cit-
ries. Vivian Nutton (1981) argues persuasively that ies as much as they were means to improve health.
early Italian interest in jurisprudence and their edi- Nevertheless, by the thirteenth century, all Italian
tions of Roman law texts led to the reestablishment cities with statutes of laws had incorporated a sys-
of public physicians in Italy. Thus, the office ac- tem of sanitary provision modeled on ancient Roman
quired legal responsibilities not typical of the an- patterns. The hallmarks of this system were mainte-
cient world. Perugia's first medicus vulnerum (be- nance of clean water sources, patrolling refuse dis-
fore 1222) probably had to provide expert testimony posal, and the posting of gatemen to identify poten-
in cases of assault and battery. Public physicians in tial sources of infection in the city. Two explanatory
succeeding centuries typically had to judge whether models underlay this approach to public health. The
a wound or injury had caused death. By the end of first was based on the assumption that polluted air
the fifteenth century, the system of hiring physicians caused disease by altering the humoral balance of
was almost universal in Mediterranean western Eu- humans and animals. The second was based on the
rope, a system undoubtedly reinforced by the recur- knowledge that some diseases, such as leprosy, could
rence of plagues, which necessitated state interven- be transmitted from one person to another.

III. 10. Public Health and Sanitation in the West before 1700 197
The first of these two models was influential East, lepers were considered diseased in soul as well
among public physicians when boards or offices of as body, were ritually separated from the commu-
public health were created. The second model of con- nity, were deemedfiercelycontagious to others, and
tagion was not widely accepted during antiquity and were subjected to religious penance and other pun-
the Middle Ages, at least among the educated elite. ishments even after diagnosis and isolation.
One exception, the practice of isolating lepers in Apart from exaggerated responses in the West to
special hospitals (leprosaria), is noteworthy because lepers (as well as to prostitutes, homosexuals, here-
the custom was later adapted and justified as a tics, and Jews), collective action to protect public
means of epidemic control. Strict social isolation of health was, as a rule, crisis-oriented. Plague and
individuals designated as lepers, whatever condi- other epidemics may not have been the most impor-
tions may have been responsible for cases of ad- tant manifestations of disease in earlier societies in
vanced skin infection and/or physical deformities, terms of mortality, but they were certainly the most
was a practice derived from the Jews of antiquity. In visible. Recurrent bubonic plague epidemics evoked
biblical times priests identified those suffering from the greatest response, making plague what Charles-
"leprosy" and used their authority to cast these peo- Edward Winslow (1943) called the "great teacher."
ple out of a settlement. Drawing on this practice, Beginning with the wave now called the Black
medieval Christian communities permitted priests Death, plague appeared in Europe at least once ev-
to identify lepers and, at least in northern Europe, ery generation between 1348 and 1720. At the first
subject them to a ritual burial and banish them from outbreak of the disease, fourteenth-century govern-
the community. ment officials in Florence, Venice, Perugia, and
Unlike Jews, medieval Christians accepted a com- Lerida called on medical authorities to provide ad-
munal responsibility for providing lepers with orga- vice on plague control and containment. Of these,
nized care - food, clothing, shelter, and religious only Lerida's adviser, Jacme d'Agramont, seems to
services — but rarely medical care. The church and have articulated a contagion model for the spread of
state cooperated in the construction and mainte- disease. The Florentine and Venetian approaches to
nance of residential hospitals for lepers. The peak of epidemic control may have been the most sophisti-
this building activity occurred in the period from cated: aggressive cleanup of refuse, filth, offal, and
1150 to 1300. other sources of corruption and putrefaction on the
Nonetheless, lepers were ostracized. Guards often city streets. They applied traditional health prac-
kept them outside city gates. Those formally identi- tices to meet an emergency, but created a novel bu-
fied as lepers were made to wear symbols of their reaucratic unit to orchestrate public efforts. In these
infection and perhaps to carry a bell or clapper to two republican city-states, small committees of
warn those who might get too near them. They could wealthy citizens were appointed to oversee the ad-
shop at markets only on designated days and hours, ministration of ordinary sanitary laws, to hire physi-
and could touch things only with a long pole. More- cians, gravediggers, and other necessary personnel,
over, practices such as these survived throughout to maintain public order and respect for property,
the early modern period even when leprosaria were and to make emergency legislation. These communi-
turned to other uses. ties saw no need for the direct intervention of the
In other societies (e.g., Chinese and Muslim) in medical guilds. By contrast, in Paris, which lacked a
which leprosy was considered to be a communicable tradition of lay involvement in public health control,
disease, social restrictions were often linked to legal members of the university medical faculty collec-
restraints on lepers' activities. In Muslim lands, tively offered advice about surviving pestilence, a
"mortal" illnesses, including both leprosy and men- practice individual doctors elsewhere followed in pro-
tal illness, cast their victims into a state of depen- viding counsel to their patients.
dency, somewhat like that of a child or slave. They For whatever reason, during the following century
lost the right to make and maintain contracts, in- there seems to have been no deliberate reappraisal
cluding the right to continue a contract of marriage. of the sanitary methods used in the earliest plague
Though a wide variety of behavioral responses to epidemic, and no temporary re-creation of boards of
lepers existed across Islamic society, ranging from health other than in Milan, the only northern Ital-
pity, to aggressive medical assistance, to isolation of ian city not stricken during the 1348 epidemic. Most
the sufferers in leper hospitals, Michael Dols (1983) cities relied instead on maintaining order, particu-
emphasizes the distinctiveness of Western Judeo- larly in the burial of bodies, acquiring information
Christian tradition. In Europe, but not in the Middle about cities that were havens from disease (or, con-

versely, cities that were stricken with plague), pro- Only during the fourteenth century do descrip-
viding physicians and other service personnel, and tions of plague note the loss of many principal citi-
transferring property and goods after the plague to zens. After that period, elites seem to have worked
heirs or to the state. Rarely, however, did cities spe- out effective patterns of flight, so that only those
cifically address the technical problems of public or who remained in the cities were exposed to danger.
community-level measures for containing plague Unfortunately, in urban areas, plague control mea-
even though the "corruption of the air" theory pre- sures may have inadvertently augmented the death
sumably should have dictated intervention. Purify- tolls. Standard practices developed in Italian cities
ing bonfires, the disinfection or destruction of the during the fifteenth century - practices that would
goods and clothing of plague victims, and fumigation be followed by northern Europeans during the late
or other cleansing of infected dwellings were prac- sixteenth and seventeenth centuries - included the
tices first employed aggressively in Milan in the late house arrest or hospital confinement of all family
fourteenth century. Elsewhere and later, antiplague members of plague victims as well as others who
measures based on either the contagion or the cor- may have had contact with them, whether or not the
ruption model of plague were adopted. Cito, longe, others were sick. This led to the construction of ram-
tarde — "Flee quickly, go far, and return slowly" - shackle buildings, lazarettos, that could segregate as
was the advice most wealthy city dwellers followed many as 5,000 to 10,000 individuals at a time. By
during the first century of plague experience, the sixteenth century, larger urban areas were quar-
thereby eschewing costlier and more direct mea- antining the still-healthy contacts of plague victims
sures against the disease. in one place, isolating the ill together with immedi-
The tiny Dalmatian colony of Venice, Ragusa (now ate family members in a medically oriented hospital,
Dubrovnik), invented the quarantine in 1377. This and placing those who recovered in houses or hos-
was a response to impending plague whereby a tem- pices for a second period of quarantine.
porary moratorium on travel and trade with the By 1500 many of the principal Italian city-states
town was decreed. The Ragusan practice, actually had created permanent boards of health to monitor
then a trentino, or 30-day waiting period, became urban sanitation and disease threats even when no
standard maritime practice by the sixteenth and crisis arose. Rarely were physicians members of
seventeenth centuries. Although the quarantine in these aristocratic boards, though in many cities the
common parlance has acquired a more aggressive lay directors employed medical officers of health.
meaning, in the maritime context it was a passive Nevertheless, local colleges of medicine and univer-
measure designed to prevent incursions of plague sity medical faculties assumed the responsibility of
rather than to segregate active cases. Through repro- providing diagnostic and therapeutic advice when
duction of a typographical error in the early nine- crises threatened. By the second half of the sixteenth
teenth century, many surveys of quarantine and pub- century, boards of health routinely consulted mem-
lic health have credited Marseilles with the use of bers of the medical establishment, one group helping
the quarantine by 1483. In reality the Ragusan mari- the other in publication efforts to dispense both
time quarantine was not widely used until the six- health advice and sanitary legislation and in the
teenth century. provision of public "debriefings" after a plague had
Another feature of what was to become regular passed. During the sixteenth and seventeenth centu-
plague control, the pest house, or lazaretto, was used ries, these basic principles of public health surveil-
during the first plague century, 1350 to 1450, but lance and epidemic control were adopted by states
chiefly as a means of delivering medical care to the north of the Alps.
poor. After the 1450s both quarantine (passive, pre- In Italy and the Mediterranean, generally, the
ventive isolation of the healthy) and active hospital boards of health developed into tremendously power-
isolation of the ill became more popular antiplague ful bureaucracies, commanding sizable portions of
measures in city-states, which can be taken as evi- state resources and the cooperation of diplomats in
dence for the increasing acceptance of a contagion securing information about the health conditions in
theory of plague. Finally, official boards of health other states. Carlo Cipolla (1976) identifies both ver-
were reestablished. Throughout the early modern tical and horizontal paths of transmitting such infor-
period, these bureaucracies identified and handled mation, emphasizing the aristocratic character of
human cases of plague and acted as arbiters of stan- health boards and their successes in superseding
dard public health controls (Cipolla 1976; Carmi- any authority that merchants might claim from the
chael 1986). state. Detailed information about plague or other

m.10. Public Health and Sanitation in the West before 1700 199
diseases thought to be contagious was gathered from order and reason, was pan-European. During the
the reports of ambassadors as well as from broad eighteenth century, the impetus for change and re-
networks of informants and spies at home. Armed form in public health thus moved northward. Reject-
with these data, health magistracies could impose ing the political bases for state medicine that had led
quarantine at will, confiscate goods, and impound, to the Italian boards of health, northern Europeans
fumigate, disinfect, or burn them. Though they usu- turned their energies to the production and consump-
ally agreed to reimburse the owners at half to two- tion of health information: popular handbooks and
thirds the value of their property, dire necessity and manuals, such as those by William Buchann and S.
heavy expenditures during great epidemics left A. Tissot; the proliferation of foundling homes, hospi-
many boards of health bankrupt in all but their tals, and infirmaries; and the earliest efforts at sys-
broad judicial authority. In fact, despite all efforts tematic information gathering. As we move closer to
and a rigorous interpretation of the contagion theory the modern world, the rhetoric and rationale on
of plague, the plagues of the late sixteenth and seven- which sanitation, care for the indigent, provision of
teenth centuries were catastrophic in the Mediterra- public physicians, and epidemic controls were based
nean countries, in terms of both human and finan- before 1700 are blended into a new campaign for
cial losses. cleanliness and order, public and private.
Not surprisingly, with the sweeping powers Ital- Ann G. Carmichael
ian boards of health were given, permanent magis-
tracies required greater justification for their exis-
tence and their policies than the control of plague. Bibliography
They could argue that plagues would have been even Basham, A. L. 1976. The practice of medicine in ancient
worse without their efforts, but the economic costs of and medieval India. In Asian medical systems, ed.
Charles Leslie, 18-43. Berkeley and Los Angeles.
quarantine and isolation policies were more than
Brody, Saul Nathan. 1974. The disease of the soul: A study
early modern populations could bear without the in the moral association of leprosy in medieval litera-
creation of widescale human misery. Yet as strong ture. Ithaca, N.Y.
monarchies emerged, legislators, physicians, and Carmichael, Ann G. 1986. Plague and the poor in Renais-
concerned aristocrats of the seventeenth and early sance Florence. New York.
eighteenth centuries were able to weave some public Cipolla, Carlo M. 1976. Public health and the medical
health controls into the evolving theories of mercan- profession in the Renaissance. New York.
tilism. Apart from epidemic surveillance, medical Dols, Michael. 1983. The leper in medieval Islamic society.
"police" extended state medicine into the licensure Speculum 58: 891-916.
of midwives, the control of drugs and markets for Hannaway, Caroline. 1981. From private hygiene to pub-
drugs, stricter control of nonlicensed practitioners, lic health: A transformation in Western medicine in
and a variety of other matters. The results were the eighteenth and nineteenth centuries. In Public
optimistically summarized at the end of the eigh- health: Proceedings of the 5th International Sympo-
sium on the Comparative History of Medicine — East
teenth century by an Austrian state physician work-
and West, ed. Teizo Ogawa, 108-28. Tokyo.
ing in Lombardy, Johann Peter Frank (Sigerist
Karmi, Ghada. 1981. State control of the physicians in the
1956). Middle Ages: An Islamic model. In The town and state
Outside the Italian sphere, where state medicine physician, ed. A. W. Russell, 63-84.
and public health carried the longest and strongest Lopez-Pinero, Jose Maria. 1981. The medical profession in
tradition, public health boards and epidemic con- sixteenth-century Spain. In The town and state physi-
trols did not evolve into permanent magistracies cian, ed. A. W. Russell, 85-98.
concerned with all aspects of public health. As Caro- Nutton, Vivian. 1981. Continuity or rediscovery? The city
line Hannaway (1981) has indicated, at the begin- physician in classical antiquity and medieval Italy. In
ning of the eighteenth century, the French, British, The town and state physician, ed. A. W. Russell, 9—46.
German, and, ultimately, U.S. traditions of public Palmer, Richard J. 1981. Physicians and the state in post-
medieval Italy. In The town and state physician, ed. A.
health relied mainly on the traditional Galenic-
W. Russell, 47-62.
Hippocratic discourse about what ensured an indi- Rosen, George. 1958. A history ofpublic health. New York.
vidual's good health. Superimposed on those inter- Russell, Andrew W., ed. 1981. The town and state physi-
ests was makeshift machinery of epidemic control cian in Europe from the Middle Ages to the Enlighten-
borrowed from the Italians. Concern for the health of ment. Wolfenbuttel.
"the people," however, spurred by general mercan- Scarborough, John S. 1981. Roman medicine and public
tilist goals and the early Enlightenment passion for health. In Public health: Proceedings of the 5th Inter-

200 HI. Medical Specialties and Disease Prevention
national Symposium on the Comparative History of economic reasons, merchants shipping food abroad
Medicine — East and West, ed. Teizo Ogawa, 33-74. promoted regulations on meat and grains in order to
Tokyo. protect their markets and save themselves from dis-
Scobie, Alex. 1986. Slums, sanitation and mortality in the honest competition.
Roman world. Klio 68: 399-433. The American colonial laws and regulations,
Sigerist, Henry E. 1956. Landmarks in the history of hy- which were patterned after those of English towns
giene. New York.
Sun Tz'u. 1981. The washing away of wrongs. Science,
and cities, illustrate the ways in which communities
medicine and technology in East Asia, Vol. 1, trans. protected their food. Most of the regulations were
Brian E. McKnight. Ann Arbor, Mich. enacted in the first century of colonization and
Temkin, Owsei. 1977. An historical analysis of the concept strengthened in the second. For example, when New
of infection. In The double face of Janus and other York City received a new charter in 1731, the old
essays, 469-70. Baltimore. bread laws were promptly reenacted. Bakers were
Varron, A. G. 1939. Hygiene in the medieval city. Ciba required to stamp their initials on loaves, the mayor
Symposia 1: 205-14. and aldermen determined the price and quality of
Winslow, Charles-Edward Amory. 1943. The conquest of bread every three months, and bread inspectors
epidemic disease: A chapter in the history of ideas. were appointed to enforce the regulations. Butchers
Princeton, N.J. could be penalized for selling putrid or "blowne"
meat, and a series of regulations governed the town
markets, with special attention to the sale of fish
and meat.
Slaughterhouses, which could be both public nui-
III. 11 sances and potential sources of bad meat, were
History of Public Health and among the earliest businesses brought under town
control. The term public nuisance in the eighteenth
Sanitation in the West since and nineteenth centuries embraced a great many
1700 sources of filth and vile odors. Wastes, rubbish, and
garbage were simply dumped into the nearest
stream or body of water, except in major cities,
The nature and role of public health are constantly which generally had one or more covered sewers.
changing, and its definition has been a major preoc- Some foul-smelling open sewers characterized all
cupation of public health leaders in the twentieth cities and towns. The water closet was rare until the
century. Essentially, public health is and always has late nineteenth century, and the vast majority of
been community action undertaken to avoid disease residents relied on privies. In the poorer areas they
and other threats to the health and welfare of indi- were rarely emptied, with the result that their con-
viduals and the community at large. The precise tents overflowed into the gutters. The work of empty-
form that this action takes depends on what the ing privies was handled by scavengers, sometimes
community perceives as dangers to health, the struc- employees of the municipality, but more often pri-
ture of government, the existing medical knowledge, vate contractors. They slopped human wastes in
and a variety of social and cultural factors. From the open, leaking carts through the streets to the near-
beginning, communities, consciously or not, have est dock, wharf, or empty piece of land.
recognized a correlation between filth and sickness, Street cleaning and garbage collection were left
and a measure of personal and community hygiene largely to private enterprise and were haphazard at
characterized even the earliest societies. best. The malodorous mounds of manure in the dair-
By the eighteenth century, personal and commu- ies and stables and the equally foul-smelling en-
nity hygiene were becoming institutionalized. A trails, hides, and other materials processed by the
wide variety of local regulations governed the food so-called nuisance industries attracted myriad flies
markets, the baking of bread, the slaughtering of in addition to offending the nostrils of neighboring
animals, and the sale of meat andfish.These regula- residents. The putrefying odors from these accumula-
tions were motivated by a concern for the poor, a tions of entrails and hides, particularly in summer,
desire for food of a reasonable quality, and commer- must have been almost overwhelming.
cial considerations. Bread was always a staple of the Early U.S. towns were spared the worst of these
poor, and regulations in the Western world invari- problems because they were smaller and their resi-
ably set the weight, price, and quality of loaves. For dents more affluent. The small size of communities

m . l l . Public Health and Sanitation in the West since 1700 201
and the cheapness of land made it easier for the town lation represented wealth, and the emergence of po-
fathers to order the slaughterers and other nuisance litical arithmetic or population statistics in the sev-
industries to move to the outskirts. By 1800, how- enteenth century provided a crude means of measur-
ever, the growing U.S. cities were beginning to expe- ing the health of a given population. John Locke's
rience the major sanitary problems faced by their Essay on Human Understanding, emphasizing the
British and European counterparts. The great bu- role of environment, encouraged intellectuals, par-
bonic plagues beginning in the fourteenth century ticularly in France, to advocate improving the lot of
had taught Europeans the value of quarantine and human beings through social reform. In his Encyclo-
isolation, but by the eighteenth century, the major pedia, Denis Diderot discussed medical care, hospi-
killer diseases had become endemic. Smallpox, one tals, and a wide range of topics related to health.
of the most deadly, was largely a children's disease Economic changes led to a population explosion in
by the second half of the eighteenth century, and no Europe beginning in the mid-eighteenth century,
longer aroused alarm. On the Continent, occasional and one result was an enormous infant mortality
resurgences of bubonic plague led governments to rate in the crowded cities and towns. A second result
establish quarantines on their eastern borders, but was the emergence of a socially conscious middle
even this threat diminished toward the close of the class out of which grew the British humanitarian
century. movement. An important aspect of the movement
The one area where quarantines were applied was a concern for infant welfare, a concern that
with some consistency was the North American colo- stimulated the rise of voluntary hospitals in Great
nies. Because of the colonies' sparse population and Britain and ultimately led to an awareness of the
geographic separation from Europe and one another, deplorable health conditions of all workers. The eigh-
great epidemic diseases could not establish them- teenth century, too, saw the publication of Bernar-
selves permanently until late in the colonial period. dino Ramazzini's classic study on the diseases of
The two most feared disorders were smallpox, workers, De Morbus Artificum Diatriba.
brought from Europe or by slaves from Africa, and Even more significant than the writings of
yellow fever, usually introduced from the West In- Ramazzini, the French philosophers, and other intel-
dies. Smallpox appeared only occasionally in the sev- lectuals in bringing government action was the
enteenth century, but it struck the colonials with work of Johann Peter Frank. In 1779 he published
devastating effect. By 1700 all of the colonies had the first volume of a comprehensive nine-volume
enacted quarantine laws of various degrees of effec- study instructing government officials on how to
tiveness and most of the port towns had established maintain the health of the people. Stimulated by the
"pesthouses" in which to isolate smallpox patients. prevailing intellectual ferment, the enlightened des-
Yellow fever did not enter the colonies until the pots of Prussia, Austria, Russia, and other states
end of the seventeenth century. Unlike smallpox, made tentative attempts to impose health regula-
which was obviously spread from one individual to tions on their subjects. At that time, however, the
another, yellow fever was a strange and unaccount- governing structures were inadequate for the task,
able pestilence that brought death in a horrible fash- and the upheavals of the French Revolution and
ion to its victims. It struck the colonies only occasion- Napoleonic Wars temporarily ended efforts at health
ally, but news of its presence in the West Indies led reform.
authorities in every coastal town to institute quaran- In Great Britain the seventeenth century had seen
tines against vessels from that area. A series of the execution of one king and the deposing of a
epidemics, which struck the entire eastern coast be- second in the course of the Glorious Revolution of
ginning in 1793, led to the establishment of perma- 1688. The resulting distrust of the central govern-
nent quarantine officers and temporary health ment meant that, for the next century and a half, a
boards in nearly every major port. The limited sani- high degree of authority remained at the local level.
tary and quarantine laws of the eighteenth century, Hence, until the mid-nineteenth century, efforts to
many of which dated back several hundred years, improve public health were the work of voluntary
were to prove inadequate under the impact of rapid groups or of local governments. Although some prog-
urbanism and industrialism after 1750. Fortunately, ress was made at the local level - most notably in
that eighteenth-century period of intellectual fer- terms of infant care, the mentally ill, and the con-
ment, the Age of Enlightenment, created a new struction of hospitals — public health was of little
awareness of the need for a healthy population. The concern to the national government. Probably the
earlier theory of mercantilism had argued that popu- most significant development was the rapid increase

in hospitals and asylums and the appearance of dis- slums, convinced public health pioneers that sani-
pensaries or outpatient clinics. In England the major- tary programs were the solution to the problems of
ity of these were funded by private charity, whereas disease and ill health. Consequently, in the prevail-
on the Continent they were largely municipal or ing argument over the value of quarantine versus
state-supported. sanitation, the sanitationists, represented by Chad-
It was no accident that England, which was in the wick in England, won out. The panic and disruption
vanguard of the Industrial Revolution, took the first in Great Britain caused by the first epidemic in 1831
effective steps toward establishing a national public undoubtedly contributed to the general unrest in
health program. The original charters of most En- England and, indirectly, was responsible for a num-
glish towns and cities gave the municipal govern- ber of major reforms. Among the significant legisla-
ment only limited powers, and these proved totally tive measures enacted in these years were the Parlia-
inadequate to meet the needs of their increasing mentary Reform Bill of 1832, the Factory Act of
populations. The first local health board in Great 1833, the Poor Law Amendment of 1834, and the
Britain came into existence in Manchester in 1796. Municipal Corporations Act of 1835. The last act
A series of typhus epidemics among the overworked was particularly important because it strengthened
cotton mill employees, who lived and worked in the authority of town officials and gave them wider
crowded, filthy conditions, led Thomas Percival, powers in the areas of health and social services.
John Ferriar, and other physicians to organize a In 1834 Chadwick was made secretary of the new
voluntary board of health. In Liverpool, James Poor Law Board, and the board's investigations un-
Currie and a small group of other physicians as- der his direction laid the basis for his great Report
sumed the same responsibility. Owing to the haphaz- on the Sanitary Condition of the Labouring Classes.
ard structure of English local government and the Its publication in 1842 led to the appointment of a
prevailing laissez-faire sentiment, little was accom- Royal Commission on the Health of Towns, and the
plished in the following half-century. grim reports of this commission eventually forced
Atrocious factory conditions, particularly as they Parliament to enact the first major national health
affected child and female workers, provided the next law, the Public Health Act of 1848, which created
stimulus to public health. Through the agitation of the General Board of Health. This board ran into
socially minded physicians, and in particular the immediate difficulties, since the medical profession
work of Sir Robert Peel, a socially responsible textile was strongly opposed to it, and local officials were
manufacturer, the first English factory law, the Pau- still reluctant to surrender any of their authority to
per Apprentice Act of 1802, was pushed through a central board. In 1858 the board was dismissed,
Parliament. Changing circumstances made the law and its public health responsibilities were trans-
meaningless, and it took years of agitation by Peel, ferred to the Privy Council. Despite its weakness,
Robert Owen, and numerous others before a rela- the board was successful in spreading the gospel of
tively effective factory act in 1833 limited the work- cleanliness and sanitation.
ing hours of children in textile mills. The most sig- During these years a series of sanitary laws, such
nificant feature of the act was a provision for four as the Nuisances Removal Act, Common Lodging
officers to inspect, report on, and enforce the law. House Act, and the Adulteration of Food Act, were
This measure marked the first time that the central shepherded through Parliament. In addition, begin-
government broke away from a laissez-faire policy ning in 1847, medical officers were appointed in a
and assumed a limited responsibility for health and number of cities. The culmination of almost half a
welfare. Equally important, the reports of the fac- century of health education was the passage (helped
tory inspectors proved invaluable to Edwin Chad- along by the third cholera pandemic) of the Sanitary
wick, Southwood Smith, Lord Ashley, and other re- Act of 1866. This measure broadened the health and
formers seeking to make the public aware of the sanitary areas under the jurisdiction of the national
brutal and degrading conditions in which workers government and authorized its officials to compel
labored and lived. municipalities and counties to meet minimum sani-
At least as important as the horrible factory condi- tary standards. Within the next nine years successive
tions in promoting government action on behalf of legislative action gradually strengthened the 1866
health was the first of the three great pandemics of law. In 1875 a comprehensive health law consolidated
Asiatic cholera to strike the Western world in the the many pieces of legislation relating to health and
nineteenth century. This disease, which devastated sanitation and gave Great Britain the best national
the poor, who were crowded in filthy, miserable health program of any country in the world.

H i l l . Public Health and Sanitation in the West since 1700 203
The Industrial Revolution was much slower in federal government. Spurred on by epidemics of Asi-
coming to France and other countries, and the en- atic cholera and yellow fever, U.S. cities began ap-
ergy devoted to improving social conditions in En- pointing permanent quarantine officers at the begin-
gland was dissipated on the Continent in wars and ning of the nineteenth century. New York City,
struggles for political freedom and national indepen- which tended to assume leaderhsip in public health,
dence. Yet the French Revolution and the Napole- created the Office of City Inspector in 1804. The
onic Wars gave France leadership in medicine and office was designed to gather statistics and other
public health by destroying much of the old order information relating to the city, but under the leader-
and releasing the energy of the lower classes. ship of such men as John Pintard and John H.
Among its contributions in these years was the publi- Griscom, it became a significant force for social
cation of the first public health journal, the Annales change. Their annual reports as city inspectors were
d'hygiene publique et medecine legate, which ap- damning indictments of the poverty, misery, and
peared in 1829. The outstanding public health figure squalor that characterized the life of so many New
in France during these years was Rene Louis Yorkers.
Villerme, whose studies in the 1820s clearly demon- Nonetheless, the prevailing spirit in the nine-
strated the relationship between poverty and dis- teenth century was laissez-faire, and except when
ease. His major report in 1840 on the health condi- epidemics threatened, government officials felt little
tions of textile workers led to the enactment the responsibility for health. The threat of an epidemic
following year of a limited child labor law. or its presence usually aroused the quarantine offi-
Continued appeals for reform by Villerme and cials from their lethargy and stimulated the city
health reformers achieved a measure of success fol- council to appoint a health board, open temporary
lowing the Revolution of 1848. The new French gov- hospitals, and initiate a campaign to clean up the
ernment under the Second Republic established a worst sanitary abuses. Once the epidemic was over,
system of local health councils (conseils de salu- the quarantine was relaxed and city hall returned to
brite). Despite the hopes of public health leaders, politics as usual. When a particular abuse, such as
these councils, which met every three months, were an unusual number of putrefying dead animals in
purely advisory and exercised no real authority. Any the streets or a particularly odorous canal or sewer
further chance of immediate health reform was down the main street, became an outrage, public
dashed in 1851 when Napoleon III overturned the opinion would demand action, but the relief was
Second Republic. The system of weak advisory usually temporary.
health councils remained in effect until the end of While the public worried about the two great epi-
the nineteenth century, and public health in France demic diseases of the nineteenth century, yellow fe-
continued to lag far behind that of Britain. ver and Asiatic cholera, and to a lesser extent about
On paper, the public health regulations of the Rus- smallpox, the major causes of morbidity and mortal-
sian imperial government seemed quite advanced, ity in both Europe and the United States were pulmo-
and because the government was autocratic, it had nary tuberculosis and other respiratory infections,
the power to enforce its laws. Unfortunately, as the enteric disorders, malaria, typhoid, typhus, and such
successive Asiatic cholera epidemics revealed, these perennials as measles, diphtheria, scarlet fever, and
regulations were seldom exercised with any degree whooping cough. These were familiar disorders that
of effectiveness. Quarantine measures against chol- killed young and old alike, and in an age when
era were belated, haphazard, and applied too ruth- almost half of the children died before the age of 5
lessly. The widespread poverty and ignorance of the and sickness and death were omnipresent, the public
Russian people made many of them resent even the attitude was one of quiet resignation.
most well intentioned government actions. Whereas One explanation of this passive acceptance of en-
the cholera outbreaks in the West aroused demands demic disorders was that before the bacteriological
for health reform, particularly in Britain and the revolution little could be done about them. Another
United States, the autocratic government in Russia is that, until the accumulation of reasonably accu-
and the lack of a socially conscious middle class rate statistics, it was impossible to gauge the signifi-
prevented any meaningful reform before the twenti- cance of these diseases. Beginning in the 1830s, indi-
eth century. The development of public health in the viduals in Great Britain, on the Continent, and in
United States closely followed that of Great Britain, the United States began collecting a wide range of
although the sheer expanse of the nation reinforced statistical information. The studies of William Fan-
the belief in local control and delayed action by the in England and Villerme and Pierre Laplace in

France were duplicated in the United States by Lem- theory, was invalid, the movement itself achieved
uel Shattuck, Edward Jarvis, and others. These notable success in improving the public's health.
early statistics, however, brought few immediate re- The major drive in all Western countries during the
sults in the United States. The same can be said of early twentieth century was to reduce or eliminate
three classic public health studies published in the the major contagious diseases. With the aid of new
years before the Civil War — Griscom's Sanitary Con- diagnostic techniques, antitoxins, and vaccines, the
dition of the Laboring Population of New York City, major killer diseases of former times gradually were
Shattuck's Report of a general plan for the promotion brought under control. Tuberculosis, probably the
ofpublic and personal health (1850), and McCready's most fatal disease in the West during the nineteenth
essay (1837) on occupational diseases. Nonetheless, century, was greatly reduced, in part by improved
these men laid the basis for substantial progress in living conditions and in part through concerted ac-
the post—Civil War years. tion by voluntary associations and governments to
Their work also contributed to arousing an inter- identify, isolate, and cure all cases. In addition, large-
est in public health and sanitation in the United scale educational campaigns informed the public
States during the 1850s. Devastating yellow fever about the disease, and visiting nurses and social
outbreaks from 1853 to 1855 raised fears throughout workers helped families of victims. As was true of
the country and led to a series of National Quaran- drives against other contagious disorders, large-scale
tine and Sanitary Conventions from 1856 to 1860. screening programs were used for the early identifica-
The major issue at these meetings was whether yel- tion of cases. Recognition of the role of vectors made it
low fever could be kept at bay by quarantine or by possible to drive malaria and yellow fever virtually
sanitation. The sanitationists won the day. By 1860 from the Western world through antimosquito cam-
they were preparing to turn the conventions into a paigns. The greatest success against disease has been
national organization of health officers and sanitary with smallpox. With the help of the World Health
reformers, but the outbreak of civil war brought the Organization and massive vaccination programs, the
project to a sharp halt. disorder literally has been eliminated from the world.
All was not lost, however, because the hygienic Even as the fight against contagious diseases was
problems engendered by crowding thousands of men getting underway, health officials began moving into
into army camps and the movements of troops other health areas. Among the more obvious social
throughout the country stimulated the public health problems in the late nineteenth century was the enor-
movement. As evidence of this, in 1866 the Metropol- mous infant death toll. In western Europe, where
itan Board of Health was established in New York nationalism was the real religion and the military
City, the first permanent municipal health depart- power to defend that religion was equated with popu-
ment. It was followed in 1869 by the first effective lation, the birthrate was falling, increasing pressure
state board of health in Massachusetts. By the end of to improve maternal and child care. The movement to
the nineteenth century, most major cities had estab- do so began in England and France, where voluntary
lished some type of health agency. Many of them, organizations began promoting dispensaries for child
particularly the state boards, were only nominal, care. In the United States a New York philanthropist,
but the principle of governmental responsibility for Nathan Straus, opened a pure-milk station in 1893 to
public health was firmly established. provide free or low-cost milk to the poor. The idea was
In the meantime the work of Joseph Lister, Robert picked up in other U.S. cities and soon spread to
Koch, Louis Pasteur, and a host of scientists working western Europe. Over the years, these stations gradu-
in microbiology was changing the whole basis for ally evolved into well-baby clinics and maternal and
public health. Sanitation and drainage, the chief child health centers.
preoccupation of health officials in the nineteenth A major step forward in the movement for child
century, were replaced in the twentieth century by care was taken in 1908 when New York City, in
specific methods of diagnosis, prevention, and cure. response to the urging of Sara Josephine Baker, be-
Yet the sanitary movement had brought remarkable came the first municipality to establish a Division of
advances in life expectancy and general health. A Child Hygiene. The success of Baker's program in
higher standard of living, the introduction of ample New York encouraged Lillian Wald and Florence
and better city water, and large-scale drainage and Kelley, who had long been advocating a children's
sanitary programs all contributed to a sharp reduc- bureau at the national level, to redouble their ef-
tion in the incidence of urban disorders. Although forts. Four years later, in 1912, President Theodore
the basis for the sanitary movement, the miasmic Roosevelt signed a bill establishing the Federal Chil-

m . l l . Public Health and Sanitation in the West since 1700 205
dren's Bureau. The next action at the national level The education of public health workers originated
was the passage of the Sheppard-Towner Act of in Great Britain in the second half of the nineteenth
1921, a measure that provided matching federal century. It was essentially a practical course to train
grants for states to encourage maternal and child food and sanitary inspectors. Early in the twentieth
health programs. Although this act was allowed to century, courses in public health were offered by the
lapse in 1929, the New Deal Program of Franklin University of Michigan, Columbia, Harvard, and the
Roosevelt in the 1930s firmly established a role for Massachusetts Institute of Technology, and in 1913
the national government, not only in maternal and Tulane University established a School of Hygiene
child care, but in all aspects of public health. and Tropical Medicine. The latter survived only
Another important health area that had its ori- briefly, and the first permanent school of public
gins in Europe in the late nineteenth century was health was opened by Johns Hopkins University in
school health. Smallpox vaccination appears to have 1918. Rather than an institution designed to train
been the entering wedge, because compulsory vacci- general health workers, it was essentially a research
nation of school children was relatively easy to en- organization intended to educate the highest eche-
force. The discovery of so many other contagious lon of public health professionals. This pattern has
disorders among children led to the introduction of been followed by all subsequent U.S. public health
school inspectors and school nurses around the turn schools.
of the century. The early twentieth century saw the Although the term public health implies govern-
beginning of physical examinations for school chil- ment action on behalf of the community, from the
dren, and these in turn created a need for school beginning voluntary work by individuals, groups of
clinics and other remedial measures. As living stan- citizens, and philanthropic foundations has played a
dards were raised, particularly after World War II, major role in promoting the general health. Citizens'
school health programs declined in importance. sanitary organizations were very active in the late
The discovery of vitamins (so named by Casimir nineteenth century, and their counterparts in the
Funk in 1912) opened up the field of nutrition, and a twentieth have been voluntary groups fighting
substantial effort has been made by health officials against particular disease and medical problems.
to educate the public on matters of diet. Commercial These associations are found in nearly all Western
firms, capitalizing on public ignorance of scientific countries, but they are most active in the United
matters and the popularity of food fads, have man- States. One of the best examples is the National
aged to confuse the issue of what constitutes a well- Tuberculosis Association, founded in 1904, which
balanced diet, thus negating much of the educa- had an active part in reducing the incidence of this
tional work. Despite this, however, food and drug disorder in the United States. Of the many founda-
regulations have generally improved the quality of tions working in the health area, the Rockefeller
the food supply. Foundation is the best known. Along with the Carne-
An effective autocracy can mandate public health, gie Foundation, it has given major support to medi-
but health officials in the Western democracies have cal education. It is equally well known for its contri-
been forced to rely largely on health education. The butions to public health, particularly with respect to
United States, which has the oldest tradition of mass the drive against hookworm in the southern United
education, was the first to recognize the value of States, the Caribbean, and Brazil and yellow fever
information and persuasion in changing people's way in Latin America and Africa. The efforts of the
of life. By the 1890s, a number of state and municipal Rockefeller Foundation also helped lay the basis for
health boards were publishing weekly or monthly the Pan American Health Organization and the
reports and bulletins. Originally, these publications World Health Organization.
were intended for physicians and other professionals Since World War II, public health agencies, having
serving as health officers, but by the early twentieth won control over most of the contagious infections
century a variety of pamphlets and bulletins were that formerly plagued the Western world, have
being distributed to the general public. By this time, turned their attention to chronic and degenerative
too, health education was given a formal status in disorders and to the problems of aging. Veneral dis-
the organization of health departments. Lacking the eases appeared to have been relegated to a position
U.S. penchant for public relations, European health of minor significance with the success of antibiotics
departments have not given as much emphasis to in the 1950s, but resistant strains and the appear-
health education, relying much more on private ance of genital herpes and AIDS have drastically
groups to perform this task. changed the picture. An area where some success

has been achieved is that of community mental ish humanitarianism, ed. Samuel C. McCulloch.
health, but progress has been slow. Philadelphia.
With the success of the sanitary movement and the 1968. A history of public health in New York City, 1826-
emergence of bacteriology in the early twentieth cen- 1866. New York.
tury, health departments tended to assume that care 1974. A history of public health in New York City, 1866-
for the environment was largely an administrative 1966. New York.
Frank, Johann Peter. 1779-1827. System einer Vollstan-
matter. Since the 1950s, they have come to recognize
digen medizinischen Polizey, 9 vols. Mannheim Tub-
many subtle, and not so subtle, forms of air and water
ingen, Vienna.
pollution and dangers from pesticides, harmful fac- Galishoff, Stuart. 1975. Safeguarding the public health,
tory wastes, and radiation. They have also sought to Newark, 1895-1918. Westport, Conn.
deal with problems of alcoholism, drug addiction, oc- Jordan, Philip D. 1953. The people's health: A history of
cupational hazards and diseases, and a major source public health in Minnesota to 1948. St. Paul, Minn.
of death and disability, automobile accidents. Katz, Alfred H., and Jean S. Felton. 1965. Health and the
The twentieth century has seen public health shift community: Readings in the philosophy and sciences
from an emphasis on the control of contagious dis- ofpublic health. New York.
eases to the broader view that public health should Leavitt, Judith W. 1982. The healthiest city, Milwaukee
concern itself with all factors affecting health and and the politics of reform. Princeton, N.J.
well-being. Whereas an original aim was to increase Lerner, Monroe, and Odin W. Anderson. 1963. Health prog-
ress in the United States, 1900-1960. Chicago.
life expectancy, today public health also seeks to
Mazyck, Ravenel, ed. 1921. A half century ofpublic health
improve the quality of life. The current view of pub-
reform. New York.
lic health is that it should actively promote health McCready, Benjamine W. 1837. On the influence of trades,
rather than simply maintain it. Achieving a longer professions and occupations in the United States, on
life expectancy is still a major aim, but it is equally the production of disease. Transactions of the medical
important to improve the quality of life. society of the state of New York, vol. 3. Reprinted 1943,
John Duffy Baltimore.
McGrew, Roderick E. 1965. Russia and the cholera, 1823-
1832. Madison, Wis.
Bibliography Pelling, Margaret. 1978. Cholera, fever and English medi-
Blake, John B. 1959. Public health in the town of Boston. cine, 1825-1865. Oxford.
Cambridge, Mass. Rosen, George. 1958. A history ofpublic health. New York.
Brand, Jeanne L. 1965. Doctors and the state: The British Rosenkrantz, Barbara G. 1972. Public health and the state:
medical profession and government action in public Changing views in Massachusetts, 1842—1936. Cam-
health, 1870-1912. Baltimore. bridge, Mass.
Duffy, John. 1950. Early English factory legislation: A Shattuck, Lemuel, et al. 1850. Report of a general plan for
neglected aspect of British humanitarianism. In Brit- the promotion of public and personal health. Boston.

PART IV
Measuring Health

IV.l. Early Mortality Data 209
1662). As this ecclesiastical registration system ex-
IV.l panded, it provided the basis for Thomas Short's
Early Mortality Data: early study (1750) of geographic variation in British
mortality. Not until 1837, however, was a national
Sources and Difficulties civil vital registration system established in En-
of Interpretation gland, and not until 1875 did registration of vital
events become mandatory.
The English system was antedated by compulsory
The subject of early (for our purposes, pre-World national civil vital registration systems in Scandina-
War II) data on mortality is a vast one, and thus this via: Finland (1628), Denmark (1646), Norway
treatment is quite broad. The emphasis is on identi- (1685), and Sweden (1686). In Sweden the ecclesiasti-
fying classes of data, sources of ambiguity, and gen- cal registration system dates from 1608, slightly
eral approaches to problems of interpretation. Wher- antedating the English Bills of Mortality. By the end
ever possible, citations are made to critical surveys of the nineteenth century, civil registration was com-
of the literature, rather than to the literature itself. pulsory in virtually all European countries, North
Some of the points discussed here can be extended, America, Japan, and a host of other countries such
with appropriate caution and revision, to the equally as Egypt (1839), Mexico (1859), and Brazil (1885).
important, but much less tractable area of early Unfortunately, not all of these early registration sys-
morbidity data. tems, enumerated by Henry Shryock and Jacob
Siegal (1980), contain cause-of-death data.
Protostatistical Populations In addition to the registration systems, a number
There are rich opportunities for studying death and of important compilations and secondary sources ex-
disease in populations for which vital statistics in ist. The International Statistical Institute of the
the modern sense are nonexistent. Primary data League of Nations published its Annuaire interna-
sources include faunal evidence obtained by archaeo- tional de statistique in 1916, 1917, 1919, 1920, and
logical excavation, epigraphic evidence from fune- 1921 and its Apergu de la demographie des divers
rary monuments, and information contained in par- pays du monde in 1922, 1925, 1927, 1929, and 1931.
ish records and family genealogies. In most cases, Publication of the latter series was suspended until
however, although these data allow inferences to be 1939, when a volume covering 1929-36 was pub-
made regarding overall mortality among specific lished. The U.S. Bureau of the Census and Library of
and highly localized populations, they contain little Congress collaborated on a compilation of interwar
information on national-level populations and, with European demographic statistics (U.S. Bureau of the
the exception of some faunal evidence, on causes of Census and Library of Congress 1946), and to this
death. We can address the first shortcoming merely may be added an earlier effort of the U.S. Bureau of
by assuming that the population studied accurately the Census and Library of Congress (1943a,b). The
represents the total population, an assumption that standard compilation of historical mortality statis-
is probably robust in very high mortality popula- tics for Latin America is that of Eduardo Arriaga
tions. The second difficulty - the lack of information (1968). Other national and international data compi-
on causes of death - is irremediable in the main. lations, as well as secondary studies of pre-World
Furthermore, these data are rarely complemented War II (mostly European) vital rates, are cited by
by accurate population statistics, which are essen- Shryock and Siegal (1980) and, in the European
tial for computing rates and probabilities. Because case, by E. A. Wrigley (1969).
of the dearth of early census data, genealogies and In the United States, although the availability of
parish records, which provide a link between birth early church records, genealogies, and epigraphic evi-
and death records, are especially important for esti- dence is impressive, particularly in New England
mating life expectancy (e.g., Henry 1956; Hollings- (Vinovkis 1972) and Mormon Utah, vital registration
worth 1964; Wrigley 1968). got off to a late start. Beginning with the seventh
census of the United States in 1850, questions regard-
Early Statistical Populations ing deaths in the household during the previous year
A key date in historical demography is 1532, when it were included in the compilation (a similar system
was mandated that London parish priests compile was adopted in nineteenth-century Canada). The de-
weekly "Bills of Mortality," which were in turn the cennial U.S. Censuses of Mortality are the main
primary source of the first known life table (Graunt source of nationwide mortality data from 1850 to

210 IV. Measuring Health
1890, but they are seriously incomplete (Condran and ria for inclusion in this authoritative compilation
Crimmins 1979). This is in contrast to the situation in were stringent: Only populations for which accurate
the United Kingdom, where civil registration data, mortality statistics, including cause-of-death detail,
including cause-of-death and limited socioeconomic and accompanied by reliable population data, are
data, are quite accurate from the mid-nineteenth cen- represented. These are daunting barriers to entry,
tury forward. A few states, such as statistically preco- but nevertheless the number of pre-World War II
cious Massachusetts, initiated state registration sys- populations included is quite large: Australia (1911,
tems during the nineteenth century, and some cities 1921,1933,1940); Canada (1921,1931); Chile (1909,
published local mortuary records. In 1900 the federal 1920, 1930, 1940); Czechoslovakia (1934); Denmark
government began collecting and publishing mortal- (1921, 1930, 1940); England and Wales (1861, 1871,
ity data from a Death Registration Area consisting of 1881, 1891, 1901, 1911, 1921, 1931, 1940); France
the 10 states (plus the District of Columbia) in which (1926,1931, 1936); Greece (1928); Italy (1881, 1891,
it was judged that at least 90 percent of all deaths 1901, 1910, 1921, 1931); Japan (1899, 1908, 1940);
were registered. Under federal urging, more and the Netherlands (1931, 1940); New Zealand (1881,
more states initiated and improved compulsory regis- 1901, 1911, 1921, 1926, 1936); Norway (1910, 1920,
tration systems, until by 1933 all of the present states 1930); Portugal (1920, 1930, 1940); Spain (1930,
except Alaska were included in a national vital regis- 1940); Sweden (1911,1920,1930,1940); Switzerland
tration system. (1930); Taiwan (1920, 1930, 1936); and the United
Among a number of compilations of U.S. vital sta- States (1900, 1910, 1920, 1930, 1940).
tistics, the most noteworthy are volumes prepared
by the U.S. Bureau of the Census (1933, 1943a,b); Problems of Interpreting Early Mortality
the U.S. Public Health Service (1961) has also pub- Data
lished in a single volume comparable U.S. life tables As already mentioned, relatively few sources of
for 1900-59. The fifteen volumes of the Vital and early mortality statistics can satisfy the Preston-
Health Statistics Monograph Series of the American Keyfitz-Schoen criteria. The deficiencies of such
Public Health Association, together with the final data are easily enumerated (Shryock and Siegal
summary volume, Mortality and Morbidity in the 1980):
United States (Erhardt and Berlin 1974), present a
comprehensive view of the U.S. case. The emphasis 1. Definition of death. This is an issue mainly in the
of the series is on the 1960s, but a wealth of case of stillbirths and neonatal deaths.
twentieth-century statistics, as well as some com- 2. Misallocation of deaths by place of occurrence. In
parative international data, are presented in many cases where large hospitals serve an extended
of the volumes. catchment area, it is common for death notices to
Statistics collected and special studies prepared by be listed incorrectly, indicating the residence of
life insurance companies represent an underutilized the deceased to be the metropolitan area in which
body of data for nineteenth-century mortality in the the hospital is located rather than the outlying
United States and Europe. Because of the financial areas.
incentive to maintain accurate death records, these 3. Misallocation of deaths by time of occurrence.
data may be quite accurate, and they contain consid- Deaths are commonly tabulated on a year-of-
erable cause-of-death detail. The greatest drawback occurrence basis, and mistakes in reporting are
is that, because such data deal with only the insured inevitable.
population, they may underestimate the true extent 4. Age misreporting. This is a problem mostly at the
of mortality among the broader population. To these older end of the age spectrum, where there is a
data sources should be added the life tables calcu- tendency for reported ages to exceed actual ages
lated by eighteenth- and nineteenth-century actuar- significantly. It is also a problem in the case of
ies such as Edward Wigglesworth, the accuracy of children.
which has been the subject of intense scrutiny 5. Completeness of registration. This is a problem
(Vinovkis 1971; Haines and Avery 1980). involving both the extent and the accuracy of regis-
One straightforward approach to setting a lower tration. In many countries, national registration
bound on the availability of early mortality data is systems were not in fact national, as in the United
simply to enumerate the pre-World War II multiple- States with its original 10-state Death Registra-
decrement life tables in the work of Samuel Preston, tion Area. In other countries, certain populations
Nathan Keyfitz, and Robert Schoen (1972). The crite- were explicitly excluded from early registration

systems, such as Maoris of New Zealand and per- that, if inclusion in the civil registration system and
sons residing in the Yukon and the Northwest inclusion in the alternative tabulation are statisti-
Territories of Canada. Even assuming that the cally independent, then completeness of civil regis-
entire population of a nation was included in the tration, say C, is equal to the ratio of deaths recorded
registration process, some degree of under- in both systems, say D(Both), to deaths recorded in
counting was inevitable. This tends to be the most the alternative system, say D(Alt):
serious problem in the case of infants, children
under 5, and persons over 65. C = Z)(Both)/£)Alt). (1)
6. Cause misreporting. Preston, Keyfitz, and Schoen It is important to note that, given statistical inde-
(1972) have categorized problems in this area into pendence, it is unnecessary to assume that the alter-
errors in diagnosing cause of death and errors in native recording system is complete. The main advan-
translating an accurate diagnosis into an entry on tage of matching studies, which have had extensive
the death registration form. The latter include historical application (e.g., Crimmins 1980), is their
errors in categorizing deaths according to interna- conceptual simplicity. They are also well suited to the
tional vital statistics convention (e.g., brain tu- study of highly disaggregated mortality data, such as
mors were once classified under diseases of the deaths in a given city from a given cause among a
nervous system, but are now grouped with neo- given segment of the population. The main difficul-
plasms) and, more important, errors arising from ties, in addition to violations of the independence
complex issues in the case of multiple causes of assumption, are empirical, particularly in deciding
death. To these two areas of difficulty should be what constitutes a true match. It should be added
added biases arising from the extent and accuracy that the matching-study approach is inherently labor
of registration. Even an incomplete death registra- intensive.
tion system can, in theory, reflect accurately the
population's cause-of-death structure. Unfortu- Indirect Approaches
nately, differential completeness of registration Most indirect approaches to estimating complete-
can skew the cause-of-death structure. For exam- ness of civil registration are of comparatively recent
ple, if deaths among the elderly are systemati- development. The basic data requirement for all
cally underreported, the resulting cause-of-death such methods is a reported age distribution of deaths
structure will understate the role of chronic and in a given year. Other requirements, depending on
degenerative diseases, among them neoplasms the method employed, include population by age in
and cardiovascular disease. the study year and age-specific population growth
rates (calculated from two censuses, neither of which
Among these problems, the fifth and sixth typi- need have been taken during the study year). Most
cally are of greatest concern, and it is to these that indirect methods require either the assumption of a
the remaining pages of this essay are devoted. stable population (i.e., one that is closed to migra-
tion and in which rates of birth and death have been
Estimating Completeness of Death constant for a long period of time) or, at a minimum,
Registration the assumption of no migration. In some cases, the
Direct Approaches methods are fairly robust to violations of these as-
There are two broad approaches to estimating com- sumptions.
pleteness of death registration: direct and indirect. Some notion of the indirect approach can be
In the direct approach, the true level of mortality is gained by looking briefly at one of the earliest and
independently estimated and compared with the simplest of these methods developed by William
level reported in the registration system. Household Brass. (The present section is based on the discus-
surveys of child survival, often performed in conjunc- sion in MacKellar 1987.) The Brass method is based
tion with census enumeration, are examples of the on the fundamental population change accounting
direct approach, but few such surveys are available identity:
for the pre-World War II era. Of more interest to
social scientists are "matching" studies, in which rix+) = b(x+) - d(x+) (2)
deaths appearing in one tabulation (e.g., a parish Here r(x+) is the actual growth rate of the popula-
register) are matched with deaths tabulated in the tion aged over x, and b(x+) is the actual birthrate of
civil registration system during the same period the population aged over x; that is, the number of rrth
(Marks, Seltzer, and Krotki 1974). It can be shown birthdays celebrated in a given year divided by the

number of person-years lived in a state of being aged inevitable resulting misassignments of correctly di-
over x in that year. d(x+) is the actual death rate of agnosed deaths. There is a large volume of postwar
the population aged over x, analogously defined; and research on the accuracy of reported cause of death
m(x+) is the actual net migration rate of the popula- (Preston et al. 1972; Manton and Stallard 1984).
tion aged over x, analogously defined. This literature is useful not only for isolating princi-
Setting x equal to zero, we find that (2) reduces to pal themes in the misdiagnosis of cause of death, but
the familiar identity whereby the growth rate of the also in setting upper bounds on the accuracy of pre-
total population equals the crude birthrate minus the war statistics.
crude death rate plus the crude rate of net migration. Prewar populations present special problems. Spe-
The population is assumed to be stable, and since cific clinical problems of diagnosis and pathology are
the age distribution of a stable population is invari- outside the scope of this essay, but several general
ant, r(x+) is constant for all x. Let this constant points are important. First, because of intracategory
growth rate be r. Since there is, by assumption, no misassignment (e.g., strokes due to cerebral hemor-
net migration, we have m(x+) = 0 for all x. The rhage being misassigned to strokes due to cerebral
completeness of death registration is assumed to be thrombosis), there are significant gains in accuracy
constant with age over age x. Let the proportion of from aggregating individual causes of death into
actual deaths enumerated be C. Then (2) can be broader categories (Preston et al. 1972). The more
rearranged to yield the following: fine-grained the category, the higher the likely de-
gree of error.
b(x+) = r + (1/C) d'(x+), (3)
Second, any death wrongly excluded from the cor-
where d'(x+) is the recorded death rate over age x. rect category, if it does not escape the registration
If N(x+) is the recorded population aged over x system entirely, represents an incorrect addition to
and N(x, x + n) is defined as the population aged another category; problems of overattribution, in
between x and x + n, b(x+) can be estimated by a other words, may be as serious as problems of un-
statistic such as the following: derattribution.
Third, as death has increasingly occurred at older
b(x+) = (N(x - n, x) + Wx, x + ri))l2nN(x+). (4)
ages from chronic and degenerative diseases, re-
Thus, given a set of observed age-specific death searchers have been forced to replace the traditional
rates and a single population census for the calcula- underlying-cause model, in which one disease or con-
tion of b(x+), linear regression or any other curve- dition is assumed to have resulted in death, with
fitting procedure can be used to estimate the popula- more complex multiple cause-of-death approaches
tion growth rate and the completeness of death reg- (Manton and Stallard 1984). In the case of historical
istration (see United Nations 1983 for a discussion populations of low life expectancy, however, use of
of estimation issues). the simple underlying-cause model is more defensi-
The primary advantages of indirect approaches ble than in the case of modern populations. Of
are, first, that their data requirements are modest, course, it is frequently inappropriate for the case of
and second, that as a result, they are much less aged persons, and the contributory role of chronic
labor intensive than direct methods. However, indi- conditions such as nutritional deficiency and low-
rect methods are applicable almost exclusively to level diarrheal disease may be significant.
national-level populations and allow no disaggre- Finally, because of the improving state of medical
gation by cause of death, residence, socioeconomic knowledge, increasing presence of an attending phy-
status, and so on. sician, and increasing frequency of competent au-
topsy, the overriding problem of the proportion of
deaths attributed to unknown, ill-defined, and bi-
The Accuracy of Cause-of-Death Data zarre or nonsensical causes in cause-of-death statis-
Errors in ascertaining true cause of death may arise tics has been in steady decline (Preston et al. 1972).
from inaccurate diagnosis by the attending physi- Among ill-defined causes, we include old age, senil-
cian (if any), failure to perform an autopsy, inaccu- ity, debility, fever, teething, dropsy, and so on. How-
rate autopsy results, including inability of the pa- ever, even in compilations as early as the 1850 U.S.
thologist to specify multiple causes of death, and Census of Mortality, the proportion of deaths as-
failure of the death certifier to take into account the signed to bizarre causes is tiny, and attributions to
results of autopsy. In the last case, problems arise unknown and ill-defined causes are confined largely
from changing vital statistics conventions and the to deaths of persons over 65.

Moreover, we are not totally ignorant of the under- Graunt, John. 1662. Natural and political observations
lying nature of many deaths assigned to unknown mentioned in a following index, and made upon the
and ill-defined causes. There is an a priori reason to bills of mortality. London.
believe that historical cause-of-death data systemati- Haines, Michael, and Roger Avery. 1980. The American
cally underreport causes of death most common in life table of 1830-1860: An evaluation. Journal of
old age because of the inherent difficulty of correctly Interdisciplinary History 11: 71—95.
Henry, Louis. 1956. Anciennes families ginevoises. Paris.
diagnosing chronic and degenerative conditions. The
Hollingsworth, T. H. 1964. The demography of the British
most likely scenario is that these deaths ended up in peerage. Population Studies, suppl. 18(2).
the unknown and ill-defined categories, a hypothesis MacKellar, Landis. 1987. U.S. adult white crude death and
in support of which Preston (1976) has adduced net migration rates, by state, in 1850. In Proceedings
strong statistical evidence. In particular, most of the Middle States Division of the Association of
deaths attributed to old age and senility can, with American Geographers, New York, New York, October
some confidence, be attributed to cardiovascular dis- 17-18, 1986, ed. Cathy Kelly and George Rengert,
ease and cancer. 66-72. Philadelphia.
Thus, there are further compositional advan- Manton, Kenneth, and Eric Stallard. 1984. Recent trends
tages, in addition to the enhanced validity of the in mortality analysis. New York.
underlying-cause mortality model, to dealing with Marks, E., W. Seltzer, and K. Krotki. 1974. Population
growth estimation: A handbook of vital statistics mea-
low-life-expectancy historical populations. Calcula-
surement. New York.
tions indicate that in a population with a life expec-
Preston, Samuel. 1976. Mortality patterns in nationalpopu-
tancy of 30, of the men 52.9 percent eventually die lations, with special reference to recorded causes of
from causes falling into fairly robust categories: death. New York.
respiratory tuberculosis, other infectious and para- Preston, Samuel, Nathan Keyfitz, and Robert Schoen.
sitic diseases, diarrheal disease, the influenza- 1972. Causes of death: Life tables for national popula-
pneumonia-bronchitis complex, and violence. In a tions. New York.
population with a life expectancy of 70, by con- Short, Thomas. 1750. New observations on city, town, and
trast, the corresponding figure is only 14.6 percent country bills of mortality. London.
(Preston et al. 1972; Preston 1976). Partially vi- Shryock, Henry, and Jacob Siegal. 1980. The methods and
tiating this compositional advantage of low-life- materials of demography. Washington, D.C.
expectancy populations is the relatively large pro- United Nations, 1983. Manual on indirect methods of demo-
portion of deaths from diseases of infancy and graphic estimation. New York.
early childhood that are difficult to diagnose. Nev- U.S. Bureau of the Census. 1923. Mortality rates: 1910-20.
Washington, D.C.
ertheless, it appears that nineteenth- and early-
1933. Introduction to vital statistics of the United States:
twentieth-century mortality statistics give a fairly 1900-1930. Washington, D.C.
accurate picture (excluding problems related to U.S. Bureau of the Census and Library of Congress. 1943a.
chronic and degenerative disease) of the actual Vital statistics rates in the United States: 1900-40.
cause-of-death structure. Washington, D.C.
F. Landis MacKellar 1943b. General censuses and vital statistics in the Ameri-
cas. Washington, D.C.
Bibliography 1946. National censuses and vital statistics in Europe:
Arriaga, Eduardo. 1968. New life tables for Latin Ameri- 1918-1939. Washington, D.C.
can populations in the nineteenth and twentieth centu- U.S. Public Health Service. 1961. Guide to United States
ries. University of California, Institute of Interna- life tables: 1900-1959. Public Health Service Publica-
tional Studies, Population Monograph Ser. No. 3. tion No. 1086, Public Health Bibliography Ser. No. 42.
Berkeley. Washington, D.C.
Condran, Gretchen, and Eileen Crimmins. 1979. A descrip- Vinovkis, Maris. 1971. The 1789 life table of Edward Wig-
tion and evaluation of mortality data in the federal glesworth. Journal of Economic History 31: 570—91.
census: 1850-1900. Historical Methods 12: 1-22. 1972. Mortality rates and trends in Massachusetts be-
Crimmins, Eileen. 1980. The completeness of 1900 mortal- fore 1860. Journal of Economic History 32: 184-213.
ity data collected by registration and enumeration for Wrigley, E.A. 1968. Mortality in pre-industrial England:
rural and urban parts of states: Estimates using the The case of Colyton, Devon, over three centuries. Dae-
Chandra Sekar-Deming technique. Historical Meth- dalus 97: 246-80.
ods 13: 163-9. 1969. Population and history. New York.
Erhardt, Carl, and Joyce Berlin, eds. 1974. Mortality and
morbidity in the United States. Cambridge, Mass.

necessary to examine a broad range of clinical, so-
IV.2 cial, political, economic, and geographic factors, all
Maternal Mortality: of which affected childbirth in different countries
and at different times. Although this is a historical
Definition and Secular exercise, some of the answers are undoubtedly rele-
Trends in England and vant to obstetric problems in certain parts of the
Third World today.
Wales, 1850-1970 To illustrate how maternal mortality is deter-
mined, the trend in England and Wales will be exam-
ined first. Maternal deaths and other data are shown
Maternal mortality signifies the deaths of women in Table IV.2.1 for certain selected decennia and in
that take place during pregnancy, labor, or the puer- Figure IV.2.1 for successive decennia from the 1850s
perium, once frequently referred to as "deaths in through the 1970s.
childbirth." Despite past claims, in the context of In England and Wales the population of women of
total deliveries, maternal death was a rare event childbearing age more than doubled between the
compared with death from disease. Even in the 1850s and the 1970s, but the birthrate more than
worst periods of the eighteenth and nineteenth cen- halved, so that the average number of births per day
turies, the mother survived in at least 98 percent of (or per decade) was almost exactly the same in the
deliveries. Nonetheless, a death rate of 1 to 2 percent 1850s and the 1970s. But the risk of childbirth had
is high when the average number of deliveries per been enormously reduced. Total maternal deaths, as
day is about 2,000, as it was in England and Wales shown in Table IV.2.1, rose from an average of 8.5
by the end of the nineteenth century. In the United per day in the 1850s to a peak of 12 per day in the
States during the 1920s, for example, death in child- 1890s before descending to the present level of about
birth claimed some 15,000 to 20,000 lives a year, and 1 per week. In the nineteenth century, a woman
it was second only to tuberculosis as a cause of death would most likely have known of at least one death
in women of childbearing age. in childbirth among her friends or neighbors, if not
This essay is about the historical epidemiology of her own family. Today, maternal deaths are so rare
maternal mortality — the distribution and determi- that very few people have personal knowledge of
nants of maternal mortality in different popula- such a tragedy.
tions at different periods. The epidemiological ap- There is a certain pattern of mortality with which
proach to the history of maternal mortality is not, historians and epidemiologists are familiar. It con-
of course, the only one, but it is the method that sists of a general decline in deaths dating either
makes the greatest use of statistics to attempt to from the mid-nineteenth century or from the begin-
discover why the mortality rate changed at differ- ning of the twentieth. This decline was seen, for
ent periods, and why one region or one country instance, in death rates from all causes, deaths from
suffered more maternal deaths than another. It is the common infectious diseases, and infant mortal-
Table IV.2.1. Birthrates and maternal deaths in England and Wales, 1851-1980
Average Average annual
Population Average number maternal deaths Maternal
of women number of maternal per million deaths
aged 15—44 of births deaths women aged per 10,000
Decennium (millions) Birthrate" per day6 per day6 15-44 births
1851-60 4.60 144.8 1,775 8.5 675 47.0
1891-1900 7.50 122.9 2,507 12.0 621 50.9
1951-60 9.27 77.1 1,938 1.1 43 5.6
1971-80 9.77 67.3 1,772 0.23 8 1.2
Note: For all three quantities, the value for the 1850s is expressed as 100; subsequent values are shown as the percentage
above or below the level of the 1850s.
"Birthrate expressed as births per 1,000 women aged 15-44.
6
Average daily births and maternal deaths for the decade.

IV.2. Maternal Mortality 215
200 with a general improvement in health and hygiene
associated with a rising standard of living.
Figure IV.2.1 shows maternal deaths per million
women of childbearing age. The graph appears at
first sight to conform to the general pattern, because
it shows that maternal deaths declined from the
1870s onward. However, this decline is seen only
when the birthrate is ignored and maternal mortal-
ity is measured solely in terms of the total number of
100
women of childbearing age. In fact, the population at
risk is not all women of childbearing age; it is only
women during pregnancy, labor, or the puerperium.
Maternal mortality has to be measured in terms of
BIRTH RATE births, not total population, and Figure IV.2.1 shows
clearly that the birthrate was declining alongside
deaths in childbirth.
\ MATERNAL OEATH RATE
The maternal mortality rate (henceforth, the
MMR) is therefore calculated by dividing the total
01 L. i i i i i i i i •"—i number of registered maternal deaths (the numera-
S S S tn -a in to
tor) by the total number of registered births (the
denominator). The quotient is then multiplied by
1,000, 10,000, or, as is usual today, 100,000. Deaths
Figure IV.2.1. Birthrates and maternal mortality rates per 10,000 births is the most convenient when one is
for England and Wales, 1851-1980. Values for 1850 = working with historical data and is used here. The
100. (From Annual reports, Decennial Supplements and
Statistical Reviews of the Registrar General for England ideal denominator for the calculation of maternal
and Wales.) mortality would, of course, be pregnancies rather
than births; but total pregnancies cannot be re-
corded when there are no statistics on abortions or
ity. The reasons for the decline have been debated for multiple births from single pregnancies. Total births
a number of years. In the past it was attributed to (or live births before stillbirths were registered) are
advances in scientific medicine. It is now generally therefore used instead.
accepted that the decline in mortality rates before When the MMR is calculated in terms of births
the Second World War had little to do with advances rather than women of childbearing age, the graph is
in medical or surgical therapy, but a great deal to do very different (Figure IV.2.2). Between the 1850s and
1850 1900 1930 1940 1980
70
80
50
40
30
S 20
I 10 Figure IV.2.2. Maternal mortality

rates for England and Wales,
1851-1980 (logarithmic scale).
Maternal mortality rates ex-
pressed as maternal deaths per
10,000 births. (From Annual re-
ports, Decennial Supplements and
Statistical Reviews of the Regis-
trar General for England and
1 . Wales.)

1930s the MMR, far from declining, remained on a
plateau while other major causes of death were declin- 70
ing. This plateau, and the steep and sustained decline U.S.A.
that started in the mid-1980s, are the two prominent
features of the graph. The plateau suggests that the 60 \ V AUSTRALIA
factors that caused a general decline in death rates ZEALAND
\ K-fiFlfi
-BELGIUM — P A R I S —
between the 1870s and the mid-1980s had no effect on
r
CD
SCOTLAND
the MMR. This is especially surprising when one
recalls that obstetrics differed from the use of medi- ENGLAND & WALES
cine in surgery in that, starting in the 1880s, certain
measures were introduced into obstetric practice that 40
should have reduced mortality. These included anti-
sepsis and asepsis, the compulsory regulation and \l
training of midwives, and the growing importance of
antenatal care. But it appears that at the national z
or
UJ
30-
V SWEDEN
NETHERLANDS
NORWAY
level they had no effect. There is yet another unusual DENMARK
5 20-
feature of maternal mortality: the correlation with
social class. For most of the common causes of death
in the past, social-class gradients existed, with the
highest mortality rates among the poor and lowest 1880 1900-10 1936-7
i
1950
I
among the well-to-do. In the case of the MMR, the Introduction • Maternal welfare:
ISulfonamides
! Blood I
gradient was reversed. of I Maternity services .transfusion j
. antisepsis . Antenatal care Penicillin
From the mid-1980s, the abrupt and sustained 'Obstetric !
jeducation I
decline in mortality is as striking as the previous
absence of any decline. Maternal mortality is puz- Figure IV.2.3. Changes in maternal mortality rates in
zling and fascinating because of these unexpected different countries, 1880-1950. (Based on the vital statis-
features. Were England and Wales, however, un- tics of the countries shown.)
usual in these respects, or were similar trends found
in other countries?
Data from the United States as a unit present a
International Comparisons of Maternal special problem because they were based on the ex-
Mortality panding Death Registration Area, established in
Few countries published vital statistics before the 1880. Initially this consisted of the states of New
mid-nineteenth century. The exception was Sweden, Jersey and Massachusetts, the District of Columbia,
where, as Ulf Hogberg (1985) has shown, the MMR and nineteen cities. Other states were added year by
fell from about 100 per 10,000 births in 1750 to year. The process was completed by 1933 with those
about 50 in the mid-nineteenth century, followed by states that recorded the highest MMRs coming last
a rise to about 63 in the 1870s. Work by R. Schofield and to some extent accounting for the rising MMR in
(1986) suggests that the MMR in England probably the United States between 1900 and 1933. In spite of
fell from about 100 per 10,000 births during 1700- this complication, however, there is little doubt that
50 to around 80 during 1750-1800 and to between the United States experienced one of the highest
50 and 60 in the first half of the nineteenth century. MMRs in the developed world during the first four
The MMR in Europe in the late eighteenth and early decades of the twentieth century.
nineteenth centuries may have been about 100 Figure IV.2.3 is a schematic representation of the
deaths per 10,000 births, but this is speculative. secular trend in the MMR in various countries be-
Data on maternal deaths were not always in- tween 1880 and 1950. In 1880 the MMR in most
cluded in early lists of causes of death, but they were developed countries lay somewhere in the range of
usually included in vital statistics (with various de- 50 to 100 deaths per 10,000 births. Between 1880
grees of reliability) from the 1850s in European coun- and 1910, some countries (e.g., Sweden and Bel-
tries, from about the 1880s in Australia and New gium) showed a substantial reduction in the MMR,
Zealand, and from 1900 in the United States (except which Hogberg (1985) has suggested was almost cer-
for the state of Massachusetts, where statistics on tainly the result of the effective use of antisepsis and
maternal mortality can be obtained from 1850). asepsis. (Although different, both techniques are de-

community. It should be as rare as sepsis after a surgical
operation.
J 60
S
From 1900 to the late 1930s, almost everywhere the
150 MMR stayed level or rose slightly, although there
were wide differences among national MMRs. The
United States showed the highest and the Nether-
lands and Scandinavia the lowest. Between 1929
30 and 1935, the MMR declined slightly in the United
States and New Zealand. Elsewhere the trend was
20 level or rising.
ENGLAND & WALES When it became obvious that maternal deaths,
SCOTLAND
' SWEDEN
and especially those from puerperal sepsis, were not
being prevented, concern about maternal mortality
increased. In many countries, including Britain,
B70 IB90 1900 1910 1920 1930 19(0 1950
Australia, New Zealand, and North America, radi-
Figure IV.2.4. Maternal mortality rates in Scotland, En- cal reforms were suggested. These eventually
gland, Wales, and Sweden, 1870-1950. (From Annual Re- led to improvements in the education and regu-
ports of the Registrar General for England, Wales, and lation of midwives (except in the United States,
Scotland. For Sweden, 1860-1910: Ulf Hogberg, Mater- where abolition of the midwife was recommended),
nal mortality in Sweden, Umea University Medical Dis- to better obstetric training for physicians (although
sertations, New Ser. 156 [Umea, 1985], 1911-1950: in practice little improvement occurred), and an
Sveriges officiella Statistik, Stockholm.) increasing number of specialist obstetricians (with
the inevitable tendency for obstetrics to become a
noted by the term antisepsis in this essay). However, branch of operative surgery). Also suggested were
other countries (e.g., Britain and Australia) failed to the encouragement of routine antenatal care (which
reduce mortality significantly, a difference that is seems to have had little effect before the 1940s) and
hard to explain but one that suggests poor antiseptic the establishment of new obstetric institutions (clin-
practice. An example of this difference can be seen in ics, maternity hospitals, and maternity depart-
Figure IV.2.4, which shows the secular trends in the ments in general hospitals in spite of the danger of
MMR in Scotland, England and Wales, and Sweden. cross-infection). There were repeated exhortations
That antiseptic techniques, rigorously employed, to use antisepsis properly (which were largely ig-
could be very effective in reducing maternal mortal- nored), and local and national governments were
ity was beyond doubt. Before 1880, the experiences urged to improve both the quality and availability
of lying-in hospitals all over the world were appall- of maternal care to women at all levels of society
ing and MMRs of 200 or more were common. By (their actions were usually weak but occasionally
1900 such hospitals as the Rotunda Hospital in Dub- effective).
lin, the York Road Lying-in Hospital in London, the Some medical authorities were optimistic. Mater-
Maternity Hospital in Basle, and the Women's Hospi- nal mortality, it was felt, was not a difficult problem.
tal in Sydney reported very low MMRs and a virtual Methods of preventing maternal death were known,
absence of deaths from puerperal sepsis. Such suc- and reforms based on them would reduce the tragic
cess, however, seems to have been confined to a mi- and unnecessary loss of so many young women in
nority of hospitals, the implication being that those the prime of their lives. Yet national MMRs showed
standards of care were the exception before the twen- an obstinate refusal to fall, and a number of studies
tieth century. This was certainly the belief of the revealed wide and disturbing regional differences
Australian Committee on Maternal Mortality of within nations.
1917, which said in no uncertain terms: Map IV.2.1 shows regional variations for England
Puerperal septicaemia is probably the gravest reproach and Wales, and Map IV.2.2 the same for the United
which any civilised nation can by its own negligence offer States. In England and Wales there was a well-
to itself. It can be prevented by a degree of care which is marked northwest and southeast divide along a line
not excessive or meticulous, requiring only ordinary in- from the Severn to the Wash, which persisted from
telligence and some careful training. It has been abol- the late nineteenth century until the 1930s. Most
ished in hospitals and it should cease to exist in the counties above the line suffered an above-average,

Rates higher than that of England and Wales [""71 Rates lower than that of England and Wales
by an amount which is definitely significant \/ A by an amount which is very probably significant
Rates higher than that of England and Wales Rates lower than that of England and Wales
by an amount which is very probably significant • by an amount which is definitely significant
Rates which do not differ significantly

from that of England and Wales
Map IV.2.1. Differences in mater-

nal mortality rates in England
and Wales, 1924-33. (From Minis-
try of Health 1937.)
and those below the line a lower-than-average, well as black, the MMR was highest in the southern
MMR. The explanation is neither simple nor certain, states, but the differential was relatively slight.
but it probably lies in the standards of obstetric care In the United States before the Second World War,
rather than standards of living (see the section on maternal mortality was usually lower in rural than
determinants). in urban areas. By the 1960s this situation had been
In the United States the divide was geographically reversed. Remote rural areas, however, often experi-
the opposite. Maternal mortality was highest in the enced special problems, and wide variations in the
South. The states with a high MMR lay along the provision of maternal care in different parts of the
curve stretching down from Wyoming, Colorado, same state were not uncommon. In mountainous
New Mexico, and Arizona across to the states of the areas with deep ravines and few roads, often no
Deep South - Louisiana, Mississippi, Alabama, Flor- trained birth attendants of any kind were available.
ida, Georgia, North and South Carolina, Tennessee, In other areas, low mortality might be achieved by
and Virginia. In the Northeast, only Maine showed a small homogeneous populations of European origin,
persistently high MMR. which included midwives trained in Europe. Yet
The secular trend for the United States as a whole other remote areas might possess small local hospi-
can be seen in Figure IV.2.5. The striking features tals where nearly all deliveries would be performed
are the high MMRs and the very large difference by physicians. In many developed countries, a lack
between white and all mothers, a difference that of uniformity was the rule rather than the exception
persisted at least to the 1970s. The high MMR in the as far as factors affecting the MMR were concerned.
South was due largely, but not entirely, to the concen- It was true of Britain, for instance, but most extreme
tration of the black population. For white mothers as in the United States. In the years 1938-40, when the

average MMR for the United States as a whole was
37.6 per 10,000 births, it ranged from 17.5 per
10,000 in North Dakota to 67.8 in South Carolina, a
ratio of lowest to highest of 1 to 3.9. In England and
Wales in the same period, the average MMR was
about 28 per 10,000 and the range between regions
was probably about 17 to 38, a ratio of 1 to 2.2.
All this was known to the authorities who made
policy in Britain and the United States. Both coun-
tries were concerned about their unacceptable
MMRs and the obstinately persistent regional differ-
ences. But they devised quite different policies. In
the United States it was thought that maternal mor-
tality could be defeated by an increase in the propor-
Map FV.2.2. Differences in maternal mortality rates in tion of hospital deliveries performed by specialist
the United States, 1938-40. (From Changes in infant obstetricians. The midwife and the general practitio-
childhood and maternal mortality over the decade 1939— ner with her or his "kitchen-table midwifery" should
1948: A graphic analysis, Children's Bureau Statistical
be abolished except in remote rural areas.
Series, No. 6, Federal Security Agency, Social Security
Administration, Children's Bureau, Washington, D.C.; In- In Britain it was felt that the backbone of obstetric
fant, fetal and maternal mortality, United States, 1963, care should continue to be home deliveries by mid-
National Center for Health Statistics, Series 20, No. 3, wives and general practitioners. Hospital care should
U.S. Department of Health, Education and Welfare, increase, but on the whole it should be reserved for
Washington, D.C.) complications of labor and high-risk cases. New Zea-
land tended to follow the U.S. pattern, Australia, the
' USA-Nonwhite British, and the Netherlands and Scandinavia also
• USA-All pursued a successful policy of home deliveries by mid-
r\ . USA-MMRby
criteria in use in
England 1 Wales
wives backed up by a minimum of hospital deliveries.
- ENGLAND & WALES
It is interesting that, in spite of such divergent poli-
cies, none of these countries experienced a significant
fall in the MMR between 1910 and the mid-1930s.
The Causes and Determinants of Maternal

Mortality
Three conditions - puerperal sepsis, toxemia, and
hemorrhage - caused the majority of maternal
deaths throughout the developed world from the
mid-nineteenth century until the mid-1930s, and
the proportion of total deaths contributed by each
was remarkably constant in different countries dur-
1910 1915 1920 1925 1930 1935 19(0 19(5 1950
ing this period.
Figure IV.2.5. Maternal mortality rates in England, Puerperal sepsis usually accounted for about 40
Wales, and the United States, 1910-50. (From Annual percent of deaths. At first, the term puerperal sepsis
Reports of the Registrar General for England, Wales, was synonymous with puerperal fever ("childbed fe-
and Scotland. For Sweden, 1860-1910: Ulf Hogberg, Ma- ver"), an infection that appeared after delivery. La-
ternal mortality in Sweden, Umea University Medical ter, it included septic abortion as well, but in most
Dissertations, New Ser. 156 [Umea 1985], 1911-50: countries the two were not distinguished until the
Sueriges officiella Statistik, Stockholm. Children's Bu-
late 1920s, when deaths from septic abortion were
reau Publication. U.S. Dept. of Labor. Washington, D.C,
U.S. Govt. Printing Office; R.M. Woodbury, Maternal
increasing, although to a widely different extent in
mortality: The risk of death in childbirth and from all different countries. By the early 1930s, the death
the diseases caused by pregnancy and confinement, Rept. rate from septic abortion had reached a high level in
no. 152 [1921]; Elizabeth Tandy, Comparability of mater- the United States. In New Zealand, deaths from sep-
nal mortality rates in the United States and certain for- tic abortion actually exceeded those from full-term
eign countries, Rept. No. 229 [1935].) sepsis. The contribution of septic abortion to mater-

nal mortality in different countries is an extremely tal), and current fashions in the management of
complex subject. But it is likely that the increase in normal and abnormal pregnancies and labors.
the MMR in the Netherlands and Sweden in the late Nonclinical factors included the attitudes and ex-
1920s and early 1930s was the result of an increase pectations of women about the conduct of childbirth,
in deaths from septic abortion superimposed on a together with socioeconomic considerations: family
more or less constant rate of deaths from puerperal income, nutrition, housing and hygiene, the ability
fever. to command and pay for obstetric care where private
Unlike deaths from septic abortion, those from care predominated, and the provision of maternal
puerperal fever were largely preventable. The risk welfare schemes by local and national government
of puerperal infection, however, was much greater in or charities where they existed.
the past than it is today because of the prevalence Some historians have suggested that high MMRs
and virulence of the organism known as the B- in the past were due largely to social and economic
hemolytic streptococcus, Lancefield group A (Strepto- deprivation. Others have asserted that the responsi-
coccus pyogenes), which was responsible for the vast bility lay not with poverty per se, but with the stan-
majority of deaths from puerperal fever. Before the dards of obstetric care available to the poor. Poor
Second World War, this organism was frequently standards of care might result from ignorance and
carried in the nose or throat of a large proportion of lack of training. Poor practice might also, and often
the healthy population ("asymptomatic carriers"). It was, caused by negligence, laziness, hurrying, and
was also common not only as the cause of scarlet dangerous, unnecessary surgical intervention by
fever and erysipelas, but as an infection in people trained practitioners. Poor practice, therefore, was
suffering from such minor complaints as sore not confined to untrained midwives or even to the
throats, whitlows, and minor abrasions, so that the often-maligned general practitioners; it was often
risk of cross-infection was high. The prevalence of found among specialist obstetricians following the
the virulent streptococcus and the inadequacy of procedural fashions of their time.
antiseptic procedures contributed to the high MMR. Clinical and nonclinical factors were not mutually
Today, asymptomatic carriers are rare, scarlet fever exclusive. They overlapped, and both could affect the
has become a minor disease, and rheumatic fever outcome of childbirth. In any particular case, mater-
and acute nephritis have virtually disappeared. The nal risk was a reflection of the complex interplay of
reasons for the change are uncertain. traditional, social, economic, and clinical features
Deaths from toxemia (eclampsia and preeclamp- that surrounded the birth of a baby and where the
sia) accounted for about 20 to 25 percent of total baby was born. Obviously, the risks of a mother
maternal deaths and hemorrhage (antepartum and giving birth in midwinter in Montana or Maine,
postpartum) for about 20 percent. Each of the re- North Wales or the Highlands of Scotland were differ-
maining causes, such as "white leg" (deep-vein ent from the risks experienced in the middle of Lon-
thrombosis) and embolism, ruptured uterus, ectopic don, Paris, or Boston.
pregnancy, hyperemesis gravidarum, puerperal ma- Yet in spite of bewildering variety, it is the task of
nia, and so on, contributed 5 percent or less to the the historian to generalize, and to try to assess the
total. relative importance of all such factors in different
populations at different times, allowing for differ-
Determinants of Maternal Mortality ences in the ways that populations are described.
Although the immediate causes of maternal deaths Europeans tend to describe populations in terms of
are not disputed, the factors that determined MMRs social class; North Americans in terms of national-
are much more debatable. They fall broadly into two ity, race, and color. One can suggest with reasonable
groups: clinical factors and socioeconomic, political, confidence, however, that black mothers as a whole
and geographic factors. in the United States would have shared with the
Clinical factors were associated with the type and lower social classes in Britain a greater than aver-
standards of obstetric care provided by the birth age likelihood of suffering from malnutrition,
attendant. Standards of obstetric care were deter- chronic disease, and the general ill-effects of poverty.
mined by a number of factors, including the status of Did they suffer a high MMR as a consequence? Two
obstetrics and thus the quality of education and lines of evidence suggest that social and economic
training, the type of birth attendant (specialist obste- factors were much less important determinants of
trician, general practitioner, trained or untrained maternal mortality than might be expected.
midwife, etc.), the place of delivery (home or hospi- A series of reports from cities in Britain, dating

from the 1850s to the 1930s, revealed that MMRs ditions. Therefore, although there were maternal
were higher among the upper classes than the lower. deaths in which anemia, malnutrition, and chronic
Thesefindingswere confirmed by the Registrar Gen- ill-health must have been contributory factors (and
eral's analysis of maternal mortality by social class it seems likely that they contributed to the high
for England and Wales for the years 1930-2. This MMR in the Deep South of the United States), the
showed that the MMR for social classes I and II weight of evidence suggests that the standard of
(professional and managerial) was 44.4, while for obstetric care was usually the most important deter-
social class V (unskilled workers) it was 38.9. minant of the MMR. Because hospital delivery car-
In the United States there was no doubt that the ried the danger of cross-infection as well as the likeli-
MMR was much higher (usually by a ratio of 3 to 1) hood of surgical interference in normal labor, it was
among black women than white. A few investiga- usually safest before the mid-1930s to be delivered
tions were carried out on the relationship between at home by a trained midwife or by a medical practi-
income and maternal mortality. Most showed a tioner who was conservative in his or her attitudes
higher MMR among the lowest income groups, but toward obstetrics and meticulous in antiseptic prac-
they generally concluded (the Massachusetts report tice. The irony is that the rich, often sought what
of 1924 is an example) that inability to pay for obstet- they considered the "best" obstetric care in plush
ric care, not poverty per se, was the explanation. private hospitals and paid for it with the added risk
The second line of evidence might be called experi- of iatrogenic maternal mortality.
mental. It came from programs in which a high
standard of obstetric care was provided in regions of Conclusion
social and economic deprivation. The classic exam- The fall in MMR that began in the late 1930s was due
ple was the Rochdale experiment. In 1929 Rochdale to a number of factors, which followed one another
(a town in Lancashire) had an exceptionally high but at slightly different rates in different countries.
MMR of slightly more than 90 deaths per 10,000 In England and Wales these were, in succession, the
births. Andrew Topping, a physician serving as the sulfonamides, blood transfusion, better obstetric care
new officer of health, undertook a vigorous reform of (in part associated with wartime organization), peni-
obstetric care during a period of severe economic cillin in 1944, and after the war a marked improve-
depression. The MMR was reduced in a few years ment in obstetric education. The National Health
from one of the highest in England to one of the Service hastened the adoption of a standard of obstet-
lowest. There was no change in the social and eco- ric care for everyone, which was available only to a
nomic environment during the experiment. minority before the war. The fact that this decline in
A similar experiment was the establishment of MMR occurred throughout the developed world at
the Kentucky Frontier Nursing Service by Mary much the same pace is a strong endorsement of the
Breckinridge in the 1920s. Highly trained nurse- notion that clinical care is the main determinant of
midwives, traveling on horseback, delivered babies MMR. Some, however, would still maintain that the
of women who lived in great poverty in isolated low maternal mortality today is due to good health,
mountain terrain and suffered from a high rate of not medical technology. In this respect the experience
chronic illness and malnutrition. An astonishingly of a religious group in Indiana in the 1970s is informa-
low MMR was achieved solely by good obstetric tive. This group rejected all orthodox medical care
practice — about one-tenth of the rate among women while engaging in the same middle-class occupations
delivered by physicians as private patients in the and earning the same incomes as their orthodox
hospital in Lexington, the nearest town. neighbors. Mothers received no prenatal care and
The countries showing the lowest MMRs - the were delivered without trained assistance. Their
Netherlands and Scandinavia - ran maternity ser- MMR was 100 times higher than the statewide rate.
vices based on a strong tradition of home deliveries We have noted the high MMRs between 1900 and
by highly trained midwives. In Britain a very low 1935. We may ask with the benefit of hindsight
MMR was achieved by a similar group, the Queen's whether it would have been possible for countries
Institute Midwives. The records of outpatient chari- such as Britain and the United States to have reduced
ties in Britain and the United States showed repeat- their MMRs significantly. The answer is almost cer-
edly that the establishment of a free or low-cost tainly yes, although it is probable that the MMRs
obstetric outpatient service in areas of severe socio- seen in the 1950s would have been out of reach in the
economic deprivation could result in low MMRs, 1930s, because of the virulence of streptococcus and
even when deliveries took place under appalling con- the absence of sulfonamides and penicillin.

A significant reduction in maternal mortality tional List of Diseases was important when it was
might have been achieved, however, through educa- adopted by England and Wales in 1911. Previously,
tion. The medical curriculum should have attached deaths due to toxemia of pregnancy (but not deaths
as much importance to obstetrics as to anatomy, from eclampsia) were entered under diseases of the
physiology, and biochemistry. It would have been kidney; after 1911 they were entered as maternal
essential to demonstrate the need for a very high deaths. Subsequent revisions of the international
standard of antiseptic practice at every delivery. It list made little difference to the calculation of total
would have been wise for every developed country to maternal mortality, but an appreciable difference in
have established a national or regional maternity the way maternal deaths were classified.
service based largely on the work of trained mid- A major problem in international comparisons
wives undertaking the majority of normal deliveries was that of associated, or, to use the modern term,
at home. Maternity hospitals were necessary, of indirect deaths. Simply stated, should the death of
course, for the management of dangerous complica- every pregnant woman be recorded as a maternal
tions and high-risk cases, but they were not the best death, regardless of the cause? There was no diffi-
place for normal deliveries. The work of hospitals, culty in identifying "true" maternal deaths such as
general practitioners, and midwives should have those due to postpartum hemorrhage, puerperal
been monitored by local maternal mortality commit- fever, or ectopic gestation; and deaths that had
tees, and care taken to establish close cooperation nothing to do with the pregnancy or general health
between all parts of the maternity service. Some of (e.g., the death of a pregnant woman in a road or
these reforms were beginning to be implemented by railway accident) were generally excluded. Difficul-
the late 1930s in Britain. None required knowledge ties arose, however, when a woman died in the
that was not then available. The examples of the course of an otherwise normal pregnancy or labor
Kentucky Nursing Service, the Rochdale experi- from influenza, or some preexisting condition such
ment, and the numerous successful outpatient chari- as heart disease, tuberculosis, or nephritis. It was
ties and services were well known. The success of argued that such deaths were due to the combina-
Scandinavia and the Netherlands, where most of the tion of general disease and the strain of pregnancy
principles just outlined were in operation, was no or labor; if the woman had not been pregnant, she
secret. might have survived. Should such deaths be en-
If such simple but potentially effective changes tered under maternal or general causes of death?
were not adopted, it was partly because no clear Different opinions were held. In the United States,
consensus existed as to the way obstetric care should Australia (but not New Zealand), Denmark (but not
be delivered. Even if there had been a consensus, it Norway or Sweden), and Scotland (but not England
would have been impossible to compel medical per- and Wales), indirect deaths were usually included
sonnel to change their ways. in the estimation of maternal mortality. There were
always borderline cases, and the way they were
treated could also differ, but these differences were
Appendix statistically negligible. Those countries that in-
The Problems of Comparative Statistics cluded associated deaths often believed that they
Certain statistical problems surround the interpreta- were more honest and commented angrily that, if
tion of the statistics on maternal mortality and inter- their MMRs seemed high, it was due solely to this
national comparisons. In England and Wales before difference in method. This was understandable, but
the compulsory registration of stillbirths in 1927, wrong. Elizabeth Tandy of the Children's Bureau
the denominator births meant live births only. After showed in 1935 that, although some differences
1927, stillbirths were included and the term total could be attributed to differences in method, they
births replaced live births in the calculation of the were only slight in comparison with the wide inter-
MMR. The difference was relatively small. In 1933, national differences that existed. An example can
for example, the MMR was 45.2 per 10,000 live be found in Figure IV.2.5, where the MMR for the
births and 43.2 per 10,000 live births plus still- United States as a whole is shown twice: once with
births. The failure to take multiple births into ac- associated deaths included in the U.S. manner and
count produces a slight distortion in the other direc- once with associated deaths excluded in the English
tion, because births rather than deliveries are used manner.
as the denominator. Again, the distortion is slight. Perhaps the most difficult problem is that of "hid-
The use of the classification based on the Interna- den" deaths - deaths from puerperal fever and abor-

tion that are hidden because of the opprobrium sur- Campbell, Janet, Isabella D. Cameron, and Dilwys M.
rounding them. A death from puerperal fever was, Jones. 1932. High maternal mortality in certain areas.
above all other deaths, one for which the physician Reports on Public Health and Medical Subjects No.
or nurse was likely to be blamed. There were there- 68. London.
fore strong motives for a physician to register a Campbell, Dame Janet. 1935. Maternity services. London.
death like this in such a way that the authorities Cullingworth, C. J. 1898. On the undiminished mortality
from puerperal fever in England and Wales. Transac-
would not know it was a maternal death. In the late
tions of the Obstetrical Society of London 40: 91—114.
nineteenth and early twentieth centuries, it was not Dart, Helen. 1921. Maternity and child care in selected
unusual for doctors to certify a death from puerperal areas of Mississippi. U.S. Department of Health, Chil-
sepsis as being due to peritonitis or septicemia with- dren's Bureau, Publ. No. 88. Washington, D.C.
out mention of childbirth. These conditions were DePorte, J. V. 1928. Maternal mortality and stillbirths in
cited because they were, in fact, the immediate New York State: 1921-1925. New York.
causes of death in puerperal sepsis. Galdston, Iago. 1937. Maternal deaths: The way to preven-
The true cause of death in cases such as these could tion. New York.
be determined, however, both by asking the offending Hogberg, Ulf. 1985. Maternal mortality in Sweden. Umea
doctor outright whether childbirth had been involved University Medical Dissertations, New Ser. 156.
or by searching the death records for an excess of Jellett, Henry. 1929. The causes and prevention of mater-
deaths from peritonitis or septicemia among women nal mortality. London.
Kaunitz, A.M., et al. 1984. Perinatal and maternal mortal-
of childbearing age. Deaths from both causes ("perito-
ity in a religious group avoiding obstetric care. Ameri-
nitis of unstated origin" and "septicemia") were more can Journal of Obstetrics and Gynecology 150: 826—32.
common in men than women once deaths from puer- Leavitt, Judith. 1986. Brought to bed: Child-bearing in
peral sepsis were excluded. This complicated statisti- America, 1750-1950. New York.
cal exercise was carried out by government statisti- Local Government Board (England and Wales). 1914-16.
cians in Britain and the United States in the 1920s. 44th Annual Report of the Local Government Board 6
Indeed, this author has carried out in some detail the (supplement on maternal mortality).
same exercise using the lists of causes of death from Loudon, Irvine. 1986a. Deaths in childbed from the eigh-
the 1880s to the 1950s. In England and Wales, in the teenth century to 1935. Medical History 30: 1-41.
period from 1900 to 1930, apparently incorrect certifi- 1986b. Obstetric care, social class and maternal mortal-
cation led to an underestimation of the true number ity. British Medical Journal 2: 606-8.
of deaths from puerperal sepsis by about 12 percent. 1987. Puerperal fever, the streptococcus and the sul-
The MMRs described by this essay for the period up to phonamides, 1911-1945. British Medical Journal 2:
the mid-1930s are therefore likely to be an underesti- 485-90.
1988. Maternal mortality: Some regional and interna-
mation; they are certainly not an exaggeration of the
tional comparisons. Social History of Medicine. 1: 2.
true figures. Needless to say, the exact MMRs of the Macfarlane, A., and M. Mugford. 1984. Birth counts: Statis-
past can never be known. Nevertheless, the extent of tics ofpregnancy and childbirth. London.
statistical distortion can to a large extent be esti- Meigs, G. L. 1916. Rural obstetrics. Transactions of the
mated. It is then reasonable to believe that a gener- American Association for the Study and Prevention of
ally correct picture of MMRs in most developed coun- Infant Mortality 7: 46-61.
tries since the 1880s can be obtained and that the 1917. Maternal mortality from all conditions connected
picture becomes increasingly accurate through the with childbirth in the United States and certain other
present century. countries. U.S. Department of Labor, Children's Bu-
reau, Publ. No. 19. Washington, D.C.
Irvine Loudon
Ministry of Health (England and Wales). 1937. Report of
an investigation into maternal mortality, Cmd. 5422.
Bibliography London.
Australia. 1917. Report on maternal mortality in child- 1937. Report on maternal mortality in Wales, Cmd. 5423.
birth. Commonwealth of Australia, Department of London.
Trades and Customs, Committee concerning causes Moore, Elizabeth. 1917. Maternity and infant care in a
of Death and Invalidity in the Commonwealth. Mel- rural county in Kansas. U.S. Department of Labor,
bourne. Children's Bureau, Publ. No. 26. Washington, D.C.
Breckinridge, Mary. 1952. Wide neighborhoods: A story of Munro Kerr, J. M. 1939. Maternal mortality and morbid-
the Frontier Nursing Service. New York. ity. Edinburgh.
Campbell, Janet. 1924. Maternal mortality. Reports of Pub- New York City Public Health Committee and New York
lic Health and Medical Subjects No. 25. London. Academy of Medicine. 1933. Maternal mortality in

New York, 1930, 1931, 1932. (Abstract in Journal of bor, Children's Bureau, Publ. No. 158. Washington,
the American Medical Association 101: 1826—8.) D.C.
Paradise, Violet. 1919. Maternity care and the welfare of Young, James. 1936. Maternal mortality and maternal
young children in a homestead county in Montana. mortality rates. American Journal of Obstetrics and
U.S. Department of Labor, Children's Bureau, Publ. Gynaecology 31: 198-212.
No. 34. Washington, D.C.
Philadelphia County Medical Society, Committee on Ma-
ternal Welfare. 1934. Maternal mortality in Philadel-
phia. Philadelphia.
Sandelowski, M. 1984. Pain and pleasure in American
childbirth: From twilight sleep to the Read method, IV.3
1914-1960. Westport, Conn.
Schofield, R. 1986. Did the mothers really die? Three cen-
Infant Mortality
turies of maternal mortality in the world we have lost.
In The world we have gained: Histories of population
and social structure, ed. L. Bonfield, R. Smith, and The infant mortality rate (which is commonly calcu-
K. Wrightson. Cambridge. lated as the number of deaths among infants under 1
Sherborne, F. B., and E. Moore. 1919. Maternity and infant year of age in a calendar year per 1,000 live births in
care in two rural counties in Wisconsin. U.S. Depart- that year) measures the probability that a newborn
ment of Labor, Children's Bureau, Publ. No. 46. Wash- baby will survive the hazards of infancy and live to
ington, D.C. celebrate his or her first birthday. Whether a given
Smith, P. M. 1986. Maternity in dispute, New Zealand, infant survives this crucial first year of life is influ-
1920-1939. Wellington. enced in part by certain biological characteristics
Steele, Glen. 1923. Maternity and child care in a mountain (e.g., genetic makeup, nature of the birth outcome,
county in Georgia. U.S. Department of Labor, Chil- susceptibility to particular diseases). But a volumi-
dren's Bureau, Publ. No. 120. Washington, D.C. nous body of research over the past century has
Topping, A. 1936a. Maternal mortality and public opinion. clearly identified the major determinants of the over-
Public Health 49: 342-9. all infant mortality rate to be, first, the nature of the
1936b. Prevention of maternal mortality: The Rochdale
physical environment, especially the state of sanita-
experiment. Lancet 1: 545—7.
U.S. Department of Health, Education and Welfare. 1966. tion, and, second, the nature and availability of
Infant, fetal and maternal mortality. National Center health care facilities. Although the health of persons
for Health Statistics, Ser. 20, No. 3. Washington, D.C. of all ages is affected by these conditions, the new-
U.S. Department of Labor, Children's Bureau. 1933. Mater- born infant is most susceptible and most likely to be
nal deaths: A brief report of a study made in fifteen adversely affected by the absence of appropriate sani-
states. Publ. No. 221, Washington, D.C. tary and health care facilities.
1934. Maternal mortality in fifteen states. Publ. 223. It has also been solidly established that within
Washington, D.C. any society infant mortality rates are strongly re-
Wertz, R. W, and D. C. Wertz. 1977. Lying-in: A history of lated to family income, which in turn is an indicator
childbirth in America. New York.
of both the nature of the environment in which an
White House Conference on Child and Health Protection.
1933. Fetal, newborn and maternal morbidity and mor- infant is born and raised and the family's ability to
tality. New York. provide the infant with optimal health care. The
Williams, W. 1895-6. Puerperal mortality. Transactions of basic aim of this essay is to review briefly some of
the Epidemiological Society of London, 100-33. the relevant research and to present empirical justifi-
1904. Deaths in childbed (being the Milroy Lectures cation for designating the infant mortality rate as
delivered at the Royal College of Physicians of Lon- the most sensitive indicator of the overall health
don, 1904; W. Williams was Medical Officer of Health status of any population group.
at Cardiff). London.
Williams, J. Whitridge. 1912. Medical education and the
Historical Evidence
midwife problem in the United States. Journal of the
American Medical Association 58: 1—76. Although precise statistical data are lacking, the
1922. Criticism of certain tendencies in American obstet- little that scientists have been able to compile from
rics. New York State Journal of Medicine 22: 493-9. various anthropological and archaeological sources
Woodbury, R. M. 1926. Maternal mortality: The risk of clearly indicates that throughout most of its exis-
death in childbirth and from all the diseases caused by tence humankind has had to contend with an ex-
pregnancy and confinement. U.S. Department of La- tremely high death rate. At least 20 percent and

probably more of all newborn babies died before that these detrimental health conditions were differ-
their first birthdays, and for most there was no more entially distributed among the population and that
than a 50 percent chance of surviving to adulthood. the lower social classes experienced much higher
More specific estimates of mortality in antiquity are infant death rates than the middle and upper classes
limited to occasional estimates of average life expec- (Woods et al. 1989). As previously mentioned, re-
tancy, the number of years lived, on the average, by search over the years has clearly established that
the members of a given population. This average life family income is the most significant determinant of
expectancy, or average age at death as it is some- the physical well-being of all family members, and
times crudely defined, is influenced most strongly by particularly that of infants and young children. Ar-
the mortality rate in infancy (Shryock et al. 1976); thur Newsholme, for example, one of the best-known
hence, where conventional birth and death statistics investigators of this topic in the late nineteenth and
are not available, this measure can be used as some- early twentieth centuries, identified poverty as a
thing of a proxy for the infant mortality rate. Avail- major corollary of poor sanitation and high infant
able historical estimates indicate that, while some of mortality. In England nearly 80 years ago he wrote,
our primitive ancestors surely attained extremely "No fact is better established than that the death
old ages, the average life expectancy in ancient rate, and especially the death rate among children,
times among most groups was probably not much is high in inverse proportion to the social status of
more than 25 or 30 years, and in some populations it the population" (Newsholme 1910).
was even lower (Russell 1958). Similarly, in summing up his classic study of in-
Although overall survival improved somewhat fant mortality in the United States during the first
over the years, average life expectancy had not quarter of this century, Robert Woodbury (1925)
greatly improved as recently as the start of the pres- noted that infant death rates were "highest when
ent century. Estimates for England and Wales, for the father's earnings were low and lowest when the
example, indicate that average life expectancy for father's earnings were relatively high." Although
the period 1891-1900 was only about 45 years (44 Woodbury's findings suggested that several other
for men and 48 for women) (Dublin, Lotka, and Spie- variables bore a causal relation to infant mortality
gelman 1949), and in the United States in 1900 it (e.g., race, physical condition of the mother, age of
was only about 50 years (48 for men and 51 for mother, type of feeding, length of interval between
women) (U.S. Bureau of the Census 1960). Moreover, pregnancies), all of these were highly correlated
it was still common at that time for as many as 15 with the earnings of the father. Thus, in summing
percent or more of all newborn babies to die before up the interrelationship between infant mortality,
their first birthdays. Data for the United States, for father's income, and the other causative factors, he
example, indicate an infant mortality rate for 1900- concluded:
2 of 162 per 1,000 live births (U.S. Bureau of the
Census 1960); and rates of comparable magnitude The analysis indicated that low earnings of the father
exerted a potent influence over the prevalence of these
(between 150 and 170) have been estimated for this factors and therefore must be regarded as primarily re-
period in a number of other western European coun- sponsible for the greater mortality associated with them.
tries (Woods, Watterson, and Woodward 1988). The presence of intermediate factors in the chain of causa-
Contemporary scholars, concerned with the high tion does not lessen the responsibility of low earnings as a
levels of infant and childhood mortality, were clearly primary cause. (Woodbury 1925)
aware of their causes. Some were environmental
factors, such as foul air, contaminated water, and Twentieth-Century Mortality Declines
poorly ventilated, overcrowded housing, which con- Mortality rates have fallen dramatically in much of
tributed to the high incidence of a variety of infec- the world since the early days of the twentieth cen-
tious, respiratory, and parasitic diseases. Other tury, although life expectancy values are still lower
causes were related to poor child care, including than 50 years in a number of the lesser developed
inadequate and unsanitary delivery conditions and countries, particularly in Africa. Recent estimates
improper feeding practices, notably a lack of breast for the more developed countries of North America
feeding and the associated consumption of contami- and Europe place the average life expectancy be-
nated milk, all of which led to high rates of mortality tween a low of 73 years for Ireland and a high of 77 to
from diarrheal diseases (Woods, Watterson, and 78 years for Iceland, the Netherlands, Sweden, and
Woodward 1989). Moreover, it had generally been Switzerland (Population Reference Bureau 1989).
known since at least the mid-nineteenth century The primary causes of this enormous mortality de-

cline in the Western world lie in the unprecedented (Gwatkin 1980). In other words, on an international
measure of control gained over those infectious and level there remains a clear and strong association
parasitic diseases that until quite recently took such between level of modernization and the infant mor-
a heavy toll, especially among the younger elements tality rate. In fact, the association is so strong that
of the population (Stockwell and Groat 1984). Indeed, the infant mortality rate is generally regarded as a
the most significant mortality trend of the twentieth much more accurate indicator of the level of socioeco-
century has been an extremely pronounced decline in nomic well-being of a people than is its per capita
the death rate among children under 1 year of age. In gross national product or any of the other more con-
the United States, for example, there has been a 50 ventional indices of economic development.
percent reduction in the total death rate since 1900
(from 17.2 to 8.6), but the infant mortality rate dur- Family Income and Infant Mortality in
ing the same period declined by approximately 94 Modern Societies
percent (from 162 to 10 per 1,000). Moreover, there is The infant mortality decline in the Western world
evidence that declines of a similar or even greater described in the preceding section represents one of
magnitude have occurred in a number of western the truly outstanding achievements of the twentieth
European countries since the beginning of the twenti- century. At the same time, however, it is very clear
eth century (Woods et al. 1988). In contrast to the that this decline has not altered the nature of the
situation at the turn of the century, when infant mor- traditional socioeconomic differential. Rather, the
tality rates were of the order of 150 or more, a number findings of a wide variety of studies have consistently
of western European countries today have single- shown that the lower income groups in all societies
digit infant mortality rates; and in three countries have been and continue to be extremely disadvan-
(Finland, Iceland, and Sweden), out of every 1,000 taged in the probability that their newborn infants
babies born only 6 fail to survive until their first will survive to adulthood. According to a recent effort
birthdays (Population Reference Bureau 1989). In directed by the present author, the existence of a
addition, an infant mortality rate of less than 6 per general inverse association between infant mortality
1,000 is found in Japan, the first non-European coun- and socioeconomic status has been documented by a
try to achieve a high level of modernization. great many studies based on widely different popula-
In sharp contrast to these single-digit infant mor- tion groups, covering different points in time, and
tality rates, or even those approaching 15 through- using a variety of methods, not only in the United
out more or less developed regions of the globe, in- States but in a number of western European coun-
fant mortality rates of the order of 100 or more per tries (Stockwell and Wicks 1981). Moreover, a follow-
1,000 live births are still fairly common in the less up investigation documented the existence of such a
developed countries of the Third World. Today they relationship for all race-sex groups and for all major
are highest in the least developed countries of Af- causes of death (Stockwell, Swanson, and Wicks
rica: 18 countries on that continent have rates of 125 1986).
or more, and in at least 4 countries (Ethiopia, This later study entailed an analysis of infant
Guinea, Mali, and Sierra Leone) the infant mortal- mortality differentials in a metropolitan aggregate
ity rate continues to exceed 150 per 1,000 live births comprising eight of the larger cities in the state of
(Population Reference Bureau 1989). Ohio covering the years 1979-81. The general de-
The high life expectancy values and corresponding sign of the research was an ecological one in which
low infant mortality rates of the more developed the primary analytic unit was the census tract of the
countries stand as an impressive testimony to the mother's usual residence. (Census tracts are small
success of those countries in improving the quality of geographic areas used in the United States to de-
life of their populations. Conversely, the low life limit neighborhoods composed of people possessing
expectancies and corresponding high infant mortal- relatively homogeneous characteristics. They have
ity rates in the less developed countries are, as was no political basis, but are merely statistical aggre-
the case in Europe a century ago, a reflection of the gates that are used primarily for various planning
poor quality of life available to the bulk of the popu- programs and for research.) The independent vari-
lation. In particular, they reflect the inability of able was defined as the percentage of low-income
existing public health programs to deal with evolv- families in each census tract at the time of the 1980
ing health problems, many of which are related to decennial census. An annual income of $10,000, or
widespread malnutrition resulting, at least in part, roughly 50 percent of the median family income, was
from a decline in social and economic progress selected as the low-income cutoff point.

Table IV.3.1. Infant mortality rates for income areas causes or groups of causes, or if it more or less charac-
in metropolitan Ohio, 1979-81 terizes all the major causes of death. In this analysis,
the census tracts were grouped into three rather
Infant mortality rate than five income aggregates. A preliminary exami-
Income area Total Neonatal Postnatal nation of the data indicated that a larger number of
groupings would introduce a serious problem of rate
All areas 16.6 10.6 6.0 instability because of smaller cell frequencies in the
I (high income) 8.9 6.3 2.6 more detailed cross-tabulations. Even with only
II 14.3 9.2 5.1 three areas, small frequencies became a problem
III 16.4 10.8 5.6 when specific causes of death were considered;
IV 19.7 12.6 7.1 hence, this analysis was confined to the total popula-
V (low income) 24.3 14.4 9.9
tion, and most of the comparisons were limited to
two broad categories of causes of death. These are
Source: Stockwell, Swanson, and Wicks (1986, 74).
exogenous causes of death (those whose origin is
farthest removed from the actual birth process) and
The dependent-variable data consisted of the num- endogenous causes of death (those whose origin is
ber of live births in each census tract during 1980 most closely associated with the physiological pro-
and the number of infant deaths, by age, in the three cesses of gestation and birth). The specific cause
years centering on the census date (1979-81). The groups, along with their identification codes from
analysis first used the income variable to aggregate the ninth revised edition of the International Statisti-
the census tracts of the study cities into five broad cal Classification of Diseases and Causes of Death,
groups in such a way that an approximately equal are as follows:
number of tracts fell into each income status group.
The resulting aggregates were then ranked and com- Exogenous causes
pared in terms of infant deaths - total, neonatal (un- Infectious and parasitic causes (001-139, 320-3,
der 1 month), and postneonatal (1 month to 1 year). 460-6, 480-7, 500-8, 771)
The results of these comparisons are presented in Injury or poisoning (800-999)
Table IV.3.1. Inspection of the data clearly reveals Endogenous causes
the existence of a consistent and pronounced inverse Congenital anomalies (740-59)
association between infant mortality and family in- Conditions originating in the perinatal period (760-
come, with the differential being especially marked 70, 772-9)
for postneonatal mortality, or for those deaths gener- Residual endogenous conditions (390-459, 470-8,
ally considered to be most influenced by the nature 490-6, and all causes not elsewhere classified)
of the environment.
Similar observations can be made with respect to The overall exogenous and endogenous death
both men and women and for both whites and non- rates for the three income areas, by broad age cate-
whites (Stockwell et al. 1986). There are occasional gory, are shown in Table IV.3.2. As is conventional
deviations from a consistent linear pattern, but they with cause-specific rates, the rates in the table are
are not sufficient to detract from the validity of the expressed in terms of 100,000 rather than 1,000 live
overall conclusion of the research: The traditional births. Two conclusions are immediately suggested
inverse association between infant mortality and by these data. First, the vast majority of infant
family income, first documented in the United deaths today are caused by the endogenous condi-
States in 1925 (Woodbury 1925), continues to be very tions that are most closely associated with the phys-
pronounced; and it characterizes both the neonatal iological processes of gestation and birth. Second,
and postneonatal components of infant mortality, for both the exogenous and endogenous cause-specific
both sexes and for both major racial groups. death rates are inversely associated with family in-
come. Not surprisingly, perhaps, the strength of the
Cause of Death relationship, as measured by the difference between
To understand more fully the association between the death rates of the highest and lowest areas, is
income status and levels of infant mortality it is much greater for the environmentally related exoge-
necessary to undertake a cause-specific analysis to nous causes such as infections, accidents, and poison-
see if the general inverse nature of the relationship ings. The exogenous death rate in Area III is nearly
can be explained largely in terms of a few selected three times greater than that in Area I. By contrast,

Table IV.3.2. Infant mortality rates (per 100,000 live births) by broad cause-of-death group for income areas
in metropolitan Ohio, 1979-81
Exogenous causes Endogenous causes

Income area Total Neonatal Postneonatal Total Neonatal Postneonatal
All areas 227 69 158 1,432 990 443
I (high) 129 57 72 998 703 295
II (medium) 201 61 140 1,453 1,023 429
III (low) 363 92 271 1,881 1,262 618
Source: Stockwell, Swanson, and Wicks (1986, 87-93).
the Area III endogenous death rate is only twice as ability of high-risk births. In other words, many
great as that of Area I. infants who a generation ago would have died
There is a tendency for the exogenous causes to within a few days or weeks after birth now have a
account for an increasing proportion of total deaths much greater chance of surviving. For some, this
as income decreases: 11 percent of the infant deaths change will mean a chance to survive infancy and
in Area I compared with 16 percent in Area III were grow to adulthood leading relatively normal lives.
due to exogenous causes. Thus, it is clear that, de- For others, however, it will mean surviving the neo-
spite the much lower absolute death rate, the in- natal period only to succumb later in infancy; the
creased risk of an infant dying as the economic sta- frequency of deaths due to endogenous causes in the
tus of its parents declines is relatively much greater postneonatal period thus increases (Miller 1985). In
from environmentally related exogenous causes any case, these findings indicate that there is no
than it is from endogenous causes. It is true that the longer any basis for assuming an age-cause proxy
inverse association between infant mortality and eco- relationship in infancy such as may have existed in
nomic status seems largely due to conditions that the past (Stockwell, Swanson, and Wicks 1987).
can generally be regarded as amenable to societal Our results demonstrated that the same general
control. However, this should not lead one to mini- conclusions apply to both sexes as well as to the two
mize the significance of a consistent and pronounced racial groups: Endogenous causes clearly predomi-
inverse relationship for those endogenous conditions nate in all categories, and both cause-specific rates
less resistant to control, which account for the vast are inversely related to income status for all sex-
majority of infant deaths. color groups (Stockwell, Swanson, and Wicks 1988).
Inspection of the exogenous—endogenous rates for Moreover, this pattern was also strongly apparent in
the neonatal and postneonatal ages reveals that the those few instances where the numbers were suffi-
pronounced inverse association with economic sta- ciently large to permit a comparison based on more
tus characterizes both of the causal groups for both specific causes of death (Stockwell et al. 1988).
segments of infant mortality. The more interesting Overall, the results of our research show that the
point here, however, is perhaps the challenge these basic inverse relationship between infant mortality
data pose to the traditional distinction between and socioeconomic status cannot be attributed solely,
neonatal-endogenous as opposed to postneonatal- or even largely, to either group of causes. Although
exogenous mortality. In the past, demographers and more deaths are due to endogenous than to exoge-
other epidemiological researchers have commonly nous causes, and more deaths occur in the neonatal
used the neonatal and postneonatal death rates as period regardless of cause, the variations in the
proxies for endogenous and exogenous mortality death rates for both broad cause groups are charac-
(Bourgeois-Pichat 1952). Yet while the Ohio data terized by a similar marked inverse differential for
show a clear preponderance of endogenous causes in all major subgroups in the society.
the neonatal period (93 percent), they also reveal a
preponderance of endogenous causes among postneo- Conclusion
natal deaths (74 percent). The increasing impor- In spite of significant progress in maternal and in-
tance of the endogenous causes in the latter period fant care and an associated substantial decline in
likely reflects the nature of the technological prog- infant mortality in this century, our research, as
ress made in recent years in enhancing the surviv- well as that of many other contemporary scholars,

points to the persistence of a strong inverse associa- control by various public health programs, and what
tion between economic status and the probability were once the major killers of infants and young chil-
that a newborn infant will survive the first year of dren now account for a very small fraction of the total
life. Although there are occasional exceptions or vari- deaths under 1 year of age. Nevertheless, because the
ous degrees of deviation from a perfectly linear pat- exogenous-disease death rates continue to vary in-
tern, the overriding conclusion is that infant mortal- versely with economic status, it is clear that the prog-
ity rates among lower income groups continue to be ress made in the prevention and treatment of these
substantially above those of higher income groups. diseases has not benefited all groups equally. There is
This conclusion implicitly assumes that causality an obvious need to continue and even accelerate ef-
runs solelyfromlow income to high infant mortality. forts to extend the full benefits of advances in medical
But though such an assumption can be justified on knowledge and health care practices to the more eco-
the grounds that we are dealing with infants rather nomically deprived segments of the population.
than adults, we cannot rule out the possibility that By far the biggest challenge today, however, con-
the general inverse relationship reflects two-way cerns endogenous conditions, which account for about
causality. That is, the poor health of parents may 80 percent of all infant deaths in the United States.
contribute to lower income, which is such a potent These causes, which have traditionally been re-
determinant of infant life chances. This possibility garded as less amenable to societal control, reflect
does not detract, however, from the validity of the such things as social class differences in reproductive
overall conclusion, namely that the infant mortality behavior (age at childbearing, length of interval be-
rate is a powerful indicator of the general health tween pregnancies), differences in the amount and
status of a population group. quality of prenatal care (timing of first prenatal ex-
The fact that infant mortality rates have declined amination, frequency of visits), and other maternal
at all income levels obviously indicates that the bene- characteristics such as adequacy of diet during preg-
fits of new and improved infant health care programs nancy, amount of weight gain, smoking habits, and
do reach all segments of the population eventually. the use of drugs or alcohol. These factors generally
However, the persistence ofthe strong inverse associa- have an indirect impact on infant mortality through
tion between infant mortality and income status their effect on pregnancy outcome - particularly on
points to the existence of a social class differential in birth weight.
access to health care services and facilities. The first It has recently been recognized that a low birth
to benefit from advances in medical technology and weight seriously impairs an infant's chances for sur-
other health care improvements are those in the high- vival. A major policy goal, therefore, should be the
est income classes, and only gradually do the fruits of prevention of low birth weights. Evidence suggests
such progress filter down to the economically de- that efforts to do this must go beyond simply provid-
prived groups. This is indicative of an elitist approach ing more and better prenatal care and concentrate
to the delivery of health care, and in the Western on enhancing the overall quality of life and general
world, where it is supposed that adequate health care health status of low-income mothers (Wise et al.
is a basic right for all citizens, and not just an expen- 1985). A similar conclusion applies to less developed
sive privilege for those who can afford it, this situa- countries, where it is also recognized that reducing
tion presents a major challenge to society. high infant mortality rates will depend more on gen-
Efforts to meet this challenge must, of course, be eral socioeconomic development than on the imple-
guided by the knowledge that a wide variety of fac- mentation of conventional health strategies (Gwat-
tors associated with a low economic status contrib- kin 1980). In the meantime, we will continue to live
ute to the observed differences in mortality, and that in a world where the level of infant mortality serves
each of these factors will require very different kinds as a major barometer of the quality of life in any
of programs to bring them under control. In the past, given environmental setting and the overall health
major efforts focused on those factors that exerted a status of the population.
direct influence on the survival chances of infants, Edward G. Stockwell
including the adequacy of their diet; the quality of
housing, water, and home sanitary facilities; and Bibliography
their immunization status. Bourgeois-Pichat, Jean. 1952. Essai sur la mortalite
These factors, which directly influence exogenous biologique de Phomme. Population 7: 381-94.
causes (e.g., parasitic diseases and respiratory infec- Dublin, Louis I., Alfred J. Lotka, and Mortimer Spie-
tions), have already been brought fairly well under gelman. 1949. Length of life. New York.

Gwatkin, Davidson. 1980. Indications of change in develop-
ing country mortality trends: The end of an era? Popu- IV.4
lation and Development Review 6: 615—44.
Miller, C. Arden. 1985. Infant mortality in the U.S. Scien-
Measuring Morbidity
tific American 253: 31-7. and Mortality
Newsholme, Arthur. 1910. Thirty-ninth annual report of
the local government board, Report C d 5312. London.
Population Reference Bureau. 1989. World population Sickness and death are individual- and population-
data sheet: 1989. Washington, D.C. level phenomena. At the individual level, they are
Russell, J. C. 1958. Late ancient and medieval populations. best understood in terms of their causes. In illness
Philadelphia. the best prognosis derives from what is known about
Shryock, Henry S., et al. 1976. The methods and materials
the cause and about the individual. At the popula-
of demography, condensed ed. by Edward G. Stock-
well. New York. tion level, sickness and death can also be understood
Stockwell, Edward G., and Jerry W. Wicks. 1981. Socioeco- in terms of incidence. Future rates of sickness and
nomic differentials in infant mortality. Rockville, Md. death can be forecast from experience, taking into
Stockwell, Edward G., and H. Theodore Groat. 1984. account the trend and likely variations from it.
World population: An introduction to demography. Population-level statements about sickness and
New York. death - morbidity and mortality rates - can be con-
Stockwell, Edward G., David A. Swanson, and Jerry W. sidered statements of comparison. As such, they un-
Wicks. 1986. Socioeconomic correlates of infant mortal- derlie many judgments about health and health
ity: Ohio, 1980. Rockville, Md. care.
1987. The age—cause proxy relationship in infant mor- Morbidity and mortality are also structural phe-
tality. Social Biology 34: 249-53.
nomena, which is to say that, considered for a sizable
1988. Economic status differences in infant mortality by
cause of death. Public Health Reports 103: 135-42. number of people, they display certain regularities.
U.S. Bureau of the Census. 1960. Historical statistics of the The most important of these relate to age and appear
United States: Colonial times to 1957. Washington, as curves or schedules when morbidity and mortal-
D.C. ity data are arranged by age. Age-specific sickness
Wise, Paul H., et al. 1985. Racial and socioeconomic dis- and death rates should not be expected to be identi-
parities in childhood mortality in Boston. New En- cal in any two populations, but their structure-
gland Journal of Medicine 313: 360-6. their distribution by age - should be similar. This
Woodbury, Robert M. 1925. Causal factors in infant mortal- makes it possible to make estimates for missing data
ity. Washington, D.C. and to compare individual- and population-level ex-
Woods, R. I., P. A. Watterson, and J. H. Woodward. 1988. perience with sickness and death over time. This
The cause of rapid infant mortality decline in En- essay summarizes the basic method of analysis,
gland and Wales, 1861-1921, Part 1. Population Stud- which employs a life table, and suggests some ways
ies 42: 343-66. in which the problem of incomplete information can
1989. The cause of rapid infant mortality decline in be overcome with various estimation procedures.
England and Wales, 1861-1921, Part 2. Population
Studies 43: 113-32.
Quantity of Life
Like other life forms, humans have a characteristic
life span, a maximum number of years over which
individuals might survive if protected from all haz-
ards. The span is currently unknown. Our only di-
rect evidence about it derives from the age at death
of exceptionally long-lived people, and the reliability
of this evidence is often marred by poor memory,
poor records, and misrepresentation. A few people
have lived longer than 110 years, and the number of
people surviving to extreme ages has increased over
time. But it is not clear - because the evidence is
inadequate - whether there has been a change in
the maximum age to which individual members of
the species survive. Given the very small number of

IV.4. Measuring Morbidity and Mortality 231
100
United States, history with survival curves for some populations,
90 1979-81,
males and females
the curves showing the number of individuals who
80
lived at each age.
For most of human history most deaths were pre-
70
mature, and the survival curve remained concave. It
I 60 first became convex in a few advantaged societies in
I 50 the nineteenth century. Since then, it has bowed out
I 40 Alsonemeci
Copper Age,
males and females
in these and some other societies, approaching a
rectangular form. The concave curve can be identi-
30 fied with the traditional mortality regime, a regime
20 in which the risk of death was high at every age. The
10
convex curve is a characteristic of the modern mor-
tality regime. And the convexity itself indicates how
0 10 20 30 40 50 60 70 80 90 100 110 the transition from one mortality regime to the
Age (years) other has altered the problems associated with mea-
suring mortality. For most of human history, expecta-
Figure FV.4.1. Survival curves. (From Acsadi and
Nemeskeri 1970; Commons Sessional Papers 1884-5;
tions or hopes about survival have been expressed by
U.S. Decennial Life Tables for 1979-81.) reference to birth. The rectangularized survival
curve directs attention instead toward life span,
modal age at death, or another value intended to
people who survive to even older ages, the life span represent a survival goal. In other words, how many
is often estimated at 110 and sometimes at a lower of the people living at the same time can be pro-
round number, 100 (Preston 1982). tected from premature death, and how long can they
An alternative procedure for estimating longevity be protected?
is based on the attempt to measure the most advanced The survival curve captures the concepts needed
age to which people survive in significant numbers. It to compare mortality experiences. The data neces-
can safely be suggested that over most of human sary to plot it are drawn from the life table, initially
existence the modal age at death - the age at which developed as a way to set insurance premiums, but
more individuals died than at any other - was during subsequently put to use in epidemiology, biology,
the first year. Among people surviving early child- and demography. The estimation of survival curves
hood, however, the modal age at death occurred in and other elements of the life table are commonplace
adulthood. Apparently it has advanced over time. A in historical discussion, although they are more of-
life table based on skeletal evidence for a Copper Age ten implicit than explicit because historians seldom
population indicates that the number of postinfant work with periods and populations for which life
deaths peaked at age 46, but late-twentieth-century tables exist.
life tables show a much later peak. For example, a One useful estimate of mortality experience is the
U.S. life table for 1979-81 indicates a postinfant crude death rate, the ratio of deaths in a given year
modal age at death of 83 (Acsadi and Nemeskeri to the mean population during that year. This rate is
1970; U.S. National Center for Health Statistics a function of the age distribution as well as the
1985). Estimates of the species-specific life span or number of deaths at each age. Consider, for example,
values for the modal age at death are used to show the crude death rates for the United States and
capacity for survival. Often expressed as a rectangle, Costa Rica in 1977 - 8.6 and 4.3, respectively. The
this capacity is a statement about how many years of lower rate for Costa Rica means a lower probability
life individuals born at the same time might accumu- of death, but it is lower because the age structure
late if they avoided hazards. was different in the United States rather than be-
These estimates have been less important in mea- cause the risk of death was lower at each age. In fact,
suring and comparing health experience than they Costa Ricans faced a higher mortality risk at most
will become. The transition can be attributed to a ages, but the younger average age offset the differ-
major change in the pattern of human survival. For ence in risk of death.
most of the history of the species, the space of life - The crude death rate is also influenced by migra-
the area represented by the survival rectangle - tion. For example, populations receiving immigrants
contained more years of life lost to premature death of a certain age group, say young adults, will appear
than years survived. Figure IV.4.1 illustrates this to have higher life expectancies based on the record

Table IV.4.1. Abridged life table for Sweden, 1751-90
Proportion Number living
dying in at beginning Number dying Years lived Accumulated Life
Age interval, interval, of age interval, in age interval, in age interval, years lived, expectation,
xtox + 1 9x h Lz Tx e«
0 0.20825 10,000 2,082 8,314 351,935 35.19
1 0.10406 7,918 824 14,884 343,621 43.40
3 0.05642 7,094 400 13,788 328,737 46.34
5 0.06700 6,694 448 32,350 314,949 47.05
10 0.03621 6,246 226 30,663 282,599 45.24
15 0.03527 6,020 213 29,567 251,936 41.85
20 0.04270 5,807 248 28,417 222,369 38.29
25 0.05065 5,559 281 27,092 193,952 34.89
30 0.05957 5,278 315 25,605 166,860 31.61
35 0.06056 4,963 300 24,065 141,255 28.46
40 0.07947 4,663 371 22,387 117,190 25.13
45 0.08611 4,292 369 20,537 94,803 22.09
50 0.10820 3,923 425 18,552 74,266 18.93
55 0.12935 3,498 452 16,359 55,714 15.93
60 0.18615 3,046 567 13,811 39,355 12.92
65 0.25879 2,479 642 10,790 25,544 10.30
70 0.36860 1,837 677 7,463 14,754 8.03
75 0.47839 1,160 555 4,443 7,291 6.29
80 0.63916 605 387 2,059 2,848 4.71
85 0.77971 218 170 789 789 3.62
90+ 1.0 48 48 (123)° (123)° 2.56
"The adaptation supplies the sum of years lived at 90 and higher ages.
Source: Adapted from Fritzell (1953).
of deaths than will more stable societies. Although the age of its members, and the number who die at
there is often no more than fragmentary information each age - or plausible estimates of these quanti-
about age structure or migration, the effects of these ties - it is possible to build a life table such as the
variables may require that the crude death rate be one for Sweden during 1751-90 presented in Table
qualified by a statement concerning its possible dis- IV.4.1. The table begins with a radix, or base
tortion. In addition to reasons already mentioned, population - in this case 10,000. The probabilities
the crude rate may be misleading if, in a regime of death at each age, the basic quantities of the life
prone to epidemics, it is not averaged over several table, are derived from age-specific death rates.
years. Both the death rate and the probability of death at
Age-specific death rates can be compared (over an age have the same numerator - the number of
time and space) in the form of the survival curves in deaths at that age within a specific time period. But
Figure IV.4.1. Comparisons can also be made on the their denominators differ. For the death rate, the
basis of age-standardized death rates, which adjust denominator is the mean population at that age
age-specific rates for a standardized population (this over the period studied, and for the probability of
procedure and others are explained by Shryock et al. dying, it is the population at that age at the begin-
1973). The reason for making these calculations of ning of the period under study. This difference is
death rates is to compare two or more populations on usually minor, except when one is considering the
the same terms, eliminating the effects of differ- probability of death between two ages that are sepa-
ences in age structure. (This procedure can also be rated by a number of years (e.g., from 5 to 10) and
applied to other characteristics according to which except for infants.
mortality or morbidity rates may differ, such as sex, A current, or period, life table makes use of death
residence, occupation, and marital status.) rates for all ages at a given time to provide a cross-
With information about the size of a population, sectional picture of a stationary population. Its val-

ues for life expectancy and other quantities are Because historians often know or can reliably esti-
termed hypothetical because the death rates used to mate the death rate at a few ages but not throughout
construct it apply to people at each age in the cur- the life course, it is helpful to employ model life
rent population; the history it relates refers to a tables to make inferences about other ages or to
hypothetical cohort, because the people alive at this estimate the overall structure of mortality. Model
time may have been subject to different death rates tables are based on the observation that mortality
in past years and may be subject to differences again risks show some regularities over time. Populations
in the future. A cohort, or generation, life table fol- that have low death rates at one age are likely to
lows the experience of one cohort from birth to have low death rates at other ages, and vice versa.
death. Its values are not hypothetical, but a cohort The regularities can be seen by plotting the mortal-
table cannot be constructed until all members of a ity schedule, which consists of a line linking age-
cohort have died. Thus, a current table, like that in specific probabilities of death. (When the change
Table IV.4.1, is preferred for many uses. from one benchmark to another is high, it is conve-
When populations are small, as Sweden's popula- nient to plot values on paper with a vertical logarith-
tion was in the eighteenth century, and when death mic scale. On this scale an exponential rate of
rates fluctuate from year to year, it is customary to change appears as a straight line.) Figure IV.4.2
average experience over several years. Table IV.4.1 shows that the form of the mortality schedule resem-
is also an abridged table, meaning that it provides bles a misshapen W across the survival rectangle.
values only for benchmark ages. Those in between Over time the W-curve has usually shifted down, so
can be interpolated. Because the number of years that at each age lower mortality rates are reported
lived by the cohort at high ages is so small, the for recent, as opposed to past, populations.
custom is to close the life table at an age that is Close scrutiny of life tables from a variety of popu-
lower than that of the oldest survivor and to sum the lations shows that the W-shape is preserved across
years lived at all higher ages. The accumulated time, but that it displays some irregularities. In
years lived by the actual or hypothetical cohort, some populations the risk of death is greater at some
which is the sum of years lived in each interval, ages than it is in other populations. In Figure IV.4.2,
provides the information necessary to calculate life for instance, the angle of change in the mortality
expectancy. From Table IV.4.1 life expectancy at risk varies among the three populations, most evi-
birth (35.2) is the sum of all years lived by the dently at adult ages. As can be seen, the U.S. 1979-
hypothetical cohort (351,935) divided by the radix 81 schedule is lower than the other two, yet its rate
population (10,000); life expectancy at age 20 (38.3) of increase between ages 40 and 80 is steeper. But for
is the sum of years lived after 20 (222,369) divided these variations, model life tables would suggest all
by the number surviving to 20 (5,807). other age-specific mortality rates when only one was
What makes the life table so useful for historical known. Because of these variations, demographers
investigation is its capacity to represent a sequence of have fashioned groups or "families" of model life
events over a long span. Thus, the life table has been tables, each representing a variation on the basic
used to estimate changes in the prevalence of specific form. One widely used collection of model tables
diseases over time. Although the events of interest in provides four families, styled West, North, South,
this essay are mortality and episodes of morbidity, and East, and a variety of mortality schedules or
other events, such as marriage and divorce, can also levels (Coale and Demeny 1966; McCann 1976).
be followed, as can conditional events, such as deaths With model tables, which are most readily conceived
among people already ill. Age-specific death rates are from their survival curves, incomplete information
conditional because they depend on survival to each about mortality experience in a given population
age. The population whose experience is followed can provide the basis for a plausible estimate of
over time may be select in the sense that its members complete experience.
differ in significant ways from the general popula- Life expectancy, which incorporates age-specific
tion. The life table need not begin at birth or be death risks, is a convenient value for making histori-
limited to single events. More complex models treat cal comparisons. Over time, life expectancy at birth
contingent events that occur in stages, such as the has advanced, and the story of that advance is part
evolution of cancer, with its various outcomes and of the history of mortality and the mortality revolu-
probabilities at each stage. The concept can also be tion. Whereas life expectancy is most commonly
applied to the longevity of political regimes or credit used as an estimate of the average remaining life-
instruments. time at birth, it also captures changes in death rates

10,000
6,000
4,000 — •1 ! .it, some representation of maximum survival and by
reporting an age-specific measure of mortality at
several points within the life course, we obtain
2,000| •i
means of detecting more subtle changes in mortal-
1,0001
'-- ity experience. Whereas life expectancy represents
600 fCMedieval Hungary
* !'// / T "=}=
1 the average remaining lifetime, another measure,
j
400 l^~ males and females
200 s^1
X
-/ 1
years of potential life lost (YPLL), compares the
average span achieved with the number of years
i that it can plausibly be supposed a population
100
60
—England / ' '— might survive. Because that value is indefinite, no
40 •"1871-80 / convention yet exists for measuring YPLL. The
IP\\-f—
males only /
U.S. National Center for Health Statistics presently
20
nited States, 1979-81, uses a base of 65 years. That gauge assigns greater
10 y
ales and females —=F
6
/
weight to causes of death the earlier those causes
4 intervene, and no weight to causes that intervene
I at ages above 65.
2 I
Although not yet applied extensively to historical
1 investigations, the YPLL provides a way to think
10 20 30 40 50 60 70 80 90 100
Age (years) about the degree to which different societies succeed
in controlling mortality. If the YPLL is not adjusted
Figure FV.4.2. Mortality risk for medieval Hungary, En-
for changes over time, more modern societies will
gland (1871-80), and the United States (1979-81).
(From Acsadi and Nemeskeri 1970; Commons Sessional systematically appear more successful than earlier
Papers 1884-5; U.S. Decennial Life Tables for 1979- societies because they have higher life expectancies.
81.) But judgments about success need not depend on the
assumption implicit in this comparison, the assump-
tion that all societies have the same potential for
at different ages. During the modern period of mor- increasing the years its members can expect, on aver-
tality decline, which began in the eighteenth cen- age, to live. If the ceiling is adjusted - perhaps using
tury and has not yet ended, the risk of death did not changing modal age at death - different interpreta-
decline in a uniform way across the age spectrum tions of changes in survival may emerge. If the ceil-
(Perrenoud 1979, 1985; Imhof 1985). In northwest- ing is adjusted with an eye on one or a few causes of
ern Europe, for example, the decline during the eigh- death of particular interest, societies can be com-
teenth century was concentrated among infants, pared according to the efficacy of their control over
youths, and young adults. Other age groups joined leading diseases (see Preston, Keyfitz, and Schoen
the shift toward declining risks later. 1971).
Life expectancy commonly appears to increase to
a greater extent when measured at birth than when Quality of Life
measured at higher ages. That is, the risk of death Mortality rates and other statistics derived from
has declined more in infancy (up to age 1) than at them imply that we have measures for the number
any later age. It is often reported that life expec- of years survived. Yet equally measured mortality
tancy at higher ages, especially in adulthood, has levels may represent quite different qualitative expe-
changed relatively little over time. In some ways riences. In search of ways to capture the quality of
this is misleading. Thinking once more in terms of life, researchers have selected mortality indexes be-
the survival rectangle, a disproportion is apparent lieved to be more revealing, such as infant or mater-
in the time at risk. At birth some members of a nal mortality, and have combined vital and economic
population might be expected to live 110 years. But statistics. One index, used widely to compare the
at each higher age their potential survival time is quality of life in Third World countries, is the Physi-
bounded by the human life span; it diminishes as cal Quality of Life Index, which uses a weighted
age rises. In short, life expectancy can also be con- average of several demographic and economic statis-
strued as an indication of how much of the avail- tics (Morris 1979). It has some possibilities for appli-
able space of life has been used. cation to historical societies for which equivalent
By turning our attention toward both birth and data are available.

FV.4. Measuring Morbidity and Mortality 235
A more promising approach to the quality of life

draws on health statistics. Unlike mortality, ill
health - morbidity - is not an unambiguous quan-
tity. Individuals and societies make different deci-
sions about the threshold between health and ill
health, and these decisions raise problems concern-
ing definitions and measurements of ill health.
Some standard gauges rely on diagnostic evidence;
these are encountered in reports of the number of
cases of specific diseases identified in a given region
and period. Other gauges are based on contact with
health institutions or personnel (hospitalizations,
physician visits). Still others depend on evidence
about individual performance, such as restricted ac-
tivity, bed disability, or work time lost; these mea-
sures are often encountered in insurance records and
health surveys. Because different sources provide
different forms of evidence, the important point is to
find a gauge whose definition is consistent (Riley
1989).
Morbidity also differs from mortality in its com- 0 20 25 30 35 40 45 50 55 60 65 70 75 80 85
plexity. Different questions are at issue. A morbid- Age (years)
ity rate may express the number of times members Figure IV.4.3. Morbidity rates for nineteenth-century
of a population fall ill during a period (incidence), Britain. (From Nelson 1982.)
the proportion of the population ill at a given time
(prevalence), or the amount of time spent in illness
by a population during a given period (duration). To
take only the two extreme cases - incidence and with mortality rates to estimate the number of ill-
duration - the age-specific risk of falling sick (inci- health episodes to be expected in the average remain-
dence) is concave and resembles the inside of a ing lifetime or, alternatively, the proportion of life-
shallow bowl, and that of being sick (duration) time remaining to be spent in ill or good health. The
looks like the misshapen W identified earlier. Fig- technique makes use of age-specific morbidity rates
ure IV.4.3 provides examples of these morbidity in combination with mortality risks in the life table.
curves, using Friendly Society records from nine- The health expectation, sometimes called the active
teenth-century Britain (Riley 1987). Like the mor- life expectation, uses the age-specific risks of mortal-
tality schedule, the morbidity schedule may move ity and being sick to estimate the remaining lifetime
up or down over time, a factor influenced by objec- and the portion of that time to be spent in good
tive health experience and by subjective decisions health (Riley 1989).
about the threshold between health and ill health. If changes in ill-health rates paralleled those in
Individual curves are likely to vary from these mortality rates, the two rising or falling together,
forms, especially when the characteristics of the then morbidity risks and health expectation could
population under observation change over time. For be estimated from mortality risks. But investiga-
example, the National Health Interview Survey tion of the association between mortality and mor-
shows a morbidity schedule with a slower rate of bidity suggests that the straightforward form of
increase at higher ages, a factor attributable in this tie - deaths are attributed to ill health - belies
part to the exclusion of institutionalized members the statistical and population-level associations.
of the population from the survey (National Center Rates of falling sick and being sick change indepen-
for Health Statistics). More investigations of health dently of mortality rates, which is to say that the
experience in historical societies will help identify risk of dying once one is sick changes over time.
the causes of variation (Larsen 1979; Beier 1985; The association is conditioned by environmental
Pelling 1985). forces, such as therapeutic regime or standard of
Morbidity rates in turn can be used in association living, and by changes in the composition of the

ri
1,000
population that can be attributed to mortality. For 600
example, insurance records and health surveys 400 JIJ
T//
show that the mortality decline of the twentieth 200
century has been accompanied by increased dura-
100 /
tion of ill health at each age (Alter and Riley
1989).
In other words, the proportion of people dying
: 60
40 j1— -181 i-40- /
from a given disease or injury - the case fatality ; 20 \ '' y / /J /
Mai
rate — has shifted. Changes have occurred in the 10 \
percentage of people surviving, a concept dramati- 6
—i y~v em ale s
cally illustrated by the history of diseases that vary 4 1—1
/
in virulence or that cause death much more often / /
among people with no prior contact with them than )79-f 3
1.0 ^ <
among people relatively resistant to them, and fa- .6 UMa les£
miliar also in terms of changes in the efficacy of y J—
therapies. The case fatality rate is a useful way to
.4
L Jr *-*
measure the severity of diseases that have a short f$ Females
course. For chronic diseases, however, it is neces- 0 10 20 30 40 50 60 70 80 90 100
sary to consider the prolonged duration of an ail- Age (years)
ment and the likelihood of death from another
cause during its course. A related notion, which Figure IV.4.4. Mortality schedules for Sweden, 1816-40
might be termed case duration, is the time between and 1979-83. (From Sundbarg 1970; Statistisk drsbok
onset and resolution. That period may change as for Sverige 1986.)
diagnostic practices shift or as a population's view
of the ill-health threshold or its recognition of ill-
health episodes changes. And it may also shift both directions: Greater wealth is partly an effect of
when new therapies are introduced. Because, with lower health risks and partly a cause.
notable exceptions, case fatality rates as high as 50
percent have been rare, it is apparent that most ill-
health episodes are resolved in recovery. Even in Disease-Specific Measurements
acute diseases, duration has been an important ele- Mortality records identifying cause of death lend
ment in the disabling effects of illness, injury, and themselves to disease-specific measurements and to
collective violence. analyses of trends of individual diseases and dis-
ease profiles (Preston et al. 1971; McKeown 1976).
Although the size of the population at risk of death
Variations is often unknown for periods before the twentieth
Some leading causes of variations in mortality and century, the annual number of deaths constitutes a
morbidity include sex, income, residence, season, denominator.
and disease profile. Separate tables are usually cal-
culated for each sex because of differences in male
and female experience, which are partly biological Heterogeneity
and partly environmental in origin. Figure IV.4.4 Average experience within a group can be a useful
shows two forms of this variation by exhibiting indicator, but there are many instances in which
mortality curves for men and women in Sweden the average, and variations on it, are misleading.
during 1816-40 and 1979-83. In recent centuries These occur when the distribution of vital events
male mortality has exceeded female mortality at within a population is uneven. Thus, life expec-
most ages, a characteristic that seems to suggest tancy at birth is a misleading measure of survival
a biological advantage for the latter (Verbrugge in seventeenth-century Europe because deaths oc-
1985). curred with two modes, infancy and late adulthood.
Socioeconomic status is another well-recognized This example is well known, and authorities regu-
cause of variation in mortality. Wealthier members larly point to the rapid increase in life expectancy
of a population, in the aggregate, face lower health among people who survived infancy and early child-
risks, although the causation appears to operate in hood. Irregular distributions - those taking a form

other than the normal or bell curve - are often en- Coale, Ansley J., and Paul Demeny. 1966. Regional model
countered. They signal something called heteroge- life tables and stable populations. Princeton, N.J.
neity - incompatible or nonproportionate elements. Curtin, Philip D. 1986. African health at home and
For example, future health is in part a function of abroad. Social Science History 10: 369-98.
prior health, so that some authorities suggest that Dublin, Louis I., Alfred J. Lotka, and Mortimer Spie-
a cohort divides itself into two modes, one with a gelman. 1949. Length of life: A study of the life table.
New York.
high and the other with a low propensity to be sick.
Fritzell, Yngve. 1953. Overlevelsetabeller for Sverige for
Thus, an average figure - such as the average age 1751-1815. Statistisk tidskrift, New Ser, 2: 406-10.
for retirement, 65 - may misstate cohort experience Great Britain, House of Commons. 1884-5. Sessional Pa-
in such circumstances. pers. Supplement to the 45th annual report of the
Members of the same cohort may have disparate Registrar-General of Births, Deaths and Marriages in
health experiences, in ways just suggested, but the England 17(365): vii-viii.
likelihood of disparity is greater still when different Imhof, Arthur E. 1985. From the old mortality pattern to
cohorts are compared. The health experiences of a the new: Implications of a radical change from the
cohort are shaped by the circumstances encoun- sixteenth century to the twentieth century. Bulletin of
tered at each stage in life, so that each cohort accu- the History of Medicine 59:1-29.
mulates a unique health history. In modern ad- Larsen, 0ivind. 1979. Eighteenth-century diseases, diag-
vantaged societies these differences remain, but nostic trends, and mortality. Paper presented at the
Fifth Scandinavian Demographic Symposium.
their magnitudes are such that they have little
Manton, Kenneth G., and Eric Stallard. 1984. Recent
measured effect on basic vital statistics. Thus, life trends in mortality analysis. Orlando, Fla.
expectancy at a given age varies little in the short McCann, James C. 1976. A technique for estimating life
run. But in historical populations the disparity may expectancy with crude vital rates. Demography 13:
be marked. In seventeenth-century England, life 259-72.
expectancy at birth shifted dramatically from co- McKeown, Thomas. 1976. The modern rise of population.
hort to cohort. The population alive in 1750, for London.
example, included individuals who had survived Morris, Morris David. 1979. Measuring the condition of the
such disparate events as the plague of 1665 and the world's poor: The physical quality of life index. New
as yet incompletely identified forces of the mid- York.
eighteenth century favoring mortality decline. Spo- Neilson, Francis G. P. 1882. The rates of mortality and
radic epidemics caused the number of deaths and sickness according to the experience of the five years,
the death rate to fluctuate, with the result that the 1871-1875, of the Ancient Order of Foresters Friendly
Society. London.
number of years lived by each cohort varied be-
Palmore, James A., and Robert W. Gardner. 1983. Measur-
tween wide boundaries (Wrigley and Schofield ing mortality, fertility, and natural increase: A self-
1981). This shifting cohort pattern is a historical teaching guide to elementary measures. Honolulu.
rhythm that deserves recognition. Pelling, Margaret. 1985. Healing the sick poor: Social pol-
James C. Riley icy and disability in Norwich, 1550-1640. Medical
History 29: 115-37.
Perrenoud, Alfred. 1979. La population de Geneve du
Bibliography seizidme au debut du dix-neuvieme si£cle: Etude
Acsadi, Gy., and J. Nemeske'ri. 1970. History of human life dimographique. Geneva.
span and mortality, trans. K. Balas. Budapest. 1985. Le biologique et l'humain dans le d£clin seculaire
Alter, George, and James C. Riley. 1989. Frailty, sick- de la mortality. Annales: Economies, sociH€s, civili-
ness, and death: Models of morbidity and mortality sations 40: 113-35.
in historical populations. Population Studies 43: 2 5 - Pressat, Roland. 1978. Statistical demography, trans.
45. Damien A. Courtney. New York.
Beier, Lucinda McCray. 1985. In sickness and in health: Preston, Samuel H., ed. 1982. Biological and social aspects
A seventeenth-century family's experience. In Pa- of mortality and the length of life. Liege.
tients and practitioners: Lay perceptions of medicine Preston, Samuel H., Nathan Keyfitz, and Robert Schoen.
in pre-industrial society, ed. Roy Porter, 101-28. 1971. Causes of death: Life tables for national popula-
Cambridge. tions. New York.
Benjamin, B., and H. W. Haycocks. 1970. The analysis of Riley, James C. 1987. Ill health during the English mortal-
mortality and other actuarial statistics. Cambridge. ity decline: The Friendly Societies' experience. Bulle-
Chiang, Chin Long. 1984. The life table and its applica- tin of the History of Medicine 61: 563-88.
tions. Malabar, Fla. 1989. Sickness, recovery and death. London.

Shryock, Henry S., et. al. 1973. The methods and materials this avenue is obviously limited by the scanty sys-
of demography. Washington, D.C. tematic evidence at our disposal (Riley and Alter
Sundbarg, Gustav. 1970. Bevolkerungsstatistik Schwedens, 1986). Another approach has been to consider mor-
1750-1900. Stockholm. tality an integral component of welfare and, in
Sweden, Statistiska Centralbyrarn. 1986. Statistisk drrs- fact, to incorporate mortality into the conventional
bok for Sverige: 1986. Stockholm. index of the material standard of living (William-
U.S. National Center for Health Statistics. [Annual] Cur-
rent estimates from the national health interview sur-
son 1981, 1982; Davin 1988). Yet this attempt to
vey. Vital and health statistics, Ser. 10. Washington, collapse the biological and material standards of
D.C. living into a single index is vexed by the inherent
1985. U.S. decennial life tables for 1979-81. Vol. 1, No. 1. difficulty of gauging the monetary value of human
Department of Health and Human Services Publ. No. life.
(PHS) 85-1150-1. Washington, D.C. Still another promising approach, and one with an
Vallin, Jacques, John H. Pollard, and Larry Heligman, abundant evidential basis from the seventeenth cen-
eds. 1984. Methodologies for the collection and analy- tury onward, is anthropometric history, meaning the
sis of mortality data. Liege. analysis of secular changes in human height, weight,
Verbrugge, Lois M. 1985. Gender and health: An update and weight for height (Tanner 1981; Fogel 1987;
on hypotheses and evidence. Journal of Health and Komlos 1987; Ward 1987; Riggs 1988; Cuff 1989;
Social Behavior 26: 156-82. Floud and Wachter 1989). This way of looking at the
Wrigley, E. A., and R. S. Schofield. 1981. The popu-
issue acknowledges outright the inherent multidi-
lation history of England, 1541—1871. Cambridge,
Mass. mensionality of the standard of living, and further-
more assumes that the several dimensions might be
orthogonal to one another, which is to say that they
generally cannot be collapsed into one indicator. The
agenda of this research program is to construct in-
dexes of the biological standard of living of various
populations over time, by social class and gender if
possible, and to ascertain how this indicator corre-
IV.5 lates with the material standard of life convention-
Stature and Health ally conceived.
Anthropometric measures are an important part
of this research program, because they enable one to
In conventional terms the standard of living has quantify nutritional status, which hitherto has
become practically synonymous with a material eluded historians. This line of reasoning is based on
standard, and consequently the concept has most medical research, which has established beyond
often been equated with and measured by per cap- doubt that the net cumulative nutritional intake of a
ita income. Yet it can be interpreted much more population has a major influence on its average
broadly to encompass the psychological and bio- height, with maternal nutrition also playing a sig-
logical dimensions of human existence (i.e., the nificant role (Fogel, Engerman, and Trussel 1982;
quality of life in all of its manifestations). Dis- Falkner and Tanner 1986). Thus, height at a particu-
tinguishing among these components of well-being lar age, as well as the terminal height attained by a
would not add much that is conceptually meaning- population, is a measure of cumulative net nutri-
ful to our understanding of the past if they all tion: the food consumed during the growing years
correlated positively and perfectly with one an- minus the claims on the nutrients of basal metabo-
other. But recent empirical evidence has tended to lism, of energy expenditure, and of encounters with
show the importance of not conflating them into disease (Tanner 1978). As nutritional status in-
one concept. creases, more calories and protein are available for
Historians have begun to explore ways to illumi- physical growth, and the closer individuals and popu-
nate this issue from another perspective, namely lations come to reaching their genetic potentials of
by considering the biological standard of living as height.
an equally valid measurement of human well- The terminal height an individual reaches in a
being (Komlos 1989). One approach has been to given population is also influenced by genetic fac-
study the health of historical populations, though tors, but this consideration does not affect studies of

IV.5. Stature and Health 239
the evolution of human height as long as the genetic metric research have been quite revealing. Height
composition of the population is not dramatically has been shown to correlate positively with socioeco-
altered by large-scale migration. nomic variables. For instance, the height of French
Holding the genetic composition of the population recruits born in the late 1840s depended on their
constant, nutritional status, measured by height, is education and wealth. Illiterates averaged 164.3 cm,
at once an indicator of exposure to disease and of whereas those able to read and write were 1.2 cm
health in general. It correlates positively with food taller. Presumably literate men were wealthier and
consumption and with life expectancy, and conse- spent more time at education and less at labor than
quently shows how well the human organism did illiterate men (Le Roy Ladurie and Bernageau
thrives in its particular economic, epidemiological, 1971). Another interesting finding is that by the
and social environment (Friedman 1982). Conse- early eighteenth century the height of the colonial
quently, height is a much more encompassing vari- North American population was already well above
able than are real wages and has the advantage in a European norms, which implies that the ecological
historical context of being available for groups, such (and nutritional) environment of the New World was
as subsistence peasants and aristocrats, for whom especially favorable from the human-biological
real wages are not pertinent. point of view (Sokoloff and Villaflor 1982). Although
Food consumption in prior centuries was the ma- slaves appear to have been neglected as children,
jor component of total expenditure (Cipolla 1980), even they benefited from the abundance of food in
and therefore height can also be used as a proxy for colonial North America, because as adults their
real income. The positive relationship between height was close to that of the white population and
height and income has been amply documented for above that of the European peasantry (Steckel
twentieth-century populations, for which both var- 1986). In contrast to that of early North Americans,
iables are available (Steckel 1983; Brinkman, the nutritional status of the poor boys of London
Drukker, and Slot 1988). Yet some caveats are in seems to have been truly miserable at the end of the
order. The distribution of income has been found to eighteenth century. They were shorter than practi-
affect the mean stature of a population. Further- cally all modern populations, with the possible excep-
more, the composition of the food consumed is also tion of such groups as the Lume of New Guinea
of some consequence, because the mix of calorie and (Eveleth and Tanner 1976; Floud and Wachter
protein intake is important to the growth process. 1982).
This question of mix is complicated by the fact that Yet there were several instances in which the
protein is made up of many amino acids, and it is trends in heights and in per capita incomes diverged
the combination of amino acids, not only their abso- from one another. They occurred during the early
lute quantity, that ultimately influences growth stages of rapid economic growth: in east central Eu-
and physical well-being. Finally, food consumption rope during the second half of the eighteenth cen-
obviously depends not only on real income, but also tury, in late-nineteenth-century Montreal, and in
on the price of food relative to all other products. In the antebellum United States. In the United States,
a society in which commercialization has not pro- the stature of army recruits declined by more than 2
ceeded very far, the availability of industrial prod- centimeters beginning with the birth cohorts of the
ucts might be limited and therefore their prices are 1830s, even though according to conventional indica-
high. Once the availability of industrial goods in- tors the economy was expanding rapidly during
creases through market integration, the structure these decades. Between 1840 and 1870 per capita net
of food consumption might change discontinuously national product increased by more than 40 percent
and rapidly as a consequence of substitution. Eco- (Gallman 1972; Fogel 1986; Komlos 1987). In the
nomic development might also lead to the introduc- Habsburg monarchy the decline in stature during
tion of new products, such as coffee, tea, or sugar, the course of the second half of the eighteenth cen-
that could be perceived as substitutes for some nu- tury was at least 3 but more nearly 4 centimeters. A
tritious food items. This, in turn, may lead to shifts similar pattern was found for industrializing Mon-
in the demand for food independently of any treal. The birth weight of infants there fell after the
changes in income per capita. These constrictions 1870s, indicating that the nutritional status of the
indicate clearly that the analysis of the stature of a mothers was declining. Such anthropometric cycles
population is not a mechanical exercise. were not known to exist previously (Ward and Ward
In spite of these caveats, the results of anthropo- 1984; Komlos 1985).

Determining the extent to which these episodes whose income rose as fast as food prices decreased
were accompanied by a deterioration in the epidemio- their food consumption because the price elasticity
logical environment requires further study, but it is of demand for food was greater than the income
already clear that all three were, in fact, character- elasticity.
ized by a decline in per capita nutrient intake. In the In east central Europe the fall in nutritional lev-
New World, periods of nutritional stress were accom- els was initiated not by sectoral shifts from the
panied by rapid economic growth, during which, by agricultural to the industrial sector, but by rapid
conventional measures, the material standard of liv- population growth pressing on scarce resources. In
ing was rising. This might be considered an anomaly contrast to the situation in the United States, in
because an increase in per capita income normally Europe the quantity of land was fixed, and there-
implies that food consumption, too, is rising. It before population growth ran into Malthusian ceilings
comes less anomalous, however, once one notes that (Komlos 1985). The subsequent limited quantity
although income determines the position of the de- and the rise in food prices meant a fall in consump-
mand curve for food, an individual who purchases tion, particularly of meat products, because the
food at higher market prices might consume less of it price of a calorie is much greater if purchased
than a self-sufficient peasant isolated from the mar- through meat than if purchased through grain.
ket by high transport and information costs, even if This fall in the intake of animal protein, an impor-
the measured income of the former is larger than tant component of nutritional status, made it more
that of the latter. Moreover, contemporaneously with difficult for the body to fight off nutrition-sensitive
the decline in human stature in the antebellum diseases. Of course, during the early stages of eco-
United States, the crude death rate was increasing nomic growth, individuals were usually not well
even as per capita income was rising, supporting the informed about the importance of a balanced diet
notion that the biological standard of living was and therefore were unaware that changing their
declining (Pope 1986). food habits would impinge on their nutritional sta-
The divergence in biological and conventional in- tus and health.
dicators of well-being can be explained by several To be sure, not all members of the society experi-
other factors. The examples of economic growth al- enced nutritional stress during the early stages of
ready provided were accompanied by rapid popula- economic development. In the United States the in-
tion growth and by urbanization. This increased the come of the urban middle class rose sufficiently in
demand for food at a time when the agricultural the 1830s and 1840s to keep pace with the rise in the
labor force was growing more slowly than the indus- price of foodstuffs and, at least initially, to permit
trial labor force and the gains in labor productivity that group to maintain its nutritional status. Not
in agriculture were still small. Hence, supply did until the Civil War disrupted the flow of nutrients
not generally match the increased demand for food, did their biological well-being begin to suffer as
and food prices rose relative to those of all other well. In a similar fashion, Habsburg and German
goods. aristocrats were not affected by the Malthusian cri-
The relative price of food also rose because rapid sis of the eighteenth century, but rather increased
technological change in the industrial sector brought their height advantage considerably compared with
with it a decline in all other prices. The rise in the the lower classes (Komlos 1986, 1990).
relative price of food was greatest in areas that Height therefore correlates positively with social
had previously been isolated from industrial cen- class. In Germany, aristocrats were 3 to 7 centime-
ters. Early stages of growth were generally ac- ters taller than middle-class boys throughout adoles-
companied by market integration, and this meant cence. The latter in turn were about 8 centimeters
that in some regions the price of food, relative to taller than boys with lower social standing of the
that of all other goods, rose sharply. This brought same age. Boys attending prestigious military
with it the potential for large movements along schools in Austria, England, France, and Germany
the demand curve for food in these regions. In addi- were all much taller than the population at large.
tion, new products changed consumers' tastes and For instance, adolescents of the English gentry were
might also have been seen as substitutes for tradi- at least 20 centimeters taller than the nutritionally
tional food products. Thus, although the real wage deprived slum boys of London (Floud and Wachter
might have risen in the industrial sector, it did not 1982; Komlos 1990).
rise as fast as food prices. Even farm operators Yet another pattern is that propinquity to nutri-

ents is a crucial determinant of nutritional status vironment. Another probable reason for the dif-
in preindustrial societies and in societies caught in ficulty of maintaining nutritional status during
the early stages of economic development. In such the initial phase of economic development is that
circumstances per capita income is not as important income distribution is more uneven during such
a determinant of human stature as is the availabil- phases than at other times. The changes in entitle-
ity of food. In the eighteenth-century Habsburg ment to goods, with the rise in food prices, cause
monarchy, recruits from areas with a large agricul- many to lose their ability to "command food" (Sen
tural sector, even if the economy was relatively 1981).
underdeveloped, were well nourished by the stan- In summary, because height is a good proxy for
dards of the time compared with those from indus- nutritional status, it is employed to measure the
trially more advanced provinces. Being isolated biological well-being of populations of the past. The
from markets by high transportation and transac- biological standard of living indicates the extent to
tions costs had its advantages as long as population which ecological circumstances are favorable to the
density did not exceed the carrying capacity of the functioning of the human organism. The concept
land, because the subsistence peasant families had encompasses such aspects of human biology as life
little choice but to consume all of their own food expectancy, morbidity, and public health. Moreover,
output. Once they became integrated into a larger in the developed economies of the twentieth century,
market, however, rising food prices and their sales height correlates positively with per capita income
of agricultural commodities tended to impinge on not only because of the rise in food intake, but also
their own food intake. because of improvements in public health and medi-
Similarly in the antebellum United States, white cal technology.
southern men were 1.5 centimeters taller than their Yet the evidence presented here also implies that
counterparts in the more industrial North, even economic growth can be accompanied by a fall in
though per capita income was greater in the latter nutritional status. Hence, the biological standard of
region (Margo and Steckel 1983). The same pattern living can diverge from real incomes during the
held between England and its colonies. Although in early stages of industrialization. This pattern is not
the eighteenth century England had a higher per anomalous, because gross national product has gen-
capita income, perhaps by as much as 25 percent, its erally grown more rapidly than the agricultural
soldiers were considerably shorter than their coun- sector, and in some cases per capita food consump-
terparts in the British colonies of North America. A tion has fallen. But it does mean that per capita
century later, Irish-born recruits into the Union income can be an ambiguous measure of welfare
army during the Civil War were also taller than during the early stages of economic development. A
soldiers born in England, although English per cap- rise in average per capita income is of ambiguous
ita income was certainly higher than that of the benefit if it is distributed unevenly and if some
Irish (Mokyr and O'Grada 1988). members of the population lead less healthy lives
Indeed, the importance of remoteness for nutri- as a by-product of economic change. Of course, in
tional status can be seen from the fact that in 1850 the long run the ambiguity disappears, because the
the tallest population in Europe was probably found productivity of the agricultural sector improves and
in Dalmatia, one of the least developed areas of the relative food prices decline. Hence, the share of food
Continent. This relationship reappears in an as- in consumer budgets fell in Europe from about 75
tounding form at the end of the century: Although percent to about 25 percent, or even less, of income.
Bosnia-Herzegovina was certainly among the least Yet for the early stages of industrialization recent
developed parts of the Habsburg monarchy, its popu- anthropometric research indicates that the conven-
lation was nonetheless the tallest (Austrian Bureau tional indicators of welfare are incomplete; they
of Health 1910). must be supplemented with a measure, such as
All of this evidence corroborates the notion that human stature, that illuminates the biological well-
being close to the supply of food during the early being of a population.
stages of industrialization had a positive effect on John Komlos
nutritional status, possibly because the costs of ob-
taining food were lower. In addition, rural pop- Bibliography
ulations doubtless benefited from a lower exposure Austrian Bureau of Health. 1910. Militar-Statistisches
to disease than those crowded into an urban en- Jahrbuch fur das Jahr 1871. Vienna.

Brinkman, Henk Jan, J. W. Drukker, and Brigitte Slot. teenth century Habsburg monarchy: An anthropomet-
1988. Height and income: A new method for the esti- ric history. Princeton, N.J.
mation of historical national income series. Explora- 1990. Height and social status in eighteenth-century
tions in Economic History 25: 227-64. Germany. Journal of Interdisciplinary History 20:
Cipolla, Carlo. 1980. Before the industrial revolution, Euro- 607-22.
pean society and economy, 1000—1700, 2d edition. New Le Roy Ladurie, Emmanuel, and N. Bernageau. 1971.
York. Etude sur un contingent militaire (1868): Mobilite
Cuff, Timothy. 1989. Body mass index of West Point cadets geographique, delinquance et stature, mises en rap-
in the nineteenth century. Unpublished manuscript, port avec d'autres aspects de la situation des conscrits.
University of Pittsburgh, Department of History. Annales de demographie historique, 311—37.
Davin, Eric. 1988. The era of the common child: Infant and Lindert, Peter, and Jeffrey Williamson. 1983. English
child mortality in mid-nineteenth century Pittsburgh. workers' living standards during the industrial revolu-
Unpublished manuscript, University of Pittsburgh, tion. Economic History Review, 2d Ser., 36: 1-25.
Department of History. Margo, Eobert, and Richard H. Steckel. 1983. Heights of
Eveleth, Phyllis B., and James M. Tanner. 1976. World- native born northern whites during the antebellum
wide variation in human growth. Cambridge. period. Journal of Economic History 43: 167-74.
Falkner, Frank, and James M. Tanner, eds. 1986. Human McMahon, Sarah. 1981. Provisions laid up for the family:
growth, a comprehensive treatise, 2d edition. New Toward a history of diet in New England, 1650-1850.
York. Historical Methods 14: 4-21.
Flinn, Michael. 1984. English workers' living standards Mokyr, Joel, and Cormac O'Grada. 1988. Poor and get-
during the industrial revolution: A comment. Eco- ting poorer? Living standards in Ireland before the
nomic History Review 37: 88-92. Famine. Economic History Review, 2d Ser., 41: 209-
Floud, Roderick. 1990. The heights of the British. Cam- 35.
bridge. Pope, Clayne L. 1986. Native adult mortality in the U.S.:
Floud, Roderick, and Kenneth Wachter. 1982. Poverty and 1770-1870. In Long-term changes in nutrition and the
physical stature, evidence on the standard of living of standard of living, Eighth Congress of the Interna-
London boys, 1770-1870. Social Science History 6: tional Economic History Association, ed. Robert W.
422-52. Fogel, 76-88. Berne.
Fogel, Robert W. 1986. Nutrition and the decline in mor- Riggs, Paul. 1988. The standard of living in Britain's
tality since 1700: Some preliminary findings. In Celtic fringe, c. 1800-1850: Evidence from Glaswe-
Long term factors in American economic growth, ed. gian prisoners. Unpublished manuscript, University
Stanley L. Engerman and Robert E. Gallman, 439- of Pittsburgh, Department of History.
555. Chicago. Riley, James, and George Alter. 1986. Mortality and mor-
Fogel, Robert W., Stanley L. Engerman, and James bidity: Measuring ill health across time. In Long-term
Trussel. 1982. Exploring the uses of data on height: changes in nutrition and the standard of living,
The analysis of long-term trends in nutrition, labor Eighth Congress of the International Economic His-
welfare, and labor productivity. Social Science History tory Association, ed. Robert W. Fogel, 97-106. Berne.
6: 401-21. Rule, John. 1986. The laboring classes in early industrial
Friedman, Gerald C. 1982. The heights of slaves in Trini- England, 1750-1850. London.
dad. Social Science History 6: 482-515. Schwartz, L. D. 1985. The standard of living in the long
Gallman, Robert E. 1972. The pace and pattern of Ameri- run: London, 1700-1860. Economic History Review,
can economic growth. In American economic growth: 2d Ser, 38: 24-41.
An economist's history of the United States, ed. Lance Sen, Amartya. 1981. Poverty and famines: An essay on
E. Davis, Richard A. Easterlin, and William Parker, entitlement and deprivation. Oxford.
15-60. New York. 1987. The standard of living. Cambridge.
Komlos, John. 1985. Stature and nutrition in the Habs- Sokoloff, Kenneth, and Georgia C. Villaflor. 1982. The
burg monarchy: The standard of living and economic early achievement of modern stature in America. So-
development in the eighteenth century. American His- cial Science History 6: 453—81.
torical Review 90: 1149-61. Steckel, Richard. 1983. Height and per capita income.
1986. Patterns of children's growth in east central Eu- Historical Methods 16: 1-7.
rope in the eighteenth century. Annals ofHuman Biol- 1986. A peculiar population: The nutrition, health and
ogy 13: 33-48. mortality of American slaves from childhood to matu-
1987. The height and weight of West Point cadets: Di- rity. Journal of Economic History 46: 721—42.
etary change in antebellum America. Journal of Eco- Tanner, James M. 1978. Fetus into man: Physical growth
nomic History 47: 897-927. from conception to maturity. Cambridge.
1989. Nutrition and economic development in the eigh- 1981. A history of the study ofhuman growth. Cambridge.

Thirsk, Joan. 1983. The horticultural revolution: A cau- Ward, Peter W., and Patricia C. Ward. 1984. Infant birth
tionary note on prices. Journal of Interdisciplinary weight and nutrition in industrializing Montreal.
History 14: 299-302. American Historical Review 89: 324-45.
Tunzelmann, G. N., von. 1985. The standard of living Williamson, Jeffrey G. 1981. Urban disamenities, dark
debate and optimal economic growth. In The econom- satanic mills and the British standard of living de-
ics of the Industrial Revolution, ed. Joel Mokyr, 207- bate. Journal of Economic History 44: 75—84.
26. Totowa, N.J. 1982. Was the industrial revolution worth it? Disameni-
Ward, Peter W. 1987. Weight at birth in Vienna, Austria, ties and death in 19th century British towns. Explora-
1865-1930. Annals of Human Biology 14: 495-506. tions in Economic History 19: 221—45.

PART V
The History of Human Disease in the

World Outside Asia

V.I. Pre-Roman World 247
potential of contracting animalborne diseases (zoo-

noses). Urbanism brought increased population
Diseases in the Pre-Roman sizes and densities and a greater likelihood of expo-
sure to dropletborne infectious agents. Extended
trade and commerce, activities associated with ur-
ban society, enhanced the spread of infectious organ-
isms between geographic areas (Cockburn 1963).
In the past 15,000 years, epochal social and cultural However significant these changes were, direct
changes have created fundamentally different rela- evidence of their having caused disease is difficult to
tionships between humankind and the environment. obtain. Paleopathology, the study of ancient disease,
One of the most important innovations has been the is hampered by several limitations. Two of the most
domestication of plants and animals, a major factor important of these are the nature of our sources and
in the gradual establishment of agriculture as the the way in which we study and interpret the data.
world's predominant economic base. The develop- Our current sources of data on disease in the pre-
ment of agriculture brought an increase in seden- Roman world include ancient texts that describe dis-
tism, in which human groups lived in more or less ease, archeological cultural artifacts that portray
permanent communities. the effects of disease on the human body, and human
Associated with farming was the domestication of skeletal and mummy remains recovered from
animals and, in some societies, nomadic pastoral- archeological sites. There are many difficulties in
ism. By about 6000 B.C., animal husbandry pro- utilizing some of these sources.
vided a relatively widespread and stable source of Although skeletal and mummy remains would ap-
high-quality protein in the Near East. Moreover, the pear to be a promising source of information, most
protein was typically produced in ways that did not diseases suffered by individuals in antiquity, and
compete directly for agricultural land resources. Do- many that caused death, leave no evidence in soft-
mestic herds grazed on agricultural land after the tissue remains or in bone as observed by gross or
harvest (Bentley 1987) or on land that was fallow, microscopic methods. In addition, attributing the
marginal, or inadequate for farming. relatively few conditions that do occur in the skele-
The greater control that agriculture and the do- ton to a specific morbid syndrome is often difficult.
mestication of animals gave people over food produc- These problems make the interpretation of the bio-
tion resulted in food surpluses. Surplus food created logical significance of skeletal disease difficult. How-
the potential for the emergence of specialists such as ever, although our sources may have limitations,
craftsmen, merchants, and a ruler class, which are much can be learned if these restrictions are kept in
essential components of urban society, another ma- mind. Even tentative observations can provide the
jor social change. Urbanism began in the Near East basis for further clarification and/or debate. We are
during the Chalcolithic Age (c. 4000-3200 B.C.) but hopeful that current avenues of research will pro-
had its major efflorescence during the Early Bronze vide new data and stimulate the development of new
Age (c. 3200-2000 B.C.) methods. For example, the work of M. Y. El-Najjar
The advent of agriculture, the domestication of and colleagues (1980) and that of N. Tuross (1991)
animals, and the development of urbanism had a suggest the possibility of recovering immunoglobu-
significant impact on human health. Although agri- lins from archeological tissues, including bone.
culture dramatically increased the calories that The second and perhaps most serious limitation to
could be produced by a given individual, the empha- the study of prehistoric human disease is that im-
sis on a few cultigens increased the vulnerability of posed by the methodological and theoretical inade-
agricultural societies to famine and malnutrition quacies of current research. There is no universally
(Cohen 1984a). Innovations associated with agricul- accepted descriptive methodology that ensures com-
ture, such as irrigation, greatly heightened expo- parability between published sources, which ham-
sure to some infectious diseases. Plowing the soil pers any attempt to integrate the data presented in
itself probably increased the risk of acquiring fun- the literature. In addition, as will be discussed in
gal diseases. Sedentary communities, unlike hunt- relation to infectious diseases, paleopathology has
ing and gathering societies, which usually changed not yet reached a theoretical consensus on the signifi-
their living areas often, lived amid their own detri- cance of many skeletal diseases.
tus with its inherent risk of causing disease (Wells In spite of the limitations and problems in the
1978). The domestication of animals brought the field of paleopathology, we have attempted some in-

248 V. Human Disease in the World Outside Asia
terpretation of the data. In addition, we have in- Finally, a helpful distinction can be made between
cluded findings of other researchers who have specific and nonspecific disease (Buikstra 1976). Spe-
sought evidence of trends of certain conditions for cific disease refers to those conditions in a skeleton
sites in specific geographic regions. However, we that can be attributed to one of a fairly limited
strongly emphasize the tentative nature of these number of disease syndromes (e.g., anemia or lep-
findings and the need for greater methodological rosy). Nonspecific disease is an abnormal condition
rigor in future research. of a skeleton (e.g., periostitis, dental hypoplasia, and
In this essay, we focus on research involving hu- Harris's lines) that cannot be attributed to a discrete
man physical remains from the Old World, begin- morbid syndrome. In a sense, specific and nonspe-
ning with the Mesolithic period (about 10,000 B.C. cific diseases represent the polar extremes of a con-
in the Near East) and ending with the emergence of ceptual gradient.
the Roman Empire. Because of the considerable chro- In samples of archeological human skeletons, ap-
nological and geographic scope of the essay, and be- proximately 15 percent show evidence of significant
cause of the complexity of understanding disease in disease. The incidence of specific disease syndromes
antiquity, particularly in relation to modern medical varies among geographic areas and cultures, as does
experience, we briefly discuss some relevant con- the expression of diseases, but generally the most
cepts, trends, and factors. common pathological conditions seen in archeolog-
First, it must be emphasized that the transitions ical human skeletons include trauma, infection, ar-
between hunter-gatherer, agricultural, and urban thritis, and dental disease. These conditions will be
societies occurred at various times in different areas the focus of our discussion. In addition, because of
of the Old World. For example, while the Near East current interest, we will briefly discuss anemias and
was in the early stages of farming with some town tumors. Most of the other general categories of dis-
life (c. 8000-5000 B.C.), Europe was still at a ease (e.g., dysplasias and metabolic diseases) are rep-
hunter-gatherer subsistence level. Therefore, at a resented by at least one syndrome that affects the
specific point in time the health problems encoun- skeleton, but archeological evidence for these syn-
tered by the human populations in these two areas dromes tends to be rare. Differential diagnosis is of-
were different. ten difficult, and low frequencies create severe limita-
Second, the relationship between humans and dis- tions in reaching paleoepidemiological conclusions.
ease is continually evolving. Over time, the viru-
lence of infectious organisms tends to become attenu- Trauma
ated, while the human host population tends to Trauma is a pathological condition that varies in type
evolve a more effective immune response to infec- and frequency depending on culture and physical en-
tious organisms (Cockburn 1963). The implication of vironment. Trauma to the skeleton can be divided
these two trends is that with the passage of time a into two categories: (1) accidental or unintentional
given infectious disease is likely to become a less trauma, such as fracture that results from a fall, and
serious threat to life and develop a more chronic (2) intentional trauma or injury purposefully caused
pathogenesis. by another human being. Intentional trauma in-
Third, the expression of disease can be influenced cludes injury resulting from violence (Figure V. 1.1) in
by many factors (e.g., age and environment). In gen- warfare or interpersonal conflict, which may result in
eral, the risk of disease increases with the age of the broken long bones or a fractured skull, as well as
individual. With the exception of many Third World trauma induced by a therapeutic procedure.
countries, people today live 30 to 40 years longer One of the most remarkable forms of trauma in
than they did in antiquity. This greatly increased antiquity was a surgical procedure known as treph-
longevity is a very recent development in human ination, whereby a portion of the skull was re-
history and means that the prevalence of many dis- moved, great care being taken to avoid penetration
eases common among modern Western peoples, such of the underlying dura. Trephination was first re-
as cancer and heart disease, is probably much ported for Paleolithic Poland (Gladykowska-Rze-
greater than it was in antiquity. Environmental con- czycka 1981). The procedure apparently became
ditions, both geographic and cultural, can also influ- more common in the Neolithic period, in France,
ence the expression of disease. For example, expo- England, Denmark, Germany, Italy, and Russia,
sure to smoke from wood-burning fires may be a and it continued into the Middle Ages (Steinbock
factor in the prevalence of nasopharyngeal tumors 1976). Trephined skulls have also been reported
in archeological skeletons (Wells 1977). from the Near East for the Neolithic period through

Early Neolithic (c. 6500 B.C.) to the Roman period

(A.D. 120), the frequency of skull wounds in men
ranged from a high of 20 percent in the Early Neo-
lithic to a low of 3 percent in the Classic period (650
B.C.). For women, the frequencies were 3 to zero
percent for the same periods (Angel 1974). In Iran
between 5000 and 500 B.C., there was a much
higher rate of head wounds among men than among
women (Rathbun 1984). At the site of Hissar in Iran,
occupied from the Chalcolithic through the Early
Bronze Age (4000-2000 B.C.), W. M. Krogman
(1940) noted that men suffered three times more
head wounds than women. In contrast, for the same
Figure V.I.I. Probable unhealed ax wound in an adult time period in neighboring Iraq, T. A. Rathbun
male skull from a rock tomb at Lisht in Upper Egypt (1984) found no difference in rates of head trauma
dated between the Twentieth and Twenty-fifth Dynasty between the sexes. In fact, the postcranial material
(c. 1100-655 B.C.). Bone fragment produced by the blow he studied for both Iran and Iraq revealed no differ-
at the time of death is reflected to the right. Note the ences between the sexes. Yet a Late Period site (664-
lack of remodeling on the cut surface indicative of death 323 B.C.) in Egypt revealed cranial trauma in 20
at the time of or shortly after the trauma. (From Cata-
percent of the adult males and 8.3 percent of the
log no. 256384, National Museum of Natural History,
Washington, D.C.)
adult females (Strouhal 1986).
Another pattern in the early skeletal material is
the rarity of evidence of fracture or trauma in chil-
the Iron Age (Wells 1964a; Lisowski 1967; Ortner dren (Grmek 1989). Specifically, this has been noted
and Putschar 1981; Rathbun 1984) and from the for Bronze Age Greece (Angel 1957), Denmark from
eastern Mediterranean for the Bronze and Iron ages the Mesolithic period through the Middle Ages (Ben-
(Ortner and Putschar 1981; Grmek 1989); however, nike 1985), Mesolithic western Europe (Meiklejohn
in the Near East and eastern Mediterranean the et al. 1984), and Late Period Egypt (Strouhal 1986).
practice apparently was not common. These observations, however, pose a potential meth-
Evidence of healing, as indicated by antemortem odological problem. Remodeling associated with
remodeling of cut edges in trephined skulls, is com- growth generally obliterates any evidence of fracture
mon. But even when there is no evidence of healing, in children, particularly if it occurs in early child-
death may have been caused by factors other than hood. Thus, evidence of fracture or other trauma in
the surgical procedure, such as a blow to the head, to children is often not seen in skeletal remains unless
which the trephination was a therapeutic response the child died shortly after the traumatic event.
(Lisowski 1967; Ortner and Putschar 1981). One of the fractures most frequently seen in the
Although it may not be possible to determine all pre-Roman world was caused when an individual, in
the reasons that trephination was performed, among attempting to protect the head, absorbed a blow with
some populations treatment for trauma seems to the forearm. This injury, called a parry fracture,
have been a common objective. Perhaps mental ill- most often involved the left ulna.
ness and epilepsy served as additional reasons. In There have been several surveys of the incidence
Danish skulls trephination is found almost exclu- of forearm fractures. J. Angel (1974) found that, in
sively in male specimens, with the left side being the prehistoric Greece and Turkey, forearm fracture was
one most commonly operated on (Bennike 1985). the most common form of injury. F. Wood-Jones
This pattern suggests that trephination was the (1910a) reported that, in pre-Dynastic through Byz-
therapeutic procedure for a blow to the cranium, antine Nubia, 31 percent of all fractures occurred in
resulting from violence among men and usually in- the forearm, with the ulna being broken more often
flicted by a right-handed opponent. than the radius and the left side more often dam-
Other types of trauma found in archeological skele- aged. In a British Neolithic to Anglo-Saxon series (c.
tal remains reveal information about early life- 3500 B.C. to A.D. 600) fracture of the forearm bones
styles. In general, male skeletons show a higher rate (radius and ulna) was the most common form of
of trauma, especially violent trauma, than do female postcranial injury, representing almost 49 percent of
skeletons. In the eastern Mediterranean, from the all fracture cases (Brothwell 1967).

In the eastern Mediterranean the next most com- affected by many variables, some of which were im-
mon fracture site was the lower thoracic vertebrae. portant factors during the history of human disease.
Fracture of the vertebral region also showed the For example, parasites may have become a greater
least amount of difference between men and women problem for human groups after the domestication of
(Angel 1974). animals, which are common vectors of diseases asso-
Fractures of the lower extremity are uncommon in ciated with these organisms. Airborne viruses,
the eastern Mediterranean (Angel 1974). In Nubian which require fairly large host populations (Fiennes
skeletons from the pre-Dynastic to Byzantine peri- 1978), may have become a significant health prob-
ods fractures of the foot are rare, and those of the leg lem with the rise of urbanism. Fungi may have be-
are less frequent than those of the arm (Wood-Jones come a more serious problem with the advent of
1910a). In Mesolithic to medieval Danish skeletal agriculture, particularly among groups who were
material, fracture of the lower extremities is rare under- or malnourished. Because fungi tend to be
(Bennike 1985). opportunistic, they are a greater problem in individu-
A review of the literature on trauma reveals sev- als who are immunologically compromised.
eral chronological trends. For the Mesolithic period Perhaps the most interesting observation about
through Iron Age, the rate of trauma generally infectious disease during the Mesolithic through the
seems to decrease. However, this decrease is related Metal Ages is its apparent low incidence in skeletal
primarily to accidental trauma; the incidence of vio- samples from most geographic areas (e.g., Wood-
lent trauma appears to remain the same. For exam- Jones 1910b; Martin et al. 1984; Rathbun 1984;
ple, Angel observed that, in the eastern Mediterra- Strouhal 1986). This low frequency has been ob-
nean, the general rate of fracture decreased with the served both for localized infection resulting from
development of civilization but the rate of violent trauma in general (Domurad 1986) and fracture in
injury to the head remained the same (Angel 1974). particular (Wood-Jones 1910b; Bennike 1985) and
Although P. Bennike (1985) did not find any time- for skeletal lesions (Martin et al. 1984), which may
related pattern for the postcranial Danish material, develop as a result of systemic disease. In fact, skele-
her data reveal that cranial trauma decreased over tal evidence of systemic infection appears to be quite
time. She also found that trauma to the skull was rare, and differential diagnosis often poses a great
more common in the Mesolithic (8300-4200 B.C.) challenge even to experienced paleopathologists or
than in the Neolithic (3200-1800 B.C.), and more orthopedic specialists.
common in the Neolithic than in the pre-Viking Iron Even though skeletal studies report a low inci-
Age (c. 500 B.C. to A.D. 800). Bennike did not differ- dence of infection, interpreting this observation re-
entiate between accidental and intentional trauma. quires caution and reflects some of the theoretical
The tendency for the incidence of trauma to de- problems involved in paleopathology. Most serious,
crease through time was also noted for western Eu- acute infectious diseases leave no evidence in gross
rope (Meiklejohn et at. 1984) and for Iran and Iraq skeletal remains. The lack of skeletal evidence of
(Rathbun 1984). C. Meiklejohn and colleagues infection may mean that the population was healthy,
(1984) tentatively hypothesize that the reduction in but it may also mean that people were dying from
trauma, in Mesolithic and Neolithic Europe, which acute infectious disease before the skeleton could be
in their sample was a reduction in overall accidental affected (Ortner and Putschar 1981; Rathbun 1984;
trauma, was due to a more sedentary existence. Ortner 1991).
Rathbun (1984) observed an apparent tendency for Several surveys have detected possible trends in
trauma in material from Iran and Iraq to decline infection rates. Rathbun (1984) notes that in Iraq
from the preagricultural to the urban phases several and Iran there appears to have been an increased
thousand years later. Although he could not differen- frequency of infectious-type lesions in the Neolithic
tiate between accidental and intentional trauma in and Chalcolithic periods. These rates declined sig-
the earlier skeletal material, he noted that much of nificantly in the later Bronze and Iron ages. Al-
the trauma of the later periods appeared to be due to though these trends may be real, they may also
human violence. reflect stochastic effects of inadequate samples. As
Rathbun (1984) suggests, however, the decline in
Infection percentage of cases exhibiting infectious lesions
Infectious diseases are caused by bacteria, fungi, from the Chalcolithic to the later Bronze and Iron
viruses, and multicellular parasites (e.g., worms). Age periods may be the result of people dying before
The health significance of each of these agents is bone was involved. Elsewhere in a study of Euro-

pean skeletal material, Meiklejohn and colleagues
(1984) noted an increase in cranial infections from
the Mesolithic to the Neolithic period. Dental evi-
dence of disease in the eastern Mediterranean sug-
gests to Angel (1984) that new diseases, including
epidemics, emerged with the increased population
sizes of the Middle Bronze Age.
Evidence from surveys of archeological skeletal
material, site reports, and individual case reports
has pointed to the existence of a number of infec-
tious diseases in the pre-Roman era - specifically,
tuberculosis, leprosy (in Egypt), osteomyelitis, and
periostitis.
There is strong evidence that tuberculosis may
have developed and/or become a problem with the
beginning of farming. Although no unequivocal
cases of destructive lesions of the spine have been
reported thus far for the prefarming Mesolithic, Figure V.I.2. Partial antemortem destruction of the
there are numerous descriptions of lesions of the fourth lumbar vertebral bone from the skeleton of a
spine for Neolithic Europe (c. 4200-1500 B.C.; young adult from the Early Bronze Age cemetery (c.
Bartels 1907; Patte 1971; Sager et al. 1972; 3100 B.C.) at Bab edh-Dhra', Jordan (Tomb A100E).
Dastugue and de Lumley 1976; Formicola, Milanesi, Note the reactive bone formation on adjacent vertebral
bodies, particularly the fifth lumbar vertebra.
and Scarsini 1987) and pre-Dynastic Egypt (c. 4800-
(Unaccessioned specimen, National Museum of Natural
3100 B.C.; Strouhal 1991), for which one possible History, Washington, D.C.)
diagnosis is tuberculosis. However, one must caution
that several disease conditions other than tuberculo-
sis produce destructive lesions of the spine, includ- and diagnosis of the purported cases of spinal tuber-
ing infection by staphylococcus bacteria and fungi. culosis in Egypt (Morse 1967; Grmek 1989; Strouhal
There were several cultural changes during the 1991), it appears that skeletal samples from this
Neolithic that would have influenced the develop- region contain at least 32 possible cases in the pre-
ment of diseases affecting the spine. In the Near East Christian era (Strouhal 1991). Donald Ortner (1979)
the use of domestic animals became an important reports two possible cases of tuberculosis in Jordan
part of the economy. Proximity to domestic animals, (Figure V.1.2) in a sample of about 300 from the
particularly bovids, was likely to have been a signifi- Early Bronze IA (c. 3100 B.C.) tombs at Bab edh-
cant factor in the development of tuberculosis (Man- Dhra'. In central and southern Europe, in addition to
chester 1983). In addition, a more sedentary life-style the Neolithic cases already cited, five cases have
and increased population density in the Neolithic and been reported between the Bronze Age and 100 B.C.
subsequent periods would have been likely to in- (Dastugue and de Lumley 1976; Steinbock 1976; An-
crease its incidence. However, farming was also gel 1984). Manchester (1984) believes that in Brit-
likely to have increased the incidence of fungal dis- ain the disease was present by the Roman period.
eases. It is thus probable that spinal lesions attribut- Evidence of tuberculosis is also reported for north-
able to both bacterial and fungal infection increased ern Europe, where it may have begun later than the
in the Neolithic period. The current skeletal evidence rest of Europe; most skeletal evidence is post-Roman
supports this expectation, although the specific etiol- (Brothwell, as cited in Manchester 1984).
ogy for the destructive lesions remains problematic. Leprosy is another infectious disease for which
Reported cases of tuberculosis show wide geo- there is skeletal evidence. In a review of the history
graphic distribution. K. Manchester (1984), basing of leprosy, Manchester (1984) cites the earliest evi-
his opinion on iconographic as well as on skeletal dence as that from Ptolemaic Egypt (second century
evidence, believes that the earliest undisputed evi- B.C.). Skeletal evidence for leprosy occurs later in
dence for human tuberculosis comes from Egypt and Europe. D. Brothwell (1961) argues that leprosy was
that the disease spread out from a near eastern cen- probably not established there before the first or
ter (Manchester 1983, 1984). Although there is con- second century A.D. and did not become a serious
siderable controversy regarding the exact dating problem until after the seventh century. By the Mid-

Research on mummy remains has provided useful
information on the antiquity of many other infec-
tious diseases. An early case of poliomyelitis was
reported in a pre-Dynastic mummy from Egypt
(Mitchell 1900) dated to 3700 B.C. The leg deformity
in the mummy of Pharaoh Siptah from the Nine-
teenth Dynasty (c. 1200 B.C.) has also recently been
recognized as having been caused by polio (Fleming
et al. 1980; Whitehouse 1980). Further possible evi-
dence of this disease has been reported in Middle
Bronze Age Greece (Angel 1971b) and sixth- to
second-century B.C. Italy (Mallegni, Fornaciari, and
Tarabella 1979).
Mummy material has also provided information
on parasites (Tapp 1986). Schistosomiasis is docu-
mented in two mummies of the Twentieth Dynasty
(c. 1100 B.C.) in Egypt (Sandison 1973) but probably
became a problem much earlier. The practice of irri-
gation, which may have begun in the Near East as
Figure V.I.3. Chronic inflammation of the left tibia and early as the Neolithic, would have facilitated the
fibula resulting from an overlying ulcer in a skeleton of spread of this disease. The roundworm, Ascaris, was
an adult woman probably over 50 years of age at the found in an Egyptian mummy dating to around 170
time of death. Specimen is from Tomb A100E in the B.C. (Fleming et al. 1980), as well as in coprolite
Early Bronze Age cemetery at Bab edh-Dhra', Jordan. material from Bronze Age Britain (Jones and Nichol-
Note the large, oval, circumscribed area of reactive bone son 1988) and Iron Age Europe (800-350 B.C.;
associated with the ulcer. Chronic inflammation involves Aspock, Flamm, and Picher 1973). The liver fluke
all bone tissue and resulted in fusion of the tibia and was found in two mummies of the Twelfth Dynasty
fibula. (Unaccessioned specimen, National Museum of
(Fleming et al. 1980). The tapeworm Echinococcus
Natural History, Washington, D.C.)
granulosus is associated with the mummy Asru
dated to about 700 B.C. (Tapp and Wildsmith 1986).
die Ages, the disease had become a serious problem
but virtually disappeared by the end of the fifteenth Arthritis
century. Manchester (1991) notes that the reduced Arthritis is a disease of the joints that includes
frequency of leprosy is associated with an increase in many syndromes. The term arthritis implies an in-
the prevalence of tuberculosis. He speculates that a flammatory condition of the joints, and inflamma-
factor in the decline of leprosy may have been cross- tion is a major factor in several syndromes. One
immunity induced by the closely related disease of general category of arthritis, and its most common
tuberculosis. syndrome, is osteoarthritis. Inflammation may occur
Both osteomyelitis and periostitis have been re- in osteoarthritis, but it is usually neither the initial
ported in ancient skeletal material. Although their nor the most significant factor. Although genetics,
frequencies show some degree of variability (e.g., physiology, trauma, and other factors appear to play
Wells, as cited in Sandison 1980; Strouhal 1986), a role, the most important condition contributing to
these conditions generally are not common. Descrip- osteoarthritis is mechanical stress. Furthermore,
tions of cases are encountered in the literature. For the effect of stress in stimulating arthritic change is
example, Wood-Jones (1910b) describes a humerus cumulative and thus the presence of osteoarthritis is
from ancient Nubia with evidence of inflammatory highly correlated with age. There is also a strong
bone formation. He attributes the inflammation to association between the type and degree of physical
an infectious complication of an injury. Ortner stress and the severity of osteoarthritis. For exam-
(1979) reports a case of reactive bone formation on ple, relatively frequent but low-level stress over a
the tibia and fibula of a skeleton (Figure V.I.3) dated long period of time probably has a different effect
to about 3100 B.C. The specimen is of an old woman than severe intermittent stress (Ortner 1968;
with an overlying skin ulcer of the lower leg that Jurmain 1977).
stimulated the inflammatory bone reaction. Because evidence of osteoarthritis is so common in

archeological human skeletons, the potential for dis- likely to be great. Perhaps a better understanding
cerning different patterns of joint stress that may be can be obtained with a detailed comparative study at
linked to variation in culture exists. However, the the site level such as was undertaken by E. Strouhal
current descriptive methodology for conducting such and J. Jungwirth (as cited in Aufderheide 1985).
research is poorly developed, and most of the pub- They found that in two contemporary Nubian skele-
lished observations on osteoarthritis do not permit tal populations dating to c. 1784-1570 B.C., agricul-
any comparative anaylsis. In addition, mean age of turists had more spinal osteoarthritis than did
population is often not carefully controlled. Because hunter-gatherers.
of the strong association between age and develop- In surveys of the incidence of osteoarthritis in other
ment of osteoarthritis, mean age is crucial to any areas of the skeleton or of the overall rate of general
comparison among populations. osteoarthritis, the same methodological problems ex-
Osteoarthritis of the spine has received the most ist. However, some tentative trends have been re-
systematic attention in paleopathological reports. ported. Meiklejohn and colleagues (1984) found that
Many surveys have found that the spine is more the overall rate of arthritis in western Europe was
frequently affected than any other area of the skele- higher in the Mesolithic than in the Neolithic, sug-
ton (Brothwell 1960; Gray 1967; Gejvall 1974; gesting greater biomechanical stress in the earlier
Meiklejohn et al. 1984; Rathbun 1984). Other sur- period.
veys, although offering no comparisons among areas Cultural factors and differences in physical envi-
of the skeleton, have noted the very frequent occur- ronment have been proposed as explanations for
rence of spinal osteoarthritis (Meiklejohn et al. changes in the incidence of the disease. Rathbun
1984; Bennike 1985), particularly among Egyptians (1984) found an overall decrease in osteoarthritis in
and Nubians (Wells 1964a; Dawson and Gray 1968; Iran and Iraq from the earlier periods to the later
Vagn Nielsen 1970). Metal Ages, which he related to the change in eco-
A variant of spinal degenerative arthritis known nomic activities accompanying urban life. He also
as spondylosis (spondylitis) deformans is reported found that the Iranian material typically showed
among some populations, such as the Late Stone Age more osteoarthritis than the Mesopotamian sam-
inhabitants of the Baltic Coast (V. Y. Derums 1964), ples - a difference that may be related to terrain.
as well as those of Neolithic Jericho (Kurth and Brothwell (1961) found that in Great Britain the
Rohrer-Ertl 1981), Neolithic Greece (Dastugue joints of the upper extremities exhibited more
1974), Third Dynasty Egypt (c. 2750-2680 B.C.; osteoarthritis in the Neolithic period through the
Ruffer and Rietti 1912; Ruffer 1918), and Bronze Age Iron Ages than they did in modern times. Manches-
Latvia, USSR (c. 2000-1000 B.C.; V. J. Derums 1987). ter (1983) attributes this difference to much greater
Detecting time related trends from the many sur- physical stress in the earlier periods.
veys of vertebral osteoarthritis remains problem- Sex-related roles also seem to affect the frequency
atic. Reports for Denmark (Bennike 1985) and Egypt and severity of osteoarthritis. Male skeletons tend to
(Wells 1964a) indicate no significant changes in the have a higher rate of the disease than female skele-
frequency and severity of the condition. Angel tons. Bennike (1985) found this to be true for the
(1971a) reported that evidence of osteoarthritis of spinal column in an Iron Age sample from Denmark.
the spine in the eastern Mediterranean changed lit- Similar findings of male skeletons were reported for
tle from the Upper Paleolithic (c. 60 percent) until Bronze Age Greece (Angel 1971b), the eastern Medi-
the Classic period, when there may have been a terranean during the Chalcolithic through the Helle-
decline (47 percent). In a later paper, however, the nistic period (Bisel 1980), Egypt during the Dynastic
estimated frequency of the disease during the Clas- period (Gray 1967), and Sudanese Nubia during the
sic period (76 percent) was as high as or higher than Second Intermediate period (Strouhal and J. Jung-
that at previous time periods (Bisel and Angel 1985). wirth, as cited in Aufderheide 1985).
The incidence of vertebral osteoarthritis in western Although greater male involvement is common,
Europe was reported to be higher in the Neolithic there are exceptions. In the Chalcolithic—Early
than in the Mesolithic (Meiklejohn et al. 1984). Bronze Age (4000-2000 B.C.) material from Kalin-
The mixed conclusions of these surveys may be kaya in Anatolia, osteoarthritis was more common
reflective of methodological problems. However, the in women according to S. Bisel (1980), who attrib-
importance of physical stress as a factor in vertebral utes this to greater physical stress from hard work.
osteoarthitis means that variability in sex roles, Female skeletons also show more arthritis at Early
type of subsistence, and environmental factors is Neolithic Nikomedeia in Greece (Angel 1973).

A second general category of arthritis is that of specimen from Iron Age Sicily (300-210 B.C.;
the inflammatory erosive joint diseases. This cate- Klepinger 1979) may represent a case of erosive
gory includes such syndromes as Reither's syn- joint disease with skeletal manifestations including
drome, psoriatic arthritis, and three that are exam- features of both ankylosing spondylitis and rheuma-
ined in this paper: rheumatoid arthritis, ankylosing toid arthritis. More recently, L. Kilgore (1989) has
spondylitis, and gout. Some syndromes of inflamma- suggested a diagnosis of rheumatoid arthritis for a
tory erosive joint disease have a known association case of erosive joint disease from Sudanese Nubia
with bacterial infection of the bowel or genitouri- dated to between A.D. 700 and 1450.
nary track. Lyme disease, for example, is initiated As mentioned earlier, a diagnosis of rheumatoid
by a tick bite that introduces a bacteria (spirochete) arthritis should be viewed with caution. However,
into the host. If untreated, the disease produces se- given the number of cases mentioned by different
vere erosive joint destruction in some patients. The authors, it does seem that rheumatoid arthritis may
prevailing theory is that other erosive arthropathies be of some antiquity in the Old World. Although the
are probably initiated by infectious agents as well. assignment to a specific syndrome of inflammatory
Inflammatory erosive joint disease occurs in some erosive joint disease may be incorrect, it seems
people when an infectious triggering agent operates likely that erosive joint disease was present by at
in combination with an individual's defective im- least the Neolithic period. Further clarification of
mune response. The major problem in inflammatory the antiquity of rheumatoid arthritis will have to
erosive joint disease is that the immune response to await additional study of Old World archeological
the infectious agent is not turned off after the trig- skeletons.
gering organisms are eliminated. Because of both Another syndrome of inflammatory joint disease
the infectious and genetic/immune components in that occurs in archeological skeletal samples is
inflammatory erosive joint disease syndromes, their ankylosing spondylitis. There is general agreement
time depth and geographic range are of particular that this syndrome has a history extending for sev-
interest in the context of human adaptation and eral thousand years (e.g., Resnick and Niwayama
microevolutionary biology. 1988). Skeletal evidence is reported in material from
Differential diagnosis of some syndromes of in- Neolithic France (Pales 1930; Torre and Dastugue
flammatory erosive joint disease in dry bone speci- 1976), Neolithic Sweden (Zorab 1961), and pre-
mens is likely to be difficult. Statements in the litera- Roman Germany (Zorab 1961). C. Short (1974) has
ture attributing inflammatory erosive joint disease concluded that there were 18 recorded cases in Egypt
in an archaeological specimen to a specific syndrome dating between 2900 B.C. and A.D. 200. G. Morlock
should be treated with caution. Even distinguishing (1986) has noted that cases of ankylosing spondylitis
these syndromes from septic arthritis and osteo- (as well as some severe forms of vertebral osteo-
arthritis can be problematic in some cases. phytosis) have been misdiagnosed. He contends that
There is currently a debate in the medical and some cases represent a syndrome of hypertrophic ar-
anthropological literature on the antiquity of rheu- thritis called DISH, whose antiquity therefore dates
matoid arthritis. B. Rothschild, K. R. Turner, and to pre-Roman Egypt, Greece, and Europe.
M. A. Deluca (1988) have argued that, in the New A third syndrome of inflammatory erosive joint
World, the disease has a history extending back at disease, gout, is well known in ancient historical
least 5,000 years. They further argue that rheuma- accounts. The Old Testament, in a passage dated to
toid arthritis may have been derived from New between 915 and 875 B.C., provides a graphic de-
World pathogens or allergens. However, reports in scription of the painful symptoms of this disease
the anthropological literature indicate that rheuma- (Resnick and Niwayama 1988). There are few good
toid arthritis may have begun as early as the Neo- descriptions, however, of gout in ancient human re-
lithic in the Old World. Brothwell (1973) suggests mains. A mummy from a Christian cemetery in
the possibility of its presence in Neolithic skeletal Egypt exhibits erosive destruction of the first
material from Great Britain. Rheumatoid arthritis metatarsals. Substance removed from the lesions
has also been reported in skeletal material from produced a reaction typical of uric acid crystals
Neolithic Sweden (2500-1900 B.C.; Leden, Persson, (Elliot-Smith and Dawson 1924; Rowling 1961). In
and Persson 1985—6), Bronze Age Denmark (c. addition, C. Wells (1973) has reported a possible case
1800-100 B.C.; Bennike 1985; Kilgore 1989), Fifth of gout in a Roman period skeleton from a site in
Dynasty Egypt (2544-2470 B.C.; May 1897), and Gloucester, England.
Iron Age Lebanon (500-300 B.C.; Kunter 1977). A Other syndromes of inflammatory erosive joint

data from dental remains. First, like bone, teeth and

their supporting tissues react to different disease
conditions in similar ways, so that one may be un-
able to attribute an abnormal condition to a specific
disease. Second, the methodology for analyzing
these dental pathologies is inexact, often making
comparisons among observations hazardous. For
these reasons, we will examine in detail only enamel
hypoplasia, a condition that has been carefully stud-
ied (e.g., Goodman, Martin, and Armelagos 1984;
Molnar and Molnar 1985; Rose, Condon, and Good-
man 1985; Goodman 1991). Although there is a con-
Figure V.1.4. Dental caries of the upper left second mo- siderable body of data on caries, methodological prob-
lar in an adult male skull from Tomb A100N in the lems hinder interpretation. Basically, variation in
Early Bronze Age cemetery at Bab edh-Dhra', Jordan. caries rate appears to be attributable to two dietary
(Unaccessioned specimen, National Museum of Natural factors: presence of carbohydrates and sugar, and
History, Washington, D.C.) presence of gritty food. (Gritty substances remove
the crevices in the dental crown, thereby eliminat-
disease may exist in ancient Old World human re- ing the locations for bacterial activity.)
mains. The diagnostic criteria for evaluating the Enamel hypoplasias can reveal a number of as-
presence of these syndromes are now being devel- pects about the health of an individual or population
oped and refined. We should have a better under- during childhood. If tooth surfaces have not been
standing of the historical dimension of these syn- worn away, enamel hypoplasias can be used to esti-
dromes in the near future. mate both the timing and severity of stress. The
presence of enamel hypoplasias in the deciduous
Dental Disease teeth indicates the occurrence of stress during the
Teeth and supporting tissues can be affected by last 5 months in utero through the first year of
many disease conditions. The size and shape of teeth postnatal life (Goodman et al. 1984). In the perma-
can be affected by systemic diseases (e.g., infection nent incisors and canines, the teeth most commonly
and malnutrition) that occur during fetal, infant, studied for enamel defects in adult dentitions,
and childhood dental development. Systemic dis- enamel hypoplasias reflect stress between birth and
eases can also leave observable defects (hypoplasia) 7 years (Goodman 1991). The onset of stress can be
in the enamel. Tooth surfaces can be destroyed by determined in half-year intervals (Goodman 1991).
bacteria, a process resulting in caries (Figure V.1.4). Enamel hypoplasias represent a disturbance last-
Caries can destroy the tooth to the point where the ing from several weeks to 2 months (Rose et al.
pulp cavity is exposed to infectious agents that can 1985). Many sources attribute these disturbances to
invade the bone and produce inflammation and ab- infection or nutritional deficiencies (y'Edynak and
scess. Finally, teeth can be traumatized by gritty Fleisch 1983; Goodman et al. 1984) such as those
materials in food, by violence, and by the use of teeth that can occur with weaning (Rathbun 1984; Smith,
as tools. Bar-Yosef, and Sillen 1984).
Other areas of the mouth can be affected by dis- A general survey of the literature on enamel
ease. Gums may become inflamed due to irritation hypoplasia reveals several interrelated patterns.
from plaque or infection, resulting in periodontal First, there seems to be a general rise in the fre-
disease and resorption of alveolar bone. The subse- quency of hypoplasia from the Mesolithic to Roman
quent exposure of tooth roots with alveolar recession period in many areas of the Old World (y'Edynak
can result in root caries and tooth loss. Supporting and Fleisch 1983; Rathbun 1984; Smith et al. 1984;
bony tissues of the jaw are subject to inflammation Molnar and Molnar 1985; Formicola 1986-7; Angel
just as bone is in other parts of the body. and Bisel 1987). This rise seems to be related to
In an archeological context, the dental pathologies general changes in the human environment.
most commonly seen are caries, periodontal disease, P. Smith and colleagues (1984) found that in Pales-
dental abscess, antemortem tooth loss, dental attri- tine the frequency of enamel hypoplasias increased
tion, and enamel hypoplasia. Unfortunately, there from the Natufian period (c. 10,000 to 8500 B.C.) to
are two major difficulties in extracting meaningful the Neolithic, and rose again in the later Chalco-

lithic and Bronze ages. They postulate that the were generally limited to male skeletons, and
slight rise in dental pathology in the Neolithic may Rathbun (1984) suggests that the greater frequency
have been due to changes in diet. However, they in males supports the contention that growing males
attribute the more definite increase in frequencies are more vulnerable to stress than are females.
in the later periods to a marked decline in health Finally, there is some indication that the severity
due to chronic disease (Smith et al. 1984). of hypoplasia in subadult populations is inversely
The Palestinian material also revealed interesting associated with age of death. Some researchers have
changes in the onset of childhood stress. In the suggested that stress, producing hypoplasia, may be
Natufian period enamel hypoplasias indicate that a linked with the factors resulting in the death of the
major period of stress occurred between 3 and 4 individual (Rathbun 1984; Goodman 1991). In con-
years of age and was probably associated with wean- trast, Smith and colleagues (1984) suggest that
ing (Smith et al. 1984). However, during the later hypoplasia is indicative of individuals who survive
Chalcolithic and Early Bronze Age periods, stress stress, unlike individuals who die before their teeth
appears to have occurred earlier in life with decidu- can be affected.
ous teeth commonly affected. This suggests to Smith
and co-workers (1984) that weaning took place ear- Anemia
lier in life in these later time periods - a pattern In archeological skeletal remains, evidence of two
that reflects a presumed decrease in birth spacing. types of anemia, although not common, are well
Angel's findings in the eastern Mediterranean known and of considerable biological consequence.
also reflect changes in the human environment. He Genetic anemias, the less common of the two, are
linked the increased frequency of hypoplasia in the restricted to a few geographic areas of the world.
Middle Bronze Age (c. 2000-1500 B.C.) skeletal sam- Anemia resulting from malnutrition can occur any-
ples of that area to the beginning of childhood epi- where. Because of the pitfalls in diagnosing ane-
demics. Epidemics were not a significant problem mia in skeletal material, an understanding of the
until that time period because human population biological processes involved in this condition is
sizes were not large enough to support the disease helpful.
organisms (Angel and Bisel 1986). In anemia there is an abnormal increase in the
A second pattern in enamel hypoplasia research is need for blood formation. This may be the result of
the often wide variation in frequencies within a spe- several conditions, including excessive blood loss
cific time period. For example, in Neolithic skeletal through chronic bleeding from intestinal parasites.
samples from Hungary (Molnar and Molnar 1985) In the genetic anemias, the hemoglobin in red blood
and Sweden (Gejvall 1974), there was no evidence of cells is defective. This reduces the normal life span
enamel hypoplasia. Enamel hypoplasia was found to of the cells, which in turn creates an increased de-
be relatively rare in Neolithic samples from West mand for new blood formation. Dietary iron defi-
Germany (Schaefer 1978), whereas Brothwell (1973) ciency can also result in abnormal hemoglobin with
reports that enamel hypoplasia in Great Britain oc- results similar to those that exist in the genetic
curred in 37 percent of Neolithic skeletons. V. For- anemias.
micola and colleagues (1987) reported the frequency Because of the increased demand for blood forma-
to be high for one Italian sample. tion, tissues that create blood occupy more space.
Inadequacies in the samples raise questions about The bone marrow spaces that in an infant or young
the results, but it does seem that variation among child are normally required for blood formation are
sites within a period can be interpreted to mean that now inadequate, and hematopoietic marrow tends to
specific local conditions such as parasite load may be expand at the expense of cortical bone. In the
more important than the general economic subsis- postcranial skeleton the marrow volume of the long
tence base. bones increases at the expense of that of the cortex,
There is other evidence that differences in rates of which decreases in thickness (Ortner and Putschar
enamel hypoplasia may be related to specific geo- 1981). In the skull the diploe enlarges primarily at
graphic factors, although it is not always clear what the expense of the outer table; the skull becomes
these factors may be. Rathbun (1984) found that thicker, and the external appearance of the skull
skeletal samples from Iran dated during the period becomes porous. Although many descriptive terms
from the Neolithic through the Metal Ages had a have been applied to this condition in the skull,
significantly higher rate of enamel hypoplasia than currently the most commonly accepted one is porotic
did analogous samples from Iraq. These differences hyperostosis, introduced by Angel (1966).

Unfortunately, there are other conditions that

may be associated with porous lesions of the skull,
including infection and metabolic diseases such as
scurvy and rickets (Ortner and Putschar 1981;
Ortner 1984, 1986). Thus, unless there is unambigu-
ous evidence of an expansion of marrow space in at
least some of the cases in the skeletal sample exhibit-
ing porous lesions of the skull, a diagnosis of anemia
should be offered with caution.
Angel (1966, 1972, 1977) proposed an intriguing
connection between falciparum malaria and porotic
hyperostosis in the eastern Mediterranean. He hy-
pothesized that this condition in the skeletal re- Figure V.I.5. Benign tumor (cartilaginous exostosis) in
mains of the region is indicative of thalassemia, one the area of fusion between the pubic and iliac bones of a
of the genetic anemias that may provide some immu- right innominate bone. Adult female from the Twelfth
nity against malaria, and further proposed an asso- Dynasty (c. 1990 B.C.) Rock Tombs, Lisht, Egypt. (Cata-
ciation between the incidence of porotic hyperostosis log no. 256474, National Museum of Natural History,
and the cycles of malarial severity throughout the Washington, D.C.)
past 10,000 years. Malaria, he argues, did not be-
come endemic until the population settlement and sarcoma of the humerus (Figure V.I.6) has been re-
increase of the Neolithic period, when the frequency ported in several publications (e.g., Ortner and
of porotic hyperostosis reached 50 percent (Angel Putschar 1981). Secondary (metastatic) tumors of
1972). After the Neolithic, porotic hyperostosis de- bone are more common than primary malignant tu-
clined to 12 percent in the Bronze Age and 2 percent mors. However, because this type of tumor occurs
in the City State period (650-300 B.C.; Angel 1972). most frequently in people over 50 years of age, it is
Angel attributes this decline in anemia, and presum- also an archeological rarity. Until very recently in
ably malaria, to changes in environment, including human history, few people lived long enough to ac-
lowered sea levels and drained marshes. In a book of quire secondary tumors of bone.
readings edited by M. Cohen and G. Armelagos Because tumors are so rare in archeological speci-
(1984b), Cohen concludes, while reviewing data pre- mens, any statement on prevalence associated with
sented during a symposium, that porous lesions of geographic areas or time periods is likely to be
the skull vault and eye orbit either appeared or
increased in frequency with the advent of agricul-
ture. He cautiously argues that this trend is indica-
tive of an increase in anemia at that time.
Tumors
Tumors of the skeleton are classified on the basis of
whether they arise in bone (primary) or invade
bone from another tissue (secondary, malignant, or
metastatic). Most of the primary bone tumors seen
in archeological human skeletons are benign. Some
primary benign tumors of bone, such as osteomas,
are well known in archeological skeletons; other
benign tumors, such as cartilaginous exostoses (Fig-
ure V.I.5), are less common but have been reported
(e.g., Ortner and Putschar 1981). These benign tu-
mors generally have minimal medical or biological Figure V.1.6. Malignant tumor (osteosarcoma or
significance. chondrosarcoma) of the proximal left humerus of a
Primary malignant tumors are uncommon in Celtic warrior (c. 800—600 B.C.) from an archeological
archeological skeletons and tend to occur in children site near Miinsingen, Bern, Switzerland. Each alternat-
and adolescents. The Celtic warrior (800-600 B.C.) ing band equals 1 centimeter. (Catalog no. A95, Natural
from Switzerland with osteosarcoma or chondro- History Museum, Bern, Switzerland.)

highly problematic. At present our data consist of plasia), the data seem inconsistent; there is varia-
case reports and surveys such as that provided by tion among sites within the same time period, as
J. Gladykowska-Rzeczycka (1991) for tumors in Eu- well as among different time periods. In general,
ropean material. However, it seems reasonable to however, from the Mesolithic to the Neolithic there
assume that carcinogens have been a problem for a seems to be a trend toward increased frequencies of
long time. As previously mentioned, Wells (1964b) nonspecific disease conditions. Whether this trend is
suggests that nasopharyngeal tumors seen in indicative of a decline in population health in the
archeological human skeletons are associated with Neolithic is a question that remains, in our opinion,
the open fires that have existed in human societies problematic. As we have suggested, an increased
for millennia. frequency of nonspecific lesions of bone may indicate
a more effective immune response; individuals with
Conclusion nonspecific lesions of bone usually must have sur-
In this essay we have presented a broad overview of vived an acute phase to enter the chronic phase of a
the specific diseases that may have existed in the disease process.
pre-Roman Old World and outlined general patterns For the urban periods, the same theoretical diffi-
of health that may have been present as human culties exist. In several areas the frequencies of
society became increasingly complex. But because of enamel hypoplasias continue to increase from the
the limitations imposed by the sources and the re- Neolithic, indicating increasing childhood stress.
search methods used, the picture is incomplete. However, the frequencies for nonspecific infectious
From skeletal and mummy material we are fairly skeletal lesions do not always increase.
certain that, depending on geographic location, pre- Ascertaining the relation between skeletal dis-
Roman populations suffered from a number of infec- ease and morbidity in antiquity requires great care.
tious diseases (i.e., multicellular parasites, tubercu- For example, is dental hypoplasia representative of
losis, poliomyelitis, periostitis, osteomyelitis, and, an acute phase of a disease process occurring during
late in the pre-Roman era, leprosy). Most of these late fetal life and childhood? Is periostitis indicative
populations were also exposed to trauma, particu- of chronic disease reflecting a good immune re-
larly in the form of head wounds and forearm frac- sponse? Issues of this type will have to be clarified
tures. Osteoarthritis, particularly of the spine, was before generalizations about population health can
prevalent, and some groups suffered from erosive be made.
joint disease. Anemia was present and apparently
The epochal nature of the cultural change that
fairly common in some geographic locations and
took place between the Mesolithic and Roman peri-
time periods. Tumors were rare. Determining the
ods offers an opportunity to study several important
frequencies and geographic site of origin of some of
problems in human biocultural adaptation. Further
these abnormal conditions will have to await future
research will require a much more effective descrip-
research.
tive and research methodology. We also need to give
One of the most intriguing ideas that has emerged more careful thought to the meaning of our observa-
from our review of infectious diseases is the possibil- tions in a skeletal sample relative to the health of
ity that tuberculosis became a problem in the Neo- the living parent population.
lithic period. Greater population densities, seden- Donald J. Ortner and Gretchen Theobald
tism, and close contact with domestic animals are all
factors that, in theory, could have led to the emer- Bibliography
gence of tuberculosis as a serious health problem in Angel, J. L. 1957. Human biological changes in ancient
the Neolithic. J. McGrath (1986) argues that large Greece, with special reference to Lerna. In Year Book
populations may not be needed for mycobacterial of the American Philosophical Society, 226—70. Phila-
infections. This may be true, but it is equally true delphia.
that some types of bacteria are more likely to be 1966. Porotic hyperostosis, anemias, malarias and
maintained in a host population when the popula- marshes in the prehistoric eastern Mediterranean.
tion is large. A careful restudy of spines in Old World Science 153: 760-3.
archeological skeletal samples would be most useful 1971a. Disease and culture in the ancient East Mediter-
ranean. In Proceedings of the 10th Congress of the
in clarifying this point. Czechoslovak Anthropological Society at Humpolec,
Outlining general patterns of health has been 1969, 503-8. Prague.
equally elusive. With respect to nonspecific disease 1971b. The people of Lerna. Washington, D.C.
conditions (e.g., periostitis, osteitis, dental hypo- 1972. Biological relations of Egyptian and eastern Medi-

terranean populations during pre-Dynastic and Dy- Britain. In Die Anfange des Neolithikums vom Orient
nastic times. Journal of Human Evolution 1: 307-13. bis Nordeuropa, ed. I. Schwidetzky, 280-99. Cologne.
1973. Early Neolithic people of Nea Nikomedeia. In Die Buikstra, J. E. 1976. The Caribou Eskimo: General and
Anfange des Neolithikums vom Orient bis Nordeu- specific disease. American Journal of Physical Anthro-
ropa, ed. I. Schwidetzky, 103-12. Cologne. pology 45: 351-67.
1974. Patterns of fractures from Neolithic to modern Cockburn, A. 1963. The evolution and eradication of infec-
times. Anthropologiai Kozlemenyek 18: 9-18. tious diseases. Baltimore.
1977. Anemias of antiquity in the eastern Mediterra- Cohen, M. N. 1984a. An introduction to t h e symposium. In
nean. In Paleopathology Association Monograph No. 2, Paleopathology at the origins of agriculture, ed. M. N.
1-5. Cohen and G. J. Armelagos, 1-11. Orlando, Fla.
1984. Health as a crucial factor in the changes from 1984b. Paleopathology at the origins of agriculture: Edi-
hunting to developed farming in the eastern Mediter- tor's summation. In Paleopathology at the origins of
ranean. In Paleopathology at the origins of agriculture, agriculture, ed. M. N. Cohen and G. J. Armelagos,
ed. M. N. Cohen and G. J. Armelagos, 51-73. Orlando, 585-601. Orlando, Fla.
Fla. Dastugue, J. 1974. Les ossements humains pathologiques.
Angel, J. L., and S. C. Bisel. 1986. Health and stress in an Bulletin de la Correspondance Hellenique 98: 749—54.
Early Bronze Age population. In Ancient Anatolia: Dastugue, J., and M.-A. de Lumley. 1976. Les maladies des
Aspects of change and cultural development, ed. J. V. hommes pre-historiques. In La Pre—historie frangaise,
Canby et al., 12-30. Madison, Wis. Vol. 2., ed J. Guilaine, 153-64. Paris.
Aspock, H., H. Flamm, and O. Picher. 1973. Intestinal Dawson, W. R., and P. H. K. Gray 1968. Catalogue of
parasites in human excrements from prehistoric salt- Egyptian antiquities in the British Museum. Vol. 1:
mines of the Hallstatt period (800-350 B.C.). Mummies and human remains. London.
Zentralblatt fur Bakteriologie, Parasitenkunde, Infek- Derums, V J. 1987. Paleopathology of Bronze Age popula-
tionskrankheiten und Hygiene 223: 549—58. tion in Latvia. Anthropologie 25: 57—61.
Aufherheide, A. C. 1985. Review of Die Anthropologische Derums, V. Y. 1964. Some paleopathologic data on Baltic
Untersuchung der C-Gruppen- und Pan-Grdber- Coast inhabitants. Arkhiv Anatomii, Gistologii i
Skelette aus Sayala, Agyptisch-Nubien, by E. Strou- Embriologii 46: 225-30.
hal and J. Jungwirth. Paleopathology Newsletter 52: Domurad, M. R. 1986. The populations of ancient Cyprus.
19-20. Ph.D. dissertation, University of Cincinnati.
Bartels, P. 1907. Tuberkulose (wirbelkaries) in der jung- Elliot-Smith, G., and W. R. Dawson. 1924. Egyptian mum-
eren Steinzeit. Archiv fur Anthropologie 6: 243-55. mies. New York.
Bennike, P. 1985. Palaeopathology of Danish skeletons. Elliot-Smith, G., and F. Wood-Jones. 1910. The archaeologi-
Copenhagen. cal survey of Nubia report for 1907-1908. Vol. 2: Re-
Bentley, G. R. 1987. Kinship and social structure at Early port on the human remains. Cairo.
Bronze IA Bab edh-Dhra', Jordan. Ph.D. dissertation, El-Najjar, M. Y., et al. 1980. Autopsies on two native
University of Chicago. American mummies. American Journal of Physical
Bisel, S. C. 1980. A pilot study in aspects of human nutri- Anthropology 53: 197-202.
tion in the ancient eastern Mediterranean, with par- Fiennes, R. N. 1978. Zoonoses and the origins and ecology
ticular attention to trace minerals in several popula- of human disease. New York.
tions from different time periods. Ph.D. dissertation, Fleming, S., et al. 1980. The Egyptian mummy: Secrets
University of Minnesota. and science. Philadelphia.
Bisel, S. C , and J. L. Angel. 1985. Health and nutrition in Formicola, V. 1986. Anthropologie dentaire des restes de
Mycenaean Greece: A study in human skeletal re- l'Epi gravettien final retrouv6s dans la grotte des
mains. In Contributions to Aegean archaeology: Stud- Arene Candide (Ligurie). Bulletin et Mimoires de la
ies in honor of William A. McDonald, ed. N. C. Wilkie Soci6te~ d'Anthropologie de Paris 3: 37-46.
and W. D. E. Coulson, 197-209. Dubuque, Iowa. 1986-7. The dentition of the Neolithic sample from West-
Brothwell, D. R. 1960. The Bronze Age people of York- ern Liguria (Italy). Ossa 13: 97—107.
shire: A general survey. Advancement of Science 16: Formicola, V, Q. Milanesi, and C. Scarsini. 1987. Evidence
311-22. of spinal tuberculosis at the beginning of the 4th mil-
1961. The palaeopathology of early British man: An lennium B.C. from Arene Candide Cave (Liguria, It-
essay on the problems of diagnosis and analysis. aly). American Journal of Physical Anthropology 72:
Journal of the Royal Anthropological Institute 91: 1-6.
318-44. Gejvall, N.-G. 1974. Description of the human skeletons
1967. The bio-cultural background to disease. In Dis- from the graves and some associated animal bones.
eases in antiquity, ed. D. Brothwell and A. T. In Gotlands Mellanneolitiska Gravar (The Middle
Sandison, 56-68. Springfield, 111. Neolithic graves of Gotland), ed. O. Janzon, 141-67.
1973. The human biology of the Neolithic population in Stockholm.

Gladykowska-Rzeczycka, J. 1981. A short review of paleo- Martin, D. L., et al. 1984. The effects of socioeconomic
pathological research in Poland. Homo 32: 125—30. change in prehistoric Africa: Sudanese Nubia as a
1991. Tumors in antiquity in East and Middle Europe. case study. In Paleopathology at the origins of agricul-
In Human paleopathology: Current syntheses and future, ed. M. N. Cohen and G. J. Armelagos, 193-214.
ture options, ed. D. J. Ortner and A. C. Aufderheide, Orlando, Fla.
251-6. Washington, D.C. May, W. P. 1897. Rheumatoid arthritis (osteitis deformans)
Goodman, A. H. 1991. Stress, adaptation and enamel de- affecting bones 5,500 years old. British Medical Jour-
velopmental defects. In Human paleopathology: Cur- nal 2: 1631-2.
rent syntheses and future options, ed. D. J. Ortner and McGrath, J. W. 1986. A computer simulation of the spread
A. C. Aufderheide. Washington, D.C. of tuberculosis in prehistoric populations of the lower
Goodman, A. H., D. L. Martin, and G. J. Armelagos. 1984. Illinois River Valley. Ph.D. dissertation, Northwest-
Indications of stress from bone and teeth. In ern University.
Paleopathology at the origins of agriculture, ed. M. N. Meiklejohn, C, et al. 1984. Socioeconomic change and
Cohen and G. J. Armelagos, 13-49. Orlando, Fla. patterns of pathology and variation in the Mesolithic
Gray, P. H. K. 1967. Radiography of ancient Egyptian and Neolithic of western Europe: Some suggestions.
mummies. Medical Radiography and Photography 43: In Paleopathology at the origins of agriculture, ed.
34-44. M. N. Cohen and G. J. Armelagos, 75-100. Orlando,
Grmek, M. D. 1989. Diseases in the ancient Greek world. Fla.
Baltimore. Mitchell, J. K. 1900. Study of a mummy affected with
Jones, A. K. G., and C. Nicholson 1988. Recent finds of anterior poliomyelitis. Transactions of the Association
Trichuris and Ascaris ova from Britain. Paleo- of American Physicians 15: 134—6.
pathology Newsletter 63: 5-6. Molnar, S., and I. Molnar. 1985. Observations of dental
Jurmain, R. D. 1977. Stress and the etiology of osteoarthri- diseases among prehistoric populations in Hungary.
tis. American Journal of Physical Anthropology 45: American Journal ofPhysical Anthropology 67:51-63.
353-66. Morlock, G. 1986. Paleopathological identification of the
Kilgore, L. 1989. Possible case of rheumatoid arthritis hyperostosic disease. In VI European Meeting of the
from Sudanese Nubia. American Journal of Physical Paleopathology Association, Proceedings, ed. F. G.
Anthropology 79: 177-83. Bellard and J. A. Sanchez, 161-8. Madrid.
Klepinger, L. L. 1979. Paleopathologic evidence for the Morse, D. 1967. Tuberculosis. In Diseases in antiquity, ed.
evolution of rheumatoid arthritis. American Journal D. Brothwell and A. T. Sandison, 249-71. Springfield,
of Physical Anthropology 50: 119-22. 111.
Krogman, W. M. 1940. The skeletal and dental pathology Ortner, D. J. 1968. Description and classification of degen-
of an early Iranian site. Bulletin of the History of erative bone changes in the distal joint surfaces of the
Medicine 8: 28-48. humerus. American Journal ofPhysical Anthropology
Kunter, M. 1977. K&mid el-Loz. Bonn. 28: 139-55.
Kurth, G., and O. Rohrer-Ertl. 1981. On the anthropology 1979. Disease and mortality in the Early Bronze Age
of the Mesolithic to the Chalcolithic: Human remains people of Bab edh-Dhra, Jordan. American Journal of
from the Tell es-Sultan in Jericho, Jordan. In Excava- Physical Anthropology 51: 589-98.
tions at Jericho, Vol. 3, ed. K. M. Kenyon, 407-49. 1984. Bone lesions in a probable case of scurvy from
London. Metlatavik, Alaska. Journal of the Museum ofApplied
Leden, O., E. Persson, and O. Persson. 1985-6. Periph- Science, Center for Archaeology [MASCA Journal] 3:
eral polyarthritis in two Neolithic skeletons. Ossa 12: 79-81.
79-88. 1986. Metabolic and endocrine disorders in human skele-
Lisowski, F. P. 1967. Prehistoric and early historic tre- tal paleopathology. In VI European Meeting of the
panation. In Diseases in antiquity, ed. D. Brothwell Paleopathology Association, Proceedings, ed. F. G.
and A. T. Sandison, 651-72. Springfield, 111. Bellard and J. A. Sanchez, 17-24. Madrid.
Mallegni, E, G. Fornaciari, and N. Tarabella. 1979. Studio 1991. Theoretical and methodological issues in paleo-
antropologico dei resti scheletrici della necropoli dei pathology. In Human paleopathology: Current synthe-
Monterozzi (Torquina). Atti della Societa Toscana di ses and future options, ed. D. J. Ortner and A. C.
Scienze Naturali, SerieB. 86: 185-221. Aufderheide, 5-11. Washington, D.C.
Manchester, K. 1983. The archaeology ofdisease. Bradford. Ortner, D. J., and W. G. J. Putschar. 1981. Identification of
1984. Tuberculosis and leprosy in antiquity: An interpre- pathological conditions in human skeletal remains.
tation. Medical History 28: 162-73. Smithsonian Contributions to Anthropology No. 28.
1991. Tuberculosis and leprosy: Evidence for the interac- Washington, D.C.
tion of disease. In Human paleopathology: Current Pales, L. 1930. Paleopathologie et pathologie comparative.
syntheses and future options, ed. D. J. Ortner and A. C. Paris.
Aufderheide, 23-35. Washington, D.C. Patte, E. 1971. Les restes humains de la grotte sepulcrale

du Laris Goguet a Feigneux (Oise). Bulletins et Mem- Untersuchung der C-Gruppen- und Pan-Grdber-
oires de la Societe d'Anthropologie de Paris 7:381-452. Skelette aus Sayala, Agyptische-Nubien. Vienna
Rathbun, T. A. 1984. Skeletal pathology from the Paleo- Tapp, E. 1986. Histology and histopathology of the Man-
lithic through the Metal Ages in Iran and Iraq. In chester mummies. In Science in Egyptology, ed. R. A.
Paleopathology at the origins of agriculture, ed. M. N. David, 347-50. Manchester.
Cohen and G. J. Armelagos, 137-67. Orlando, Fla. Tapp, E., and K. Wildsmith. 1986. Endoscopy of Egyptian
Resnick, D., and G. Niwayama. 1988. Diagnosis of bone mummies. In Science in Egyptology, ed. R. A. David,
and joint disorders, 2d edition. Philadelphia. 351-4. Manchester.
Rose, J. C , K. W. Condon, and A. H. Goodman. 1984. Diet Torre, S., and J. Dastugue, 1976. Neolithiques de Basse
and dentition: Developmental disturbances. In The Normandie: Le Deuxieme tumulus de Fontenay-le-
analysis of prehistoric diets, ed. R. I. Gilbert, Jr., and Marmion (Pathologie). I'Anthropologie 80: 625—53.
J. H. Mielke, 281-305. New York. Tuross, N. 1991. Recovery of bone and serum proteins from
Rothschild, B. M., K. R. Turner, and M. A. DeLuca. 1988. human skeletal tissue: IgG, osteonectin and albumin.
Symmetrical erosive peripheral polyarthritis in the In Human paleopathology: Current syntheses and fu-
Late Archaic period of Alabama. Science 241: 1498- ture options, ed. D. J. Ortner and A. C. Aufderheide,
1501. 51-4. Washington, D.C.
Rowling, J. T. 1961. Pathological changes in mummies. Vagn Nielsen, 0.1970. The Nubian skeleton through 4000
Proceedings of the Royal Society of Medicine 54: 409- years. Denmark.
15. Wells, C. 1964a. Bones, bodies and disease. New York.
Ruffer, M. A. 1918. Studies in palaeopathology: Arthritis 1964b. Two Mediaeval cases of malignant disease. Brit-
deformans and spondylitis in ancient Egypt. Journal ish Medical Journal 1: 1611-21.
of Pathology and Bacteriology 22: 152-96. 1973. A paleopathological rarity in a skeleton of Roman
Ruffer, M. A., and A. Rietti. 1912. On osseous lesions in date. Medical History 17: 399-400.
ancient Egyptians. Journal ofPathology andBacteriol- 1977. Disease of the maxillary sinus in antiquity. Medi-
ogy 16: 439-65. cal and Biological Illustration 27: 173—8.
Sager, P., M. Schalimtzek, and V. M0ller-Christensen. 1978. Disease and evolution. Biology and Human Af-
1972. A case of spondylitis tuberculosa in the Danish fairs 43: 5-13.
Neolithic Age. Danish Medical Bulletin 19: 176-80. Whitehouse, W. M. 1980. Radiologic findings in the Royal
Sandison, A. T. 1973. Evidence of infective disease. In mummies. In An x-ray atlas of the royal mummies, ed.
Population biology of the ancient Egyptians, ed. D. R. J. E. Harris and E. F. Wente, 286-327. Chicago.
Brothwell and B. A. Chiarelli, 213-24. New York. Wood-Jones, F. 1910a. Fractured bones and dislocations. In
1980. Diseases in ancient Egypt. In Mummies, disease The archaeological survey of Nubia report for 1907-
and ancient cultures, ed. A. Cockburn and E. Cock- 1908. Vol. 2: Report on the human remains, ed.
burn, 29-44. New York. G. Elliot-Smith and F. Wood-Jones, 293-342. Cairo.
Schaefer, U. 1978. Menschliche Skelettfunde aus dem Neo- 1910b. General pathology (including diseases of the
lithikum im Gebiet der Lander Schleswig-Holstein, teeth). In The archaeological survey of Nubia report
Niedersachsen, Nordrhein-Westfalen und Hessen for 1907-1908. Vol. 2: Report on the human remains,
(BRD). In Die Anfdnge des Neolithikums vom Orient ed. G. Elliot-Smith and F. Wood-Jones, 263-92. Cairo.
bis Nordeuropa, ed. I. Schwidetzky, 66-92. Cologne. y'Edynak, G., and S. Fleisch. 1983. Microevolution and
Short, C. L. 1974. The antiquity of rheumatoid arthritis. biological adaptability in the transition from food-
Arthritis and Rheumatism 17: 193-205. collecting to food-producing in the Iron Gates of Yugo-
Smith, P., O. Bar-Yosef, and A. Sillen. 1984. Archaeologi- slavia. Journal of Human Evolution 12: 279-96.
cal and skeletal evidence for dietary change during Zorab, P. A. 1961. The historical and prehistorical back-
the Late Pleistocene/Early Holocene in the Levant. In ground of ankylosing spondylitis. Proceedings of the
Paleopathology at the origins of agriculture, ed. M. N. Royal Society of Medicine 54: 415-20.
Cohen and G. J. Armelagos, 101-36. Orlando, Fla.
Steinbock, R. T. 1976. Paleopathological diagnosis and
interpretation. Springfield, 111.
Strouhal, E. 1986. Anthropology of the Late Period ceme-
tery in the tomb of King Horemheb ad Saqqara
(Egypt) (preliminary report). International Journal of
Anthropology 1: 215-24.
1991. Vertebral tuberculosis in ancient Egypt and
Nubia. In Human paleopathology: Current syntheses
and future options, ed. D. J. Ortner and A. C.
Aufderheide, 181-94. Washington, D.C.
Strouhal, E., and J. Jungwirth. 1984. Die Anthropologische

and gonorrhea (YOVOQQTIICO, mean something more
V.2 than the modern clinical entities whose names they
Diseases of Western bear; in fact, it is not altogether certain that lepra
denoted Hansen's disease or that gonorrhea denoted
Antiquity the disease that today is positively diagnosed only by
the presence of gonococcus.
A second consequence, far more formidable than
There are good reasons for believing that diseases the philological one just noted, concerns the very
and complaints of various kinds and degrees of sever- foundations of classical medicine. Beginning with
ity were as much a part of everyday life in classical Hippocrates, and accepted by the better medical writ-
antiquity as were the assorted battle wounds and ers throughout classical antiquity, was the notion of
injuries so dramatically portrayed from Homer on- disease as a process. Regardless of the philosophical
ward. This is indicated not only by the surviving theory that supported the etiology, whether hu-
Greek and Latin medical texts and the fragments moralism or solidism, a disease, theoretically, could
preserved in Greco-Egyptian papyri, but also by the be described as a series of stages with a predictable
large corpus of nonmedical Greek and Latin texts, outcome. Each of those stages normally occupied a
some of which are still being read today. In poetry, narrowly circumscribed period of time, such as 7,14,
tragedy, and comedy, in history and annals, in phi- or 20 days. Associated with the chronological devel-
losophy and theology, as well as in botanical, agricul- opment was a series of changes in the condition of
tural, and pharmacological texts, illness and health the patient, each of which was described in specific,
and life and death constitute distinctive motifs. though not necessarily unique, terms representing
To be certain, the evidence, both written and the symptom or symptoms associated with that spe-
nonwritten, has survived in different states of preser- cific stage of the disease. It is with respect to the
vation. It permits us, nonetheless, to reconstruct in latter point that grave difficulties are encountered
part the intellectual and technological achievements in an attempt to identify some of the diseases of
of our past. Large gaps, however, exist in our knowl- classical antiquity. First of all, it was widely be-
edge of that past, and the absence of crucial details lieved that some diseases were capable of passing
has led to hypotheses and inferences that cannot be into or changing into another disease. The latter was
tested directly. then characterized by its distinctive symptom or
Our knowledge of the diseases of classical antiq- symptoms, which often were similar to the principal
uity stands somewhere between demonstrative cer- symptom or symptoms that characterized the origi-
tainty and complete ignorance. There is, after all, a nal disease process. The newly arisen disease was
sizable body of Greek and Latin medical texts, and then regarded as a species of the disease from which
it, in turn, has generated an even larger body of it originated at a certain stage in the morbid process.
secondary literature. But for all that, our knowledge Then it too ran its predictable course, although
of the diseases of classical antiquity is far from com- therapeutic intervention (drug therapy, regiminary
plete. There are several reasons for its incomplete- therapy, or surgery) might alter its course.
ness, but it is important to keep in mind the enor- There was considerable discussion in antiquity con-
mous differences between the conceptual bases of cerning the proper nomenclature and, of course, ther-
the modern medical sciences and those of antiquity. apy of these so-called species or varieties of a disease;
These differences have important consequences in and as one might guess, there was little agreement
any attempt to identify the diseases of classical an- concerning details, especially with regard to their
tiquity and to understand their effects. classification. On one issue, however, there was agree-
One significant consequence is primarily philologi- ment and that was the widely adopted classification
cal: Many Greek and Latin medical terms cannot be of diseases as acute or chronic. In the main, acute
rendered adequately by any single term in most mod- diseases were characterized by a sudden onset, a
ern languages. A case in point is the specialized vo- clearly circumscribed febrile stage, and the involve-
cabulary denoting diseases, used primarily though ment of a specific localized area, frequently the respi-
not exclusively by the ancient medical writers. Obvi- ratory or digestive system. As such, most of our infec-
ously this has a bearing on the study of disease. Some tious diseases were regarded as acute diseases in
ancient medical terms appear to cover an indetermi- classical antiquity. Those disease processes in which
nately wider range of meaning than is expressed by a clearly demarcated febrile stage was absent and
their modern equivalents. For example, lepra (Xercpa) whose outcome could not be predicted on the basis of a

V.2. Western Antiquity 263
specified sequence of stages fell into the larger, less cous phlegm by Paul of Aegina (see also Galen).
organized category of chronic disease (e.g., gout, lead Finally, a solidist etiology was proposed by the Meth-
poisoning, and scurvy). odist sect — for example, by Soranus, whose last
Because it was not possible to base an etiology on work was translated into Latin by Caelius Aure-
specific microscopic, pathological organisms, close lianus. The latter states that apoplexy is a disease
attention was paid to the description of symptoms at caused by strictures (passio stricturae) of the tube
each stage of the disease process, from onset to out- and pore structure of the human body. Isidore of
come. Thus, many of the so-called species or vari- Seville suggests quite a different theory, but offers
eties of a disease acquired distinctive names; these no evidence or source. In fact, Isidore's entire entry
were based on a few of the salient symptoms or on a for apoplexy consists of one sentence: "Apoplexia is a
consistent clinical pattern, the latter resembling sudden effusion of blood, by which those who die are
what later came to be called a syndrome (literally, a suffocated."
"running together" of symptoms). In addition to the clinical relationship between
It must be stressed,finally,that ancient therapeu- apoplexy and paralysis, there is evidence of a more
tics was almost wholly symptomatic. Consequently, primitive distinction between apoplexy and tempo-
the large body of literature surviving from classical rary mental confusion (e.g., the state of being dumb-
antiquity must be used with due recognition of the founded, astounded, speechless), which is translated
fact that the illnesses for which the many hundreds as 'aKonkynoi; and/or aKvuXynxmoq in the non-
of recipes and remedies were designed must be con- medical literature, such as that by Herodotus, Aris-
sidered, in the main, to be symptoms and syndromes. tophanes, and Sophocles.
These caveats notwithstanding, some of the dis- It is difficult to separate neatly the classical be-
eases of classical antiquity can be identified with liefs regarding the incidence and epidemiology of
assurance and others can be identified with degrees apoplexy because of the ignorance surrounding its
of confidence that vary in proportion to both the qual- etiology. A few brief passages, here and there, sug-
ity and the quantity of the evidence at our disposal. Ingest, however, that its incidence in particular must
either case, however, efforts have been made to sum- have been a subject of some discussion. Thus, there
marize the etiologic, epidemiological, and pathologi- are two Hippocratic aphorisms concerned with age
cal evidence in such a fashion that the diseases of incidence: The first contains a short list of com-
classical antiquity can be correlated historically with plaints common to old men, including apoplexy. The
the same diseases viewed in later terms. meaning of old is specific in another: "Apoplexy oc-
curs chiefly between the ages of forty and sixty." (See
Apoplexy also Caelius Aurelianus, who notes that old women
Apoplexy (Greek apoplexia) is sometimes also called have special therapeutic problems.) Data on sea-
paraplexia or paralysis. The name apoplexia, accord- sonal incidence are also scarce. Hippocrates simply
ing to Caelius Aurelianus, is derived "from the fact stated that apoplexy was one of several diseases that
that it involves a sudden collapse, as if from a deadly frequently occurred in rainy weather. Caelius
blow. It is a sudden seizure (oppressio), in general Aurelianus, however, thought it most prevalent at
without fever, and it deprives the body of all sensa- the end of autumn or in the winter.
tion; it is always acute and never chronic." With regard to the pathology of apoplexy, detailed,
The etiology of apoplexy was stated in different clinical descriptions are provided by Celsus, Caelius
ways by the ancient medical authors. The earliest Aurelianus, Galen, and Paul of Aegina. Though their
account is from the Hippocratic corpus: It is caused descriptions do not agree verbatim, we can summa-
by winds or breaths (qruoag), "so, if copious breaths rize them by noting the major areas of consensus:
rush through the whole body, the whole patient is
affected with apoplexy. If the breaths go away, the 1. Sudden onset (with no or few antecedent indica-
disease comes to an end; if they remain, the disease tions)
also remains." Centuries later, Celsus wrote that the 2. Lack of fever
relaxation of the sinews (resolutio nervorum) was a 3. Feeble pulse and shallow respiration following
common disease everywhere. "It attacks at times the the stroke
whole body, at times part of it. Ancient writers 4. Lack of sensation
named the former, apoplexia, the latter, paralysis." 5. Impairment of muscular control, sometimes ac-
Elsewhere a humoralistic etiology was advanced: companied by tremors
black bile (melancholy) by Hippocrates, or cold, vis- 6. Comatose state

If there is recovery, the victim may show evidence and the "plague of Justinian." Many different com-
of mental impairment, especially in his or her municable diseases have been proposed for these
speech and uncontrolled muscular action. This cata- "epidemics" (a term that in Hippocrates' Epidemics
logue of signs was important to the physician not does not always mean what we mean by an epidemic
only for making a diagnosis but also for differentiat- disease; see Deichgraber 1933). Likewise, many dif-
ing apoplexy from other diseases, especially epi- ferent diseases have been proposed for the less well
lepsy, lethargy, and some forms of paralysis. known, but equally sporadic and frightening epidem-
ics whose echoes frequently resound in classical
Asthma texts, such as those of Karl Jax, Jiirgen Grimm, and
"The disease called orthopnoia," wrote Aretaeus, "is Jean-Marie Andre. Some of those epidemic diseases
also called asthma because those who have parox- may have been bubonic plague but, save for the
ysms pant for breath (asthmainousi)." The Greek description by Rufus and the acknowledged exis-
term asthma, used by Homer for a gasping, painful tence of the plague of Justinian (sixth century A.D.),
breathing, had acquired a distinct medical sense by the evidence is inconclusive. The likelihood of bu-
the time of Hippocrates. bonic plague cannot be dismissed totally, however,
The two terms asthma and orthopnoia are not because there is good evidence, first, that the plague
uncommon in ancient literature, but on the basis of was endemic in the Near East in the preclassical
the adjectival form, asthmatikos, a nonmedical us- period and, second, that the Greeks and Romans had
age (e.g., the labored panting of an athlete) may be frequent contact with the people of the Near East
suspected. from the sixth century B.C. onward and could easily
Like many diseases, the etiology of asthma was have contracted diseases thereby. It is, finally, al-
explained in humoralistic terms. "The cause," most certain that bubonic plague was not unknown
Aretaeus states, "is the coldness and moistness of in late antiquity, as Byzantine reports by Paul of
the pneuma but the matter is moist, cold, and gluti- Aegina and Arabic and early Western medieval re-
nous." Airborne pollen and dust do not seem to have ports testify.
been implicated in the sometimes sudden onset of an It is, then, in the context of the later stages of
allergic reaction, the latter a concept not explicitly Greco-Roman civilization that one must consider the
associated with asthma in classical texts. It may be passage from Rufus noted at the beginning of this
significant, however, that Hippocrates notes that section. Rufus of Ephesus, a highly regarded physi-
asthmatic attacks are frequent in the autumn. cian and medical writer, lived during the reign of the
Aretaeus's account of the symptoms, the best sin- emperor Trajan (A.D. 98-117). He is known to have
gle description in classical antiquity, refers in unmis- been active in Rome and to have spent some time in
takable terms to the overt characteristics of asthma Egypt. A short passage referring to the buboes typi-
and emphasizes the dry wheezing, often unproduc- cal in a case of plague was preserved, presumably
tive cough, inability to sleep in a prone position, and because of its unusual interest, by the later (fourth-
labored efforts to breathe leading to gulping or gasp- century) Greek physician Oribasius in his chapter
ing. He seems not to have recognized, however, the on buboes. Because of its historical importance, I
constriction of the lumen of the bronchi or the possi- have translated the passage from Rufus:
bility of neurological or hereditary factors.
The buboes termed pestilential are the most fatal and the
Bubonic Plague most acute, especially those that are seen in Libya, Egypt,
In the large, sometimes uncritical literature in the and Syria, as reported by Dionysius the Kyrtos. Diosco-
rides and Poseidonius have studied especially the plague
history of bubonic plague, the earliest, unimpeach- (Xoir)O5) which occurred in Libya in their time. They have
able reference to the plague in classical antiquity is said that [it was characterized by] high fever, pain, distur-
that provided by Rufus of Ephesus. There are also a bance (crucrtaai?) of the entire body and the formation of
considerable number of Greco-Roman descriptions of large buboes, hard and non-suppurating. They develop not
and references to epidemics in our sense of the term only in the ordinary places but also in the groins and the
(or, in Greek and Latin, Xoyog [whence our word neck. (Translated from Oribasius.)
plague] and pestis pestilentia). These were of various
kinds, usually unidentifiable, with various degrees It may be noted that buboes had been mentioned
of morbidity and mortality, and not always chrono- many centuries earlier by Hippocrates. Sometimes
logically or geographically positioned. The most fa- they meant glands, but in other cases they seemed to
mous were those of the Iliad, the "plague of Athens," refer to the large lymphatic swellings associated

with the plague. Because Hippocrates does not as- developed an elaborate taxonomy, with correspond-
sign a name to the disease of which the buboes are ing names, for a wide range of conditions that are
one of the most dramatic signs, it is difficult to de- reproduced in English by the nonspecific, generic
cide whether bubonic plague was known to him. term swellings. Celsus's distinctions were carried
Before Oribasius, Aretaeus referred to pestilential further by Galen, who distinguished among a wide
buboes of the liver, whereas Pliny the Elder referred range of diseases, localized morbid conditions, and
to a plant, bubonium, whose name derived from the various dermatological complaints. But Galen intro-
fact that it was considered especially beneficial for duced one important improvement: He identified as
swellings of the groin (inguinum). These bits and malignant only those oyxoi (tumor[s]) that most
pieces of information (and undoubtedly others exist), closely resemble our concept of malignant neo-
especially when coupled with references to "pestilen- plasms and called them xaxovSy.
tial times" by Marcus Aurelius and Aristides, sug- The large amount of space devoted to recipes and
gest that bubonic plague may have been implicated, other therapeutic forms for "swellings" and abscesses
more often than we have recorded, in the numerous (e.g., by Cato, Paul of Aegina, Pliny, and Hippocrates)
outbreaks and epidemics, though not recognized as a strongly suggests that malignant, often fatal, condi-
discrete clinical entity. tions were not uncommon, despite the lack of con-
sensus on signs and symptoms and the equally obvi-
Cancer ous lack of a standardized nomenclature. Slightly
The term cancer derives from the Latin cancer, more certain to have involved cancer is a series of in-
which in turn derives from the Greek xoxxi/uoco both operable, incurable, or fatal conditions of specific
originally meaning a crab. Other medical terms organs or bodily parts that were, more or less, amena-
used in classical antiquity derive from the same ble to examination, such as the breast, testicles, nose,
root. These terms, however, do not necessarily mean and throat. It is even more problematic that
or refer to a neoplastic growth or malignant lesion. neoplastic growths of internal organs were recog-
There is some evidence, in fact, that ulcers and le- nized, but perhaps it was to these that Hippocrates
sions associated with other diseases (e.g., erysipelas was referring by the phrase xeamxoi xaexicooi (hidden
and gangrene) were not always distinguished from cancers).
malignancies. Reflecting the uncertainties in the diagnosis and
As a medical term, xoxxiuoco first appears in therapy of what Galen called "swellings contrary to
Hippocrates but in contexts that only suggest what nature," their etiology was equally uncertain.
is meant today by cancer. Later uses of the term by Galen, however, twice explicitly stated that black
Galen and his followers were similar to the medical bile was the cause of cancers. A hint of another, not
and clinical uses that prevailed up to the time of necessarily incompatible etiology is contained in
Rudolph Virchow. In the same way, the more re- Celsus's statement that, whereas some ulcers arise
stricted term carcinoma might have denoted a malig- from an external cause, carcinomata and the like
nant condition, especially when the condition termi- "arise from within, from some part of the body which
nated fatally as, for example, in Hippocrates, has been corrupted."
Caelius Aurelianus, and Cassius Felix. The most
extended account of cancer, next to Galen's, was that Diphtheria
of Celsus, who attempted to distinguish a variety of The term diphtheria, introduced by Pierre Bre-
swellings (tumors). He gave special names (e.g., tonneau to replace his earlier term diphtheritis, de-
atheroma, steatoma, and therioma) to some of these - rives from the Greek, literally "skin, hide," referring
probably not the malignant ones. However, he also to the characteristic tough, white pseudomembrane
described certain, more serious conditions, perhaps of the trachea and other respiratory organs in ad-
complications of erysipelas and gangrene, and these vanced cases. There do not appear to be any classical
he likened to cancer. He reserved the term carci- Greek or Latin terms to designate this once-dreaded
noma or carcinode for other tumors that, when they infectious disease. Aretaeus's terms (Egyptian and
did not appear to have been the result of another, Syriac ulcers) were not adopted by later writers.
antecedent disease, may have been malignant. Diphtheria seemingly was not always differentiated
The terms just noted and other Greco-Roman cog- from other infectious diseases, and it was not unam-
nates such as cancroma are not as common in the biguously described until many centuries later.
medical literature as one might expect and are even The two best accounts of diphtheria in classical
rarer in the nonmedical literature. Instead, there antiquity are those of Aretaeus and Aetius of

Amida. These two passages, supplemented by the especially infants, were highly susceptible, and the
more vague accounts of Hippocrates, described the season of highest incidence was winter. There
principal signs and symptoms on the basis of which seems to be no evidence for a disproportionate sex-
classical diagnoses were made before Friedrich ual incidence.
Loffler's identification and isolation in 1884 of Bacil-
lus diphtheriae, now Corynebacterium diphtheriae. Dysentery
The Hippocratic passages alluded to and a remotely The word dysentery (Latin dysenteria) derives from
possible reference by Soranus describe a condition the Greek dys (bad) plus enteria (intestine), thereby
that is not incompatible with diphtheria, but the indicating the system involved, though not, of
absence of crucial data make a more positive identifi- course, the causative agent.
cation impossible. Although explicit references are not common, it is
At any rate, these passages together provide a probable that dysentery was widespread in antiq-
clinical picture similar to the early modern accounts uity. Some evidence is provided by a series of four
of angina maligna, one of the many names in use aphorisms in Hippocrates, as well as the explicit
before Bretonneau. Signs and symptoms as reported statement that dysentery was common in the sum-
by Aretaeus and Aetius of Amida (Hirsch 1886) in- mer and autumn. Elsewhere, in an attempt to estab-
clude the development of a phlegmatic, whitish film lish the disease pattern and age incidence, it is writ-
in the mouth and throat, rapidly spreading to the ten that men (beyond the age of young men, i.e., 30
trachea, accompanied by a foul odor. The disease, years and older) commonly suffer from 11 diseases, 2
often accompanied by fever, is rapidly fatal, espe- of which are chronic diarrhea and dysentery. This
cially among juveniles. Death is caused by suffoca- fits the pattern of men of military age and the condi-
tion, but weakness due to an aversion to food and tions of crowding and lack of proper sanitation facili-
drink may be a contributing factor. The voice is tating local outbreaks, if not small epidemics.
hoarse and strangely modulated; respiration is rapid Various philosophical and medical theories were
but shallow; and liquids are sometimes passed out advanced to explain the sudden outbreak, its spread,
through the nose (due to a paralytic destruction of and the distinctions, not always clear, between acute
the soft palate, though not explicitly so stated by the and chronic dysentery, on the one hand, and between
classical authors). dysentery and diarrhea, on the other. Roughly, there
As is well known, diphtheria epidemics have oc- were two different kinds of etiologic proposals, each
curred, and both morbidity and mortality rates can of which had its adherents, some of whom tried to
be high, especially for children. For those reasons combine the salient features of the two competing
one would expect prima facie a larger number of theories. Whether the humoral explanation came
classical references to diphtheria. There are perhaps earlier is difficult to judge; at any rate, Hippocrates
two reasons for the paucity of data. First, diphtheria seems to have been the earliest exponent of the
might have been confused with other diseases (e.g., theory that one of the humors, in this case black bile,
aphthae, tonsilitis, candidasis). Second, the rapid was the causative agent. Other writers (e.g., Plato,
course of fatal diphtheria did not permit the ancient Timaeus, and Cassius Felix) selected other humors
physicians sufficient time to examine the patient as the causative agent. The other theory, equally
with an eye on prognosis. reasonable at that stage of medical inquiry, was that
The source material at our disposal suggests that unconcocted or undigested food, not necessarily
the etiology of diphtheria was somewhat uncertain. "bad" food, was the cause. This theory is represented
An overabundance of phlegm easily accounted for the by Aristotle and Aretaeus. At the end of the classical
development of the characteristic pseudomembrane. period, Paul of Aegina suggested that the mucus
A further explanation is provided by Aretaeus's re- found in the feces indicated undigested food, al-
mark that the natural heat of young children is though he opted for black bile as the principal cause.
cooled by the rapid respiration and inspiration of cold We may note here, before discussing the pathology of
air (apparently thus hastening the development of dysentery, that no evidence is available at present as
the phlegmatic pellicle). Finally, a dietetic cause is to whether the dysentery of the classical writers was
subjoined by Aretaeus: The thick and impure food bacillary (shigellosis) or amebic.
and drink of the Egyptians lead to morbid changes, The literature on the signs and symptoms of dysen-
the so-called Egyptian ulcers. tery corroborate the belief that dysentery was both
Only the barest facts on incidence are available, widespread and common. All authorities are in agree-
but they highlight two important facts: Children, ment that a compelling need to defecate, the fre-

quency of which is proportionate to severity, quickly sions, and contusions must have provided easy access
becomes unproductive and that the production of to the pathogens. Third, even without therapeutic
well-formed stools, within 48 to 72 hours, changes to intervention, many cases of self-limiting erysipelas
the production of watery stools. Such watery stools, ran their courses with little lasting trauma to the
from ones tinged reddish to ones highly colored with patient.
blood, were often thought to contain fleshlike shreds The symptoms of erysipelas are so clearly de-
of undigested food (i.e., mucus or pus). In addition, the scribed by the classical medical writers as to leave
gripings in the lower abdomen, so ran the prevailing little doubt about the accuracy of the identification.
theory, led to typical straining - tenesmoi - that both These include redness and swelling with a spreading
physically evacuated the inadequately concocted food painful lesion (Celsus), usually accompanied by fe-
products and dehydrated and physically enervated ver (Hippocrates). In agreement with modern symp-
the victims. tomatology, erysipelas was described on most of the
There was less agreement regarding other signs. more exposed portions of the body; specifically, it
Celsus, for example, asked whether the patient was was noted as involving the face and the mucous
always fevered, and Alexander of Tralles tried to membranes of the mouth and throat (Hippocrates),
determine the extent to which the liver was in- thus perhaps as being one of the causes of
volved. Galen has left us the best account of the noninfantile aphthae. Celsus and Hippocrates noted
typical ulcerated lower intestine. Finally, Hippo- appearance of erysipelas soon after the infliction of a
crates seems to have regarded dysentery following wound, and Celsus made the distinction, though not
an enlarged spleen (perhaps of malarial origin) as a with complete understanding, between idiopathic
favorable condition, doubtless with the thought in and traumatic erysipelas. It is more difficult to un-
mind that a natural catharsis would help to reduce a derstand what is meant by erysipelas of specific,
swollen organ by removing impurities. usually internal, organs, for example, uterus and
lungs (Hippocrates) and brain (Paul of Aegina). A
Erysipelas Hippocratic aphorism suggests that the phrase
Erysipelas is a direct transliteration of the Greek, inward-turning erysipelas (regarded as a dangerous
literally "red skin," referring to its most obvious sign) is simply a way of expressing the fact that
characteristic. It was usually termed ignis sacer other, more serious symptoms accompanied the ex-
(holy fire) in classical Latin, and the synonym is ternal, reddened areas.
confirmed by Celsus and Cassius Felix. It is impor- The etiology of erysipelas was not altogether clear
tant to note that the erysipelas termed ignis sacer is but, as was frequently the case with infectious dis-
distinct from ergotism, sometimes also called ignis eases of rapid onset, a humoralistic explanation was
sacer or St. Anthony's Fire. advanced by Galen and Paul of Aegina.
Although noted several times by Hippocrates, Hippocrates noted that "early in the spring" was
erysipelas was not given much attention in classical the season of highest incidence and that "those of
medical writings and is very rare in nonmedical about sixty years" were especially prone; however,
writings (but see Lucretius and possibly Virgil). It his detailed case history in Epidemics describes the
was considered to be serious, however, and an epi- nonfatal case of an 11-year-old boy.
demic was reported by Hippocrates. Fatalities were
reported by Hippocrates and Paul of Aegina. It is Malaria
clear that the erysipelas of classical texts is not In the opinion of most scholars, malaria was common
always restricted to the streptococcal infection in classical antiquity. Moreover, it seemed to be wide-
known by that name today, for apparently some- spread geographically, as references to both local ma-
times it was confused with gangrene and herpes, as, larious and malaria-free regions indicate. Malaria, in
for example, by Scribonius Largus. fact, may have been endemic in some regions; if so, it
Despite the relatively slight attention paid to the undoubtedly colored the clinical findings of some
etiology and incidence of erysipelas by classical writ- chronically ill patients and may have been responsi-
ers, there are reasons for believing that, in fact, it was ble for infant deaths not otherwise indicated. Less
far from rare. First, the disproportionately large certain are the socioeconomic consequences of en-
amount of space devoted to a host of different thera- demic malaria, although work efficiency must cer-
peutic forms by Caelius Aurelianus, Scribonius, tainly have been impaired in malarious regions and
Pliny, and Oribasius strongly suggests it was not among those who suffered from chronic malaria.
uncommon. Second, the prevalence of wounds, abra- Despite the large literature on the history of ma-

laria and the innumerable surveys undertaken in classical medical texts and a comparison of those
conjunction with malaria eradication programs (in texts with the numerous but scattered references to
which patients were examined before or in the ab- "fever" in the nonmedical texts leaves little doubt
sence of chemotherapy, and hence were clinically that malaria was indeed common and well known.
analogous to patients of classical times), it is not The best evidence for this claim is provided by the
easy to document the early history of malaria. conjunction of signs and symptoms that would be
There are many reasons for our lack of certainty recognized as malarial today, in the absence of any
regarding malaria in classical antiquity, and since chemotherapy. Principally, three signs, when associ-
they are so intimately bound up with our interpreta- ated with other data (e.g., cachexia or habitation in
tions of classical sources, it is worth listing some of an area known to be "unhealthful," especially when
them. This will help us to do what the ancient physi- situated near a marsh or estuary), established diag-
cians tried to do, namely to distinguish malaria from noses until the advent of blood smears. First was
a host of other diseases and pathological conditions. splenomegaly. In routine physical examinations of
First, until the late nineteenth century, there was the sort that Hippocrates advocated, palpation of the
no knowledge of the pathogenic organisms (the hypochondrium would often reveal an enlarged, ten-
Plasmodia) involved. Thus, any diagnosis of malaria der spleen according to Celsus and Hippocrates. Sec-
(or of one of the diseases with which it was often ond was the invariable sequence of chills, fever, and
confused) depended, to a great extent, on the accu- sweats, which was noted in many texts, among them
rate recording of the signs and symptoms exhibited those of Celsus, Pliny, and Hesychius. Third was the
by a patient. Second, and perhaps as a function of its periodic nature of the disease, usually indicated in
widespread distribution, malaria was often confused Latin by accessia. This is a more complex issue be-
with other febrile conditions (e.g., phrenitis). On this cause of the nosological tendencies of medical writ-
matter, we have the explicit testimony of Galen's ers who divided and classified fever into various
works, as well as smaller texts such as that of Alex- forms: cottidian (daily); tertian (every third day;
ander of Aphrodisias. Diodes and Crasistratus both counting day of onset and day of crisis = every 48
wrote books entitled On Fevers, which have been hours); quartan (every fourth day; counting day of
lost. Third, and as a consequence of the first two onset and day of crisis = every 72 hours). To these
points, the nomenclature was confused and inconsis- may be added the more puzzling quintans, septans,
tent. Until the postclassical term, literally meaning nonans, semitertians, and other mathematical,
"shivering fever," came into use, other terms were though not necessarily clinical, entities.
commonly employed. None of them were completely It was presumably through a long period of noting
satisfactory because they had other conflicting defi- and recording the constellation of such signs, and
nitions such as "nightmare" or the shivers that ac- patients' symptoms, that a "malarial constitution"
companied the disease. The term febris was too was denned, according to Hippocrates. This, in turn,
broad, and hence although the root meanings of fire, led to the establishment of the typical malaria ca-
heat, and burning were applicable to malaria fever, chexia and its common occurrence in classical Rome,
they could and did apply to other febrile conditions; as indicated by Martialis, Juvenal, Horace, and Livy.
xcnjoog, or febris ardens, also signified intense, burn- The same wide range of opinion covering the differ-
ing heat, though, of course, there was no way of ential diagnosis of malaria applies equally well to its
translating the subjective sensations of a feverish etiology. There are hints of a very ancient belief in a
patient into thermometric terms. Other, more re- supernatural origin. Sophocles, when describing an
stricted terms existed, but they will be examined epidemic (of unknown origin) at Thebes, refers to a
later. Fourth, the different types of Plasmodium in- "fever-bringing god." This does not prove that ma-
fection, best exemplified by the well-known terms laria was the cause of the epidemic any more than
tertian and quartan malaria, were so well recognized the presence of a temple dedicated to the goddess or
that they were regarded as separate diseases; more- numen Febris in Rome (according to Cicero and
over, other diseases (e.g., phrenitis and lethargy), Pliny) proves that malarial fevers could always be
which may have had a malarial basis, were regarded distinguished from other fevers.
as capable of passing or changing into other febrile In Hippocrates, the etiology of four types of fever
conditions and hence confounded diagnosis, progno- was explained in humoralistic terms. Three of the
sis, and therapy alike. fevers are clearly malarial: cottidian, tertian, and
These difficulties notwithstanding, a close reading quartan. The first two of these were caused by vari-
of the chapters devoted to "fever" and so forth in the ous amounts of surplus yellow bile; quartan was

caused by a mixture of yellow and black bile. It was Grimm, Jiirgen. 1965. Die literarische darstellung der pest
the "mixed humoral state" that was responsible for in der antike und in der Romania. Munich.
the longer cycle, which explained why quartan was Herodotus of Halicarnassus. 1958. The histories of Herodo-
more recalcitrant to therapy. tus of Halicarnassus, trans. Harry Carter. New York.
In addition to a humoralistic etiology, Galen wrote Hesychius of Alexandria. 1965. Hesychii Alexandrini Lexi-
con, ed. Moriz Wilhelm Constantin Schmidt and Ru-
of a "feverish constitution" being due to a pestilen-
dolph Menge. Leipzig.
tial air, which could also be described as a "pestilen-
Hippocrates. 1894-1902. Opera, 2 vols., ed. H. Kuehle-
tial constitution." It was also observed, for example wein. Leipzig.
by Celsus, that fatigue and hot weather led to fever; Hirsch, August. 1883-6. Handbook of geographical and
elsewhere he states, however, that therapy is diffi- historical pathology, 3 vols., trans. Charles Creighton.
cult because fever can have both evident and hidden London.
causes. Homer. 1950. The Iliad, trans. A. H. Chase and W. G.
Both medical and nonmedical writers (e.g., Hippoc- Perry, Jr. Boston.
rates, Horace, and Juvenal) agreed that late summer Horace. 1936. The complete works of Horace, ed. Casper J.
and autumn were the most likely seasons to be char- Kraemer, Jr., trans. Hubert Wetmore Wells. New
acterized by fever - a vestige of which survived until York.
recently in the phrase estivoautumnal fever for Isidore of Seville, Saint. 1964. Etymologiae, trans. William
falciparum malaria. D. Sharpe. Philadelphia.
Jax, Karl. 1932. Aegypten in Hellenistischer und Romi-
Jerry Stannard scher zeit nach antiken papyris. Munster.
Juvenal. 1965. Juvenal: Satires, trans. Jerome Mazzaro.
Bibliography Ann Arbor, Mich.
Andre, Jean-Marie, and Alain Hus. 1974. L'Histoire a Livy. 1976. Livy: In fourteen volumes, ed. G. P. Goold and T.
Rome: Historiens et biographes dans la litterature la- E. Page, trans. B. O. Foster et al. Cambridge, Mass.
tine. Paris. Loffler, Freidrich. 1884. Untersuchungen uber die be-
Aretaeus of Cappadocia. 1828. Aretaei Cappadocis opera deutung der mikroorganismen fur die Entstehung
omnia, ed. C. G. Kiihn. Leipzig. der Diphtherie beim Menschen, bei der Taube und
Aristides, Aelius. 1958. Aelii Aristidis Smyrnaei quae su- beim Kalbe: Mittheilung kaiserlichen Gesundhante 2:
persunt omnia, ed. Bruno Keil. Berlin. 421-99.
Aristophanes. 1988. The wasps, ed. Douglas M. McDowell. Lucretius Carus, Titus. 1937. Der rerum natura, trans.
Oxford. R. C. Trevelyan. Cambridge.
Aristotle. 1908-52. The works of Aristotle translated into Marcellus Empiricus. 1567. Writings. In Medicae artis
English, 12 vols., ed. J. A. Smith and W. D. Ross. principes post Hippocraticum et Galenum, Graeci La-
Oxford. tinitate donati, ed. H. Stephanus. Geneva.
Aurelianus, Caelius. 1950. On acute diseases and on Marcus Aurelius. 1983. The meditations, trans. G. M. A.
chronic diseases, trans. Israel Edward Drabkin. Chi- Grube. Indianapolis.
cago. Martialis, Marcus Valerius. 1947-50. Epigrams, trans.
Blass, Fredrich Wilhelm. 1895. Ada apostolorum: Sive, W. C. A. Ker. Cambridge.
lucae and theophilum liber alter. Gottingen. Oribasius. 1964. Oribasii collectionum medicarum reli-
Bretonneau, Pierre Fidele. 1826. Des inflammations sp6- quiae, 4 vols., ed. Johann Raeder. Amsterdam.
ciales du tissu muqueux et en particulier de la Ovidius Naso, Publius. 1933. Ovid's Metamorphoses, 2
diphtherite, ou imflammation pelliculaire. Paris. vols., ed. and trans. Brookes More. Boston.
Cassius, Felix. 1879. Casii Felicis de medicina: Ex graecis Paul of Aegina. 1844—7. The seven books of Paulus
logicae sectae auctoribus liber, translatus sub Artabure Aegineta, 3 vols., trans. Francis Adams. London.
et Calepio consulibus, ed. Valentin Rose. Leipzig. Pliny the Elder. 1855-87. The natural history of Pliny,
Cato, Marcus Porcius. 1966. De agricultura, trans. Ernest trans. John Bostock and H. T. Riley. London.
Brehaut. New York. Rufus of Ephesus. 1726. De vesicae renumque morbis. De
Celsus, Aulus Cornelius. 1938. De medicina, trans. Walter purgantibus medicamentis. De partibus corporis hu-
George Spencer. Cambridge. mani, ed. William Clinch. London.
Deichgraber, Karl. 1933. Die epidemien und das corpus Scribonius Largus. 1887. De compositionibus medica-
Hippocracticum: Voruntersuchungen zu einer Ge- mentorum liber unus, ed. G. Helmreich. Berlin.
schichte der Koischen Artzeschule. Berlin. Sophocles. 1970. Philoctetes, ed. T. E. L. Webster. Cam-
Dioscorides, Pedanius. 1906-14. De materia medica, 3 bridge.
vols., ed. Max Wellmann. Berlin. Soranus of Ephesus. 1927. Sorani Gynaeciorum libri IV,
Galen. 1821-33. Opera omnia, 22 vols., ed. C. G. Kuhn. De signis fracturarum, De faciis, Vita Hippocratis
Leipzig. secundum Soranum, ed. Johannes Ilberg. Leipzig.

Thucydides. 1921-30. History of the Peloponnesian War, 4 (half of thefieldssown in the autumn to take advan-
vols., trans. Charles Forster Smith. London. tage of winter rains in the south, half left fallow to
Trallanius, Alexander. 1963. Alexander von Tralles: restore fertility) were ultimately replaced by the
Original-text und Uebersetzung nebst einer einlei- heavy plow, the horse, and a three-field rotation
tenden Abhandlung: Ein Beitrag zur Geschichte der system. A new plow, usually mounted on wheels and
Medizin, 2 vols., ed. and trans. Theodor Puschmann. heavy enough to require eight animals to pull it,
Amsterdam.
turned the soil so thoroughly that no cross-plowing
was required and produced long, narrow fields in-
stead of the square plots of the south. The moldboard
of the new plow, which could turn the turf in either
direction to assist drainage of the fields, was ideal
V.3 for the opening of alluvial bottomland, the richest
Diseases of the Middle Ages land of all. After the development of nailed horse-
shoes and a padded horse collar with harness at-
tached (the old oxen neckstrap tightened across the
During the Middle Ages (roughly A.D. 500-1500), jugular vein and windpipe of the horse), horses
Europe changed from an agrarian society composed gained greater speed and staying power, which not
of relatively small and isolated communities to an only increased the amount of land a peasant could
increasingly commercial and urban world, though farm but also the distance he could travel to reach
still predominantly agricultural. After centuries of his outermost strips.
static or declining growth in late antiquity, the popu- But horses eat more than oxen do and prefer oats,
lation of Europe increased approximately threefold which are planted in the spring; therefore, the wide-
between 800 and 1300. Generally, the history of medi- spread use of the horse had to await the food sur-
eval diseases reflects these demographic and eco- pluses of the three-field rotation system. Spreading
nomic facts. While the ancient diseases of pneumo- outward from the Frankish lands between the Rhine
nia, tuberculosis, and smallpox, and others including and the Seine, this system faced great practical ob-
typhoid, diphtheria, cholera, malaria, typhus, an- stacles in the creation of the third field and was
thrax, scarlet fever, measles, epilepsy, trachoma, firmly established only in the wake of the devasta-
gonorrehea, and amebiasis persisted throughout our tion caused by raids of Vikings and Magyar horse-
period, many diseases of Europeans during the early men in the ninth and tenth centuries. By approxi-
Middle Ages were related to deficient diet. mately 1200, most of northern Europe had accepted
Improved nutrition in the later Middle Ages led to the three-field system, whereby one-third of arable
a relatively larger population. As Fernand Braudel land was planted in spring to catch the abundant
(1979) has emphasized, an increase in population summer rains, one-third was planted in autumn,
alters all aspects of life, bringing advantages but at and one-third was left fallow. The system meant an
the same time threatening the existing standard of overall increase in production of 50 percent.
living and hope of improving that standard. In addi- Before this revolution, the peasantry, which com-
tion, it can bring disease. Ironically, the improved prised 98 percent of the European population, had
nutrition that made possible the growth of popula- subsisted on a high-carbohydrate diet ingested as
tion, towns, and trade in the Middle Ages in turn bread, porridge, and beer, whether derived from bar-
created fertile opportunities for the contagious dis- ley, as in some parts of the north, or from rye and
eases that ultimately changed the face of Europe. wheat. When a peasant's principal crop failed, he
and his family might well starve. Moreover, even
Nutrition and Disease with optimal harvests, they very likely experienced
A revolution in agricultural techniques in northern severe protein deprivation. The agricultural revolu-
Europe has been credited with this remarkable popu- tion brought them not only greater yields, but a
lation growth (e.g., White, Jr. 1962). Agrarian meth- diversity of crops, including legumes and peas,
ods inherited from the Roman Empire were suitable which served as a protection against famine and
for the warm, dry lands of the Mediterranean and provided more vegetable protein. These nutrients
Near East, but proved inadequate on the broad, fer- were to be of far-reaching nutritional consequence,
tile plains of northern Europe. The old scratch plow for the peasant seems to have received little animal
that required the double labor of cross-plowing to protein in the early Middle Ages.
turn the soil, plodding oxen, and two-field rotation It is true that abundant meats - domestic and

V.3. Middle Ages 271
game - as well as poultry and fish covered the tables ton, or veal, suggest that by then these meats had
of the rich. But the peasants are believed to have become the food of ordinary people (Drummond and
consumed what very little animal protein they re- Wilbraham 1959). Finally, the agricultural revolu-
ceived in the form of what was known, with unmis- tion brought surpluses in a variety of crops, so that
takable irony, as "white meat," that is, dairy there was less risk of starving when one crop failed.
products - milk, cheese, and eggs (Drummond and The result was better nutrition for all, which pre-
Wilbraham 1959). Peasants might own some live- served the lives of those less fit, especially children.
stock and poultry, which wandered freely in the vil- Women are believed to have suffered more than
lage; however, early medieval animals were subject men from the deficient diet of antiquity and the
to the frequent hazards of disastrous epidemics, win- early Middle Ages. Many sources from the ancient
ter starvation, and sacrifice in time of famine, and world indicate that men outlived women, and an
consequently they could not be regarded as a depend- examination of French and Italian records from the
able source of food (Drummond and Wilbraham ninth century shows that, whereas more female
1959). Seemingly conflicting evidence has been ob- childern than male reached the age of 15, males
tained from excavations of several ports and other nonetheless enjoyed a greater life expectancy than
emporia of the ninth century (Dorestad, Holland; females (Herlihy 1975). Numerous explanations of
Southampton, England; and others) that reveals this paradox have been offered, including the un-
that not only prosperous merchants, but humble citi- derreporting of women because they were living in
zens with small houses and farm plots within the concubinage and death in childbirth (for a survey of
town, consumed a considerable amount of meat and theories, see Siegfried 1986).
seafood, judging by bones and shells found in pits In the thirteenth and fourteenth centuries, how-
(Hodges 1982, 1984). However, town dwellers, espe- ever, writers begin to indicate a surplus of women.
cially in coastline communities, were not representa- Rheims had an excess in 1422, Fribourg in 1444, and
tive of the great portion of the population that was Nuremberg in 1449 (Herlihy 1975). Some scholars
tied to the land, and as a general rule, early medi- explain this reversal by the greater iron content of
eval peasants can be assumed to have seldom eaten the average diet of the later Middle Ages that accom-
meat - usually what they could obtain by hunting or panied the greater consumption of meat and le-
poaching on the manor lord's land (Drummond and gumes. Until the onset of menstruation at 12 to 14
Wilbraham 1959). (the average age mentioned in ancient and medieval
Hunting diminished as population increased and medical treatises; see Bullough and Campbell 1980),
the forests yielded to the plow. Presumably, as the young girls need no more iron than boys, but after
forest dwindled, poaching penalties became more se- menarche, they require replacement iron of 1 to 2
vere, though the trapping of small animals must milligrams per day.
have remained common. Freshwater fish filled mill In the early Middle Ages women probably re-
ponds, of which England had 5,624 in 1086 accord- ceived no more than 0.25 to 0.75 milligram and
ing to the Domesday Book, and ocean fish became consequently must have become progressively iron
far more available after the salting of herring was deficient. Cooking in iron pots can increase iron in-
introduced in the thirteenth century or soon after. take, but pottery probably was in common use until
Rabbits spread northward slowly across northern the twelfth or thirteenth centuries. During preg-
Europe from Spain in the early Middle Ages, reach- nancy and lactation, a woman's iron requirements
ing England by 1186 at least (White 1976). Neverthe- are considerably greater, rising to as much as 7.5
less, it was only after the agricultural revolution milligrams per day in late pregnancy. Severe ane-
produced food surpluses that could sustain food live- mia predisposed women to death from other causes -
stock, as well as humans and horses, that animal respiratory, coronary, or hemorrhagic - and by the
protein became readily available. That this was the third pregnancy, a woman's life must have been at
case by the early fourteenth century is evidenced by severe risk (Bullough and Campbell 1980).
the fact that the church saw fit to urge abstinence Unfortunately for historians, few medieval records
from eating flesh on fast days, indicating that regu- exist to document protein or iron deficiency or the
lar meat consumption must have become an ordi- other numerous deficiency diseases recognized by
nary practice (Bullough and Campbell 1980). In addi- modern science. Still, rickets, known since ancient
tion, protests against the enclosure movement of the times, can be assumed to have existed in regions
sixteenth century, in which country people com- where neither ample sunshine nor a diet containing
plained that they could no longer afford beef, mut- substantial amounts of seafood or dairy products was

available. Ophthalmia, caused by vitamin A defi- because they were growing, ingested more ergot per
ciency, would have been a problem wherever famine unit of body weight - exhibited dramatic symptoms,
or severe poverty was found. Scurvy may be assumed writhing and screaming from burning pains in their
to have been prevented by the inclusion of cabbage or limbs. In fact, a close correlation has been made
other vegetables or fruits in the diet, though fruits between the growing of rye, cold and damp weather,
were expensive, available only for a limited season, and the persecution of what was regarded as witch-
and widely regarded with suspicion (Drummond and like behavior in sixteenth- and seventeenth-century
Wilbraham 1959; Talbot 1967). Pellagra, however, England (Matossian 1983).
was not a problem in Europe until maize, which is
deficient in niacin, was brought from the New World Infectious Disease
in the sixteenth century and became the staple crop As the agricultural revolution progressed, it pro-
in some areas. moted population growth and a much greater popula-
Although malnutrition or undernutrition can pro- tion density - indeed, a density not known since the
duce higher infection rates, history shows us that decline of Rome in the late empire. This density in
epidemics by no means regularly follow famines. It turn became the new enemy of population growth in
is true that in the process known to biologists as the the West. The Near East had long been characterized
synergism of infection, victims cease to eat well, by a relatively high density of population and urban
even though they have greater metabolic needs and centers, and consequently the peoples of the region
are exhausting their protein reserves in the fight had long been developing resistance to the disease
against infection. But the host's immune system generated in such dense populations. Thus, Europe-
fails only when actual starvation exists. Indeed, ans who came in contact with the old centers of civili-
chronic malnutrition may actually assist the host in zation were at serious risk of developing infection.
withholding nutrients necessary for a microorgan- Nonetheless, travel to these centers increased
ism, in the natural defense mechanism known as throughout the Middle Ages. Simple pilgrimages
nutritional immunity, and many virulent infections drew Europeans to the Holy Land as early as the
appear without any synergism in victims of poor fourth century. Wars of Christian reconquest in Sar-
nutrition (Carmichael 1983). dinia, Spain, and Sicily reopened the Mediterranean
Although not a deficiency disease, ergotism, called Sea in the eleventh century, and from 1096 to 1271
ignis sacer or St. Anthony's fire, is associated with Crusaders struck out for the Holy Land. Contact with
such diseases because it attacked whole communi- the East stimulated a taste for its products, especially
ties that had consumed rye grain infected with the textiles, furs, and spices, and led to the establishment
ergot fungus. Because the fungus grows in damp of permanent trade routes, with caravans regularly
conditions, contamination of the crop occurred most traveling as far as the Mongol Empire.
frequently after a severely cold winter (which re- This trade contributed to the widespread growth
duced the resistance of the grain) and a rainy spring, of European cities and the birth of new towns.
or when rye had been planted in marshy land, such Overcrowding in poorly ventilated dwellings with
as land newly cultivated because of the pressures of thatched roofs and dirtfloors,and infested with rats
population growth. Figuring prominently in the his- and fleas, provided fertile ground for the spread of
tory of French epidemics in the Middle Ages, er- communicable diseases inevitably brought in, often
gotism can be traced as far back as 857, with five from afar.
outbreaks in the tenth century and several in each The water supply in these urban areas was usu-
successive century. It occurred most frequently in ally dependent on a river, which underwent seasonal
the Loire and eastern French provinces. Its cause variation in volume and was subject to contamina-
was not then recognized, and miraculous cures were tion from sewage and refuse. Brewers, dyers, tan-
claimed through the intercession of St. Anthony the ners, and other trades people dumped waste into
Hermit, who was generally associated with ignis waterways, as did butchers and fishmongers; in
sacer. It was in his name that an order of hospi- 1369 London butchers were ordered to stop polluting
tallers was founded at La Motte, in a mountainous the Thames (Talbot 1967). Perhaps the greatest pol-
region of France (inhabitants of alpine areas were lution was found in the streets: Household waste
particularly vulnerable to ergotism because of cool was thrown from windows, dead animals were left to
weather), which became a pilgrimage center for decay where they fell, and the entire contents of
those who suffered from the disease (Talbot 1967). stables were swept outside.
Victims — frequently children and teenagers, who, The absence of good personal hygiene also predis-

posed the populace to contagious disease. Although tims of scrofula (tuberculosis of the cervical lymph
physicians prescribed steam, cold, or herb baths, and nodes) by touching them. Called the king's evil or
bathing had a role in rituals such as those performed the royal disease, this form of tuberculosis was suffi-
upon induction into knighthood or on certain feast ciently widespread to have attracted the attention of
days (Talbot 1967), baths, partly because of limited the court. According to English records of the king's
water supplies, could not have been as common as pence given as alms to the sick, Edward I touched
they are today, even for the well-to-do. Urban dwell- 1,736 victims during 1289-90, 983 during 1299-
ers were undoubtedly better served: Public baths 1300, and 1,219 during 1303-4 (Bloch 1973). In part
were available in many towns, even for the less because of the natural remissions of scrofula (if, in-
wealthy. Country people surely bathed less than deed, these cases were correctly diagnosed), which
town dwellers, and had few changes of clothing. Ap- were thought to be effected by the God-given pow-
parel, predominantly woolen in northern Europe, ered of the monarch, the practice persisted, in some
was relatively expensive and difficult to launder. For form at least, into the nineteenth century in France.
rich and poor alike, clothing and hair sheltered lice No doubt, the design of medieval farm homes, in
and fleas, according to medical treatises of the time which cattle and humans were housed under the
(Talbot 1967). All of these conditions greatly as- same roof, contributed to the spread of the bovine
sisted the spread of contagious diseases. tuberculosis bacillus to humans, and thus spread of
With population density at a critical level, the last tuberculosis in Europe. Bovine tuberculosis existed
few centuries of the Middle Ages saw the unique in Po Valley dairy cattle before their introduction to
social, intellectual, economic, and demographic influ- northern Europe in the thirteenth century (Manches-
ence of four contagious diseases - plague, influenza, ter 1984). Crowded conditions in the new towns also
leprosy, and tuberculosis. The dramatic impact of increased the diffusion of the disease, for it can
the Black Death in 1347-50 inspired contemporary spread by droplets produced by sneezing, coughing,
accounts as well as subsequent studies, now literally and the like.
in the thousands. Leprosy has also been a favorite Tuberculosis is caused by Mycobacterium tubercu-
subject for historians. The study of influenza, how- losis, which is of the same genus as Mycobacterium
ever, has long suffered from problems of correct iden- leprae, the causative agent of Hansen's disease,
tification. And the presence and importance of medi- termed leprosy by commentators in the Middle Ages.
eval tuberculosis must be largely inferred. Exposure to tuberculosis confers an immunity to
leprosy. Because tuberculosis was often transmitted
Tuberculosis to small children by human or cow milk, early immu-
The incidence of tuberculosis, an age-old malady, is nity to both tuberculosis and leprosy might have
believed to have increased greatly during the Middle been acquired by those who survived the first few
Ages, although this is difficult to document. Al- years of life. One factor in the late medieval decline
though excavation of medieval graves has disclosed of leprosy may have been the concurrent increase in
only a few skeletons showing tuberculosis of the tuberculosis in the densely populated urban centers.
bone, this tells us very little since the disease is Unfortunately, leprosy does not confer an immunity
known today to affect the bone in only 5 to 7 percent to tuberculosis (Manchester 1984).
of untreated cases (Steinbock 1976; Manchester
1984). Leprosy
Tuberculosis is a population-density-dependent ill- Leprosyflourishedin Europe during the twelfth and
ness, and the growth of towns may well have been thirteenth centuries, afflicting as much as 1 percent
accompanied by an increase in the disease. Relying of the populace, according to some authorities. Possi-
on the assumption that a high death rate in the bly brought to the West from India with the returning
years from 20 to 40 is evidence of widespread tuber- army of Alexander in 327-6 B.C., leprosy traveled
culosis, (historically it has ravaged this age group across Europe with Roman colonization. Skeletons
the most), investigators examining skeletons dating from fifth-, sixth-, and seventh-century England dis-
from the years 1000 to 1348 in Germany and other play clear evidence of lepromatous leprosy in the
areas have concluded that an increase in the disease skull or limbs, with loss of phalanges. Anglo-Saxon
did indeed parallel urbanization (Russell 1985). Evi- England apparently did not segregate lepers, because
dence for the importance of tuberculosis in the Mid- the bones of victims have been found in general ceme-
dle Ages is provided by the ancient custom among teries (Manchester 1984), but a few lazar houses were
French and English kings of attempting to cure vic- established as early as the eleventh century. The

disease seems to have reached a high point in En- cases, even untreated, are known to involve bones.
gland during the first half of the thirteenth century, Therefore, it can be speculated that only those most
when 53 hospitals were constructed. In all, some 200 severely affected by the disease were confined there
such institutions are known to have been established. (M0ller-Christensen 1969). As John of Gaddesden
By the fifteenth century no new ones had been built, advised in the fourteenth century, "No man is to be
and by the sixteenth century the disease had nearly adjudged a leper and isolated from all his fellows
disappeared from England. until the appearance and shape of his face be de-
The pattern in other European countries was simi- stroyed" (as cited by Cholmeley 1912). This was a
lar. In the twelfth and thirteenth centuries almost merciful criterion in view of the grief and penalties
every Italian town had a leper house outside its of banishment, but one that allowed the population
walls. France was said to have had 2,000 leprosaria to contract the disease from those with early or less
in the thirteenth century. Medieval Denmark had apparent forms.
31, and in the cemetery of the leprosarium of St. Medieval physicians had repeatedly observed that
Jorgens in Naestved, Denmark, 650 patients were the blood of lepers was thick, greasy, or gritty (Ber-
buried between 1250 and 1550 (M0ller-Christensen nard of Gordon 1496; Guy de Chauliac 1890; John of
1969). Gaddesden, cited in Cholmeley 1912). Recently, labo-
The Third Lateran Council in 1179 directed that ratory tests have substantiated these descriptions.
lepers be segregated from the rest of society, and that Blood samples show two or three times normal plate-
separate churches and burial places be provided for let adhesiveness, among other qualities (Parvez et
them. Great differences in the stringency of rules al. 1979; Ell 1984a). The age-old claims that lepers
among communities existed, varying from clement were unusually sexually active and that leprosy was
care to the burning of live victims. Typically, a cere- sexually transmitted have been harder to explain. It
mony was conducted over a male leper in which he has been demonstrated, first, that subclinical lep-
was declared to be "dead unto the world, but alive rosy may become overt during pregnancy (Duncan et
unto Christ." As the leper stood in a grave, a priest al. 1981), thereby giving the impression that the
threw earth over him (Brody 1974). He, in fact, lived disease has sexual origin, and second that remis-
on, but he was dead in the eyes of the law, and his sions of leprosy in men might heighten sensitivity to
heirs inherited his possessions, though divorce was testosterone. In addition, confinement in a leper
usually not permitted. Bishops or abbots endowed house could have released the sexual inhibitions of
leprosaria with income from tithes, rents, and tolls; both sexes (Ell 1984a). Yet because of the similari-
and in parts of Europe — northern Italy, for example - ties of the early stages of leprosy and syphilis, syphi-
lepers were under civic control. A leper house usually lis may in fact have been present in medieval Eu-
lodged 6 to 12 people, but might be built for one victim rope and mislabeled leprosy. Modern lepers show an
alone. Such community efforts to prevent the spread unusually high incidence of syphilis, suggesting an
of the disease were no doubt motivated by terror of unknown affinity (Murray 1982; Ell 1984a). V.
the dire symptoms of leprosy, despite widespread ec- M0ller-Christensen (1969), however, found no skele-
clesiastical declarations that the illness was caused tal evidence of syphilis in the 650 leprosy victims at
not by mere exposure to the disease but by divine Naestved.
punishment for lechery and other sins. Though the Historians have long believed that the Black Death
mechanism of contagion might be unclear, medieval greatly diminished the incidence of leprosy during
Europe was ready to be empirical. Lepers were pro- the second half of the fourteenth century, attacking
vided with cloaks and bells and ordered to keep their the weakened victims in their leper houses, which
distance on penalty of death, and lazar houses were were found virtually empty at the end of the plague.
built downwind from towns. However, it has recently been recognized that leprosy
Historians long believed that "leprosy" in the was already in decline when the plague began. The
Middle Ages actually included a range of skin disor- immune defect in the lepromatous patient is specific;
ders, perhaps including syphilis. However, the exca- it is not a generalized immune deficiency until the
vation of medieval leper cemeteries, principally in disease becomes advanced. In many ways, leprosy
Naestved, Denmark, has demonstrated that diagno- represents a hyperimmune state (Ell 1987). Lepro-
sis by medieval doctors was actually conservative. saria were probably found empty because members of
Approximately 80 percent of the 650 skeletons at the religious orders serving as keepers suffered a
Naestved showed evidence of advanced lepromatous high death rate (Biraben 1975; Russell 1985), and the
leprosy, whereas only a small percentage of modern lepersfledtofindfood, escape the plague, or run from

persecution as scapegoats. Alternatively, leprosy has "rain be excessive . . . so that the ground is com-
been claimed to confer an immunity to plague, be- pletely saturated, and the mists attract baneful exha-
cause leper houses consistently served meals very lations out of the earth."
sparse in meat, whereas the plague bacillus requires Even August Hirsch (1883) accepted the unique
a high serum iron level (Richards 1977; Ell 1984b, nature of the English sweating sickness, and not
1987). For all these reasons some medieval scourge until the twentieth century were the five British
other than plague may have hastened the end of epidemics recognized to be influenza, an illness
leprosy. Tuberculosis, as noted earlier, confers an im- known to be caused by an unstable microorganism
munity to leprosy (only one leper with tuberculosis having variable disease patterns.
was found among the victims at Naestved; M0ller- Traditionally, the first influenza epidemic, as iden-
Christensen 1969), though leprosy does not confer tified by Hirsch (1883), occurred in 1173 in Italy,
immunity to tuberculosis (Manchester 1984). Thus, Germany, and England, during which the monk
tuberculosis itself may have promoted the end of the Godefridus described an intolerable cough as a symp-
leprosy epidemic in the late thirteenth and four- tom. There were major bouts of influenza in France
teenth centuries as tuberculosis increased among the and Italy in 1323, when nearly all of the citizens of
new urban population. Florence fell ill with chills and fever, and again in
1387, when the disease was described as ex
Influenza influentia coelesti, giving rise to the use in Italy of
Believed in the Middle Ages to be a singularly En- the term una influenza. When the disease struck
glish disease, "sweating sickness" (now widely ac- Paris in 1411, one of the symptoms was a cough so
cepted as influenza) first appeared in the very month severe that it caused women to abort. Influenza re-
in 1485 in which Richard III was defeated at Bos- turned in 1414 to Italy and to Paris, where some
worth Field. Four other outbreaks - in 1508, 1517, 100,000 cases were claimed, and again in 1427'. Fol-
1528, and 1551 - occurred in the first half of the lowing this, Hirsch (1883) described no more epidem-
sixteenth century, before, according to the theory ics until the great 1510 outbreak, with general diffu-
that prevailed until recent times, the disease van- sion all over Europe, starting in Sicily in July and
ished forever. After the eminent Tudor physician reaching northern Italy in August, France in Sep-
John Caius had treated victims in 1551, he described tember, and the Netherlands and Spain in October.
the disease as a sweat and fever with pains in the But even as the visitations of influenza in Europe
back, extremities, head, with "grief in the liver and were increasing and the incidence of leprosy dimin-
the nigh stomacke," killing "some in one hour, many ishing, a greater scourge than either was about to
in two," but lasting only 24 hours if the patient strike.
survived (Caius 1912).
Even though an epidemic of fever and sweats was Bubonic Plague
known to have devastated much of northern Europe Bubonic plague (Black Death or the Black Plague)
in 1529 at approximately the same time as an En- was commonly known as the Great Mortality or the
glish outbreak of the sweating sickness, no relation- Great Pestilence. Probably in the majority of cases,
ship between the two phenomena was seen at the certain symptoms were characterized as "black." In
time. In keeping with the prevailing doctrine of hu- the words of Giovanni Boccaccio (1978), an eyewit-
moral pathology, which accounted for all disease as ness: "There appeared . .. certain swellings, either
an imbalance of the four natural humors - blood, on the groin or under the armpits . . . of the bigness
phlegm, black bile, and yellow bile - the English of a common apple . . . [or] an egg. From these . . .
sweating sickness was believed to be drawn to a after awhile . . . the contagion began to change into
constitution predisposed by an excess of one of the black or livid blotches . . . in some large and sparse
humors and possibly by an immoderate life-style. and in others small and thick-sown." Other sources
The immediate cause was believed to be, in the describe small black blisters spread widely over the
words of Caius, "evel mists and exhalations drawn body, swollen glands and boils surrounded by black
out of the grounde by the sune in the heate of the streaks, or the throat and tongue black and swollen
yeare." Explanations of the causation and character with blood. But many victims experienced no
of the disease remained localist and miasmatic into "black" symptoms. As a consequence, many believe
the nineteenth century, when in 1844 German histo- that the block in the name of the disease derives
rian J. F. C. Hecker (1844) called it a "spirit of the from a too-literal translation in sixteenth-century
mist" and said that epidemics were inevitable if Scandinavia of a common fourteenth-century Latin

phrase, atra mors meaning "terrible death," as other human travelers. Traders hauling grain, fod-
"black death." der, forage, hides, furs, and bolts of cloth also trans-
In 542, during the reign of Justinian, bubonic ported rats, fleas, and other vermin. Pilgrimage
plague was reported to have taken the lives of 25 routes and trade routes to fairs were natural paths of
percent of the population of the Roman Empire, in the disease, which first broke out in London at the
what has been called the first European epidemic. time of the Bartholomew Fair. When Edward III
Though the exact nature of this outbreak has been began the construction of Windsor Castle in 1359,
debated, plague is now believed, on the basis of liter- plague attacked the workforce (Shrewsbury 1970).
ary and cemetery evidence, to have spread across Plague is a millennia-old disease of wild rodents.
Europe, reaching the British Isles in 544 and return- In a cycle widely believed to be the method of trans-
ing there in 664 (when, significantly, the Venerable mission of the Black Death, rat fleas (Xenopsylla
Bede described St. Cuthbert as having a tumor [or cheopis) carry the Yersinia pestis bacillus to the
bubo] on the thigh) and again in 682 (Russell 1976). black or house rat, Rattus rattus. When the host rat
Probably, episodes of plague attacked Rome in 1167 dies, its fleas leave to find another living rat, but
and 1230, Florence in 1244, and Spain and southern failing that, they may jump temporarily to less fa-
France in 1320 and 1333. It was during the last vored hosts, human beings, and by biting them trans-
outbreak that Roch of Languedoc, who was on a mit the disease.
pilgrimage to Rome, contracted the disease, was In humans, plague has three major forms: bubonic,
cured, began to nurse plague victims, and subse- septicemic, and pneumonic. The first form results
quently became the patron saint of plague. from an insect bite, with the bacillus moving through
In 1331 civil war and plague struck Hopei, China, the lymphatic system to the nearest lymph node,
and both soon raged throughout that nation; chroni- frequently in the groin, where it forms a palpable
cles report that two-thirds of the population per- swelling, the characteristic "bubo," from the Greek
ished. The disease moved west along the caravan word for groin. Other possible sites for buboes are the
routes through Tashkent, Astrakhan, and other cit- armpits and the neck, depending on the location of
ies of southern Russia, transmitted by rats and fleas the bite. In the septicemic form, the insect injects the
perhaps lodged in the grain supplies of the caravans bacillus directly into the bloodstream of the victim,
(for a discussion of caravan transportation, see Mc- where it multiplies quickly. Blood seeps from the
Neill 1976). It reached the Crimea in 1346, where mouth and the nose, and death results in a few hours.
Genoese merchants were being attacked in their for- Septicemic plague is virtually always fatal. Neverthe-
tified trading post of Caffa by a Mongol army. The less, the most menacing form is pneumonic plague. A
attackers were suffering from plague, and before modern outbreak in Manchuria in 1921, for example,
they withdrew they transmitted their affliction to was 100 percent lethal (McNeill 1976). Because the
the besieged town by catapulting corpses of victims pneumonic form is a lung infection, it can be trans-
over the walls. ferred directly from human to human by airborne
Fleeing Caffa, the ships of the now-diseased Geno- sputum or by fomites (clothing and other articles
ese were driven away from Messina, Sicily, and the contaminated by victims).
disease was carried to North Africa and the western All three forms of the disease were found in the
Mediterranean. Soon Corsica and Sardinia, Spain fourteenth-century pandemic, and judging by a
and southern Italy were affected, then all of Italy, study of 300 contemporary literary sources, the rela-
Austria, Hungary, Yugoslavia, and Bavaria. Mar- tive importance of the three types may have been 77
seilles was the destination of one of the ships, and the percent bubonic, 19 percent septicemic with secon-
disease quickly spread up the Rhone and then dary pneumonia, and 4 percent pneumonic (Ell
throughout France. By 1348 most of France and Swit- 1980).
zerland were under siege by the plague, which soon Because of the entrenched medieval belief in the
reached the southern coast of England, Germany, humoral pathology inherited from the Greeks, which
Sweden, and Poland. The plague's assault on Russia had not been seriously challenged in more than a
was delayed until 1351, good evidence that the dis- thousand years, therapeutic measures were based on
ease traveled by the international trade routes and correction of the imbalance of humors. The imbalance
not by river transport, or it might have reached Rus- might be precipitated by an immoderate intake of
sia from the Crimea several years earlier. food or drink or by meteorological or astronomical
Plague was transported by armies and ships, mer- phenomena. Because plague was of a short incuba-
chants, pilgrims, fair goers, transient laborers, and tion period and therefore could readily be seen to be

transferred from person to person, the best etiologic 1369, and 1375. It has been estimated that the death
explanation consistent with the traditional, pathol- rate in Britain decreased with each successive wave,
ogy was that corrupt air emanated from the ill person starting with 25 percent in 1348 and becoming 22.7
or a corpse, or even from someone still not ill but percent in 1360, 13.1 percent in 1369, and 12.7 per-
coming from a place of sickness. Standing only a few cent in 1375. It is assumed that the disease lost its
feet away from such a source might be enough to virulence at the same time that people's immunity
contract the disease. Belief in the vital role of air wasincreased (Russell 1948; Carpentier 1978).
so strong that the clergy of Avignon imagined that Persistent questions about the Black Death per-
mountain dwellers had been immunized against the plex modern historians. Was bubonic plague the sole
plague by their own pure air and so imported them as disease, or where there others? Why was no unusual
gravediggers in 1348. Unfortunately, they died of the black rat mortality mentioned by contemporary writ-
infection as soon as they arrived (Biraben 1975). ers? Why is the black rat unknown today in Europe
Medieval physician and surgeon Guy de Chauliac except in a few port cities? Was a sylvatic, or wild,
(1890) wrote the most accurate and complete medi- home for the plague ever created in Europe - either
cal account of the 1348 plague epidemic of any con- at the time of the sixth-century eruption or in the
temporary observer. In it he described both the fourteenth century? If so, what eradicated it? Mod-
pneumonic and bubonic types of the disease, and ern sylvatic foci, in the southwestern United States
may also have recognized the septicemic type with a and Russia, are almost impossible to eradicate (Mc-
reference of blood spitting. His first counsel was the Neill 1976).
traditional injunction "Fuge cito, vade longe, rede It has been suggested that more than one disease
tarde" - "Flee quickly, go far, and come back slowly." was active during the fourteenth-century epidemics,
But he also advised such surgical and medical mea- with typhus, smallpox, and anthrax as candidates.
sures as reducing blood volume by phlebotomy, puri- Scholars have been puzzled by records of high infec-
fying the air by fire and incense, and opening or tion rates during the winter months, since plague is
cauterizing buboes. Most of the medical texts of the a warm-weather disease. This and other contradic-
time echo the treatments Guy de Chauliac advo- tory factors support the case for anthrax, which is
cated. Surgical intervention, baths, and apothecary caused by a much hardier organism, is characterized
cures were recommended. Physicians visiting the by pustules with a jet-black center, often precipi-
sick were accompanied by boys carrying incense tates the voiding of black blood, and also has a pul-
burners to purify the air, and all held before their monary form (Twigg 1984).
noses a sponge soaked in vinegar and spices. When Doubts about the classical explanation of plague
Philip VI of France ordered the Paris medical faculty transmission derive partly from the present-day ab-
to ascertain the cause of the disease, a confident sence of R. rattus in northern Europe, except in a few
report came back that the pestilence was caused by port cities. Moreover, no medieval record exists of
the conjunction of Saturn, Jupiter, and Mars, which the explosive black rat mortality that would have
had occurred at 1 P.M. on March 20, 1345 (Campbell been expected. Finally, R. rattus is timid and not
1931). normally migratory (Shrewsbury 1970; Ell 1980).
Those who could afford to, including physicians, As already mentioned, spring and summer are the
fled the infected towns. Orvieto, for example, had to seasons of ratborne plague in cities (infection occurs
offer a doctor 100 livres per year to stay and treat most commonly when both Fahrenheit temperature
the poor. The Catalonian Cortes fled Barcelona, and and humidity are between 68 and 80; Russell 1976),
all the inhabitants of Agrigento, Sicily, ran away in yet the Black Death occurred throughout the year.
1347. Citizens of Marseilles burned the La Rousselle The explanation may lie in two possible forms
quarter to contain the plague (Biraben 1975). Per- of interhuman transmission: Respiratory infection,
haps because both cities forbade entry by travelers, which produces pneumonic plague, would explain the
Milan and Parma remained largely free of the dis- winter occurrences, and transmission by the human
ease during its first outbreak in 1347-50. In Milan flea, Pulex irritans, would account for the undoubted
early victims were also heartlessly walled up in majority of bubonic cases (Ell 1980). P. irritans, which
their houses (Ziegler 1970; Ell 1984b). At Ragusa can transmit plague, would have needed no rat host
(now Dubrovnik, Yugoslavia), ships were isolated and could have lodged in long, loose clothing, travel-
for 40 (quaranta) days, in a first effort at quarantine. ing from person to person. Lice, ticks, and bedbugs,
The first great outbreak of the Black Death was which can also transmit plague, may have been vec-
followed by three waves in the same century, in 1360, tors as well (Biraben 1975; Ell 1980).

As for the sylvatic foci in rodents, an alternative stop the spread of plague. A new charitable impulse,
explanation would be that multiple human and ani- encouraged by the religious revival after the plague,
mal reservoirs, based on complete and partial immu- led to the building of hospitals, both religious and
nities, perhaps constantly shifting, propagated the civic. New religious orders were devoted to the care
plague bacillus without a sylvatic home. Plague im- of the sick. Owing to the heavy loss among scholars,
munity is known or suspected to be conferred by physicians, and other educated men, Latin ceased to
salmonella infections, Yersinia enterocolitica, tube the sole language of important texts, and medical
laremia, and typhus, as well as leprosy (Ell 1984b). as well as other books began to be written in the
Explanations for the final disappearance of plague vernacular (Campbell 1931).
from Europe in the eighteenth century included A widespread interest in disease prevention be-
speculations that the bacillus mutated to a less viru- came current, and many works on diet, hygiene,
lent form, that R. rattus was replaced by Rattus proper clothing, and other topics of health care were
norvegicus, and that new practices of housing con- published. Because surgeons had made heroic efforts
struction, shipping, personal hygiene, nutrition, and to lance or cauterize buboes during the plague, the
public health finally brought the disease to an end status of this profession was considerably enhanced,
(for reviews of theories see Appleby 1980; Ell 1984b). rising relative to that of physicians, too many of
In addition, the rats themselves may have become whom hadfled.The growth of surgery as a discipline
immune. Communities of immune rats are known to and desire to ascertain the causes of the pandemic
have existed in India in the twentieth century. The led to an increased sanctioning of postmortem exami-
reason the rats did not become immune in northern nations, a practice that was to contribute directly to
Europe until the seventeenth century (and a few the growth of academic anatomic dissections in the
decades later in the south) may be that a certain following century.
high density of population would have been required Finally, humoral pathology suffered a serious
for all remaining susceptible rats to be infected and blow - from which it would ultimately expire in cen-
finally killed (Appleby 1980). turies to come — because of its complete failure to
Historians have long accepted a type of Malthu- palliate suffering and effect cures, not only for
sian theory to account for the appearance of plague plague but for the other contagious illnesses of lep-
in 1348. According to this theory, a too rapid popula- rosy, tuberculosis, and influenza that ravaged the
tion expansion led to the clearing of all arable land late Middle Ages.
and crowding into already overpopulated cities. The Ynez Violi O'Neill
populace then suffered a series of crop failures and
famines when the weather turned unusually cold
early in the fourteenth century. As rats fled empty Bibliography
Appleby, Andrew B. 1980. The disappearance of plague:
granaries to find food in human dwellings, the hu-
A continuing puzzle. Economic History Review 33:
man population, weakened by starvation, fell vic- 161-73.
tim to a chance epidemic. Critics of this Malthusian Bernard of Gordon. 1496. Tabula practice Gordonii dicte
position have objected that the weakest members of lilium medicine. Venice.
society were not eliminated by the plague; men Biraben, Jean-Noel. 1975. Les hommes et la peste en
between 20 and 40 died in larger proportion than France et dans les pays europiens et mediterraniens, 2
women, children, the aged, or even lepers. The Y. vols. Paris.
pestis organism requires exogenous iron for growth Bloch, Marc. 1973. The royal touch: Sacred monarchy and
and replication, and young men were the least iron- scrofula in England and France, trans. J. E. Ander-
deficient group in the medieval population (Ell son. London.
1984b, 1987). Boccaccio, Giovanni. 1978. Plague in Florence: A literary
Believed to have left in its wake some 20 million description. In The Black Death: A turning point in
history? ed. William M. Bowsky, 7-12. Huntington,
dead in Europe in the four years from 1346 to 1350,
N.Y.
the Black Death brought about critical social and Braudel, Fernand. 1979. The structures of everyday life,
ideological changes. Considering the medical world trans. Sian Reynolds. New York.
alone, we find that the public health tradition, inher- Brody, Saul Nathaniel. 1974. The disease of the soul: Lep-
ited from the care of lepers, was strengthened - even rosy in medieval literature. Ithaca, N.Y.
though social efforts to clean streets, collect garbage, Bullough, Vern, and Cameron Campbell. 1980. Female
empty sewers, remove bodies, regulate the sale of longevity and diet in the Middle Ages. Speculum 55:
food, and enforce quarantines of ships did little to 317-25.

V.4. Renaissance and Early Modern Europe 279
Caius, John. 1912. A boke or counseill against the disease Parvez, M., et at. 1979. A study of platelet adhesiveness in
commonly called the sweate or sweatyng sicknesse. In leprosy. Leprosy in India 51: 363—8.
The works ofJohn Caius, MD, ed. E. S. Roberts, 3-36. Richards, Peter. 1977. The medieval leper and his northern
Cambridge. heirs. Cambridge.
Campbell, Anna Montgomery. 1931. The Black Death and Russell, Josiah Cox. 1948. British medieval population.
men of learning. New York. Albuquerque, N.M.
Carmichael, Ann G. 1983. Infection, hidden hunger, and 1976. The earlier medieval plague in the British Isles.
history. Journal of Interdisciplinary History 14: 249- Viator 7: 65-78.
64. 1985. The control of late ancient and medieval popula-
Carpentier, Elisabeth. 1978. The plague as a recurrent tion. Philadelphia.
phenomenon. In The Black Death: A turning point in Shrewsbury, J. F. D. 1970. A history of bubonic plague in
history? ed. William M. Bowsky, 35-37. Huntington, the British Isles. Cambridge.
N.Y. Siegfried, Michael. 1986. The skewed sex ratio in a medi-
Cholmeley, H. P. 1912. John of Gaddesden and the Rosa eval population: A reinterpretation. Social Science
Medicinae. Oxford. History 10: 195-204.
Drummond, J. C , and Anne Wilbraham. 1959. The En- Steinbock, R. Ted. 1976. Paleopathological diagnosis and
glishman's food: A history of five centuries of English interpretation: Bone diseases in ancient human popula-
diet. London. tions. Springfield, 111.
Duncan, M., 1981. The association of leprosy and preg- Talbot, C. H. 1967. Medicine in medieval England. London.
nancy. Leprosy Review 52: 245-62. Twigg, Graham. 1984. The Black Death: A biological re-
Ell, Stephen R. 1980. Interhuman transmission of medi- appraisal. London.
eval plague. Bulletin of the History of Medicine 54: White, Lynn, Jr. 1962. Medieval technology and social
497-510. change. Oxford.
1984a. Blood and sexuality in medieval leprosy. Janus 1976. Food and history. In Food, man, and society, ed.
71: 153-64. Dwain N. Walcher, Norman Kretchmer, and Henry L.
1984b. Immunity as a factor in the epidemiology of Barnett, 12-30. New York.
medieval plague. Reviews of Infectious Diseases 6: Ziegler, Philip. 1970. The Black Death. London.
866-79.
1987. Plague and leprosy in the Middle Ages: A para-
doxical cross-immunity? International Journal of Lep-
rosy and Other Mycobacterial Diseases 55: 345-50.
Guy de Chauliac. 1890. La grande chirurgie, ed.
E. Nicaise. Paris. V.4
Hecker, J. F. C. 1844. The epidemics of the Middle Ages,
trans. B. G. Babington. London. Diseases of the Renaissance
Herlihy, David. 1975. Life expectancies for women in medi-
eval society. In The role of woman in the Middle Ages,
and Early Modern Europe
ed. Rosmarie Thee Morewedge, 1-22. Albany, N.Y.
Hirsch, August. 1883-6. Handbook of geographical and
historical pathology, 3 vols., trans. Charles Creigh- The Renaissance in European history was a time of
ton. London. political, intellectual, and cultural change that had
Hodges, Richard. 1982. Dark age economics: The origins of its origins in Italy during the fourteenth century.
towns and trade, A.D. 600-1000. London. Beginning roughly during the lifetime of the poet
1984. Diet in the dark ages. Nature 310: 726-7. Francesco Petrarch, who died in 1374, literati began
Manchester, Keith. 1984. Tuberculosis and leprosy in antiq- to look to classical Greece and Rome for models of
uity: An interpretation. Medical History 28: 162-73. human political behavior and stylistic models of dis-
Matossian, Mary Kilbourne. 1983. Bewitched or intoxi- course and artistic representation. This humanistic
cated? The etiology of witch persecution in early mod- quest involved the energies of philosophers and art-
ern England. Medizin Historisches Journal 18: 33-42. ists throughout the fifteenth, sixteenth, and seven-
McNeill, William H. 1976. Plagues and peoples. Garden teen centuries, as Renaissance ideas spread north-
City, N.J. ward. Though narrowly conceived in scholarly and
M0ller-Christensen, V. 1969. Provisional results of the artistic circles, the Renaissance matured in urban
examination of the whole Naestved leprosy hospital
churchyard - ab. 1250-1550 A.D. Nordisk medicin-
settings. Because this time period coincides with
historisk drsbok 29-41.
technological innovations and the subsequent explo-
Murray, Katherine A. 1982. Syphilis and leprosy. Journal
ration and conquest of new worlds, we are inclined to
of the American Medical Association 247: 2097. associate the issue of Renaissance diseases with both

the growth of cities and the age of European discov- rounding countryside, and market economies re-
ery. The period also frames the era of recurrent epi- sponded to this growth with the development of local
demics of bubonic plague in Europe. industries, particularly in cloth, and with the devel-
Population growth in Europe was steady during opment of trading networks that would facilitate
the central, or "High," Middle Ages but did not lead to further urban growth. During the sixteenth century,
the growth of large metropolitan centers. Urbaniza- an impressive demographic recovery of rural popula-
tion was earliest and most dramatic in the Mediterra- tions seems to have fueled still more urban growth
nean lands, where city cultures had also been the as more and more individuals migrated steadily,
basis of ancient Roman hegemony. By the late thir- even relentlessly, to the cities from the countryside.
teenth century, Florence and Venice, as successful Thus, even though struck by epidemics of plague,
commercial centers, had populations of more than the populations of Venice, Florence, Milan, and
100,000. Rome, Milan, and Barcelona may have been Rome all exceeded pre-1348 levels. During the six-
equally large. Smaller urban areas of 50,000 to teenth century, Madrid expanded 10-fold in popula-
80,000 individuals existed throughout northern Italy tion while increasing only 4-fold in size, a dramatic
and Spain. These cities were roughly twice as large as example of the problems of crowding that the growth
the "urban" areas of England, including London. Uni- of Renaissance cities created.
formly dense, mixed urban and village networks In both Renaissance and early modern Europe, so-
were also characteristic of the Low Countries at the cial and economic conditions help to identify and de-
end of the Middle Ages, and the Seine valley could fine the diseases then common. Naturally the disease
boast of at least one true city, Paris. experience of urban settlements differed signifi-
Outside the urban Mediterranean, the period of cantly from that of rural town networks. City admin-
the Renaissance is better labeled the late Middle istrators were forced to deal with increasingly serious
Ages. Most people lived in small villages and market health threats, particularly with problems of refuse
towns, where goods, information, and epidemic dis- disposal and the provision of clean water, and of
ease passed through at a more leisurely rate. The course with recurrent epidemic diseases.
British Isles, for example, had no town larger than At a time when at least one-third of all babies born
50,000 people until after 1600. But by the late six- died before their fifth birthdays, chronic infections
teenth century, France, Germany, and England be- mediated the lives of most adults, and two-thirds of
gan to grow in population and in number of cities. rural residents did not survive to reproductive age,
The Thirty Years' War effectively eclipsed growth in the acute crises of plague and other epidemics may
Germanic Europe during the early seventeenth cen- not have been the most important diseases of the
tury. London and Paris, however, became the largest Renaissance. But they were certainly the most visi-
cities of Europe. By the eighteenth century, Scotland ble disease threats, and this shapes modern-day per-
and Scandinavia began the processes of urbaniza- ceptions of the period as a dark age of plagues and
tion, commercialization, and protoindustrialization. other acute infections.
A general improvement in health and longevity ac- In early modern Europe the specter of famine
companied economic growth, even though the preva- loomed over the rural landscape. Although the ad-
lence of infectious diseases remained high. age "First famine, then fever" did not hold true for
The "Black Death" epidemic of bubonic plague in all periods of food shortage, periodic subsistence
1348—50 caused up to 40 percent overall mortality in crises tended to provoke mortality crises. Normal
large cities, and as much as 60 percent mortality in annual mortality was as high as 3 percent of a popu-
smaller Italian cities such as Siena. Nevertheless, lation. But these crises generally carried away 6 to
the greatest proportional destruction of the plague 10 percent of the population, and when very acute
and subsequent periodic epidemics of disease in the could claim as much as 30 to 40 percent. This short-
fourteenth century seems to have fallen on villages run instability of mortality rates, what Michael
and towns of western Europe, necessitating changes Flinn (1981) has described as the demographic sys-
in landholding and land usage, and forcing individu- tem of the ancien regime, was also nonuniform, so
als to migrate to cities in search of nonagricultural that neighboring towns could be affected quite differ-
work. From 1350 to 1500, recovery was slow and ently during any given crisis. Across a community,
uneven, but as early as the 1450s the great cities of the highest death rates occurred among those less
Italy, Spain, and the Low Countries began to wrestle than 10 years of age, with most deaths occurring
with the sanitary pressures brought about by new within the first 2 years of life.
growth. These cities grew at the expense of the sur- The basic problem, then, is to identify the cause or

causes of such high mortality. Famine, epidemics, or Only during the fourteenth century do descrip-
war could singly or in combination precipitate a tions of plague note the loss of many principal citi-
mortality crisis, though infectious disease usually zens. After that period elites seem to have estab-
became the proximate cause of death. Yet rural popu- lished effective patterns of flight. For those who did
lations often made up the losses quickly through notflee,plague controls may have increased the risk
reproduction, and years immediately before and af- of death, because both sufferers and their healthy
ter a period of crisis were times of lower than aver- contacts were isolated for weeks in pesthouses, tem-
age mortality. Certainly it would seem that the most porary shacks, or, if they were lucky, their own
vulnerable members of a population were systemati- homes. The maintenance of normal standards of hy-
cally pruned away during a mortality crisis, a classic giene and alimentation was difficult in such circum-
Malthusian picture. stances, and many undoubtedly died from less extra-
ordinary causes than plague.
Plague Whatever the individual causes of death in these
Beginning with the wave now called the Black mixed epidemics, for more than 300 years bubonic
Death, plague appeared in Europe at least once ev- plague recurred in Europe at least every quarter-
ery generation between 1350 and 1720. During the century. Then it disappeared during the late sev-
late fourteenth century, smaller communities may enteenth and early eighteenth centuries, a phe-
have been disproportionately affected, for depopula- nomenon that has prompted two vexing, unsettled
tion and deserted villages were uniform phenomena questions about diseases of the Renaissance and
throughout Europe. Indeed, smaller centers may not early modern Europe. First, why did plague disap-
have remained economically or demographically via- pear? Second, was its disappearance in any way re-
ble settlements after an episode of plague, leading to sponsible for the early phases of the modern rise of
the reaggregation of people in villages, towns, and population? The first of these two questions has
cities. By the fifteenth century, however, no matter rather clearer options, if not firm answers. Some
how uniform the distribution of rodent vectors re- scholars argue that quarantine and other efforts to
sponsible for conveying plague to smaller human interrupt the spread of plague from town to town,
settlements and however sophisticated the develop- region to region, or country to country effectively
ment of trade networks to supply food to nonagri- localized the outbreak of the plague. Admittedly
cultural centers, the written records of plague recur- these sanitary measures were designed to thwart a
rence suggest that the human plague epidemics disease spread by human-to-human contact and did
were largely confined to urban areas. 0. J. Bene- little to disturb rodent colonies that harbored the
dictow (1987), however, has argued that a knowl- plague. But because rodents are commensal, rarely
edge of the ecology and epidemiology of plague al- traveling far from human settlements, it is felt by
lows us to infer that there were heavy losses in the some that the dispersal of plague ultimately de-
rural areas surrounding affected cities. pended on human actions. The proponents of this
Bubonic plague epidemics were principally sum- "quarantine-worked" model argue that humans inad-
mer infections, no doubt augmented in severity by vertently carried rodents and infected fleas in con-
diarrheal diseases. Most surviving records of these tainers ranging from satchels to ships. This explana-
epidemics suggest that overall mortality rates of 10 tion has much to recommend it, but depends on the
percent were common among the people who could assumption that plague was always imported to Eu-
not escape the city. Nevertheless, devastating popula- rope and that efforts to intercept and deter such im-
tion losses from plague epidemics, comparable to portation ultimately succeeded even when quaran-
those from the Black Death, occurred in the six- tine stations were poorly maintained and were, at
teenth and seventeenth centuries in the heavily ur- best, sieves straining out only gross contaminants.
banized areas of north central Italy and Castille and Others argue that either climatic changes or
may have led to the economic decline of the Mediter- changes in trade patterns led to the retreat of plague
ranean areas by the seventeenth century. During from Europe. The disease hit northern Europe for
the seventeenth and eighteenth centuries, northern the last time in the 1660s and southern Europe (Mar-
European countries witnessed the growth of cities seilles and Provence only) in 1720. The interval be-
and large towns, whereas Mediterranean centers tween these last European plagues corresponds
slipped into a period of stagnation, probably because roughly to the "Maunder minimum" of sunspot activ-
the epidemic waves of 1575-7, 1596, and 1630 were ity and to the peak phases of the "little ice age."
particularly severe in southern Europe. Insofar as global climate changes could have af-

fected rodent colonies in central Asia, where bubonic food has a positive influence on human survival even
plague has a perennial home, the number of infected in the presence of serious infectious diseases.
fleas and rodents reaching Europe could have de-
clined independently of efforts to control plague. Al- Other Epidemics
ternatively, the fact that northern Europeans turned During the Renaissance period, influenza pandemics
to an Atlantic-based trade, shifting markets away recurred frequently enough to be well described by
from the Mediterranean to colonies in the Western the fifteenth century. At least three influenza epidem-
Hemisphere and to the Far East, may be related to ics were quite severe during the sixteenth century,
the decline of plague first in Great Britain, Scandina- those of 1510,1557-8, and 1580. The last in particu-
via, and the Low Countries. The plague was always lar resembled the devastating influenza of 1918, in
conveyed east to west across the Mediterranean and that the first wave occurred in the summer and early
principally by sea. The relatively later survival of fall, and morbidity and mortality were high among
plague in Italy and Spain, where plague surveil- young adults. The periodic influenza in the seven-
lance and quarantines had long been used, adds teenth century has not been a subject of scholarly
some weight to these latter explanations. study, though the epidemics of 1627 and 1663 seem to
Whether the retreat of plague had any measur- have been quite lethal. In contrast, epidemics of the
able effect on subsequent population growth is more eighteenth century have received considerable atten-
difficult to answer, for there is no easy way to frame tion. K. David Patterson (1986) points to two epi-
a model showing what would have happened had demic periods in particular, from 1729 to 1733 and
plague continued its assaults. Urban population from 1781 to 1782, that mirror sixteenth-century pan-
growth in northern Europe was well underway be- demic influenza, suggesting that worldwide distribu-
fore the two great plagues of 1630 and 1665-6. tion of this common infectious disease antedated ad-
Even if Benedictow is right in stating that bubonic vances in global transportation.
plague epidemics claimed horrifying percentages, Virulent smallpox, by contrast, may have appeared
on the order of 40 to 85 percent, of both the urban in Renaissance Europe only in the mid-sixteenth
and rural populations exposed, net European popu- century (Carmichael and Silverstein 1987). Before
lation growth was not reversed during the six- that time measles and smallpox were described as
teenth and seventeenth centuries. relatively mild infections of childhood, an observa-
John Hatcher (1977) and others have claimed tion resting on those of ninth- and tenth-century
that the profound demographic depression of the Muslim physicians, Rhazes and Avicenna. Unless
late fourteenth and fifteenth centuries was due in many of the fourteenth- and fifteenth-century epi-
part to the combination of plague with other lethal demics of plague were in fact mixed epidemics of
epidemics, often staggered in such a way that few plague and smallpox, with the latter masked by the
children reached reproductive age. Nonetheless, the horror of the plague, records of epidemics of small-
frequency of recorded epidemics of diseases other pox were sparse before the 1560s and 1570s. More
than plague increased during the later centuries, likely a milder strain of smallpox prevailed before
and yet did not bring on population stagnation, as virulent smallpox entered England in the sev-
may have been the case in the late Middle Ages. enteenth century. Smallpox has a much more
Thus, the economic expansion of Europe, with some prominent — if not preeminent — place among the dis-
improvements in travel, trade, and communication eases of the seventeenth and eighteenth centuries
and dramatic improvements in regional and in- and will thus be discussed later in more detail.
terregional markets, seems to best account for the The history of other infections transmitted by air-
beginnning of the European mortality decline in borne droplets is a patchy one during the Renais-
early modern times. The Europeans found them- sance. Diphtheria was certainly described well in
selves increasingly insulated from local famines, peri- epidemics of malignant sore throat, as was whooping
odic harvest shortfalls, and other crises that evoked cough, the earliest examples dating from the
great fear of accompanying plague and pestilence, sixteenth-century epidemiologist Guillaume de Bail-
and were gradually able to overcome the hemor- lou. In Spain, accounts of epidemics of garoffilo ap-
rhagic demographic impact of recurrent epidemic peared during the early seventeenth century, depict-
plague. To understand how this could have happened, ing what was presumably a considerable threat to
it is necessary to assess what other infections threat- young children. Yet diphtheria was confused with
ened human survival at this time and to ask whether epidemics of streptococcal sore throat as late as the
improved nutrition because of regularly available mid-nineteenth century.

The German physician Daniel Sennert is credited ries governing the description of disease changed
with having written the first unambiguous descrip- during the Renaissance, making difficult a retrospec-
tion of scarlet fever. Rheumatic fever, another mani- tive assessment of what was new and different then.
festation of severe streptococcal infection, was de- In others words, evidence for the sudden appear-
scribed well by Baillou in the sixteenth century and ance of many common diseases in the sixteenth and
by the English physician Thomas Sydenham in the seventeenth centuries is somewhat artifactual — a
seventeenth century. Epidemic typhus fever seems "reporting phenomenon." During the Renaissance,
to have been a new disease in Renaissance and early physicians increasingly turned to models of conta-
modern Europe. gion to explain (and, hence, control) the spread of
One of the great problems facing historians of plagues and pestilences, and were aided considerably
Renaissance diseases is the difficulty of discerning by adoption of ontological theories of disease. That is,
the precise cause of an epidemic much before 1500. physicians crafted new medical definitions of dis-
For example, the following account from a Parisian eases, which had long possessed common lay names,
chronicler in 1414 suggests both whooping cough describing them as individual entities with unique
and influenza: and distinguishing characteristics. Though chronic
"diseases," such as fevers, consumption, arthritis,
And it pleased God that a foul corrupt air should fall upon gout, cancer, ulcers, and fistulae, were still best ex-
the world, an air which reduced more than a hundred plained and treated only by a thorough understand-
thousand people in Paris to such a state that they could
ing of the Galenic-Hippocratic humoral system that
neither eat, drink, nor sleep. They had very sharp attacks
of fever two or three times each day, especially whenever
dominated medicine until the nineteenth century,
they ate anything. Everything seemed very bitter to them, medical accounts from the sixteenth century onward
very rotten and stinking, and all the time, where ever they tended to identify acute health problems in terms of
were, they shook and trembled. Even worse, besides all specific diseases. These new ways of looking at illness
this they lost all bodily strength so that no one who had had a profound effect on the recognition and descrip-
this disease could bear to touch any part of his body, so tion of diseases known today. Moreover, the spread of
wretchedly did he feel. It continued without stopping three medical information through the medium of print
weeks or more; it had begun in early March of the same accelerated and normalized the understanding of
year and was called the tac or herion.... As well as all the many diseases as specific and individual.
misery described above, people had with it such a fearful
cough, cattarh, and hoarseness that nothing like a high In the sixteenth and seventeenth centuries, dozens
mass could be sung anywhere in Paris. The cough was so of "new" diseases seemed to demand or defy medical
much worse, night and day, than all the other evils that explanation, which resulted in some of the earliest
some men suffered permanent rupture of the genitals medical descriptions we possess for scurvy, rickets,
through it and some pregnant women gave birth prema- typhus, syphilis, scarlet fever, the "English sweate"
turely because of this coughing, alone and without help, (whatever that was), and even anorexia nervosa.
and died, mother and child, in great distress. When people Thus, one of the fundamental problems for historical
began to get better they passed a lot of clotted blood epidemiologists is determining which of these, if any,
through nose, mouth and below, which frightened them were indeed new or newly important during the pe-
very much. Yet no one died of it. But it was with great
riod from 1400 to 1800. And by "newly important," we
difficulty that people managed to recover from it, even
after the appetite came back it was still more than six
mean diseases that changed in incidence and preva-
weeks before they were really cured. No physician could lence in a society rather than those that became im-
say what this disease was. (Shirley 1968) portant to some groups within these societies. For
example, was gout "important" to Renaissance and
This vivid description is echoed by a brief mention of early modern elites because it became a noble form of
a contemporary catarrhal illness in the other urban suffering - in contrast, for example, to the ignominy
areas of Europe, suggesting that the disease was of syphilis - or because meat consumption among the
influenza. The cough and low case fatality, however, upper classes, together with a heavy consumption of
indicate whooping cough (the chronicler is unlikely dehydrating alcohol, increased the clinical expres-
to have noted the deaths of babies). But if either sion of gout? In many cases we will never know the
whooping cough or influenza was a truly new dis- answer, and thus must make some assumptions based
ease in the early fifteenth century, then the implica- on those data that did not change over the reporting
tions for changing disease patterns in the later Re- period while considering significant shifts in the crite-
naissance would be considerable. It is more likely ria for definition and diagnosis. In this respect, much
that the criteria for diagnosis and the medical theo- scholarly attention has been devoted to smallpox and

syphilis, which thus form two illustrative case stud- lenged this picture with an even broader equilib-
ies of the problems involved in tracing the history of rium model, arguing that the reason the difference
diseases of early modern Europe. between deaths and births was quite large in the
cities was that many adult migrants temporarily
Smallpox and the Modern Rise resided in the city, without marrying or contributing
of Population to the replenishment of the population. Thus, an
Smallpox was long recognized as a contagious dis- excess of nonreproductive adults in the cities ac-
ease with a pustular rash. Distinctive clinical fea- counts for a good part of the difference between rural
tures, such as the simultaneous maturation of pus- and urban mortality statistics.
tules (this distinguishes it from chickenpox) and the William H. McNeill (1976) portrays cities as the
centripetal distribution of pustules over the body, frontlines of the human battle against microbes
were not noted. Oddly, the residual facial scarring that entered these cities through commerce and mi-
among recovered variola major victims, was rarely gration. City residents were usually the first group
mentioned. Nevertheless, by the early seventeenth to be hard hit by a novel infection, but over the long
century, smallpox was recognized by both lay and run city populations were, on the whole, immunized
medical observers as a distinctive disease. earlier in life to viral diseases, which produced life-
Even if many cases were missed because the vic- long immunity. Young adults migrating into the
tim was severely infected, or was very young, and city from the countryside might add to the pool of
died before the rash appeared, mortality records individuals susceptible to common infections. Un-
from England, Italy, Sweden, and elsewhere testify healthy-appearing, impoverished urban dwellers
to the accelerating intensity of smallpox over the would better survive an epidemic of measles than a
course of the seventeenth and eighteenth centuries. comparable group of strapping young adults from
Epidemic years of smallpox in Italian cities of the the provinces.
eighteenth century could account for up to 30 per- McNeill's view would make smallpox an excellent
cent of the annual mortality, and recurrences swept example of the long-term advantages, largely immu-
urban areas at least once a decade (Panta 1980). In nological, to city dwellers, and John Landers and
London, the largest city of Europe by the eighteenth Anastasia Mouzas (1988) have found robust empiri-
century, there were no gaps between major out- cal support for this view in the records of London
breaks of smallpox. Annual mortality in the metropo- mortality. Moreover, Landers (1987) has found the
lis averaged 10 percent of all deaths. Thus, there is beginning of a decline in the summer peaks of
much agreement that smallpox was one of the princi- deaths from gastrointestinal infections by the late
pal causes of morbidity and mortality after plague seventeenth century. Thus, he doubts the view of an
disappeared. The residual questions are: Why was endogenously unhealthy city, with its citizens at the
smallpox increasing in incidence and prevalence, mercy of microbes. Moreover, with the immunity of
and what effect on population and other diseases did survivors of exogenous killer diseases, such as small-
inoculation and vaccination against smallpox have? pox, urban mortality changed significantly during
Finally, can the stepwise retreat of smallpox with the "long" eighteenth century, 1670-1830. Hidden
the introduction of innovative therapies explain any in those changes, he believes, are the reasons for the
part of the modern rise of population, which began in initial modern rise of population.
the eighteenth century? In addition, A. J. Mercer (1985) argues that small-
The answers to these questions depend in part on pox may have been uniquely important in a demo-
the assumptions demographers and epidemiologists graphic sense not only because it killed a large num-
make about the principal causes of death in early ber of young children, but because its survivors often
modern cities. Many view cities as death traps, their succumbed to other infections, once "weakened" by
highly unsanitary environments containing a rich smallpox. Although general crisis mortality, in city
variety of gastrointestinal pathogens that tipped the or countryside, cannot be linked to famine or to
balance between births and deaths and necessitated weather conditions, statistically it can, in the eigh-
in-migration to maintain populations. Nonrespira- teenth century, be linked to epidemic waves of small-
tory tuberculosis, water- and foodborne infections, pox. Mercer is not willing to ascribe a determinant
and, to a somewhat more limited extent, midwinter role to smallpox among the diseases of the eigh-
respiratory infections complete the list of pathogens teenth century, but he is convinced that vaccination,
that plagued the cities. However, Allan Sharlin and where adopted even halfway, contributed signifi-
Roger Finlay (1981; see also Sharlin 1978) have chal- cantly to the survival of children to adulthood, accel-

erating population growth in the early nineteenth of little children, came under control, population
century. growth was dramatic, even though exposure to multi-
Other scholars consider typhus and tuberculosis ple infections and specific medical measures did not
to have been as important as smallpox. There is change the features of disease experience for
once again an artifactual aspect to the high preva- nineteenth-century Europeans.
lence of typhus, for it was only during the eigh- At just the time McKeown finds general improve-
teenth century that physicians first described its ments in human nutrition, the appearance of wide-
clinical and epidemiological features well and differ- spread deficiency diseases marked further change in
entiated typhus from a miscellany of other fevers - the European disease experience. The prevalence of
nervous, biliary, inflammatory, continuous, hectic, scurvy increased, including that of "land scurvy" suf-
and intermittent. fered by the most impoverished city dwellers. Pella-
Most have accepted Hans Zinsser's (1935) argu- gra was described first in the eighteenth century
ment in his celebrated Rats, Lice and History that among the desperately poor farmers of northern Italy
epidemic typhus fever was a new disease in the late and Spain, who became dependent on American
fifteenth century, brought to Spain and Italy during maize. Potato and squash cultivation eased the lives
the battles against Turkish expansion in the Medi- of many northern Europeans, helping them to avoid
terranean. The dramatic urbanization of northern famine crises that had been common before the eigh-
Europe (London grew from c. 400,000 in 1650 to teenth century, but well into the nineteenth century
more than 1 million by the early nineteenth cen- the dependence on single crops or foodstuffs often
tury) accelerated crowding and poverty, optimal so- gave the poor no relief from a miserable nutritional
cial conditions for the spread of typhus by body lice. regimen. Thus, in many instances, the benefits of
Crowding and poverty also supported the transmis- improvements in nutrition may have largely accrued
sion of respiratory tuberculosis, which many have to upper- and middle-class urban dwellers. It would
argued was at a peak at about 1800. seem that the disappearancefirstof plague - a relent-
It was during this era of earliest industrialization less killer of young adults - and then smallpox per-
that population began to swell, and thus the model mitted the survival of a greater number of reproduc-
of the city as a death dispensary or as a provider of tive adults, well nourished or not.
immunity may not be especially relevant. Indeed,
Thomas McKeown (1976) has been the principal Chronic Infectious Diseases
spokesperson for a view that credits improving nutri- The attention of demographers and others trying to
tion rather than declining disease with that growth. explain the modern rise of population has seldom
According to McKeown, whether an individual sur- turned to the chronic infectious diseases. Thus, the
vives a disease, be it an acute viral infection such as steady silent killer, tuberculosis, and the flashy new
measles or a chronic infection such as tuberculosis, infection of Renaissance Europe, syphilis, are sel-
depends on the individual's state of nutrition. Yet dom discussed in this context. Yet there exists a
this argument is based more on experiential data reciprocal relationship between copathogens, acute
generated by physicians treating well-nourished and chronic. For example, survivors of smallpox
and undernourished mothers and children than on might have been weakened by this disease and thus
laboratory studies of human nutrition and specific succumbed to tuberculosis. Conversely, an underly-
infectious diseases. With many diseases, there is ing tuberculosis infection should have weakened the
little direct relationship between the outcome of inability of individuals to fight off smallpox and other
fection and the prior nutritional state of the host. epidemic illnesses. A reduction in the morbidity of
Yet the ability to outlast several serious infections chronic infectious disease may play an important
does depend on steady access to food and, obviously, role in the decline of mortality from acute infectious
to protection from further health insults. In a few disease. Thus, Stephen Kunitz (1983) has argued
diseases, such as measles and tuberculosis, there is, that the cause of the modern rise of population was
moreover, a positive association between poor nutri- stabilization of mortality from all causes.
tion and severity of infection. Insofar as these two Those historians, such as Alfred Crosby (1972),
were among the most common diseases of the early William McNeill (1976), Emmanuel Le Roy Ladurie
modern period, nutritional security and the gener- (1981), Kenneth Kiple (1984), and others, who have
ally improved standards of living this implies may
taken very grand perspectives of the period from 1400
have permitted the survival of more children to re-
to 1800 have seen Europeans participating in a saga
productive age. When smallpox, the last great killer
of unprecedented success because of their outward

migration and colonization. European population ex- early in life, recovered, and lived a normal life span,
panded externally far beyond the bounds of a modest then 40 to 55 years. The heaviest mortality from
modern rise of population. They unintentionally ex- tuberculosis occurred in infancy, the heaviest mor-
ported both chronic and acute infectious diseases, bidity probably in the middle adult years. A small
which had disastrous consequences for the native percentage of older children died of pulmonary tuber-
populations of the Western Hemisphere and Austral- culosis, chronic diarrhea, or any of the many vari-
asia. In return, Europeans brought back home only a eties of extrapulmonary infection. A slightly larger
few infections that caused serious concern. percentage of the once-infected succumbed as young
Foremost among these may have been syphilis. adults.
Imported, at some time during the late fifteenth Thus far we have concentrated mainly on mortal-
century, possibly with the Spanish colonization of ity. But the biography of Alexander Pope by Marjorie
the Americas, possibly with earlier Portuguese con- Nicholson and George Rousseau, This Long Disease,
quests in western Africa, syphilis suddenly appeared My Life (1968), provides a classic illustration of the
in the mid-1490s, uncharacteristically as a pustular process of chronic disease in individuals who escaped
rash, a large pox in contrast to the small pox. Within plague and the ravages of smallpox. Pope was struck
half a century, however, syphilitic patients suffered by a tubercular infection that left him disabled. He
the same general pathology that untreated victims labored to keep up his correspondence and wrote
would in the twentieth century, including long, poetry between visits to the baths and visits from
chronic bouts with ulcers and fistulae. The records of physicians. Throughout his life, he valiantly bore
both the initial pandemic wave and individual cases the great pain of travel by coach, a harrowing experi-
of syphilis from 1550 to 1800 are intertwined with ence for a body as gnarled as his, bravely sampled
heightened moral concerns and fears of stigmatiza- the latest remedies, and occasionally confessed his
tion, so that it is difficult to assess the prevalence of trials to his numerous invalid friends: "I am grown
syphilis during this period. Police and public health so tender as not to be able to feel the air, or get out of
officers of the nineteenth century took an aggressive a multitude of Wastcotes. I live like an Insect, in
interest in the control of syphilis, especially in the hope of reviving with the Spring." One of the last
control of prostitution. They thereby generated our visitors to Pope's deathbed observed, "He dyed on
earliest numerical surveys of syphilis, comparable to Wednesday, about the Middle of the Night, without a
earlier records of plague and smallpox. Pang, or a Convulsion, unperceived of those that
Because of European contacts with Africa and the watched him, who imagined he was only in a
tropical world, mosquitoborne diseases also tra- sounder Sleep than ordinary."
versed Europe increasingly after 1500. Malaria One suspects that the gradual recession of both
may have increased in prevalence, partially from acute and chronic infectious diseases also went un-
increased contact with Africans and partly from perceived even among those who were watching. But
increased rice cultivation. A more alarming mos- the human costs of epidemic diseases as well as
quitoborne disease, however, was yellow fever, epi- chronic infections lessened as people gained greater
demics of which increased in frequency through the access to food, as well as more nutritional variety,
seventeenth and eighteenth centuries and culmi- and developed means of distancing their exposure to
nated in the catastrophic Barcelona outbreak of acute infectious diseases during the economic expan-
1821. The eighteenth-century expansion of urban sion of the eighteenth century.
environments, especially of port cities and other Ann G. Carmichael
trade centers, along with the construction of irriga-
tion ditches for agriculture and canals for transport Bibliography
between markets, increased the number of breeding Appleby, Andrew B. 1975. Nutrition and disease: The case
places for mosquitoes. of London, 1550—1750. Journal of Interdisciplinary
History 6: 1-22.
Finally, we should mention again tuberculosis, as
1980. The disappearance of the plague: A continuing
John Bunyan called it in Pilgrim's Progress, "cap- puzzle. Economic History Review 33: 161-73.
tain of all these men of death." Scourge of the Benedictow, O. J. 1987. Morbidity with historical plague
wealthiest Renaissance families and a persistent epidemics. Population Studies 41: 401-31.
problem in Renaissance Italian cities, tuberculosis Carmichael, Ann G., and Arthur M. Silverstein. 1987.
followed the pulse of European urbanization, mov- Smallpox in Europe before the seventeenth century:
ing northward as cities appeared, to peak in the Virulent killer or benign disease? Journal of the His-
eighteenth century. Most city children were infected tory of Medicine and Allied Sciences 42: 147-68.

V.5. European Mortality Decline, 1700-1900 287
Crosby, Alfred W. 1972. The Columbian exchange: Biologi-

cal and cultural consequences of 1492. Westport, V.5
Conn.
Flinn, Michael W. 1981. The European demographic sys-
Diseases and the European
tem, 1500-1820. Baltimore. Mortality Decline, 1700-1900
Hatcher, John. 1977. Plague, population and the English
economy, 1348-1530. London.
Kiple, Kenneth F. 1984. The Caribbean slave: A biological In his study of world population published more
history. Cambridge. than 50 years ago, A. M. Carr-Saunders (1936) ob-
Kunitz, Stephen J. 1983. Speculations on the European served that the population of western Europe had
mortality decline. Economic History Review, Ser. 2,
begun to increase by the early eighteenth century, if
36: 349-64.
not earlier, as a result of a growing gap between
Landers, John. 1987. Mortality and metropolis: The case of
London, 1675-1825. Population Studies 41: 59-76.
births and deaths. The gap was accounted for primar-
Landers, John, and Anastasia Mouzas. 1988. Burial sea- ily by the fact that mortality was declining whereas
sonality and causes of death in London, 1670-1819. fertility was high and in some countries was even
Population Studies 42: 59-83. growing. Addressing the reasons for the decline in
Le Roy Ladurie, Emmanuel. 1981. A concept: The unifica- mortality, he, like others both before and since, clas-
tion of the globe by disease, fourteenth to seventeenth sified the causes into several categories:
centuries. In The mind and method of the historian,
ed. Emmanuel Le Roy Ladurie, 28-83. Chicago. For the purposes of this discussion the conditions, of which
note must be taken, may be classified into four groups,
Major, Ralph H. 1945. Classic description of disease, 3d
though the boundaries between them are indefinite and
edition. Springfield, 111.
though there is much overlapping: (1) political, that is
McKeown, Thomes. 1976. The modern rise of population.
conditions in relation to the maintenance of external and
New York.
internal order; (2) social, including the state of knowledge
McNeill, William H. 1976. Plagues and peoples. Garden
in relation to the production and use of food, and to the
City, N.Y.
making and use of clothing; (3) sanitary, that is conditions
Mercer, A. J. 1985. Smallpox and epidemiological-
relating to housing, drainage, and water-supply; (4) medi-
demographic change in Europe: The role of vaccina-
cal, including both the state of knowledge concerning the
tion. Population Studies 39: 287-307.
prevention and cure of disease and its application to the
Nicholson, Marjorie, and George S. Rousseau. 1968. A
public at large.
medical case history of Alexander Pope. In This long
disease, my life: Alexander Pope and the sciences, 7 - Because Carr-Saunders was dealing with the pe-
82. Princeton, N.J. riod after 1700, he thought that the first category -
Panta, Lorenzo del. 1980. La epidemie nella storia social order - no longer applied because conditions
demografica italiana. Turin.
in England and the rest of northwestern Europe
Patterson, K. David. 1986. Pandemic influenza, 1700-
1900: A study in historical epidemiology. Totowa, N.J.
were by that time comparatively stable and orderly.
Sharlin, Allan. 1978. Natural decrease in early modern
Thus, the other three categories were of most value
cities: A reconsideration. Past and Present 79:126-38. in explaining the mortality decline in northwestern
Sharlin, Allan, and Roger Finlay. 1981. Debate: Natural Europe in the eighteenth and nineteenth centuries.
decrease in early modern cities. Past and Present 92: Under (2) he included the adoption of root crops, the
169-80. improvement of gardening, and the use of cotton for
Shirley, Janet, trans, and ed. 1968. A Parisian journal, clothing, which improved personal cleanliness. Un-
1405-1449. London. der (3) he included the improvement of towns and
Slack, Paul. 1979. Mortality crises and epidemic disease in their water supplies, the paving and cleaning of
England, 1485-1610. In Health, medicine and mortal- streets, and the substitution of brick for timber. Cate-
ity in the sixteenth century, ed. Charles Webster, 9-59. gory (4) included increased scientific knowledge,
New York.
practical applications even when the theory was not
1981. The disappearance of plague: An alternative view.
Economic History Review, 2d Ser., 34: 409-76.
understood, a profession of practitioners (apothecar-
Stevenson, Lloyd. 1965. "New diseases" in the seven- ies in England), and the construction of hospitals
teenth century. Bulletin of the History of Medicine 39: (Carr-Saunders 1936). He did not attempt to deter-
1-21. mine which category was most significant.
Walter, John, and Roger Schofield. 1989. Famine, disease He then pointed out that in the countries of south-
and the social order in early modern society. New York. western Europe (excluding France) mortality did not
Zinsser, Hans. 1935. Rats, lice and history. Boston. begin to decline until the 1890s, probably as a result

of the late introduction of improvements in catego- could not possibly have had the effect attributed to
ries (2), (3), and (4). Finally, in eastern Europe the them. In fact, some may have done more harm than
course of mortality showed some resemblance to that good, as R. Dubos (1959) also pointed out.
of southwestern Europe, but began to decline even Others have argued that, at worst, hospitals and
later, when the same three causal categories were dispensaries, inoculations for smallpox, and "man-
first introduced. midwives" had no discernible effect and may have
In general, writers before Carr-Saunders had been beneficial. McKeown (1976), in The Modern
taken a similarly broad approach. After World War Rise of Population, has suggested that improved nu-
II, however, the situation changed. In an article on a trition in the eighteenth century initiated the de-
century of international mortality trends, George cline. Others have their favorite "first causes" as
Stolnitz (1955) observed the following: well: J. Riley (1987) has suggested environmental
Increasing life chances are almost always explained by improvements, and W. H. McNeill (1976), among
reference to two broad categories of causes: rising levels of others, has advanced the increasing genetic resis-
living on the one hand (income, nutrition, housing, liter- tance to infectious diseases of European populations.
acy), and on the other technological advances (medical It is likely that the mortality decline proceeded in
science, public health, sanitation). The usual approach has stages, with certain classes of diseases being reduced
been to regard these sets of factors as more or less coordi- in sequence (Omran 1971). The first to be reduced
nate, with little attempt to assess their relative impor- were pandemic and epidemic diseases not responsive
tance. At the same time there has been considerable em- to the nutritional status of the host. Next were dis-
phasis on their interdependence, a common observation eases that caused lifelong immunity after an infec-
being that the developing and application of disease con-
trol techniques would have been very different in the
tion. Last to decline were diseases that were either
absence of widespread social change. Both of these views, identifiable nosological entities or clusters of signs
which evolved largely on the basis of Western mortality and symptoms (i.e., the so-called pneumonia-
experience, have also been traditional explanations of the diarrhea complex), all of which were made espe-
contrasting patterns found in other parts of the world. cially lethal by the malnourished state of the host.
Only recently has their adequacy been seriously ques- Different conditions were causally associated with
tioned, mainly as a result of developments in Latin the decline of each disease.
America—Africa—Asia. The introduction of new disease- By the early 1700s the great pandemics of plague,
control methods in this region, usually unaccompanied by as well as subsistence crises, had receded from west-
any important shifts in socio-economic conditions, has led ern Europe. As Carr-Saunders (1936) had suggested,
to drastic mortality declines in the last few years. It is
worth noting, therefore, that a similar causal process may this was largely the result of the growing stability of
have been operative in the acceleration of Western survi- governments. More recently M. W. Flinn (1981) has
vorship a good deal earlier. elaborated this point, suggesting that a number of
factors were responsible for the diminution of mortal-
The measurable reduction in mortality rates fol- ity from wars, famines, and plague. There was, he
lowing the introduction of antibiotics and pesticides suggests, a change in warfare: a shift to naval and
led not only to revisionist views of the past accom- colonial wars, the development of a science of mili-
plishments of medical technology. It led as well to a tary hygiene, greater discipline of armies, and in-
major reshaping of the biomedical research and edu- creasing isolation of armies from civilian populations
cation establishment in the United States in the (all of which would have contributed to a decline in
decades following World War II, at a time when the typhus, among other causes of death). There was also
United States had emerged as the dominant force in a diminution of subsistence crises, attributable to the
scientific research in the West. spread of new crops, the opening (in eastern Europe
Both the intellectual and institutional changes especially) of new lands, improved transportation,
evoked a response from others with different ways of and more sophisticated "social administration" and
explaining historical and contemporary disease pat- famine relief. There was, finally, a diminution of
terns. We may call theirs a "holistic" approach, for it plague in western Europe, which a number of observ-
emphasized the significance of the social context, ers have attributed to increasingly effective quaran-
economic forces, and modes of life, and placed less tine procedures, for example, the Hapsburgs' cordon
weight on medical factors. For example, in 1955 sanitaire along the boundary of their empire with the
Thomas McKeown and R. G. Brown wrote that the Ottoman Empire. All of these measures were a reflec-
medical interventions usually invoked to explain de- tion of growing efficiency in the administration of
clining mortality in eighteenth-century England increasingly large states (Flinn 1981).

Thus, by 1700, the start of the period under consid- agricultural patterns and industrial and urban de-
eration, a major transformation in mortality was velopment, is not appropriate here. It is sufficient
well underway. The great waves of mortality were to note simply that, even before industrialization
ebbing and, by the mid-eighteenth century, death occurred, northwestern Europe differed signifi-
rates were stabilizing - albeit at high levels. Not cantly from the rest of Europe with respect to land
until about the turn of the nineteenth century, how- use, the organization of work, and household size
ever, did they begin a definite decline. and composition. However, it is also appropriate to
These observations refer primarily to northwest- suggest some of the ways in which these differences
ern Europe. Eastern Europe and the Balkans, and to may contribute to an explanation of the differences
a lesser degree southern Europe, still suffered from in mortality rates and patterns across Europe in
high and fluctuating mortality rates, as can be seen the eighteenth and nineteenth centuries after the
in the devastating plague epidemic that afflicted recession of great pandemics. Indeed, distinctions
Moscow in the 1770s (Alexander 1980). Indeed, it remained even into the twentieth century.
was in the eighteenth century that mortality in It has been said that mortality stabilized in north-
northwestern Europe began to diverge from that of western Europe during the eighteenth century as a
the rest of Europe. These large regional differences result of growth of stable states, and that elsewhere
will be dealt with first, followed by mortality in rates tended to fluctuate widely as epidemics per-
northwestern Europe. sisted into the nineteenth century. Nonetheless,
It is beyond the limits of this essay to account for even in the more peripheral regions of Europe, there
the rise of urban industrial societies in northwest seems to have been a diminution of pandemics and
Europe during the eighteenth century, and more ru- famines as compared with their occurrence in previ-
ral, agricultural societies elsewhere. That both pro- ous centuries. The diseases that remained were en-
cesses were somehow related is generally agreed, demic. They included named diseases such as tuber-
though precisely how is much less clear. Certainly as culosis, typhoid, scarlet fever, measles, as well as
cities grow, they must draw on a hinterland of in- various forms of pneumonia, enteric infections, and,
creasing size for agricultural produce. Just why in children, the so-called pneumonia-diarrhea com-
rings of production within nations or across Europe plex. Even smallpox, which in the past had caused
(and the globe) acquired the characteristics they did such fearsome epidemics, became in the course of the
in the eighteenth and nineteenth centuries is a sub- eighteenth century and even more in the nine-
ject of disagreement. Clearly, ease of transport and teenth, increasingly a disease of children rather
magnitude of demand are important variables than of young adults, a result of both the growth and
(Dodgshon 1977). integration of populations and inoculation and vacci-
Whatever the cause, it appears that in the eigh- nation. Most of these diseases were made more le-
teenth century agricultural production was differen- thal by the malnourished state of the host, although
tiated across Europe such that the east central, east- smallpox seems to have been an exception.
ern, and southern areas were devoted largely to the There were several ways in which agricultural
production of staples on large estates, worked by an and household organization affected this constella-
impoverished peasantry. In contrast, agriculture in tion of airborne, foodborne, and waterborne diseases.
northwest Europe was characterized largely by For example, early marriage associated with early
mixed dairy and arable activities on farms of 20 to childbearing increased the risk of infant death.
50 hectares (Abel 1980), usually worked by individ- Large households were likely to be crowded, and
ual families and servants. density increased the risk of contracting airborne
Family organization and household size differed infections as well as the opportunity of spreading
significantly among regions of Europe as well, body lice (vectors of typhus) in particularly unsani-
again for reasons that are poorly understood. North- tary conditions. Indeed, typhus continued to be com-
west European family organization tended to be mon in the civilian populations of Russia and the
neolocal, and household size to be smaller than else- Balkans well into the nineteenth century.
where in Europe, where households were large and The pattern of agriculture that persisted in the
complex in organization. In northwest Europe, too, peripheral regions of Europe throughout the nine-
marriage tended to occur at an older age than else- teenth century - agricultural wage laborers or serfs
where, and it was not universal (Laslett 1983). working on large estates devoted to monocropping -
Even to attempt to explain the genesis of these required the exploitation of female labor. In addition
differences, or their association with differences in to imposing physiological stress on women, it pre-

vented them from breast feeding for as long as might region in Calabria, the crude mortality rate aver-
have been desirable. Moreover, the fact that dairying aged about 50 per 1,000 in the latter part of the
was not common probably meant that, when infants nineteenth century. In one commune of this area
were weaned, they were put on a very modified adult between 1861 and 1875, the average annual crude
diet rather than one that included a large amount of mortality rate had been about 60 per 1,000 and the
nonhuman milk. Under such circumstances, so- infant mortality rate averaged about 500 per 1,000
called weanling diarrhea was probably very common. live births. There was no natural increase in the
Weanling diarrhea is a lethal syndrome in which a population (Kunitz 1983).
malnourished child develops diarrhea and in which There are no available data from nineteenth-
diarrhea may precipitate malnutrition. Diarrhea century Spain that permit a distinction to be made
may or may not be caused by malnutrition, but mal- between areas of latifundia and areas where peas-
nutrition increases the likelihood that an episode of ants owned their own land. Similarly, nineteenth-
diarrhea will be fatal. century data from the Balkans are somewhat sparse.
Studies in Russia at the end of the nineteenth Crude mortality rates in Croatia were almost 40 per
century showed that infant mortality increased dur- 1,000 between 1800 and 1870 and began to decline
ing the summer, when mothers often worked long significantly only in the 1870s. Rates were lower in
hours in the fields, generally leaving their children Slovenia, probably reflecting the greater influence
at home, where they could not be nursed. In addi- of Austria. Data from Serbia are available from
tion, the practice of using a pacifier rather than 1860, with rates ranging from 27 to 33 per 1,000
breast feeding increased the chances both of malnu- between 1860 and 1890 (Gelo 1982-3). It is likely
trition and of the acquisition of infections, since the that mortality stabilized gradually over the century
pacifier was "a rag covering crumbled bread or rolls, as the Ottoman Empire instituted reforms modeled
wet dough, or milk kasha - a device ripe with bacte- on those of Western governments, including efforts
ria, especially when combined with milk or, as was to control plague. The fact that it stabilized at high
the custom, prechewed by an adult" (Frieden 1978). rates was undoubtedly due to continuing backward-
Medical reformers who attempted to change these ness, for throughout the area feudal or semifeudal
practices frequently met resistance from people for relations persisted for much of the nineteenth cen-
whom domestic arrangements within an extended tury. In the Hapsburg lands, where servile obliga-
family reinforced traditional beliefs and child- tions were formally revoked in 1848, the state devel-
rearing practices. oped semifeudal relationships between members of
Germany provides another example of the associa- its bureaucracy and the peasantry, but in Bosnia-
tion between peasant life on large estates and mor- Herzegovina, under Hapsburg domination from
tality. In eastern Prussia the growth of Junker es- 1878, and in Macedonia, feudalism persisted until
tates devoted to grain monoculture gave rise to a 1918. In Serbia the state and money lenders were
peasant class that needed to exploit women in order the chief forces dominating the peasantry (Kunitz
to subsist, the result being, as in Russia, an inability 1983).
to breast feed properly and a high rate of infant Turning now to a consideration of mortality pat-
mortality. In western Prussia, by contrast, land re- terns within northwestern Europe during the eigh-
forms in the early nineteenth century led to a wider teenth and nineteenth centuries, we have already
distribution of peasant landownership, a greater va- observed that mortality had stabilized and even be-
riety of crops, and greater ownership of livestock by gun to decline in the eighteenth century. This was
more people. Thus, spontaneous abortions and in- primarily a rural phenomenon. Urban mortality re-
fant, perinatal, and maternal mortality were all mained high well into the nineteenth century,
lower in the West than in the East (Kunitz 1983). though a widely shared definition of urban is some-
Similar regional differences were observed in It- times difficult to arrive at.
aly, where the south was distinguished from the The points made about the consequences for mor-
north by a high proportion of latifundia and high tality rates of agricultural and household organiza-
crude mortality rates. Interestingly, however, in this tion in the peripheral regions of Europe suggest, by
case infant mortality did not differ from one region way of contrast, why mortality in the rural parts of
to another. No explanation for the lack of difference northwestern Europe declined more rapidly. House-
is available; rates all over Italy continued to be holds were smaller and presumably less crowded;
among the highest in Europe right to the present marriage and therefore childbirth occurred at later
century. Indeed, in one particularly poor "latifondo" ages; dairying became increasingly common and

was practiced year round beginning in the eigh- dramatically throughout the century as a result of
teenth century; there seems to have been less exploi- vaccination. And unquestionably the pneumonia-
tation of female labor; increasing emphasis was diarrhea complex of childhood declined significantly
placed on breast feeding of infants and young chil- as well.
dren; and when weaning occurred, infants were It will never be possible to apportion credit with
likely to be given cows milk rather than a watered- total accuracy to the many preventive measures that
down version of adult table foods. The result was contributed to the decline in urban mortality. Public
lower rates of infant, child, and crude mortality in health interventions, changing standards of individ-
rural northwestern Europe than elsewhere. ual behavior, and improved housing and diets pre-
In contrast, urban mortality in northwestern Eu- sumably played more or less important roles. Efforts
rope throughout most of the nineteenth century was to sort through all of these factors will doubtless
often as high as in the high-mortality countries of raise more questions.
Europe; rates in some cities seem actually to have For example, because it has proved difficult to get
increased in the first part of the nineteenth century. good direct measures of the standard of living in past
The issue of whether urban mortality did in fact in- times, individual stature, an ingenious indirect mea-
crease is bound up with the so-called standard of sure, has increasingly been relied on (Fogel, Enger-
living debate (Woods and Woodward 1984). On one man, and Trussell 1982). It is generally assumed
side are the "pessimists" - usually to the left of the that height is a good reflection of nutritional status.
political spectrum - who claim with Friedrich Engels Thus, if better diets were responsible for the stabili-
that industrial development resulted in a deteriora- zation of or increase in life expectancy, there should
tion of living conditions of the working class. On the have been an accompanying increase in stature. Un-
other side are the "optimists," who claim that develop- fortunately, the association is complicated by the
ment made life better for all and that in some regions fact that height also reflects the impact of disease,
of Europe industrial development averted a subsis- particularly gastrointestinal afflictions. Permanent
tence crisis, so severe was rural poverty (Komlos stunting may not occur if the intervals between
1985). As almost always happens, there is a middle bouts of childhood sickness are sufficiently long that
position, whose advocates in this case claim that ur- catch-up growth can take place. In developing coun-
ban mortality did increase but that it was never as tries this is often not the case, however, and it has
high as it had been in the seventeenth and eighteenth been said that "infections are as important a cause of
centuries, when epidemics could run amok (e.g., Arm- malnutrition as is the limited availability of food"
strong 1981). (Martorell and Ho 1984).
In both England and France, urban mortality The same may have been true in eighteenth- and
seems to have begun to decline in the second half of nineteenth-century Europe. Thus, the findings re-
the nineteenth century. The diseases that declined garding variations in height among European popu-
were spread in different ways: through the air (e.g., lations (Floud 1984), between urban and rural popu-
respiratory tuberculosis), food, or water (e.g., ty- lations (Sandberg and Steckel 1987), and within
phoid and gastroenteritis of all sorts). Many of them populations over the course of 100 or 200 years (Fo-
seem to be more lethal if the host is malnourished. gel et al. 1982) are difficult to interpret if one wants
Indeed, McKeown (1976) has argued that the decline to use them as a measure of the availability of food.
in deaths from tuberculosis in England was the re- This is important because an increase in height
sult of improved host resistance resulting from bet- (which began in most western European countries in
ter nutrition, whereas the decline of foodborne and the nineteenth century) could be interpreted as a
particularly waterborne diseases was the result of reflection of the increased availability of food or a
improvements in public health measures, such as reflection of declining sickness resulting from public
protected water supplies and sewage disposal, which health measures and from changes in personal be-
seem to have been introduced with increasing fre- havior, or - what is more likely — both.
quency in the second half of the nineteenth century. In England, at least, fluctuations in life expec-
Some diseases such as scarlet fever may have de- tancy diminished by the mid-eighteenth century, sta-
creased in virulence as a result of genetic shifts in bilized at relatively low levels, and then began to
the microorganism itself. Others, such as diphthe- increase in the first decades of the nineteenth cen-
ria, may have increased in virulence for the same tury. Height also began to increase in the early nine-
reason. There seems little doubt that, in both urban teenth century. Unfortunately, regional data on
and rural places, the incidence of smallpox declined height are not yet available. But these observations

can be interpreted tentatively to mean that the stabi- for Europeans but for all peoples. Its causes were
lization of mortality was not caused by improved bound up with the very creation of the world as we
nutritional status and that, when both height and now know it and will continue to be a topic of debate
life expectancy began to increase in the nineteenth for as long as we disagree about why the world is as
century, the effects could have been reciprocal: re- it is.
duced sickness contributing to increased height, im- Stephen J. Kunitz
proved nutrition (partially reflected in increased
height) making people less susceptible to the lethal
effects of the most prevalent infectious diseases. In Bibliography
other words, height is a good measure of the stan- Abel, W. 1980. Agricultural fluctuations in Europe from
the thirteenth to the twentieth centuries. London.
dard of living, but it is difficult to determine
Alexander, J. T. 1980. Bubonic plague in early modern
whether more food or less disease was responsible Russia. Baltimore.
for the height increase. Armstrong, W. A. 1981. The trend of mortality in Carlisle
There are several points on which most observers between the 1780s and the 1840s: A demographic
seem to agree. First, the initial recession of pan- contribution to the standard of living debate. Eco-
demics seems to have been a result of the growth of nomic History Review 34: 94—114.
nation-states. Second, specific curative measures ap- Carr-Saunders, A. M. 1936. World population: Past growth
plied by individual physicians to individual patients and present trends. Oxford.
had little if any impact on mortality, regardless of Dodgshon, R. A. 1977. The modern world system: A spatial
the comfort or distress they may have caused pa- perspective. Peasant Studies 6: 8-19.
tients and their families. Third, the recession of a Dubos, R. 1959. The mirage of health. New York.
variety of endemic diseases had a mix of causes: Fildes, V. 1986. Breasts, bottles and babies: A history of
infant feeding. Edinburgh.
environmental cleansing and active public health Flinn, M. W. 1981. The European demographic system,
interventions; changes in personal behavior (more 1500-1820. Brighton.
frequent bathing, hand washing, the cessation of spit- Floud, R. 1984. Measuring the transformation of the Euro-
ting in public, the covering of one's mouth and nose pean economies: Income, health and welfare. Discus-
when sneezing and coughing); and improvements in sion paper series, No. 33, Centre for Economic Policy
living conditions. Fourth, urban mortality in west- Research, London (2d Ser.) 34: 94-114.
ern Europe increased for a generation or two in the Fogel, R. W., S. L. Engerman, and J. Trussell. 1982. Explor-
early nineteenth century. ing the uses of data on height: The analysis of long-
There are also significant areas of disagreement. term trends in nutrition, labor welfare, and labor pro-
One, the standard-of-living debate, has already ductivity. Social Science History 6: 401-21.
been mentioned. Another, which has received less Fogel, R. W., S. L. Engerman, and R. Floud. 1983. Secular
attention, is the degree to which individual behav- changes in American and British stature and nutri-
tion. Journal of Interdisciplinary History 14: 445-81.
ior, as opposed to collective measures, affected mor- Frieden, N. M. 1978. Child care: Medical reform in a tradi-
tality. McKeown (1976) has argued that, in de- tionalist culture. In The family in imperial Russia, ed.
veloped nations, individual behavior is now more D. L. Ransets, 236-59. Urbana, 111.
significant than environmental conditions in deter- Gelo, J. 1982—3. Usporedna slika demografshih promjena
mining health status whereas in the past environ- Hrvatske i odabranih zemalja od 1780. do 1980. go-
mental conditions were more important than indi- dine (Demographic change in Croatia and selected
vidual behavior. There is certainly disagreement countries between 1780 and 1980: A comparative pic-
with regard to the truth of this assertion. It has ture). Stanovnistuo 20-1: 85-98.
been argued, for example, that attitudes toward Komlos, J. 1985. Stature and nutrition in the Habsburg
breast feeding and personal cleanliness had a mea- monarchy: The standard of living and economic devel-
surable impact on mortality in the eighteenth and opment in the eighteenth century. American Histori-
cal Review 90: 1149-61.
nineteenth centuries (Razzell 1974; Fildes 1986).
Kunitz, S. J. 1983. Speculations on the European mortal-
Another subject of disagreement has to do with ity decline. Economic History Review, 2d Ser., 36:
the notion that European populations were selected 349_64.
for resistance to a wide variety of infectious diseases. Laslett, P. 1983. Family and household as work group and
Some claim that this was an important determinant kin group: Areas of traditional Europe compared. In
of declining mortality, whereas others deny that it Family forms in historical Europe, ed. R. Wall,
was. What is clear is that the European mortality J. Robin, and P. Laslett, 412-20. Cambridge.
decline was a momentous phenomenon, not simply Martorell, R., and T. J. Ho. 1984. Malnutrition, morbidity,

V.6. Sub-Saharan Africa to 1860 293
and mortality. In Child survival: Strategies for re- This does not mean that they enjoyed perfect
search, ed. W. H. Mosley and L. C. Chen, 49-68. health. They were tormented by a variety of ar-
Cambridge. thritic conditions and suffered from accidents con-
McKeown, T. 1976. The modern rise of population. New nected with hunting and warfare. Those living
York. within the line of 40-inch rainfall would have been
McKeown, T., and R. G. Brown. 1955. Medical evidence infected from time to time by the trypanosome,
related to English population changes in the eigh-
which is presumably a very ancient parasite of wild
teenth century. Population Studies 9: 119-41.
McNeill, W. H. 1976. Plagues and peoples. New York.
animals. When it is transmitted to humans and
large animals by the tsetsefly,it causes often-deadly
Omran, A. R. 1971. The epidemiologic transition: A theory
of the epidemiology of population change. Millbanksleeping sickness. Indeed, as William McNeill points
Memorial Fund Quarterly 49: 509-38. out, the disease probably set some limits on the
territory in which early humans were able to hunt
Razzell, P. E. 1974. An interpretation of the modern rise of
and gather. Those living close to the forest would
population: A critique. Population Studies 28: 5-17.
Riley, J. C. 1987. The eighteenth-century campaign to also have been infected on occasion by arboviruses
avoid disease. London. (carried by primates) such as dengue and yellow
fever, and it would appear that vivax malaria was
Sandberg, L., and R. H. Steckel. 1987. Heights and eco-
nomic history: The Swedish case. Annals of Human ubiquitous at some stage of human development in
Biology 14: 101-10. sub-Saharan Africa. Plasmodium vivax is thought to
Stolnitz, G. 1955. A century of international mortality
be the oldest of the malaria types that presumably
trends: I. Population Studies 9: 24-55. were passed along to humans by their primate cous-
Woods, R., and J. Woodward, eds. 1984. Urban disease and
ins. That this occurred quite some time ago is sug-
mortality in nineteenth-century England. London.
gested by the fact that the blood of most (95 percent
or more) black Africans and those of African descent
scattered around the globe lack Duffy antigen,
which makes them absolutely refractory to this ma-
larial parasite. Indeed, vivax malaria has died out in
Africa, presumably for a lack of hosts.
V.6
It is perhaps ironic that, by domesticating plants
Diseases of Sub-Saharan and animals in the first gigantic effort of humans to
Africa to 1860 control their environment, they created a disease
environment over which they had no control, one
over which even today only a small measure of con-
Disease in Africa, as elsewhere, has been and contin- trol has been gained. We will probably never know
ues to be intimately linked with the ways that hu- with certainty what prompted hunter-gatherers to
man populations have fed themselves. Throughout become sedentary agriculturalists. A good guess,
most of the evolutionary journey of Homo sapiens on however (for Africa as elsewhere), is that the rela-
the African continent (again, as elsewhere), the spe- tively disease-free environment contributed to popu-
cies existed in small bands of hunter-gatherers with lation growth, that slowly a band of fewer than a
generally fewer than 100 members. As such, indi- hundred individuals became more than a hundred
viduals were constantly on the move, seldom paus- and divided, and that these bands grew too large and
ing in one place long enough to foul their water divided again, until at some point there were simply
supplies or let their garbage and excrement pile up. too many people for even the huge expanse of Africa
They were, as a consequence, spared a host of water- to support in their hunting and gathering.
borne parasites and insect disease vectors. Because If this is true, then another factor was the expan-
hunter-gatherers did not have domesticated ani- sion of the Sahara desert, which meant the shrink-
mals, they were also spared the incredible number of ing of resources. The concept of sub-Saharan Africa
ailments that animals pass along to human masters. is a relatively recent one. Some 50,000 years ago
Moreover, their numbers were too small to support that desert was no desert at all, but rather a region
directly transmitted microparasitic diseases such as covered by Mediterranean flora, and as late as 4,000
smallpox and measles. Finally, evidence suggests years ago fanners and pastoralists inhabited many
that hunter-gatherers were essentially free from the regions that are dry and barren today. The effect of
predominant noncommunicable diseases of today, the desiccating desert was to split the continent into
such as cancer, heart-related diseases, and diabetes. two subcontinents, cut off most intercourse between

the two, and leave the lower subcontinent in relative It is likely that this political consolidation on the
isolation from the rest of the world. The isolation of savannas, coupled with the advent of the Iron Age,
eastern Africa, which fronted on the Indian Ocean, hastened the occupation of the West African forest.
was less severe than that of the West, where a hos- For one thing, the forest was a place of refuge from
tile Atlantic Ocean formed still another barrier to that consolidation, which was based to some extent
the rest of the world. on slavery, and from mounted slave hunters who
were frustrated by the lack of mobility in the forest
They were Stone Age peoples who found themselves and whose horses were vulnerable to the tsetse fly
slowly pressed south by the expanding Sahara. At and sleeping sickness in many forest areas. Another
first they lived by harvesting the seeds of wild reason that people gravitated to the forest had to do
grasses on its fringes. Then, gradually, they learned with both the development of iron tools that were
how to sow those seeds, which, with repeated effort, used to clear it and the efficient cultivation of newly
would become domesticated sorghums and millets. imported Southeast Asian food plants such as the
To the south, on the edge of the forest, dwelled other Asian and coco yams: These yams were considerably
Stone Age peoples, who fed themselves by trapping higher yielding than any African food plant and
small animals and collecting the roots and fruits of grew well in forest clearings.
the forest, which they also learned to domesticate. Accompanying this conversion to sedentary agri-
To the east, however, hunting and gathering contin- culture for most sub-Saharan Africans were parasite
ued, although some cattle were apparently herded in proliferations. They came from herds of domestic
the northern regions. animals in the north, they arrived via caravan
It was in the south on the eve of the Iron Age, across the desert as people from the northern subcon-
which is to say, the first millennium B.C., probably tinent came to trade, and they developed internally.
in the Congo basin, that there developed an agricul- The hot, rainy, humid portions of Africa harbor a
turally oriented people who would soon spread over vast and nasty collection of disease-bearing insects,
much of sub-Saharan Africa. These were the Bantu. among them some 60 of the world's species of
Their language, proto-Bantu, was not a language of Anopheles mosquitoes. The creation of clearings and
hunters, but rather of farmers with words for domes- slash-and-burn agriculture made fine breeding
ticated animals and plants. It would seem, however, places for many of them, including Anopheles gam-
that at first they were not the cereal agriculturalists biae, the most efficient vector for malaria. With sta-
that most later became, but rather yam and palm oil tionary humans acting as reservoirs for the disease,
cultivators who had discovered that these plants human being to mosquito to human being malaria
grew best in the wetness of cleared-forest areas. cycles began. Vivax malaria was in recession but
While the language was still in a formative stage, it was replaced by the new and much more deadly
incorporated words for ax and knife and iron and falciparum malaria, which forced populations to
bellows. These agricultural people with a knowledge build genetic defenses against it, such as sickle trait,
of ironworking made up the groups that began to glucose-6-dehydrogenese deficiency, and thalasse-
expand southward and eastward from their nuclear mia traits. In addition, the less lethal but none-
area to absorb, conquer, and supplant other peoples theless debilitating Plasmodium malariae became
until the Bantu culture (and agriculture) predomi- widespread, and genetic defenses notwithstanding,
nated in almost all of sub-Saharan Africa save for immunity acquired by suffering a few bouts of ma-
West Africa. laria and surviving them was doubtless the first line
The latter region was, in the meantime, filling up of defense.
as the expanding desert continued to nudge people, With the development of sickle trait, however, Af-
as well as the forest itself, farther and farther south, rican youngsters probably began to develop deadly
with the densest populations staying just to the sickle cell anemia. Although sickle-shaped cells
north of the retreating forest. Many of these peoples somehow limit the extent of parasitization in the
were perhaps slower than the Bantu to become ac- case of Plasmodium falciparum, that protection
complished agriculturalists, but by the end of the comes at a very dear price. When both parents of a
first millennium A.D. most had done so. By this time child have the trait, the odds are 1 in 4 that the child
the region had achieved a good deal of urbanization will be born with sickle cell anemia. In the past, an
on the savannas of Sudan, Mali, northern Ghana, afflicted child would most likely have died. Thus, in
and Nigeria, and obviously a well-developed agricul- the more malaria-ridden regions of Africa, where
tural base was necessary to support the cities. the frequency of sickle trait reached 40 percent or

more, sickle-cell anemia must have been an impor- the single crop generally produced by sedentary agri-
tant killer of the African young. culturalists, nutritional illnesses must have joined
Permanent villages in and near the forest accumu- the list of new diseases in Africa. A diet that is
lated human junk, such as broken pottery, which essentially vegetable in nature and limited to a very
encouraged the breeding of another disease vector, few nutriments is low in iron, the vitamin B com-
the Aedes aegypti mosquito. As the latter came to plex, and essential amino acids. In these circum-
depend on closely packed human populations for stances it is the young, just weaned from the high-
blood meals, it began to spread yellow fever among quality protein in breast milk to a vegetable pap,
them. Depending on location, villages were cursed who suffer the most from protein-energy malnutri-
with dracunculiasis (guinea worm infection), schisto- tion with kwasiorkor and marasmus as its sympto-
somiasis, and filariasis (elephantiasis) including matic poles. Animal milk would have prevented the
onchocerciasis (river blindness, craw craw), and disease, but as hinted at previously those within the
loiasis (loa loa). Individuals now living in close prox- line of 40-inch rainfall could not develop a dairying
imity to one another in large numbers passed yaws industry because of the blood-sucking tsetse fly,
and leprosy back and forth. Fouled water supplies which seeks out large animals and infects them with
supported endless rounds of typhoid fever and African trypanosomiasis. This explains, in large
amebic and bacillary dysentery. In addition, the part, the high frequency of lactose "intolerance
blood of the animals that were domesticated and among those of West African descent. If they did not
lived cheek to jowl with their masters attracted the drink milk after infancy, there was no reason to
tsetsefly,which infected humans as well with sleep- maintain the lactose enzyme.
ing sickness (sleepy distemper). They also attracted Most West Africans, in particular, were limited to
disease-bearing insects with their dung and passed raising a few animals such as goats, chickens, dogs,
along parasites like tapeworm, ascaris, and trichuris and perhaps a pig or two. But because these animals
worms. These and other worms, such as the hook- were slaughtered only on festive occasions, and be-
worm, became ubiquitous in towns and villages cause of taboos against drinking goats milk and eat-
where fecal material was disposed of casually, if at ing eggs, animal protein figured very little in the
all, and individuals went barefoot. Indeed, for rea- diet. Moreover, African soils in the tropical belt are
sons yet to be explained, West Africans, at least, had heavily acidic, nitrogen deficient, and leached by
so much experience with hookworm infection that rains of their mineral content, especially calcium
they developed a natural resistance to hookworm and phosphorus. As a result, crops that grow on
anemia. them, as well as animals that graze on them, are
protein and mineral deficient. That the West African
If the forest offered protection from human preda- diet was extraordinarily low in high-quality protein
tors, a price of that protection was frequently isola- is suggested by the fact that slaves from Africa reach-
tion: Self-sustaining village-states were remote from ing the Caribbean Islands were significantly shorter
one another as well as from the larger world outside than island-born counterparts, despite the miserable
the forest. One consequence of this was the develop- quality of the slave diet in the West Indies.
ment of a rigid social structure that guaranteed the In addition to deficiency diseases, sedentary agri-
social stability so necessary for survival, but at the culture led to a reliance on crops that could and did
expense of innovation and change. Another likely fail because of insects, drought, and warfare. Thus,
consequence was frequently sufficient isolation from periodic famine, famine-related diseases, and starva-
the disease pools of the outside world that when tion thinned populations that had swelled during
epidemics did strike they proved to be of exceptional good times, and this synergism became another un-
virulence. pleasant fact of African life. In short, in the switch
It is important to stress that the shift to sedentary from hunting and gathering to sedentary agricul-
agriculture among both cereal farmers and yam and ture, Africans became what Thomas Malthus called
palm oil cultivators was not an overnight phenome- a "forced population," meaning that although the
non (and indeed, Africa today has hunter-gatherers). population grew, this growth was managed only at a
Rather, the shift was the result of a process in which decreased level of subsistence for everybody.
expanding food supplies created expanding popula-
tions, which in turn sought new areas to bring under Contact with Europeans and, through them, their
cultivation. However, as the diet narrowed from the American empires brought a second agricultural
variety of foodstuffs enjoyed by hunter-gatherers to revolution to sub-Saharan Africa. Cassava (manioc),

maize, peanuts, and sweet potatoes, high-yielding latter part of the nineteenth century, Hirsch pro-
plants imported from America, spread throughout nounced the disease "very malignant" in sub-
Africa until they became much more important than Saharan Africa. Yet eighteenth-century European
indigenous crops and further stimulated population observers saw little of it and called it rare.
growth. Ironically, much of that growth was drained It may be that the observers in question simply
off to America via the slave trade. In addition to did not recognize the disease, because tuberculosis
population growth, however, the new plants stimu- can have atypical symptoms. Certainly the isolation
lated disease. It has been discovered that those Af- of many African groups and the relative lack of
ricans whose diets centered on maize very often urban life probably also help to account for the phe-
suffered from pellagra, and those who consumed cas- nomenon. Another possibility, however, deserves
sava were assaulted by beriberi. Also, given the vege- some attention.
table nature of their diets coupled with the parasites Leprosy and tuberculosis are both caused by bacilli
that infected them, most sub-Saharan Africans were from the genus Mycobacterium and an inverse rela-
anemic. Moreover, the tell-tale spongy and bleeding tionship between the two diseases has been noticed
gums of scurvy were not uncommon. (e.g., where leprosy is prevalent, tuberculosis is not
With the Europeans, and with more contact with and vice versa). It is generally thought that, although
the outer world, also came increased exposure to tuberculosis protects against leprosy, the converse is
contagious diseases. The earliest European report of not the case. Yet in Nigeria, in the heart of the leprosy
smallpox in sub-Saharan Africa dates from Angola belt, where it is assumed that the disease has been
in the 1620s, but the strong probability exists that it endemic for many centuries, tuberculosis was very
had been present there for several preceding centu- slow to take hold. As late as 1936, for example, a
ries. In fact, August Hirsch pinpointed regions of British physician reported much leprosy in Nigeria,
central Africa along with India as the "native foci" of but made no mention of tuberculosis.
the disease, and others have also reported that small- Bacillary pneumonia, like tuberculosis, was
pox was a very old disease on the African continent. brought to Africa by the Europeans, and like tu-
This was very likely true of measles, chickenpox, berculosis it would prove to be of extraordinary viru-
and most other Eurasian diseases as well. Evidence lence among the Africans, at least by the nineteenth
for this assumption derives from the fact that, un- century. Observers reported much lung disease
like the American Indians or the Pacific Islanders, around the Bight of Benin; the disease was viewed as
sub-Saharan Africans did not die in wholesale fash- one of the most serious to torment the people of An-
ion after contact with the Europeans. The Europe- gola; and Hirsch reported pneumonia as "common"
ans, however, were extremely susceptible to African on most of the African West Coast and the East Coast
illnesses, especially to the African fevers - yellow as well.
fever and malaria. Indeed, white sailors on slaving Syphilis was also a late arrival in sub-Saharan
vessels, and especially soldiers stationed in Africa, Africa and, like tuberculosis, was slow to spread.
suffered such horrendous levels of mortality (in But here we are on more solid ground in explaining
some instances soldiers died at a rate of 500 to 700 its slow diffusion. The causative agents of both syphi-
per 1,000 per annum) as to earn West Africa the lis and yaws are of the same family (the two diseases
sobriquet "the white man's grave." Thus, it was not may be only one illness with different symptoms and
until the advent of modern medicine that Europeans means of transmission) and thus provide cross-
were able to colonize much of sub-Saharan Africa. immunity. Because yaws was endemic to much of
One Eurasian disease that was slow to make in- sub-Saharan Africa, it would seem that syphilis had
roads in Africa was tuberculosis. There seems no much difficulty finding hosts - so much so that Da-
doubt that whereas tuberculosis was a disease of vid Livingstone was convinced that "pure Africans"
many ancient civilizations and even prehistoric peo- could not develop the disease. Earlier, Mungo Park,
ple in Europe, it was unknown in sub-Saharan Af- the great explorer of the Niger River at the turn of
rica until the arrival of the Europeans. Because a the nineteenth century, saw a great deal of yaws but
long experience with this disease appears to confer no syphilis. In contrast, Father Giovanni Cavazzi, in
some ability to resist it, and conversely, because it his classic treatment of the diseases of the Congo
falls on "virgin-soil" peoples with considerable fury, and Angola, writes of the "mal Frances," called
one might have expected tuberculosis to have be- "bubas" by the Portuguese, as the most common
come a severe health problem in Africa long before it disease of the region. Though incomplete, his descrip-
did in the nineteenth and twentieth centuries. In the tion suggests syphilis racing through a virgin-soil

people, which may well have been the case, for the the abundance of tropical diseases - helminthic, vi-
padre was describing people who had been in contact ral, microbial, and protozoal — in sub-Saharan Af-
with Europeans longer than had most others. Yet rica are diverse. The existence of numerous popula-
the disease he reported could also have been leprosy, tions of primates that could harbor diseases and
because until well into the twentieth century, physi- pass them on to humans is obviously one. Another
cians have had difficulty differentiating between has to do with the high average temperatures and
syphilis and leprosy in Africa. humidity that, along with lush vegetation, make
To the extent that they were successful in making tropical Africa a paradise for the myriad insects
this distinction, reporters indicate that the disease that are free from the seasonal controls of more
had apparently overcome the resistance of yaws to temperate climates and thus can abuse humans on
become common at least in the port cities of West a year-round basis. The same, of course, is true of
and West Central Africa during the nineteenth cen- the many helminthic parasites that find the ecology
tury, although it remained rare in Mozambique until of the African tropics ideal. As a result, Africans
the early twentieth century. From the reports of were seldom free of disease, and most likely suf-
Livingstone and Park, however, the disease was slow fered from more than one at the same time.
to spread inland. Moreover, those born into this world were not pro-
Gonorrhea, the other major sexually transmitted vided with much good nutrition to combat their ill-
disease of yesterday, was present much earlier in nesses, and in fact illness often worked synergisti-
sub-Saharan Africa and probably had been acquired cally with malnutrition. The chief sufferers of both
from the Arabs. Unlike syphilis, gonorrhea had no the disease and nutritional environments were, of
yawslike disease to hinder its spread and quickly course, the young. Infants died at horrendous rates,
became ubiquitous. The disease is usually not life as did children, and it is likely that 50 percent of
threatening. But it may cause ophthalmia neona- those born in sub-Saharan Africa did not live until
torum, which along with onchocerciasis was proba- age 5. Yet such high infant and child mortality con-
bly responsible for much of the blindness reported stitutes a powerful selective mechanism, and it
among the African natives. seems clear that, in the face of sickness and malnu-
Other nonlethal ailments that tormented sub- trition, Africans adapted to both in ways we know
Saharan Africans include still more eye ailments, and in ways we have yet to discover.
which must have been caused by an absence of Kenneth F. Kiple
vitamin A, since night blindness was regularly
seen. The skin complaints that seemed to plague Bibliography
almost everyone resulted from riboflavin deficiency Curtin, Philip. 1967. Epidemiology and the slave trade.
as well as from pellagra, yaws, syphilis, onchocer- Political Science Quarterly 83: 190-216.
ciasis, and a variety of insect pests including the Daniell, William F. 1849. Sketches of the medical topogra-
mites that produce scabies, which were widely re- phy and native diseases of the Gulf of Guinea, Western
Africa. London.
ported. Ainhum, sometimes called the "dry gan-
Ford, John. 1971. The role of the trypanosomiasis in Afri-
grene of the little toe" by European observers, can ecology: A study of the tsetse fly problem. Oxford.
which involved the constriction and eventual loss of Hartwig, G. W., and K. David Patterson, eds. 1978. Disease
that digit, was another ailment reported with some in African history. Durham, N.C.
frequency; and rheumatism and arthritis were rife Hoeppli, R. 1969. Parasitic diseases in Africa and the West-
across the continent. Finally, women and children ern Hemisphere: Early documentation and transmis-
often ate dirt and clay, presumably in response to sion by the slave trade. Basel.
mineral deficiencies. Kiple, Kenneth F. 1984. The Caribbean slave: A biological
history. Cambridge.
By 1860, then, sub-Saharan Africans were being Kiple, Kenneth F., ed. 1987. The African exchange: To-
ward a biological history of black people. Durham,
born into a world teeming with pathogens. Almost
N.C.
all of the major diseases of the rest of the world had Kiple, Kenneth F., and Virginia H. King. 1981. Another
been introduced, including cholera, which had al- dimension to the black diaspora: Diet, disease and
ready paid visits to East Africa in 1821, 1836-7, racism. Cambridge.
and 1858-9, to enrich a disease pool already brim- Latham, Michael. 1965. Human nutrition in tropical Af-
ming with tropical ailments that much of the rest of rica. Rome.
the world had been spared (cerebrospinal meningi- Lewiki, Tadeuz. 1976. West African foods in the Middle
tis and plague were yet to arrive). The reasons for Ages. London.

McKeown, Thomas. 1988. The origins of human disease. Recent technological advances, especially in elec-
London. tron microscopy, coupled with the rapidly expanding
McNeill, William H. 1976. Plagues and peoples. Garden specialties of molecular biology, genetics, and immu-
City, N.Y. nology, have given rise to an equally rapid expan-
Miller, Joseph C. 1988. Way of death: Merchant capitalism sion of virology. Scientists are now on the threshold
and the Angolan slave trade, 1730-1830. Madison, of making important new discoveries that it is hoped
Wis.
will lead to cures for viral infections to equal those
Ransford, Oliver. 1984. "Bid the sickness cease": Disease in
the history of black Africa. London.
available for many bacterial, fungal, and parasitical
Shaw, Thurstan. 1977. Hunters, gatherers, and first farm- infections. Unfortunately, however, the identifica-
ers in West Africa. In Hunters, gatherers, and first tion of Africa as the home of "exotic new diseases"
farmers beyond Europe: An archaeological survey, ed. has reinforced the widespread view of that continent
J. V. S. Megaw, 69-125. Leicester. as a major source of disease-causing germs.
Disease has been an important factor in the his-
tory of sub-Saharan Africa since 1860. Across the
continent people have been under constant attack by
endemic diseases in their struggle for survival, and
V.7 epidemic diseases have decimated millions. In 21
countries, life expectancy today ranges from only
Diseases of Sub-Saharan about 44 to 56 years according to I. Timaeus (per-
Africa since 1860 sonal communication). In some countries, mortality
rates have grown recently, and in most regions they
remain high. Increases have occurred in Angola,
Africa was long characterized as the "dark conti- Ethiopia, Mozambique, Niger, Nigeria, and Rwanda.
nent," impenetrable, disease-ridden, and dangerous. In the first three there were 250 to 299 deaths per
To many Europeans, Africans personified degener- 1,000 live births, and in Gambia, Sierra Leone, Mali,
acy and suffering, and their environment seemed a and Malawi child mortality rates were more than
hothouse of fever and affliction. Europeans had good 300 per 1,000 (United Nations 1987). The direct
reason to connect sub-Saharan Africa with disease. causes of this mortality in most developing countries
For centuries, their attempts to penetrate the are the following: diarrhea, malnutrition, malaria,
coastal fringes of the continent had been effectively measles, acute respiratory infections, tetanus, and
frustrated by diseases against which they had little other neonatal causes. Now AIDS reminds us of the
or no resistance (Carlson 1984). In the early nine- potential havoc of an epidemic disease in Africa.
teenth century, Europeans arriving in West Africa Nevertheless, other countries have experienced an
suffered appalling mortality from disease (most of- appreciable decline in infant and child mortality in
ten yellow fever and hyperendemic malaria) at rates the past 20 years. In Kenya in the late 1950s, the
of between 350 and 800 per 1,000 per annum (Curtin child mortality rate (for children less than 5 years of
1968), and the West African coast became known as age) was 265 deaths per 1,000 live births, whereas in
the "white man's grave." With such mortality rates, 1989 it had declined to 150 per 1,000 (Blacker 1989).
it is no surprise that Europeans believed that Africa It must be made clear that in some regions of Africa
was more disease-ridden than other parts of the there have been significant increases in population
world. growth, whereas other regions such as Kivu in east-
In fact, many continue to believe that tropical Af- ern Zaire have been densely populated for many
rica has a well-deserved reputation as a vast breeding decades. African demography is a rapidly expanding
ground and dispersal center for dozens of diseases and field of study among social scientists and members of
thus would subscribe to the recent assertion that the medical and scientific communities, and there is
"Africa is a sick continent, full of sick and . . . starv- a continuing debate concerning the relationship be-
ing people" (Prins 1989). This view has been re- tween biomedical provision and morbidity and mor-
inforced by scientific speculation concerning the ap- tality rates in sub-Saharan Africa. Some observers
pearance of so-called exotic new diseases like Ebola, contend that over the past century, medical provi-
Marburg, and Lassa fevers in the 1960s and 1970s sion has been the major factor in lower morbidity
(Westwood 1980; Vella 1985). The HIV viruses that and mortality, whereas others believe that improved
cause the acquired immune deficiency syndrome socioeconomic conditions, more than medical provi-
(AIDS) are the most recent additions to this list. sion, have resulted in less illness and death among

V.7. Sub-Saharan Africa since 1860 299
Africans. Proponents of this view refer to the appar- portant disease of this environment is cerebrospinal
ent paradoxical situation in some regions of the con- meningitis.
tinent in which populations have increased in spite Analyses of disease patterns that focus more on
of the quite dramatic disintegration of health care the role of social, cultural, political, and economic
delivery systems that were inherited from the colo- factors emphasize the dynamic relationships that
nial period. We shall probably have to await the exist between humans and their total environment.
twenty-first century for satisfactory explanations of This is the approach of those concerned with the
the dynamics of African demography and its history. "social production of health and disease" (Turshen
An analysis of disease environments can be made 1984). Only rarely do analyses of disease patterns
in terms of both natural factors and socioeconomic combine both the deterministic and the socioeco-
considerations. Natural factors, crucial to proponents nomic approaches and thus reveal the complex inter-
of the "determinist" school of disease causation, in- relations between natural and socioeconomic factors
clude such items as altitude, temperature, rainfall, (Blacker 1989). John Ford's (1971) brilliant study of
humidity, and soil, as well as the proliferation of the tsetse problem is an example of a successful
potential disease hosts and vectors like animals, combining of the two.
birds, insects, and parasites. Epidemiologists de- Yet in the case of Africa, climate and geography
scribe three major disease patterns in sub-Saharan are less important determinants of health than are
Africa roughly akin to the three main climatic zones: the social, economic, and political factors. (The ma-
damp uplands, damp lowlands, and savanna regions jority of sub-Saharan Africa is not the sweltering,
with a long dry season. Damp uplands include the humid tropics of popular imagination but is rather
Kenyan highlands, southwestern Uganda, mountain temperate savanna or forest.) Medicine has only a
slopes of eastern and western Africa (mounts Elgon limited role in ameliorating the health of popula-
and Kilimanjaro), and parts of Rwanda and Burundi. tions (McKeown 1979), and upon closer examina-
The much vaster damp lowlands include coastal West tion, it can usually be shown that the root causes of
Africa and the massive Congo basin, which are the ill health are embedded in social and economic struc-
regions of Africa that most readily fit the popular tures. Indeed, in much of sub-Saharan Africa, it is
notion of "the tropics." The third and most extensive precisely because of social and economic upheaval
climatic pattern is identified by a limited rainy sea- that we have recently seen a rapid increase in mor-
son and a longer dry season. At one extreme in this bidity and mortality, and medical services in some
climatic pattern is the Sahel, where the dry season regions have deteriorated so seriously as to be non-
dominates, but the pattern pertains to savanna re- existent (Dodge and Wiebe 1985).
gions as well (Bradley 1980).
Disease patterns vary immensely throughout Overview of Disease in Africa Since 1860
these three zones, yet generalizations can be made. Most of the written sources for the history of dis-
In the damp uplands, including the Kenya high- eases in Africa since 1860 derive from Europeans,
lands, the southwestern tip of Uganda, parts of who had very specific interests in health. Their first
Rwanda and Burundi, and the southern Kivu dis- concern was for their own health and that of fellow
trict of eastern Zaire, population densities are high Europeans, whereas concern for the health of Afri-
and the predominant infections are respiratory and cans was extended mainly to those people the Euro-
diarrheal, both largely diseases of poverty and poor peans needed as laborers or producers. It was clear
sanitation. In the damp lowlands with their prolific from the outset that Africans were human capital.
insect vectors, malaria dominates the disease pat- Medical opinion of the mid-nineteenth century set
tern, with almost every person infected within the the pattern for most of the colonial period when it
first year of life. Yaws, hookworm, the diarrheas, expounded the view that only blacks could labor in
typhoid, infective hepatitis, and numerous viruses the tropical regions of Africa, and in this, science
are also common. The third disease pattern, that of allegedly corroborated the imperialist view that the
the savannas, is again dominated by malaria, with physical constitution of the African was different
diarrheal diseases and waterborne diseases predomi- from that of the European.
nating. The latter include schistosomiasis and Certainly it must have seemed so. Early European
dracunculiasis (guinea worm), whereas another dev- accounts describe the devastating morbidity and
astating disease, sleeping sickness, is especially mortality they suffered, but we learn very little
prevalent along waterways, the haunt of many about the impact of disease on African populations
tsetseflies,which transmit the disease. Another im- apart from those employed as porters and soldiers.

Non-Eurocentric accounts of diseases and health con- most often poorly nourished, these Africans often
ditions among African populations are rare for the attracted the attention of colonial authorities, who
earlier period, and those dating from World War II considered them an important source of disease, espe-
are also limited in number and scope. Nearly all cially venereal disease. Military leaders commonly
Europeans in Africa — explorers, traders, missionar- complained about the threat to public health posed
ies, or colonials - were concerned primarily with the by prostitutes and female "camp followers."
diseases that threatened their own health, and this In all colonies, there was constant fear among
must be borne in mind by anyone looking at early European colonizers that the new "detribalized" indi-
accounts of diseases of Africa. viduals gravitating toward the new urban centers
Between 1860 and 1885 European exploration and were spreading disease, which in turn contributed to
trade along with coasts of Africa increased and fi- the development of powerful stereotypic images of
nally culminated in the full expression of foreign Africans. Technologically inferior, Africans were
imperialism with formal colonization; by 1920 most thought to be less "civilized" (Comaroff and Coma-
of equatorial, eastern, and central Africa had been roff 1991), and because civilization was equated with
taken over by Europeans. The result for much of the hygiene, many believed that Africans were by na-
region was a series of catastrophes in the form of ture unhygienic. Consequently, all colonies by the
wars of conquest and the initial consolidation of colo- early decades of the twentieth century had imple-
nial rule. The primary motive for colonization was mented a public health policy of racial segregation
economic exploitation of natural resources and hu- in order to protect the health of whites (Spitzer 1968;
man populations. In their rush for profit, Europeans Swanson 1977).
often employed roughshod, even brutal, methods By 1940 many African societies had been literally
that greatly affected disease patterns. "restructured" as a result of the need to meet the
Some African societies, like those located along the increasing demands of European industries and mar-
west coast of the continent, had long been in contact kets. Throughout the continent, millions of Africans
with outsiders and thus did not seem to be as immedi- were forced to migrate annually to labor in unsafe
ately affected by new pathogens and other stresses as and unsanitary conditions in mines, on plantations,
were populations in eastern and central Africa, and in public works projects such as road and rail
which had been more isolated. For many societies of building. In addition to the more apparent effects of
eastern, central, and southern Africa, however, the heavy labor in harsh conditions on African health
period 1890—1920 was so traumatic as to have been were those that attended the proletarianization and
described as a time of tumultuous "ecological disas- urbanization of millions of Africans across the conti-
ter" (Ford 1971; Kjekshus 1977). New diseases were nent. This had the important effect of disrupting and
spread to nonimmune populations, and previously often destroying African forms of social organiza-
endemic diseases became epidemic. It is clear that the tion, which also had an adverse effect on the health
great epidemics of human sleeping sickness through- of Africans.
out the Congo basin beginning in the late nineteenth Migrant laborers, who were usually malnour-
century, which in Uganda produced an estimated ished, poorly clothed, crowded into miserable dwell-
300,000 deaths between 1901 and 1905, were a result ings, and overworked, were victims of a wide range
of violent disruptions to those regions. In fact, the of infectious and contagious diseases. Similarly, men
history of sleeping sickness illustrates well the ef- and women left behind in the rural sector were bur-
fects of upheavals in large parts of sub-Saharan Af- dened with the crushing labor of agricultural produc-
rica around the turn of the century. Increased stresses tion, which was required by the colonial administra-
accompanied by reduced nutritional and immune sta- tors to feed the migrant labor force as well as the
tus led to greatly increased morbidity and mortality rapidly expanding urban populations. The result
for millions of Africans. was that nutrition declined everywhere in Africa,
During the four decades between 1920 and 1960, and given the complex interaction of disease and
colonial rule and economic exploitation of the land malnutrition we can guess the result.
and people were refined and greatly extended. Ever- Large parts of sub-Saharan Africa experience a
increasing numbers of Africans were drawn, often "hungry" season, which takes place after the long
unwillingly, into colonial economies as laborers and dry season, just as the rains start and food stores are
tax payers. Others were forced into an "informal" low or depleted. This period is the point in the agri-
economy earning cash as prostitutes or petty traders cultural calendar when intense labor is required,
and by providing other services. Highly mobile and but it is also the time when people are ill. Recent

studies have revealed that it is at the end of the dry A number of accounts of the overall health of Afri-
season when measles and pneumonia deaths peak cans since 1860 have stressed the point that
for a combination of reasons. Among them are lower biomedicine and improved public health were the
standards of child care because mothers have to la- most valuable legacies of the colonial powers. Cer-
bor in the fields and suppressed immune responses tainly there were some notable successes starting in
exacerbated by malnutrition, both of which must the 1920s with the introduction of the sulfa drugs.
have played a major role in disease incidence during Yaws, a widespread endemic disease, responded al-
the colonial period. Other contributing factors were most miraculously to sulfonamides; Africans by the
the widespread colonial practice of implementing thousands eagerly sought injections, and in many
cash crop economies, which were often based on regions yaws was almost eradicated. Similarly, sleep-
monoculture. In Ghana, for example, where cocoa ing sickness, endemic throughout much of eastern,
production formed the basis of the colonial economy, central, and western Africa, was by the 1950s and
when prices were high, staple food production fell off 1960s under control as a result of sometimes enor-
and people suffered accordingly. mous campaigns aimed at this one disease. In the
The two world wars compounded the burden of Belgian Congo and French Equatorial Africa, the
colonial labor and production for African popula- systematic examination and medication of the entire
tions. The wars were also periods of nutritional depri- population was the goal, and at the same time all
vation for millions of people. Thousands of men were affected colonies practiced some degree of mass re-
recruited into military service, and disease and death moval and resettlement of populations thought to be
were rife. Mass recruitment programs during the at risk of infection.
First World War revealed the poor state of African Yet even where biomedical solutions have proved
health to colonial authorities, and as a consequence effective, the serious problem of their costs remains.
plans were launched to provide medical services to Large-scale medical campaigns launched against sin-
the masses. The emphasis remained, however, on the gle diseases like those aimed at sleeping sickness,
curative as opposed to the preventive approach. yaws, malaria, and more recently smallpox are
Since the 1960s, when most African colonies called "vertical" campaigns and are expensive. More
gained political independence, there has been a con- general, or "horizontal," health programs address a
siderable increase in population throughout much of broad spectrum of public health issues such as con-
the subcontinent. This is a subject that in the last trol of endemic and epidemic diseases, infant and
part of the twentieth century has become the focus of mother care, vaccinations, and primary health clin-
much study and debate and that in all likelihood ics and are usually far more cost effective in their
will have to wait the next century for an in-depth use of personnel, infrastructure, and supplies. Unfor-
explanation. While population has increased in tunately, throughout much of the colonial period in
many regions, in many African states economic de- sub-Saharan Africa, medical services tended to be
cay has been accompanied by a reduction in the more vertical than horizontal. The huge and costly
immune and nutritional status of large segments of campaigns launched against single diseases ab-
the population. An important cause has been pro- sorbed scarce resources and drew money away from
tracted wars of independence such as those in An- other crucial areas of health provision. For Africans,
gola, Mozambique, Zimbabwe, and Namibia and closely related to this problem of health economics is
civil wars such as those in Nigeria, Sudan, and another: Most pharmaceutical companies have been
Uganda. These political upheavals have caused the and remain reluctant to invest heavily in the re-
widespread destruction of human lives, a decline in search and development of medicines for diseases
agricultural production, the disruption of civil soci- that afflict mainly impoverished, often rural popula-
ety, and the creation of hundreds of thousands of tions in underdeveloped regions of the world. Since
displaced persons and refugees. Closely related to the late 1800s, the combination of vertical medical
the political upheavals have been a series of campaigns and the reluctance of pharmaceutical
droughts, famines, and epidemics that have further companies to invest in research has had profoundly
increased the toll on human life. If current World adverse affects on the health of millions of sub-
Health Organization projections are even only par- Saharan Africans.
tially correct, mortality from AIDS in sub-Saharan Nonetheless, by the time of their independence in
Africa can be expected to devastate parts of the conti- the 1960s the health of many African populations
nent, where it threatens to strike down young adults was considerably better than that of preceding gen-
in their productive and reproductive prime. erations. Vaccination campaigns in many countries

had become routine. In some regions, more often ments having serious implications for the new Afri-
urban centers, public health programs had imposed can colonies.
a degree of control over malaria. Maternal and child Most important in the new science was the role of
health programs were also well established in many the laboratory, which became the real battlefield on
colonies. Large-scale employers such as mines and which questions of life and death would be settled.
plantations had expressed some concern for the well- Laboratories could be mobile, as they were soon to be
being of their labor forces, and in some regions work- in the new specialty of tropical medicine. Between
ing conditions were improved. Mortality and morbid- 1860 and 1900, Joseph Lister, Louis Pasteur, and
ity rates were lower than ever, and major epidemics Robert Koch transformed forever our understanding
occurred far less frequently than before. of the relationships of humans and their disease-
Departing colonial administrations took credit for causing pathogens. The new sciences gave specific-
these improvements, which were seen as stemming ity to diseases whose etiologies could now be ascer-
from the ameliorating effects of those medical ser- tained. With more concrete understanding of the
vices that, as we noted, many believed to be the most pathology of a specific disease and knowledge of its
valuable colonial legacy. In other words, it was be- particular cause, the pathogen or germ, scientists
lieved that the incidence of disease had been de- could think in terms of equally specific therapies
creased through the beneficial effects of Western (e.g., Paul Ehrlich's "magic bullet").
biomedical staff, infrastructure, and techniques. At There was an unfortunate consequence, however,
that time few would have credited improvements in for these exciting developments prompted scientists
the standard of living of many millions of Africans involved in tropical health in Africa to cast aside
for the decreased incidence. Yet as Thomas McKe- most of the earlier theories of disease causation.
own has argued convincingly, it was improved socio- Earlier ideas concerning the influences of environ-
economic conditions, rather than medical therapies, ment on health, a view that stressed the relation-
that accounted for the overall improvements in the ships between humans and their environment, were
health of Western populations. Doubtless this also overshadowed by the empiricism of the new labora-
played a substantial if not well-recognized role in tory science with its method of verifiable experi-
ameliorating the health of Africans as well. ment. Thus, budding theories of the "social construc-
tion of diseases" were, by the turn of the century,
Science and Disease in Africa almost entirely superseded by powerful theories of
The last quarter of the nineteenth century was an the "biological determinism of disease." The latter
exciting chapter in the history of science and medi- approach would dominate most medical and public
cine. It was also the period when much of sub- health thinking throughout the colonial period.
Saharan Africa was formally colonized by Europeans
and, indeed, the two phenomena were not unrelated. The Disease Environment
By the late nineteenth century, important develop- In addition, Africans had their own tropical illnesses:
ments in the areas of scientific, statistical, and malaria, blackwater fever, yellow fever, trypanoso-
epidemiological thought had combined with the devel- miasis (sleeping sickness), filariases, leishmaniasis
opment of specificity in disease etiologies and thera- (kala-azar), schistosomiasis (bilharziasis), onchocer-
pies to enable Europeans to penetrate and perma- ciasis (river blindness), leprosy, yaws, guinea worm,
nently settle the interior regions of the continent. helminthiasis, relapsing fever (louse- and tickborne),
Late Victorians had great confidence that Carte- and tropical ulcer. A number of these are caused by
sian science and new, rapidly evolving technology parasites that are transmitted to humans by insects.
would provide humans with the means to reshape Because both the parasites and the insects require
their environment to suit themselves. In fact, medi- very specific conditions of temperature and moisture
cal advances seemed to be elegant proof of this abil- and because many of the other diseases are water-
ity to overcome the dangers of the environment. borne, the emphasis on "tropical" is understandable.
During the 1854 expedition along the Niger, for ex- Also understandably, diseases that had such complex
ample, the successful prophylactic use of quinine and fascinating etiologies and that required the com-
demonstrated that it was at last possible for Europe- bined expertise of zoologists, protozoologists, epide-
ans to survive the onslaughts of malaria. Then miologists, chemists, and biologists overwhelmingly
around the turn of the century, new concepts of what attracted the attention of early investigators in Af-
constituted disease rapidly evolved, as did the role of rica. Unfortunately, other important causes of mor-
the new expert health professionals - both develop- bidity and mortality, such as respiratory diseases,

childhood diseases, and malnutrition, were not given members of the community are exposed to pathogens
research priority. "Tropical" diseases were mistak- or when newcomers in large enough numbers reach
enly conceptualized as distinct from other communi- a disease environment containing pathogens against
cable diseases. In this way, tropical medicine evolved which they have no immune protection. Poor hy-
as a specialty outside of mainstream medicine. giene resulting from ignorance of disease causation
By the mid-nineteenth century, tropical Africans coupled with the widespread lack of safe water sup-
were afflicted by most of the diseases of the temper- plies and sewage disposal also profoundly affect a
ate Old World, such as brucellosis (Malta fever), society's disease environment.
undulant fever, cerebrospinal meningitis, cholera, As stated previously, disease environments are af-
diphtheria, influenza, measles, plague, pneumonia, fected by both natural and sociocultural factors. A
poliomyelitis, smallpox, tuberculosis, typhoid fever natural factor of much importance in Africa is the
(enteric fever), typhus and other rickettsial infec- proliferation of insects, many of which serve as vec-
tions, venereal diseases, and whooping cough. The tors of disease-causing pathogens. Another factor is
causes of 50 to 90 percent of illness and death among climate, which can be a major determinant of those
the poor in the underdeveloped world, including Af- diseases that have specific requirements of tempera-
rica, fall into two main groups: nutritional deficien- ture, humidity, or aridity. An equally important fac-
cies and communicable diseases (Sanders 1985). The tor encompasses the sociocultural practices of com-
major causes of adult mortality are infectious and munities. For instance, ritual practices may bring
parasitic diseases, acute respiratory infections, car- humans into regular and intimate contact with cer-
diovascular disease, and accidents and violence. tain features of the physical environment that re-
Most childhood mortality is caused by a limited num- sults in contact with disease-causing pathogens.
ber of infectious diseases: diarrheal diseases, acute Shrines hidden deep in forested regions may bring
respiratory infections, malaria, measles, and neona- humans into contact with pathogen-bearing insects
tal tetanus (I. Timaeus, personal communication). such as the tsetse fly and anopheles mosquito. In
Moreover, there is evidence that in recent years the addition, agricultural practices, such as the cultiva-
incidence of noninfectious and degenerative diseases tion of certain crops close to homesteads, often bring
is increasing. humans into contact with pathogens. And changes
What constitutes a disease environment and what in crops or techniques often provide new ecological
causes it to change? Every human community coex- niches in which disease-bearing pathogens flourish.
ists with specific microorganisms that contribute to An example of this is the introduction by a British
the disease environment of the group. Many diseases colonial officer of a new variety of hedge, the
represent the failure of one organism, in this case lantana, from India into Uganda in the 1940s. The
human beings, to cope successfully with competing lantana flourished in its new environment, gradu-
organisms, in this case microorganisms, in the cease- ally spreading northward toward the southern Su-
less struggle for survival. A disease environment con- dan. Unfortunately, it provided an excellent habitat
tains many elements: humans, animals, various for a species of tsetse fly, Glossina pallidipes, which
other forms of flora and fauna, microorganisms, cli- in turn introduced new strains of trypanosomes, the
mate, and geographic features. Many disease envi- cause of human sleeping sickness.
ronments are often located close to one another, and Perhaps the most important factors in disease envi-
these undergo frequent and sometimes rapid change. ronments are water supply and human excreta. Wa-
For instance, after a period of interaction with a sta- terborne diseases include typhoid fever, poliomyeli-
ble human population, disease-causing pathogens tis, infectious hepatitis, cholera, schistosomiasis,
can adapt and produce new strains in response to the dracunculiasis, and leishmaniasis. Water supplies
immune defenses produced by that population. In and sewage disposal are complex subjects of much
recent decades this has been demonstrated in parts of concern to health planners in the late twentieth
the world by the appearance of new strains of century. But during much of the nineteenth century
chloroquinine-resistant Plasmodium falciparum, the these two vitally important areas of public health
cause of the most deadly of the malarial diseases. were given very little serious attention and even less
Conversely, human host communities develop im- investment. Indeed, despite John Snow's brilliant
munity to endemic diseases. In other words, humans 1849 analysis of the epidemiology of cholera in Lon-
who survive the diseases of their environment often don when he revealed that a water pump was respon-
acquire some resistance to further infection. Epidem- sible for the spread of the disease, the supply of safe
ics of disease occasionally flare up when nonimmune water and the disposal of sewage remained for more

than a century conceptually separate from the con- Health in tropical Africa during the colonial period,
cerns of medicine with its focus on cure. ed. E. E. Sabben-Clare, D. J. Bradley, and K. Kirk-
Rather, clean water supplies and sanitary sewage wood, 6-12. Oxford.
disposal, as means of disease prevention, were, until Carlson, Dennis, G. 1984. African fever: A study of British
very recently, solely the concern of the engineer. science, technology, and politics in West Africa, 1787-
Thus, a major source of much human disease was 1864. Canton, Mass.
neglected by medical people. The colonial legacy in- Chirimuuta, R. C, and R. J. Chirimuuta. 1987. AIDS,
Africa and racism. London.
cluded very little in the way of safe/water supplies
Comaroff, Jean and John. 1991. Of revelation and revolu-
and effective sewage disposal systems, except in a tion: Christianity, colonialism, and consciousness in
few of the urban areas where the Europeans them- South Africa, vol. 1. Chicago and London.
selves resided. And Africans are suffering the effects Crosby, A. 1986. Ecological imperialism: The biological
to the present day. expansion of Europe, 900—1900. Cambridge.
Last but hardly least among the African "patho- Curtin, P. 1961. The white man's grave: Image and reality,
genic factors" is protein-energy malnutrition, for 1780-1850. Journal ofBritish Studies 1: 94-110.
the excessive mortality of African children under 5 1968. Epidemiology and the slave trade. Political Sci-
years of age is due largely to the synergism between ence Quarterly 83: 190-216.
protein-energy malnutrition and infectious and Dodge, Cole P., and Paul D. Wiebe. 1985. Crisis in
parasitic diseases. Until fairly recently, nutrition Uganda: The breakdown of health services. Oxford.
has been largely ignored in relation to morbidity, yet Ford, John. 1971. The role of the trypanosomiases in Afri-
can ecology. Oxford.
it is a vitally important key to understanding the Hartwig, G., and K. D. Patterson. 1978. Disease in African
widespread perception of Africa as a "disease- history: An introductory survey and case studies. Dur-
ridden" continent. ham, N.C.
Earlier theories of epidemiology held that expo- Headrick, Rita. 1987. The impact of colonialism on health
sure to new pathogens was sufficient cause for epi- in French Equatorial Africa, 1880-1934. Ph.D. disser-
demic outbreaks, and much emphasis was laid on tation, University of Chicago. University Microfilms
the increased interactions of African populations, DA 48A: 2955.
witnessed by Europeans from the mid-nineteenth Kjekshus, Helge. 1977. Ecology control and economic devel-
century on, as an explanation for apparently in- opment in East African history: The case of Tangan-
creased rates of morbidity and mortality. More re- yika. London.
cently, however, it has been argued that more than McKeown, Thomas. 1979. The role of medicine: Dream,
mere exposure is needed to explain why humans fall mirage or nemesis? Oxford.
1988. The origins of human disease. Oxford.
ill and why epidemics flare. Thomas McKeown
Packard, Randall. 1989. White plague, black labor: Tuber-
(1979) argued convincingly that, for almost the culosis and the political economy of health and disease
whole of human existence, disease and early death in South Africa. Berkeley and Los Angeles.
have resulted from basic deficiencies or from haz- Prins, Gwyn. 1989. But what was the disease? The present
ards related to them and that the role of nutrition is state of health and healing in African studies. Past
of paramount importance. and Present 124: 159-79.
Thus, medical services, specific remedies, and the Sanders, David, with Richard Carver. 1985. The struggle
increasingly complex technology of biomedicine may for health: Medicine and the politics of underdevelop-
not provide the best solutions to African health prob- ment. London.
lems; rather, the total ecology of health and disease Spitzer, Leo. 1968. The mosquito and segregation in Si-
may be a more fruitful area of study for future erra Leone. Canadian Journal of African Studies 2:
49-62.
health planners.
Swanson, Maynard. 1977. The sanitation syndrome: Bu-
Maryinez Lyons bonic plague and urban native policy in the Cape
The author thanks Ian Timaeus for his help. Colony, 1900-1909. Journal of African History 18:
387-410.
Turshen, Meredeth. 1984. The political ecology of disease
Bibliography in Tanzania. New Brunswick, N.J.
Blacker, J. G. C. 1991. Infant and child mortality: Develop- United Nations. 1987. Mortality of children under age 5:
ment, environment and custom. In Disease and mortal- World estimates and projections, 1950-2025. Depart-
ity in sub-Saharan Africa, ed. R. G. Feachem and D. T. ment of International Economic and Social Affairs,
Jamison, 75-86. Washington, D.C. 1987 (ST/ESA/SER A/105). New York.
Bradley, David J. 1980. The situation and the response. In Vella, Ethelwald E. 1985. Exotic new diseases: A review of

V.8. Pre-Columbian Americas 305
the emergent African viral haemorrhagic fevers. Lon- 1989). Given the wide variety of settings available
don. for human occupation in the Americas, ranging from
Westwood, John C. N. 1980. The hazard from dangerous stark Arctic polar environments to lush tropical for-
exotic diseases. London. ests, we should anticipate that human cultural and
biological adaptions ranged widely within the con-
text of changing cultural systems and environmen-
tal regimes. The quality of life, as measured by
health status, would have depended on the nature of
V.8 these interactions as well as those among the human
groups themselves.
Diseases of the Pre- Beginning with the earliest colonists - the Ameri-
Columbian Americas cans who entered this continent before the end of the
Pleistocene - we find a rich fabric of evolving rela-
tionships between people and their natural and cul-
Although the antiquity of the earliest colonists in tural environments that held strong implications for
the Americas remains a controversial subject, hu- both health and the history of disease. Although
man presence is well established by the close of the certain groups maintained life-styles without plant
Pleistocene, approximately 10,000 B.P. (before the and animal domestication (or management) through-
present) (Bryan 1978, 1986; Shutler 1983; Fagan out their history, the Americas also saw the develop-
1987). Kill sites and habitation areas, in conjunction ment of complex civilizations. The Maya, the Aztec,
with lithic tools and a few human remains, provide the Inca, and - on a smaller scale - the eastern
convincing evidence for the presence of highly mo- North American agriculturalists, known to archeolo-
bile, small groups whose subsistence was based on gists as Mississippian peoples, all developed cities
hunting and gathering of naturally available "wild" where thousands of people lived together in perma-
resources. nent settlements. Problems of health, sanitation,
The health of these most ancient American popula- and nutrition common to such large agglomerations
tions, poorly documented owing to a paucity of hu- of humans throughout the world emerged in each of
man remains (Hrdlicka 1907, 1912; Stewart 1946, these situations.
1973; Young 1988), can best be inferred by analogy Although animal husbandry never assumed the
with recent hunting and gathering peoples. In mak- importance that it did in the Old World, the dog was
ing inferences we must keep in mind that such one of several domesticated New World animals,
groups today tend to occupy marginal environments, along with the turkey, the Muscovy duck, the guinea
unlike the often resource-rich ecosystems that at- pig, the alpaca, and the llama (Crosby 1972). These
tracted early human populations. If we use con- animals, living close to humans, could have served
temporary hunter-gatherers for our model, then as vectors or intermediate hosts of disease. Simi-
parasitic infections, infections for which insects and larly, the nutritional adequacy of ancient diets de-
animals serve as the primary vectors or intermedi- pended on these as well as wild animal resources.
ate hosts, and traumatic episodes would have been Inedible, but economically important plants, such
among the primary sources of ill health among the as cotton and tobacco, along with many comestibles
earliest Americans (Dunn 1968; Truswell and Han- including maize, manioc, squash, beans, cocoa, sun-
sen 1976; Howell 1979; Lee 1979; Cohen 1989). De- flower, potatoes, chiles, chenoa, and tomatoes, were
generative diseases, neoplasms, and epidemic dis- domesticated (Crosby 1972). These crops attracted
eases would have been extremely rare, as would the attention of Europeans and are presently part of
have been chronic undernutrition. Seasonal periods Western cuisine (Crosby 1972, 1986). Other indige-
of nutritional stress would, however, have been ex- nous plants were also cultivated prehistorically, with
pected. Thus, health status would have reflected the some being truly domesticated, that is, showing dis-
exceptionally close relationship between hunter- tinctive morphological changes due to human inter-
gatherers and their environment. vention or growing beyond their natural range. In
We must be careful, however, not to overgener- eastern North America, for example, a group of culti-
alize and thus simplify our picture of hunter- vated indigenous plants, termed the eastern horticul-
gatherer adaptations, which were undoubtedly com- tural complex, included sumpweed (Iva annua),
plex and rich with the knowledge gained through goosefoot (Chenopodium berlandieri), knotweed (Po-
intimate acquaintance with the landscape (Cohen lygonum erectum), and little barley (Phalaris carotin-

TIME CULTURES SITES AND REGIONAL NAMES
1950 OBP
ad Sadlerlmlut
1450 500 Norrlt Farms #36 Averbuch
Mlsslsslpplan I". Ancient
950 1000 Md.. Llbben
Late Woodland
450 1500
| Middle Woodland
ad/bc 2000 (Hopewell)
I •
550 -|— 2500 I Early Woodland
1050 3000
1550 3500 Late Archaic
2050 4000
2550 4500
3050 5000
3550 5500
4050 6000
4550 Middle Archaic
6500
5050 7000
5550 7500
6050 8000
6550 8500
7050 9000 Early Archaic
7550 9500
8050 10,000
8550 10,500
9050 11,000
Figure V.8.1. Model time line for 9550
Paleoindlan
11,500
prehistoric eastern North Amer- 10,050 12,000
ica. (Based on Buikstra 1988.)
iana), as well as sunflower (Heliantus annuus) and V. 8.1 follows J. Buikstra (1988); Figure V. 8.2 is
various cucurbits (Asch and Asch 1985; Smith 1987). based on the sequences presented in R. Keatinge
In that nutritional adequacy is closely linked to (1988) and B. Fagan (1972). Sites discussed in this
health status, these components of ancient diets must text are placed appropriately on these time lines.
also be mapped when one is investigating paleo- This brief chronological review is developed in order
pathological conditions. to establish a broad time scale against which to
This review of health conditions in the pre- display disease patterning. In general, North Ameri-
Columbian Americas focuses primarily on the evi- can materials are emphasized, given that the major-
dence gained through the study of skeletal material. ity of the relevant literature is based on North
Mummified remains, a very rich data source, are American collections.
unfortunately found only in a few settings favoring We first focus on trephination, distinctly South
soft-tissue preservation, especially the arid North American and an enormously successful form of an-
American Southwest and coastal Peru and Ecuador. cient surgery. Following this we consider the expres-
Dry caves, such as those of the Mammoth Cave sys- sion of two forms of trauma in human skeletal mate-
tem in North America, also yield mummified human rials, fractures and osteoarthritis. A discussion of
remains, but only in small numbers (Watson 1974). fractures and true degenerative joint disease centers
Other sources of information concerning disease and on North American materials, as does a consider-
medical treatments, such as the Mochica and Mexi- ation of rheumatoid arthritis in adults. Brief men-
can figures, and various pictographs will not be con- tion, however, is made of an example of juvenile
sidered here. These renderings are notoriously am- rheumatoid arthritis that was recovered from a c.
biguous, frequently charged with symbolic meanings 1000 B.P. Peruvian grave. The subsequent discus-
that relate to ritual life rather than accurate repre- sion of two forms of infectious pathology, trepone-
sentations of maladies and deformities. matosis and tuberculosis, ranges widely across the
Figures V. 8.1 and V. 8.2 present model chronolo- hemisphere, as does the description of techniques for
gies for eastern North America and coastal Peru and inferring diet from bones and teeth. We close with a
Ecuador, two regions frequently referenced in the consideration of parameters used to estimate popula-
following text. The chronological basis for Figure tion health, dealing primarily with North American

TIME PERIOD (CULTURE) SITES
1950 -I- OBP

ad Late Horizon (Inca)
1450 - - 500
Late Intermediate
4
950 — — 1000 Middle Horizon (Tlwanaku)
450 - - 1500
Early Intermediate Caaeronea
ad/bc - - 2000
550 - - 2500 Early Horizon
1050 - - 3000
Initial Period
1550 - - 3500
2050 - - 4000 Preceramic Period VI
2SS0 - - 4500
3050 - - 5000 Preceramic Period V
3550 - - 5500
4050 - - 6000
4550 - - 6500 Figure V.8.3. Different methods of trepanation. 1, Scrap-
5050 - — 7000 Preceramic Period IV ing; 2, grooving; 3, boring and cutting; 4, rectangular
5550 - - 7500 intersecting incisions. (After Lisowski 1967, with permis-
6050 - - 8000 sion, Charles C. Thomas, Publisher.)
6550 - - 8500
Precsramlc Period III
7050 - - 9000 1500 and 2500 B.P., trephination encompassed sev-
7550 - - 9500 eral distinctive techniques with various results. One
8050 - - 10,000
of the most extensive descriptions is that of
8550 - -10,500 Preceramic Period II
M. Meyer (1979), who reports 10 different types of
9050 - -11,000
9550 - -11,500 i
surgical method in his study of 374 trephined crania
Preceramic Period 1 from Peru. Most common were the scraping and
10,050 - -12,000 1r grooving procedures (Figure V. 8.3, after Lisowski
1967), which had been performed on more than 61
Figure V.8.2. Model time line for prehistoric Peru and percent of this sample. Meyer (1979) attributes the
Chile. (Based on Keatinge 1988 and Fagan 1972.) popularity of the scraping technique to its high suc-
cess rate (85 percent). Given that the key problem in
skeletal samples that chronicle the development and surgery of this type is the removal of bone without
intensification of maize agriculture. penetrating the dura, the finer control afforded by
the scraping technique rendered it maximally effec-
Trephination (Trepanation) tive (Ortner and Putschar 1981).
Trephination, one of the earliest surgical procedures The overall recovery frequency reported by Meyer
involving the skull, was first reported in prehistoric (1979) is 61.9 percent, which compares quite favor-
skeletal remains during the nineteenth century ably with the rate of 62.5 percent reported by J. Tello
(Squier 1877; Rytel 1956; Lisowski 1967; Steinbock (1913) in a sample of 400 Peruvian skulls. Meyer
1976; Ortner and Putschar 1981). E. Squier's early also reports similar figures for researchers dealing
description of trephination in Peruvian remains led with smaller series. Thus, fewer than half of these
to the recognition that this procedure was frequently ancient Peruvian patients died as a result of skull
practiced in pre-Columbian South America (Stewart surgery.
1958; Steinbock 1976). The success rate of this sur- Various motives have been attributed to those who
gery, which exceeded 50 percent in the South Ameri- performed trephination, ranging from the utilitar-
can examples (Stewart 1958), is particularly sig- ian to the spiritual. Meyer (1979) observed cranial
nificant for the history of medicine. It far exceeded pathology, due either to infection or to trauma, in
recovery predictions for individuals subjected to association with 42.0 percent of his trephined sam-
brain surgery in eighteenth- and nineteenth-century ple. As he notes, the rate would undoubtedly have
Europe, where death was the expected result been higher, given the fact that either the operation
(Schroder 1957, cited in Lisowski 1967). itself or subsequent healing would have obliterated
The removal of a segment of skull without injur- symptoms visible at the time of surgery. He also
ing the underlying meninges and brain is an exceed- reports that fractures were more commonly, but by
ingly delicate operation. Commonly practiced in no means exclusively, associated with men in his
South America during the millennium between sample, with infection appearing more frequently in

trephined women. There tended to be a larger num- Table V.8.1. Healed fracture frequencies for North
ber of healed trephinations among men than among American prehistoric remains
women, which contributes to Meyer's observation
that relatively few young men appear in his tre- Population Percent
phined sample. He attributes "ritual practice" to Middle Archaic
this pattern, but male survival rates must also be Indian Knoll, Ky. No. 1 10.7
considered. Indian Knoll, Ky. No. 2 9.8
Meyer also suggests, on the basis of observation of Late Archaic
stains and osteoporotic pitting in the trephined re- Robinson site, Tenn. 9.6
gion, that Peruvian surgeons used antiseptics. Un- Morse site, 111. 9.7
like earlier observations by T. Stewart (1958) on a
less extensive series, Meyer's (1979) observations Woodland
revealed that most trephinations in his sample oc- Tollifero site, Va. 5.4
curred on the parietal bone. The left side of the skull Steuben site, 111. 5.5
Klunk site, 111. 5.0
was more commonly trephined than the right, which
may reflect the agonistic origins of many cranial Mississippian
fractures. Clarksville site, Va. 3.9
Contemporary examples of trephination using Dickson Mounds, 111. 3.3
primitive technology include the African cases cited Emmons site, 111. 1.2
by E. Margetts (1967) and Bolivian examples re-
Source: After Steinbock (1976, 23).
ported by K. Oakley and colleagues (1959). The Afri-
can techniques were similar to prehistoric methods,
whereas in Bolivia a young man was operated on Indian remains that pre-dates 8500 B.P. is a healed
with "a rusty nail and a stone" (as cited in Meyer fracture in the right eighth rib of a skeleton from the
1979). The African operations were quite successful; Pelican Rapids site, Minnesota.
in one instance of multiple trephinations, for exam- As noted by Steinbock (1976), and emphasized by
ple, the subject continued to live a "normal" life. Lovejoy and Heiple (1981), Steinbock's frequencies
Clearly, ancient peoples had discovered a surgical may be unreasonably low, due to his method of re-
strategy that was remarkably successful, even in the porting. Steinbock's use of the individual as the unit
absence of modern antibiotics. for analysis led him to include incomplete remains
whose missing elements might have presented
Fractures healed fractures. Also, as pointed out by this author
Evidence of healed fractures has been reported for nu- (1981a), Middle Archaic cemetery samples can be
merous skeletal series throughout the Americas. Few segregated by health status. Thus, archeological re-
workers, however, have attempted to develop a bio- covery may have emphasized those areas where indi-
behavioral model for interpreting etiology, through viduals with fractures were more likely to be buried.
either a rigorous diachronic approach or the develop- Lovejoy and Heiple (1981), basing their analysis
ment of an epidemiological viewpoint. Exceptional on the Late Woodland Libben site of northern Ohio,
perspectives have been developed by R. Steinbock report that each individual within this series had a
(1976), who surveys temporally sequential North 45 percent chance of fracturing a major limb long
America samples, and by C. Lovejoy and K. Heiple bone. The clavicle was most frequently broken, with
(1981) in an intensive investigation of the Libben site the humerus showing the fewest healed fractures.
(900-1200 B.P.). The rather high rate of forearm fractures is attrib-
Using the individual as the basis for comparison, uted to falls rather than to conflict owing to the low
Steinbock reports postcranial fracture frequencies prevalence (n = 2) of classic "parry fractures." That
for 12 skeletal series from North America (V.8.1). only two cranial fractures were observed in the se-
The highest fracture frequency occurred in Middle ries also supports this conclusion. Although these
and Late Archaic populations — those considered to data have undoubtedly been affected by the ease of
be hunters and gatherers. Given our previous model reduction for each of the elements surveyed, it is
derived from ethnographically documented groups, very clear that the Libben series represents a sam-
this observation is not unexpected. As an aside, ple for which there is little evidence of conflict.
G. Steele (personal communication) noted that the After developing a years-at-risk analysis, Lovejoy
only pathological condition in a survey of Paleo- and Heiple (1981) concluded that there were two

periods within the Libben life span in which the risk promote degeneration of joint surfaces in the human
of fracture was greatest: 10 to 25 years years and 45 skeleton. Thus, the "wear and tear" of ancient life-
plus years. Youthful activity and senescence un- styles can be read through an analysis of the porosity,
doubtedly explain this pattern. eburnation, and lipping characteristic of arthritic
A contrasting picture is presented by the Norris joints. One of the most careful studies of extensive
Farms No. 36 sample described by G. Milner, V. degenerative joint changes is that of Ortner (1968),
Smith, and E. Anderson (1991). Slightly more recent who details the patterning discovered in Alaskan
than the Libben sample, this Oneota series is de- Eskimo and Peruvian skeletons. Ortner's work is
rived from a late prehistoric population that lived reminiscent of the methods pioneered by J. Angel
near major Mississippian settlements. Healed frac- (1966) and T. Stewart (1932). Stewart's careful inves-
tures within the Norris Farms No. 36 series include tigation of intraindividual patterning established
many in the trunk and upper limb, with the skull the standard of comparison of vertebral osteo-
also heavily involved. In addition, 33 individuals, phytosis, whereas Angel's creative inferences con-
approximately 12.5 percent (33/264), show evidence cerning behavior (e.g., atlatl [spear or dart throwing
of mutilation, including scalping, decapitation and stick] elbow) are oft-cited attempts to link individual
postcranial dismemberment, actual injuries, such as activities to bone pathology.
projectile points in bone and spiral fractures, or both R. Jurmain (1977) has compared arthritic patterns
forms of damage to bone. Many of these skeletons, as characterizing the Alaskan Eskimo shoulder, elbow,
well as 10 others for a total of 43, exhibit carnivore knee, and hip with those of Pueblo Indians and mod-
gnawing that is thought to have occurred after death ern skeletons. Jurmain emphasizes the multifac-
but before the recovery of the body for burial in the torial nature of osteoarthritis, although he believes
village cemetery. Those who were older than 15 that functional stress is of paramount importance.
years at the time of death are evenly divided be- After an extensive survey of degenerative joint
tween men (18) and women (18). This represents disease among the Native Point Sadlerimiut Eskimo
about 33 percent of the total male subset of the from Southampton Island, Canada, C. Merbs (1969,
population and 29 percent of the female subset. The 1983) identified distinctive male and female activity
male proportion is not unexpected in tribal-level soci- patterns that yielded arthritic change. Typical male
eties; however, the female frequency is extremely activities that produced upper-limb arthritis in-
high, suggesting the presence of intensive raiding cluded harpoon throwing and kayak paddling. Fe-
and social conflict. male skeletons bore evidence of activities related to
The contrasting patterns presented by the Libben the processing of skins.
and Norris Farms No. 36 series underscore the im- Following the recording strategy developed by
pact that life-style and living conditions can have on Ortner (1968) and Merbs (1969), J. Tainter (1980)
the expression of trauma in prehistoric remains. observed distinctive arthritic patterning across sta-
Just as there appears to be no typical late prehistoric tus groups of Middle Woodland men from Illinois. He
pattern, it would be foolhardy to generalize concerji- interpreted these patterns to mean that the day-to-
ing any other temporal or chronological unit without day activities differed significantly across socially
contextual data. defined segments of Hopewell communities.
A more recent study (Pickering 1984) has ex-
Arthritis tended Tainter's earlier synchronic investigation to
As pointed out by D. Ortner and G. Theobald in their an analysis of diachronic changes associated with
examination of the diseases of prehistory in the West the development of maize agriculture. Also embed-
in this volume, a great many conditions can lead to ded in this work is an attempt to isolate patterns in
inflammation of the joints. In the Americas, most the male upper limb that were associated with the
diagnostic attention has been paid to articular documented shift in hunting technology between the
changes that may be characteristic of tuberculosis, spear, characteristic of Middle Woodland groups, and
treponematosis, rheumatoid arthritis, and osteo- the bow and arrow, used by Late Woodland and Mis-
arthritis due to mechanical stress. Our current sissippian populations.
knowledge of the first two conditions is discussed in Although an altered hunting technology was in-
the relevant sections of this essay. Here we will focus deed documented within west-central Illinois during
on recent studies of osteoarthritis (degenerative the period in question, no significant difference in
joint disease) and rheumatoid arthritis. symmetry, timing of onset, patterning, or degree of
Daily activities produce stresses that over time arthritic expression in the upper limb was discov-

ered in the male subsample. The arthritic costs of The nature of the debate has changed, however.
agricultural intensification are clearly written, how- Today few would disagree with the notion that the
ever, in age-corrected severity scores for the female skeletal lesions presented by these prehistoric re-
upper back. The demands of repetitive food produc- mains resemble most closely the constellation of re-
tion activities associated with maize agriculture and lated diseases collectively known as the trepone-
larger family size are implicated in the apparent matoses. Included within this group are venereal
differences in degenerative joint disease. syphilis, yaws, and endemic syphilis. In her rigorous
In provocative new work based on observations in consideration of clinical and epidemiological pattern-
two large prehistoric North American skeletal popu- ing from recent medical literature, D. Cook (1976)
lations, B. Rothschild and colleagues argue that argues compellingly that either nonvenereal syphi-
rheumatoid arthritis "is a New World disease that lis or yaws is the best modern model for the observed
subsequently spread to the Old World" (Rothschild, prehistoric pathology. Her thesis is based on the
Woods, and Turner 1987; Rothschild, Turner, and high prevalence of lesions observed in American pre-
DeLuca 1988; Woods and Rothschild 1988). Their historic series, the age-accumulative patterning of
conclusions are based on the form and distribution of incidence, and the total absence of dental changes
erosive lesions in several series of skeletons, includ- diagnostic of congenital syphilis, such as Hutchin-
ing the Libben Late Woodland sample (900-1200 son's incisors or mulberry molars.
B.P.) and Archaic skeletons from Alabama that are Yet it is clear that, in isolated examples, venereal
at least 5,000 years old (Rothschild et al. 1987,1988; transmission of this disease occurred. The most con-
Woods and Rothschild 1988). A convincing case of vincing cases are two prehistoric burials that in-
juvenile rheumatoid arthritis in an adolescent from clude both adults and juveniles with the stigmata of
the Tiwanaku period (c. 1100 B.P.) in Peru has also venereal syphilis. In one of these, a mulberry molar
been described (Buikstra 1991). was found in juvenile remains in a burial site that
also included adult skeletons having treponemal
Treponematosis long-bone lesions (Clabeaux Geise 1988). A second
Evidence of inflammatory response, usually appear- example is represented by the remains of a prehis-
ing as symmetric periostitic expressions on the sur- toric achondroplastic dwarf recovered from a Middle
faces of the limb long bones, is common in North Woodland burial mound in Illinois (Charles, Leigh,
American skeletal series. South American materials and Buikstra 1988; Burgess 1988). This adult
are said to present similar symptoms (Williams woman, whose left lower limb is heavily remodeled,
1932; Goff 1967). At times accompanied by evidence died in childbirth. Her fetus presents evidence of
of osteomyelitic changes, as well as occasional periostitic changes, as well as dwarfing. Although
stellate scarring of the external table of the skull, the data are scant, they suggest that at least some
these lesions are the basis of a long-standing contro- prehistoric American women acquired treponemal
versy concerning the possible New World origin of infections as adults, presumably through sexual in-
venereal syphilis (e.g., Jones 1876; Whitney 1883; tercourse. The infection thus acquired would have
Williams 1932; Goldstein 1957; Bullen 1972; Cook been in an acute stage during the childbearing
1976; Brothwell 1981). Theoretical articles by medi- years, which would have facilitated transplacental
cal historians enrich this literature (e.g., Cockburn infection (Grin 1956; Powell 1988).
1963; Hudson 1965; Hackett 1967; Crosby 1969, The most recent overview of theoretical and em-
1972). pirical arguments concerning the origin of venereal
The cause of these lesions, which are characteris- syphilis is that of B. Baker and G. Armelagos (1988).
tic of many cemetery samples from throughout east- After extensively reviewing current evidence, these
ern North America, has been a matter of debate for authors conclude that pre-Columbian American
more than a century. In 1876 J. Jones argued that skeletal materials reflect a treponematosis that
the "erosions" he observed in burials from stone box spread to the Old World through nonvenereal con-
graves and mounds in Tennessee and Kentucky tact. European social and environmental conditions
were syphilitic, a conclusion cautiously supported by favored the development of venereal transmission,
W. F. Whitney (1883), curator of the Warren Ana- and thus originated the "French disease."
tomical Museum of the Harvard Medical School, a Doubtless the question of treponematosis and the
decade later. Such notables as the anatomist R. development of venereal forms will remain contro-
Virchow have disputed this conclusion, thus fueling versial for some time. Eagerly awaited is further
an argument that continues today (Jarcho 1966). skeletal evidence from Europe, as well as the devel-

opment of an immunological technique that will frequency are misspecified, or the modern tuberculo-
make it possible to identify treponemal antigens in sis model is not fully transferable to prehistoric con-
ancient materials (Baker and Armelagos 1988). texts. The important role of effective population size
Even though there is little evidence for venereal in the spread of disease is emphasized in McGrath's
transmission of treponematosis in pre-Columbian conclusions, underscoring the importance of rela-
American skeletons, it is important to underscore tively brief periods of contact involving a large num-
the presence on this continent of a chronic tre- ber of individuals. Thus, the role of socially impor-
ponemal disease that affected a significant number tant economic and religious collective activities that
of individuals. Beginning in childhood and progress- encourage population aggregation - however brief-
ing throughout life, inflammations produced by the must be considered in explaining patterns of disease
illness doubtless created a considerable health bur- spread and maintenance in prehistoric groups.
den for prehistoric peoples of the Americas.
Diet
Tuberculosis Although paleobotanic and paleofaunal residues are
A form of pathology distinctly different from the the most accurate indicators of resources available
treponematosis syndrome also affected prehistoric to prehistoric peoples, estimates of ancient diets are
peoples from North and South America (Allison, best derived from the actual physical remains of the
Mendoza, and Pezzia 1973; Buikstra 1981b). Ex- consumers. Dental health, for example, can assist in
pressed most commonly as erosive spinal lesions, dietary determinations. Caries rates in adults are
less frequently affecting joint surfaces of the limb widely recognized as an indication of maize in the
long bones, this disease is found in North American diet of native North Americans (Cohen and Arme-
populations postdating 1100 B.P. The Chilean mate- lagos 1984; Powell 1985). One must postulate such
rials reported by M. Allison and colleagues (1981) an association with care, however, because it ap-
predate the North American examples by over a pears that an intake of high-carbohydrate seeds
millennium. Pulmonary involvement is reported for from the eastern horticultural complex can also lead
three individuals from the Caserones site (c. 1660 to an elevated frequency of caries (Rose, Marks, and
B.P.), as well as an isolated case of Potts's disease Tieszen 1990). Circular caries in Late Woodland juve-
dating toe. 2110 B.P. nile dentitions have been used by Cook and Buikstra
Epidemiological patterning considered with le- (1979) to argue for a significant proportion of carbo-
sion location suggests that the most closely analo- hydrates in the weanling diet, most likely a disad-
gous modern disease is tuberculosis rather than vantageous circumstance.
blastomycosis, a fungal infection. Both blastomy- More sensitive to dietary differences, however, are
cosis and tuberculosis present similar skeletal le- the chemical constituents of the skeleton. The compo-
sions, but their expected age-specific mortality pat- sition of both the mineral and the organic phases of
terns differ. Young adults are disproportionately bone is to some degree influenced by diet. Trace
represented among those dying with clinically docu- elements, such as stable strontium and barium, are
mented bone tuberculosis, whereas blastomycosis carried from the soil to an herbivore's bones through
tends to present an age-accumulative profile. The plant consumption. Because both strontium and bar-
age-specific disease pattern observed in large se- ium tend to concentrate in osseous rather than soft
ries, including those from west-central Illinois, re- tissue, primary and secondary carnivores receive
sembles tuberculosis more closely than blastomy- relatively little dietary strontium. Thus, within a
cosis (Buikstra and Cook 1981; Buikstra 1991). region, the relative herbivory of an omnivorous spe-
The tuberculosis diagnosis developed from modern cies such as Homo sapiens can be estimated. Zinc
clinical literature does not, however, provide a per- tends to concentrate in flesh and is thus a dietary
fect diagnostic fit for our prehistoric example. marker for animal protein consumption.
Through simulation analysis, J. McGrath (1986) has The strontium content of bones has been used by
modeled the course of a tuberculosislike disease in M. Schoeninger (1979) in her investigation of status
Middle Woodland, Late Woodland, and Missis- clusters of graves from the Chalcatzingo site,
sippian populations from west-central Illinois. She Morelos, Mexico. Her careful argument concludes
concludes that a disease resembling modern tubercu- that diet varied by status group at this prehistoric
losis would have rendered our prehistoric peoples Meso-American site dating from 2900 to 3100 B.P.
extinct or would have itself ceased to exist. Thus, Zinc and strontium have been used to investigate
either our estimates of group size and interaction dietary differences within and between Middle and

Late Woodland groups in west-central Illinois (Lam- sippian cultures is well known. Debate has centered,
bert, Spzunar, and Buikstra 1979; Buikstra et al. however, on the degree to which the timing of maize
1989). Although other elements such as vanadium intensification was directly associated with the de-
co-vary with diet and would thus be desirable di- velopment of Mississippian lifeways and the relative
etary markers, most are subject to postdepositional importance of maize to Mississippian peoples. The
enrichment or depletion (diagenesis) and are thus carbon isotope technique has provided a means of
contextual signatures rather than dietary signals. resolving these and related issues concerning agri-
Focused on intrasite variation, the earliest Illinois cultural intensification in the eastern United States.
studies examined patterning across status groups This significant methodological advance, developed
in Middle Woodland mounds and sought gender- only within the past 10 years, has facilitated the
related differences within Middle and Late Wood- resolution of century-old arguments about the role of
land samples. The nonrandom distribution of trace corn in North American prehistory.
elements across burial groups in Hopewell mounds Partial differential carbon-13 values from across
suggests the presence of status-related dietary hab- eastern North America clearly document the fact
its within Middle Woodland communities. Although that maize consumption predates the Mississippian
no gender differences were observable in Middle period (Lynott et al. 1986; Buikstra et al. 1988). In
Woodland data, bones of Late Woodland men con- the central Mississippi valley, these values suggest a
tained significantly more zinc and less strontium rather gradual increase during the terminal phases
than those of women. This may reflect either a true of Late Woodland, including a highly variable period
gender-based dietary difference or the increased of experimentation. Values stabilize during Missis-
metabolic demands that Late Woodland women sippian times, indicating that corn was a significant
faced owing to closer birth spacing (Buikstra et al. component of the diet for the late prehistoric peo-
1987). ples. Of special interest is the fact that corn consump-
Diachronic study of Illinois Middle and Late Wood- tion was apparently higher in the "farmstead" com-
land samples indicates that, although zinc values do munities of the lower and central Illinois valley than
not vary chronologically, strontium levels do de- it was at the major ceremonial center of Cahokia
crease during Late Woodland times. This decrease during the early, expansive phase of the Missis-
may seem enigmatic, given the development of maize sippian period (Buikstra and Milner 1988). Also sig-
agriculture during this period. Maize, however, is nificant is the fact that the partial differential
relatively poor in elements, and thus the observed carbon-13 values from Illinois never reach the ex-
pattern is expected. The values for zinc suggest that tremely positivefigures(—7.8 to —8.0 o/oo) that char-
the proportion of animal protein in the diet did not acterize the Mississippian peoples of the Ohio Valley
vary significantly across Woodland groups. Similar and the Nashville Basin of Tennessee. These very
patterning has been reported for a temporally se- positive values are currently a source of debate, with
quential series of skeletal samples from Ontario suggested causal factors ranging from true dietary
(Katzenberg and Schwarcz 1986; Katzenberg 1988). contrasts to varietal differences in corn (Buikstra et
A second form of chemical study has focused on al. 1988). Certain of these late prehistoric popula-
the collagen fraction of bone. The results of studies tions present evidence of severe ill health (Cassidy
based on stable carbon isotope ratios derived from 1984; Eisenberg 1986). The degree to which nutri-
bone collagen make it possible to predict the pres- tional deficiencies are implicated remains a point of
ence of maize in diets with a precision far beyond controversy (Buikstra et al. 1988).
estimates based on the paleobotanic record or dental Ratios of nitrogen-15 to nitrogen-14 have been
health. Maize, a tropical grass, fixes carbon through used to identify the presence of legumes in prehis-
the Hatch-Slack, or C4 pathway. This contrasts with toric diets, as well as to distinguish between marine
the usual pattern for temperate-climate vegetation and terrestrial resource utilization (DeNiro, Schoen-
in which the common pathway is Calvin, or C3. As inger, and Tauber 1983; Schoeninger and DeNiro
partial differential carbon-13 values - the standard 1984; DeNiro 1987). A bivariate plot of partial differ-
transformation used in such studies - become more ential carbon-13 and nitrogen-15 values enables the
positive, the presence of maize in the diet is more researcher to distinguish the effects of marine en-
likely. Values derived from human collagen that are richment from those of maize utilization. Diets com-
more positive than —20 or —21 are considered evi- posed of marine resources derived from coral-reef
dence of C4 plant consumption. habitats appear to present an anomalous pattern
The association of maize agriculture with Missis- (Schoeninger et al. 1983; Keegan and DeNiro 1988).

At present, most studies of coastal series using both These studies have employed various markers of
carbon and nitrogen ratios are limited to small sam- health status, including stature attainment rates in
ples. Expanded applications of these promising tech- juveniles, adult stature, sexual dimorphism, corti-
niques are anticipated. cal thickness, demographic patterning, and porotic
hyperostosis, as well as the Harris lines and dental
Nonspecific Indicators of Stress defects mentioned previously (Lallo 1973; Lallo,
Within the past two decades there has been an explo- Armelagos, and Rose 1978; Rose, Armelagos, and
sion of interest in applying the so-called nonspecific Lallo 1978; Cook 1979, 1981, 1984; Lallo, Rose, and
indicators of stress to questions of community Armelagos 1980; Buikstra 1984; Cassidy 1984;
health. These indicators range from those that appar- Goodman et al. 1984; Larsen 1984; Perzigian,
ently mark episodes of acute stress and recovery, Tench, and Braun 1984; Goodman and Armelagos
such as Harris lines and dental defects, to those that 1985). In general, it is assumed that populations
are associated with chronic mal- or undernutrition. with disadvantaged health status will exhibit
Each type of change has been observed to be associ- slower growth, depressed adult stature, less sexual
ated with disadvantaged health status in modern dimorphism, reduced cortical thickness, elevated
clinical examples, with predisposing factors includ- death rates, and increased frequencies of porotic
ing nutritional inadequacy, infectious disease, and hyperostosis when compared with closely related
even severe emotional episodes. Working with an- groups in advantaged situations. In this context, it
cient materials, the observer cannot precisely deter- should be noted that the cranial porosities termed
mine the cause of a specific condition, but instead porotic hyperostosis and cribra orbitalia are usually
assumes that a sample with more evidence of nonspe- considered to be evidence for nutritional anemias in
cific stress is less advantaged than one with fewer the New World. No convincing arguments have
indicators of poor health. The popularity of this ap- been made for the existence of anemias of genetic
proach has been influenced by an emphasis on popu- origin, such as sickle-cell anemia and thalassemia,
lation biology in physical anthropology, as well as by in the prehistoric Americas.
archaeological interest in human ecology (Buikstra The regional studies cited earlier generally sup-
and Cook 1980; Cohen and Armelagos 1984). port the notion that a certain health risk was associ-
Harris lines, observed as radiopaque lines perpen- ated with the development of maize agriculture.
dicular to the cortex of limb long bones, result from Late Woodland agriculturalists in West-Central Illi-
episodic stress. Because the lines, which can also be nois, for example, present evidence of disadvantaged
visualized as disks in the affected diaphyses, can health status in juveniles, including such features as
remodel, they are less satisfactory indicators of poor depressed growth curves, elevated weaning age, ele-
health than are dental defects that include both vated death rates, and decreased cortical thickness
hypoplastic bands and microdefects such as Wilson's (in juveniles). However, as Cook (1984) pointed out,
bands (Rose, Condon, and Goodman 1985). Even so, the more recent and increasingly maize-dependent
Harris lines have proved useful in documenting the Mississippian peoples in the same region show less
presence of annual periods of growth arrest, which evidence of nonspecific stress. Their only liability
appear to be characteristic of archaic peoples in Illi- appears to have been a tuberculosislike pathology
nois, Kentucky, and California (McHenry 1968; (Buikstra and Cook 1981), a density-dependent dis-
Buikstra 1981a; Cassidy 1984). Such repetitive pat- ease, which is most closely linked to effective popula-
terning is not characteristic of sedentary groups, tion size and only indirectly reflects subsistence
whose storage facilities may have buffered them base.
from seasonal stress. A. Goodman and co-workers (1984; see also Lallo
A number of North American studies have focused 1973; Lallo et al. 1978, 1980; Rose et al. 1978; Good-
on the biological costs and benefits of increased depen- man and Armelagos 1985) report deteriorating
dence on maize agriculture. As noted at the beginning health for Mississippian peoples from Dickson
of this essay, maize cultivation represented a late pre- Mounds, located in the central Illinois River valley. It
historic intensification of a trend in plant utilization is clear, however, that the shift to maize intensifica-
begun many centuries before. Estimates of relative tion in this region does not correlate tightly with the
maize dependence suggest that maize comprised a periods of extreme ill health (Buikstra and Milner
very significant part of the diet for certain late prehis- 1988). The residential sites associated with Dickson
toric peoples, including the Fort Ancient Late Missis- Mounds are fortified during the Mississippian period,
sippian communities of Ohio and Kentucky. which suggests that socially mediated stresses may

have been at least as important as diet in explaining ing the quality of life of peoples who left few clues
the health status of the skeletal sample excavated other than their tissues. This productive trend is vital
from the Dickson Mounds cemeteries. to the full appreciation of America's unwritten past,
Farther to the east, there is evidence of extreme as it is to research concerning the history of disease.
maize dependence among late prehistoric popula- Jane E. Buikstra
tions from Ohio, Kentucky, and Tennessee (Broida
1983, 1984; Buikstra et al. 1988). Disadvantaged
health status is clear for many of these same groups Bibliography
Allison, M. J., et al. 1981. Tuberculosis in pre-Columbian
(Cassidy 1984; Eisenberg 1986). In fact, the popula- Andean populations. In Prehistoric tuberculosis in the
tion profile for the Averbuch site (Eisenberg 1986) is Americas, ed. J. E. Buikstra, 49-61. Evanston, 111.
consistent with the presence of disease epidemics Allison, M. J., D. Mendoza, and A. Pezzia. 1973. Documen-
(Buikstra et al. 1988). Thus, however probable it is tation of a case of tuberculosis in pre-Columbian
that Western diseases caused severe depopulation America. American Review of Respiratory Disease
during protohistoric times (Ramenofsky 1987), there 107: 985-91.
is also convincing evidence for severe ill health in at Angel, J. L. 1966. Early skeletons from Tranquility, Cali-
least some American native populations that clearly fornia. Smithsonian Contributions to Anthropology
predates Columbian contact. 2(1): 1-19.
Asch, D., and N. Asch. 1985. Prehistoric plant cultivation
Summary in West-Central Illinois. In Prehistoric food produc-
This essay has presented an overview of recent re- tion in North America, No. 75, ed. R. I. Ford, 149-203.
search on ancient disease in the Americas. Materials Ann Arbor, Mich.
from North America and the west coast of South Baker, B. M., and G. J. Armelagos. 1988. The origin and an-
America have been emphasized, as they have been tiquity of syphilis. Current Anthropology 29: 703-37.
Broida, M. O. 1983. Maize in Kentucky Fort Ancient diets:
in studies of pathology. Our survey highlights the
An analysis of carbon isotope ratios in human bone.
success of ancient Peruvian surgeons, and as well Master's thesis, University of Kentucky.
illustrates the frequency of healed fractures and 1984. An estimate of the percents of maize in the diets of
osteoarthritis in North American materials. North two Kentucky Fort Ancient villages. In Late prehis-
American remains also dominate the recent investi- toric research in Kentucky, ed. K. Pollack, C.
gations of nonspecific indicators of population Hockensmith, and T. Sanders, 68-82. Frankfurt, Ky.
health, as they do studies of bone chemistry de- Brothwell, D. R. 1981. Microevolutionary change in the
signed to reveal the approximate content of ancient human pathogenic treponemes: An alternative hy-
diets. Recent studies emphasizing the biological pothesis. International Journal ofSystematic Bacteriol-
costs and benefits of maize agriculture, as summa- ogy 31: 82-7.
rized in this essay, illustrate synergism between diet Bryan, A. L. 1986. New evidence for the Pleistocene peo-
and health status, as well as the importance of cul- pling of the Americas. Orono, Me.
Bryan, A. L., ed. 1978. Early man in America. Occasional
tural and environmental contexts in explaining dis-
Paper No. 1 of the Department of Anthropology, Uni-
ease in the past. versity of Alberta.
Several of the subjects addressed here are a source Buikstra, J. E. 1981a. Mortuary practices, palaeode-
of debate in the 1990s. The antiquity of rheumatoid mography and palaeopathology: A case studyfromthe
arthritis in the New World has received recent atten- Koster site (Illinois). In The archaeology of death, ed.
tion, as has the long-standing question of venereal R. Chapman, I. Kinnes, and K. Randsborg, 123—31.
syphilis and its origins. In the 1950s the prevailing New York.
opinion was that no tuberculosislike pathology ex- ed. 1981b. Prehistoric tuberculosis in the Americas. Sci-
isted in the prehistoric New World (Morse 1961), a entific Paper No. 5, Northwestern University Archeo-
view that has been reversed. Even so, the conditions logical Program.
under which this tuberculosislike pathology devel- 1984. The lower Illinois River region: A prehistoric con-
oped remain obscure and controversial. text for the study of ancient diet and health. In
Paleopathology at the origins of agriculture, ed. M. N.
As noted by Buikstra and Cook (1980) in their Cohen and G. J. Armelagos, 215-34. New York.
review of paleopathology in the Americas, there has 1988. The mound-builders of Eastern North America: A
been increased emphasis on the study of ancient dis- regional perspective. Amsterdam.
ease since 1970. Frequent collaboration between Buikstra, J., and D. C. Cook. 1980. Paleopathology: An
medical and social scientists, with input from chem- American account. Annual Review of Anthropology 9:
ists, is producing remarkable new insights concern- 433-70.

1981. Pre-Columbian tuberculosis in West-Central Illi- 1981. Mortality, age structure and status in the interpre-
nois: Prehistoric disease in biocultural perspective. In tation of stress indicators in prehistoric skeletons: A
Prehistoric tuberculosis in the Americas, ed. J. E. dental example from the Lower Illinois Valley. In The
Buikstra, 115-39. Scientific Paper No. 5, Northwest- archaeology of death, ed. R. Chapman, I. Kinnes, and
ern University Archeological Program. K. Randsborg, 133-44. New York.
Buikstra, J. E., and G. R. Milner. 1988. Isotopic and ar- 1984. Subsistence and health in the Lower Illinois Val-
chaeological interpretations of diet in the Central Mis- ley: Osteological evidence. In Paleopathology at the
sissippi valley. Paper presented at the 2nd Conference origins of agriculture, ed. M. N. Cohen and G. J.
on Diet and Human Evolution, Capetown. Armelagos, 235-69. New York.
Buikstra, J. E., and S. Williams. 1991. Tuberculosis in the Cook, D. C , and J. E. Buikstra. 1979. Health and differen-
Americas: Current perspectives. In Human paleopath- tial survival in prehistoric populations: Prenatal den-
ology: Current syntheses and future options, ed. D. J. tal defects. American Journal of Physical Anthropol-
Ortner and A. C. Aufderheide, 161-72. Washington, ogy 51: 649-64.
D.C. Crosby, A. W. 1969. The early history of syphilis: A reap-
Buikstra, J., et al. 1987. Diet, demography, and the devel- praisal. American Anthropology 71: 218-27.
opment of horticulture. In Emergent horticultural 1972. The Columbian exchange. Westport, Conn.
economies of the Eastern Woodlands, ed. W. Keegan, 1986. Ecological imperialism: The biological expansion
67—85. Occasional Papers of the Center for Archaeo- of Europe, 900-1900. Cambridge.
logical Investigations, Southern Illinois University. DeNiro, M. J. 1987. Stable isotopy and archaeology. Ameri-
Buikstra, J. E., et al. 1988. Diet and health in the Nash- can Scientist 75: 182-91.
ville Basin: Human adaptation and maize agriculture Dunn, F. L. 1968. Epidemiological factors: Health and
in Middle Tennessee. In Diet and subsistence: Current disease in hunter-gatherers. In Man the hunter, ed.
archaeological perspectives, ed. B. V. Kennedy and R. B. Lee and I. DeVore, 221-40. Chicago.
G. M. LeMoine, 243-59. Eisenberg, L. E. 1986. Adaptation in a "marginal" Missis-
Buikstra, J. E., et al. 1989. Multiple elements: Multiple sippian population from Middle Tennessee: Biocul-
expectation. In The chemistry of prehistoric human tural insights from paleopathology. Ph.D. disserta-
bone, ed. T. D. Price, 155-210. Cambridge. tion, New York University.
Buikstra, J. E., et al. 1991. A case of juvenile rheumatoid Fagan, B. 1972. In the beginning, 2d edition. Boston.
arthritis from pre-Columbian Peru. In In honor of J. 1987. The great journal. London.
Lawrence Angel, ed. J. E. Buikstra. Washington, D.C. Goff, C. W. 1967. Syphilis. In Diseases in antiquity, ed. D. R.
Bullen, A. K. 1972. Paleoepidemiology and distribution of Brothwell and A. T. Sandison, 279-93. Springfield, 111.
prehistoric treponemiasis (syphilis) in Florida. Flor- Goldstein, M. S. 1957. Skeletal pathology of early Indians
ida Anthropologist 25: 133-74. in Texas. American Journal of Physical Anthropology
Burgess, S. 1988. The Achondroplastic Dwarf from the 15: 299-311.
Elizabeth site. M. A. thesis, University of Chicago. Goodman, A. H., and G. J. Armelagos. 1985. Disease and
Cassidy, C. M. 1984. Skeletal evidence for prehistoric death at Dr. Dickson's mounds. Natural History 94:
subsistence adaptation in the central Ohio River val- 12-18.
ley. In Paleopathology at the origins of agriculture, Goodman, A. H., et al. 1984. Health changes at Dickson
ed. M. N. Cohen and G. J. Armelagos, 307-45. New Mounds, Illinois (A.D. 950-1300). In Paleopathology
York. at the origins of agriculture, ed. M. N. Cohen and G. J.
Charles, D. K., S. R. Leigh, and J. E. Buikstra, eds. 1988. Armelagos, 271-305. New York.
The Archaic and Woodland cemeteries at the Elizabeth Grin, E. T. 1956. Endemic syphilis and yaws. Bulletin of
site in the Lower Illinois Valley. Kampsville, 111. the World Health Organization 15: 959-73.
Clabeaux Geise, M. 1988. Comment. Current Anthropol- Hackett, C. 1967. The human treponematoses. In Diseases
ogy 29: 722-3. in antiquity, ed. D. R. Brothwell and A. T. Sandison,
Cockburn, A. 1963. The evolution and eradication of infec- 152-69. Springfield, 111.
tious diseases. Baltimore. Howell, N. 1979. Demography of the Dobe !Kung. New
Cohen, M. N. 1989. Health and the rise of civilization. New York.
Haven, Conn. Hrdlicka, A. 1907. Skeletal remains suggesting or attrib-
Cohen, M. N., and G. J. Armelagos, eds. 1984. Paleo- uted to early man in North America. Bulletin of the
pathology at the origins of agriculture. New York. Bureau of American Ethnology Vol. 33.
Cook, D. C. 1976. Pathologic states and disease process in 1912. Early man in South America. Bulletin of the Bu-
Illinois Woodland Populations: An epidemiologic ap- reau of American Ethnology Vol. 52.
proach. Ph.D. dissertation, University of Chicago. Hudson, E. H. 1965. Treponematosis and man's social evo-
1979. Subsistence base and health in prehistoric Illinois lution. American Anthropologist 67: 885—901.
Valley: Evidence from the human skeleton. Medical Jarcho, S. 1966. Human palaeopathology. New Haven,
Anthropology 3: 109-24. Conn.

Jones, J. 1876. Explorations of the aboriginal remains of Illinois River valley. Ph.D. dissertation, Northwestern
Tennessee. Smithsonian Contributions to Knowledge University.
No. 259. Washington, D.C. McHenry, H. 1968. Transverse lines in long bones in pre-
Jurmain, R. D. 1977. Stress and the etiology of osteo- historic California Indians. American Journal of
arthritis. American Journal of Physical Anthropology Physical Anthropology 29: 1-17.
46: 353-65. Merbs, C. F. 1969. Patterns of activity-induced pathology
Katzenberg, M. A. 1988. Changing diet and health in in a Canadian Eskimo isolate. Ph.D. dissertation, Uni-
pre- and protohistoric Ontario. Social Science and versity of Wisconsin.
Medicine. 1983. Patterns of activity-induced pathology in a Cana-
Katzenberg, M. A., and H. P. Schwarcz. 1986. Paleonu- dian Eskimo population. National Museum of Man
trition in southern Ontario: Evidence from strontium Mercury Series, No. 119. Ottawa.
and stable isotopes. Canadian Review of Physical An- Meyer, M. 1979. Trephination in Pre-Columbian Peru.
thropology 5: 15—21. B.A. honors thesis, Harvard University.
Keatinge, R. W., ed. 1988. Peruvian Prehistory. Cam- MilnerG. R., V. G. Smith, and E. Anderson. 1991. Conflict,
bridge. mortality, and community health in an Illinois
Keegan, W. E, and M. J. DeNiro. 1988. Stable carbon- and Oneota population. In Between bands and states, ed.
nitrogen-isotope ratios of bone collagen used to study S. Gregg. Carbondale, 111.
coral-reef and terrestrial components of prehistoric Morse, D. 1961. Prehistoric tuberculosis in America. Re-
Bahamian diet. American Antiquity 53: 320-36. view of Respiratory Diseases 83: 489-504.
Lallo, J. 1973. The skeletal biology of three prehistoric Oakley, K. P., et al. 1959. Contributions on trepanning or
American Indian societies from Dickson Mounds. trephination in ancient and modern times. Man 59:
Ph.D. dissertation, University of Massachusetts. 287-9.
Lallo, J., G. J. Armelagos, and J. C. Rose. 1978. Ortner, D. J. 1968. Description and classification of degen-
Paleoepidemiology of infectious disease in the Dick- erative bone changes in the distal joint surface of the
son Mounds population. Medical College of Virginia humerus. American Journal of Physical Anthropology
Quarterly 14: 17-23. 28:139-55.
Lallo, J. W., J. C. Rose, and G. J. Armelagos. 1980. An Ortner, D. J., and W. G. J. Putschar. 1981. Identification of
ecological interpretation of variation in mortality pathological conditions in human skeletal remains.
within three prehistoric American Indian populations Smithsonian Contributions to Anthropology No. 28.
from Dickson Mounds. In Early native Americans: Washington, D.C.
Prehistoric demography, economy, and technology, ed. Perzigian, A. J., P. A. Tench, and D. J. Braun. 1984. Prehis-
D. Browman, 203-38. The Hague. toric health in the Ohio River valley. In Paleo-
Lambert, J. B., C. B. Spzunar, and J. E. Buikstra. 1979. pathology at the origins of agriculture, ed. M. N. Cohen
Chemical analyses of excavated bone from Middle and and G. J. Armelagos, 347-66. New York.
Late Woodland sites. Archaeometry 21: 115-29. Pickering, R. B. 1984. Patterns of degenerative joint dis-
Larsen, C. S. 1984. Health and disease in prehistoric Geor- ease in Middle Woodland, Late Woodland, and Missis-
gia: The transition to agriculture. In Paleopathology sippian skeletal series from the Lower Illinois Valley,
at the origins of agriculture, ed. M. N. Cohen and G. J. Ph.D. dissertation, Northwestern University.
Armelagos, 367-92. New York. Powell, M. L. 1985. The analysis of dental wear and caries
Lee, R. B. 1979. The .'Rung San. Cambridge. for dietary reconstruction. In The analysis of prehis-
Lisowski, E P. 1967. Prehistoric and early historic tre- toric diets, ed. R. I. Gilbert and J. H. Mielke, 307-38.
panation. In Diseases in antiquity, ed. D. R. Brothwell New York.
and A. T. Sandison, 651-72. Springfield, 111. 1988. Status and health in prehistory. Washington, D.C.
Lovejoy, C. O., and K. G. Heiple. 1981. The analysis of Ramenofsky, A. 1987. Vectors of death. Albuquerque, N.M.
fractures in skeletal populations with an example Rose, J. C, G. J. Armelagos, and J. W. Lallo. 1978.
from the Libben site, Ottawa County, Ohio. American Histological enamel indicators of childhood stress in
Journal of Physical Anthropology 55: 529-41. prehistoric skeletal samples. American Journal of
Lynott, M. J., et al. 1986. Stable carbon isotopic evidence Physical Anthropology 49: 511-16.
for maize agriculture in Southeast Missouri and Rose, J. C, K. W Condon, and A. H. Goodman. 1985. Diet
Northeast Arkansas. American Antiquity 51:51-65. and dentition: developmental disturbances. In The
Margetts, E. L. 1967. Trepanation of the skull by the analysis ofprehistoric diets, ed. R. I. Gilbert and J. H.
medicine-men of primitive cultures, with particular Mielke, 281-305. New York.
reference to present-day native East African practice. Rose, J. C, M. K. Marks, and L. L. Tieszen. 1990. Bioarche-
In Diseases in antiquity, ed. D. R. Brothwell and A. T. ology and subsistence in the central and lower por-
Sandison, 673-701. Springfield, 111. tions of the Mississippi valley. In What mean these
McGrath, J. W. 1986. A computer simulation of the spread bones? The dynamic integration ofphysical anthropol-
of tuberculosis in prehistoric populations of the Lower ogy and archaeology in the Southeast, ed. M. L. Powell,

V.9. The Americas, 1492-1700 317
A. M. Mires, and P. Bridges. University of Georgia among the !Kung. In Kalahari hunter-gatherers, ed.
Press. R. B. Lee and I. DeVore, 166-94. Cambridge, Mass.
Rothschild, B. M., K. R. Turner, and M. A. DeLuca. 1988. Watson, P. J., ed. 1974. Archeology of the Mammoth Cave
Symmetrical erosive peripheral polyarthritis in the area. New York.
Late Archaic period of Alabama. Science 241: 1498- Whitney, W. F. 1883. On the existence of syphilis in Amer-
1501. ica before the discovery by Columbus. Boston Medical
Rothschild, B. M., R. J. Woods, and K. R. Turner. 1987. and Surgical Journal 108: 365-6.
New World origins of rheumatoid arthritis. Arthritis Williams, H. U. 1932. The origin and antiquity of syphilis:
and Rheumatism (Suppl.) 30: S61. The evidence from diseased bones, as reviewed, with
Rytel. M. M. 1956. Trephinations in Ancient Peru. Quar- some new material from America. Archives of Pathol-
terly Bulletin of the Northwestern Medical School 30: ogy 13: 799-813, 931-83.
365-9. Woods, R. J., and B. M. Rothschild. 1988. Population analy-
Schoeninger, M. J. 1979. Diet and status at Chalcatzingo: sis of symmetrical erosive arthritis in Ohio Woodland
Some empirical and technical aspects of strontium Indians (1200 years ago). Journal of Rheumatology
analysis. American Journal of Physical Anthropology 15: 1258-63.
51: 295-309. Young, D. 1988. An osteological analysis of the Paleo-
Schoeninger, M. J., and M. J. DeNiro. 1984. Nitrogen and indian double burial from the Horn Shelter, No. 2.
carbon isotopic composition of bone collagen from ma- Central Texas Archaeologist 11: 13-115.
rine and terrestrial animals. Geochimica et Cosmo-
chimica Acta 48: 625-39.
Schoeninger, M. J., M. J. DeNiro, and H. Tauber. 1983.15N/
14
N ratios of bone collagen reflect marine and terres-
trial components of prehistoric human diet. Science
220: 1381-3. V.9
Schroder, G. 1957. Radiologische Untersuchungen an tre- Diseases of the Americas,
panieten Schadeln (Neolithikum-Mittelalter). Zeit-
schrift fiir Morphologie und Anthropologic 48: 298- 1492-1700
306.
Shutler, R., Jr., ed. 1983. Early man in the new world,
Beverly Hills, Calif. During the first 200 years of European exploration
Smith, B. D. 1987. The independent domestication of in- and settlement of the Americas, native populations
digenous seed-bearing plants in eastern North Amer- experienced catastrophic die-offs from the introduc-
ica. In Emergent horticultural economies of the East- tion of acute infectious diseases. Pinpointing which
ern Woodlands, ed. W. F. Keegan, 3-47. Carbondale, parasites were responsible for this decimation is not
111.
a simple matter. European knowledge of the infec-
Squier, E. G. 1877. Peru: Incidents of travel and explora-
tion in the land of the Incas. New York.
tious disease process was primitive in the sixteenth
Steinbock, R. T. 1976. Paleopathological diagnosis and and seventeenth centuries, with the result that con-
interpretation. Springfield, 111. querors, settlers, and clergy were ill-prepared to
Stewart, T. D. 1932. Vertebral column of the Eskimo. Ameri- describe the illnesses they witnessed. Statements
can Journal of Physical Anthropology 17: 123-36. that simply describe the death experience of native
1946. A reexamination of the fossil human skeletal re- peoples are the most common. In the Roanoke docu-
mains from Melbourne, Florida. Smithsonian Miscel- ments of 1588, for instance, T. Hariot described
laneous Collections 106: 1-28. native death from disease, but he attributed the
1958. Stone age skull surgery. Annual Report of the outbreaks to witchcraft:
Board of Regents of the Smithsonian Institution for
1957 53: 469-91. There was no towne where he had any subtile devise
1973. The people of America. New York. practiced against us, we leaving it unpunished or not
Stout, S. D. 1978. Histological structure and its preserva- revenged (because we sought by all meanes possible to win
tion in ancient bone. Current Anthropology 19: 601-4. them by gentlenesse) but that within a fewe dayes after
Tainter, J. A. 1980. Behavior and status in a Middle Wood- our departure from every such town, the people began to
land mortuary population from the Illinois valley. die very fast, and many in short space, in some townes
American Antiquity 45: 308-13. about twentie, in some fourtie, and in one sixe score,
Tello, J. C. 1913. Prehistoric trephining among the Yauyos which in trueth was very many in respect to their
of Peru. In International Congress of Americanists, nombers. This happened in no place that we could learne,
1912, 75-83. London. but where we had bene, where they used a practice against
Truswell, A. S., and D. L. Hansen. 1976. Medical research us, and after such a time. The disease, also strange, that

they neither knew what is was, not how to cure it. (Hariot from Pheiffer's bacillus to swine influenza (Crosby
1973) 1976).
The quality of disease descriptions in the Americas At least four methods are employed to reconstruct
disease agents in historical epidemics: (1) evolution-
greatly improved during the eighteenth century. A de-
ary theory; (2) disease loads in nonimmune popula-
scription of the frequency of colds among the Natchez
tions; (3) historical documents; and (4) skeletal biol-
stands in stark contrast to Hariot's sixteenth-century
ogy. Typically, researchers rely on one or, at the
description of disease: most, two of these methods. To determine the
Colds, which are very common in winter, likewise destroy strengths and weaknesses of any epidemiological re-
great numbers of natives. In that season they keep fires in construction, the assumptions of each method must
their huts day and night; and as there is no other opening be evaluated.
but the door, the air within the hut is kept excessively
warm without anyfreecirculation; so that when they have Parasite Evolution and Ecology
occasion to go out, the cold seizes them, and the conse-
quences are almost always fatal. (Le Page du Pratz 1975) Darwinian evolution is the theoretical framework
for explaining the differential persistence of varia-
Because of epidemiological advances, it is easier tion. Variation and natural selection are the princi-
for historical epidemiologists to reconstruct disease ples that account for this persistence. Variation
etiology in the Americas from the eighteenth cen- arises through such processes as mutation and ge-
tury to the present. Unfortunately, focusing epidem- netic drift. Mechanisms of selection determine
iological reconstructions on later centuries to the which variations persist or become extinct (Lewon-
exclusion of the sixteenth and seventeenth centuries tin 1974; Levins and Lewontin 1985).
is comparable to measuring the destruction of a hur- In the disease drama, individual variation be-
ricane that strikes the Gulf Coast by its effect in St. tween parasites and hosts determines, in part, which
Paul, Minnesota. As has been stressed (Burnet and parasites become fixed in the disease load of the
White 1972), the earliest epidemics among virgin- population. Parasites are predators seeking to maxi-
soil populations are the most severe. mize their reproductive fitness by colonizing hosts
Although new pathogens, such as cholera (Benen- (Burnet and White 1972; Youmans, Paterson, and
son 1976a), reached America's shores in later centu- Sommers 1980). Not all predators are successful.
ries, they operated at reduced scales, affecting only Those that are take over cell machinery; cells then
those who had survived a microbial war of 200 produce parasites at the expense of host cells.
years. Thus, this essay attempts to reconstruct the The host's defenses, including skin, cilia, mucous
group of diseases that spread to the Americas be- membranes, and antibodies or immunoglobins, are
tween A.D. 1492 and 1700. Although multicellular the primary selective agents working to repel para-
organisms, including round- and pinworms, un- sites. If the host's defense mechanisms are success-
doubtedly reached the Americas during the six- ful, there will be no predatory invasion. If they are
teenth and seventeenth centuries, this discussion not, illness and death of the host may ensue.
focuses largely on unicellular or subcellular organ- Besides explaining the relationship between pred-
isms, viruses, bacteria, and protozoa, that are de- ator and prey, Darwinian principles focus attention
fined as acute and infectious and that periodically on how and why the relationship changes through
erupt as epidemics. time. If the parasite is specific in its reproductive
requirements and kills the host before a new gen-
Disease Source Material eration of parasites is released, the parasite faces
Whether explicitly stated or not, the identification of death. A more successful strategy for the parasite is
parasites responsible for past epidemics is always to inhibit or neutralize host defenses without caus-
indirect. The truth of this statement is dramatized ing the death of the host. As suggested by the Euro-
by the 1918 influenza pandemic that killed millions pean experience with epidemic or venereal syphilis
of people in less than a year and a half (Jordan (C. J. Hackett 1963; Hudson 1968; Crosby 1972),
1927). Despite early-twentieth-century advances in over time a kind of symbiosis evolves in which the
public health, microbiology, and immunology, an un- host works for the parasite, but both host and para-
derstanding of the variations of the influenza vi- site survive.
ruses was not attained until the 1970s (Mackenzie The pattern from initial virulence to relative quies-
1980; Stuart-Harris 1981). In 1918 and 1919 sugges- cence has implications for the reconstruction of past
tions regarding the source of the disease ranged infections. Quite simply, as I have stated elsewhere

V.9. The Americas, 1492-1700 319
(Ramenofsky 1987), present diseases cannot be ac- On a global scale, these abstract treatments sug-
cepted as analogs for diseases of antiquity. New para- gest that a variable set of diseases have infected
sites have becomefixedby human populations; older human populations through time. Small mobile or
parasites have evolved less destructive adaptive sedentary populations are expected to have chronic
strategies; still other parasites, most likely unidenti- or latent microbial flora. As population size or den-
fiable, have died out. Although present processes of sity of movement between populations increases, hu-
infection and transmission may be comparable to man groups are subject to acute infectious parasites
those of the past, the present human disease load does that periodically erupt as epidemics. To determine
not mirror the past. whether these expectations hold on a local scale re-
Epidemiologists with an interest in understand- quires the use of other data sets.
ing past diseases are well aware of this problem of In summary, Darwinism is crucial for any discus-
analogs. To overcome it, they have focused on recon- sion of historical epidemics. Variability and selection
structing the human ecological settings most condu- explain the evolution and differential persistence of
cive to the fixing and persistence of human infec- human diseases under differing environmental condi-
tious parasites (Cockburn 1963, 1971; Black 1966, tions. These simple principles account for the extinc-
1980; Fenner 1971, 1980). Immunology, population tion of older diseases and the sudden onset of new
size and density, and population mobility are the key ones. Ecological factors, including population distri-
variables considered in this approach. bution, nature of settlement, and immunology, are
Most of the diseases considered in this essay have useful for stipulating the global distribution of
one trait in common: Recovery from the infection chronic and acute infections.
confers long-term or permanent immunity. Because Although important, Darwinian theory is also sub-
of this protection, parasites require a continual pool ject to limitations. Because of evolutionary changes
of susceptible hosts to survive. in hosts and parasites, present diseases cannot be
Large nucleated populations, such as those of cit- accepted as analogs for past diseases. In addition,
ies, meet the criterion for such a pool. As docu- theory, by definition, is ideational. Without testing
mented archeologically, nucleated populations of ideas against the complexity of empirical variability,
any magnitude did not become a consistent feature ideas about how evolution, persistence, or extinction
of the human landscape until after the evolution of occurred are empty.
agricultural systems. Cities developed shortly there-
after, having a temporal depth in western Asia of Infectious Diseases in Population Isolates
approximately 5,000 years (Wenke 1984). Although The second method of reconstructing historical epi-
it is likely that acute, infectious parasites periodi- demics is to study the effects of introduced acute
cally colonized individuals or populations before infections on living population isolates. Because of
5000 B.P., natural selection fixed these parasites population size, distribution, or geography, these iso-
only when population density passed a threshold lates, or virgin-soil populations, do not maintain
necessary for parasitic survival. Even after 5000 acute infections endemically. These infections must
B.P., the distribution of acute infections probably be introduced from external sources. The temporal
was uneven across Asia and Europe simply because lapse between introductions of the same parasite
population distribution was uneven. coupled with the immunological responses of previ-
Smaller nucleated populations that are sedentary ously infected individuals determine whether the
or consist of those who practice a mobile settlement foreign parasite will have a minimal or maximal
strategy are likely to be infected by other types of effect. Whereas temporal isolation of one year may
parasites. The list of potential parasites varies, de- be sufficient to cause an epidemic of the common
pending on the degree of mobility, the presence or cold (Burnet and White 1972), a six- to eight-year
absence of herd animals or pets, and the size of the lapse may be necessary to cause a smallpox epidemic
population. Both F. Fenner (1980) and F. L. Black (Pitkanen and Eriksson 1984).
(1980) think chronic or latent infections, including There are two approaches to the study of acute
chickenpox (Varicella zoster) and Herpes simplex, are infectious outbreaks in nonimmune populations.
probable candidates for persistence in small popula- During an epidemic, surveillance teams may con-
tions. Zoonotic infections, including yellow fever tinuously monitor the appearance of new victims
(arbovirus) and tetanus (Clostridium tetani), that and the recovery or death of older victims (e.g., Paul
are transferred from animal reservoirs to humans by and Freeze 1933; Nagler, Van Rooyen, and Sturdy
accidents of proximity are also likely. 1949; Christensen et al. 1953a,b; Peart and Nagler

1954; Phillip et al. 1959; Monrath et al. 1980; are useful guides to understanding epidemic condi-
Brenneman, Silimperi, and Ward 1987; Gerber et al. tions in the past. These studies document the ease
1989). Alternatively, antibody reactions can be mea- with which infectious parasites spread and the
sured in sputum or serological samples (Black and trauma that follows in the wake of epidemics. Rather
Rosen 1962; Adels and Gajdusek 1963; Brown, Gaj- than single epidemic events, it is likely that native
dusek, and Morris 1966; Black et al. 1970; Brown Americans in the sixteenth and seventeenth centu-
and Gajdusek 1970; Neel et al. 1970). ries experienced waves of infections. The deteriora-
Although both attack and mortality rates can be tion of health following an initial disease event estab-
determined from disease notifications, the accuracy lished conditions appropriate for the invasion of
of the rates varies according to the severity of the other, allochthenous and autochthenous, parasites.
outbreaks, the rapidity of spread, and the number of
surveillance teams. In severe disease episodes, it is Historical Descriptions of Epidemics
likely that both morbidity and mortality are greatly Consulting historical documents is the third method
underestimated (Crosby 1976). of reconstructing past epidemics. Although lumped
Because of immunological memory, antibody test- within a single heading, these sources vary from
ing can be done at any time. Consequently, an entire casual references to disease outbreaks to detailed
population can be surveyed for the presence of mea- descriptions of a single epidemic. Finding these docu-
sles antibody 15 years after the epidemic. Unfor- ments demands great investments of time. Rarely
tunately, the resulting trends apply only to the sur- are medical data indexed or otherwise distinguished
vivors. Without independent evidence (e.g., death in archives. Consequently, researchers may search
certificates, disease notifications), trends in mortal- assiduously through primary documents before com-
ity cannot be measured. ing across a single description of a disease event.
In addition to incomplete reporting, contemporary Descriptions of epidemics among native Ameri-
studies of epidemics in virgin-soil populations are cans during the Columbian period are subject to
subject to the problem of analogs. Although it is three sources of error. First, because contacts during
tempting to use modern morbidity and mortality the period were irregular, descriptions of any sort,
data to account for what might have occurred 500 including references to disease, are also irregular.
years ago, such an approach is erroneous for two Consequently, the first reference to a disease event
reasons. First, as previously described, less deadly may not mark the onset of introduced parasites. As
symbioses between parasites and hosts evolve late as 1800 contact between Europeans and native
through time. Second, where present, medical inter- groups of the North American plains was still irregu-
vention will curtail the course of a disease outbreak. lar. When Meriwether Lewis and William Clark vis-
Because of these factors, contemporary responses of ited the Upper Missouri tribes, the Mandan de-
virgin-soil populations to acute infectious parasites scribed a smallpox epidemic that had occurred 20
are likely to be rather pale reflections of sixteenth- years earlier (Thwaites 1904).
or seventeenth-century disease events. Second, as discussed previously, the crudeness of
Despite these limitations, knowledge of contempo- European knowledge during the Columbian period
rary epidemics is crucial for understanding the infec- affected the nature of early disease descriptions. For
tious process. As demonstrated by the accidental one thing, it is likely that observers failed to record
introductions of measles to southern Greenlanders many outbreaks. Moreover, a lack of familiarity
in 1951, stochastic contacts between infected and with the people being described made it difficult for
susceptible individuals still occur (Christensen et al. even the most conscientious explorers to estimate
1953a,b). In addition, these contemporary studies the number of deaths that diseases wrought. The
detail the complex interactions between the health Gentleman of Elvas (Bourne 1904), for instance, sim-
of the hosts and primary and secondary invasions. ply described the abandonment of villages visited by
Between 1942 and 1943 in the Yukon, a small band the expedition of Hernando DeSoto. Similarly, Dan-
of Tlingit experienced six epidemics, including mea- iel Gookin (1806) described an epidemic event from
sles, malaria, whooping cough, diarrhea, and menin- hearsay evidence that had decimated native groups
gitis. With each episode, the health of the population of New England seven or eight years before the En-
deteriorated, allowing for the invasion of other para- glish established New Plymouth.
sites (Marchand 1943). Third, there is confusion over disease names. Be-
In summary, contemporary studies of the infectious cause Europeans were writing about native disease
process and disease loads of nonimmune populations experiences, knowledge of what was known in Eu-

V.9. The Americas, 1492-1700 321
rope is crucial for understanding this ambiguity. an epidemic episode (Blakely 1989; Blakely and
C. Creighton's (1894) sourcebook on epidemics in Detweiler-Blakely 1989). Moreover, the frequency
Britain continues to be one of the finest and most and type of skeletal pathologies can provide informa-
readily available compendiums of evolving medical tion on the presence, absence, and, perhaps, type of
knowledge. acute infectious agent (Steinbock 1976).
Before 1743, influenza was frequently confused The use of reconstructed demographic profiles to
with other agues or catarral fevers. Diphtheria was infer past epidemics requires two assumptions, how-
not defined as a separate illness until the eighteenth ever. First, the mortuary population represents a
century. Before that time, it was lumped with scar- single temporal interval comparable to an epidemic
letina or the purples. Because measles and smallpox interval. Second, the burial sample is representative
both produced rashes, the two terms were used inter- of those who lived. Both assumptions are difficult to
changeably until 1593. By 1629, however, when the support archeologically.
Bills of Mortality were established, smallpox and Although archeologists are skilled in controlling
measles were consistently differentiated. Smallpox for time, the temporal resolution obtainable from
was noted as "flox or smallpox." the archeological record is rarely comparable to a
Because smallpox, measles, influenza, and diph- single epidemic event. Only in unique depositional
theria are acute and infectious, they all could have settings, such as the Tathum burial mound in west
been introduced to the Americas at the time of first Florida (Mitchem 1989; Hutchinson 1990), does the
contact. Whether they were requires careful reading weight of evidence suggest that the burial popula-
of documents informed by contemporary epidemio- tion represents an epidemic episode. Mortuary set-
logical knowledge. Historical documents by them- tings that incorporate 50 to 100 years are far more
selves are of marginal utility. The confusion over common.
names, which they reflect, coupled with medical na- Even if the temporal dimension is controlled for,
ivete and unfamiliarity with the populations being the problem of the representativeness of the burial
described by observers, has led one microbiologist to sample remains. Skeletal populations are typically
state that documentary evidence "provides, at best, biased samples of those who lived. Some age-sex
an accumulation of suppositions, since most ac- classes are underrepresented; others may be over-
counts give insufficient details of symptoms or of represented (Buikstra and Cook 1980). Controlling
epidemiological patterns for us to impute an for these biases is challenging, especially under epi-
aetiological agent" (Mackenzie 1980). demic conditions. As suggested by historical descrip-
Despite these limitations, historical descriptions tions and rarity of burial populations during the
are crucial sources of information and must be inte- Columbian period (Ramenofsky 1987), native popu-
grated into any disease reconstruction. Documents lations may have ceased interment in some areas.
not only highlight the presence of some infectious This practice raises serious questions about the na-
parasite, but force the historical epidemiologist to ture of available burial samples: Do they represent
investigate what and why the disease event occurred. the victims or survivors of epidemics? Without con-
trolling for sampling biases, accurate reconstruc-
Burial Populations tion of demographic profiles from cemetery data is,
Irregularity of initial contact and the limitations of at best, difficult.
medical knowledge among observers during the Co- As with skeletal analyses, the investigation of
lumbian period have been recognized as sources of osteological evidence of epidemic mortality has seri-
error for some time. To compensate for these prob- ous shortcomings. First, not all acute infections are
lems, other types of data have been deployed in re- expressed osteologically. In illnesses such as vene-
constructing historical epidemics. Human skeletal real syphilis, or tuberculosis, bone cells become in-
remains are of some importance here (Milner 1980; volved only when the disease has progressed to a
Blakely 1989). G. R. Milner (1980) has argued that severe stage. If the individual dies before that point,
the analysis of mortuary populations from the earli- the disease will not be reflected osteologically.
est period of contact is of central importance in un- Second, bone cells have limited ways of respond-
raveling the timing and magnitude of aboriginal ing to infectious agents: tissue loss, tissue gain, both
population loss from introduced infectious diseases. loss and gain, or abnormal morphology (Ortner and
Skeletal populations are employed in two ways. Putschar 1981). The remodeling may be variously
Analysis of the age-sex structure of a population expressed, but different causative agents can result
can suggest whether its demographic profile reflects in the same osteological expression (Steinbock 1976;

Ortner and Putschar 1981). Although osteological Table V.9.1. Diseases suggested to have been
remodeling may suggest the presence of an acute introduced to the Americas
infection, stipulating the causative agent responsi-
ble for the remodeling is frequently impossible. Crosby Crosby Dobyns Ramenofsky
Even in those rare instances where a specific acute Disease (1972) (1986) (1983) (1987)
infectious parasite is implicated as causing osteo- Chickenpox X X
logical remodeling (Jackes 1983), it is unlikely that Dengue fever X
the individual died from the infection. The process of Influenza X X X X
osteological remodeling is of longer duration than Measles X X X X
the illness. Mumps X X
Because of inherent difficulties in isolating caus- Rubella X
ative agents, bioarcheologists have begun to consider Smallpox X X X X
nonspecific stress indicators, especially osteomylitis Cholera X X
Diphtheria X X
and periostitus (Detweiler-Blakely 1989). If the
Pneumonia X
health of native populations deteriorated after con- X X
Pertussis
tact, the frequency or intensity of stress responses Scarlet fever X X X
should have increased. To determine whether the Typhoid fever X X
suggested association holds requires the analysis of Anthrax X
burial populations through time. Even if such a series Bubonic plague X X
were available and the appropriate pattern were docu- Malaria X X
mented, the cause or causes of the stress responses Typhus X X
would remain elusive (Buikstra and Cook 1980). Yellow fever X X X
Periosteal responses, for instance, can be caused by Total 3 11 12 14
anemia, treponemal infections, scurvy, trauma, or
osteomylitis (Ortner and Putschar 1981).
In summary, inadequate control of the temporal (e.g., Stearn and Steam 1945), whereas others have
dimension, biases present in cemetery populations, studied the introduction of all diseases to a specific
and nonspecific skeletal responses to disease limit region (e.g., Cook 1982). Few have attempted a com-
the utility of skeletal populations as primary sources prehensive treatment of the introduction of all dis-
of data for reconstructing epidemic mortality in the eases to both continents. Table V.9.1 summarizes the
Americas during the Columbian period. As a secon- conclusions of three scholars regarding the introduc-
dary resource, these investigations may provide intion of acute infectious agents to the Americas.
formation unobtainable through other sets of data. It will be noted that none of the lists includes
The reconstruction of past epidemics is challeng- epidemic (venereal) syphilis or tuberculosis. The
ing because it is elusive. Instead of a single infallible omission of these two major diseases should not be
method, historical epidemiologists must employ a interpreted as supporting the notion that either dis-
suite of methods. Results of one investigation can ease originated in the Americas. Controversies over
then be weighed against those obtained from other their origins are extensive (regarding syphilis:
inquiries. Even then, we can never be certain Crosby 1972; Ramenofsky 1987; Baker and Arme-
whether smallpox or malaria was the biggest killer lagos 1988; regarding tuberculosis: Black 1980;
of native Americans in the sixteenth century. At the Clark et al. 1987; Ramenofsky 1987). Until this ques-
same time, the integration of evidence from Darwin- tion is resolved, these diseases cannot be considered
ian theory, contemporary disease investigations of to be either allochthonous or autochthonous to the
nonimmune populations, historical documents, and New World.
skeletal analyses can suggest the magnitude of the There are some disagreements about specific intro-
parasitic invasion that faced native peoples during ductions that stem from the temporal or intellectual
the earliest centuries of European contact. focus of the work. In 1972 A. Crosby considered only
sixteenth-century introductions. In 1986 he adopted
Allochthonous Parasites in the Americas a much larger temporal framework; his suggested
introductions reflect that change. Although in 1983
Previous Syntheses H. Dobyns described more introduced infections
Some researchers have investigated the introduc- than those listed in Table V.9.1, the summary is
tion of specific diseases to the Americas in general limited to those diseases that arrived during the

V.9. The Americas, 1492-1700 323
sixteenth and seventeenth centuries. My own list The bacterial pneumonias are caused by a group of
(1987) is also limited to the first two centuries of unrelated organisms. Some of these (Streptococcus
European contact. pneumoniae) are part of the normal flora of the hu-
In developing that list, I weighed evidence from man upper respiratory tract. Thus, some causative
all sources described previously. Although my total agents of severe lung infections in humans had to
was greater than either Crosby's or Dobyns's, sev- have been present in the Americas before European
eral diseases were excluded; other diseases were in- contact. In contrast, contemporary studies (Brenne-
cluded. Cholera was excluded because according to man et al. 1987) suggest that some native American
current opinion (Creighton 1894; Benenson 1976a) it populations are at higher risk from other agents of
spread to the Americas in the eighteenth century. pneumonia (Hemophilis influenzae). This elevated
Diphtheria was excluded because of the ambiguity of risk may indicate that not all causative bacteria of
the name (Creighton 1894). pneumonia were present before Europeans arrived
Typhoid (enteric) fever was excluded for several in the Americas. Moreover, because pneumonias are
reasons. Although native populations of the Ameri- major secondary invaders that follow such viral in-
cas certainly suffered from diarrheal infections in the fections as measles and influenza, and because both
postcontact period, the question becomes whether measles and smallpox were allochthonous to the
these infections were new and whether Salmonella Americas, it is likely that at least some types of lung
typhi caused some of the infections. Thefirstquestion infection spread to the Americas with Europeans. As
cannot be answered; the second can be addressed health deteriorated from viral infections, bacterial
indirectly. The disease was not isolated from typhus agents could invade and cause death.
or other nonspecific childhood fevers until the nine- Although both Dobyns and I view epidemic typhus
teenth century (Creighton 1894; Overturf and Un- as an Old World introduction to the Americas,
derman 1981). In addition, although rare, typhoid H. Zinsser (1947) thought that it predated European
fever can take a chronic form and can spread to hu- contact. The vector of typhus is the human body
mans from nonhuman reservoirs including turtles louse. The current worldwide distribution of people
(Youmans et al. 1980). The combination of a chronic means that epidemic typhus is also worldwide
state and the indisputable presence of turtles in (Wisseman 1976). Although it is likely that body lice
precontact America suggested that S. typhi could predated Europeans in the Americas, I think it un-
have been present in the Americas before 1492. likely that typhus-infected lice were present. The
The diseases that I listed as introductions, but not disease thrives under conditions of intense crowding,
treated by Crosby or Dobyns, include anthrax, ru- poor sanitation, and social or economic upheaval asso-
bella, and pneumonia. Anthrax is typically a rela- ciated with war. Despite the archeological evidence of
tively minor infection in humans. Domestic stock, warfare in the Americas, the distribution of human
cattle, sheep, horses, and goats are the primary populations was inappropriate for fixing epidemic
source of the infection; humans become ill through typhus as part of the disease load of native popula-
accidents of proximity (Whiteford 1979). In those tions. Dense concentrations of people were simply too
areas, such as the Southwest or the pampas of South rare.
America, where domestic stock were part of the cul- In summary, a minimum of 11 and a maximum of
tural baggage of European colonists, anthrax could 14 viral, bacterial, or protozoal diseases are sug-
have been a source of infection. gested in Table V.9.1 as having diffused to the Ameri-
Rubella was added to the list for two reasons. cas during the first two centuries of European con-
First, although a relatively mild disease in adults, it tact. There is unanimous agreement on five disease
can seriously affect the reproductive fitness of a introductions (influenza, measles, smallpox, scarlet
population. If a woman develops German measles fever, and yellow fever). I have increased the total
during the first trimester of pregnancy, the fetus introductions from 11 to 14 by adding anthrax, ru-
may be born with major congenital defects, includ- bella, and pneumonia.
ing cataracts, heart disease, microcephaly, and men-
tal retardation (Top 1976). Second, although rubella Current Synthesis
was confused with measles and smallpox until the After reexamining the evidence for and against the
eighteenth century, the presence of measles and introduction of diseases listed in Table V.9.1,1 have
smallpox in America during the sixteenth and seven- removed one disease. Chickenpox is omitted from
teenth centuries suggested that rubella could have Table V.9.2 because it is present in small nucleated
been introduced at the same time. populations that lack antibodies for acute, infectious

Table V.9.2. Viral, bacterial, and protozoal agents determined whether any new outbreak would be lo-
introduced to the Americas cal or regional in scale (Bartlett 1956; Black 1966;
Cockburn 1971).
Mode of Recently, the 1520 introduction of smallpox to the
transmission Viral Bacterial Protozoal Americas has been a subject of some interest. It is a
Direct Influenza Pneumonia classic example of disease transmission and spatial
Measles Scarlet fever diffusion. On the basis of information drawn from
Mumps Pertussis historical documents, Dobyns (1983) has argued that
Rubella the virus became the initial New World pandemic,
Smallpox spreading as far south as Chile and as far north as
Zoonotic Yellow Fever Anthrax Malaria the Canadian border. The Caribbean islands were
Bubonic plague the initial focus of infection in 1518. The virus was
Typhus then carried to Mexico by a crew member of Panfilo
de Narvaez's expedition. The large size and extreme
density of aboriginal populations in the valley of
microbes (Black 1980). In addition, Varicella zoster Mexico encouraged the rapid dissemination of the
can follow a chronic course, expressing itself as virus.
chickenpox in children and as shingles in adults The question of spatial diffusion beyond the valley
(Brunell 1976). of Mexico has been investigated by historians and
Table V.9.2 lists viral, bacterial, and protozoal archeologists. Noble Cook (1981), historian, has not
agents, characterized by two modes of transmission. found evidence of spatial diffusion into the Peruvian
Eight of the 13 viruses (influenza, measles, mumps, Empire. A second introduction of smallpox to Pan-
rubella, smallpox) and bacteria (pneumonia, scarlet ama in 1524 did, however, spread down the Andean
fever, pertussis) colonize humans only and are trans- chain (Cook 1982). Using climatic data to explain
mitted by them only. Of the remaining 5 diseases, the persistence of smallpox, S. Upham (1986) argued
yellow fever is viral; anthrax, plague, and typhus that the smallpox epidemic did spread to southwest-
are bacterial; and malaria is protozoal. All 5 of these ern groups. Other archeologists (Ramenofsky 1987;
agents are classified as zoonoses, meaning that the Campbell 1989) have relied on archeological indica-
primary reservoir is a nonhuman, invertebrate or tors of population change and time. Although gener-
vertebrate species (except in rare cases, e.g., ally supportive of an early-sixteenth-century intro-
pneumonic plague [Benenson 1976b]). duction of the parasite to North America, the
Previously discussed difficulties of reconstructing archeological evidence of catastrophic population
past epidemics by a single method have direct impli- loss was ambiguous. Evidence of a sixteenth-century
cations for the current synthesis. I will not attempt disease introduction was not documented in central
to reconstruct the precise date or port of entry of New York or the Middle Missouri (Ramenofsky
each disease introduction. My goal is to build gen- 1987). S. Campbell (1989) documented a large popu-
eral expectations about the postcontact spatial per- lation decline in the Chief Joseph Reservoir during
sistence of parasites, and to accomplish this I will the early sixteenth century. I discovered a compara-
use data on transmission cycles, evolution, ecology, ble population decline in the Lower Mississippi val-
and history. ley between 1540 and 1600. The magnitude and ra-
For those viruses and bacteria that colonize and pidity of the loss argued in favor of some acute,
reproduce only in humans, density of human popula- infectious parasite. Neither the 1520 nor the 1524
tions, regularity of communication, and incubation smallpox epidemic could be implicated directly.
period of the parasite determined the size of spatial In summary, for directly transmitted viruses and
epidemic waves. As population density decreased or bacteria, the distribution of susceptible populations,
communication became irregular relative to the in- communication systems, and incubation periods of
cubation period of the parasite, the parasite died out. the parasite determined whether local disease
Whether a second introduction of the same parasite events became regional or multiregional. Even with
caused another epidemic outbreak varied according detailed historical records, it is difficult to define the
to the number of reproductively active survivors and spatial extent of a specific parasite. Although the
time. Although individuals who escaped infection scale of resolution currently obtainable from re-
during the first disease event could be subsequently gional archeological data bases may be sufficient for
infected at any time, the size of the susceptible pool concluding that acute infectious microbes caused ca-

V.9. The Americas, 1492-1700 325
tastrophic die-offs, current knowledge is simply in- on human blood, the rickettsial agent is transmitted
sufficient for stipulating whether one or another epi- to humans (Zinsser 1947; Wisseman 1976).
demic event was causal. Plague and anthrax are bacterial infections trans-
Transmission cycles of zoonotic infections are fun- mitted to humans from nonhuman mammalian res-
damentally different from infections transmitted ervoirs. The distribution of the reservoir largely de-
solely between humans. Because vertebrate or inver- termines the distribution of the disease. Wild rodent
tebrate species other than humans are the primary populations in wooded or desert areas are the true
reservoir of the parasite, niche requirements of the reservoir of the plague bacterium: In these set-
reservoir and microbe determined the postcontact tings, the disease is endemic (Meyer 1963; Benenson
spatial pattern across the American continents. Hu- 1976b). In urban areas, the causative agent, Yer-
mans became infected through accidental interac- sinia pestis, is transmitted to humans through a
tions with the reservoir and causative agent. The secondary vector, the rat flea, Xenopsylla cheopis.
following focuses on those aspects of reservoir or The proximity of humans to rats and their fleas
microbial niches pertinent to reconstructing the creates a tertiary focus of the disease.
postcontact spatial patterning of these infections. As previously mentioned, anthrax is a bacterial
Temperature severely curtails the distribution of disease of domestic ungulates. The causative agent,
yellow fever. The viral disease is transmitted to hu- Bacillus anthracis, is transmitted to humans through
mans or other nonhuman primates by several mos- the ingestion of contaminated meat or milk products,
quito vectors, including Aedes and Haemagogus contact with infected animals, or the inhalation of
(Taylor 1951). The optimal temperature for incuba- viable airborne spores (Brachman 1976; Whiteford
tion of the arbovirus and the transmission ability of 1979).
the vectors is approximately 30°C (Whitman 1951). Because not all New World habitats were appropri-
At temperatures less than 24°C Haemagogus, for ate for the reproduction of reservoirs, vectors, and
instance, cannot transmit the disease, and the incu- parasites, it is likely that zoonotic infections were
bation period of the virus lengthens. In addition, the more limited spatially than were directly transmit-
vectors have preferred breeding habitats. Aedes ted viruses and bacteria. Yellow fever became fixed
aegypti breeds in clay-bottomed containers; other in tropical climates; malaria survived between 60°
species of Aedes and Haemagogus prefer breeding in north latitude and 40° south latitude (Watson and
trees of climax rain forests (Carter 1931). Hewitt 1941); epidemic typhus survived where hu-
Like yellow fever, malaria is a vectorborne dis- man groups were concentrated; herds of domestic
ease that is transmitted to humans by numerous ungulates became the focus of anthrax; bubonic
species of Anopheles. The temperature limitations plague was fixed as a disease of ports. As rats mi-
and elevational preferences of these species vary grated away from ports, plague also migrated.
greatly. Whereas Anopheles maculipennis can repro- The variability in reproductive requirements and,
duce in cold pools along lake margins at elevations therefore, transmission cycles of parasites has impli-
greater than 4,000 feet in the western United cations for the postcontact spatial patterning in the
States, Anopheles quadramaculatis prefers breed- Americas. Because all native populations were vir-
ing in swampy nonbrackish pools or bayous typified gin soil, the accidental introduction of any parasite
by the Lower Mississippi valley (Hackett 1941; Wat- could decimate a single population aggregate.
son and Hewitt 1941). In addition, the body tem- Whether the parasite diffused spatially and ac-
perature of the vector affects the reproductive poten- quired an endemic status in the rich American envi-
tial of the protozoans. Plasmodium vivax and ronment depended on a number of factors.
Plasmodium malariae will not develop in anophe- The probability of fade-outs of directly transmit-
lines if the body temperature is less than 15°C; Plas- ted viruses and bacteria varied according to stochas-
modium falciparum requires an anopheline body tic contacts between infected and susceptible hosts,
temperature of greater than 18°C for reproduction the overall distribution of population, and the time
(Zulueta 1980). separating introductions of the same parasite. As
Epidemic typhus is an acute infectious disease for just described, the spatial pattern of zoonoses de-
both vector and human populations. The human pended on reproduction requirements of reservoirs,
body louse, Pediculus humanus, is the vector; the vectors, and parasites. Certainly by the seventeenth
causative agent is a bacterium, Rickettsia prowaze- century, natural selection had fixed the spatial vari-
kii. After ingesting the agent, the typhus-infected ability of all introduced parasites. Like threads join-
louse dies within 7 to 10 days. When the louse feeds ing patches of a quilt, communication mechanisms

linked sources of infection to potential recipients. Blakely, R. L. 1989. The life cycle and social organization.
Each epidemic wave further reduced survivors of In The King site: Continuity and contact in sixteenth-
previous disease outbreaks. century Georgia, ed. R. L. Blakely, 17-34. Athens, Ga.
Blakely, R. L, and B. Detweiler-Blakely. 1989. The impact
Conclusions of European diseases in sixteenth-century Southeast:
As demonstrated by this synthesis, simple questions A case study. Midcontinental Journal of Archaeology
are frequently the most difficult to answer. Determin- 14: 62-89.
Bourne, E. G., ed. 1904. Narratives of the career of
ing which diseases were allochthonous in the Amer-
Hernando De Soto, 2 vols. New York.
icas before A.D. 1700 requires the expertise of nu-
Brachman, P. S. 1976. Anthrax. In Communicable and
merous disciplines, including the study of evolution, infectious diseases, 8th edition, ed. F. H. Top, Sr., and
ecology, microbiology, history, archeology, and geogra- P. F. Wehrle, 137-42. St. Louis, Mo.
phy. The integration of diverse and sometimes contra- Brenneman, G., D. Silimperi, and J. Ward. 1987. Recur-
dictory sets of information provides a means of evalu- rent invasive Haemophilis influenzae type b disease
ating past and present assumptions and of suggesting in Alaskan natives. Journal of Pediatric Infectious
future directions. Although skeptical of the possibil- Diseases 6: 388-92.
ity of reconstructing the exact number of introduc- Brown, P., and D. C. Gajdusek. 1970. Disease patterns and
tions, or dates and places of entry during the Colum- vaccine response studies in isolated Micronesian popu-
bian period, I support serious interdisciplinary efforts lations. American Journal of Tropical Medicine and
aimed at establishing the nature of the parasitic en- Hygiene 19: 170-5.
vironment that confronted native populations during Brown, P., D. C. Gajdusek, and J. A. Morris. 1966. Epi-
the sixteenth and seventeenth centuries. I hope that demic A2 influenza in isolated Pacific island popula-
this preliminary synthesis will promote such efforts. tions without pre-epidemic antibody to influenza
types A and B, and the discovery of other still unex-
Ann Ramenofsky plored populations. American Journal of Epidem-
iology 83: 176-88.
Bibliography Brunell, P. A. 1976. Chickenpox. In Communicable and
Adels, B. R., and D. C. Gajdusek. 1963. Survey of measles infectious diseases, 8th edition, ed. F. H. Top, Sr., and
patterns in New Guinea, Micronesia, and Australia. P. F. Wehrle, 165-73. St. Louis, Mo.
American Journal of Hygiene 77: 317-43. Buikstra, J. E., and D. C. Cook. 1980. Paleopathology: An
Baker, B. J., and G. J. Armelagos. 1988. The origin and American account. Annual Review of Anthropology 9:
antiquity of syphilis: Paleopathological diagnosis and 433-70.
interpretation. Current Anthropology 29: 703-36. Burnet, Macfarlane Sir, and D. O. White. 1972. Natural
Bartlett, M. S. 1956. Deterministic and stochastic models history of infectious disease, 4th ed. Cambridge.
for recurrent epidemics. Proceedings of the Third Campbell, S. K. 1989. Postcolumbian culture history in
Berkeley Symposium on Mathematical Statistics and the northern Columbian Plateau: A.D. 1500-1900
Probability 4: 81-109. Ph.D. dissertation, University of Washington.
Benenson, A. S. 1976a. Cholera. In Communicable and Carter, H. R. 1931. Yellow fever: An epidemiological and
infectious diseases, 8th edition, ed. F. H. Top, Sr., and historical study of its place of origin, ed. L. A. Carter
P. F. Wehrle, 174-83. St. Louis, Mo. and W. H. Frost. Baltimore.
1976b. Plague. In Communicable and infectious dis- Christensen, P. E., et al. 1953a. An epidemic of measles in
eases, 8th edition, ed. F. H. Top, Sr., and P. F. Wehrle, southern Greenland, 1951:11. Measles in virgin soil.
502-7. St. Louis, Mo. Acta Medica Scandinavica 144: 430-49.
Black, F. L. 1966. Measles endemicity in insular popula- 1953b. An epidemic of measles in southern Greenland,
tions: Critical community size and its evolutionary 1951: III. Measles in virgin soil. Acta Medica Scandi-
implication. Journal of Theoretical Biology 11:207-11. navica 144: 450-4.
1980. Modern isolated pre-agricultural populations as a Clark, G. A., et al. 1987. The evolution of mycobacterial
source of information on prehistoric epidemic pat- disease in human populations: A reevaluation. Cur-
terns. In Changing disease patterns and human behav- rent Anthropology 28: 45-62.
ior, ed. N. F. Stanley and R. A. Joske, 37-54. London. Cockburn, A. 1963. The evolution and eradication of infec-
Black, F. L., and L. Rosen. 1962. Patterns of measles anti- tious diseases. Baltimore.
body in residents of Tahiti and their stability in the 1971. Infectious diseases in ancient populations. Cur-
absence of reexposure. Journal of Immunology 88: rent Anthropology 12: 45-62.
727-31. Cook, N. D. 1982. Demographic collapse: Indian Peru,
Black, F. L., et al. 1970. Prevalence of antibody against 1520-1620. Cambridge.
viruses in the Tiriyo, an isolated Amazon tribe. Ameri- Creighton, C. 1894. History of epidemics in Britain, 2 vols.
can Journal of Epidemiology 91: 430-8. Cambridge.

V.9. The Americas, 1492-1700 327
Crosby, A. 1972. The Columbian exchange: Biocultural human behavior, ed. N. F. Stanley and R. A. Joske,
consequences of 1492. Westport, Conn. 129-49. London.
1976. Epidemic and peace 1918. Westport, Conn. Marchand, J. F. 1943. Tribal epidemics in the Yukon. Jour-
1986. Ecological imperialism: The biological expansion nal of the American Medical Association 123:1019-20.
of Europe, 900-1900. Cambridge. Meyer, K. F. 1963. Plague. In Diseases transmitted from
Detweiler-Blakely, B. 1989. Stress and the battle casual- animals to man, ed. T. G. Hull, 527-87. Springfield, 111.
ties. In The Kino site: Continuity and contact in Milner, G. R. 1980. Epidemic disease in the post-contact
sixteenth-century Georgia, ed. R. L. Blakely, 87-100. Southeast: A reappraisal. Mid Continental Journal of
Athens, Ga. Archeology 5: 39-56.
Dobyns, H. F. 1963. An outline of Andean epidemic history Mitchem, J. M. 1989. Redefining Safety Harbor: Late
to 1720. Bulletin of the History of Medicine 37: 493- prehistoric/protohistoric archaeology in west peninsu-
515. lar Florida. Ph.D. dissertation, University of Florida.
1983. Their number became thinned. Knoxville, Tenn. Monrath, T. P., et al. 1980. Yellow fever in Gambia, 1978-
Fenner, F. 1971. Infectious diseases and social change. 1979. Epidemiological aspects with observations on
Medical Journal ofAustralia 1: 1043-7,1099-201. the occurrence of orungo virus infections. American
1980. Sociocultural change and environmental diseases. Journal of Tropical Medicine and Hygiene 29: 912—28.
In Changing disease patterns and human behavior, ed. Nagler, F. P., C. E. Van Rooyen, and J. H. Sturdy. 1949.
N. F. Stanley and R. A. Joske, 7-26. London. An influenza virus epidemic at Victoria Island,
Gerber, A. R., et al. 1989. An outbreak of syphilis on an N.W.T., Canada. Canadian Journal of Public Health
Indian reservation: Descriptive epidemiology and 40: 457-65.
disease-control measures. American Journal of Public Neel, J. V., et al. 1970. Notes on the effect of measles and
Health 79: 83-5. measles vaccine in a virgin-soil population of South
Gookin, D. 1806. Historical collections of Indians of New American Indians. American Journal of Epidemiology
England, 1674. Collections of the Massachusetts His- 91: 418-29.
torical Society, Ser. 1 (1792), 1: 141-227. Ortner, D., and W. G. Putschar. 1981. Identification of
Hackett, C. J. 1963. On the origin of the human pathological conditions in human skeletal remains.
treponematoses. Bulletin of the World Health Organi- Smithsonian Contributions to Anthropology 28. Wash-
zation 29: 1-41. ington, D.C.
Hackett, L. W. 1941. Malaria and community. In A Sympo- Overturf, G. D., and A. E. Underman. 1981. Typhoid and
sium on human malaria with special reference to enteric fevers. In Communicable and infectious dis-
North America and the Caribbean region, ed. F. R. eases, 9th edition, ed. P. F. Wehrle and F. H. Top, Sr.,
Moulton, 148-56. Washington, D.C. 736-45. St. Louis, Mo.
Hariot, T. 1973. A brief and true report of the new found Paul, J. H., and H. L. Freeze. 1933. An epidemiological and
land of Virginia (1588). In Virginia voyages fromHak- bacteriological study of the "common cold" in an iso-
luyt (1589), ed. D. B. Quinn and A. M. Quinn, 46-76. lated arctic community (Spitzbergen). American Jour-
Oxford. nal of Hygiene 17: 517-35.
Hudson, E. H. 1968. Treponematosis and human social Peart, A. F, and F. P. Nagler. 1954. Measles in the Cana-
evolution. American Anthropologist 67: 885-92. dian arctic. Canadian Journal of Public Health 45:
Hutchinson, D. L. 1990. Postcontact biocultural change 146-56.
and mortuary site evidence. In Columbian conse- Phillip, R. N., et al. 1959. Observations on Asian influenza
quences 2. Archaeological and historical perspectives on two Alaskan islands. Public Health Reports 74:
on the Spanish borderlands east, ed. D. H. Thomas. 737-45.
Washington, D.C. Pitkanen, K., and A. W. Eriksson. 1984. Historical
Jackes, M. K. 1983. Osteological evidence for smallpox: A epidemiology of smallpox in Aland, Finland: 1751—
possible case from seventeenth-century Ontario. 1890. Demography 21: 271-95.
American Journal of Physical Anthropology 60: 7 5 - Ramenofsky, A. F. 1987. Vectors of death: The archaeology
81. of European contact. Albuquerque, N.M.
Jordan, E. O. 1927. Epidemic influenza. Chicago. Stearn, E. W, and A. E. Stearn. 1945. The effects of small-
Le Page du Pratz, A. S. 1975. The history of Louisiana pox on the destiny of the Amerindian. Boston.
(1758), ed. J. G. Tregle. Baton Rouge, La. Steinbock, R. T. 1976. Paleopathological diagnoses and
Levins, R., and R. C. Lewontin. 1985. The dialectical biolo- interpretations. Springfield, 111.
gist. Cambridge. Stuart-Harris, C. 1981. The epidemiology and prevention
Lewontin, R. C. 1974. The genetic basis of evolutionary of influenza. American Scientist 69: 166—72.
change. New York. Taylor, R. M. 1951. Epidemiology. In Yellow fever, ed. G. K.
Mackenzie, J. S. 1980. Possible future changes in the Strode, 427-538. New York.
epidemiology and pathogenesis of human influenza A Thwaites, R. G., ed. 1904. Original journals of Lewis and
virus infections. In Changing disease patterns and Clark, 1804-1806, vols. 1, 5. New York.

Top, F. H., Sr. 1976. Rubella. In Communicable and infec- ing England. Like eastern Europe, it was character-
tious diseases, 8th edition, ed. F. H. Top, Sr., and P. F. ized by large estates worked by a servile peasantry.
Wehrle, 589-97. St. Louis, Mo. This pattern was replicated in the Americas, where
Upham, S. 1986. Smallpox and climate in the American the Spanish encountered an extensive indigenous
Southwest. American Anthropologist 88: 115—28. agricultural population with whom they established
Watson, R. B., and R. Hewitt. 1941. Topographic and re- a semifeudal relationship. There was no such indige-
lated factors in the epidemiology of malaria in North
America, Central America, and the West Indies. In A
nous population in the north, and the British either
symposium on human malaria with special reference pushed aside or killed those they did encounter. As a
to North America and the Caribbean region, ed. F. R. result, socioeconomic and settlement patterns dif-
Moulton, 135-47. Washington, D.C. fered. With the exception of the southeast, family-
Wenke, R. J. 1984. Patterns in prehistory: Man'sfirstthree owned and -operated farms became the dominant
million years, 2d edition. New York. pattern in English America. In most of Latin Amer-
Whiteford, H. H. 1979. Anthrax. In Bacterial, rickettsial ica, haciendas and plantations became the dominant
and mycotic diseases, Handbook Series in Zoonoses, pattern. In the areas where an extensive agricul-
vol. 1, ed. J. H. Steele, 31-66. Boca Raton, Fla. tural society was conquered, Indians provided the
Whitman, L. 1951. The arthropod vectors of yellow fever. servile labor force. Elsewhere, primarily in the Ca-
In Yellow fever, ed. G. K. Strode, 228-98. New York. ribbean islands and in what became Brazil, slaves
Wisseman, C. L. 1976. Rickettsial diseases. In Communica- imported from Africa provided the servile labor force
ble and infectious diseases, 8th edition, ed. F. H. Top, on plantations originally devoted to sugar growing.
Sr., and P. F. Wehrle, 567-84. St. Louis, Mo. Only in the southeastern part of English America
Youmans, G. P., P. Y. Paterson, and H. M. Sommers. 1980. were there plantations worked by slaves.
The biologic and clinical basis of infectious disease. 2d
edition. Philadelphia. Upon achieving independence, these two former
Zinsser, H. 1947. Rats, lice, and history. New York. colonial regions continued to develop in entirely dif-
Zulueta, J. de. 1980. Man and malaria. In Changing dis- ferent ways. The former Iberian colonies remained
ease patterns and human behavior, ed. N. F. Stanley producers of raw materials for export (Stein and
and R. A. Joske, 175-86. London. Stein 1970), whereas within a century the former
English colony became one of the leading manufac-
turing nations in the world. It is beyond the bounds
of this chapter to offer an explanation for these differ-
ences save to suggest the following: (1) In the new
V.10 Latin American nations there persisted local land-
owning elites with an interest in perpetuating the
Diseases and Mortality in the former colonial system, complete with its depen-
Americas since 1700 dence on a servile, illiterate population for the ex-
traction of staples and raw materials. (2) The set-
tlers in English America came from a society "which
It has been clear to virtually every observer of demo- generally treated literacy, toleration, individual
graphic patterns in the Americas that the differences rights, economic liberty, saving and investment as
between Anglo and Latin America are traceable to inseparable elements of the process of change and
the differences between the nations that colonized growth" (Stein and Stein 1970).
each region, as well as to the characteristics of the
indigenous populations of each region. The settle- Latin America
ment of North America by the British was a commer- Not all Iberian settlement in the Americas took
cial venture, the numerous settlements reflecting the place in areas in which Indians or black slaves
economic and religious diversity of the English Refor- formed a servile labor force. Grassland sections of
mation and the growing economic complexity of Brit- what became Argentina, Uruguay, and southern Bra-
ain itself. By contrast, "in Spanish America, the di- zil were without a sedentary indigenous agricultural
verse conditions of an entire continent had to find population and did not attract extensive European
expression in the same set of standard institutions" immigration until the latter part of the nineteenth
(Lang 1975). and the twentieth centuries. The areas in which
Moreover, by the sixteenth century the Iberian there were sedentary agricultural populations at-
Peninsula was becoming "underdeveloped" in contracted the most attention and as a result suffered
trast to the countries of northwestern Europe, includ- devastating pandemics. The magnitude of the result-

V.10. The Americas since 1700 329
ing population collapse is a matter of debate, but seem to have resulted in a stabilization of mortality
that it was catastrophic is beyond question. Though at levels that were high but nonetheless low enough
crisis mortality caused by pandemics and famines for population to grow.
receded over the three centuries following first Euro- It appears that among the most important identifi-
pean contact, mortality remained high enough that able endemic diseases or syndromes were the follow-
there was essentially no population growth during ing: the pneumonia—diarrhea complex of infancy and
the eighteenth century (McGovern-Bowen 1983). In- childhood, the severity of which is exacerbated by
deed, significant growth did not begin until the early protein-energy malnutrition; in some regions ma-
decades of the nineteenth century (McEvedy and laria; and tuberculosis, which was widespread.
Jones 1978). The increase resulted partially from the Among black troops serving in British West Indian
importation of African slaves (particularly to Brazil regiments in the West Indies, for instance, the aver-
and the Caribbean) and European immigration from age annual death rate from tuberculosis was 6 per
Mediterranean countries (particularly to Brazil and 1,000 in the 1860s, 8.5 in the 1870s, 5 in the 1880s, 3
Argentina) and partly from changes in mortality in the 1890s, and less than 1 in the 1900s. Diseases of
patterns. the respiratory tract, including tuberculosis, were
Data on mortality are sparse until about the mid- the leading cause of death. Over the same period
nineteenth century. Some scattered estimates of black deaths from malaria ranged between 1 and 2.5
crude mortality rates from the early years of the per 1,000 per year (Curtin 1987). Life table estimates
century are as follows: between 21.2 and 28.9 per are available from the middle of the nineteenth cen-
1,000 in Sao Paulo, Brazil, during the years 1777- tury for all of Latin America, except Argentina, Uru-
1836; between 36 and 46 per 1,000 in Havana be- guay, and Cuba. From 1860 to 1900, life expectancy at
tween 1801 and 1830; 44 per 1,000 in the town of birth increased from 24.4 to 27.2 years. These aver-
San Pedro in Guatemala in 1810-16 (the most valid age figures mask differences among countries. The
of several estimates from a series of neighboring Dominican Republic, Guatemala, and Nicaragua had
towns); and probably never fewer than 30 to 35 per a lower life expectancy in 1900 than Brazil, Chile,
1,000 in Mexico City at any time until the mid- Colombia, Costa Rica, Mexico, and Panama had had
nineteenth century. In Sao Paulo at the end of the in 1860 (Kunitz 1986). Diversity within some of the
eighteenth century, infant mortality is estimated to large nations, such as Mexico, was probably every bit
have been 288 per 1,000 live births and life expec- as great as it was among nations.
tancy at birth about 38 years (Kunitz 1986). The differences in mortality among nations, as
Judging by population estimates and scattered es- well as in the rate at which it declined in the latter
timates of mortality as well as fertility, it was in the half of the nineteenth, century and the first several
first half of the nineteenth century that births began decades of the present century, were primarily reflec-
to outnumber deaths with sufficient consistency for tions of their economic development. These in turn
population to begin to grow. This presumed stabiliza- were a reflection of the degree to which countries
tion of mortality, albeit at a high level, coincides were dependent on a servile labor force or had, like
with the period when independence was achieved by Argentina and Uruguay, attracted a large European
most Latin American nations. The two are not unre- population. Starting in the 1930s, however, the ra-
lated, for the result of independence was that the pidity with which mortality declined increased sub-
monopoly on trade long held by Spain and Portugal stantially, particularly in the high-mortality coun-
was broken, and the new nations began to trade tries, and the rate at which improvement occurred
openly with the industrial nations, particularly En- became essentially the same among all of them.
gland. Moreover, relative social stability character- Eduardo Arriaga and Kingsley Davis (1969) attrib-
ized most of the new nations during the nineteenth ute this to the widespread availability of public
century. "In sum, in Latin America the colonial heri- health programs that were imported from the indus-
tages reinforced by external and internal factors pro- trial nations beginning at about this time or some-
duced economic growth without appreciable socio- what earlier. This interpretation is supported by the
political change during the nineteenth century" observation that among Latin American nations
(Stein and Stein 1970). Thus, political and social with the lowest crude mortality rates at the turn of
stability and economic improvements - still within the twentieth century were Cuba and Panama, both
a neocolonial context characterized by an illiterate places in which the U.S. government had important
and servile labor force working on plantations and interests and in which major public health activities
haciendas producing raw materials for export- had been established (Kunitz 1986).

Thus, crisis mortality seems to have been reduced to public health and medical measures than the infec-
by the development of relatively stable societies with tious diseases (Arriaga 1981).
a slowly improving standard of living. But because It appears that what differentiates the contempo-
living conditions did not improve dramatically due to rary mortality experience of most Latin American
the neocolonial structure of most of these nations, nations is mortality rates among infants and young
mortality rates remained high. Dramatic improve- children rather than rates and patterns at older
ments began to occur in the twentieth century when ages. That is to say, mortality at all ages beyond
public health measures were introduced. These mea- about age 5 is due primarily to violence, accidents,
sures were aimed primarily at controlling the vectors and noninfectious diseases such as cancers and car-
of the most lethal and most prevalent infectious dis- diovascular diseases. It is the magnitude of the con-
eases, most notably perhaps malaria and yellow fever tribution of infectious diseases to deaths among chil-
(Mandle 1970; Soper 1970; Giglioli 1972), and were dren during the first 5 years of life that accounts for
not especially concerned with changing either the most of the international differences, and these rates
living conditions or the socioeconomic status of the are highest in the poorest countries. The explana-
bulk of the population. Thus, up to a point, technical tion that has been offered for these observations by
interventions could play the same role in reducing the United Nations (1982) is as follows:
mortality that economic and social development
played in western Europe and North America. The The departure of Latin American countries from the Euro-
question remains, where is that point? In other pean experience is related to a disequilibrium between
words, at what point can technical interventions no improvements in socio-economic conditions and health in-
longer take the place of socioeconomic development? terventions. While the latter may have a significant influ-
ence on adult mortality in the complete absence of the
Mortality continued to decline after World War II, former, the connexions between one and the other are
although to the present there has been a strong more subtle at the beginning of life. The longer the popula-
positive association between life expectancy and per tion is exposed to health interventions in the absence or
capita gross national product, along with adult liter- under conditions of precarious improvements in standards
acy, and an inverse relationship with the proportion of living the greater will be the disparity between child
of the labor force involved in agriculture. These eco- and adult mortality.
logical data as well as individual-level studies
(Kunitz 1986) suggest that in much of Latin Amer- This is so, it is argued by some, because neither
ica, the relationships persist between agricultural therapy (including oral rehydration) nor public
production for the international market, low levels health measures are likely to have a profound im-
of economic development, and high mortality. pact on infant and child mortality caused by the
Between 1950-5 and 1980-5 there were substan- interaction of malnutrition, pneumonia, and diar-
tial increases in life expectancy in most Latin Ameri- rhea in the absence of significant economic develop-
can nations, the rate of improvement being inversely ment. Others disagree, claiming that, rather than
associated with the life expectancy in 1950-5, which economic development, relatively simple interven-
is to say, the greater the life expectancy at the begin- tions such as equitable distribution of food, in-
ning of the period, the less was the proportionate creased literacy, and a few simple primary health
increase over the following 30 years (PAHO 1986). care measures are all that are required (Halstead,
The reason for this seems to be that populations with Walsh, and "Warren 1985). How easily achieved even
greater life expectancy to begin with were those in such "minor" measures are is a question that will
the economically more developed nations, in which a undoubtedly engender debate.
relatively large proportion of deaths were due to In either case, to the degree that reductions in
noninfectious diseases. Low life expectancy was asso- infant and child mortality are dependent on in-
ciated with high death rates, particularly at young creased spending for health and social services, as
ages, for those infectious diseases most responsive to well as on improving standards of living, the current
public health interventions. Thus, the diminution in economic crisis and international indebtedness may
the rate at which life expectancy has improved over make such improvements difficult to achieve. The
the past two decades has been associated with a shift evidence for an association between international in-
in the proportionate contribution to mortality of infec- debtedness and a diminution in the rate of improve-
tious and noninfectious diseases. Noninfectious dis- ment of life expectancy has been suggestive but not
eases are accounting for an increasing share of mor- overwhelmingly persuasive, however, largely be-
tality, and they have continued to be less responsive cause changes in domestic policies may mitigate the

worst effects of the economic crisis, at least in the dence now exists that mortality rates increased in
short term (Musgrove 1987). the course of the first half of the nineteenth century
Thus, there are two observations about contempo- (Meindl and Swedlund 1977; Kunitz 1984; Fogel
rary mortality changes in Latin America that, 1986). This coincided with the first great wave of
though not necessarily at odds with each other, place Irish immigration to the United States, and it is
emphasis on different elements of the process. One likely that the new settlers were poorer than their
emphasizes that continuing improvements in life ex- predecessors, lived in more squalid circumstances,
pectancy will result from continuing socioeconomic and spread new diseases to the rest of the population
improvements, which will have their most profound while suffering disproportionately from diseases
impact on the health of infants and children. The themselves. Nonetheless, in the North at least, mor-
other suggests that the pattern of causes of death tality rates remained remarkably low.
now reflects the overwhelming significance of Though mortality crises seem not to have been
human-made and noninfectious conditions among frequent in New England during the colonial period,
adults and that behavioral change at the individual regular epidemics of measles and smallpox did
level is likely to contribute most to further signifi- sweep the population. They seem to have diminished
cant declines in the future (Litvak et al. 1987). by the end of the period as both diseases increasingly
afflicted children, a sign that the population was
North America becoming sufficiently large to convert the diseases
The indigenous peoples of North America suffered as into endemic diseases (Kunitz 1984). In general, how-
catastrophic a population decline as did those in ever, the curve of mortality from year to year re-
what became Latin America. As already suggested, tained the jagged, saw-toothed shape characteristic
the North American Indians did not live in the same of the presence of epidemics (Omran 1975), although
sort of extensive agricultural societies as existed to these were never of sufficient magnitude or fre-
the south, nor did the new settlers come from a quency to keep populations from growing.
society like those of the Iberian Peninsula. Settle- Mortality began to decline after the Civil War,
ment patterns therefore tended to differ, with though whether this occurred in the 1870s or 1880s
family-owned and -operated farms predominating in is still a matter of disagreement (Kunitz 1984). Rob-
most of the region except the southeast. ert Higgs (1973) has estimated that the crude mortal-
Endemic diseases such as dysentery and malaria, ity rate declined from between 23 and 29 per 1,000
and epidemic diseases such as measles, smallpox, in the 1870s to 15 to 17 per 1,000 in the 1910s in
and yellow fever, were prevalent throughout the colo- urban areas; and from 21 to 23 per 1,000 to 14 to 15
nial period, but their severity seems to have differed per 1,000 in rural areas over the same period. These
substantially from North to South. Life expectancy rates are roughly comparable to those observed
was lower in Maryland than in New England in the among Catholics in Canada in the 1860s: 20.9 per
seventeenth century, for example, and crude mortal- 1,000 (Kalbach and McVey 1971). Among the most
ity rates were higher and epidemic diseases more important of the identifiable syndromes and dis-
severe in the South than the North throughout the eases were the pneumonia-diarrhea complex of in-
eighteenth and nineteenth centuries. fancy and childhood and tuberculosis. Both afflicted
In the eighteenth century, crude death rates in Amerindians, blacks, and immigrants more than
New England ranged from 6 to 20 per 1,000 popula- native-born whites, and both declined in the late
tion, depending on the location of a given commu- nineteenth and twentieth centuries.
nity as well as its age structure (Meindl and Yet even at their zenith in the middle decades of
Swedlund 1977; Dobson 1987). In French Canada the nineteenth century, mortality rates in North
during the eighteenth century, the crude mortality America were low compared with the rates in most
rate varied from 23 to 39 per 1,000, again probably of Latin America half a century later, with the excep-
depending on the changing age structure of the popu- tions noted previously: Uruguay and Argentina,
lation (Henripen 1954). with no indigenous Indian populations and a high
In the early nineteenth century, crude mortality proportion of European settlers, and Cuba and Pan-
rates varied widely as well. In northern U.S. cities ama, which both benefited and suffered from the
they tended to be in the range of 18 to 25 per 1,000, presence of the U.S. army (Sanchez-Albornoz 1974).
increasing as one moved south to 80 or 90 per 1,000 The significance of the decline in mortality from
in such cities as Savannah and New Orleans (Dob- midcentury onward is enhanced by the fact that
son 1987). Though there is some disagreement, evi- these were the very years during which masses of

immigrants from poverty-stricken regions of eastern on mortality (Omran 1977). At that time, however,
and southern Europe flocked to the United States first sulfonamides and then antibiotics were intro-
and Canada. Although, in general, immigrants had duced. The result was a small but measurable impact
higher mortality rates than native-born people, they on mortality rates. In the last seven years of the pre-
tended to have lower mortality rates than were ob- chemotherapy era (1930-7) the age-adjusted mortal-
served in their countries of origin (Kunitz 1984). ity rate declined an average of 4.28 deaths per
The very low mortality observed during the colo- 100,000 population per year. From 1937 through
nial period is explicable in terms of the dispersed 1954, when antibiotics became widely available, the
nature of settlement and the fact, supported by data age-adjusted rate declined on average 19.4 deaths per
on heights, that the population tended to be well 100,000 population. From 1955 through 1968 the de-
nourished. With the exception of blacks brought as cline all but ceased, averaging 2.1 deaths per 100,000
slaves to work on plantations in the South, there population per year. At the time many people argued
was not a large servile class such as existed in much that the decline had ceased because infectious dis-
of Latin America. The increase in mortality that eases had ceased to be a significant cause of death,
seems to have occurred after the colonial period has and the noninfectious and human-made causes of
been attributed to the influx of a large and impover- death were refractory to any intervention. It will be
ished immigrant population living in unsanitary recalled that the same explanation was given for the
and rapidly growing cities. diminution in the mortality decline in Latin America.
What, then, explains the decline in mortality after Beginning in the late 1960s, however, the decline re-
the Civil War, when an even larger influx of immi- sumed. From 1968 to 1978 the average annual decline
grants every bit as poor as those who had preceded was 11.8 deaths per 100,000 population, and this de-
them flooded the cities? It seems likely that the cline has continued to persist (McDermott 1981).
sources of the change were the remarkable productiv- The decline in mortality since the late 1960s has
ity of the industrializing U.S. economy and the re- been accompanied by a shift to later and later ages
form movements that resulted in sanitary improve- at death, a pattern sufficiently unusual that some
ments in many cities, as well as in small towns and observers have claimed it represents a new and pre-
villages (Levison, Hastings and Harrison 1981). viously undescribed stage of epidemiological history
There were, of course, differences in the mortality (Olshansky and Ault 1986). The debates generated
rates of different cities. By the end of the nineteenth have been about several issues. First, what has
century, these were attributable largely to differ- caused the decline in mortality since the late 1960s:
ences in deaths of infants and young children caused medical care, changes in behavior, or environmental
by endemic conditions such as the pneumonia- changes? There is no doubt that early, widespread,
diarrhea complex. Variations in death rates among and vigorous treatment of hypertension has had a
cities were explainable by differences in socioeco- measurable impact on the prevalence of that condi-
nomic measures, except among southern cities, in tion. Presumably that is reflected in a decreasing
which the proportion of blacks living in extreme number of deaths from cardiovascular disease.
poverty was an important variable (Crimmins and There have also been changes in smoking patterns,
Condran 1983). the consumption of meat, and the degree to which
In the course of the eighteenth and nineteenth cen- people exercise.
turies, then, there was a shift from epidemics afflict- Second, is survival to older and older ages accompa-
ing people of all ages to endemic infectious diseases nied by improvements in morbidity and level of func-
afflicting primarily infants and children. The change tion? On one hand are those who argue that there is a
occurred earlier in the North than the South, al- finite life span of about 85 years; that more and more
though by the 1920s and 1930s, malaria was in de- people are living that long in a healthy state; and that
cline south of the Mason—Dixon line. In the course of they will then die of "natural causes" without linger-
the twentieth century, the pneumonia-diarrhea coming illnesses. This has been called the "rectangu-
plex continued to decline as economic conditions con- larization" of the mortality and morbidity curves
tinued to improve, literacy increased, and public (Fries and Crapo 1981). On the other hand are those
health measures were strengthened. By the 1930s tu- who argue that 85 does not seem to be the upper limit
berculosis and other infectious diseases caused fewer to the human life span; that the survival of more and
deaths than cardiovascular diseases and cancer. This more people to older and older ages will be accompa-
change was unrelated to medical therapy, for until nied by a disproportionate increase in disability and
the late 1930s such therapy had no discernible effect morbidity; and that the presence of lingering chronic

conditions will impose an enormous cost on the Curtin, Philip D. 1987. African health at home and
health care system (Schneider and Brody 1983). abroad. In The African exchange, ed. Kenneth F.
Finally, what causes of death have been responsi- Kiple, 110-39. Durham, N.C.
ble for most of the decline in mortality at older ages? Dobson, Mary J. 1987. From old England to New England:
Although cardiovascular conditions are generally im- Changing patterns of mortality, Research paper 38,
Oxford: Oxford University, School of Geography.
plicated, sorting out causes among chronically ill peo-
ple with multiple health problems is often difficult. Early, John D. 1982. The demographic structure and evolu-
tion of a peasant system: The Guatemalan population.
Gainesville, Fla.
Conclusions Fogel, R. W. 1986. Nutrition and the decline in mortality
Whether one is considering mortality in highly de- since 1700: Some preliminary findings. In Long-term
veloped or less developed countries, similar ques- factors in American economic growth, ed. S. L. Enger-
tions frequently emerge: To what degree have public man and R. E. Gallman, 439-555. Chicago.
health and therapeutic interventions made a differ- Fries, J. F., and L. M. Crapo. 1981. Vitality and aging. San
ence? To what degree has economic development Francisco.
been responsible for increasing life expectancy? And Giglioli, G. 1972. Changes in the pattern of mortality
following the eradication of hyperendemic malaria
to what degree are changes in individual behavior
from a highly susceptible community. Bulletin of the
important? World Health Organization 46: 181-202.
It is generally agreed that in the developed coun- Halstead, Scott B., Judith A. Walsh, and Kenneth S. War-
tries development itself has been responsible for ren. 1985. Good health at low cost. New York.
most of the change. In contrast, much of the improve- Henripen, J. 1954. La population canadienne au debut du
ment in mortality in less developed countries is said XVIIIe siecle. Paris.
to have been caused by imported public health mea- Higgs, Robert. 1973. Mortality in rural America, 1879-
sures, especially those that could be widely and in- 1920: Estimates and conjectures. Explorations in Eco-
expensively applied in the absence of fundamental nomic History 10: 177-95.
changes in the socioeconomic characteristics of the Kalbach, W. E., and W. W. McVey. 1971. The demographic
population itself. bases of Canadian society. Toronto.
More evident disagreement surrounds the question Kunitz, Stephen J. 1984. Mortality change in America,
1620-1920. Human Biology 56: 559-82.
of what is required to reduce mortality further in less
1986. Mortality since Malthus. In The state of popula-
developed countries: relatively modest technical as- tion theory, ed. D. Coleman and R. Schofield, 279-302.
sistance from abroad and a domestic policy of literacy Oxford.
and equitable food availability or major socioeco- 1987. Explanations and ideologies of mortality patterns.
nomic change. In developed countries, disagreement Population and Development Review 13: 379-408.
has to do with the degree to which individual behav- Lang, J. 1975. Conquest and commerce: Spain and En-
ioral changes, on one hand, and environmental gland in the Americas. New York.
changes, on the other, have been important, as well as Levison, C. H., D. W. Hastings, and J. N. Harrison. 1981.
what will be the future role of biomedical research The epidemiologic transition in a frontier t o w n -
and health care in addressing the health care prob- Manti, Utah: 1849-1977. American Journal of Physi-
lems of the very old. The questions are fraught with cal Anthropology 56: 83-93.
political implications and the answers are by no Litvak, J., et al. 1987. The growing noncommunicable
means obvious. disease burden, a challenge for the countries of the
Americas. PAHO Bulletin 2: 156-71.
Stephen J. Kunitz
Mandle, J. R. 1970. The decline of mortality in British
Guiana, 1911-1960. Demography 7: 301-15.
Bibliography McDermott, Walsh. 1981. Absence of indicators of the in-
Arriaga, Eduardo E. 1981. The deceleration of the decline fluence of its physicians on a society's health. Ameri-
of mortality in LDCs: The case of Latin America. can Journal of Medicine 70: 833-43.
IUSSP International Population Conference, Manila McEvedy, C , and R. Jones. 1978. Atlas of world population
1981. Liege. history. New York.
Arriaga, Eduardo E., and Kingsley Davis. 1969. The pat- McGovern-Bowen, C. G. 1983. Mortality and crisis mortal-
tern of mortality change in Latin America. Demogra- ity in eighteenth century Mexico: The case of Patz-
phy 6: 223-42. cuaro, Michoacan. Syracuse, N.Y.
Crimmins, Eileen M., and Gretchan A. Condran. 1983. Meindl, Richard S., and Alan C. Swedlund. 1977. Secular
Mortality variation in U.S. cities in 1900. Social Sci- trends in mortality in the Connecticut valley, 1700—
ence History 7: 31-59. 1850. Human Biology 49: 389-414.

Musgrove, P. 1987. The economic crisis and its impact on the population lived in the countryside at a sub-
health and health care in Latin America and the sistence level and often at the mercy of nomadic dep-
Caribbean. International Journal of Health Services redations. The medical works have the serious dis-
17: 411-41. advantage of being largely nonclinical and highly
Olshansky, S. J., and A. B. Ault. 1986. The fourth stage of derivative of classical medical texts, and the anec-
the epidemiologic transition: The age of delayed de- dotes of renowned physicians are frequently apocry-
generative diseases. Milbank Memorial Fund Quar- phal. Yet major features of a "pathological tableau"
terly 64: 355-91.
do emerge, in which illness is inextricably tied to
Omran, Abdel R. 1975. The epidemiologic transition in
North Carolina during the last 50 to 90 years: I. The
poverty as both cause and effect. Blindness is con-
mortality transition. North Carolina Medical Journal spicuous, particularly in Egypt; the result of a num-
36: 23-8. ber of diseases, blindness seems to have afflicted a
1977. A century of epidemiologic transition in the large percentage of the population, and the blind
United States. Preventive Medicine 6: 30—51. were traditionally employed as Koran reciters in
PAHO. 1986. Health conditions in the Americas, 1981- mosques. Deafness was often congenital, and mut-
1984, Vol. 1, Scientific Publication No. 500. Washing- ism was associated with nervous disorders. Paraly-
ton, D.C. sis, epilepsy, and mental disorders are frequently
Sanchez-Albornoz, N. 1974. The population ofLatin Amer- described in the medical and nonmedical texts,
ica: A history. Berkeley and Los Angeles. which include surviving magical incantations and
Schneider, E., and J. Brody. 1983. Aging, natural death, prayers directed against demonic possession.
and the compression of morbidity: Another view. New
England Journal of Medicine 309: 854—6. Among internal maladies, digestive and excretory
Soper, Fred L. 1970. Building the health bridge. Blooming- complaints are commonly referred to; the descrip-
ton, Ind. tions suggest dysentery, internal parasites, typhoid-
Stein, S. J., and B. H. Stein. 1970. The colonial heritage of paratyphoid, and cancer. In Moghul India, cholera
Latin America. New York. and dysentery were clearly the major diseases from
United Nations. 1982. Levels and trends of mortality since the sixteenth century; Asiatic cholera does not ap-
1950. New York. pear to have afflicted the Middle East until the early
nineteenth century. Schistosomiasis (bilharzia) has
been present in Egypt since pharaonic times, but it
attracted no special interest in the medieval period.
Dropsy and elephantiasis are often mentioned in the
medical texts. Along with these conditions are obser-
V.ll vations of muscular problems, fatigue, and general
Diseases of the Islamic World malaise; the last-named might be attributed to ma-
laria, but its endemic and chronic forms were not
always recognized as a specific illness and were ac-
The advent of Islamic culture is well defined by the cepted as a natural state of health.
life of the founder of Islam, Muhammad (c. 570 to Some of the most common complaints were derma-
632). Shortly after his death, Muslim Arabs began a tological disorders, which are particularly difficult
series of dramatic conquests of the Middle East and to distinguish in the historical sources but appear to
North Africa, so that by A.D. 750 their hegemony have aroused considerable apprehension. Skin ul-
stretched from Andalusia (southern Spain) to the ceration, infections, and bleeding disorders appear
Sind (modern Pakistan). Islam was gradually estab- to have been due to nutritional deficiencies. There is
lished as the predominant religion in these areas, also some evidence of an endemic, nonvenereal form
and Arabic became the preeminent language in of syphilis in the rural population. More certain are
most of them. In the later Middle Ages, Islam spread the existence and recognition of smallpox and mea-
appreciably in sub-Saharan Africa, Turkey, eastern sles. In the tenth century, Rhazes (al-Razi), who was
Europe, the Indian subcontinent, and Southeast atypical of Muslim medical writers in giving de-
Asia; the only areas in which it retreated were the tailed clinical descriptions of diseases, was the first
Iberian Peninsula and eastern Europe. to provide a complete description of the symptoms of
Most of our information about disease has been both diseases and their treatment.
derived from literary sources, including Muslim ha- Plague (t&'un), leprosy, and syphilis are given spe-
giography and medical texts. The former are biased cial attention here. They seriously endangered per-
toward urban conditions, although the majority of sonal and public life, and consequently illustrate

V.ll. Islamic World 335
well Muslim cultural responses to life-threatening cycle of plague recurrences, but the reappearances
diseases. These three diseases were also generally in the Middle East (roughly about every nine years)
distinguishable in the past because of their distinc- were far more damaging because of the nature of the
tive symptoms and, therefore, are amenable to his- epidemics and their persistence. In the Near East,
torical investigation. recurrences until the end of the fifteenth century
included pneumonic plague (the form of plague that
Plague is most infectious and almost always fatal) as well as
There have been three major plague pandemics in the other two forms, bubonic and septicemic; all
recorded history: the plague of Justinian in the mid- three forms had been present in the Black Death.
sixth century, the Black Death in the mid-fourteenth The result of these plague recurrences was clearly a
century, and the Bombay plague in the late nine- sustained decline in population in the late four-
teenth century. Apart from the high mortality rates teenth andfifteenthcenturies. This decrease in popu-
and the social dislocation caused by these pan- lation was the essential phenomenon of the social
demics, each initiated a long series of plague epidem- and economic life of Egypt and Syria in the later
ics with significant cumulative effects. Middle Ages.
Before the Arab conquests in the seventh century, There is little evidence for pneumonic plague in
plague had recurred cyclically in the Near East fol- Europe after the Black Death, except in isolated Rus-
lowing the plague of Justinian, but it apparently had sian epidemics. The recurrent epidemics in the Near
little effect on the Arabian Peninsula, where environ- East were frequent and lasted until the end of the
mental conditions for plague were unfavorable. In nineteenth century, whereas epidemics of plague dis-
638-9, however, a plague epidemic struck the Arab appeared from most parts of Europe in the seven-
army after its conquest of Syria and it spread to Iraq; teenth century. Generally, the Middle East was at the
the disease killed many soldiers of the conquering crossroads of a number of endemic foci of plague,
army as well as the native population. During the which accounts for the numerous and seemingly cha-
Umayyad caliphate (661-749), plague reappeared a otic occurrences of the disease since the Black Death.
number of times in Syria, Iraq, Egypt, and North By land and sea, the movements of men and their
Africa. Inexplicably, however, the disease disap- cargoes promiscuously carried the disease over the
peared after 749 and did not reappear again until entire region, giving the appearance of endemicity
913, when it struck Baghdad. There were occasional throughout the Middle East. The endemic foci, how-
outbreaks of "pestilence" until the fourteenth cen- ever, that were the generators of recurrent plague
tury, but they cannot be clearly identified as plague before the twentieth century in the Middle East ap-
because of the imprecision of the Arabic sources and pear to have been the following: central Asia, western
the lack of any distinct epidemic pattern. Arabia (Assir), western Asia with its center in
In 1347 plague dramatically reappeared in the Kurdistan, central Africa, and northwestern India.
Middle East, being carried overland from central Plague was a well-recognized disease in Muslim
Asia to the Crimea in 1346. From the Black Sea society after its first appearances in early Islamic
region, it was transported by Italian merchants to history. Drawing on classical Greek medical works,
Constantinople and from there to the major Mediter- physicians adequately described the disease, and al-
ranean ports. Egypt was infected by the autumn of though it had not been discussed by Hippocrates and
1347 and Syria by the following spring. In addition, Galen, they interpreted it according to humoral
the plague spread inland; the central Middle East theory, attributing it to a pestilential miasma. Not
may have been infected from southern Russia as until the Black Death, however, do we have rela-
well. There is, incidentally, no evidence for the tively accurate medical observations of plague and
theory that the pandemic was transmitted from In- historically reliable accounts in the Arabic sources,
dia via the Persian Gulf and the Red Sea to the which are primarily plague treatises and chronicles.
Middle East and Mediterranean littoral. In 1348-9 Three of the treatises at the time of the Black
plague attacked Arabia for the first time and in- Death in Andalusia were mainly medical works.
fected Mecca. This pandemic was the same one that Comparable medical tracts devoted to plague do not
struck medieval Europe and is known familiarly as seem to have been written in the Middle East, but it
the "Black Death." From all indications, the effects was discussed in most of the standard medical
of the Black Death in Muslim lands were as devastat- compendia written both before and after the Black
ing as they were in Europe. Death. Following the Black Death, Muslim scholars
In both regions the Black Death also established a in the Middle East composed treatises of a largely

legal nature that interpreted the disease according Muslim world. The subject of plague in that world
to the pious traditions of the Prophet, instructed the alone inspired a large European literature, espe-
reader on proper conduct during an epidemic, and cially among physicians, who gave conflicting inter-
gave some peripheral medical advice. In addition, pretations and advocated conflicting prophylaxes.
these works usually ended with a chronology of By and large, this literature is surprisingly uninfor-
plague occurrences from early Islam until the mative despite some interesting accounts, such as
writer's own time. These treatises virtually form a those of the English physicians Alexander Russell
genre of religiolegal literature, inspired by the con- and his brother Patrick Russell on plague in Aleppo
stant reappearances of plague from the time of the in the mid-eighteenth century.
Black Death until the end of the nineteenth century. The immediate and long-term consequences of
The treatises are obviously important for their plague epidemics are difficult to judge, but in the
chronicling of plague epidemics but also for the evi- cities of Egypt and Syria at the time of the Black
dence they provide of an ongoing concern of a reli- Death and later plague recurrences, no serious break-
gious elite that was split on the issue of the religious down of urban life was noted, although there were
tenets regarding plague, some arguing for them and certainly disruptions in food supplies. The organiza-
some against them. The tenets in question were the tion of large processions, funerals, and burials would
following: Plague is a mercy and a source of martyr- suggest the maintenance, if not a heightening, of
dom for the faithful Muslim and a punishment for the public order. There is evidence that, despite religious
infidel; a Muslim should neither enter nor flee a proscription, people did flee from infected regions -
plague-stricken region; and plague is noncontagious. both to and from the cities - which doubtless aggra-
There must have been serious doubts about the vated the situation, because they would often have
soundness of these precepts. The treatises are repeti- carried the disease to unaffected areas while expos-
tive concerning this conflict between martyrdom ing themselves to other illnesses and to starvation.
and health, although they often supply original ob- In the Egyptian countryside, by contrast, consider-
servations of the symptomatology of contemporary able evidence exists of depopulation through either
plague epidemics. In one respect, the series of tracts death or flight from the land, and thus the most
show an increasing interest in pseudomedical or disruptive, long-term effect of plague epidemics ap-
magical methods of plague prevention and treat- pears to have been the changes that were wrought in
ment. It would be hazardous, however, to conclude rural areas. Reduced cultivation led to a decrease in
that this is evidence for the decline of medical prac- the amount of food available for the cities, which
tice in the Islamic world, because the discussion of depended on surplus rural production, as well as in
magical practices may indicate merely a greater rec- tax revenues. The first consequence was less impor-
ognition by legal scholars of common folk practices, tant than the second because (based on evidence sug-
which had always existed side by side with profes- gesting that there was no long-term price inflation
sional medical practices. In any event, the treatises for agricultural products in Egypt in the aftermath of
explain to a great extent the Muslim attitudes to- the Black Death) reduced agricultural production
ward plague. was apparently feeding a diminishing population.
The historical chronicles are relatively abundant The government's attempts to maintain tax reve-
for the Black Death and the recurrences of plague nues, however, were disastrous because a larger
during the latter half of the Mamluk period in Egypt share of taxes was imposed on a smaller rural popula-
and Syria (1250—1517), although we have only one tion, which in turn encouraged peasant indebtedness
complete eyewitness account of the Black Death it- andflightto the cities. Symptomatic of the social and
self. These chronicles diminish sharply in quality economic plight caused by plague epidemics in Egypt
and quantity in the last half of the fifteenth century, was the virtual disappearance of Christian monasti-
and we are no longer supplied with the kind of spe- cism, which had begun in Egypt and thrived there for
cific descriptions of epidemics that enable us to deter- more than a millennium.
mine with a fair degree of accuracy the duration and
nature of the various epidemics. Leprosy
From the late fifteenth century, the Arabic sources Unlike plague, leprosy (Hansen's disease) was often
can be supplemented by information from European a disfiguring, lifelong disease, and it posed very dif-
observers, including merchants and pilgrims, physi- ferent social problems. Leprosy appears to have ex-
cians and diplomats, whose reports increase in num- isted in the Middle East from the early Christian
ber with an increasing Western involvement in the Era. The earliest proof of the presence of leprosy in

the Middle East has been found in the bone lesions of Atypically, leprosy was believed by some to be a
two skeletons from Aswan (Egypt) that date from punishment by God for immorality and thus was
about A.D. 500. Therefore, there can be little doubt sometimes invoked as a curse for immoral behavior.
that genuine leprosy was present from the early But there were also traditions of the Prophet that
Islamic period and that physicians had sufficient recommended supplication to God for relief from lep-
opportunity to observe it. Practically every Arabic rosy, for the matter should not be left entirely to fate.
medical writer discussed leprosy to some degree. The Medically, both traditions seem to express an im-
pathology and therapeutics of the disease in these plicit belief in contagion, which is incompatible with
accounts are largely consistent with earlier Greek the predominant Muslim view of noncontagion. The
medical texts. The Arabic medical works said that pious legend of the Prophet advising flight from the
leprosy was both contagious and hereditary; yet it leper is, in fact, preceded by a complete denial of
was not viewed as fiercely contagious, and those contagion in the canonical collection of such tradi-
sources lack any element of moral censorship of the tions by al-Bukhari, which was made in the ninth
diseased. Moreover, the medical texts did not recom- century. Certainly those who argued in favor of
mend flight from lepers or their isolation from the noncontagion would have been able to make a good
community. case, because leprosy is only moderately contagious
The Arabic terminology for leprosy was created on and some people are not susceptible to it at all.
the basis of its symptomatology. Yet aside from the The legal status of the leper was directly related to
distinctive signs of advanced lepromatous leprosy, the pious traditions. Leprosy is not discussed in the
these terms were not restricted to leprosy and were Arabic legal texts as a separate subject, but it is
applied to other skin disorders as well. No clinical treated as a disability within such broad areas as
case descriptions of leprosy have survived in the marriage, divorce, inheritance, guardianship, and
medieval Arabic medical literature that might clar- interdiction of one's legal capacity. Because leprosy
ify the terminology. (The best clinical description in was considered a moral illness, the leper was limited
the medieval Near East is, curiously, the early- in his legal rights and obligations - along with mi-
thirteenth-century description by William, bishop of nors, the bankrupt, the insane, and slaves. In fact,
Tyre, of the condition of Baldwin IV, king of the the leper's status seems to have been particularly
Latin Kingdom of Jerusalem. This description con- close to that of the insane in legal matters, espe-
tains incontrovertible evidence of the anesthetic cially with regard to marriage and divorce: A mar-
symptoms of leprosy.) The difficulty is certainly due riage could be dissolved by either person because of
to the numerous forms that leprosy can take, particu- the disease. In Maliki law, a man in an advanced
larly in its early stages, and its mimicry of other state of leprosy was to be prevented from cohabiting
sKin diseases. with his slave wives and even more so with his free
The Arabs in pre-Islamic Arabia were afflicted by wives. In addition, whereas Maliki law allowed an
leprosy, along with a large number of other communi- automatic guarantee of three days against any
cable diseases. Leprosy is mentioned by the famous "faults" in a slave, that guarantee was extended to
Arabic poets of the period. The Koran mentions in one year in the case of leprosy. Moreover, the develop-
two places the healing of lepers by Jesus. More im- ment of the disease could be cause for his or her
portant for Muslims were the pious traditions of the manumission.
Prophet concerning the disease, which were in con- The differing religiolegal traditions served as the
tradiction to the medical texts. For example, the best bases for various interpretations of leprosy, and un-
known of these traditions is the statement that a derlie a wide spectrum of behavior by and toward the
Muslim should flee from the leper as he would flee leper, from total freedom of action to segregation in
from the lion. Similarly, another familiar tradition leprosaria. The range of popular responses to the
asserts that a healthy person should not associate leper is reflected in the early Arabic literature that
with lepers for a prolonged period and should keep a deals with the disease and other skin irregularities.
spear's distance from them. The two traditions are The famous Arab prose writer al-Jahiz, in the ninth
prescriptions for social behavior and appear to deal century, collected poetry and narrative accounts on
with both moral and medical difficulties posed by this subject. One of his works is devoted to physical
the leper. The traditions may have strengthened the infirmities and personal idiosyncrasies. His objective
desire of those who wished to avoid individuals who was to show that they did not hinder an individual
were conspicuously afflicted by the disease because from being a fully active member of the Muslim com-
it was morally as well as physically offensive. munity or bar him from important offices. Al-Jahiz

maintained that such ailments were not social stig- many must have been genuinely leprous, it was not
mas but were what could be called signs of divine unusual for men and women to feign the disease by
blessing or favor. The afflicted were spiritually com- intentional disfigurement in order to receive public
pensated by God, and special merit was to be attached charity. Deception of the opposite kind was also com-
to their lives. He also cited numerous references to mon in the slave market, where (despite guarantees)
leprosy in early Arabic poetry and mentioned those a buyer had to be on his guard against the conceal-
poets who were themselves leprous. ment of leprous sores on the bodies of slaves. More-
Nonetheless, there are indications of discrimina- over, during the late Middle Ages, the reappear-
tion against lepers. According to a late-medieval ances of plague must have destroyed a large number
Egyptian handbook for urban market inspectors, of lepers because debility increased their vulnerabil-
they were not supposed to allow people suffering ity to other infections.
from leprosy to visit the baths. Lepers were also In the Islamic West, leprosaria were established
excluded from employment in endowment works. and special quarters were designated for lepers. The
Such discrimination shows that the theological pro- quarters seem generally to have been located out-
scription of contagion might have had very little side the walls of many Muslim cities, often in con-
practical effect. junction with leper cemeteries. In Anatolia the Otto-
Leprosy certainly existed throughout the Islamic mans built leper houses as well as hospitals. A leper
world in the medieval period, but there is no way of asylum was built at Edirne in the time of Murad II,
determining its extent. Individual cases of leprosy the first half of the fifteenth century, and functioned
are occasionally mentioned in the historical litera- for almost two centuries. In 1514 the sultan Selim I
ture. The most important political figure in early established a leprosarium near Istanbul and in 1530
Islam who was afflicted by leprosy was Abd al-Aziz Sulayman II built one in Scutari, and both survived
ibn Marwan, an early governor of Egypt who died in until modern times. Lepers and leprosaria were in-
704. It is reported that he suffered from "lion sick- creasingly noticed by Western travelers, and their
ness," that is, leprosy. He was given many medica- accounts add to our knowledge about the plight of
tions for the ailment, but they were ineffective. the diseased. There is, however, no reliable observa-
Therefore, his physicians advised him to move to tion of true leprosy by these travelers in the Middle
Hulwan because of its sulfurous springs, and he East during the medieval and early modern periods,
built his residence there. Hot springs were a popular except for the report of leprosy in Egypt by Prosper
treatment for skin disorders in the medieval period Alpin in the late sixteenth century. The disease
and especially for leprosy. It is known, for example, seems to have been as common in the countryside as
that the Jews commonly sought healing for leprosy in the cities, and leprosy, syphilis, and elephantiasis
in the hot springs and salubrious air of Tiberias. are all reported to have occurred frequently in Egyp-
Shortly after the time of Abd al-Aziz, the caliph al- tian villages in the nineteenth century.
Walid I conferred a number of benefits on the people
of Damascus, the capital, in 707. The chronicles say Syphilis
that "he awarded the lepers arid said: 'Do not beg Syphilis presents us with a new disease, or what was
from the people.' And he awarded every invalid a believed to be a new disease when it first appeared in
servant and every blind man a leader." As he did Muslim societies, beginning in the late fifteenth cen-
with the invalids and the blind, the caliph appar- tury. Syphilis and other European diseases were intro-
ently made provisions for the lepers. The passage duced into the Middle East in the early modern period
seems to imply that he had the lepers separated from by Europeans, who also brought their own methods of
the rest of the population. Al-Walid's unusual act is treatment. Western medicine was disseminated by
traditionally considered by Arab historians to be the missionaries and merchants, travelers, and consular
institution of the first hospital in Islam. One may doctors. Before the era of translating Western medi-
well imagine that the caliph created a hospice for cal textbooks into oriental languages, the extent of
the afflicted in the city, comparable to Byzantine the transmission of Western medicine can be gauged,
practice. The later well-known hospitals of the Ab- in some degree, by the recommendation by native
basid period appear to have treated lepers and those physicians of Western treatments for the new West-
with other chronic ailments in special quarters. ern diseases.
Still, lepers commonly begged in the streets of the In the early sixteenth century, whooping cough
medieval cities, despite the pious endowments on and syphilis were reported, for example, by the Per-
their behalf and laws against mendicancy. Though sian Baha ad-Dawla. In one of his works he de-

scribes, in considerable detail, "the Armenian sore" warmly for a week and eats proper and unsalted food, he
that had spread from Europe to Constantinople and recovers after suffering gangrene of the mouth, salivation,
Arabia. Reportedly, syphilis had appeared in 1498 and tumefaction of the throat. If he becomes cold, he will
in Azerbaijan, and then in Iraq and Persia. Because feel pain in the joints. The ointment should be used three
of some symptomatic similarities with smallpox, it times a week. It is a well-known treatment in the hospital
was known as "European pox" or "little fire." It was of Cairo. Sometimes one begins by applying the ointment
also confused with anthrax or ignis persicus. Baha to the extremities and the neck and only after a purge.
ad-Dawla observed the rash, sore throat, and neu- Interestingly, al-Antaki provides the entire mercury
ral involvement of the disease. He recommended treatment for syphilis in his textbook as it was prac-
purges, venesection, and appropriate foods and ticed in Europe until the eighteenth century.
drugs, and he referred to European physicians, The broader context in which al-Antaki worked is
whom he did not mention by name. He recom- presented by Prosper Alpin in his description of medi-
mended a salve known as the "European pox medical practices in sixteenth-century Egypt. His ac-
cine," which he believed could restore health if prop- count, first published in 1591, is surely one of the
erly employed. Baha ad-Dawla did not say what the earliest studies of non-European medicine, and Alpin
salve contained, but he mentioned a few lines later himself well represents the means whereby Western
that mercury could be given in an electuary. An- medicine most effectively reached Egypt. He was an
other of his recipes and one of the European physi- Italian physician-botanist; in 1580 he became physi-
cians also contained mercury. cian to the Venetian consul in Cairo, where he spent
According to Leo Africanus, who wrote in the first three and a half years. Alpin did not confine himself
half of the sixteenth century, syphilis was brought to to the closed European community in Cairo. He
North Africa by Jews driven out of Spain, and it sought the widest possible contacts with Egyptians of
spread rapidly among the Berber population. In Fez all classes and religions. He treated their illnesses in
"the first to be contaminated were regarded as lep- collaboration with Egyptian doctors, and profited
ers, driven from their homes, and obliged to live from the experience of these native physicians. Alpin
with the lepers." The first mention of the appearance watched them operate, observed their instruments,
of syphilis in Egypt was made by Ibn Iyas in his and talked at length with them since they shared the
contemporary chronicle of Egypt for the year 1497- same Galenic tradition; he often criticized their
8. Among the unhappy events of that year, an evil knowledge of Galen but admired their empirical
known as "the French pox had appeared among the knowledge, which he believed went back to ancient
people . . . the doctors were powerless in the face of Egyptian practice. He remarked particularly on the
this disease that had never appeared in Egypt before indigence and malnutrition of the poor and their
the beginning of this century; countless people died medications. The habits of the ordinary people and
of it." the women's remedies drew his attention, so that he
Naturally, the indigenous physicians took cogni- returned to Italy with a large number of recipes for
zance of the new disease, and it is discussed in the dishes, medicaments, clysters, and refreshments, in-
medical textbook of Dawud ibn Umar al-Antaki, cluding coffee. Alpin also observed the widespread
who wrote in the later sixteenth century and was and dangerous use of bloodletting as a panacea for all
perhaps the last great Arabic medical author in the ills, as well as the common resort to baths for their
Greek tradition. His textbook displays an intriguing therapeutic effects and the employment of numerous
mixture of hallowed Greco-Arabic medicine and the drugs and medications. These methods had been
first indications of exposure to European learning, adopted, according to Alpin, for the new Western dis-
even in matters as small as the Western names for eases, especially syphilis.
the months of the year. In the long term, the appearance of these new dis-
More important, al-Antaki gives the earliest medi- eases, in addition to periodic reappearances of
cal description of syphilis in Egypt in his chapter on plague, and the measures taken against these dis-
carbuncles. He says that syphilis was popularly eases by all the foreign European communities
called "the blessed" in Egypt as a way of avoiding a helped to diminish traditional Muslim opposition to
mental association with the disease and contamina- the notion of contagion. Thus, in the seventeenth
tion. As for treatment: century, Evliya Chelebi, a renowned Turkish trav-
eler, described the contagion of syphilis in Cairo quite
If one mixes mercury withfrankincense,resin, wax, and matter-of-factly. The seventeenth century also wit-
oil and uses it as an ointment and if the patient is covered nessed clear evidence of the new age of European

medicine, when Ibn Sallum, physician to the midcen- eval Islamic medicine: Ibn Ridwdn's treatise "On the
tury Ottoman sultan Mehmet IV, wrote his medical prevention of bodily ills in Egypt." Berkeley and Los
textbook. In this work Ibn Sallum not only described Angeles.
the new illnesses - for example, chlorosis, syphilis, Ebied, R. Y., ed. 1971. Bibliography of medieval Arabic
scurvy, and Polish plait (plica polonica) — but an alto- and Jewish medicine and allied sciences. London.
gether new system of medicine, namely the "chemical Elgood, C. 1951. A medical history of Persia and the East-
medicine of Paracelsus." Although the Paracelsian ern Caliphate. Cambridge.
1970. Safavid medical practice. London. The encyclope-
system was erroneous and Ibn Sallum's influence
dia of Islam. 1908—38. 1st edition. Leidon-London.
may have been slight, the work clearly marks the I960-. 2d edition. Leiden-London.
advent of European medicine in the Middle East. Gallagher, N. E. 1983. Medicine and power in Tunisia,
With the introduction of Western-style medical 1780-1900. Cambridge.
schools in Cairo and Istanbul in the second quarter of Goitein, S. D. 1967-83. A Mediterranean society, 4 vols.
the nineteenth century, the ascendancy of Western Berkeley and Los Angeles.
medicine was assured. All of this, however, was to the Guliamov, A. G. 1958. Consumption (pulmonary tuberculo-
detriment of many traditional values and native sis) in the "Canon of Medical Science" of Abu Ali Ibn
forms of healing. Sina [in Russian]. Meditssinskii Zhurnal Uzbekistana
1: 69-72.
Michael W. Dols
Hamameh, S. M. 1978a. Ibn al-'Ayni Zarbi and his defini-
tion of diseases and their diagnoses. Proceedings of the
Bibliography First International Symposium for the History of Ara-
Africanus, Leo. 1956. Description de I'Afrique, 2 vols., ed. bic Science 2: 305-23.
and trans. A. Epaulard. Paris. 1978b. Ar-Razi's independent treatise on gout. Physis,
Alpin, Prosper. 1980. La medecine des Egyptiens. 1581- Rivista Internationale di Storia della Scienza 20: 3 1 -
1584, trans. R. de Fenoyl. Cairo. 48.
al-Razi, Abu Bakr Muhammad Ibn Zakariya. 1939. A trea- Hau, F. R. 1975. Razis Gutachten iiber Rosenschnupfen.
tise on the smallpox and measles, trans. W. A. Green- Medizin Historisches Journal 10: 94—102.
hill. Reprinted in Medical classics, Vol. 4. Baltimore. Ibn Sina. 1983. Avicenna's tract on cardiac drugs and
Browne, E. G. 1962. Arabian medicine. Reprint, Cam- essays on Arab cardiotherapy, 2 vols., trans. H. M.
bridge. Said, ed. H. A. Hameed. New Delhi.
Conrad, L. 1.1982. Td'un and Wabd: Conceptions of plague Iskandar, A. Z. 1960. Rhazes on smallpox and measles.
and pestilence in early Islam. Journal of the Economic Hamdard Medical Digest 4: 29-32.
and Social History of the Orient 25: 268-307. Izzeddine, C. 1909. Le cholera et I'hygiene d la Mecque.
Dols, M. W. 1974a. Ibn al-Wardi's Risdlah al-naba' 'an al- Paris.
waba': A translation of a major source for the history Judaeus, Isaac. 1980. On fevers (The third discourse: On
of the black death in the Middle East. In Near Eastern consumption), ed. and trans. J. D. Latham and H. D.
numismatics, iconography, epigraphy and history: Isaccs. Arabic Technical and Scientific Texts No. 8.
Studies in honor of George C. Miles, ed. Dickran K. Cambridge.
Kouymjian, 443—55. Beirut. Klein-Franke, Felix. 1982. Vorlesungen iiber die Medizin
1974b. Plague in early Islamic history. Journal of the im Islam. In Sudhoffs Archiv, Supplement 23. Wies-
American Oriental Society 94: 371-83. baden.
1977. The black death in the Middle East. Princeton, Leiser, Gary, and M. W. Dols. 1987. Evliya Chelebi's de-
N.J. scription of medicine in seventeenth-century Egypt,
1979a. Leprosy in medieval Arabic medicine. Journal of part 1. Sudhoffs Archiv 71: 197-216.
the History ofMedicine and Allied Sciences 34:314-33. 1988. Evliya Chelebi's description of medicine in
1979b. The second plague pandemic and its recurrences seventeenth-century Egypt, part 2. Sudhoffs Archiv
in the Middle East: 1347-1894. Journal of the Eco- 72: 49-68.
nomic and Social History of the Orient 22: 162-89. Maimonides, Moses. 1963. Treatise on asthma, trans, by
1983. The leper in medieval Islamic society. Speculum S. Muntner, Vol. 1 of The medical writings of Moses
58: 891-916. Maimonides. Philadelphia.
1986. Malarya [malaria], in The encyclopaedia of Islam Meyerhof, Max. 1941. An early mention of sleeping sick-
5: 229-30. London. ness in Arabic chronicles. Journal of the Royal Egyp-
1987a. Insanity and its treatment in Islamic society. tian Medical Association 24: 284—6.
Medical History 31: 1-14. Meyerhof, Max, and M. Monnerot-Dumaine. 1942. Quel-
1987b. The origins of the Islamic hospital: Myth and ques maladies d'Europe dans une encyclopedie medi-
reality. Bulletin of the History of Medicine 61: 367-90. cale arabe du XVIIe siecle. Bulletin de I'Institut
Dols, M. W., and A. S. Gamal, eds. and trans. 1984. Medi- d'Egypte 24: 33-44.

1984. Studies in medieval Arabic medicine: Theory and phy of Meyerhof's numerous works on ophthalmol-
practice, ed. Penelope Johnstone. London. ogy]. Osiris 9: 6-32.
Panzac, Daniel. 1985. La Peste dans I'Empire Ottoman, Seidel, E. 1913. Die Lehre von der Kontagion bei den
1700-1850, Collection Turcica No. 5. Leuven. Arabern. Archiv fur Geschichte der Medizin 6: 81—93.
Pearson, J. D., ed. 1958-. Index Islamicus. Cambridge. Serjeant, R. B. 1965. Notes on the 'Frankish chancre'
Pringle, G. 1957. Oriental sore in Iraq: Historical and (syphilis) in Yemen, Egypt and Persia. Journal of Se-
epidemiological problems. Bulletin of Endemic Dis- mitic Studies 10: 241-52.
eases 2: 41-76. Spies, O. 1966. Zur geschichte der pocken in der
Qusta ibn Luqa. 1987. Abhandlung iiber die Ansteckung. arabischen literatur. Medizingeschichte Spektrum 7:
In Abhandlung fur die Kunde des Morgenlandes, Vol. 187-200.
48, ed. and trans. Harmut Fahndrich. Stuttgart. Theodorides, J. 1955. La Parasitologie et la zoologie dans
Rahman, Fazlur. 1987. Health and medicine in the Islamic Foeuvre d'Avenzoar. Revue d'Historie des Sciences et
tradition. New York. de Leurs Applications 8:137—45.
Raymond, Andre. 1973. Les grandes epidemies de peste au Thies, Hans-Jurgen. 1971. Der diabetestraktat 'Abd al-
Caire aux XVIIe et XVIIIe siecles. Bulletin d'Etudes Latlf al-BaghdadVs. Untersuchungen zur geschichte
Orientales 25: 203-10. des krankheitsbildes in der arabischen medizin. Bon-
Reddy, D. V. S. 1940. Medicine in India in the middle of ner Orientalistischen Studien, N.S., 21.
the XVI century. Bulletin of the History of Medicine Ullmann, Manfred. 1970. Die Medizin im Islam. In
8: 49-67. Handbuch der Orientalistik, ed. B. Spuler. Leiden.
Renaud, H. P. J. 1934. Les maladies pestilentielles dans 1978. Islamic medicine, Islamic Surveys no. 11. Edin-
l'orthodoxie islamique. Bulletin de I'Institut d'Hygiene burgh.
du Maroc 3: 5-16. Watson, A. M. 1983. Agricultural innovation in the early
Richter P. 1913. Uber die allgemeine dermatologie des 'Ali Islamic world: The diffusion of crops and farming
Ibn al-'Abbas (Haly Abbas) aus dem 10 jahrhundert techniques, 700-1100. Cambridge.
unserer zeit rechnung. Archiv fur Dermatologie und Yar-Shater, Ehsan, ed. 1985-. Encyclopedia Iranica. Lon-
Syphilis 118: 199-208. don.
Schacht, J. 1950. Max Meyerhof [Obituary with bibliogra-

PART VI
The History of Human Disease in Asia

VI. 1. Antiquity in China 345
writings of the second half of the second millennium
VI. 1 B.C.; (2) epigraphical (especially sphragistic) evi-
Diseases of Antiquity dence in the form of seals and other objects found in
tombs during the first millennium B.C.; and (3) texts
in China of the various classical writings ranging from the
Shu Ching and the Shih Ching not long after 1000
B.C.; to the first of the great dynastic histories, the
Only because of a great movement in China that has Shih Chi, completed in 90 B.C.; to the great medical
been going on for about 70 years have we been able classic, the Nei Ching, which took its present form
to review the records of diseases in ancient China probably about the first century B.C. This material
and publish them in a Western language. This move- provides, all told, a quite astonishing wealth of tech-
ment has been closely allied with a revaluation of nical terminology. Although its analysis is not yet
the practice of traditional Chinese medicine by those complete, it still provides afirmbasis for our conclu-
who have taken a special training in it. Many valu- sions as to the diseases known during this period.
able works have been written in Chinese on the The imprecise definitions of some of the terms pres-
history of Chinese medical art and science. So far, ent perhaps the greatest difficulty, but in fact they
however, all this material has remained practically are much clearer than one might anticipate before
unassimilated by sinologists and other Western stu- undertaking such an investigation. Moreover, the
dents of Chinese culture. Thus, for example, most of great continuity of Chinese civilization should not
the dictionary definitions in common use are quite be ignored. Almost unique among the cultures,
out of date. Among the works that we have used in China possesses continuous traditions of interpreta-
preparing the present contribution is the brilliant tion in this field, directly linking the "sorcerer-
monograph of Yii Yiin-hsiu on ancient nosology, or physicians" of the second millennium B.C. with the
what might be called pathognostics - the recognition profoundly learned and enlightened medical expo-
and classification of individual disease entities. West- nents of the Ming dynasty (sixteenth century A.D.).
ern historians of medicine should be aware that the It would be possible to organize our material in
treatise of Wu Lien-te and Wang Chi-min (K. C. several ways: purely chronologically, listing texts
Wong and Wu Lien-teh 1932) on Chinese medicine and their content; or purely nosologically, listing
(nearly always the only one they know) may be de- diseases and the terminology relating to them. Both
scribed as the very small exposed piece of an iceberg, of these approaches would, however, produce ex-
90 percent of which is "below the surface" (i.e., in the tremely dull reading, and therefore we shall adopt a
Chinese language and therefore inaccessible to most combination of approaches. Moreover, we can pro-
historians of medicine). Since about the mid-1950s, vide only a limited number of examples. We propose
the study of Chinese medicine has been revitalized; to bring the story down to the end of the first century
a great number of rare medical books from ancient B.C., but in so doing we intend to utilize the Nei
and medieval times have been republished in photo- Ching only in part; we cannot mention all the dis-
graphic form, and some ancient texts have been re- eases that are described in that fundamental medi-
produced in the modern colloquial (pai-hua) style, cal classic. It will be convenient also to consider
"translated" as it were from the ancient (ku-wen) diseases in the light of the macrocosm-microcosm
style, either abridged or complete. For this reason, theories current in early Chinese medicine. The phy-
we feel no need to apologize for departing from sicians of the Chou period, which lasted most of the
former translations and identifications. Limitations first millennium B.C., were extremely conscious of
of space in the present work will prevent us from the relation of diseases to geography, to the prevail-
providing extensive documentation for our state- ing climate, and to the seasonal changes of the year.
ments, but the reader can consult our more expan- They therefore very markedly shared the Hippo-
sive work, Science and Civilisation in China, Volume cratic conception of "airs, waters and places."
6 (Needham et al. 1954).
Oracle-Bone and Bronze Inscriptions

Overview The oldest form of Chinese writing is that found on
There are three sources of information concerning the scapulae and tortoise-shells used for divination
diseases prevalent among the people of ancient in the Shang Kingdom (fifteenth to eleventh centu-
China during the 1V2 millennia before the beginning ries B.C.). From this was derived the scripts found
of the present era: These include (1) the oracle-bone on bronze vessels recovered from tombs of the Chou

346 VI. Human Disease in Asia
shows again a man lying on a bed, but the spots are
actually indicated (Figure VI.l.lc). Li1 also means
an epidemic fever, and in this case the oracle-bone
form seems to show a scorpion (for that is the mean-
ing of the phonetic in this case) occupying the bed
31? X f alone, with little remaining of the patient; or, per-
haps the maggotlike object is the patient, and the
scorpion is represented by the little numeral " 1 "
(Figure Vl.l.ld). Another term for epidemic disease,
a i, combines the disease radical with a phonetic that
X
is a pictogram of a hand holding a stick (Figure
Vl.l.le). This, however, has been found only on
bronzes. The last of these oracle-bone terms is the
word nio, which combines the disease radical with
pictograms for tiger and hand; the drawing in Fig-
ure Vl.l.lf is complex, and the significance of it is
not clear. In later ages, this word came to be confined
to fevers of malarial type, but in ancient times it was
used to indicate all kinds of fevers.
Among the bronze forms we find the word pi (Fig-
ure Vl.l.lg), which means "thin scabs" or "lesions on
Figure VI. 1.1. Oracle-bone and bronze terms specifying
disease entities: (a) ni — sickness (radical); a bed. (b) the head," suggesting eczema and lichen or alopecia
chi — epidemic disease; a man with arrows of disease at- or psoriasis, for which there were other words used
tacking him, or lying on a bed. (c) chieh - "itching later on. On the bronze we also find yuan (Figure
scabies-like epidemic"; a man with spots of rash lying on Vl.l.lh), which signified arthritic pains in the
1
a bed. (d) li — epidemic fever; man, bed, and scorpion, (e) joints.
i - epidemic fever; bed, and hand holding stick; the pa- The medical content of the oracle bones is, of
tient belabored by the disease, (f) nio - fever (later more course, far from exhausted by mere consideration of
specifically malarial); man, bed, and spots, with other the few technical terms that had been developed at
pictographic components of unknown significance, (g) that early time. Many inscriptions show that ill-
pi - thin scabs or lesions on the head; bed, and unknown
pictographic components, (h) yuan - arthritic pains; bed,
nesses were defined without relying on technical
and other pictographic components of unclear signifi- terms. From these we know that there were diseases
cance, (i) ku — poison or disease; insects or worms within of the special sense-organs such as eyes and ears;
a vessel. (From Yii 1953.) dental problems; speech defects; abdominal diseases;
dysuria; diseases of the extremities, including
beriberilike syndromes; and pregnancy abnormali-
period (first eight centuries of the first millennium ties and diseases of women and children. We also
B.C.). Chinese writing was stylized into approxi- know of epidemic diseases coming at a particular
mately its modern form after the first unification of time of year and causing death. All these they men-
the empire under the Chhin dynasty in the third tion without recourse to a technical phraseology.
century B.C. There is one other oracle-bone term of great interest,
The radical ni, under which the great majority of however, and that is the poison or disease ku (Figure
diseases were later classified, is revealed by the ora- Vl.l.li): This pictogram indicates insects or worms
cle bones to have been the pictogram of a bed (Figure within a vessel. Although we know that in later ages
Vl.l.la). Of the 20 or more medical terms that are ku did indicate particular poisons prepared artifi-
found on bronze inscriptions, some four of these are cially by humans, there is also reason to think that
clearly recognizable already on the oracle bones. For it referred to a particular disease. This has been
example, chi, which subsequently invariably meant identified by Fan Hsing-chun and others as schistoso-
"epidemic disease in general," shows a man alone or miasis, partly because the term ku occurs so often in
1 2
lying on a bed with the arrow of the disease shooting combination with the term chang (ku chang, ku
into him (Figure Vl.l.lb). The word chieh, in great chang) and hence indicates without any doubt
use afterward to designate an "itching scabieslike edematous conditions of various kinds - in particu-
epidemic" (i.e., infectious fever preceded by rash), lar, ascites. And the Nei Ching describes similar

syndromes; certainly in schistosomiasis the liver coming in winter; although from early times this
and spleen become enlarged, and ascites occurs meant scabies, it must be translated here as an "itch-
when the disease is chronic. ing, scabieslike epidemic." Under any winter condi-
tions, exanthematic typhus is perhaps to be sus-
Seals of Excavated Tombs pected, but the descriptions of chieh also sometimes
Another valuable source of information about the include convulsions, with arched back, and speech-
diseases of the late Chou period (the Warring States less "lockjaw," so that the word sometimes may have
period, i.e., the fifth to third centuries B.C.) is the been used for tetanus. We shall suggest immediately
seals that have been discovered in excavated tombs. below a more satisfactory meaning for it.
These are important also because they demonstrate The Yiieh Ling text has other interesting features:
an early development of specialization in medical It says, for example, that if cool spring weather
practice. Thus, for example, we have the seal of comes in what would normally be a very hot sum-
physician Wang, who specialized in speech defects mer, there will be much feng kho (i.e., tonsillitis,
(yin); physician Chang, who claimed to be able to bronchitis, pneumonia, etc.). It also says that if hot
cure external lesions (yang); physician Kao, who spe- summer weather comes in autumn, there will be
cialized in the care of ulcers (yung); physician Kuo, many cases of fever (nio chi). This is the word later
who dealt with edematous conditions (teo), very appropriated to malarial fevers, but in the ancient
likely beriberi; physician Thu, who specialized in times of which we are now speaking, it was simply
removing nasal polypi (hsi); and physician Chao, associated with rapid alterations of shivering cold
who was expert in psychological diseases (yii1). and hot fever. The text also says that if the hot rainy
These are only a few examples taken from those that season continues into the autumn, there will be
Chhen Chih has collected. From the Warring States many cases of chhou chih (i.e., diseases involving
period also there are a large number of records writ- sneezing, such as colds and catarrhs with some fe-
ten with ink on strips of wood or bamboo, but these ver). The last part of the text says that if spring
have not so far yielded much of medical interest. weather occurs in the last month of winter, there
Medical material on this medium indeed exists, but will be many problems of pregnancy, especially mis-
it derives largely from the army records of the later carriages and stillbirths {thai yao to shang). A possi-
Han dynasty (first and second centuries A.D.), which ble explanation for this association might be shocks
is later than the period we are discussing here. to the body caused by going out without sufficient
clothing.
Classical Writings Another feature of this particular kind of unsea-
sonableness was described as a high incidence oikii3
Diseases and the Seasons
ping. Ku3ping - literally, "obstinate diseases" or "en-
Yiieh Ling. The Yiieh Ling (Monthly Ordinances) feebling diseases" (fei) - might be described as those
is admittedly an ancient text, but opinions differ as in which the patient is enfeebled and cannot easily
to its date; some would put it as late as the third help him- or herself; such "handicapped" people
century B.C., when it was incorporated in the Lii were not considered fit to participate in social af-
Shih Chhun Chhiu, or also later in the Li Chi; but fairs. The Kuliang chuan, one of the three great
internal astronomical evidence tends to place it ear- commentaries on the Chhun Chhiu (Spring and Au-
lier (seventh to fifth centuries B.C.). In the course of tumn Annals) of the State of Lu (722-481 B.C.),
its description of the activities proper to the different defines four forms of handicap that prevented social
seasons, information is given about what is likely to competency: (1) thu, a skin disease of the scalp; (2)
occur if the weather is entirely unseasonable. Thus miao, an eye defect, possibly ankyloblepharon or
if autumn or summer weather comes in the spring, Homer's syndrome but more probably trachoma; (3)
or autumn weather in the summer, or spring po, lameness, often congenital; and (4) lu, meaning
weather in the winter, there will be great epidemics "hunchback" or "a person with arthritic limbs," the
(ta i, ping i, chi i, yang yii i). In one of these cases the descriptions also covering rickets in advanced form,
word li1 is used; here it is taken as standing for and osteomalacia. We shall mention this again.
another word, li2, and not for lai, which it often could
do later on, for lai specifically refers to leprosy. As Texts of the centuries just subsequent to the Yiieh
we shall see later in this chapter, the first indication Ling (if we may regard it as of the late seventh cen-
of leprosy occurred just about the sixth century B.C. tury B.C.) began to differentiate clearly between ter-
Now chieh refers to one of the evils of spring weather tian and quartan malaria, the former being generally

termed hsien or tien and the latter kai or chiai. There demic. The word that later would be universally
is considerable reason, however, for believing that at used to denote diarrhea and dysentery, li3, does not
some of these periods chiai nio was a joint expression seem to occur much in texts of this date earlier than
used for a disease of slow development ending in the Nei Ching itself.
hemoptysis, which we can identify as tuberculosis.
Diseases and "Airs, Waters, and Places"
Chou Li. Another interesting description of the In theLM Shih Chhun Chhiu, Chapter 12, we read as
seasonal incidence of disease occurs in the Chou Li follows:
(Record of Institutions of the Chou Dynasty). Al- In places where there is too much "light" (chhing, clear)
though much of the material in this book may well water, disease of the scalp (thu; alopecia, ringworm, psoria-
date from the Chou period, its compilation must sis, etc.) and goitre (ying) are commonly found. In places
undoubtedly be considered a work of the early Han where there is too much "heavy" (chung, turbid) water,
(second century B.C.). It gives a detailed account of people suffering from swellings and oedematous ulcers of
what the people of that time considered the ideal the lower leg (thung1) are commonly found and there are
democratic organization of the state. Here in Chap- many seriously affected who are unable to walk at all (pi).
ter 2 we read as follows: Where sweet (kan) water abounds, men and women will be
health[y] and handsome. Where acrid (hsin) water
Each of the four seasons has its characteristic epidemics abounds there will be many skin lesions, such as abscesses
(lil chi). In spring there comes feverish aches and head- (chii) and smaller boils (tso); where bitter (khu) water
aches (hsiao shou chi); in summer there are "itching abounds there will be many people with bent bones (wang
scabies-like epidemics" (yang chieh chi); in autumn there yu).
are malarial and other fevers (nio hart chi); in winter there
are respiratory diseases (sou shang chhi chi). These technical terms are of much interest. The scalp
diseases (thu) we have already encountered, but this
How is one to interpret these technical terms? No is the first time that we have seen goiter, for which
doubt the feverish aches and headaches of the the term ying is characteristic and indubitable. In
spring refer to influenza, catarrhs, and so forth, but the next sentence the term thung1 (more correctly
the "itching, scabieslike epidemics" of the summer written in medical usage thung2) associated with
were certainly far more serious. In the light of the pi, which means lame in both feet, and bedridden,
passage that we have just studied in the Yiieh Ling, strongly suggests beriberi, indeed the wet form. This
it would seem that cerebrospinal fever (menin- term occurs again in a much older text, in one of the
gococcal meningitis, spotted fever) may have been poems in the Shih Ching (approximately eighth cen-
one of the important components of these epidemics, tury B.C.) where it is associated with another word,
for the course of the disease links together severe wei, both meaning ulceration of the lower leg. The
rash, fever, and convulsions. Here epidemic encepha- commentators of the Book of Odes describe it as
litis is less likely, though it certainly occurred a disease of swampy places, where, no doubt, the
widely in North China down to our own times, and vitamin in the stored grain was destroyed by moulds.
one must also leave a place for scarlet fever and The word wang resembles that for edema in general
other less important infectious diseases. In the au- (chung), which is to be distinguished from the terms
tumn, apart from malaria, one would naturally also for ulcers: yung if edematous and unbroken; and chii
think of dysentery of both kinds and gastroenteritis if open, much worse and generally fatal. The probable
(enteric fever caused by Salmonella, etc.) as consti- identification of beriberi in the Shih Ching as well as
tuting the meaning of the words nio han chi (i.e., in the Lii Shih Chhun Chhiu is accepted by Hu
epidemics caused by a cold, internal or external). Hou-hsiian and Chhen Pang-hsien, who indeed find
The winter picture almost certainly involved pneu- evidence of it as far back as the oracle bones them-
monia, acute and chronic bronchitis, and similar selves, but there only with reference to disease of the
pulmonary afflictions. This is obviously indicated feet. It is pleasant to hear of one place at least where
by the words used, which suggest the rising of the people were healthy and handsome, but immediately
pneuma into the region of the lungs, with coughing afterwards we learn of places where chii were plenti-
and difficulty in breathing. Among the epidemics of ful; chii means carbuncles, furuncles, and perhaps
summer and autumn, one would obviously also also cancer, whereas tso refers to smaller skin lesions
want to leave a place for typhoid-type diseases and such as acne. Rickets and osteomalacia are certainly
perhaps staphylococcal bacteremia, though tubercu- to be recognized in the last sentence. The bronze
losis would hardly have been classified as an epi- script form of wang is a pictogram of a person with a

crooked back, and many famous people of antiquity and the sixth, cardiac disease. The classification
are said to have been deformed in this way, even the into six divisions is of extreme importance, because
great Duke of Chou himself. Yii2 undoubtedly means it shows how ancient Chinese medical science was
hunchback; it occurs in the expression yyu2 lu, which independent of the theories of the Naturalists, who
we find in Chapter 7 of the Huai Nan Tzu book classified all natural phenomena into five groups
(approximately 120 B.C.). There Tzu-Chhiu at 54 associated with the Five Elements. Chinese medi-
years of age "had an illness which left his body cine never entirely lost its 6-fold classification; but
deformed. He was so bent that his coccyx was higher that is a long story, which cannot be told here.
than his head and his sternum was so lowered that Physician Ho diagnosed the illness of the Prince of
his chin was bent below the level of his spleen." There Chin as ku1, by which he did not mean the artificial
can be no doubt that rickets and osteomalacia were poison nor, so far as we can see, schistosomiasis, but
widespread in ancient China. There are a number of rather some kind of physical exhaustion and melan-
other valuable texts of the "airs, waters, and places" cholia arising from excessive commerce with the
type, such as those found in the Huai Nan Tzu book women of his inner compartments.
(Chapter 4) and in the Nei Ching, Su Wen itself
(Chapter 12). Tso Chuan
There is something of interest in every one of the
Shih Ching medical passages of the Tso Chuan. For example, in
Nosological data in the Shih Ching (Book of Odes, 638 B.C. a deformed (wang) sorceress, doubtless suf-
about eighth century B.C.) have been analyzed in fering from rickets or osteomalacia, was to be burnt
detail by Yii Yiin-hsiu, but there is a special diffi- as a remedy for drought, but a skeptical statesman,
culty here because these ancient folksongs natu- Tsang Wen-chung, intervened and said that other
rally took advantage of poetic license and it is some- means would be much more efficient, so this method
times difficult to determine whether the disease was not used. Two years later, we hear of Chhung
terms are being used in their proper medical sense; Erh, the son of Prince Hsien of Chin State, who
some of them may have been used to indicate mal- suffered from phien hsieh (i.e., his ribs were so dis-
aise or depression in general. Nevertheless, shou torted and deformed as almost to meet in front of the
chi (feverish headaches), shu (enlarged neck glands, sternum). Moved by scientific curiosity perhaps, the
perhaps goiter, tuberculosis, or Hodgkin's disease) Prince of Tshao succeeded in getting a view of him
and meng, sou (various forms of blindness) are all of while in the bathhouse. In an episode of 584 B.C., a
interest. Nosological data derived from the Tso certain country was described as dangerous for giv-
Chuan, the greatest of the three commentaries on ing people a disease named o, although in this par-
the Chhun Chhiu already mentioned, are more reli- ticular case the disease endemic there seems to have
able and also much more abundant. More than 55 been beriberi, because there is talk of edematous leg
consultations or descriptions of diseases occur in swellings and waterlogged feet (chui). We encounter
these celebrated annals. Perhaps the most impor- the same term again (o ping) in the Lun Yii, the
tant is the consultation dated 540 B.C. which the discourses of Confucius, dating from about a century
Prince of Chin had with an eminent physician, Ho, later. One of his disciples, Po Niu, suffered from o
who had been sent to him by the Prince of Chhin. ping, and the universal interpretation of all the com-
Physician Ho, as part of his bedside discourse, in- mentators since that time has been that this disease
cluded a short lecture on the fundamental princi- was leprosy. We do not find the term lai at such an
ples of medicine that enables us now to gain great early date, but there seems no reason to reject so old
insight into the earliest beginnings of the science in and continuous a tradition that this was the first
China. Especially important is his division of all mention of leprosy in Chinese literature.
disease into six classes derived from excess of one or Another case relating to the date 569 B.C. was
other of six fundamental, almost meteorological, death by heart disease (hsin chi, hsin ping); it hap-
pneumata (chhi). Excess of Yin, he says, causes han pened to a general, Tzu-Chung (Kung tzu Ying-chhi
chi; excess of Yang, je chi; excess of wind, mo chi; of Chhu), who was greatly distressed after a military
excess of rain, fit chi; excess of twilight influence, failure, and we may regard it as angina pectoris
huo chi; and excess of the brightness of day, hsin brought on by anxiety. Soon afterward, the term
chi. The first four of these are subsumed in the Nei shan came into use to denote this disease, the symp-
Ching classification under je ping, diseases involv- toms and psychosomatic nature of which are so char-
ing fever; the fifth implies psychological disease; acteristic. We find this word in the Nei Ching, used

instead of the term just mentioned for the parallel The earliest grew up in the western state of Chhin;
hsin thung of the Shan Hai Ching, an ancient geo- the other was located in the eastern seaboard state
graphical text that belongs to the middle of the Chou of Chhi. From Chhin came the physician Huan,
period. In 565 B.C., the Tso Chuan notes another whose attendance on the Prince of Chin in 580 B.C.
case of fei chi, some kind of chronic disability that long remained famous; the physician Ho, already
prevented the normal life of a minister's son. Hydro- mentioned as examining another Prince of Chin 40
phobia is also fairly clearly indicated in an entry years later, also came from there. More celebrated
connected with 555 B.C., where a mad dog (chi kou than either of them was Pien Chhio, about whom
or hsia kou) entered into the house of Hua Chhen, a there is much to be said, but as the records concern-
minister of Sung State. The word khuang was used ing him do not give us very much in the field of
indiscriminately for the mad dog itself and for the disease nomenclature, we mention him only in pass-
disease that it caused. Toward the end of the Tso ing. But Shunyu I is a different persona entirely.
Chuan we have a story dated 497 B.C., in the latter Born in 216 B.C. in Chhi, he studied under Kungsun
part of the life of Confucius, which includes the fa- Kuang and Yang Chhing, practicing medicine suc-
mous remark that "only he who has thrice broken cessfully from about 180 B.C. on. In 167 B.C., he was
his arm can make a good leech." accused of some crime and taken to court, but he was
acquitted after the supplication of his youngest
Shan Hai Ching daughter. As he had been attending on the Prince
We have already mentioned the Shan Hai Ching. and lords of Chhi, he was summoned to answer an
This is a strange book, full of legendary material, inquiry from the imperial court some time between
which reached its present form probably about the 164 and 154 B.C., then released again, and he contin-
second century B.C., but which contains much far ued in practice until his death about 145 B.C. It is
older material. Many legendary and mythological owing to this perquisition by the imperial authority
elements pervade its descriptions of the mountains that we possess today the records of some 25 detailed
and forests of the Chinese culture area, the spirits case histories which Shunyu I reported. For every
proper to be worshiped by travelers in any particular one we have the name of the patient, the circum-
region, and also the peculiar plants and animals and stances in which the disease was contracted, the
their virtues. More than 30 herbs, beasts, and stones details of the attendance of Shunyu I, the treatment
are recommended to ward off various diseases, and that he prescribed, the explanations that he gave of
this is where the nosological interest comes in. Many his diagnostic reasoning, in which the pulse played a
terms we have already met with, such as epidemic very prominent part, and finally the ultimate result.
fevers (i, li1), epidemics with rash (chieh), edematous We also have the answers that Shunyu I gave to
swellings (chung), goiter (ying), rodent ulcers (chu), eight general questions, answers that throw a flood
and eye defects, probably trachoma (mi). Kul disease of light upon the general conditions of medical educa-
is also mentioned. Yul we have not encountered pre- tion and practice in the second century B.C. R. F.
viously; it means both swellings in the neck and also Bridgman (1955), who had given us a pioneer study
torticollis or palsy. If equivalent to yu2 or chan, the of Shunyu I and his times, has concluded that the
commentators interpret it as paralysis agitans or general level of Chinese medicine thus revealed was
senile tremor, but it may also refer to an affliction in no way inferior to that of the contemporary
called yu3 chui. This consists not only of large swol- Greeks, and in this judgment we concur. For the
len lymph glands or the parotitis of mumps, but also present purpose the point is that the clinical descrip-
small, wartlike tumors on the head, neck, and ex- tions are so detailed that we can see exactly what
tremities which recall verruca, the multiple warts Shunyu I meant by his own technical terminology.
produced by a rickettsia. Another of the disease Let us first look at some of the less severe cases
terms met with in the Shan Hai Ching is chia, which that Shunyu I was able to cure — or at least relieve
undoubtedly refers to a massive infestation with infor a time. In a child, chhi ko ping was clearly diffi-
testinal worms (ascariasis or oxyuriasis). This culty in breathing, probably influenza or catarrh,
brings us to the great period of Han case-histories, perhaps acute laryngitis; some fever is implicit in
and so to the work of Shunyu I. the explanation. In a palace superintendent, yung
shan was evidently vesical schistosomiasis, accompa-
Han Period: Shunyu I nied by hematuria, urinary retention, vesicular
During the Warring States, Chhin, and early Han calculi, perhaps prostatorrhea. Other similar cases,
periods, there were two great schools of medicine: however, were too far gone to recover - for example,

a police chief who seems to have had bladder cancer One of the most extraordinary cases reported by
accompanied by intestinal obstruction due to heavy Shunyii I was that of another royal physician, by
ascaris infestation {chid). The Chief Eunuch of the name Sui. He must have been interested in Taoist
Palace of Chhi fell into a river and got very cold and arts, for he had himself prepared elixirs from the
wet, so his je ping due to han was surely bronchitis "five mineral substances," and when Shunyii I saw
or pneumonia; Shunyii I gave antipyretic drugs and him he was suffering from chung je, apparently in
pulled him through. Then the Queen Mother of Chhi this case a pulmonary abscess, presumably brought
had feng tan, which is clearly interpretable as acute on by arsenical or mercury poisoning. Shunyii I
cystitis, probably connected with nephritis. She had warned him that it would be hard to avoid a fatal
hematuria, but she got better under Shunyii's treat- result, and in fact some months later the abscess
ment. An old nurse of the princely family had je burst through under the clavicle, and Sui died. An-
chiieh, with hot and swollen feet; this may have been other man had what Shunyii I described as ping khu
gout accompanied by chronic alcoholism, or possibly tho feng (i.e., some progressive paralysis), possibly
simply a traumatic infection of the extremities. disseminated sclerosis or possibly progressive muscu-
Chhiu chih was clearly dental caries, and one of the lar dystrophy.
grand prefects of Chhi had it. One of the concubines More rapidly fatal in termination were other
of the Prince of Tzu-chhuan had a difficult child- cases. A palace chamberlain had a peritoneal ab-
birth; Shunyii I gave nitrate and obtained the rejec- scess, perhaps a perforating ulcer {chil, leading to
tion of postpartum blood clots. A young courtier had chung je); perhaps the perforation was due to heavy
shen pi — traumatic lumbago or muscular strain ascarid infestation. Another man died of fei hsiao
caused by trying to lift a heavy stone, together with tan with delirious fever {han je). This would have
dysuria, perhaps caused by compression of the hypo- been acute hepatic cirrhosis, probably caused by
gastric plexus; he also got better. By means of a liver and blood flukes. In this case, the royal physi-
vermifuge prepared from the gingko tree, a girl was cian of Chhi had diagnosed and treated it quite
cured of an intense Enterobius infestation (oxyuria- wrongly. It is curious that up to this time we have
sis). Here the description is particularly precise be- not found the characteristic term for cholera {ho
cause the term used was jao chin, and already by luan), but it seems that Shunyii I may well have had
this time there were several other terms {hui, chiao, a case of it among his records, for a minister of the
pa, etc.) for other types of intestinal parasites. An- Lord of Yang-hsii died of "penetrating pneuma"
other case of pi was that of a young prince who had {tung feng), the description of which suggests total
acute lobar pneumonia but recovered. failure of digestion, intense diarrhea, possibly due to
One of the more striking features of Shunyii I's enteric fever, perhaps to cholera. The word shan
practice was the way in which he was able to give a appears again in a combination mu shan, where it
long-term diagnosis. For example, on one occasion clearly refers to an aortic aneurism that caused the
he was asked to give a general health checkup of the death of a general. The last case we shall mention
serving maids of the Prince of Northern Chhi, and was that of a Court Gentleman of Chhi who had a
among these he found one who was certainly not ill fall from his horse onto stones; the resulting trau-
but in his opinion was going to be. She was, he said, matic abdominal contusion followed by intestinal
suffering from shang phi, and this must have been perforation of a gut probably already weakened by
tuberculosis because it ended in a sudden and fatal parasitic infestations of one sort or another was
hemoptysis some 6 months later. No one would be- termed fei shang, that is, injury not to the lung but
lieve that Shunyii I was right in saying that she was to the tract {ching) of the lung. This brings us to the
ill, but events confirmed his opinion. On another last subject that we can touch upon here, namely the
occasion he was alarmed by the appearance of a medical system of the Nei Ching.
slave of the client of the Prime Minister of Chhi, who
again, in his view, had a shang phi chhi, although The Nei Ching
the man himself did not feel particularly ill. Shunyii The Nei Ching was, we think, approximately already
I said that he would not last through the following in its present form by the first century B.C. The full
spring, and he did not. Here the clinical description title under which it is commonly known is the Huang
suggests hepatic cirrhosis, almost certainly of para- Ti Nei Ching (The Yellow Emperor's Manual of Eso-
sitic origin, caused by liver flukes (hepatic distomia- teric Medicine), consisting of two parts, the Su Wen
sis); jaundice was apparent, and the case might also (Pure Questions and Answers) and the Ling Shu
have been one of acute yellow atrophy of the liver. (Spiritual Pivot). This was the recension that came

from the editorship of Wang Ping in the Thang dy- the manifestation and interrelationship of symp-
nasty, but it is probable that this was not the toms; using the concepts of Yin Yang (the two funda-
recension that the Han people had. Another one, mental forces in the universe), Wu Hsing (the five
known as the Huang Ti Nei Ching, Thai Su, which elements), Pa Kang (the eight diagnostic princi-
was edited 100 years or so earlier than Wang Ping, by ples), and Ching Lo (the circulatory system of the
Yang Shang-shan in the Sui period, and which has chhi). The five elements had not been part of the
only come to light in very recent times, may be consid- most ancient Chinese medical speculations; they
ered nearer the original text of the Han. The Nei derived from another school, that of the Naturalists
Ching system of diagnosis classified disease symp- (Yin-Yang chia) whose greatest exponent and sys-
toms into six groups in accordance with their relation tematizer had been Tsou Yen (c. 350-270 B.C.)
to the six (n.b., not five) tracts (ching) which were Five-element theory (a lengthy discussion of which
pursued by the pneuma (chhi) as it coursed through can be found in Science and Civilisation in China,
and around the body. Three of these tracts were allot- Volume 2 [Needham et al. 1954]) was so influential
ted to Yang (Thai-Yang, Yang-Ming, Shao-Yang) and and so widespread in all the nonmedical sciences
three to Yin (Thai-Yin, Shao-Yin, and Chueh-Yin). and protosciences of ancient (and medieval) China
Each of them was considered to preside over a "day," that the physicians could not remain unaffected by
one of six "days" - actually stages - following the it, but in incorporating it into their theoretical disci-
first appearance of the feverish illness. In this way, plines they added a sixth unit or entity to conform
differential diagnosis was achieved and appropriate with their 6-fold categories. Thus there were five
treatment decided upon. These tracts were essen- Yin viscera (liver, heart, spleen, lungs, and urino-
tially similar to the tracts of the acupuncture special- genital organs) and five Yang viscera (gallbladder,
ists, though the acupuncture tracts were composed of stomach, larger and small intestines, and bladder)
two 6-fold systems, one relating to the hands and the recognized by all schools. To these the physicians
other to the feet, and crossing each other like the added a further entity in each category, the hsin
cardinal (ching) and decumane (lo) streets of a city pao lo (pericardial function) and the san chiao
laid out in rectangular grid arrangement. Moreover, (three coctive regions); and the particular interest
by the time of the Nei Ching the physicians had of this lies in the fact that these additions repre-
achieved full recognition of the fact that diseases sented physiological operations rather than morpho-
could arise from purely internal as well as purely logically identifiable structures. The six "viscera"
external causes; the ancient "meteorological" system could thus correspond readily with the six chhi, the
explained by physician Ho had therefore been devel- six tracts, and so on. It must not be supposed that
oped into a more sophisticated 6-fold series, namely the state of Chinese medicine at the time of the Nei
feng, shu, shih, han, sao, huo. As external factors, Ching synthesis was destined to remain unchanged
they could be translated as wind, humid heat, damp, through the following nearly two millennia of
cold, aridity, and dry heat; but as internal causes we autochthonous practice; on the contrary, there were
could name them blast (cf. van Helmont's bias), fotive great developments, many elaborations, and a pro-
chhi, humid chhi, algid chhi, exsiccant chhi, and liferation of diverging schools. However, if we are to
exudative chhi. It is interesting to notice the partial think of any presentation of Chinese medicine as
parallelism with the Aristotelian-Galenic qualities, classical, this is what deserves the name.
which were part of a quite different, 4-fold, system. The ancient Chinese physicians were extremely
In the brief remaining space of this contribution, conscious of the temperature-regulating and -per-
it would be impossible for us even to sketch the ceiving systems of the human body, so that al-
etiologic and diagnostic system of the Nei Ching, though they had no means of measuring tempera-
but it is fair to say that the system provided an ture accurately, the observation of subjective chill
elaborate classificatory framework into which the or fever, together with algophobia or algophilia,
results of keen clinical observation could be fitted. was extremely important for them. By this time
A rather comprehensive theory of medicine, both also the study of the pulse and its modifications had
diagnostic and therapeutic, was now available. In- advanced to a highly developed state.
terpreting a whole millennium of clinical tradition, All fevers were placed in a category of shanghan
the physicians of the former Han dynasty were able diseases and termed diseases of temperature (je
to combine into one science the influences of exter- ping). Every sign that is still examined today (pain,
nal factors on health, the abnormal functioning of perspiration, nausea, etc.), short of the results of
internal organs whether by excess or by defect, and modern physicochemical texts, was studied by them

and meant something to them. For example fu man, diabetes (hsiao kho, hsiao chung) had not been devel-
or abdominal fullness, was an important sign. This oped by the end of this period, there can be little
could mean edema (chung). The Nei Ching actually doubt that diabetes was here in question. The sweet-
says that "fluid passing into the skin and tissues by ness of the urine was discovered a good deal later,
overflow from above and below the diaphragm forms indeed in the seventh century A.D.
oedema." It could also mean ascites occurring in
liver cirrhosis, heart failure, and especially schistoso-
miasis, undoubtedly so common in ancient China. The fact that mummification was not practiced in
Fu man was also accompanied by the excretion of ancient Chinese civilization has no doubt militated
watery feces with undigested food (shift i) found in against the acquisition of a mass of concrete evi-
gastroenteritis, cholera, and the like. Fu man was dence concerning many of the diseases from which
also called fu chang and tien. This latter word is a people suffered in those times, such as has been
good example of a word that can be pronounced in developed for ancient Egypt. As far as we know,
two ways; pronounced tien, it meant abdominal dis- almost nothing has been done on the pathological
tension; but pronounced chen, it meant various anatomy of the skeletons that have been excavated
forms of madness and, in the binome chen hsien, from ancient tombs in China, whether in the Neo-
epilepsy. It is clear from the clinical description that lithic or in the Chou, Chhin, and Han periods. Since
from Han times onward the terms lao feng and lao there must be a mass of skeletal material in the
chung referred to tuberculosis. The term feng by Chinese museums, it may be that this task could
itself always had the connotation of convulsion or still be accomplished with valuable results by Chi-
paralysis; it might be regarded as a violent pneuma, nese archeological pathologists. However, the study
in distinction from the mild pneuma (chhi), which of the written records of ancient China, from the
was part of the physiology of the normal body. Other middle of the first millennium B.C. down to the
forms of chung feng, therefore, were hemiplegia beginning of our era, shows that they have pre-
(phien khu) and cerebral hemorrhage giving full apo- served a veritable mass of information concerning
plexy (fi). Among the fevers {wen ping) we now find the diseases prevalent in those times, and although
fairly clear descriptions of diphtheria, as she pen Ian the study of human remains themselves may bring
(lesions at the root of the tongue), doubtless compli- precious confirmation of what the writings reveal, it
cated by streptococcal infections. Diphtheria is also may well be that on balance the written records,
clearly denoted by meng chix, "fierce ulcer" (of the when fully analyzed, will present a broader picture
throat). Hepatic cirrhosis caused by liver and blood than the study of the skeletal remains themselves
flukes was now called kan je ping; tuberculosis, phi alone could ever give us.
je ping; pneumonia, feije ping. Lu Gwei-Djen and Joseph Needham
It does not always follow that the organs referred We acknowledge with thanks an earlier version of this essay
to in descriptions (in the three preceding cases: liver, printed under the title "Records of Diseases in Ancient China" in
spleen, and lungs, respectively) were those to which the American Journal of Chinese Medicine (1976, 4 [1]: 3-16),
we might refer the diseases today. Rather these were published by the Institute for Advanced Research in Asian Sci-
ence and Medicine, Inc., which was previously printed in Don
the organs concerned with the six tracts already Brothwell and A. T. Sandison's Diseases in Antiquity, 1967, pub-
spoken of, each one of which was connected with an lished by Charles C. Thomas.
organ. Of the malarial types of fever (chiai nio) we
have already spoken. The terminology now contin-
ued with little change, but one disease, tan nio, may Bibliography
be identified with relapsing fever caused by Borrelia Bridgman, R. F. 1955. La medecine dans la Chine antique.
spirochetes as Sung Ta-jen has suggested. Milanges Chinois et Bouddhiques 10: 1-20.
One last word on diabetes. Polyuria was recog- Chhen Chih. 1958. Hsi Yin Mu Chien chung Fa-hsien-ti
nized as the sign of a special disease in the Nei Ku-Tai I-Hsueh Shih-Liao (Ancient Chinese medicine
Ching, where it is called fei hsiao. Han ideas about as recorded in seals and on wooden tablets). Kho-
Hsueh Shih Chi-Khan 1: 68-87.
this illustrate the principle of successive involve-
Chhen Pang-hsien. 1957. Chung-Kuo I-Hsiieh Shih (His-
ment or shifting (i) when some pathological influ- tory of Chinese medicine). Shanghai.
ence spreads from organ to organ in the body. Thus Fan Hsing-chun. 1954. Chung Kuo Yu Fang I-Hsiieh Ssu-
in fei hsiao the cold chhi in the heart passes over into Hsiang Shih (History of the conceptions of hygiene
the lungs and the patient excretes twice as much as and preventative medicine in China). Peking.
what he drinks. Though the characteristic name for Hu Hou-hsiian. 1943. Yin Jen Ping Khao (A study of the

tant early medical thinkers, specified in the early
diseases of the Shang (Yin) people (as recorded on the
oracle-bones). Hsiieh Ssu, No. 3, 73; No. 4, 83. fourth century A.D. that the Shanghan diseases in-
Needham, J., and Lu Gwei-djen. 1978. Proto-endocrinol- cluded not only those caused by winter cold but also
ogy in medieval China. Bucharest. those caused by spring warmth and by seasonal liqi
Needham, J., et al. 1954. Science and Civilisation in (epidemic "breath"). However, he conceded that dif-
China, 7 vols. Cambridge. ferences among the origins of the three types of
Sung Ta-jen. 1948. Chung-Kuo Ku-Tai Jen Thi Chi-
Sheng-Chhung Ping Shih (On the history of parasitic
diseases were slight and they should therefore be
grouped into a single category. This ambiguous con-
diseases in ancient China). J-Hsiieh Tsa Chih 2 (3-4):
44. ception of epidemic "fevers" as part of a more gen-
Wang Chi-min, and Wu Lien-te (K. C. Wong and Wu Lien- eral category of "cold fevers," despite some minor
teh). 1932. History of Chinese medicine. Shanghai. modifications, remained relatively unshaken in Chi-
Yu Yun-hsiu. 1953. Ku-Tai Chi-Ping Ming Hou Su I (Ex- nese medical thought until the seventeenth century
(late Ming and early Qing dynasties).
planations of the nomenclature of diseases in ancient
times). Shanghai. Widespread epidemics during the late Ming dy-
nasty (Dunstan 1975) induced certain medical think-
ers to reject the entire shanghan theory because most
of the diseases they were called on to treat were found
not to be caused by winter cold. The most representa-
tive of these pioneer thinkers was Wu Youxing, a
VI.2 seventeenth-century native of the epidemic-stricken
Diseases of the Premodern eastern Jiangsu region. His work Treatise on Warmth
Epidemic Disease, written in 1642, put forward the
Period in China theory that seasonal epidemics were caused by devi-
ant qi ("ether") in the atmosphere (Dunstan 1975).
The "warm factor" was now favored over the "cold
Old Diseases factor" as cause for the disease. Even diseases such as
It is very difficult to trace precisely the historical smallpox that had traditionally been considered
development of particular epidemic diseases in manifestations of the body's internal "fire" or "poi-
China. First, traditional Chinese medical terminol- son" were now grouped with communicable diseases
ogy is based on a system hardly translatable into caused by external qi.
modern Western terms. Second, not only the con- Even this important development in understand-
cepts of disease, but the diseases themselves have ing the etiology of epidemic diseases in premodern
changed, so much so that it is impossible to deter- China does not help us understand all diseases in
mine whether an ancient classical term meant the this period in Western terms. Insufficient descrip-
same thing when used in premodern texts, or to find tions of the symptoms of diseases in medical texts as
the exact modern counterpart of a disease discussed well as in local gazettes and dynastic histories where
in old texts. most of the information on epidemics can be found
Only during the second half of the nineteenth cen- constitute the main obstacle to such understanding.
tury did diseases in China begin to be scrutinized by Moreover, China's vast size implies regional differ-
Western medical practitioners, and as late as the ences in disease history that are still grossly
early twentieth century, it was difficult to construct unappreciated. At the present stage of research,
a complete picture because "there were classes of with the exception of a few diseases that are easily
disease that were rarely brought for treatment to identifiable, the best guesses as to the identity of
modern doctors" (Polunin 1976). most remain highly hypothetical.
One principal feature of the traditional Chinese
medical system (a system that achieved classical Old and New Diseases
form by the second century) that makes it difficult to The sixteenth century can be considered a water-
identify individual epidemic diseases in premodern shed in China's disease history. With the coming of
China is the ancient categorization of both epidemic European traders to China's southeast coast and the
and endemic diseases along with other afflictions intensification of international commercial activi-
into a large group labeled shanghan ("affection by ties in South and Southeast Asia, China entered the
cold," although today it is the modern term for ty- world community and a few new epidemic illnesses
phoid fever). Ge Hong, one of China's most impor- entered China. Scarlet fever, cholera, diphtheria,

VI.2. Premodern Period in China 355
and syphilis are the more important ones to be added east China during the early twentieth century
to the reservoir of older diseases that had been ravag- (Chen 1982).
ing China for centuries. Among the latter were The history of plague in China is a controversial
smallpox, pulmonary diseases, malarial-types of fe- subject. Some believed that it arrived in China in
vers, other febrile illnesses, dysentery, and possibly the early seventh century (Twitchett 1979), whereas
plague. However, the social and demographic impact others date the first appearance in the 1130s in
of the new diseases on China after the sixteenth Canton (Fan 1986). Yet both of these views are based
century is a field largely unexplored despite its im- at least in part on simple descriptions of symptoms
portant historical implications. (appearance of he, "nodes"; or houbi, "congestion of
Smallpox is one of the oldest diseases known to the throat"), which is far from conclusive evidence.
China. An early sixth-century medical work claimed By tracing the development of plague epidemics in
that the malady (then called luchuang, "barbarian the Roman Orient, and in Iraq and Iran from the
boils") was introduced around A.D. 495 during a war mid-sixth century to the late eighth century,
with the "barbarians" in northern China (Fan 1953; D. Twitchett (1979) has argued that at least some of
Hopkins 1983). Little is known of the development of the epidemics that struck China from the seventh
smallpox thereafter, until the late eleventh century and eighth centuries were those of bubonic plague.
(Northern Song period) when treatises on the dis- By contrast, those who feel that plague burst out as
ease written by pediatricians first appeared. devastating epidemics only in the early thirteenth
That pediatricians wrote of smallpox suggests or fourteenth century (McNeill 1976; Fan 1986) sug-
that by this time it had developed into a childhood gest a possible relationship to the European Black
illness among the Chinese population (Leung Death of the same period.
1987b). The technique of variolation using human Unfortunately, there is no direct evidence to sup-
pox was first practiced in the lower Yangtze region port either of the above hypotheses. Even as late as
not later than the second half of the sixteenth cen- the seventeenth century, when China was again
tury, and vaccination became popular in the early struck by a series of epidemics, it is impossible to
nineteenth century, when Jennerian vaccination prove that these were outbreaks of plague (Dunstan
techniques were introduced through Canton. Yet, 1975). The first epidemic in China, which we have
despite the early practice of variolation, smallpox substantial reason to believe was plague, was that
was rampant in China, especially in the north (the first striking Yunnan in 1792. It then spread to the
Manchus and the Mongolians were the most vulnera- southeastern provinces of Guangdong and Guangxi,
ble, and two of the Manchu emperors died of the up the Chinese coastline to Fujian and to the north-
disease) where variolation was much less practiced ern part of China (Benedict 1988). But it was only in
than in the south (Leung 1987b). the late nineteenth century that medical works on
Malarial-types of fevers (nue or zhang) first ap- the "rat epidemic" (shuyi) began to be published
peared in medical texts in the seventh century, when (Fan 1986).
the economy of the subtropical regions south of the In addition to the epidemic diseases discussed
Qinling Mountains became of great importance to above, several endemic ailments were likely to be
the northern central government. From the twelfth equally devastating. Among these were pulmonary
century on, after northern China was occupied by diseases (probably pneumonia and tuberculosis), dys-
the Jurchens and the Song government fled to the entery, various fevers (the shanghan category of
south, specialized medical books on malarial fevers fevers), which probably included typhoid fever, ty-
and other subtropical diseases believed to be caused phus, and possibly meningitis, cerebrospinal fever,
by the "miasma" (zhangqi) of these regions appeared influenzas, and the like. Most popular almanacs and
in increasing number (Fan 1986). Some scholars be- family encyclopedias of the Ming-Qing period that
lieve that temperatures during the Tang period contained chapters on common illnesses and their
(A.D. 618-907) were probably higher than those of treatment mentioned dysentery, the shanghan dis-
today, which suggests that the northern limits of eases, and coughs. Skin diseases, huoluan (pros-
diseases associated with the southern climates (ma- trating fever with diarrhea), beriberi, and nue
laria, schistosomiasis, and dengue fever) were fur- (malarial-type fever) were also frequently discussed
ther north than they are today (Twitchett 1979). The (Leung 1987a).
number of victims of these diseases was therefore Perhaps some notion of the relative importance of
likely to be larger than previously thought. In fact, these endemic diseases, especially in southern
malaria was still a major killer in South and South- China, can be gleaned from surveys done in Taiwan

during the Japanese occupation period (1895-1945). eastern coast up to Fujian and Taiwan. It usually
The disease that caused the highest mortality in struck in the months of August and September.
Taiwan from 1899 to 1916 was malaria. In 1902, it Some scholars suspect that an epidemic in 1564,
accounted for 17.59 percent of mortality among the which had reportedly killed "10 million people," may
native Taiwanese, causing 4.62 deaths per 1,000. have been cholera. But regardless of the possibility
Malaria was followed by dysentery and enteritis un- of cholera's presence at an earlier date, there is no
til 1917, after which "pneumonia" became the re- question about the devastating effects of cholera in
gion's biggest killer (4.42 deaths per 1,000 in 1935). nineteenth-century and early twentieth-century
Next in importance was dysentery (2.55 deaths per China, especially in crowded urban centers (B. Chen
1,000 in 1935), whereas other contagious diseases 1981; S. Chen 1981; Fan 1986).
including parasitic ailments accounted for 1.5 Scarlet fever and diphtheria came to China in the
deaths per 1,000 in 1935 (Chen 1982). early and late eighteenth century, respectively. Scar-
That pulmonary diseases and dysentery persisted let fever was epidemic in the lower Yangtze region in
as the major fatal diseases among southern Chinese the 1730s during the winter-spring transition and
from the premodern period to the early twentieth was then called "rotten-throat fever" (lanhousha).
century seems obvious. The secondary place that The contemporary epidemiologist Ye Gui (1665-
Ming-Qing almanacs accorded to the malarial-type 1745) noticed that the illness struck all age groups
fevers, despite the fact that malaria was the princi- and that the victims were covered with dense red
pal killer in nineteenth-century Taiwan, can be ex- spots and had red sore throats. The disease seemed
plained by the fact that few, if any, of these alma- to be more devastating in the north. In the Peking
nacs were written by authors from subtropical and area of the 1930s, the estimated mortality of scarlet
frontier regions. It is also possible that malaria was fever was 80 per 100,000 (S. Chen 1981).
confused with some of the shanghan diseases in Diphtheria was confused with scarlet fever when
almanacs. it first reached China in the late eighteenth century.
Parasitic diseases, which ranked third on the list It became widespread and epidemic in the decades of
of high-mortality diseases in Taiwan in the 1930s the 1820s through the 1850s, spreading from the
and 1940s, were rarely mentioned in the almanacs. lower Yangtze region to southwestern China and to
But their importance was emphasized by Western the northeastern regions before it reached the north-
scientists who came to China in the early twentieth west in the late nineteenth century. The first medi-
century. Thus G. F. Winfield claimed that feces- cal work on diphtheria (then called "white-throat
borne diseases caused about 25 percent of all deaths disease," baihoulong or baichanhou) was also pub-
in China, especially among peasants in the rice and lished in the mid-nineteenth century (Fan 1986).
silk regions of the south (Winfield 1948). It is difficult to estimate quantitatively the mortal-
Syphilis was one of the first "new diseases" that ity caused by the new diseases. Their older counter-
reached China. It was probably first introduced to parts seemed to remain on the top of the list of high-
Guangdong through Portuguese traders in the early mortality diseases into the early twentieth century.
sixteenth century, as a 1502 medical work recorded However, as scarlet fever was the tenth leading
that syphilis was called the "boils of Guangdong" cause of mortality in the Peking area between 1926
(guangchuang) or "plum boils" by the people of the and 1932 (S. Chen 1981), and as syphilis (with gonor-
lower Yangtze region. The disease was already much rhea) accounted for 2 to 5 percent of all deaths in
discussed in sixteenth- and seventeenth-century China, their roles cannot be underestimated. Per-
medical texts, some of which clearly stated that it haps the reason why the impact of cholera and diph-
was transmitted through sexual intercourse (B. theria epidemics in the premodern period was not
Chen 1981; Fan 1986). Along with gonorrhea, syphi- quantified was that the former was too seasonal and
lis probably accounted for 2 to 5 percent of all Chi- the latter basically a childhood disease.
nese deaths in the 1930s (Winfield 1948). According to local gazetteers of the southern prov-
Cholera probably arrived after syphilis. The mod- inces, epidemics usually struck during the spring-
ern term for the disease - huoluan - was in the past summer and the summer-autumn transitions. This
a name for any disease that caused sudden and dras- seasonability of disease prevalence was confirmed
tic vomiting and diarrhea. Reliable records date the by the 1909 Foochow Missionary Hospital Report,
first real cholera epidemics in China from the 1820s. which recorded 2,004 patients treated in May, 1,943
Like syphilis it also was first introduced in in June, and 1,850 in October - equaling about one
Guangdong and spread from there along the south- third of the 17,456 patients treated during the entire

year (Kinnear 1909). Dysentery was generally the 130 million by the turn of the following century and
biggest killer in the summer, whereas cholera did its soared to 150 million by 1600 (Ho 1959). Another
most important damage in October. drastic decline seems to have occurred in the mid-
Unlike Japan whose isolation from the important seventeenth century, which may have reduced the
world trade routes kept major diseases away from its population to 83 million in 1651 (Wu 1988). Momen-
shores during premodern times (Jannetta 1987), tum was regained during the eighteenth century by
China was always exposed to epidemic disease. the end of which the population had tripled, reach-
Trade through the old silk route, war with the north- ing 313.2 million in 1795. By comparison, China's
ern "barbarians," travel to and from India and population in 1686 was ony 101.7 million.
Indochina - all brought the "old" diseases to China, Scholars have attributed some of these drastic
whereas the coming of the Europeans by sea from population declines to epidemics. Twitchett (1979),
the sixteenth century onward brought a few "new" for example, argues that epidemics had some effect
ones. upon demographic trends in the seventh, eighth, and
The low mortality rate resulting from diseases in ninth centuries, and might have been one major
premodern Japan preceded a period of low fertility, reason for population stagnation before the tenth
all of which shaped Japan's demographic develop- century. It is also tempting to attribute the mysteri-
ment (Jannetta 1987). Comparison with Japan in ous but real decline of population in north China
turn raises the question of the extent to which epi- during the fourteenth century to plague, as does
demic diseases in China may have been an impor- William McNeill (1976). Some scholars would go
tant factor in its population growth. For example, even further by hypothesizing that plague was rav-
did China ever experience something similar to the aging northern China as early as the thirteenth
Black Death, which struck Europe in the fourteenth century. The beginning of the century saw a series of
and fifteenth centuries, or the smallpox epidemics epidemics in Hebei and Shanxi, and then an epi-
that paralyzed the Amerindian communities in the demic struck Kaifeng (Henan) in 1232, reportedly
sixteenth century? killing nearly 1 million people within 50 or 60 days
(Fan 1986).
Population and Disease Moving to the late Ming period, of the sixteenth
Questions such as those above have always in- and seventeenth centuries, H. Dunstan's (1975) pre-
trigued historians of China because the Chinese liminary survey of epidemics suggests that these
population has experienced mysterious declines that catastrophes also had long-term effects on popula-
were possibly caused by widespread epidemics. One tion growth and that the prosperity of the ensuing
such decline of population occurred in north China early and middle Qing dynasty was the result of an
in the late seventh century, whereas another was a easing of pressure on land resources brought about
decline in the lower Yangtze region during the ninth by huge die-offs from disease, as well as from war
century. Other examples are the drastic depopula- and famine around the middle of the seventeenth
tion of north China during the Mongol dynasty in century.
the fourteenth century, and the decline during the Yet the question of the impact of disease on
Ming-Qing transition in the mid-seventeenth cen- China's population remains controversial because of
tury (Cartier and Will 1971; Zhou 1983; Wu 1988). different interpretations of demographic sources
Indeed, despite the nature of Chinese sources that do (Cartier and Will 1971; Bielenstein 1975; Wang
not permit any precise demographic reconstruction, 1988). Also remaining is the question of how re-
it is generally conceded that China's population in gional differences in population development can be
the tenth century remained very much the same as related to local epidemics. Natural catastrophes like
it had been nine centuries earlier. A significant epidemics or famines were usually local rather than
growth, however, took place during the three centu- widespread occurrences and of smaller magnitude
ries following the tenth century and in the early and shorter duration than impressionistic accounts
thirteenth century, when the population was esti- have led many to believe. In fact, it could be argued
mated to have reached an unprecedented high of that they were unlikely to have had long-term demo-
between 100 million and 120 million people (Cartier graphic impact (Watkins and Menken 1985).
and Will 1971). Yet the fourteenth century was one Thus, it is perhaps most reasonable to see the
of demographic disaster. Ho Ping-ti estimates the presence or absence of epidemic disease in China as
population level at the end of the fourteenth century just one of the determining factors in long-term popu-
to have been around 65 million, although it exceeded lation growth. The unprecedented upsurge in popula-

tion during the Song period (eleventh to thirteenth from poorer areas to the centers who were most
centuries) is generally believed to be closely related likely carriers of contagious diseases (Liang 1986;
to a series of revolutionary changes in agriculture in Leung 1987a).
the more developed southern regions, especially Thus, with fertility rates already high, the demo-
with rice growing. The period witnessed the introduc- graphic upsurge of the eighteenth century is best
tion of early-ripening rice as well as improvements explained by a remarkable decline in mortality. At
in irrigation and other agricultural technologies all least the initial stage of the upsurge can be ex-
of which greatly increased land productivity (Ho plained in terms of mortality decline, although sub-
1959, 1969; Bray 1984). The next upsurge in popula- sequent increases in populations were likely to have
tion, however, was from the eighteenth century on- been generated largely by the internal dynamics of
ward, a period in which there was no comparable an already huge population. The industrialization of
technological revolution. Could the "stagnation" be- the period was neither important nor modern
tween the two upsurges be explained by differing enough to cause a significant rise in tuberculosis.
mortality rates in which infectious diseases had a Ann Jannetta (1987) suggests that the practice of
role? infanticide and abortion in Tokugawa Japan was a
Stagnations in "preindustrialized" populations oc- sign of attempts to control fertility because of an
curred when high or moderately high fertility rates already slowly declining mortality. This may also
were balanced by similarly high mortality rates re- have been the cause in China, for it was the case
sulting from uncertain food supplies and unavoid- from the late seventeenth century onward that
able diseases. It is generally agreed that in Asia, foundling homes were widely established, possibly
where marriage was early and nearly universal, fer- reflecting increasing infanticide and child abandon-
tility was higher than in preindustrialized western ment. Interestingly, the only precursor to this move-
and northern Europe, where women married late ment was in the thirteenth century when China
and forced celibacy was more common (Coale 1986). experienced its first population boom (Leung 1985).
Therefore, a stagnation in population development
in China can best be explained by high "normal" Decline in Chinese Mortality
mortality rates. Why then did mortality decline? Ho Ping-ti's (1959,
Subsistence crises were always a constant threat 1978)findingson the introduction of new crops from
to the Chinese, which, by causing undernutrition (if the Americas during the sixteenth century provide
not death from starvation), reduced their resistance us with one of the more persuasive answers. These
to disease. The prevalence of dysenteries, shanghan easy-to-grow crops - for example, sweet and white
(discussed earlier), and respiratory diseases might potatoes and maize-may well have substantially
be an indication of general dietary deficiencies stabilized food supplies for the poor in less fertile
(Polunin 1976). Certainly, beriberi, which was often and mountainous regions. D. H. Perkins (1969), how-
discussed in the family encyclopedias, could cause ever, suggests that changing cropping patterns and
death directly or indirectly by leaving the individual rising traditional capital inputs increased crop
less able to resist diseases, whereas infantile yields per acre. Either way an improved food supply
beriberi has proven to be a major killer of nursing was certain to have reduced the chances of starva-
infants in thiamine-deficient populations. tion for the people and consequently their suscepti-
In addition, parasitic diseases probably killed mil- bility to various diseases.
lions of peasants because the use of human feces as Some would argue that long-term climatological
fertilizer was a universal practice for centuries. evolution was the main factor: the post-fifteenth-
Flooded rice fields were also breeding grounds of century population growth, its decline in the mid-
mosquitoes — the carriers of malaria and other infec- seventeenth century, as well as the explosion in the
tions. In addition to malnutrition and agricultural eighteenth century, all corresponded to climate
practices, poor hygienic conditions, especially in changes of the time (Eastman 1988). Here even the
some of the southern provinces and frontier regions, changes in food production and the disease factor
must also have been an important factor in encourag- can be considered as affected by the climate.
ing insect-borne diseases like malaria and plague. Another important factor that should be consid-
Other important factors that could account for high ered is that in its earliest stages, a mortality decline
morbidity rates, especially in urban centers in the is the result of lowered mortality rates for the young.
late Ming period, were the absence of sewage and This was the case in modern Europe and in
water control, and the inflow of masses of vagrants Japanese-occupied Taiwan (Chen 1982; Riley 1986).

The health of the mother is an important variable in the twelfth and thirteenth centuries took responsibil-
infant mortality, whereas better resistance to child- ity for providing medical help to the poor through
hood diseases typically explains a reduced mortality public pharmacies. The Mongol dynasty continued
in children over one year of age. Surely mother's this tradition by creating a nationwide system of
education and infant mortality are directly related; "medical schools" to train local doctors. Yet, the tra-
however, the relationship is impossible to verify in dition began to decline in the late fourteenth cen-
this period. In addition, the lowering of mortality in tury, and by the late sixteenth century such institu-
children in modern Europe and early twentieth- tions had largely disappeared. To some extent, this
century Taiwan was closely linked to the improve- void was filled by local philanthropists who took
ment in general hygiene (Chen 1982; Riley 1986). responsibility for providing regular medical help to
Unfortunately, it would be mere speculation to say the needy from the seventeenth century on. They
anything about the improvement in the hygienic organized charitable dispensaries that provided the
conditions (especially the provision of clean water local people with medical care and medicines, and
for drinking, washing, and bathing) in premodern sometimes decent burials for the dead. These public
China at this stage, and in any event, there must but nonstate medical organizations could be found in
have been enormous regional differences. many urban centers in the eighteenth and nine-
However, the early practice of variolation against teenth centuries (Leung 1987a), and the free or very
smallpox is a possible factor in explaining the de- cheap medical treatment offered must have provided
cline in Chinese mortality. An eighteenth-century at least a minimum of necessary care to the urban
smallpox specialist, for example, claimed that over poor. Moreover, the burying of dead bodies collected
80 percent of the children of wealthy families in from the streets also helped to upgrade the sanitary
China had been inoculated (Leung 1987b). On the conditions of these urban centers. According to an
other hand, the majority of children were not inocu- 1860 report by the American Presbyterian mission-
lated, and clearly, no single factor is likely to serve ary in Shanghai, John Kerr, the local charitable
as an explanation. Avenues of research that may dispensary, which was staffed by eight or nine Chi-
prove fruitful in examining the question of reduced nese physicians, was visited daily by 300 to 500
infant and child mortality include changing con- individuals "of all classes" (Kerr 1861).
cepts of pregnancy, childbirth, and infancy (Leung After weighing the many changes that together
1984; Furth 1987); the attitudes behind the nation- brought about the mortality decline in China, we
wide establishment of foundling homes; improved find it probable that an improved supply of food,
hygiene and immunization; and traditional diet ther- which strengthened the nutritional status of the gen-
apy based on the humoral dimensions, and the whole eral population, was the most important factor from
folk nutritional science built largely on empirical the late seventeenth century onward. The spread of
observation (Anderson 1988). variolation and an increasingly denser network of
If we are uncertain of the positive effects of new charitable dispensaries in the same period may also
developments in agriculture, new crops, or variola- have contributed to a reduction in mortality, espe-
tion on reducing mortality, we can at least be confi- cially in southern China. Improved hygiene and
dent that diseases no longer hindered long-term popu- child care practices were also probably important
lation growth, and that the contribution of disease to factors in bringing about what seems to have been a
the mortality rate was no longer as great as it had decline in infant mortality rates, but this has yet to
been in the past, despite the introduction of some new be demonstrated.
diseases from the sixteenth century onward. Im-
proved therapy and medication may have played a Chinese Medicine
limited role in reducing the importance of disease, as, Discussion of some prominent features of Chinese
for example, the increasing use of herbal-based drugs medicine and the traditional reaction of the people
(before the introduction of quinine in the eighteenth toward disease will help us understand the Chinese
century) to fight malaria instead of the more dan- system and allow us to gauge its relative effective-
gerous arsenicals used in the Ming-Qing period ness from the modern point of view. Quarantine,
(Miyasita 1979). But like variolation, the effects of which was a common practice in Europe from the
herbal-based drugs, probably only used by small sec- fifteenth century onward, was never widely prac-
tions of the population, are difficult to estimate. ticed in China. There were, however, instances of
Certain institutional changes may have had some isolation of individuals for certain diseases such as
indirect effects on mortality rates. The Song state in smallpox and especially leprosy.

Apparently, lepers were put into "lazaretto"-type Popular Ming-Qing almanacs and encyclopedias
hospices as early as the Qin dynasty (221-207 B.C.), must also have reinforced this trend (Leung 1987a).
and examples of such institutions are also found in As in premodern Europe, peddler-doctors, self-
sixth-century sources (Xie 1983). Unfortunately, trained midwives, women-pharmacists and other
there is no systematic documentation relating to "heterodox" healersflourishedespecially in the coun-
hospices, and there is only sporadic mention of them tryside. Women and children were often treated by
in later sources. In the mid-nineteenth century, for female healers exclusively (Leung 1987a). In 1759, a
example, we know that leper hospices existed in book on the principles and practices of peddler-
eastern Guangdong, where interned lepers were al- doctors, A Collection of Proper Methods (Chuanya),
lowed to marry only among themselves. Moreover, was published by the scholar-pharmaceutist Zhao
their offspring were freed only after the third genera- Xuemin. The work was based on his interviews with
tion, when the genetic "poison" was believed to be a peddler-doctor and reveals a long tradition of popu-
exhausted (Liang 1982). In the same period, leper lar healing that relied heavily on acupuncture, purg-
hospices were also organized by overseas Chinese ing either through ding (provoked vomiting) or
communities in Batavia (Yang 1842). chuan (provoked diarrhea), and other methods (jie)
As for smallpox-quarantine measures, there is at that aimed at stopping symptoms instantly. Yet heal-
least one instance on record. In 1645, when the ers who practiced these "violent" methods were the
Manchus had just conquered Peking, they decreed lowest stratum in a system that emphasized memori-
that all smallpox victims and their families be ban- zation of abstract theories from the medical classics,
ished 40 li (about 3 miles) from the city wall. The subtle diagnosis, and a long and respectable family
policy was still in force in 1655 (Hopkins 1983; tradition of medical practice.
Leung 1987a). Yet, as noted above, these were ex- More often than not during epidemics, state finan-
ceptional instances, and it is difficult to understand cial aid was used for buying coffins to bury the dead
the Chinese lack of interest in quarantine (Leung (Leung 1987a), and people, high and low alike, com-
1987a). Ethics, however, probably had something to monly resorted to rituals and shamanistic practices
do with it. Moralists like Zhu Xi of the twelfth when illness struck. Indeed, healing by charms and
century, for example, condemned the "abandoning" amulets (zhuyou ke), which had its roots in antiq-
of one's relatives and friends who fell victim to uity, was part of the curriculum of the Imperial Acad-
contagious diseases. Rather, one should risk infec- emy of Medicine since Tang times. Diseases and
tion by remaining behind to care for the sick, and especially epidemic diseases were firmly believed to
there existed some conviction that moral power be caused by unpacified ghosts and spirits of the
thus manifested would somehow keep the epidemic locality; thus rituals were essential in disease avoid-
spirit away (Huizhoufu zhi 1502). On the other ance (Huangchao jingshi wenbian 1897). Individuals
hand, the concept that diseases were caused by afflicted by illness were likely to ask help from vari-
broad environmental influences - ether or vital en- ous deities, or to correct moral faults that were be-
ergy (qi), wind (feng), fire or heat (huo), and water lieved to be the source of the physical corruption
(Xie 1983) — would also seem to have discouraged (Leung 1987a).
quarantine measures. Such fatalistic attitudes toward illness and lack of
Chinese medicine as a body of knowledge to fight total confidence in medicine should not be cause for
disease never developed into a "science" as it did in surprise. To a certain extent, this behavior is still
Europe from the seventeenth century onward. For prevalent among the Chinese populace today.
the scholar, medicine was a respectablefieldof study Angela Ki Che Leung
linked to philosophy, although the practicing physi-
cian was not accorded a high social status (Hymes
1987; Leung 1987a). Medical skills were transmitted Bibliography
within families and not by government-authorized Anderson, E. N. 1988. The food ofChina. New Haven, Conn.
Benedict, C. 1988. Bubonic plague in nineteenth-century
institutions. The Imperial Academy of Medicine (tai-
China. Modern China 14.2: 107-55.
yiyuari) trained doctors only for government service Bielenstein, H. 1975. Review on the article of Cartier &
and for the imperial family, and had no obligation to Will. ToungPao 61: 181-5.
standardize medical knowledge or control the medi- Bois, G. 1984. The crisis offeudalism: Economy and society
cal profession. Under such circumstances, medicine in eastern Normandy c. 1300—1550. Cambridge.
had a tendency to become "democratized," because Bray, F. 1984. Agriculture. Vol. 6 of Part II of Science and
all educated people had access to medical literature. civilisation in China, ed. J. Needham. Cambridge.

Cartier, M., and P.-E. Will. 1971. Demographie et institu- l'enfant en Chine aux XVIe et XVIIe siecles. Cahiers
tions en Chine: Contribution a l'analyse des recense- Internationaux de Sociologie 74: 51-69.
ments de l'Gpoque imperiale (2 ap. J.—C. - 1750). An- 1985. L'Accueil des enfants abandonnes dans la Chine
nales de Demographie Historique 1: 162-245. du bas-Yangzi aux XVIIe et XVIIIe siecles. Etudes
Chen B.-x. 1981. Zhongguo yixue shi (History of Chinese chinoises 4.1: 15—54.
medicine). Taipei. 1987a. Organized medicine in Ming-Qing China: State
Chen S.-k. 1981. Zhogguo jibing shi (History of Chinese and private medical institutions in the lower Yangzi
diseases). Taipei. region. Late Imperial China 8.1: 134—66.
Chen S.-x. 1982. Taiwan di renkou bianqian yu shehui 1987b. Mingqing yufang tianhua cuoshi zhi yanbian
bianqian (Population and social change in Taiwan). (Smallpox prevention in the Ming and Qing dynas-
Taipei. ties). In Guoshi shilun (Collection of essays on Chi-
Coale, A. J. 1986. The decline of fertility in Europe since nese history), 239-54. Taipei.
the eighteenth century as a chapter in human demo- Liang Q.-z. (Leung, K. C.) 1986. Mingmo Qingchu minjian
graphic history. In The decline of fertility in Europe, cishan huodong di xingqi (Rise of private charitable
ed. A. J. Coale & S. C. Watkins, 1-30. Princeton. activities during the late Ming and early Qing pe-
Dunstan, H. 1975. The late Ming epidemics: A prelimi- riod). Shih-huo Monthly 15.7/8: 52-79.
nary survey. Ch'ing-shih wen-t'i 3.3: 1-59. Liang S.-r. 1982. Liang ban qiuyu an suibi (Notes of the
Eastman, L. E. 1988. Family, fields and ancestors: Con- Two Autumn Rains Study). Shanghai (original edi-
stancy and change in China's social and economic tion, 1837).
history, 1550-1949. Oxford. McNeill, W. 1976. Plagues and peoples. New York.
Fan X.-z. 1953. Zhongguo yufang yixue sixian shi (History Miyasita, S. 1979. Malaria (yao) in Chinese medicine dur-
of immunization in China). Shanghai. ing the Chin and Yuan periods. Ada Asiatica 36: 90—
1986. Zhongguo yixue shilue (A brief history of Chinese 112.
medicine). Peking. Perkins, D. H. 1969. Agricultural development in China
Furth, C. 1987. Concepts of pregnancy, childbirth, and 1368-1968. Chicago.
infancy in Ch'ing dynasty China. Journal of Asian Peter, J.-P. 1972. Malades et maladies a la fin du XVIIIe
Studies 46.1: 7-35. siecle. In M6dicins, climat et epidemies a la fin du
Ho P.-t. 1959. Studies on the population of China, 1368- XVIIIe siecle, ed. Jean-Paul Desaive et al., 135-70.
1900. Cambridge. Paris.
1969. Huangtu yu Zhongguo nongye di qiyuan (The Polunin, I. 1976. Disease, morbidity, and mortality in
Loess and the origin of Chinese agriculture). Hong China, India, and the Arab world. In Asian medical
Kong. systems: A comparative study, ed. C. Leslie, 120—32.
1978. Meizhou zuowu di yinjin, chuanbo ji qi dui California.
Zhongguo liangshi shengchan di yingxiang (The intro- Riley, J.C. 1986. Insects and the European mortality de-
duction of American crops and their impact on Chi- cline. The American Historical Review 91(4): 833-58.
nese food productivity). In Dagong Bao zai Gang Twitchett, D. 1979. Population and pestilence in T'ang
fukan sanshi zhounian jinian wenji (Volume to cele- China. In Studia Sino-Mongolica: Festschrift fiir Her-
brate the 30th anniversary of the re-publication of the bert Franke, ed. Wolfgang Bauer, 42—53. Wiesbaden.
Dagong Bao in Hong Kong), 673-731. Hong Kong. Wang Q.-j. 1988. Ming chu quan guo renkou kao (Survey
Hopkins, D. 1983. Princes and peasants: Smallpox in his- on the national population at the beginning of the
tory. Chicago. Ming dynasty). Lishi yanjiu (Historical research) I:
Huangchaojingshi wenbian (Collection of works on practi- 181-90.
cal administration of the country). 1897. 1972 facsim- Watkins, S. C , and J. Menken. 1985. Famines in historical
ile edition (Taipei) of the original. perspective. Population and Development Review 11.4:
Huizhoufu zhi (Gazetteer of Huizhou prefecture). 1502. 647-75.
1987 facsimile edition (Taipei) of the original Huizhou Winfield, G.F. 1948. China: The land and the people. New
edition. York.
Hymes, R. 1987. Not quite gentlemen? Doctors in Sung Wu, H. 1988. Qing dai renkou di jiliang wenti (Quantita-
and Yuan. Chinese Science 8: 9-76. tive problems in Qing demography). Zhongguo shehui
Jannetta, A. B. 1987. Epidemics and mortality in early jingji shi yanjiu (Research on Chinese social and eco-
modern Japan. Princeton. nomic history) I: 46—52.
Kerr, J. 1861. Report of the medical missionary for the Xie X.-a. 1983. Zhongguo gudai dui jibing chuanran xing
year 1860. (Pamphlet). Report for Canton hospital. di renshi (Concepts of disease contagion in old China).
Canton. Zhonghua yishi zazhi (Journal of Chinese Medical
Kinnear, H. N. 1909. The annual report ofPonasang Mis- History) 13(4): 193-203.
sionary Hospital. Foochow. Yang B.-n. 1842. Hailu (Record of the seas). 1984 facsimile
Leung, K. C. 1984. Autour de la naissance: la mere et edition (Taipei) of the original edition.

child policy was introduced. From 1965 to 1980, the
Zhou Y.-h. 1983. A study of China's population during the
Qing dynasty. Social Sciences in China, 61-105. annual population growth rate averaged 2.2 per-
cent; and from 1980 to 1985, 1.2 percent. Owing to
a slower rate of decline in the birth rate it is now
estimated that China's population may stabilize at
1.6 billion by around the middle of the twenty-first
century.
VI.3 By 1985, life expectancy at birth was estimated to
Diseases of the Modern reach 69 years, and infant mortality had dropped to
about 35 per 1,000 according to the World Bank
Period in China (1987). In specific regions, however, the rates were
quite different. In the People's Daily of April 26,
1989, the government admits that in about 300 of
Overview the poorer regions infant mortality averages 100 per
Modern China, with a 1985 population of 1.04 billion 1,000. UNICEF estimates infant mortality rates at
(World Development Report 1987), is by far the most 190 per 1,000 for Tibet.
populous country on earth, though its surface area of Despite a large number of small nationality
9.56 million square kilometers ranks it third in size groups who speak many different languages, China
(behind the former Soviet Union and Canada). has a relatively homogeneous population. Approxi-
Ninety-five percent of the population live on less mately 93 percent of the population are Han, or
than 50 percent of the total area, primarily along the ethnic Chinese. Most of China's peoples speak one of
great river systems of the east and southeast, and the two major spoken languages, which, though
only 22 percent of those in the population are classi- quite different, share the same written characters.
fied as urban residents. The climate covers a broad
range of patterns, extending from the hot, humid, Patterns of Disease
and wet provinces in the south and southeast to China has been witness to one of the most rapid and
those provinces in the north and northwest, which profound changes in health patterns that has ever
are for the most part dry and subject to hot summers occurred in recorded history. This chapter gives pri-
and cold winters. By 1985 China's per capita gross mary consideration to the disease patterns present
national product in current dollars was estimated at in China in the 1980s; however, to place current
U.S. $310 (World Development Report 1987). Approxi- events in context, one must start with a brief descrip-
mately 33 percent of the gross domestic product was tion of the social, economic, and health situations
derived from agriculture, down from about 39 per- that prevailed in 1949, the year the People's Repub-
cent in 1965. An estimated 74 percent of the labor lic was proclaimed.
force was in agriculture, 14 percent in industry, and Midcentury China emerged from yet another of
12 percent in services in 1980 (World Development what must seem to the Chinese a near endless cycle
Report 1987). of natural and human-made disasters, in this case,
China's population growth has slowed dramati- more than two decades of foreign invasion, occupa-
cally. In 1956, Ma Yin-chu, China's well-known eco- tion, and civil war. The country was completely
nomic expert, urged the government to introduce exhausted. The World Bank estimated that in 1950
population control, and to slow down population the Chinese population was 603 million; the birth
growth. But China's leader, Mao Zedong (Mao Tse- rate, 42 per 1,000; the death rate, 33.5; the infant
tung) rejected this advice vehemently. In 1965, how- mortality rate, 252; and life expectancy at birth, 32
ever, the slogan was "yige bushao, liangge zheng- years (World Development Report 1987). With a
hao, sange duole" ("One [child] is not too few, two very low per capita income and an extremely lim-
[children] are just right, three are many"). By 1972, ited health-care system, the predominant diseases
population control was justified by eugenic argu- were those associated with malnutrition and com-
ments: "quality instead of quantity." The slogan municable disease.
was (and still continues) shaosheng yousheng ("few China's disease patterns have changed so rapidly
births but superior births"; or "few lives but supe- since the 1950s that it is helpful to compare the
rior lives"). A policy announced in 1978 was de- present situation with that estimated, by much less
signed to achieve a stable population at the 1.13 complete statistics, at around the time of the declara-
billion level by the year 2000, and in 1979 the one- tion of the People's Republic in 1949. The first two

VI.3. Modern Period in China 363
sections look at the causes of mortality and morbid- Communicable diseases
ity, with a brief consideration of regional variations,
and the last section looks at selected causes of dis-
ease, especially those that are unusually prevalent
in China. Unless otherwise indicated, disease-
specific data are from the 1984 World Bank report
entitled China: The Health Sector. This source, as Cardiovascular diseases
and malignant tumors
well as the 1986 publication Public Health in the
People's Republic of China, relies primarily on offi-
cial Ministry of Public Health data sources, which 194951 53 55 57 59 61 63 65 67 69 71 73 75 77 79 81 83
are still subject to numerous limitations in both cov- year
erage and quality despite many improvements since Figure VI.3.1. Mortality rates for the urban population
the 1950s. The reader will therefore need to inter- of Shanghai, 1949-83. (From Public Health in the Peo-
pret the reported findings with caution. ple's Republic of China (1986), p. 86.)
Mortality 32.3 percent of all deaths, whereas by 1984 they

Good historical data on mortality for all of China amounted to less than 10 percent. By 1984 the top
are not available. Figure VI.3.1, based on data three causes - heart disease, cancer, and stroke -
from the urban population of Shanghai, China's accounted for 64.9 percent of urban deaths and
largest city, dramatically depicts the shift from 54.9 percent of those in rural areas. Collectively,
mortality due largely to communicable disease, to the top 10 causes accounted for almost 90 percent
a situation in which cardiovascular disease and of all deaths in 1984, as compared with only two-
malignant tumors predominate. The 10 leading thirds ofthose in 1957.
causes of death in selected cities in 1957 and in Wide interprovincial variations exist in the death
both urban and rural areas in 1984 are listed in rates due to the top three causes (see Table VI.3.2).
Table VI.3.1. The top three causes of death in Although these are likely explained in part by re-
1957, all communicable diseases, accounted for porting errors and age differences, they are probably
Table VI.3.1. Leading causes of death, selected cities and counties of Shanghai, 1957 and 1984
13 cities (1957) 28 cities (1984) 70 counties (1984)
6 6
Cause Rate" Percent Cause Rate" Percent Cause Rate" Percent 6
Respiratory disease 120.3 16.9 Heart disease 124.6 22.7 Heart disease 158.5 24.6
Communicable dis- 56.6 7.9 Cerebrovascular 116.3 21.1 Cerebrovascular 98.8 15.3
ease disease disease
Pulmonary TB 54.6 7.5 Malignant tumors 116.2 21.1 Malignant tumors 97.0 15.0
Digestive disease 52.1 7.3 Respiratory disease 48.4 8.8 Respiratory disease 78.5 12.2
Heart disease 47.2 6.6 Digestive disease 23.8 4.3 Digestive disease 36.4 5.6
Cerebrovascular 39.0 5.5 Trauma 19.4 3.5 Trauma 27.6 4.3
disease
Malignant tumors 36.9 5.2 Pulmonary TB 10.2 1.9 Pulmonary TB 26.9 4.2
Nervous disease 29.1 4.1 Intoxication 10.2 1.9 Intoxication 20.8 3.2
Trauma/ 19.0 2.7 Urinary disease 9.5 1.7 Communicable dis- 15.3 2.4
intoxication ease
Other TB 14.1 2.0 Communicable dis- 8.1 1.5 Neonatal disease' 79.5 .2
ease
Total 468.9 65.7 Total 486.7 88.5 Total 639.3 87.0
"Deaths per 100,000 population.

6
Percent of total deaths.
'Deaths per 1,000 newborns.
Source: Adapted from Public Health in the People's Republic of China (1986), table 4, p. 86.

Table VI.3.2. Leading provincial causes of death in China, 1985
Cause #1 Cause #2 Cause #3

East China
Anhui Province Accidents (90)° Respiratory (85) Heart (83)
Fujian Province Cancer (91) Heart (83) Respiratory (82)
Jiangsu Province Cancer (122) Respiratory (98) Heart (85)
Shandong Province Respiratory (128) Cancer (77) Heart (73)
Shanghai Municipality Cancer (105) Stroke (101) Heart (97)
Zhejiang Province Cancer (102) Respiratory (99) Heart (97)
West China
Gansu Province Communicable (96) Respiratory (93) Digestive (77)
Ningxia Aut. Region Respiratory (13) Communicable (116) Congenital (101)
Qinghai Province Communicable (157) Respiratory (152) Heart (101)
Xinjiang Aut. Region Respiratory (164) Communicable (129) Heart (116)
Xizang (Tibet) Aut. Region Respiratory (153) Heart (152) Digestive (100)
Northeast China
Heilongjiang Province Heart (148) Respiratory (67) Stroke (57)
Jilin Province Heart (188) Respiratory (83) Stroke (78)
Liaoning Province Heart (131) Respiratory (81) Cancer (72)
North Central China
Beijing Municipality Heart (165) Stroke (137) Cancer (76)
Hebei Province Heart (182) Stroke (101) Cancer (98)
Henan Province Heart (120) Respiratory (115) Cancer (93)
Nei Mongol (Inner Mongo- Heart (162) Respiratory (101) Cancer (68)
lia) Aut. Region
Shaanxi Province Respiratory (125) Heart (125) Cancer (83)
Shanxi Province Heart (168) Respiratory (107) Cancer (106)
Tianjin Municipality Heart (147) Stroke (129) Cancer (79)
South Central China
Hubei Province Respiratory (115) Accidents (106) Heart (93)
Hunan Province Respiratory (138) Heart (112) Accidents (90)
Jiangxi Province Respiratory (125) Heart (113) Accidents (90)
Southwest China
Sichuan Province Heart (162) Respiratory (153) Accidents (101)
Yunan Province Respiratory (200) Heart (147) Communicable (113)
South China
Guizhou Province Respiratory (258) Communicable (168) Digestive (137)
Guangdong Province Respiratory (74) Cancer (57) TB (18)
Guangxi Aut. Region Respiratory (79) TB (57)
"The numbers in parentheses refer to the death rate per 100,000.

*The classification of causes of death in Guangxi differs from that in other regions; the leading cause of death in Guangxi
in 1985 was "aging and feebleness," and the deaths attributed to this cause were omitted from the source table.
Source: Based on data in Public Health in the People's Republic of China (1986), table 3, p. 94.
also due to regional differences in environmental, Morbidity

nutritional, and other factors. Heart disease death Communicable diseases reported for 1985 are given
rates are highest in the northern provinces, ranging in Table VI.3.3. Though these estimates, especially
from a high of 188 per 100,000 population in Jilin for the less serious illnesses, are likely very much
Province down to 73 in Shandong. Cancer rates are underreported, they do give some notion of the rela-
highest in the east, ranging from 122 in Jiangsu to tive frequency with which the various conditions are
57 in Guangdong. reported to the authorities.

Table VI.3.3. Communicable diseases in China, or ascariasis (the roundworm). Ancylostomiasis re-
1985 mains prevalent in 14 southern provinces, and
ascariasis is widespread in most of China. Improved
Number of Number of environmental sanitation and night soil manage-
cases deaths ment have reduced the prevalence of both parasites,
Cholera 6 2 but the limited information available indicates that
Cerebrospinal fever 654 7 both remain a public health concern.
Diphtheria 1,423 184
Dysentery 3,280,596 2,352 Filariasis. In the 1950s, filariasis, transmitted by
Encephalitis B 29,065 2,433 a mosquito vector, was said to have affected between
Epidemic hemorrhagic fever 103,778 3,111 20 million and 30 million people. By 1958, more
Forest tick-borne encephalitis 270 15 than 700,000 patients had been treated, and the
Influenza 3,407,383 361 Patriotic Health Movement led to major improve-
Leishmaniasis 145 1 ment of environmental sanitation in many localities
Leptospirosis 26,632 544 and to widespread extermination of mosquitoes.
Malaria 563,400 44 Shandong Province, with a population of 75 million,
Measles 418,159 2,654 had eradicated the disease by 1983, and by 1985
Pertussis 147,298 237 about 76 percent of China's endemic areas were es-
Plague 6 1 sentially disease free. In the mid-1980s filariasis
Poliomyelitis 1,537 95 was prevalent in 864 counties and cities in 14 prov-
Scarlet fever 61,591 17 inces, autonomous regions, and municipalities.
Tsutsugamushi disease 1,695 6 Slightly over half of the jurisdictions were endemic
Typhoid and paratyphoid fever 86,482 251 with Bancroftian filariasis, about one-fourth were
Viral hepatitis 794,269 2,313 endemic with Malayan filariasis, and the rest had
mixed infections.
Source: Excerpted from Public Health in the People's Re-
public of China (1986), table 13, p. 218.
Leishmaniasis (Kala-Azar). A 1951 survey showed
the area of China endemic for visceral leishmaniasis
No national data exist on causes of morbidity or to be entirely north of the Yangtze River, covering 1.2
reasons for seeking health care, but a 1981 study of million square kilometers. Prevalence was 1 to 5 per
737 households in Shanghai County (Parker et al. 1,000, with an estimated 530,000 cases, most of whom
1982) provides some indication of what illness pat- were children. Destruction of dogs and treatment of
terns may be like. On the basis of a 2-week recall it human cases with a specially produced antimony
was estimated that area residents annually aver- drug played a major role in decreasing transmission.
aged 6.0 days of restricted activity, 2.4 days in bed, Reduction in incidence may also have resulted from a
7.6 days lost from work, and 2.6 days lost from decline in the sandfly vector due to insecticide spray-
school. There were 44 hospitalizations per 1,000 re- ing for both sandflies and malarial mosquitoes. Since
spondents per year, and every 2 weeks there were 1958, kala-azar outbreaks have become sporadic,
156 morbidity conditions, 49 cases of acute disabil- with fewer than 100 cases reported every year.
ity, and 187 primary care visits. In a survey of 3,122
people, 499 ill persons experienced 487 conditions. Malaria. Prior to 1949, malaria incidence in
The percentages reporting the five leading condi- China was estimated at more than 30,000,000 new
tions were as follows: respiratory, 27.3; gastrointesti- cases annually (5 per 100 people), with 300,000
nal, 14.4; cardiovascular, 13.3; musculoskeletal, 7.8; deaths (a 1 percent case-fatality rate). Seventy per-
and nervous system, 5.1. cent of China's counties were endemic for malaria
in the early 1950s. Surveys in 1957 reported 70
Communicable Diseases percent prevalence among children in Guangdong
and 48 percent in counties in Yunnan. Vigorous
Parasitic Diseases
efforts to control mosquito breeding sites - con-
Ancylostomiasis and Ascariasis. Estimates of the sisting of environmental management, mass chemo-
1945-59 period suggest that up to 100 million peo- prophylaxis during the transmission period, and
ple in China have had intestinal infestation with mass treatment - caused disease rates to fall rap-
parasites causing ancylostomiasis (the hookworm) idly in the 1950s.

Since 1974, the five provinces of Jiangsu, Shan- Efforts to reduce the source of infection have in-
dong, Henan, Anhui, and Hubei, which together ac- cluded early detection and treatment of patients at
count for about 80 percent of the national total of all stages of the disease, with emphasis on those who
malaria cases and which represent the main tertian handle diseased animals. People in snail-infested
malaria areas, have worked jointly to bring the dis- areas are encouraged to wear protective gear and
ease under control. In 1985, the number of new cases take prophylactic medicines when coming into con-
in the five provinces was 350,000, compared to the tact with water. Measures are also taken to ensure
14 million cases recorded in 1973 before the joint the safe collection and use of feces, and to encourage
prevention and control measures were taken. Over- the use of safe water supplies.
all, approximately one third of China's population is By the end of 1985, schistosomiasis was declared
now living in malaria-free areas, another third in officially eradicated in Shanghai and Guangdong,
areas with minimum risk, and the remaining third while Fujian, Jiangsu, and Guangxi have virtually
in endemic areas. The 563,400 cases reported for all eradicated the disease with more than 98 percent of
of China in 1985 represent an incidence of approxi- the endemic areas cleared of snails and over 90 per-
mately 5 per 10,000 population, close to the goal of cent of the known patients cured. Among the 371
under 1 per 10,000 by the year 2000. endemic counties and cities, 110 have been declared
eradicated and 161 have almost eradicated the dis-
Schistosomiasis. Schistosomiasis japonica, the ease. In the remaining 100 counties and cities, more
form of the disease found in China, is prevalent in than 50 percent of the townships and about two-
the provinces of Shanghai, Jiangsu, Zhejiang, thirds of the villages have eradicated or almost eradi-
Anhui, Fujian, Guangdong, Guangxi, Hunan, Hu- cated the disease. Accomplishments by 1985 in-
bei, Yunnan, Sichuan, and Jiangxi. It is carried by cluded the following: 95 percent of the 11.6 million
snails and is endemic in three types of environ- patients were treated; 77 percent of the infested area
ments: water courses, hilly regions, and lakes and was cleared of snails; and 92 percent of the 1.2 mil-
marshlands. Water courses account for 8 percent of lion head of afflicted cattle were treated or disposed
the endemic areas and 33 percent of the patients; of.
comparable values are 10 and 26 percent for hilly Despite these gains, concerns are being expressed
regions, and 82 and 41 percent for the lake and by Chinese and foreign schistosomiasis experts
marshlands areas. about the future. UNICEF's Situation Analysis for
Control efforts have been deployed on a large China of 1989 estimated that schistosomiasis was
scale. In December 1955, China set up prevention still present in 12 provinces with a combined popula-
and control stations in epidemic areas, and by 1958, tion of 50,000,000 and that the total of old cases
197 stations were staffed by more than 1,200 medi- approached 1,000,000 to which several thousand
cal teams and 17,000 specialized personnel (Chien new cases were added annually (UNICEF 1989). The
1958). By 1985, there were only 371 endemic coun- schistosomiasis control problem seems to have
ties with a total of 11.6 million cases and 14,000 shifted over the decades from that of devising meth-
square kilometers of snail-infested areas. During ods to control a major endemic parasitic disease to
the early stage of the nationwide prevention and that of identifying the few lightly infected individu-
control program, infestation rates typically ranged als in a sea of negatives, and ensuring that past
from 20 to 30 percent and in some areas reached 40 gains are maintained without backsliding (Basch
percent. Of those affected, about 40 percent were 1986).
symptomatic and about 5 percent evidenced ad-
vanced illness. Cattle and other domestic animals Nonparasitic Diseases
were also seriously afflicted by the disease.
The elimination of snails has been a key objective Acquired Immune Deficiency Syndrome (AIDS). As
of the program through such measures as draining of August 1989, China had reported only 22 human
marshlands, digging new ditches and filling up old immunodeficiency virus (HlV)-infected individuals
ones, changing paddies into dry crops, tractor plough- and three cases of AIDS. All were foreigners except
ing, field rolling, building snail trenches, and killing for four Chinese who were infected through contami-
snails by chemical methods. The construction of nated blood products (China Daily, Sept. 7,1989). The
dikes and the use of chemicals have proved very first indigenous case acquired through homosexual
effective along the banks of the Yangtze River in contact with a foreigner was reported in late 1989
Jiangsu Province. (China Daily, Nov. 2, 1989). Persons from areas of

high endemicity who wish to extend their visa stay populations have been found to be effective in con-
beyond a limited period of time are required to have a trolling the disease. Early diagnosis, rest, and hospi-
test for HTV antibodies performed in China, and must tal care in order to reduce the incidence of coma and
leave China immediately if the test is positive. By renal failure have lowered the case fatality rate to
December 1990 {China Daily, Dec. 31, 1990), China about 3.2 percent in 1984 {Public Health in the PRC
had identified a total of 446 HIV-positive cases, since 1986).
it started monitoring the epidemic in 1985, including
68 persons "from overseas." Influenza. Influenza is the most frequently re-
ported disease in China. Surveillance has been un-
Cholera. Cholera was said to be "virtually elimi- der way since 1968, yielding an epidemic pattern in
nated" by 1960 (Lampton 1977), and in 1985 only six south China that peaks in the summer and early
cases and two fatalities were reported. More recent fall, and an epidemic pattern in north China that
data from the Ministry of Public Health suggest that peaks in the winter. As China's population ages and
the disease is again of some importance, perhaps in grows more vulnerable to influenza because of other
part owing to better reporting. In 1989, the Ministry serious chronic diseases, influenza will become more
of Public Health reported that cholera still threatens important as an immediate cause of death. An exten-
residents of Hainan, Zhejiang, and Guandong prov- sive immunization campaign has been carried out in
inces, a part of suburban Shanghai, and Guangxi recent years, resulting in a reduction from 8 million
Zhuang Autonomous Region. In 1988 more than cases in 1975 to about 500,000 in 1980 and 1981. An
3,000 cholera cases were reported, but cases dropped unknown part of this decline may simply reflect the
to about 1,000 by the end of 1989 {.China Daily 1989). cyclic nature of the disease.
Dengue. The first recognized dengue epidemic Japanese B Encephalitis. Japanese B encephalitis
since 1949 occurred in Guangdong Province between is a mosquito-transmitted viral disease seen through-
June and September 1978, with an estimated 20,000 out much of East Asia and is thought to be present in
cases affecting persons of all ages. Approximately 25 all of China except Tibet and Xinjiang. The case-
percent had hemorrhagic manifestations. Because fatality rate in 1949 was estimated at about 30 per-
the usual vector, the Aedes aegypti mosquito, is cent, and large epidemics were frequently seen near
thought to be absent from this area of China, suspi- Shanghai, where the annual incidence was over 50
cion has focused on the Aedes albopictus. Epidemi- per 100,000. Since 1965 the incidence in the Shang-
ologists who investigated this epidemic assumed hai area has been only 2 to 3 per 100,000. Mosquito
that refugees from Vietnam (estimated to exceed vector control and vaccination of children have been
200,000) imported the virus. Another dengue out- priorities. Human cases peak at 4 to 5 years of age.
break occurred on Hainan Island in 1980, and spo- About 100,000 cases are reported annually in China.
radic cases continued until 1982. Transmitted by the
A. aegypti mosquito, the epidemic resulted in a peak Leprosy. Leprosy has been present in China for
morbidity rate of 2,146 per 10,000 and caused 64 more than 1,000 years. High prevalence areas are in
deaths (Qiu Fu-xi and Zhao Zhi-guo 1988). Dengue southeast and southwest China; low prevalence ar-
has been added to the list of officially notifiable eas are in the northeast and north. The official esti-
diseases, and no cases were reported in 1985. mate for prevalence in China in 1951 was 1.2 mil-
lion, although some international estimates placed
Epidemic Hemorrhagic Fever. Epidemic hemor- the prevalence as high as 3 million.
rhagic fever was first found in Heilongjiang province Since the 1950s about 500,000 cases have been
in the 1930s and then in the construction sites of the found, and more than 400,000 have been success-
northeast China forest zones and the Baoji-Chengdu fully treated. Methods used included specialized
Railway. The disease became more common in later training for health personnel, prevention and con-
years as the population increased in endemic areas trol networks, early diagnosis and treatment, and
as a result of water conservation, land reclamation, infection control. In Shandong, the average annual
and other construction projects. incidence declined from 5.1 in the late 1950s to 0.14
China has three types of epidemic foci: house per 100,000 in the early 1980s; the prevalence de-
mouse, field mouse, and the "mixed type." Gamasid clined from 91 in 1950 to 2.3 per 100,000 in 1984. In
and Trombiculid mites may also carry the virus. 1958, 17,535 villages reported leprosy cases, this
Measures directed primarily at reducing mouse number dropping to only 1,500 villages by 1984.

Current estimates suggest a total of 100,000 to During the early phase of the antiplague cam-
200,000 patients and a prevalence of less than 20 per paign, the state encouraged and subsidized rat-
100,000. China has recently embarked on a cam- killing drives by agricultural collectives along with
paign to eliminate most leprosy by the year 2000 programs to reduce other potential host animals.
through intensified efforts of education, research, Measures were also taken to destroy the ecological
and early diagnosis and treatment (Pubic Health in environment of major hosts in the course of planting
the PRC 1986). trees or in carrying out farmland improvement and
water conservation projects. As a result, rodent
Measles. In 1950 the measles case-fatality rate was plague has been virtually eliminated from most here-
6.5 percent, declining to 1.7 percent in 1956 with tofore endemic foci, and the ground squirrel, mar-
improved nutrition. When mass vaccination began mot, and other host populations have been sharply
in 1969, the incidence was estimated at about 3,000 reduced.
per 100,000, but it now has dropped to below 20 per By the end of the 1950s, the annual incidence of
100,000 for most big cities. The 1989 Ministry of plague in China had declined to about 30 per
Public Health epidemiologic report gave a time se- 100,000, and by the end of the following decade it
ries estimate of 2.4 million cases in 1978, and was under 12. The number of counties reporting
418,000, 199,000, 105,000, and 96,000 cases in 1985 plague cases annually ranged from 26 to 61 in 1950-
through 1988, respectively. During the years 1986- 4, 6 to 15 in 1955-60, and 0 to 8 after 1961 (Public
8, the proportion of infants under 1 year immunized Health in the PRC 1986). There were only 6 cases of
for measles rose steadily from 63 percent to 78 and plague in 1985, and the case fatality rate in recent
95 percent. The total annual reported deaths from years has been less than 8 percent.
measles since 1985 has been less than 1,000.
Poliomyelitis. Prior to 1955, epidemics of poliomy-
Neonatal Tetanus. Although data for pre-1949 are elitis were common in China. In 1959 in Nanning
unavailable, it is likely that neonatal tetanus ac- the incidence was 151 per 100,000, and incomplete
counted for as much as 20 percent of infant mortal- statistics for 17 administrative jurisdictions showed
ity, a percentage similar to that reported in the early an overall incidence of 5 per 100,000. There were
1980s in rural Thailand. Maternal and child health polio epidemics early in the Cultural Revolution
services in China now monitor more than 90 percent (1968-70), during which all immunizations were
of deliveries in most provinces, and neonatal tetanus said to have been neglected. The generation of those
is now said to be a rarity. Sample surveys have 10 to 20 years old at that time was most affected. As
detected neonatal tetanus in some of the more re- a result of a vigorous live-vaccine immunization cam-
mote counties, with an average death rate of approxi- paign, the incidence had declined to around 0.5 to
mately 3 per 1,000, ranging from 0.3 to over 13. By 0.75 per 100,000 by the mid-1980s. About 3,600 polio
using very fragmentary data from various sources, cases were reported from January to September
UNICEF has estimated that there are perhaps 1989 - up substantially from the approximately 700
10,000 neonatal tetanus deaths per year, or a rate of cases during the previous year (China Daily 1989).
about 0.5 per 1,000 live births.
Smallpox. The incidence of smallpox may have
Plague. The earliest known outbreak of plague in been as high as 200 per 100,000 population before
China was in Lu'an County, Shanxi Province in 1644 1949. A massive immunization campaign was
(Public Health in the PRC 1986). A well-documented started, and by 1953 over 50 percent of China's then
massive outbreak of pneumonic plague occurred in 600 million population had been vaccinated. The
1911 in Manchuria. This epidemic, in which 60,000 last cases, in Tibet and Yunnan, were seen in 1960
people were affected, led to the first international (Rung 1953).
medical conference in China and to the establish-
ment of the Manchurian Plague Preventive Service. Trachoma. Trachoma, an infectious eye disease
The failure of traditional Chinese medicine to con- that can cause blindness, was a major public health
trol the outbreak (practitioners of traditional medi- problem in China. Half of the population was esti-
cine experienced a 50 percent case-fatality rate) and mated to have been affected in the mid-1950s, and in
the success of Western methods (a case fatality rate some areas the prevalence may have reached 90
of 2 percent) were important factors in the rise of percent. Trachoma was estimated to have caused 45
Western medicine in China (Bowers 1972). percent of the visual impairment and between 25

and 40 percent of the blindness in China. Although diseases and were reported to have successfully
the current prevalence is unknown, trachoma is no "eradicated" them in China by the mid-1960s.
longer a public health problem. Education against Patients with venereal disease, however, began to
towel sharing ("one person one towel, running water be seen again in 1984, and by 1988 "tens of thou-
for washing face") had been very important as a sands" of such cases had been reported. Preliminary
control mechanism. reports from the country's 16 venereal disease inspec-
tion stations for the first 9 months of 1989 showed a
Tuberculosis. Tuberculosis was a leading cause of 61 percent rise in new VD patients over the 1988
death in China in the late 1940s, with a death rate of figure, bringing the cumulative total for the period
200 per 100,000 and a morbidity rate of 5,000 per to more than 220,000 (China Daily 1989). The high-
100,000 in major cities. At that time there were only est incidence has been in coastal areas, such as
13 prevention and control institutions and five small Guangdong, Guangxi, and Fujian provinces, though
prevention and control stations in the country, and cases have also been reported in Beijing, Shanghai,
only 7,500 people in all of China received bacillus Tienjin, Harbin, and Xinjiang. More than 70 percent
Calmette-Guerin (BCG) vaccine as immunization be- of the patients are male, and the most common dis-
tween 1937 and 1949 (Public Health in the PRC eases are gonorrhea, syphilis, and condyloma. Ac-
1986). cording to the head of a national venereal disease
Government control efforts resulted in the creation prevention committee, the renewed spread "arises
of a tuberculosis prevention and control network to from the reemergence of prostitutes, the increased
find, register, and treat patients at the earliest dis- activities of 'sex gangs,' as well as changing atti-
ease stage possible. In addition, BCG immunization tudes toward sex on the part of some young people
campaigns were launched, with emphasis on new- seeking sexual freedom" (Beijing Review 1988). In
borns and on the reinoculation of primary school stu- response, the State Council has issued a "strict ban"
dents. The BCG immunization campaign began in on prostitution; sex education courses have been
1950, and by 1979 an estimated 500 million immuni- widely introduced in middle schools; courses on vene-
zations had been given. A sample survey in the latter real disease are being reintroduced at medical col-
year indicated that prevalence had been reduced to leges; a national center for prevention and treat-
ment of venereal disease has been established; and
717 per 100,000, with sputum-positive cases averag-
monitoring and treatment stations have been set up
ing only 187 per 100,000.
around the country.
Since 1984, the Ministry of Public Health has pro-
moted the creation of tuberculosis prevention and
control in existing antiepidemic stations. By the end Viral Hepatitis. Since the 1950s hepatitis has been
of 1985,1,686 such institutions had been established increasing in many countries. In China, outbreaks
at the county level, and there were 117 tuberculosis have occurred in the northeast and north, with fluc-
hospitals throughout the country. A sample survey tuation in the incidence. In 1979-80 an extensive
of nine provinces and cities in 1984 found a preva- nationwide survey of the disease was conducted cov-
lence of less than 500 per 100,000. The incidence ering 277,186 people in 88 large, medium-sized, and
remains high, however, in remote areas and those small cities and 121 rural counties. Positive sero-
inhabited by minority nationalities (Public Health reactivity to anti-HBV averaged 71.4 percent and to
in the PRC 1986). hepatitis B surface antigen (HBsAg), 88 percent.
Infection appeared predominantly in two peak age
Typhoid and Paratyphoid Fevers. National data on groups, those under 10 and those between 30 and 40
typhoid and paratyphoid fevers were not available years; rates for males were higher than for females.
until recently. In 1975, Shanghai registered an esti- HBsAg seropositivity was higher in family groups
mated 600 cases of typhoid fever (Lampton 1977), and did not seem to be particularly correlated with
and in 1985 there were an estimated 86,000 cases of occupation (Public Health in the PRC 1986).
typhoid and paratyphoid nationwide. Viral hepatitis research became a priority under
the sixth five-year plan (1981-5), with particular
Venereal Disease. In the early 1950s, the prevalence emphasis directed toward development of a low-cost
of venereal disease in China was estimated at 3 to 5 vaccine and on the improvement of prevention and
percent in the cities, and as high as 10 percent among control measures. Research and development of a
those who lived in the frontier areas (Lampton 1977). hepatitis B hemogenetic vaccine began in 1978 and
Extraordinary efforts were mounted to combat these was completed in 1983. Confirmatory tests in 1985

showed that the vaccine was safe and effective, and pollution from factories, transport, home cooking
mass production is planned. over open stoves, and, with increasing frequency,
Responsibility for hepatitis prevention and control cigarette smoking. Although national statistics are
is vested in the sanitation and antiepidemic stations still inadequate to distinguish between cor pulmo-
at all administrative levels. Stations collect and ana- nale and COLD, data from the Disease Surveillance
lyze morbidity data, conduct epidemiologic studies, Point (DSP) system covering a population of about
and provide assistance to medical units, to patients' 10 million will soon be able to provide better esti-
families, and to organizations on such matters as mates of the magnitude of these and other health
patient isolation, sterilization, food and water man- problems. COLD morbidity has been estimated at 20
agement, environmental sanitation, and personal hy- times COLD mortality and appears to affect rural
giene. They also provide regular medical examina- residents substantially more than those in urban
tions to food industry and nursery personnel. areas.
Strengthened hygienic legislation, standards, and Rheumatic heart disease has accounted for a ma-
administrative guidelines have also contributed to a jor portion of heart disease morbidity and mortality
reduction in the spread of both hepatitis A and B. in the past, but today, with the widespread use of
For example, many hospitals have set up hepatitis antibiotics, its significance is on the decline. In 1986,
wards to prevent hepatitis B from spreading. Special an estimated 50,000 deaths resulted from this dis-
attention has been given to screening blood donors ease, with perhaps some 1 million infected.
and to the strict management of blood products. Coronary heart disease, the main form of heart
Most health facilities now use disposable needles disease in the industrialized countries, is in fourth
and syringes and have tightened the control and place in China but is expected to gain rapidly in
disposal methods of blood stained water and objects. importance as a result of the delayed effects of richer
diets and more cigarette smoking. In four urban
Chronic Diseases districts of Beijing, for example, the coronary heart
Chronic diseases now account for almost two-thirds disease death rate doubled from 71 per 100,000 in
of all mortality in China and are expected to become 1958 (10.8 percent of all deaths), to 141 per 100,000
even more significant in the future, owing to an in 1979 (25 percent of all deaths).
aging population and to changing environmental
and life-style factors. This section considers briefly Cerebrovascular Disease. More commonly known
the three main chronic disease categories: heart disas stroke, cerebrovascular disease is most often a
ease, stroke, and cancer. complication of hypertension and is currently the
third leading cause of death in China. In the same
Heart Disease. Heart disease is now the leading four urban districts of Beijing mentioned above,
cause of death in China. Among the deaths from stroke was responsible for 152 deaths per 100,000
heart disease the causes are, in declining order of population in 1979 (27.3 percent of all deaths), as
frequency, hypertensive heart disease, cor pulmo- compared to 107 per 100,000 in 1958. The ratio of
nale, rheumatic heart disease, and coronary heart stroke to coronary heart disease mortality (a rela-
disease. The importance of coronary heart disease is, tively small part of all heart disease mortality) in
however, increasing rapidly. China is about 4:1 as compared with about 1:3 in the
Hypertension's contribution to stroke and renal United States, though this is expected to change
disease as well as to hypertensive heart disease rapidly as the effects of dietary and smoking habits
probably makes this condition the largest single risk come to be fully manifest.
factor for death in China. Based on age-specific hy-
pertension rates observed in a 1979 national hyper- Cancer. Cancer has become one of China's top
tension sample survey, by 2010 China could have three causes of death. According to 1986 Disease
more than 110 million cases of hypertension. With Surveillance Point mortality data, the five leading
rising incomes, however, and a probable parallel rise cancers in men were, in rank order, lung, stomach,
in age-specific rates, this may be a low estimate. liver, esophagus, and colorectal, while for women
Cor pulmonale, manifested by right ventricular cervix cancer replaced colorectal in fifth place. Those
hypertrophy and decreased output, appears to be who live in urban areas have a 50 percent higher
linked to the high prevalence of chronic obstructive cancer mortality rate than do rural residents, and
lung disease (COLD). This condition is most often men are about 50 percent more at risk than are
the end result of pneumoconiosis secondary to air women, regardless of location. When compared with

the results of a retrospective survey of all deaths in Occupational Diseases
mainland China for the years 1973-5, these data The safety of the workplace has received increasing
suggest that overall cancer mortality rates are ris- attention since the first industrial health organiza-
ing, lung cancer is gaining in relative importance, tion was established in 1950. By 1985 there were
and esophageal cancer may be declining. more than 170 such organizations and industrial
Three examples from the 1973-5 survey illustrate health sections at more than 3,300 sanitation and
the wide regional variations that can be observed in antiepidemic stations, and about 25,000 persons
cancer mortality according to site, variations that were employed in this field. Starting with the pro-
have recently been mapped by the government's Na- mulgation of regulations on the control of silicon
tional Cancer Control Office. Nasopharyngeal can- dust at the workplace in 1956, health authorities
cer is virtually limited to south China, with the have extended industrial health regulations until by
highest incidence in Guangdong Province, from 1985 there were 122 industrial health standards and
which it decreases in concentric bands. Mortality 16 standards for diagnosing occupational diseases.
due to cancer of the esophagus varies more than The decline in the incidence of silicosis documents
sixfold across China's counties, with higher preva- both what has been accomplished and what remains
lence locations often separated by long distances. to be done. According to a recent study of silicosis in
Liver cancer tends to be concentrated in coastal 26,603 dust-exposed workers at seven mines and
plains in the southeast. industrial plants, the 8-year cumulative incidence of
The diverse patterns in the geographic distribu- silicosis declined from 36.1 percent among workers
tion of cancer have led to epidemiological research employed before 1950 to 1.5 percent for those em-
on selected cancers (see, e.g., Armstrong 1982). With ployed after 1960 (Lou and Zhou 1989). During the
60 percent of all fatal cancers originating in the same period, the cumulative incidence of tuberculo-
upper alimentary tract, particular attention has sis decreased from 54.7 to 16.7 percent, and the silico-
been given to the role of diet and food hygiene. Can- sis case-fatality rate declined from 53.9 to 18.3 per-
cer epidemiology has also focused on trend analysis. cent. The average age at the detection of silicosis
Through such studies it has been found that whereas increased from 41.3 to 52.7 years from the 1950s to
the incidence of stomach cancer in China has been the 1970s, while the average survival times of silico-
decreasing in recent years, that of lung cancer has sis patients increased from 2.0 to 12.2 years.
increased rapidly. This latter trend had been espe-
cially pronounced in urban areas and is presumably Nutritional Diseases
associated with rising levels of smoking, as shown
by studies such as that by Y. T. Gao and colleagues Endemic Fluorine Poisoning. Endemicfluorinepoi-
(1988). High lung cancer rates have also been found soning is a chronic disease caused by an excess in
in rural areas subject to serious problems of indoor intake of fluorine. On the basis of epidemiological
air pollution (Chapman, Mumford, and Harris surveys, it is currently estimated that in all areas of
1988). endemicity there are some 21 million people suffer-
Chinese authorities have recently begun to ad- ing fromfluoride-causedmottled enamel and 1 mil-
dress the public health hazards of smoking. Surveys lion from bone disease caused by fluorine poisoning
have found that some 69 percent of Chinese men and (Public Health in the PRC 1986). Efforts to control
7 percent of women above the age of 20 smoke, and, the disease include the use of rainwater, along with
although the rate for women is still low, this is likely wells and other low-fluorine water sources, for drink-
to increase rapidly in the future. Antismoking ing purposes, and treating water supplies to reduce
measures - including education, cigarette price in- the fluorine content. The provision of fluorine-free
creases, limits on tobacco production, and banning of drinking water became one of China's projects in a
smoking in certain locations - have not had much 10-year world program for attaining a safe drinking-
effect thus far. Rather, cigarette production in- water supply and environmental hygiene.
creased 9-fold between 1949 and 1980. Chinese ciga-
rettes have about double the world average of tar, Endemic Goiter and Endemic Cretinism. Endemic
and now with the government deriving significant goiter is caused by lack of iodine in the diet. Surveys
revenues from the sale of cigarettes, and the sudden suggest that about 35,000,000 people in China suf-
increase in the importation of foreign brands, the fered from endemic goiter and another 250,000 from
potential for a rapid increase in tobacco consumption endemic cretinism. However, over the past three de-
is great indeed. cades more than 2,500 monitoring stations have

been set up to supervise the production, marketing, used sodium selenite and vitamin E to treat 224
and use of iodized salt. By 1985 this salt was avail- children suffering from the early-stage Kaschin-
able to about 85 percent of the counties in the en- Beck disease. In areas where the disease is present,
demic areas, and as a result of these and other mea- the lower the ambient selenium levels, the greater
sures, over 22,000,000 endemic goiter patients have the prevalence. From 1981 to 1985, Shaanxi Prov-
been successfully treated. The average incidence of ince experimented with use of seleniumized table
the disease has been reduced to under 4 percent, and salt to prevent the disease. Measures to increase
few patients with endemic cretinism are now found selenium intake, now used among more than 8 mil-
(Public Health in thePRC 1986). lion people, are considered a major approach to the
prevention of Kaschin-Beck disease (Public Health
Kaschin—Beck Disease. This disease is a chronic in the PRC 1986).
degenerative osteoarthropathy of unknown cause.
The major pathological changes include degenera- Keshan Disease. Keshan disease is a myocardial
tive necrosis of leg and arm joints and of epiphyseal disease found in a long, narrow strip of land covering
plate cartilage. The earliest written record of the 309 counties from northeast to southwest China.
disease was made in 1934, but it is believed to have The disease is sudden in onset and often acute, with
existed in China for a long time. a high case-fatality rate of around 20 percent. House-
Surveys conducted since the early 1950s show that wives and teenagers are at particular risk. Keshan
Kaschin-Beck disease prevails in a wide area from disease has been endemic in China for about 100
the northeast to the southwest, covering 287 coun- years, and a 1935 outbreak of the disease in Keshan
ties and cities in 15 provinces, autonomous regions, County, Heilongjiang Province, led to its name. En-
and municipalities. It is estimated that 1.6 million demic areas have been found to have low selenium
people suffer from the disease, 65 percent of whom levels in the water, earth, grain, and vegetables, and
are youths and teenagers. Disease incidence fluctu- residents suffer from a deficiency of selenium. Con-
ates substantially, and a rainy autumn usually re- siderable success in reducing disease incidence has
sults in an increased incidence the next year. There been achieved with oral sodium selenite, but sele-
are three views as to the etiology of Kaschin-Beck nium deficiency may not be the only cause.
disease: poisonous organic matter in water, the fusar- Effective measures to prevent and control Keshan
ium tox in grain, and excessive or insufficient trace disease include keeping homes warm, dry, and free
elements in water, soil, and grain (Public Health in of smoke, ensuring safe drinking water, improved
the PRC 1986). eating habits, early diagnosis, and treatment. The
Several methods have been used to prevent and principal treatment methods are intravenous injec-
treat Kaschin—Beck disease. One includes the use of tion of high doses of vitamin C and blood expanders;
deep wells, alternate water sources, or water treat- oral selenite is used to prevent acute and subacute
ment with active carbon and magnesium sulfate to Keshan disease. There have been no widespread out-
improve its quality. A study done in Fusong County breaks of the disease for 15 years. In 1985, only 374
of Jilin Province from 1972 to 1977 showed that cases of acute and subacute Keshan disease were
disease incidence for people drinking water diverted found, with 92 deaths, the lowest rates ever. The
from nearby springs was 1.2 percent, as compared number of chronic patients has decreased from
with 13.5 percent for those who continued to drink 220,000 in the early 1970s to 76,500 by the mid-
from old sources (Public Health in the PRC 1986). 1980s. A total of 4.1 million people now take oral
Another method is to provide grain from non- selenite, contributing to the falling incidence (Public
affected areas to people in affected areas. Mean- Health of the PRC 1986).
while, efforts are made to prevent grain in storage
from becoming mildewed. A 7-year study in Shuang- Summary
yashan City which compared two areas using the China has undergone a remarkably rapid epidemio-
same water sources found no new cases in an area logical transition over the past 40 years, from a
where outside grain was available. By contrast, the preponderance of deaths due to communicable dis-
incidence continued to rise in the area using indige- ease to a preponderance of deaths due to chronic
nous grain (Public Health in the PRC 1986). disease. As China looks ahead to the twenty-first
More recent studies have demonstrated a relation- century, with its reduced birth rate and longer life
ship between selenium intake and Kaschin-Beck expectancy, it faces the prospect of ever higher per-
disease. Between 1974 and 1976, Gansu Province centages of older people. According to World Bank

VI.4. Antiquity in Japan 373
estimates, by 2025 China could have 185 million Lou, Jiezhi, and Chen Zhou. 1989. The prevention of silico-
people aged 65 and over or about 12 percent of its sis and prediction of its future prevalence in China.
projected 1.5 billion population, and the burden of American Journal of Public Health 79: 1613-16.
chronic disease will be great. With the 2025 per Nathan, Carl F. 1967. Plague prevention and politics in
capita gross national product unlikely to exceed U.S. Manchuria, 1910-1931. Cambridge.
$2,000, China will find it very difficult to provide the The National Cancer Control Office of the Ministry of
Health. 1980. Investigation of cancer mortality in
high technology, institution-based care for chronic China. Beijing.
disease that has become the dominant pattern in Parker, R. L., et al. 1982. The sample household health
industrialized countries. Innovative and inexpen- interview survey. American Journal of Public Health
sive methods for the prevention of and care for 72 (Suppl., Sept.): 65-70.
chronic illnesses, for providing continuing patient People's Daily. 1989. April 26.
care, and for maintaining past gains in the control of Public health in the People's Republic of China. 1986.
communicable disease, are therefore even more im- Beijing.
portant in China than in the economically developed Qiu Fu-xi, and Zhao Zhi-guo. 1988. A pandemic of dengue
countries. These challenges will be all the greater as fever on the Hainan Island: Epidemiologic investiga-
China undergoes major social, economic, and politi- tions. Chinese Medical Journal 101: 463-7.
cal changes that have reduced its ability to mobilize Sidel, Ruth, and Victor W. Sidel. 1982. The health of
China. Boston.
mass patriotic campaigns and to provide organized
UNICEF. 1987. UNICEF in China.
rural health care. 1989. Children and women of China - A UNICEF situa-
Thomas L. Hall and Victor W. Sidel tion analysis. Beijing.
The authors gratefully acknowledge the assistance of Mr. Gu World Development Report. 1987. Published for the World
Dezhang of the Chinese Medical Association, Beijing, in obtain- Bank.
ing and verifying some of the data used in this chapter. Worth, Robert. 1973. New China's accomplishments in the
control of diseases. In Public Health in the People's
Bibliography Republic of China, ed. Myron E. Wegman, Tsung-yi
Armstrong, Bruce. 1982. The epidemiology of cancer in Lin, and Elizabeth F. Purcell, 173-84. New York.
China. World Health Forum 3: 95-101.
Basch, Paul F. 1986. Schistosomiasis in China: An update.
American Journal ofChinese Medicine 14(1-2): 17-25.
Beijing Review. May 30, 1988. VD spread causes public
concern. VI.4
Bowers, John Z. 1972. Western medicine in a Chinese pal-
ace. New York. Diseases of Antiquity in
Chapman, R. S., J. L. Mumford, and D. B. Harris. 1988.
The epidemiology of lung cancer in Xuan Wei, China:
Japan
Current progress, issues, and research strategies. Ar-
chives of Environmental Health 43: 180—5.
Cheng Tien-hsi. 1973. Disease control and prevention. In Our knowledge about diseases in the prehistoric era
Public health in the People's Republic of China, ed. of Japan is extremely limited because not much
Myron E. Wegman, Tsung-yi Lin, and Elizabeth F. paleopathological research has been done thus far.
Purcell, 185-207. New York. For the little information we have about the occur-
Chien Hsin-chung. 1958. Summing up of mass technical rence of diseases during the early historic period we
experience with a view to expediting eradication of have to rely on a small number of literary sources.
the five major parasitic diseases. Chinese Medical One general assumption, however, may be made
Journal 77: 521-32. from the geographic situation of the Japanese is-
China Daily. 1989. Science and medicine. Sept. 7, Nov. 2, lands: Prior to more extensive contact with the
and Dec. 12.
Asian continent, Japan may have been free from
China: The health sector. 1984. The World Bank. Washing-
ton, D.C.
regular epidemics of certain contagious diseases
Gao, Y. T., et al. 1988. Lung cancer and smoking in Shang- such as smallpox and plague.
hai. International Journal of Epidemiology 17:277-80. The most important sources on the early history of
Kung, N. C. 1953. New China's achievements in health Japan are the Kojiki (The Ancient Chronicle), com-
work. Chinese Medical Journal 71: 87-92. pleted in A.D. 712, and the Nihonshoki (The Chroni-
Lampton, David M. 1977. The politics of medicine in cles of Japan), completed in A.D. 720. Both these
China. Boulder, Co. chronicles include references to diseases that af-

fected individuals, as well as to epidemics. The ary works of ancient Japan. In these passages, per-
Kojiki informs us that there "raged many plagues" sons are said to "suffer from the chest." The
at the time of Emperor Sujin, who was supposed to Ishinpo, a collection of excerpts from Chinese medi-
be the first Emperor and to have reigned around the cal books, compiled by the Japanese scholar Tamba
end of the third century A.D. The Nihonshoki con- Yasuyori in 984, records a disease called denshi-
firms that "plagues spread out everywhere in Ja- byo. The symptoms of this illness were similar to
pan." These epidemics may have been caused by those of tuberculosis.
climatic irregularities at that period; one passage in The Ishinpo also lists nine helminthic parasites,
this source states: "Because the winter and the sum- among which the tapeworm, roundworm, and
mer exchanged their places and the cold and heat pinworm can be identified; in ancient Japan all
occurred in irregular order, the plagues spread and three were called suhaku. With the understanding
the people suffered." Considering the influence of that the Japanese compiler of this book selected sub-
these climatic changes on the crops, one may specu- jects from Chinese medical literature that were ap-
late that these epidemics were famine-related dysen- plicable to the situation in Japan at the end of the
teries. A passage in the Nihonshoki describes the first millennium, it seems safe to assume the exis-
symptoms of a princess at the court who had fallen tence of a wide array of parasitosis there as well.
ill, by stating that she "lost her hair and became Another text of the period describes a woman suffer-
very thin" - symptoms suggestive of high fever and ing from suhaku, who was pale and had dropsical
dehydration that might accompany such forms of swellings. A physician drew from her body a white
dysentery. On the other hand, it would appear un- worm, 12 to 14 meters in length.
likely that famine would have reached the immedi- Although there are some indications of the exis-
ate environment of the emperor. Hence, with so little tence of lice in ancient Japan, there is no proof for
information a diagnosis can hardly be made with the occurrence of exanthematous typhus. Nor is
any degree of probability. there any source prior to the nineteenth century
Undoubtedly, poor sanitation and a lack of hy- suggesting an outbreak of the bubonic plague, a
giene must have been responsible for epidemics of disease that raged in China for decades around the
dysentery; these were recorded as ribyo or kakuran. turn of the eighth to the ninth century.
The epidemic recorded for the year 861 was identi- Beriberi, a disease caused by thiamine deficiency
fied as sekiri, possibly meaning bacillary dysentery. and often associated with cultures that relied on rice
From the first mention of this illness onward, it as staple food, was endemic in Japan. It was called,
appears to have reappeared frequently. One of the alternatively, kakke, kakubyo, or ashinoke, the latter
representations on the Yamai-no-Soshi (Scrolls of meaning "illness of the legs." The oldest record of
Disease) made during the twelfth century, at the end beriberi in Japan refers to the son of the Emperor
of the Heian Era, carries a caption stating that a Shomu, who died of this disease in A.D. 744, at the
woman "has a sharp pain in the bowels, vomits wa- age of 17 years. The Ishinpo, compiled one and a half
ter, has diarrhea and stumbles around to create a centuries later, contains a detailed description of the
strange spectacle"; these symptoms suggest bacil- symptoms, such as pain, paralysis of the legs,
lary dysentery. anasarca, and palpitations.
Diaries written by members of the gentry of the In A.D. 733, Yamanoueno Okura, the famous poet
same period refer to the occurrence of malaria. The of the Manyoshu (the oldest existing anthology of
Anopheles mosquito, the host of various types of poetry), died at the age of 74. According to his poem
plasmodia, seems to have been present in Japan at he had suffered from a disease for 10 years that
all times. Malaria was called either okori or caused him considerable discomfort: "The hands and
warawa-yami, the latter meaning high fever and feet do not move, every joint aches, the body is like a
chills. Another name, also found in the scrolls, was heavy stone and walking is difficult." Hattori
gyaku-shitsu: According to this source, illness was Toshiro (1945) has concluded that this disease was
characterized by fever and chills that recurred rheumatoid arthritis. Others believe that arthritis
throughout an individual's life. deformans is a more likely possibility. Both condi-
Tuberculosis, especially pulmonary tuberculosis, tions must have tormented ancient Japanese,
may also have been present in ancient Japan. Possi- whereas neuralgia of the hands and feet must have
ble references to pulmonary tuberculosis are con- been quite common because of agricultural labor.
tained in certain passages in the Genji-Monogatari The oldest Japanese statutory law, the Yoro-ryo,
and in the Makura-no-Soshi, the two greatest liter- enacted in 718, classified diseases of laborers and

VI.4. Antiquity in Japan 375
military men into three grades, ranging from severe nologically defenseless population of the Japanese
to relatively mild. Among the most severe of diseases archipelago. Smallpox, most probably originating
was leprosy. In this text it is described as follows: from India, reached China in the wake of Indian
"The intestines are eaten by worms, the eyebrows fall Buddhist missionaries via the Silk Road. It was first
down, the nose is out of shape, the voice changes, the described by a Daoist, Ge Hong, in his Zhou-hou bei-
body bends over, and it is contagious." Leprosy was ji fang. The first record of a smallpox epidemic in
called rai or rei or elsetenkei-byo,which means liter- China appeared in the Jianwu Era (around A.D.
ally "disease of heavenly punishment." Although lep- 495), when it was called hu-dou, "barbarian pox." It
ers were regarded as untouchables and had to be spread to Korea, and eventually reached Japan with
strictly separated from the healthy population, a Bud- the first Buddhist missionaries, arriving there in
dhist legend has it that Empress Komyo (701-60), 552. In the same year a series of epidemics started
while cleaning pus from a leper's body, discovered ravaging the country and continued periodically un-
that the man was Buddha. til 582. There is no proof as to whether the disease
As in all premodern societies, skin diseases, par- was smallpox in every instance; measles or influ-
ticularly inflammatory afflictions, were known enza could have been similarly devastating. Since
among the Japanese. The Ishinpo includes chapters the relationship between the opening of the country
on afflictions that can be identified as scabies, and the arrival of these diseases was apparently
pustular and other forms of suppurative dermatitis, understood, there is little wonder that opinions
carbuncles, scrofula, felon, and erysipelas. Some about the question of whether Buddhism should or
sources indicate that gonorrhea and soft chancre should not be introduced to Japan divided society
occurred in ancient Japan, under the names rin- and the influential feudal families.
shitsu, bendoku, and genkan. However, these terms Shoji Tatsukawa
appear in medical books only from the fifteenth cen-
tury onward. Similarly, syphilis is encountered for Bibliography
the first time during this period. Japanese pirates Cloudsley-Thompson, J. L. 1976. Insects and history. Lon-
apparently brought the bacterium into the islands don
from European ports in China. Dohi, K. 1921. Sekai baidoku-shi (History of syphilis).
Among the diseases of the nervous system, we Tokyo.
have an illustration of cerebral apoplexy in the Fujikawa, Yu. 1912. Nihon shippei-shi (History of dis-
eases in Japan). Tokyo.
Yami-no-Soshi. Not unfrequently, diaries and liter-
Hattori, Toshiro. 1945. Nara-jidai igaku no Kenkyu (Medi-
ary works describe instances of mental disorders cine in Nara-Era). Tokyo.
that can be identified as schizophrenia, or other neu- 1955. Heian jidai igaku no kenkyu (Medicine in Heian
rological conditions such as epilepsy. period, 784-1185). Tokyo.
A well-documented and typical case of diabetes Henschen, Folke. 1966. The history and geography of dis-
mellitus may be found in the medical history of eases, trans. Joan Tate. New York.
Fujiwara no Michinaga, a very powerful nobleman McNeill, W. 1976. Plagues and peoples. New York.
of the Heian Era. In 1016, at the age of 62 years, he Tatsukawa, Shoji 1976. Nihonjin no byoreki (History of
began suffering from thirst, weakness, and emacia- diseases in Japan). Tokyo.
tion. His disease was diagnosed as insui-byo. As the
illness advanced, he suffered from carbuncles, devel-
oped cataracts, and finally died from a myocardial
infarction. As a matter of fact, this disease was he-
reditary in this branch of the Fujiwara family:
Michinaga's elder brother, his uncle, and his nephew
all died of diabetes at fairly young ages.
The relative isolation of Japan long protected it
from the great epidemics, such as smallpox, plague,
and influenza, which raged in other areas of Asia.
This isolation was, however, as William McNeill
(1976) has pointed out, a "mixed blessing." As Bud-
dhism flourished, and contacts with Korea and
China increased, diseases that were endemic in
these countries began to strike the dense and immu-

disease, the regions afflicted, or levels of mortality
VI.5 inflicted. In addition, local records that would en-
Diseases of the Premodern hance our knowledge of diseases that prevailed are
largely lacking before 1100, and the job of ferreting
Period in Japan through village and town documents for signs of
pestilence after 1100 has yet to be attempted.
About the time that the Japanese government bor-
The role of disease in Japanese history is a topic that rowed the Chinese custom of recording outbreaks of
has attracted the interest of Western historians only pestilence, it also borrowed their medical theory.
recently. The strongest stimulus for the study of The description, diagnosis, and treatment of disease
disease and its effects on Japan's premodern society in premodern Japan almost always derive from Chi-
was the publication of a new edition of Fujikawa nese texts. Buddhist scriptures from India also influ-
Yu's classic Nikon shippei shi in 1969 with a fore- enced how disease and medicine were perceived in
word by Matsuda Michio (A History of Disease in early Japan. It is unclear how much the Japanese
Japan, originally published in 1912). Along with his knew about disease and its treatment before Chi-
History of Japanese Medicine {Nihon igaku shi, nese and Indian influences. Some medical practices
1904), A History ofDisease in Japan provided histori- reported during early epidemics may well derive
ans with a detailed list of many of the epidemics that from native roots, as during the Great Smallpox
ravaged the Japanese population in the premodern Epidemic of 735-7 (Farris 1985). For the most part,
era, including original sources of information and a however, the native Japanese view of disease was
diagnosis of many diseases in terms of Western medi- that it was demonic possession to be exorcised by
cine. Hattori Toshiro supplemented and updated shamans and witch doctors.
Fujikawa's work in the postwar era with a series of It is important to distinguish between infectious
books on Japanese medicine from the eighth through diseases, which can create epidemics, and other af-
the sixteenth century. flictions, which, to use McNeill's terminology (1976),
William McNeill also kindled interest with form the "background noise" to history. Japanese
Plagues and Peoples (1976), a book that fit the dis- sources provide information on a wide variety of
ease history of East Asia into the context of world diseases, especially when they attacked a states-
history. Both William Wayne Farris (1985) and Ann man, artist, or priest. However, it is often difficult to
Bowman Jannetta (1987) have investigated pesti- classify the illness in Western terms. For this reason,
lence in premodern Japan in detail, but the field is the focus of this essay will be chiefly on epidemic
still relatively undeveloped, as compared to work on outbreaks, with occasional reference to identifiable,
Western history. The influence of the Annales school noninfectious ailments.
of France on Japanese scholars, which began in the The relationship between disease and Japan's ge-
late 1970s, may draw more scholars into work on ography is significant in two respects. First, Japan
disease, especially for the well-reported but un- presents a good case of "island epidemiology" (Mc-
studied period between 1300 and 1600. Neill 1976). Because of its comparative isolation,
Data for the study of disease in Japan present both Japan remained relatively free of epidemic out-
opportunities and frustrations. The quantity of infor- breaks as long as communication with the continent
mation on disease, especially epidemic afflictions, is was infrequent. Consequently, the populations grew
better than for most other civilizations, including dense. However, once an infectious disease was intro-
possibly western Europe. The reason for this is that duced to the archipelago, it ravaged those dense
the Japanese imported the Chinese practice of report- populations that had had virtually no opportunity to
ing diseases among the common people around 700. develop resistance to it. Thus, immunities were built
Many of these reports were included in court chroni- up only slowly in a process that took centuries.
cles in abbreviated form. The custom of reporting Second, because of Japan's mountainous terrain,
epidemics suffered, however, as the links between one cannot always assume that an epidemic reached
the provinces and the capital waned after 900, and the entire Japanese populace at once. Severe out-
many outbreaks of pestilence undoubtedly went un- breaks undoubtedly afflicted isolated villages and
noticed by the aristocrats at court who did the record- regions even in the Edo period (1600-1868). Cer-
ing of disease. Moreover, even when the reporting tainly, more study of the important relationship be-
system was operating at its best, the sources often do tween Japan's topography and transportation routes
not provide important facts such as the nature of the and disease transmission is needed.

VI.5. Premodern Period in Japan 377
The history of epidemics in Japan until 1600 The 552 and 585 {not 587, as some have reported)
(when Japan banned travel and trade with most outbreaks are the only signs of pestilence between
nations) falls into four periods: (1) from earliest 500 and the end of the seventh century. There are
times to 700, when little is known about disease; (2) two ways to interpret the absence of data on disease
700-1050, an age of severe epidemics; (3) 1050- for this epoch. First, the sixth and seventh centuries
1260, a transitional stage when some killer diseases may have been relatively disease-free, in which case
of the past became endemic in the population; and the era must have seen a population boom - a boom
(4) 1260-1600, a time of lessening disease influence that would have coincided with the introduction of
despite the introduction of some new ailments from Chinese institutions into Japan. A second and more
the West. likely answer is that the chroniclers simply did not
record epidemics. Sources from the period 500 to 700
Pre-A.D. 700 are notoriously scarce and inaccurate. Moreover, dur-
The record of disease in Japan's prehistory is a mating these two centuries Japan sent 11 embassies to
ter of guesswork. In the earliest times, the Paleo- China, received 7 from China, and had about 80
lithic (150,000 B.C. to 10,000 B.C.) and Neolithic exchanges with Korea (Farris 1985). Given these
(10,000 B.C. to 200 B.C.) periods, population was too contacts with the outside world, it is therefore con-
sparse to sustain many afflictions. Evidence indi- ceivable that disease was an important feature of
cates that there was a Malthusian crisis in the late Japanese demographic history for the era 500 to 700.
Neolithic epoch, about 1000 B.C., but archaeologists Beginning in 698, it definitely was. Historical
have not been able to discern any signs of infectious sources disclose an alarming number of epidemic
diseases in the skeletons of Neolithic peoples (Kito outbreaks. There are 34 epidemics for the eighth
1983). The bronze and iron ages (200 B.C. to A.D. century, 35 for the ninth century, 26 for the tenth
300), when rice agriculture was imported from the century (despite a marked decline in the number of
Asian mainland, would seen to have been an age of records), and 24 for the eleventh century, 16 of which
great population increase and therefore of potential occur between the year 1000 and 1052 (SZKT 1933
disease outbreak as well. However, again the ar- and 1966; Hattori 1945; Tsuchida 1965; Fujikawa
chaeological record gives no indication of illnesses in 1969; and Farris 1985).
those few skeletons that remain. Similarly, there is Because of this spate of pestilential outbreaks, the
little evidence on disease for the era from 300 to 500. period from about 700 to about 1050 stands out as
Japan's age of plagues. Records suggest that the
700-1050 diseases were imported from the Asian mainland as
Most scholars of Japan agree that the historical age the Japanese traveled to China and Korea to learn of
begins with the sixth century, and hard evidence of superior continental political and cultural systems
disease in the region also originates with this time. and to trade. Disease became a major influence on
Japan's first court history, The Chronicles of Japan, Japanese society, shaping tax structure, local govern-
records that in 552 many were stricken with disease. ment, land tenure, labor, technology, religion, litera-
It is no accident that this epidemic occurred at the ture, education, and many other aspects of life. Cer-
same time that the gifts of a statue of the Buddha tainly, the epidemics in these centuries held back
along with sutras arrived at the Japanese court from economic development of the islands. On the other
Korea (Aston 1972). Disease doubtless also arrived hand, by undergoing such trauma early in their his-
with the carriers, although the court blamed the tory, the Japanese people built immunities at a rela-
outbreak on the introduction of a foreign religion tively early date and thus escaped the onslaught of
and destroyed the gifts. diseases that came to the civilizations of the Incas,
In 585, the court again banned the worship of the Aztecs, and others with Western contact in the six-
Buddha, and this time chroniclers noted that many teenth century.
people were afflicted with sores. The Chronicles of Unfortunately, historical documents do not often
Japan states that those attacked by the sores were reveal the nature of the diseases in question. Histori-
"as if they were burnt," a condition suggesting fever. ans can identify only five of them: smallpox, mea-
According to Hattori Toshiro (1943), the 585 epi- sles, influenza, mumps, and dysentery. In addition,
demic was the first outbreak of smallpox in Japanese McNeill (1976) has suggested that plague may have
history, although it should be noted that some found its way to Japan in 808, and his argument has
sources from later centuries record that the 585 epi- a great deal to recommend it. Plague was then afflict-
demic was measles. ing the Mediterranean and the Middle East, and

Arabic traders and sailors frequented Chinese, Ko- vocated a variety of palliatives, including wrapping
rean, and Japanese ports. Denis Twitchett (1979) the patient in warm covers, drinking rice gruel, eat-
has shown that China received many diseases from ing boiled scallions to stop the diarrhea, and forcing
the West via the Silk Route. The presence of plague patients with no appetite to eat. Medicines were
in Japan would also go a long way in explaining seen as of little use against the disease. After the
several severe epidemics that have yet to be identi- illness, those who recovered were admonished not to
fied. Yet because there is no description of symptoms eat rawfishor fresh fruit or vegetables, drink water,
by the Japanese sources, the existence of plague in take a bath, have sex, or walk in the wind or rain.
Japan during this period remains in doubt. Doctors also advocated mixing flour from red beans
and the white of an egg, and applying the mixture to
Smallpox the skin to eliminate the pox. Bathing in a woman's
The most deadly killer among the five diseases that menstrual flow or wrapping a baby in a menstrual
are known to have assaulted early Japan was small- cloth to wipe out the blotches; and applying honey,
pox (mogasa, "funeral pox"). Epidemics of the pesti- powdered silkworm cocoons, white lead, or powdered
lence are listed for the years 735-7, 790, 812-14, falcon feathers and lard was also suggested.
853, 915, 947, 974, 993-5, 1020, and 1036 (compiled Tax records extant from the time of the epidemic
from data in SZKT 1933; Hattori 1955; Fujikawa provide a glimpse of the mortality inflicted by the
1969; Farris 1985). During this era, especially in the Great Smallpox Epidemic of 735-7. In the year 737
eighth and ninth centuries, smallpox was primarily alone, the province of Izumi near the capital lost 44
a killer of adults. According to Jannetta (1987), percent of its adult populace, while Bungo in north-
smallpox had become endemic in the population by ern Kyushu and Suruga in eastern Japan sustained
1100 or even earlier, but the basis for this belief is death rates of about 30 percent. The average mortal-
not clear. ity for all known areas was about 25 percent in 737
The best example of a smallpox, and indeed of any alone. Population depletion for the 3 years probably
epidemic in this period, is the Great Smallpox Epi- amounted to between 25 and 35 percent, making the
demic of 735-7, the earliest well-reported smallpox Great Smallpox Epidemic of 735-7 comparable in its
epidemic in world history (Farris 1985). It began in death toll to the European Black Death of the four-
northern Kyushu, transported there by a Korean teenth century.
fisherman. The foreign port of Dazaifu was the first Disastrous as it may have been, one great out-
to feel the effects of the disease, a sure sign that the break of pestilence would not have halted demo-
affliction was imported. Kyushu suffered through- graphic growth for long. But harsh epidemics contin-
out the summer and fall of 735, and the disease ued to follow on its heels. In 790, smallpox struck
raged again in 736. Just as the epidemic was burn- again, borne from Chinese ports and afflicting those
ing itself out in western Japan, a group of official aged 30 or less. The historical record is fragmentary
emissaries to Korea passing through northern and difficult to read for the epidemic of 812-14, but
Kyushu encountered the ailment and carried it to it seems likely that the dread killer entered Japan
the capital and eastern Japan. The epidemic as- via its foreign port in northern Kyushu as early as
saulted all levels of Japanese society, killing peasant 807 and spread across the archipelago to the east.
and aristocrat alike. One record reads that "in re- According to the records, "almost half" of the popula-
cent times, there has been nothing like this" (Farris tion died. In 853, the disease seems to have focused
1985). on the capital, Heian (modern Kyoto), but the epi-
Two remarkable records survive that describe the demic also spread to the countryside.
symptoms and treatment of smallpox. The disease The disease, however, still seems to have been
began as a fever, with the patient suffering in bed for primarily an ailment of adults. In 925, for example,
from 3 to 6 days. Blotches then began to appear, and the Emperor Daigo contracted smallpox at the age of
the limbs and internal organs became fevered. After 41. The smallpox outbreak of 993-5 was particu-
the fever diminished and the blotches started to dis- larly severe. In 993, the Emperor Ichijo was a victim
appear, diarrhea became common. Patients also suf- at the age of 15, but the disease was probably not yet
fered from coughs, vomiting, nosebleeds, and the endemic, as smallpox appeared in Kyushu the next
regurgitation of blood. spring, suggesting a foreign source. The disease was
The prescribed remedies are as fascinating as the so bad in the capital that 70 officials of the fifth court
descriptions of the symptoms. Government doctors rank or higher died; the roads were littered with
trained in Chinese, Indian, and native medicine ad- corpses serving as food for dogs and vultures. In

1020 smallpox returned to Kyushu again, possibly indicated that the sickness was marked by a swell-
reaching Japan with one of the continental invaders ing of the neck.
the year before. A diary states that those aged 28 The final pestilence of the age of plagues was
and under were especially afflicted (Tsuchida 1965; dysentery (sekiri, "red diarrhea"). Epidemics are
Farris 1985). documented for 861, 915, and 947 (Hattori 1955).
The season for dysentery was the late summer and
Measles fall. Often dysentery appeared in tandem with other
The second killer disease that attacked the Japanese afflictions, as in the Great Smallpox Epidemic of
populace in the era between 700 and 1050 was mea- 735-7. The dysentery epidemic of 861 was followed
sles (akamogasa, "red pox"). Two epidemics are by influenza in 862 and 863. In 915 and 947, small-
known, in 998 and 1025, although it is not clear that pox was again an accompanying malady. The mea-
Japanese doctors were always able to distinguish sles epidemic of 1025 was also probably related to
between measles and smallpox in this early age. dysentery infections among the Heian nobility.
Nonetheless, A Tale ofFlowering Fortunes, a chroni- Their diaries indicate that when patients caught
cle of the tenth and eleventh centuries, clearly differ- dysentery they quickly lost their appetites and suf-
entiates the 998 affliction from smallpox, stating fered from fever.
that the disease caused a "heavy rash of bright red
spots" (McCullough and McCullough 1980). The pes- Other Maladies
tilence began in the early summer in the capital, In addition to these five epidemic afflictions, other
where the wives of high officials were the first af- illnesses were common among the populace. Accord-
fected. Foreigners did not die from the disease, a clue ing to The Pillow Book, a series of essays written by
that reinforces McNeill's (1976) thesis about Japan's a lady at court (Sei Shonagon) about the year 1000,
island epidemiology. Later in the year, the ailment the three diseases most feared by the tiny coterie of
attacked the rest of Japan, killing more people than aristocrats at the Heian court were chest trouble
any other in recent memory. (munenoke), evil spirits (mononoke), and beriberi
In 1025, measles once again returned to Japan. (ashinoke). Chest trouble undoubtedly refers to tu-
The disease afflicted people of all classes who.had berculosis, although Hattori (1975) suspects that
not suffered from the disease in the 998 epidemic. heart-related afflictions were also common. Tubercu-
The diaries of aristocrats indicate that several noble losis is one of the oldest diseases known to humanity,
houses suffered from the illness. The focus of the and it may have been that because the tuberculosis
disease seems to have been the capital, although one bacillus is often transmitted via unpasteurized milk,
source states that "all under heaven" caught the the aristocracy contracted the malady by eating a
malady. yogurtlike food product of which they were fond.
Evil spirits suggest mental illnesses, and Hattori
Influenza (1975) has found evidence of schizophrenia, autism,
A third ailment was influenza (gai byo or gaigyaku and manic-depressive behavior in the imperial line.
byd, "coughing sickness"), which struck in 862-4, Beriberi, a disease caused by a deficiency of thia-
872, 920, 923, 993, and 1015 (Hattori 1955; mine (probably due to a lack of fats in aristocratic
Fujikawa 1969). Unlike smallpox and measles, diets), is noted in several sources for the early period
which were most active in the spring, summer, and (Hattori 1964).
fall, influenza generally struck in the late winter Some diseases were never diagnosed by court doc-
and early spring. The epidemics of 862-4 and 872 tors who were trained only in Chinese medicine.
were particularly severe, killing many people in the Japanese records tell of a "water-drinking illness"
capital region. In general, however, the death toll (mizu nomi yami) common to the Fujiwara family,
from influenza probably did not match the mortality the mating line for the imperial house (Hattori
from smallpox or measles. 1975). According to Hattori, this disease was diabe-
tes, and was hereditary in that family. Several promi-
Mumps nent Fujiwara statesmen, including the great
Mumps (fukurai byo, "swelling sickness") was the Michinaga (the model for Prince Genji in The Tale of
fourth epidemic illness encountered by the Japanese Genji), complained of the malady and its related
in this period. Records state that the disease flour- afflictions such as glaucoma and impotence (Hurst
ished in 959 and 1029, mainly in Heian, the popu- 1979).
lous capital of the era. In both epidemics, historians Another malady that did not kill many victims

but had a great effect on all levels of society was vate lands continuously. In 743, after the 735-7 out-
malaria (warawayami, furuiyami, or okori, "the break, the aristocracy attempted to stimulate farm-
chills"). Even Prince Genji himself suffered from the ing by enacting a policy giving permanent private
malady (Seidenstecker 1985). Doctors of this era tenure to anyone who would take up a hoe. In 1045,
were unaware that the disease could be carried by lawgivers countered unparalleled field abandon-
mosquitoes, although a court lady seemed to believe ment by recognizing all previously banned estates.
that butterflies were common where the disease Fourth, outbreaks of pestilence stimulated migra-
broke out. Japan is a land with many swamps; it is tion and made for a shortage of laborers. The court
interesting to speculate about the effects of malaria enacted legislation to bind peasants to their land
on a peasantry trying to convert these low-lying throughout the eighth and ninth centuries, but to
lands into productive rice paddies. little effect. Labor shortages often made it difficult
In addition to the plentiful information on dis- to finish temple construction or rice planting on
eases supplied by court histories, literature, and time, and by the year 800, the court had given up
other records, medical texts and an encyclopedia capital construction and the conscription army.
called the Wamyo ruiju sho also list medical termi- Fifth, disease was responsible for a growing
nology (Hattori 1945). Among the infections in- maldistribution of income. A new class of regional
cluded are idiopathic cholera (shiri yori kuchi yori strongmen, called the "rich" in the documents, came
koku yamai, kakuran), leprosy (raibyo), elephantia- into being by capitalizing on opportunities arising
sis (geju), bronchitis (shiwabuki yami), hepatitis from famines and epidemics. The "rich" often re-
(kibamu yamai), dropsy (harafukuru yamai), asca- sorted to violence to resist provincial tax collectors
rids (kaichu), threadworms (gyochu), meningitis and exploit the peasantry.
(fubyo), infantile dysentery (shoji kakuran), diphthe- Sixth, the stagnation of population growth result-
ria (bahi), bronchial asthma (zensoku), epilepsy ing from disease reduced the demand for manufac-
(tenkari), chronic nephritis (shokatsu), tonsilitis tured goods. At the same time, because epidemics
(kohi), osteomyelitis (fukotsuso), thyroiditis (ei), kill people but do not destroy wealth, survivors of
erysipelas (tandokuso), ringworm (senso), gastritis the pandemic among the aristocracy were left with
(iso), palsy (kuchi yugamu), and scabies (kaiso). Rec- great riches. Reduced overall demand and the in-
ords from the era 700-1050 also have led scholars to creased opulence of a few gave rise to industry that
infer the existence of cancer, pneumonia, tape- produced luxury goods for a tiny elite.
worms, rheumatoid arthritis, and hookworms. In the political realm, epidemics brought several
alterations in tax structure. After the Great Small-
Effects of Plagues on Japanese Society pox Epidemic, provincial governors were converted
The effects of the age of plagues (700-1050) on Japa- into tax farmers, which put them into competition for
nese society and culture were many and varied. Par- revenues with the leaders of the smaller district units
allels with the Black Death pandemic that struck that comprised the province. The competition for
western Europe in the fourteenth and fifteenth cen- taxes among local officials while the tax base was
turies are tempting to draw, and it may be true that shrinking helped engender a society that looked to
pestilence stimulates the same human responses in violence to solve its problems. By 1050, the district
widely disparate societies. In the social and eco- had disappeared as a unit of administration, primar-
nomic realm, the epidemics were responsible for sev- ily because it could not compete with the larger prov-
eral phenomena. First, disease caused population ince. Moreover, epidemics provided political opportu-
stagnation. Sawada Goichi estimated the population nities. After the 735-7 epidemic, for example, all four
of Japan at 6 million in the eighth century, and it is of the Fujiwara brothers from a powerful aristocratic
unlikely that population grew significantly through family had passed away, and Tachibana no Moroe, a
the year 1050 (Kito 1983). bitter rival, became the new head of the government.
Second, plagues caused the desertion of villages. Or again in 994, when smallpox raged in the capital
After the Great Smallpox Epidemic of 735-7, an and many aristocrats fell victim, a beneficiary of the
entire layer of village administration was abolished. deaths was Fujiwara no Michinaga, who became per-
Later, after the epidemics of 990—1030, the court haps the greatest of all Fujiwara leaders.
once again abandoned the current village system in In addition, disease influenced inheritance. To
favor of new laws. cope with the horrendous number of deaths of family
Third, pestilence inhibited agriculture, especially members from plagues, the aristocracy practiced po-
rice monoculture, because it became difficult to culti- lygamy. Often property and children were retained

in the woman's line against the advent of an un- (mappo), dominated Japanese thought. According to
timely demise by her husband. Survivors inherited this doctrine, three ages of 500 years each followed
unparalleled wealth and political power. the death of the Buddha: the first era, when salva-
Finally, plagues reduced the size of administration was simple; the second, when it was more diffi-
tion. In the early eighth century, the government cult; and the latter day, when delivery from hell
bureaucracy numbered about 10,000 persons. By the would come to just a few. Ironically, the latter day
early ninth century, leaders were already cutting was believed to begin in 1052, just as the epoch of
back the size of government, and although hard fig- plagues drew to a close.
ures are difficult to come by, the bureaucracy did not Popular culture also reflected a concern for dis-
again reach that size until the fourteenth century. ease. The Gion Festival, today celebrated from the
The age of plagues also influenced religion and July 17 to July 24 (the 14th of the sixth month
culture. Unquestionably, the epidemics played a role according to the old lunar calendar) began as an
in both the adoption of Chinese culture in the eighth attempt to rid the capital of Heian of epidemics. The
century and a return to the native culture in the festival was first conducted by Gion Shrine (later
tenth and eleventh centuries. It is unlikely that the Yasaka Shrine) in eastern Heian in 869, just after an
Japanese of the 700s borrowed Chinese civilization epidemic. Sixty-six spears, one for each province in
simply because it seemed superior to their own. Only Japan, were placed on end and marched through the
coercion, such as military force or epidemic disease, city to chase the disease away. In 970 the festival
would have inspired the Japanese to adopt such an became an annual affair, suggesting the growing
obviously foreign culture. On the other hand, dis- endemicity of disease in the capital.
ease played a role in the demise of Chinese culture The smallpox pestilence of 993-5 gives another
in Japan because the constant plagues killed off ex- rare glimpse of popular reaction to epidemics. Late
perts in Chinese language and the classics, thus in the sixth month of 993, a festival to drive away
making these subjects harder to learn. Disease was disease gods was held in the Kitano section of the
also a factor in the development of a major motif in capital. Two palanquins were built by the govern-
Japanese literature, mono no aware, the ephemeral ment, Buddhist monks recited a sutra, and music
nature of all living things. Disease is a constant was provided. Several thousand persons gathered
presence in the classic The Tale of Genji, which in- and offered prayers to the gods. The palanquins,
cludes reference to an epidemic (Seidenstecker invested with the gods of the epidemic, were then
1985). Many of Genji's friends and lovers pass away borne by the populace several miles to the ocean to
after the briefest time, and in most cases the villain wash the smallpox affliction away (Tsuchida 1965;
was disease. To have reached one's forties was consid- Fujikawa 1969).
ered to have lived a long life (Hattori 1975).
The repeated outbreaks of pestilence also influ- 1050-1260
enced Japanese religion profoundly. The introduc- The era from 1050 to 1260 marks a time of declining
tion of Buddhism occurred amidst a plague of small- importance of disease in Japan. There were 50 epi-
pox. As a transcendental religion, Buddhism was demics over 210 years, an average of one outbreak
perfectly adapted for an environment in which dis- every 4.2 years, compared to one epidemic every 2.9
ease outbreaks were common. Early believers years in the 700s and one every 3.8 years in the poorly
reached out to Buddhism because of the promise of documented 900s (cf. Hattori 1955, 1964; Fujikawa
protection from illness. After the Great Smallpox 1969). The killers of the former age retreated into en-
Epidemic of 735-7, the Emperor Shomu increased demicity. As always, the record is most complete for
state support of the religion by ordering the construc- smallpox. Epidemics broke out in 1072, 1085, 1093-
tion of the great state temple Todaiji and branch 4, 1113, 1126, 1143, 1161, 1175, 1177, 1188, 1192,
temples throughout the countryside. By the tenth 1206-7,1225,1235, and 1243 (cf. Hattori 1955,1964;
and eleventh centuries, Buddhism had become a Fujikawa 1969). Although some plagues of smallpox
faith of good works, as Christianity was during the appear to have been severe, especially those in 1072
plague pandemic in the fourteenth andfifteenthcen- and 1175, the disease showed clear signs of becoming
turies. The frequency of pilgrimage in both religions an affliction of childhood. A letter of 1085 records a
is another striking parallel. By the eleventh century, mother's concern for her infant who had contracted
Japanese religious thought was characterized by pes- smallpox (Hattori 1975). In the late twelfth century,
simism and a flight from the intellect. Millen- Minamoto no Yoriie, the eldest son of the great war-
nialism, symbolized by "the latter day of the law" rior leader Yoritomo, had smallpox as a boy. His sick-

ness seems to suggest the growing significance of the this affliction appears in records as early as the
disease in eastern Japan, away from the greatest eighth century, Hansen's disease seems to have be-
centers of population. The record of the 1243 epidemic come a serious social problem in the thirteenth cen-
of smallpox specifically states that the disease af- tury. The colder climate probably caused people to
flicted young children, which led McNeill (1976) to huddle together, thereby facilitating the transmis-
assert that the ailment was endemic by that date. sion of the malady as in western Europe. Healthy
In the case of measles, epidemics struck in 1077, commoners spurned lepers and treated them as out-
1093-4, 1113, 1127, 1163, 1206, 1224, 1227, and casts. The Buddhist monk Ninsho became renowned
1256 (Fujikawa 1969). In the plague of 1077, young for his treatment of lepers in a sanatorium at
children were afflicted, although the record also re- Kuwagatani. The Portuguese missionary Luis de
veals that many adults died. That the 1224 affliction Almeida would gain a similar reputation for his
seems to have attacked mainly young children, how- work in the 1500s (Hattori 1964,1971).
ever, suggests to McNeill (1976) that, like smallpox, Medical texts and other sources list other ailments
measles was probably endemic by that time. On the as well; they include cirrhosis of the liver (daifuku
other hand, Jannetta (1987) has found evidence that suicho), bronchitis, dropsy, idiopathic cholera, hepati-
the disease was still a foreign-borne plague as late tis, worms, malaria, furunculosis (oryo shi), diabe-
as the nineteenth century. Analysis of additional tes, and tuberculosis (denshi byo). The Hanazono
records between 1200 and 1600 is still required to Emperor and Fujiwara no Kanezane were afflicted
determine the precise status of measles in Japanese with beriberi (kakke), whereas the poet Fujiwara
history, but it is important to note that at least Teika suffered from repeated bouts with bronchial
Jannetta agrees with McNeill that the disease was asthma (Hattori 1964).
not a major factor in the region's demographic his- Because the effects of disease in the age 1050-
tory by 1200. 1260 were limited, especially during the period
Influenza, a disease for which no permanent immu- 1050-1150, decreasing mortality from both old and
nity is conferred, took a devastating toll in the era new afflictions possibly spurred some population
1050-1260. According to the records, epidemics oc- growth. Demographic expansion was particularly
curred in 1150, 1228, 1233, 1244, and 1248. The evident in the Kanto region (modern Tokyo and vi-
outbreak in 1150 was extremely severe, carrying off cinity), as the warriors cleared lands for cultivation.
many elderly persons. The epidemic of 1244 was also The land clearance of this epoch was the basis for the
harsh, afflicting all those aged 10 and above. An estate {shoeri) system adopted in the late eleventh
important reason for the grave plagues of influenza century. The extent of population growth, however,
was undoubtedly the weather, which turned much remains undetermined.
colder and damper after 1150 (Kito 1983). Yet, no matter how much the impact of pestilence
Dysentery also continued to attack the populace. on Japanese society decreased during the years
There is evidence of a dysentery outbreak in the 1050-1150, there is little doubt that disease com-
year 1077, and prominent individuals contracted the bined with unusually harsh weather in the following
malady in 1144,1240, and 1243 (Fujikawa 1969). As century to restrict population growth. Temperatures
during the age of plagues, the malady usually accom- turned much colder and the amount of moisture in-
panied other diseases; the 1077 affliction of dysen- creased dramatically, especially in eastern Japan
tery coincided with a measles epidemic. where there was the greatest potential for growth.
In addition to diseases from the previous era, the In three years - 1182, 1230, and 1259 - the inclem-
period 1050—1260 also witnessed the first accounts ent weather induced widespread famine and accom-
of a new ailment. Fujikawa (1969) argues that in panying sicknesses. The Great Famine of 1230 was
1180 the Japanese first became aware of the exis- said to have killed one-third of the population. In all
tence of a smallpox-like affliction that may have three cases, epidemics assisted famine as Grim Reap-
been chickenpox. Eventually, doctors in Japan came ers of the peasantry. Thus, despite the growing en-
to call the disease "water pox" (suito or henamo), and demicity of many formerly severe diseases, the poor
chronicled an epidemic in 1200. It is unlikely that performance of the agricultural sector greatly re-
the disease had a great demographic impact, and stricted Japan's potential for population growth.
may well have existed in Japan long before the Japa-
nese medical establishment became aware of it. 1260-1600
A disease that gained new prominence in the era The final era in the history of disease in Japan be-
from 1050 to 1260 was leprosy (raibyo). Although fore 1600 encompasses the years 1260-1600, which

are critical for any real comprehension of the role of The period contains 45 epidemics of various descrip-
pestilence in Japanese history. Yet this period has tions, or one outbreak of pestilence for every 2.7
not been investigated in detail by historians, al- years, representing an increase over the previous
though they have access to thousands of unpub- era. Smallpox was particularly active, coming in
lished records from this era. Fujikawa (1969) has 1452-3,1477, 1495,1523, 1525, 1531, and 1537. In
listed some of the epidemics for this epoch, but, as all years excepting 1495 and 1525, however, the
Jannetta (1987) and Hattori (1971) have pointed out, disease struck only children. The Portuguese mis-
it is likely that he has missed some. A major diffi- sionary Luis Frois wrote that nearly all Japanese
culty is that reporting mechanisms of disease were bore pockmarks from smallpox, and he believed that
hindered by warfare, especially in the periods 1333- the ailment was more severe among the Japanese
65 and 1460-1550. Thus, records kept at the capital than the Europeans (Fujikawa 1969; Hattori 1971).
in Kyoto are simply inadequate for the systematic Measles appeared more frequently, as well, attack-
analysis of disease in this period. ing the populace in 1441, 1471, 1484, 1489, 1506,
Despite problems with the sources, however, broad and 1513. The outbreaks of 1471, 1484, and 1512
contours can be sketched if this age is broken down were harsh, killing many people of all ages. Influ-
into three subperiods: 1260-1420, 1420-1540, and enza is recorded as epidemic in 1428 and 1535. Dys-
1540-1600. In the first subperiod, harsh weather entery and chickenpox are not documented. The era
and war assisted disease in limiting population 1460-1550 was a period of chronic warfare in Japan,
growth from 1261 to 1365. There were 29 epidemics which leads one to suspect a link between the in-
over this 105-year span, or one every 3.6 years. From creased social strife and the higher incidence of pesti-
1366 to 1420, there were 16 epidemics, or one every lence (Fujikawa 1969; Hattori 1971).
3.4 years. The era included smallpox outbreaks in The period from 1540 to 1600 was an era of great
1314, 1342, 1361, 1365, and 1374, with that of 1365 population growth in Japan, which represents the
appearing to have been the only harsh epidemic. beginning of the Edo demographic explosion. Evi-
Measles is recorded for 1306-7, 1320, 1362, 1380, dence of 14 epidemics has survived in the records, or
and 1405 and afflicted mainly children in 1306-7. one for every 4.3 years (Fujikawa 1969; Hattori
Influenza struck in 1264, 1329, 1345, 1365, 1371, 1971). An epidemic of 1593-4 should probably be
1378, and 1407-8, with the attacks of 1365 and 1371 linked to Hideyoshi's invasion of Korea. Smallpox
being particularly widespread; Hattori finds strong was present only in 1550, and measles struck only in
evidence that, beginning in the 1300s, more people 1578 and 1587. Influenza was reported in 1556,
suffered and died from respiratory diseases than when many children died, but, again, dysentery and
smallpox or measles. No epidemics of dysentery or chickenpox are not noted in the historical record.
chickenpox are documented (Hattori 1964; Fujikawa In 1543, the first Westerners visited Japan, but
1969). unlike notable other areas, Japan did not suffer un-
Perhaps the most important event in the disease duly from this new contact. Only two new diseases
history of Japan during the years 1260-1365 was entered the archipelago at this time. The first was
one that did not occur. In 1274 and 1281, the Mon- syphilis, which may also have been a new ailment in
gols attempted to invade the archipelago, but failed western Europe. The first appearance of syphilis in
both times; in the last invasion, Japan was saved by Japan, however, predates contact with Westerners,
the intervention of the "divine winds" of a typhoon. for it arrived in 1512 (Hattori 1971, citing Fuji-
As McNeill (1976) has argued, the Mongols carried kawa). The Japanese immediately dubbed syphilis
the plague bacillus from southern China, where it the "Chinese pox" (togasa), and often confused it
was endemic, to new territories such as China with both leprosy and smallpox. Frois wrote that
proper and western Europe. If the Mongols had suc- syphilis did not cause the embarrassment to the
ceeded in their invasion of the islands, then Japan, Japanese that it did to the Europeans (Hattori 1971).
too, undoubtedly would have suffered from the Its demographic impact was probably small.
plague. But Japan remained plague-free, population The second new disease was introduced directly by
continued to grow, and the country moved toward an the West, specifically by the Portuguese (Boston
agrocentric society, a condition western Europe Globe 1984). Robert Gallo, chief of the Laboratory of
avoided in the plague pandemic of 1350-1450. Tumor Cell Biology at the National Cancer Insti-
Although the historical record is difficult to read tute, has discovered an AIDS (acquired immune defi-
for the era 1421-1540, it appears that disease re- ciency syndrome) virus in the blood of many Japa-
mained an important factor in demographic change. nese living in the southern islands. The virus is

called human T-cell leukemia/lymphoma virus clear that smallpox and measles were attacking pri-
(HTLV) I and II, and is somewhat different from the marily children by the mid-thirteenth century, and
AIDS virus found in the United States, which is probably even earlier. Influenza, however, may have
named HTLV-III. Of the southern Japanese people grown in virulence, especially after 1150, when the
who are infected with the virus, only 1 person in 80 climate turned colder and wetter. Other serious mala-
develops cancer. The rest suffer from a viral disease, dies included leprosy and chickenpox. The period
characterized by fever, rash, and malaise. Gallo sur- from 1050 to 1260 may have seen some demographic
mises that Portuguese sailors coming to Japan in the expansion, notably in the east, but disastrous
1500s brought infected monkeys and African slaves, weather patterns and ensuing famine and pestilence
who transmitted the disease to the Japanese popula- began to close this "window of opportunity" around
tion. Historical records betray no evidence of this 1150.
malady. The last subperiod, 1260-1600, represented an ep-
The other diseases of the early modern period in och when disease had a decidedly decreased impact
the West, such as typhus, do not appear to have been on the archipelago. The Japanese escaped importa-
transported to Japan until the Edo period. Thus the tion of the plague by defeating the Mongols in the
Japanese were extraordinarily fortunate when com- 1200s, and by 1365 neither infection nor famine nor
pared to the natives of the New World or the south- war was restricting the growth of Japan's popula-
ern Pacific, who were subjected to the onslaught of tion. The era 1420-1540 may have seen some in-
unfamiliar Western parasites. Many inveterate af- creased virulence of disease, accompanied by civil
flictions, such as malaria, beriberi, dysentery, war, but the second half of the sixteenth century was
asthma, pneumonia, worms, idiopathic cholera, remarkably disease-free. Two new infections, syphi-
dropsy, hepatitis, diabetes, chickenpox, rheumatoid lis and a relatively harmless variant of the AIDS
arthritis, tuberculosis, and stomach cancer, contin- virus, were brought to Japan from the West, but the
ued to leave their mark on Japanese culture. Muso effect of these ailments seems to have been limited.
Kokushi, the Zen prelate, died of malaria, whereas Examination of the sweep of 1,100 years of disease
several Ashikaga shoguns probably had diabetes. history suggests that demographic trends in Japan
were almost the mirror opposite of western Europe.
Recapitulation Only in the eras 1050-1150 and 1500-1600 did Ja-
The history of disease in Japan over the era 500 to pan and the West both experience population growth.
1600 can be divided into four subperiods. During the To the extent that one equates population growth
first, 500 to 700, evidence indicates the importation with economic growth, it seems clear that Japan and
of maladies such as smallpox, and frequent communi- western Europe were each led along substantially
cation between the Japanese and their continental different paths by a differing biological past.
neighbors would suggest that epidemics were more W. Wayne Farris
common than the sources indicate.
In the second subperiod, from 700 to about 1050, Bibliography
the population suffered from repeated devastating Aston, Williams, trans. 1972. Nihongi, Vol. 2. Tokyo.
epidemics of killer diseases including smallpox, mea- Boston Globe. 1984. May 7.
sles, influenza, dysentery, and mumps. These impor- Farris, Wayne, 1985. Population, disease, and land in early
tant infections attacked a population that by and Japan: 645-900. Cambridge.
large had no immunities and killed great numbers of Fujikawa, Yu. 1904. Nihon igaku shi (History of Japanese
adults. The epidemics resulted in population loss, medicine). Tokyo.
agricultural stagnation, a shortage of labor, revi- 1969. Nihon shippei shi (A history of disease in Japan).
sions in laws dealing with land tenure, tax struc- Tokyo.
ture, and local government, a growing maldistribu- Gottfried, Robert. 1983. The black death. New York.
tion of income, the rise of a transcendental religion Hattori, Toshiro. 1943. Joko shi iji ko. Nihon Ishi Gaku
Zasshi 1312: 64-76.
(Buddhism) and millennialism, as well as a sensitiv-
1945. Narajidai igaku no kenkyu (Medicine in the Nara
ity to the evanescence of life in literature. Other period, 710-784). Tokyo.
important diseases of this age of plagues included 1955. Heian jidai igaku no kenkyu (Medicine in the
beriberi, malaria, diabetes, and tuberculosis. Heian period, 784-1185). Tokyo.
The third subperiod, 1050-1260, saw the killer 1964. Kamakura jidai igaku shi no kenkyu (A history of
infections of the former period transformed into en- medicine in the Kanakura period, 1185-1333). Tokyo.
demicity and thus to childhood illnesses. It is fairly 1971. Muromachi Azuchi Momoyama jidai igaku shi no

VI.6. Early Modern Period in Japan 385
kenkyu (A history of medicine in the Muromachi U.S. fleet forced Japan to open its ports to interna-
Azuchi and Momoyama periods, 1333-1600). Tokyo. tional commerce in the 1850s.
1975. Ocho kizoku no byojo shindan. Tokyo. Elsewhere explorers, adventurers, traders, and set-
Hurst, Cameron. 1979. Michinaga's maladies. Monu- tlers were circumnavigating the globe, carrying new
menta Nipponica 34: 101-12. diseases to previously unexposed peoples, and caus-
Jannetta, Ann B. 1987. Epidemics and mortality in early ing waves of high mortality among the populations
modern Japan. Princeton, N.J.
of many world regions. By 1850 the increasing vol-
Kito, Hiroshi. 1983. Nihon nisen nen nojinko shi. Tokyo.
McCullough, William, and Helen McCullough, trans. 1980.
ume of international contacts had produced a world-
A tale of flowering fortunes, Vol. 1. Stamford, Conn. wide system of disease dissemination, but Japan,
McNeill, William. 1976. Plagues and peoples. New York. remaining aloof from world affairs, had also re-
Seidenstecker, Edward, trans. 1985. The tale ofGenji. New mained largely unaffected by the epidemiological
York. events of the early modern world. The diseases of
SZKT (Shintei zoho kokushi taikei), 1933. Ruiju fusen sho. Tokugawa Japan were, for the most part, diseases
Tokyo. that had reached the islands centuries earlier.
1966. Nihon Montoku tenno jitsuroku. Tokyo. Japan was part of an East Asian disease dissemi-
Takeuchi, Rizo, et al., eds. 1979. The tale of the Masakado. nation system that differed in certain respects from
In Nihon shiso taikei; Kodai seiji shakai shiso, Vol. 8. that of western Eurasia. Human populations in East
Tokyo.
Asia were larger and more dense than those in the
Tsuchida, Naoshige. 1965. Nihon no rekishi: Ocho no
kizoku. Tokyo.
West, and many human disease organisms were able
Twitchett, Denis. 1979. Population and pestilence in Tang to establish permanent reservoirs of infection with
China. In Studia Sino-Mongolica: Festschrift fur Her- little difficulty. In earlier times, epidemic diseases
bert Franke, ed. Wolfgang Bauer, 42-53. Wiesbaden. were disseminated outward from the large popula-
tion centers of China to the less densely settled re-
gions of the periphery. Occasionally these epidemics
would reach Japan, and Japan's population, which
was heavily concentrated along the coastal plains,
provided an environment highly conducive to dis-
VI.6 ease propagation and dissemination. By 1600, Ja-
pan's population was large enough to support many
Diseases of the Early Modern disease organisms in endemic fashion that in earlier
Period in Japan times had been imported as epidemics from China.
The most important changes in the disease environ-
ment of early modern Japan, relative to earlier peri-
The diseases of early modern Japan (the Tokugawa ods, were brought about by domestic rather than in-
period) are of particular interest to the history and ternational developments. Japan's population grew
geography of disease. The Japanese Islands, situated from about 18 million to approximately 30 million
as they are at the far eastern periphery of East Asia, people during the seventeenth century, and Edo
had relatively little contact with the people of other (present-day Tokyo) became one of the world's largest
world regions until the late nineteenth century. His- cities with a population of around 1 million inhabit-
torically Japan's isolation afforded the people some ants. Economic development, which included the
measure of protection from exposure to certain of the commercialization of agriculture, regional specializa-
world's diseases, and in the early seventeenth cen- tion, and interregional trade, accompanied popula-
tury, the Tokugawa shoguns reinforced this natural tion growth. All these developments served to inten-
protection when they imposed severe restrictions on sify disease transmission within Japan, and by 1850
foreign contacts. They limited official foreign trade to few communities were remote enough to avoid either
the port of Nagasaki, restricted the number and the the indigenous diseases of Japan or the imported dis-
nationality of ships that could enter that port, denied eases that sometimes managed to penetrate the cor-
mobility beyond the port to the crews of foreign ships, don sanitaire that served to protect the country from
and prohibited the Japanese from going abroad and the international traffic in pathogens.
returning to Japan. These policies were a response, in
part, to the unwelcome activities of Westerners who Sources on Diseases of Japan
had begun to reach the islands in the second half of Japanese sources that contain information about the
the sixteenth century. They remained in effect until a diseases of Japan are abundant and of excellent qual-

ity. The most important are contemporary reports of was almost entirely an illness of children under the
epidemics, medical books with descriptions of the age of 5 years, with few escaping it and many dying of
symptoms and treatment of important diseases, gov- it. As late as 1850, at least 10 percent of the popula-
ernment documents that issued warnings or commis- tion died of smallpox, and Western observers wrote in
sioned relief measures, temple registers that re- the 1860s that smallpox in Japan was so common that
corded causes of death, and general writings of the virtually every countenance was pockmarked. The
period. Early in the twentieth century, two pioneer- introduction of smallpox vaccine in 1849 would re-
ing Japanese medical historians, Fujikawa Yu and duce the importance of the disease as a cause of death
Yamazaki Tasuku, compiled references to disease by the late nineteenth century.
from many Japanese sources. Their works still stand
as basic references on the history of disease in Japan. Measles
Some Western sources also contain references to The history of measles in Japan is unlike that of
disease in Japan, but most of these were written western Europe. In the parts of Europe for which
before or after the Tokugawa period because during there are good records, measles epidemics were re-
that period there were few Western visitors. Thus ported frequently. At the end of the eighteenth cen-
Portuguese, Spanish, English, and Dutch adventur- tury, for example, epidemics were occurring regu-
ers who lived in Japan in the late sixteenth and larly in England in about one of every 3 years, and
early seventeenth centuries wrote of illnesses that in Germany at regular intervals of about 4 to 5
were observed among the Japanese as well as dis- years. But in Japan, only 11 measles epidemics were
eases that seemed to be absent. And two and one- reported between 1616 and 1862, and contemporary
half centuries later, in the late nineteenth century, accounts also provide evidence that epidemics were
when Westerners again arrived in Japan, they, too, very rare. Consequently, measles was regarded as a
wrote of the diseases they noticed. Western observa- dread disease because unlike smallpox, which was
tions reported at the beginning and the end of the omnipresent, measles seemed to come out of no-
Tokugawa period are of value as benchmarks that where, and infected young and old alike.
help to identify the illnesses that were prevalent The different epidemiological patterns of measles
during this period. epidemics in Japan on the one hand and in western
The diseases of early modern Japan can be divided Europe on the other seem to be related to different
into two general categories: those that are easily patterns of contact between populations in which the
identified on the basis of their symptoms and virus circulated. Frequent contact between the
epidemiological characteristics, and those that are many trading centers of western Europe promoted
not. Ailments in the first category are primarily the dissemination of the virulent measles virus and
acute infectious diseases that have distinctive symp- caused frequent epidemics. By contrast, the restric-
toms, affect many people within a short period of tion of trade and the infrequent and seasonal pat-
time, and are therefore highly visible. These infec- tern of maritime trade between Japan and other
tions, which have well-established histories, are eas- countries of East Asia may have prevented the mea-
ily recognized in Japanese sources. Diseases in the sles virus from being imported very often.
second category present symptoms that are vague or In Japan the measles virus invariably spread from
general. They may have been very important in caus- the port of Nagasaki in the southeast to the major
ing illness or death, but they cannot be subsumed cities of Kyoto, Osaka, and Edo to the northeast, and
under any modern disease classification. from there to the more remote parts of central and
northern Japan. Moreover, it spread very rapidly
Infectious Diseases because the population was densely concentrated
Smallpox along internal trade routes, and because, with infre-
Among the acute infectious diseases that can be quent epidemics, an unusually large segment of the
clearly identified from the sources, smallpox emerges population was susceptible to infection. In these cir-
as the major killer and the most common cause of cumstances, the measles virus quickly ran out of
premature death. Certainly, more medical books new hosts to infect and thus died out, which meant
were written about this illness than any other. An old that a new importation of the virus was required for
disease in Japan, smallpox was endemic in the large another epidemic to occur.
cities well before 1600, and by the late eighteenth and Unusually good records of measles epidemics were
early nineteenth centuries, epidemics struck even kept during the Tokugawa period, presumably be-
remote parts of Japan every 3 or 4 years. Smallpox cause they infected so many people. These records

VI.6. Early Modern Period in Japan 387
document epidemics in 1616,1649,1690,1708,1730, large-scale epidemics seem to have been fairly rare
1753, 1776, 1803, 1824, 1836, and 1862. The geo- in the early modern period. Fujikawa mentions only
graphic pattern of dissemination, the age distribu- seven epidemics of diarrheal diseases for the Toku-
tion of the cases, and other contemporary evidence gawa period in his chronology of epidemics in Japan.
suggest that measles remained an imported disease It is impossible to distinguish between the different
that caused infrequent but severe epidemics in Ja- kinds of enteric diseases known today, because the
pan until after 1850. symptoms of diarrheal infections are much the same
Measles was clearly distinguished from smallpox regardless of the infecting agent. Such infections
in the Japanese records because of its very different were most likely to be reported in Japanese histori-
epidemiological pattern. A person was most likely to cal sources when a large city or an important person
get smallpox as a young child because the virus was was stricken, and these occasions were quite rare.
always circulating through the population, whereas The absence of major dysentery-type epidemics is
a person would get measles only when the virus not too surprising. Because enteric diseases are
happened to sweep through the country. Morbidity caused by contaminated water or food, they nor-
and mortality rates were high in measles epidemics mally have a local or at most a regional distribution.
because of the large proportion of the population Local records, however, suggest that in certain locali-
that became ill at once. However, measles mortality ties, diarrheal diseases were fairly common. For ex-
over the long term was much lower than smallpox ample, a temple death register from Hida province
mortality. that recorded causes of death in the late eighteenth
and early nineteenth centuries documents a fairly
Other Airborne Infections severe epidemic in the autumn of 1826. Dysentery
Other well-known airborne infections that cause claimed 59 lives within a 6-week period; the victims
skin rashes or eruptions are also described in Toku- were mostly children under 10 years of age. But such
gawa sources. Chickenpox, for example, seems to epidemics were unusual. It was more common for
have been common. In fact, in the shogun's palace, diarrheal diseases to claim a few lives each year in
special ceremonies were held to celebrate a child's the later summer or autumn than to erupt in major
recovery from smallpox, measles, and chickenpox, epidemics.
indicating that all of these diseases were considered An enteric disease that did attract national atten-
a threat to life in Tokugawa Japan. tion in the late Tokugawa period was "Asiatic" chol-
Influenza is also prominently mentioned in the era. The first cholera pandemic, which began to
Japanese sources from early times, and 27 influenza spread outside of India in 1817, reached Japan to-
epidemics are described in contemporary accounts of ward the end of 1822. It followed the pattern typical
the Tokugawa period. The Japanese accounts are of imported diseases in Japan by breaking out first
similar to accounts of influenza epidemics elsewhere: in the port of Nagasaki, where it ws heralded as a
They describe a coughing epidemic that spread ex- new disease. It spread from there in a northeasterly
tremely rapidly, infecting everyone - young and old, direction to Kyoto and Osaka, but died out, presum-
male and female. As is typical of influenza, the mor- ably because of the cold weather, before reaching the
tality rate was highest among the very young and the capital at Edo. Ironically, the disease that was
very old. Influenza epidemics, like other imported known in the West as "Asiatic" cholera was known
epidemics, were said to enter Japan through the port in Japan as "the disease of the Western barbarians."
of Nagasaki. In the seventeenth and eighteenth centu- There is no further evidence of cholera in Japan
ries, the timing of epidemics was different from those until 1858, when it once again arrived in Nagasaki,
reported in Europe; but by the nineteenth century, this time on the American ship Mississippi. The fact
influenza epidemics were noted in both regions at that there were no outbreaks of cholera in Japan
very nearly the same time. It appears that two dis- between 1822 and 1858 is remarkable, because it
tinct regional dissemination systems for influenza was during this period that the disease became a
may have merged during the early modern period as major threat to cities of the West. But Japan's politi-
the frequency of contact and speed of transport be- cal cordon sanitaire seems to have been effective in
tween East and West increased. keeping cholera out. By the late 1850s, however,
after its ports had beeen opened to international
Diarrheal Diseases trade by American gunboats, Japan was stricken by
In Japan, epidemics of diarrheal diseases were re- the same pandemics that affected other world
ported as early as the ninth century, but severe, regions.

Chronic Diseases mentions other common illnesses, but, as noted ear-
It is much more difficult to identify the nonepidemic lier, it is usually impossible to identify them within
or chronic diseases of the early modern period, but modern nosology. The kinds of diseases referred to,
there is no doubt that venereal diseases were com- however, were those experienced by many early mod-
mon. Gonorrhea was an old disease in Japan and ern societies. Ailments of the eye were apparently
presumably had a wide distribution. However, a new very common, as they were featured in medical
venereal disease that was probably syphilis reached books and in general accounts of the period. Pompe
Japan around 1513. The Japanese called it "the van Meerdervoort, a Dutch physician who arrived in
great pox" - the same name that Europeans had Japan in the 1850s, writes that he was struck by the
given to syphilis a short time before. The Japanese number of Japanese people who were visibly af-
later claimed that syphilis had been brought to them flicted, often blinded, by eye diseases. These people
by the Portuguese, but as the Portuguese did not probably suffered from trachoma, a disease that was
reach Japan until 1543, this conclusion is question- common in Japan in the late nineteenth century, and
able. Syphilis probably spread from Portuguese to presumably in earlier times as well.
Japanese or Ryukyuan traders in the East Indies in Other health problems frequently mentioned in
the early sixteenth century, and then subsequently contemporary literature include beriberi, tooth-
entered Japan on East Asian ships. aches, hemorrhoids, ringworm, coughing disease,
By 1600 syphilis was a major health problem in kidney problems, and food poisoning. In addition to
Japan's large cities. Sixteenth-century European ob- these common ailments, there are two others, which
servers had reported that it was widespread among are called senki and shaku. These two terms, used in
the Japanese population, and contemporary Japa- Japan as early as the tenth century, appear to refer
nese writers claimed that in Edo more doctors to a host of diseases that cause stomach, intestinal,
treated syphilis than any other disease. Fully 9.64 or back pain. Senki seems to refer to chronic disease,
percent of the human skulls that have been exca- and shaku to more acute problems.
vated from several Edo period sites in and around The various treatments recommended for these
Tokyo show cranial lesions caused by tertiary syphi- two illnesses suggest that they may have been
lis (8.8 percent male; 5.9 percent female). This rate caused by worms or other intestinal parasites, tu-
seems quite high, especially when one considers that mors, diseases of the stomach or gallbladder, ulcers,
the incidence of earlier stage syphilis in the popula- kidney disease, and various problems involving the
tion would have been much higher than the inci- lower back. In other words, these were catch-all
dence of tertiary syphilis. However, when one consid- terms that covered many of the different diseases
ers the high proportion of males in the population of that afflict humanity. The various manifestations of
Edo and the numerous licensed pleasure quarters senki and shaku were featured in Tokugawa medical
and widespread prostitution, perhaps a high rate of books, and, depending upon the symptoms, it was
syphilis morbidity and mortality was to be expected. the task of the physician to recommend appropriate
treatment.
Other Diseases
Bubonic plague and epidemic typhus, the two most There are few surprises in the kinds of disease
important vector-borne diseases in early modern Eu- described in the Tokugawa sources. Of greater inter-
rope, seem not to have afflicted early modern Japan. est is the failure to find evidence of certain diseases
Rather plague was first reported in Japan at the end that were common in the West. Plague and epidemic
of the nineteenth century and believed to have ar- typhus, already mentioned, are conspicuous by their
rived on ships from China that carried plague- absence. And Westerners who arrived in Japan in
infested rats. Typhus probably arrived somewhat the late nineteenth century commented on the rarity
earlier, but typhus and typhoid were confused in of scarlet fever, diphtheria, tuberculosis, typhoid,
Japan as they were in Europe, so it is difficult to cholera infantum, epidemic dysentery, and severe
determine which disease is being referred to in the forms of malaria. Even tuberculosis seemed much
Japanese sources. A Japanese variant of typhus, less prevalent in Japan in the 1860s than in contem-
called tsutsugamushi disease, is fairly common in porary Europe, but tuberculosis death rates were
the Shinano River Valley. It is carried by a mite, and rising sharply by the end of the century. The differ-
although the illness can be fatal, it has a much more ences in the disease histories of Japan and the West
benign history than European typhus. suggest again that Japan's isolation from world
The popular literature of the Tokugawa period trade gave the islands a measure of protection from

VI.7. Antiquity in Korea 389
some of the major diseases of the early modern to attack Japan, or by Japanese armies establishing
period. a base from which to attack the Asian mainland.
Ann Bowman Jannetta Undoubtedly, these contacts must have brought in-
fectious diseases to Korea.
Bibliography To discuss diseases of antiquity in Korea means to
Fujikawa, Yu. 1939. Nihon shippei shi, 3d edition. Tokyo. discuss those illnesses that occurred during the Old
Jannetta, Ann B. 1987. Epidemics and mortality in early Choson Period (traditionally dated 2333 B.C. to A.D.
modern Japan. Princeton, N.J. 562), and the Three Kingdoms Era encompassing
Maekawa, Kyutaro. 1976. Sasuyu kiroku yori mita Toso, the Kingdoms of Koguryo (37 B.C. to A.D. 688),
mashin, suito. No Ooku e no denpa. Nihon ishigaku Paekche (18 B.C. to A.D. 660), and Silla (57 B.C. to
zasshi 22: 157-68. A.D. 935), as well as the Koryo Era (918-1392). By
Matsuda, Takeshi. 1971. Edo jidai no mashin ryuko. the ninth century B.C., rice-cultivating Bronze Age
Nihon Ishigaku Zasshi 17: 206-12. cultures had been established on the Korean penin-
Morse, Edward. 1917. Japan, day by day, 1877,1878-79,
sula. During the Three Kingdoms Era, the Chinese
1882-83. Vol. 1. New York.
Suda, Keizo. 1973 Hida "O" jiin kakocho no kenkyu.
writing system was adopted by the courts in order to
Takayama.
ensure the writing down of state chronicles. Only
Suzuki, Takao. 1984. Paleopathological andpaleoepidemio- fragments of these texts have survived by being in-
logical study of osseous syphilis in the Edo period. corporated in the Samguk sagi (History of the Three
Tokyo. Kingdoms), which was compiled in 1145 and consti-
Tatsukawa, Shqji. 1974. Shomin shiryo ni miru Edo jidai tutes the oldest preserved history of Korea.
no shippei. Nihon ishigaku zasshi 20: 313—35. The introduction of Buddhism to Korea from
1976. Nihonjin no byoreki. Tokyo. China during the fourth century A.D. increased con-
Yamazaki, Tasuku. 1931. Nihon ekishi oyobi boeki shi. tacts with the Asian mainland. Particularly during
Tokyo. the Three Kingdoms Era, many Korean Buddhist
monks studied in China and were responsible for the
influx of many aspects of Chinese culture to the
peninsula. When, after long periods of warfare, the
Three Kingdoms were unified in 661, the resulting
VI.7 Kingdom of Unified Silla extended cultural and eco-
Diseases of Antiquity nomic contacts with China. Besides an increasing
number of Buddhist monks, students interested in
in Korea Confucian learning went to China. Some Buddhists
even reached India, endeavoring to study their reli-
gion at its source. This period also saw increasing
The history of diseases in Korea, especially the dis- cultural and economic exchange with Japan, and
eases of the early historic period, constitutes a still commercial intercourse with Arab traders.
largely unexplored area, save for the efforts of a few Although Korea was epidemiologically not as iso-
pioneering scholars whosefindingsare not yet avail- lated as Japan, and the development of immunities
able in English translations (Miki 1962; Kim 1966). within the population must have set in earlier and
However, thisfieldshould be of considerable interest more intensively, the long periods of unrest, poverty,
to students of Asian history as well as those con- and famine during the wars of unification must have
cerned with the history of medicine. favored the outbreak of epidemics and famine-
related diseases. Social reforms during the Koryo
Geography, History, and Background Era (918-1392) may have improved this situation.
Much of Korea's epidemiological past has been Relief programs, sponsored by the government and
shaped by its geography. The country occupies a by the Buddhist church, were implemented; grana-
peninsula south of Manchuria that is separated from ries were built as a precaution against years of
the Chinese mainland to the west by the Yellow Sea, drought; infirmaries were created; and a system of
and from nearby Japan to the east by the Korean medical care in the countryside was established.
and the Tsushima Straits. Forming a land bridge Despite all these efforts, however, the vast majority
between northern Asia and the islands of Japan, of the population stayed in poverty and, conse-
Korea has time and again been subjected to inva- quently, remained particularly vulnerable to conta-
sions by armies from the Asian mainland intending gious diseases.

Diseases leans strongly on the tradition of Chinese medicine.
Textual sources relevant to the study of diseases in Thus, symptoms such as hemorrhages, blockages of
the early history of Korea are scarce. The Shin Jip the throat, loss of consciousness, and sudden death
Ban (Anthology of Paekche Prescriptions) and the from various infectious diseases are discussed. A
Bup Sa Ban (Prescriptions of the Masters of Silla), combined study of the Hyang-yak kugup pang and
medical texts compiled in the states of Paekche and official annals such as the History of Koryo would
Silla, respectively, are lost. Only some passages and provide more insights into the epidemiology of that
prescriptions have survived by being incorporated period. It must be noted, however, that the official
into Chinese and Japanese texts. The Ishinpo, a historical writings expressed little awareness of
collection of mainly Chinese medical texts, com- medical problems in the country except in case of
piled by the Japanese scholar Tamba Yasuyori in extended and devastating epidemics, those that in-
984, refers to the Shin Jip Ban in a discussion volved the capital city or its environs, or cases of
concerning abscesses. illness within the royal family.
Korean physicians were very much influenced by The following represents a survey of diseases or
Chinese medical thinking, and adopted Chinese groups of diseases, endemic or epidemic, the occur-
medical terminology. But they also reinterpreted rence of which can be inferred from miscellaneous
Chinese material in their own way and added infor- textual sources:
mation obtained from Indian sources.
Owing to the lack of genuine medical literature of Smallpox
that period, we have to rely on historical literature Historians generally agree that smallpox originated
for information regarding diseases. The Samguk from India. According to the Tongui pogam (Exem-
sagi mentions a first occurrence of an epidemic dur- plar of Korean Medicine 1610), smallpox had ap-
ing the reign of Onjo, king of Paekche, in 15 B.C. peared in China already at the end of the Zhou
There are a great number of different terms for epi- dynasty and the beginning of the Han dynasty (i.e.,
demic diseases in ancient Korean writings such as during the late third century B.C.). A first mention-
"poison epidemic," "evil epidemic," "epidemic of the ing of smallpox in a Chinese source suggests a later
time," "epidemic of disease," and others. Identifica- date {Zhou-hou bei-ji fang by Ge Hong, first half of
tions of these terms are, however, difficult. Thus, the the fourth century A.D.), whereas a first docu-
Chinese character that could be translated "leprosy mented smallpox epidemic can be dated A.D. 495.
epidemic" might simply refer to a widespread dis- A terminus antequem for the arrival of smallpox
ease of a very severe nature. to Korea may be deduced from the fact that Korean
Diseases were discussed in terms of their major envoys of King Song (523-54) of Paekche, who
symptoms. However, often no clear distinctions were brought Buddhist scriptures and statues to Japan,
made, and death from famine was recorded with the transmitted the disease to that country in 552.
same wording as death from an epidemic. No need Shortly after Emperor Kimmei legalized Buddhism,
for precision may have been felt in a society that an epidemic of smallpox broke out, and led to the
attributed misfortune, disease, and death to the ac- immediate abolition of the new religion. In 584, Japa-
tion of ghosts, devils, and demons. Although the nese officials visited Korea and brought back to Ja-
more rational principles of Chinese medicine were pan the disease together with two images of Buddha.
known to the physicians, they rarely made distinc- Emperor Bidatsu himself became a victim of the
tions solely based on these criteria. ensuing epidemic the following year. Two years la-
The only complete extant medical book of the ter, with the epidemic still raging, Emperor Yomel
Koryo Era is the Hyang-yak kugup pang (Emer- (585-7) died of the disease, too. Also the epidemics of
gency remedies of folk medicine). This collection of 735-7 and of 763 are supposed to have been trans-
simple relief measures and preparations was committed to Japan from the Korean peninsula. At any
piled during the reign of King Kojong, in 1236. It rate, during the Three Kingdoms Era, Korea was a
deals mainly with emergency measures such as em- frequent victim of the disease; two kings, Sondock
ployed in accidents; injuries; bites by insects, rep- (780-5) and Munjong (839-57), died of smallpox.
tiles, and other animals; drowning; sunstroke; food For the Koryo Era there is no evidence for the
poisoning; drunkenness; and toothache. It describes, occurrence of smallpox epidemics. Yet, the Hyang-
however, also symptoms of diseases and their treat- yak kugup pang refers to eruptive diseases in the
ment. This book may be considered to reflect the chapter "Various Childhood Diseases"; the text
scholarly attitude toward health care because it speaks of "pea-sized boils" and "bean-sized boils in

VI.7. Antiquity in Korea 391
the child." This could well be a reference to small- including the twisting stomachache and bloody
pox. If we correctly interpret this passage, and if stools. Besides, this book mentions "cold dysentery,"
smallpox had become one of the common children's "dysentery with blue color," "hot dysentery with
diseases, then it would have been firmly established reddish-yellow color," "red dysentery with stomach-
in Korea at this period. It should, however, be noted ache," and others.
that measles was apparently not distinguished from
smallpox until the beginning of the Yi dynasty Venereal Diseases
(1392-1910). One of the main symptoms of advanced gonorrhea,
difficult urination, is mentioned in the Hyang-yak
Other Febrile Illnesses kugup pang. Besides this book distinguishes five
There can be little doubt that malaria was epidemic types of gonorrhea. That the nature of contagion of
on the Korean peninsula from time immemorial. A this disease was understood is implied in the follow-
first mentioning of the disease, however, is as late as ing passage in the History of Koryo:
the History of Koryo. The Hyang-yak kugup pang
One night Mr. Hong took the previous King Chunghye
contains a passage on "malaria disease" and its ther- (1330-1332) to his house and they feasted. The King or-
apy. Although not always strictly differentiated from dered a priest-doctor to cure Mr. Hong's gonorrhea. The
other febrile illnesses, the symptoms of the "3-day King always took a fever drug and visited many ladies. As
fever," as it was usually called, are sufficiently dis- a result he had disease. The King and Mr. Hong received
tinct to recognize it with some degree of certainty; curing methods from the priest. The King. . . used the
various drugs were employed to obtain relief during fever medicine to increase his stamina. (Miki 1962)
the attacks (Miki 1962). Although typhoid fever may
have been subsumed under and classified together Diseases due to Nutritional Deficiencies
with other febrile diseases, when one considers the In a largely agricultural society, only sufficient local
social and hygienic conditions of the period, there can harvests could avert famine and famine-related dis-
be little doubt of its role in Korean medical history. eases. In the early Three Kingdoms period, the king
The same may apply to diphtheria; perhaps the term of Paekche was held responsible for crop failure and,
"blockage of the throat" refers to this disease. in such cases, removed from the throne or even
killed (Lee 1984). One of the most common nutri-
Respiratory Diseases tional diseases in rice-growing societies up to recent
The Hyang-yak kugup pang refers to illnesses that, times has been beriberi, that is, thiamine or vitamin
in modern terms, would be classified as respiratory B deficiency. Although there is no description of the
diseases. In fact, there seem to be references to symptoms in Korean sources prior to the Yi dynasty
asthma, pleurisy, and hydrothorax. Whether or not (1392-1910), we may assume that this disease was
pulmonary tuberculosis and pneumonia, frequent common, whenever rice was polished and the husk,
diseases in many premodern societies, were recog- which contains this vitamin, was stripped from the
nized as individual diseases cannot be ascertained grain.
from the text.
Skin Diseases, Tumors, and Leprosy
Parasitic Infestations The Hyang-yak kugup pang contains a section on
The texts mention a disease with bloody saliva. This tumors. However, whether these refer to abscesses,
symptom is characteristic of pulmonary distomato- carbuncles, and other inflammatory swelling re-
sis, an infestation with Paragonimus westermani, mains uncertain, particularly because these descrip-
which is still prevalent in East Asia, particularly in tions are mixed with those of other skin diseases
Korea. such as furunculosis, dermatitis, scabies, and
erysipelas; erysipelas of the head and face is empha-
Diarrhea and Dysentery sized in the text. Another skin disease marked by
Taking the minute categorization of diseases accom- boils that is mentioned in this text most probably
panied by diarrhea, as found in the Hyang-yak refers to leprosy. The History of Koryo frequently
kugup pang, as an indicator, this group of illnesses refers to leprosy as the "bad disease" which is wide-
appears to have been common and well known. spread, malignant, and hard to cure. That persons
Whereas the official chronicles omitted these, the stricken with this disease not only spread horror to
Hyang-yak kugup pang gives a description of an the healthy population but also tended to elicit pity
epidemic with precise details of its symptomatology, and gave rise to benevolent deeds is shown by a

passage from the History ofKoryo in which a devoted
son cut off a piece of his own flesh in order to cure his VI.8
father's disease. Diseases of the Premodern
Miscellaneous Diseases and Conditions Period in Korea
The Hyang-yak kugup pang gives a clear-cut defini-
tion of tetanus by stating that a spear wound will be
fatal if it has caused lockjaw and spasms. Similarly, Medical Literature
brief descriptions are given for rabies, stroke, epi- In 1392 Yi Songgye assumed the throne as King
lepsy, hemorrhoids, prolapsed anus, and diabetes T'aejo and the Yi Dynasty (1392-1910) began. His
mellitus. The latter is defined as causing much supporters initiated a sweeping land reform pro-
urine, being unrelated to gonorrhea, and resulting gram that began with a cadastral survey of landhold-
in very thin patients. Somewhat obscure is the cate- ing throughout the country and the destruction of
gory of "water-swelling" diseases. Obviously refer- previous registers of public and private landhold-
ring to edemas, this term may include not only pri- ings. New developments in agriculture as well as in
mary heart or kidney disease but also edemas of wet science, technology, and medicine followed, stimulat-
beriberi; consequently, the symptoms of "water- ing inventions and publications. For example, the
swelling" diseases are also listed in this book under agricultural manual called The Art ofFarming, com-
the heading of "paralysis," this being one of the piled in 1430, was based on the reasonable but novel
cardinal symptoms of dry beriberi. premise that because Korean climate and soil dif-
Finally, the Hyang-yak kugup pang has a section fered from those of China, agricultural methods
on insanity, termed "uneasiness of mind," "unusual- should be designed to meet the specific conditions
ness of mind," or, in the case of psychosis, "true found in the peninsula. Improvements in agricul-
madness." However, insanity was a health problem tural techniques produced increased yields, and the
that was considered outside the confines of scholarly spread of cotton cultivation provided improved cloth-
medicine; treatment called for the mudang (sha- ing for the common people.
man) rather than the physician. Important developments in medical knowledge
Lois N. Magner took place in the early years of the Yi dynasty, as the
government encouraged its study and created two
Bibliography specialized institutions for medical care. One served
Ackerknecht, Erwin H. 1965. History and geography of the the royal family and elite officials, and the other was
most important diseases. New York. to serve the general population. Candidates who
Fujikawa, Yu 1934. Japanese medicine, trans. John scored well on the "Miscellaneous Examinations"
Ruhr ah. New York. could be employed in the Palace Medical Office,
Han Woo-keun. 1970. The history of Korea, trans. Lee which trained regional medical officials.
Kyung-shik, ed. Grafton K. Mintz. Seoul, Korea. The concept that indigenous conditions must be
Henschen, Folke. 1966. The history and geography of dis-
eases, trans. Joan Tate. New York.
considered was increasingly incorporated into medi-
Huard, Pierre, and Ming Wong. 1972. Chinese medicine, cal as well as agricultural writings. China's influ-
trans. Bernard Fielding. New York. ence on medical philosophy remained strong, but
Kim Tu-jong. 1966. Han'guk uihaksa (A history of Korean interest in the study and exploitation of Korea's own
medicine). Seoul, Korea. traditional folk remedies stimulated the develop-
Lee Ki-baik. 1984. A new history of Korea, trans. Edward ment of independent medical scholarship as may be
W. Wagner. Cambridge, Mass. seen in the Hyang-yak kugup pang (Emergency
Miki, Sakae. 1962. History of Korean medicine and of Remedies of Folk Medicine 1236).
disease in Korea. Japan. [In Japanese] A major milestone in the development of Korean
Ponsonby Fane, R. A. B. 1959. The Imperial House of medical science was the publication of a medical ency-
Japan. Japan. clopedia in 85 volumes entitled the Hyangyak
chipsong pang (Compilation of Native Korean Pre-
scriptions 1433). A similar format was followed by
the compilers of the Uibang yuch'wi (Classified Col-
lection of Medical Prescriptions), which was com-
pleted in 1445. In an attempt to include all known
theories of medicine, the compilers assembled 264

VI.8. Premodern Period in Korea 393
volumes. Unfortunately, this resulted in a massive because of this latter epidemic that Ho Chun was
collection unsuited for general use, and only a few ordered to compile a new book of detailed curing
copies were ever produced. In 1596 the King ordered methods, and certainly his account leaves the im-
Ho Chun to prepare a more useful text. The project pression that this disease was a member of the ty-
took Ho Chun and his group more than 10 years to phus fever group.
complete. It resulted in the highly respected 25 vol- As with typhus, little historical evidence of major
umes of Tongui pogam (Exemplar of Korean Medi- epidemics of typhoid fever in Korea exists. Yet occa-
cine 1610), which were still being reprinted in Korea, sionally whole villages contracted a disease with
China, and Japan during the eighteenth century. The symptoms suggestive of typhoid. It is likely that
work's preparation was, at least in part, a response to typhoid fever was endemic and epidemic during the
the devastation caused throughout almost all of Ko- Yi Dynasty, but few local outbreaks were noted in
rea during the 7-year struggle of the Hideyoshi Inva- official records. Until recent times, typhus and ty-
sion (1592-8). In the most severely affected provinces phoid were not distinguished from each other. Ty-
some villages were totally destroyed, population was phoid fever remained endemic in modern Korea, but
markedly decreased, and famine and epidemic dis- many people viewed typhoid as a rather minor dis-
ease inevitably compounded the misery of the people ease of about the same severity as "red dysentery."
(Lee 1984). Relapsing fever, a tick-borne disease that was con-
The Hyangyak chipsong pang and the Tongui sidered one of the forms of typhus, may have ap-
pogam served as the models for many other medical peared in Korea during the sixteenth century when
books of this era. Ho Chun, the author of the Tongui epidemics occurred in China and Manchuria, but the
pogam, was a Taoist, and his medical philosophy evidence from the early Yi Dynasty is obscure. Two
rested on the three Taoist essences: mind, sense, and other diseases that might have existed in Korea
spiritual power. His classification of disease was during this time period are leptospirosis (Weil's dis-
based on causes as well as symptomatology and the ease or leptospiral jaundice) and rat-bite fever. Most
physical location of disorders. The view of disease Korean therapeutic texts included a brief account of
initiated by the Tongui pogam exerted a profound certain curing methods that suggest knowledge of
influence on the Korean medical world during the rat-bite fever.
second half of the Yi Dynasty. Epidemics were collec-
tively referred to as "bad disease" in the ancient Bubonic Plague
period, but as medical knowledge developed, refer- Although waves of devastating epidemics of bubonic
ences to epidemic diseases became more specific. plague have been recorded in China since 1331, the
Generally, the epidemic diseases recorded as "bad surviving literature from Korea does not seem to
disease" in the Yijo Sillok (True History of the Yi contain specific descriptions of similar epidemics
Dynasty) constituted those other than the eruptive (Miki 1962).
fevers, among them influenza, epidemic meningitis,
typhoid and typhuslike diseases, and other diseases Influenza
that have no particularly well-marked external The Hyangyak chipsong pang, the Tongui pogam,
manifestations. and other medical texts of the Yi Dynasty discuss
symptoms of epidemic disease best explained as in-
fluenza. Although large and small epidemics of influ-
Typhus and Typhoid Fever Group enza probably occurred many times during this pe-
Clear descriptions of typhus begin to appear only in riod, the historical records are ambiguous; perhaps
modern times, but epidemic occurrences of ty- the outbreaks were not sufficiently striking or wide-
phuslike diseases in ancient times can be recognized spread to be separated from other epidemic diseases.
in China and Korea. For example, an epidemic that However, major influenza epidemics occurred in Ja-
started in P'yongan Province in July 1524, and pan during this period, and it seems reasonable to
spread continuously until it reached the middle prov- assume that there were comparable epidemics in
inces of the peninsula, seems suspiciously ty- Korea. Moreover, given the nature of influenza, epi-
phuslike. The epidemic lasted until the spring of demics could have ricocheted back and forth be-
1527, and contemporary accounts emphasized the tween Korea and Japan (Fujikawa 1934).
high fever and contagious nature of the ailment.
Another typhuslike epidemic seems to have occurred Smallpox
in 1543, and still another in 1612 in the province of Smallpox was the most feared disease on the penin-
Hamgyong and then spread to the south. It was sula because epidemics were extensive and mortality

rates were high. Before the practice of vaccination that occurred in 1613 was similar to measles, but
was established, few people avoided an encounter was a separate disease. This epidemic may have
with smallpox. been scarlatina, as doctors were unable to differenti-
Most references to the epidemiology of smallpox ate between scarlatina and measles.
during this era are found in the Yijo Sillok, histori- Subsequent medical books say nothing significant
cal records of the Yi Dynasty. Thus, the records are or new about the "dot-eruptive disease" until the
biased toward epidemics that occurred near the capi- eighteenth century, when doctors influenced by the
tal and affected the royal family. For example, in "School of Positivism" began to write specialized
1418 the Prince died of the "disease with bean-sized medical texts based on their own experiences and
eruptions." In 1424, King Sejong's son died of an case studies. A measles outbreak that occurred in
eruptive disease. In 1675, King Sukchong contracted 1707 stimulated interest in the disease, and several
smallpox. In 1680, an epidemic broke out in the specialized books on measles were written in re-
capital city, and the Queen contracted the disease sponse to the epidemics of 1752 and 1775. Such texts
(the King had previously moved to another palace). provided comprehensive discussions of the symp-
During the seventeenth and eighteenth centuries, toms and treatment of measles and smallpox, and
Western science and technology were coming into made it possible for doctors to differentiate the erup-
Korea and stimulating progress in science and medi- tive diseases.
cine. An example of this trend was the Makwa
hoefong (Comprehensive Treatise on Smallpox), a Rubella
specialized medical treatise published in 1798 (Lee It is difficult to determine whether physicians of this
1984). period were familiar with rubella, for even the most
specialized eighteenth-century books on smallpox
Chickenpox and measles do not seem to describe it. In the chroni-
Although chickenpox was confused with smallpox cles of King Yongjo (1724-76), however, there are
until very recent times, the history of the reign of entries noting that the 9-year-old Prince had mea-
King Myongjong (1545—67) refers to "big" and sles in 1743. Then, when the Prince was 18 years
"small" eruptive diseases. The big eruptive disease old, he had measles again, and two years later he
probably corresponds to smallpox; however, whether had "dot-measles." There was a major epidemic of
the small eruptive disease corresponds to chickenpox measles when the Prince was 18 years old, so pre-
or measles is uncertain. In the Sukchong Sillok sumably the Prince really had measles at that time.
(Sukchong reigned from 1674 to 1720), a description Because an individual has measles only once, the
of eruptive diseases with big and small efflorescences other episodes could have been rubella and scarla-
survives that suggests a slightly different meaning tina. There are several other examples of such cases.
from previous records of these eruptive diseases. At
this time, measles was generally distinguished from Scarlatina, or Scarlet Fever
smallpox, so the small eruptive disease could have Scarlatina was not described as an independent dis-
been chickenpox. In the records of the period 1724- ease in Korea at this time, but a disease that might
76, references to episodes of illness and recovery of be scarlatina occurred in 1613 under the name "poi-
the Queen and the Prince included all the symptoms sonous epidemic of the T'ang." A detailed study of
of chickenpox. Similar examples can be found follow- the epidemic, symptoms of the disease, and curing
ing the middle period of the Yi Dynasty. methods was prepared by Ho Chun.
Measles Dysentery
During the early period of the Yi Dynasty, medical Diseases with the characteristic symptoms of dysen-
texts such as the Hyangyak chipsong pang indicate a tery existed in ancient times in China, Korea, and
dawning recognition that measles was a disease that Japan. Dysentery-like diseases were given many de-
could be separated from smallpox. Seventeenth- scriptive names, such as red dysentery, bloody dysen-
century Korean texts described a "dot-eruption dis- tery, red-white dysentery, thick-blood dysentery, and
ease" that appears to be measles. However, doctors so forth. The major symptoms common to the entire
seemed to have had difficulty securing knowledge of group were fever, stomachache, bloody excretions,
this eruptive disease, suggesting that epidemics of spasms, and frequent diarrhea. Major epidemics are
measles were rare. It is worth noting that Ho Chun generally associated with true Shigella dysentery,
suggested that the "poisonous epidemic of the T'ang" but both bacillary and amebic dysentery were en-

demic in Korea. Compared to other epidemic dis- March of the following year, but the unusual nature
eases, dysentery was not considered very grave, and of the epidemic attracted the attention of the central
therefore, it was often omitted from official chronolo- government. Medical officials were dispatched to the
gies of epidemics. province to dispense medicines and report on the
The Hyangyak chipsong pang divided all diar- causes and symptoms. According to the official ob-
rheas into 23 different forms, including red dysen- server, the disease occurred mainly within Hwang-
tery. The text also describes various diarrheas that hae Province. In comparison to other epidemic dis-
affect children and lists 10 different forms based on eases, its ability to spread was weak, and thus the
the symptoms that predominated under different number of individuals affected was not very large.
conditions. Medical books written during the middle The disease had probably occurred previously in the
and late years of the Yi Dynasty also describe dysen- same province as early as 1434. Outbreaks contin-
tery symptoms. ued into 1458, but the number and dates of out-
breaks cannot be ascertained.
Diphtheria The first symptoms of the disease included blurred
In Korea, as in China and Japan, there are no clear vision, loss of vision, delirium and babbling, frenzy,
descriptions of a disease corresponding to diphtheria and finally prostration and collapse. Other symp-
until the modern age. Differential diagnosis of sore toms were difficulty of movement of the whole body,
throat diseases, such as diphtheria, scarlet fever, and paralysis below the waist, swelling of the lower abdo-
tonsillitis, is just as difficult as sorting out the erup- men, pains, blackening of the teeth, weakness in the
tive fevers and the typhuslike diseases. Moreover, extremities, coughing, and gasping. If one member
diphtheria is not strongly associated with dramatic of the family fell ill, the whole family might sicken
epidemics of high mortality. Indeed, mild cases are and die. When all the symptoms are considered, a
not unusual, and immunity is often quietly acquired tentative diagnosis of epidemic cerebrospinal menin-
at an early age. Since ancient times, however, many gitis seems reasonable (Miki 1962).
different names have been applied to various diseases
of the throat. It therefore appears probable that diph-
theria was recognized as a particular disease marked Malaria
by a characteristic symptomatology. Malaria was the most common of the infectious dis-
eases in Korea, where it almost always appeared as
Two diseases consistent with a diagnosis of diph- the "3-day fever" and where knowledge about it de-
theria are listed in the Hyangyak chipsong pang veloped relatively early. The relief methods in the
under the heading "Throat." The Tongui pogam lists Hyangyak chipsong pang are based on a combination
several different forms of throat disease, including a of Chinese remedies and those in the Hyang-yak
contagious disease that might correspond to diphthe- kugup pang.
ria. Korean medical treatises of the eighteenth cen-
tury also described throat diseases with symptoms
similar to those of diphtheria. Sexually Transmitted Diseases
Syphilis probably came to Korea from China be-
Whooping Cough or Pertussis tween 1506 and 1521, and by the seventeenth cen-
Symptoms similar to those of pertussis appear in the tury had spread among all classes of people through-
Hyangyak chipsong pang. A list of various "coughing out the country. Venereal diseases were known in
diseases" includes symptoms suggesting pertussis, the Orient long before syphilis spread throughout
and the section on pediatrics describes symptoms the world. Korean texts contain descriptions of such
similar to pertussis under the heading "Children's diseases, but the venereal diseases described in the
Coughing." The Tongui pogam and texts from the older texts were not associated with skin lesions;
eighteenth century also describe symptoms that sug- their main symptoms were increased frequency and
gest whooping cough. urgency of urination. Other symptoms were rather
ambiguous. However, references to a disease alleg-
Epidemic Meningitis edly occurring only in males, involving the "bad
A disease that might have been epidemic cerebro- nature of eruptions on the genitals related to consort-
spinal meningitis is described in the annals of the ing with women," found in the Yijo Sillok probably
reign of King Songjong (1469-94). According to indicate syphilis.
these records, in November 1471, an epidemic dis- Japan and the continent were the two possible
ease appeared in Hwanghae Province. It died out by routes for the transmission of syphilis to Korea.

Yet trade between foreign countries and the penin- Tuberculosis and Other Respiratory
sula during the first half of the sixteenth century Diseases
was rather limited, especially with Japan. In fact, During the Yi Dynasty, medical knowledge of tuber-
the only contacts with the Japanese during this culosis became more abundant and precise. The
period would have been invasions by those maraud- Hyangyak chipsong pang describes pulmonary tuber-
ers who had been attacking the Korean coast since culosis and recognizes the contagious nature of the
the thirteenth century. Thus, the possibility that disease as well as the relationship between the most
syphilis could have been brought from Japan to common form, pulmonary tuberculosis, and its other
Korea cannot be absolutely ruled out, but it is forms (Miki 1962). The Tongui pogam also contains
more likely that the primary route was from the a good description of pulmonary tuberculosis and the
continent, for trade between Korea and Ming symptoms of other forms of the disease. Moreover, it
China occurred many times per year through spe- describes symptoms suggesting scrofula, which was
cial emissaries, including numerous officials and considered primarily childhood tuberculosis.
merchants. Moreover, the first Korean medical The Hyangyak chipsong pang discusses the symp-
texts to discuss the new disease suggest that syphi- toms of asthma clearly, and the Tongui pogam has a
lis came from China. discussion of asthma under the heading of "cough-
At the time, it was thought that the immoral and ing." Asthma was divided into eight different forms;
illegal use of medicines made of human flesh and asthmatic attacks were attributed to excess eating,
gallbladder were linked to the arrival of syphilis in fear, and shock. Further, under the column dealing
Korea. Thus, the following was reported in February with symptoms of "lung swelling," there is a discus-
1566: sion of a condition that may be related to emphysema.
Ailments that appear to correspond to modern pleu-
There were many people in Seoul who killed people to take risy and hydrothorax also appear in the medical lit-
the gallbladder and this was said to be for the use of very erature of this period in discussions of "heart pain"
promiscuous people. Many beggars disappeared from the
street. After several years there were no longer any beg-
and "waist pain." The Hyangyak chipsong pang and
gars and the killers turned to child murder. Officials and the Tonqui pogam describe symptoms that suggest
other people who consorted with prostitutes got the dis- hydrothorax in a discussion of conditions attributed
ease. They tried to cure it with human gallbladder and to the accumulation of "chest water," which indicate
used up all the beggars. (Miki 1962, author's translation) observations of both the accumulation of water in the
chest and swelling of the whole body.
Whatever the authenticity of this story, it reflects Lobar pneumonia is probably one of the illnesses in-
the desperation of the sick and their willingness to cluded in the "harm caused by cold" category of fever
resort to murder as well as superstition to procure diseases. Within this category, the Hyangyak chip-
remedies for their ailments. The exact origin of this song pang and the Tongui pogam discuss diseases
aberration is unknown, but throughout the world marked by high fever, coughing, and bloody mucus.
there are many accounts of the use of human blood
and organs against diseases such as leprosy, syphi- Heart Disease
lis, and tuberculosis; Korean and Chinese pharmaco- The precise diagnosis of various forms of heart dis-
poeias included a wide range of human parts and ease was achieved only after the development of
products under the general category "human medi- pathological anatomy, auscultation, and the stetho-
cine" (Cooper and Sivin 1973). scope. Under Chinese medical philosophy, abstract
The Hyangyak chipsong pang refers to eight arguments concerning the pulse, combined with
kinds of gonorrhea, and the descriptions are quite heart pain and shortness of breath, were used for
detailed. The Tongui pogam also describes various diagnosis of heart diseases. Under the heading
symptoms of the eight different kinds of gonorrhea. "heart pain," the Hyangyak chipsong pang lists nine
Although the relationship between the disease and different kinds. These entries and similar discus-
sexual intercourse was apparently recognized, the sions in other texts composed during the later years
contagious nature of disease does not seem to have of the Yi Dynasty suggest knowledge of angina
been understood. pectoris as well as other symptoms of heart disease.
The writings of the Yi Dynasty suggest the exis-
tence of chancroid, but it is difficult to separate this Digestive Disorders
ancient venereal disease from gonorrhea and syphi- Gastritis seems to be the major disease in the cate-
lis. gory of stomach diseases. The Hyangyak chipsong

pang and the Tongui pogam described symptoms disease was usually acquired by eating raw crab
that suggest gastritis. Gastric ulcer might be the meat, and references to a disorder characterized by
modern diagnosis for the disorder associated with a rusty-brown mucus in the ancient texts probably
"wound of the stomach spilling blood" accompanied reflect paragonimiasis.
by severe stomach pains. In the Hyangyak chipsong pang under the heading
A precise diagnosis of peritonitis, intestinal tu- "pediatrics" are descriptions if infestations of round-
mors, or obstructions was very difficult in both the worms and pinworms. The section on "worms" in the
East and West in ancient times, but some of the Tongui pogam describes various disease symptoms
symptoms discussed in the Tongui pogam suggest attributed to nine different worms. Many plant reme-
intestinal tumors. Tumors behind the intestine that dies were used to remove these parasites. Ancylosto-
were not movable were called "cancer," whereas a miasis (hookworm disease) and secondary anemia
kind of tumor that moved was ascribed to parasites. are not specifically described, but symptoms of ane-
Stomach cancer, liver cancer, tuberculous peritoni- mia due to ancylostomiasis seem to be described
tis, uterine cancer, and probably many other forms among the forms of jaundice.
of cancer were included in this category. Still, other
intestinal disorders, such as acute appendicitis, en-
teritis, acute enteritis, and enterostenosis are also Kidney Disease, Urinary Disease, and
discussed. Diseases of the Reproductive Organs
Clinically, the main symptom of nephropathy is
Acute enteritis, in which the symptoms are simi-
swelling; thus, the "water-swelling diseases" of the
lar to those of food poisoning and cholera, was
ancient texts probably included symptoms due to
treated in the medical texts composed in the later Yi
disorders of the cardiovascular system as well as
Dynasty. Ascites and meteorism (tympanites) might
kidney diseases. Kidney disease might be found in
be indicated in the category that contained diseases
the ancient texts under the headings of swelling,
in which the abdomen swelled. Disorders of the rec-
tum, such as hemorrhoids and prolapse of the anus, water disease, or water-"cancer" disease (ascites).
"Water-swelling diseases" associated with irregular
were described in detail, along with methods of treat-
pulse probably indicated disorders due to heart dis-
ment and dietary restrictions.
ease, rather than kidney disorders. The section on
"water-swelling disease" in the Hyangyak chipsong
Liver Disease pang lists ten different forms.
The Hyangyak chipsong pang lists 25 forms of jaun- Because symptoms of diseases of the urinary blad-
dice, but these conditions were not linked to problems der are conspicuous and painful, they were the sub-
of the liver and gallbladder. By contrast, the Tongui ject of considerable medical interest. The Hyangyak
pogam reduced all the subdivisions simply to jaun- chipsong pang discusses dysuria, ischuria, pol-
dice. Its cause was explained in terms of "damp fe- lakiuria, urinary incontinence, hematuria, gross
ver," in which the blood evaporates and becomes hot hematuria associated with high-fever diseases, and
and dark in color. This dark color first appears in the enuresis. Various symptoms of urinary problems are
eyes and face, but as it spreads, the whole body be- also discussed in connection with gonorrhea. Some of
comes yellow. Causes of jaundice included alcohol the "disorders of urine" might have been caused by
poisoning, lack of appetite, excessive sexual indul- tuberculosis of the urogenital system.
gence, and yellow sweat. Some texts apparently de- The Tongui pogam discusses the urinary bladder
scribed gallstones along with colic, but all the painful and diseases of urination in detail. The five colors of
"stone diseases" were essentially indistinguishable. urine were said to provide diagnostic clues to the
Although cirrhosis of the liver was not uncommon, origin of illness. Diseases related to difficult urina-
this disorder was not specifically ascribed to the tion were followed by a discussion of various forms of
liver. The symptoms of cirrhosis were probably con- gonorrhea symptoms.
sidered along with ascites, meteorismus, and other
disorders involving abdominal swelling.
Diabetes Mellitus
According to the Tongui pogam the thirst associated
Parasitic Infestations with diabetes mellitus was due to "heart fever." The
Paragonimiasis or pulmonary distomiasis is caused symptoms of diabetes included intense thirst and
by infection with a worm of the genus Paragonimus, hunger, increased eating and drinking, frequent uri-
especially Paragonimus westermani. In Korea the nation, weakness, and wasting. Although the pa-

tient ate and drank large quantities, all the food Skin Diseases and Leprosy
consumed turned to urine, and the patient became The texts describe many interesting and important
very thin. In advanced cases the disease was accom- skin diseases, but the most dreaded was certainly
panied by "bad boils," usually referring to ulcera leprosy. In ancient Korea leprosy was nonspe-
cruris. cifically referred to as "bad disease." Although vari-
To prevent or treat diabetes mellitus, it was said ous conditions that were included under this rubric
that one must abstain from three things: alcohol, were considered malignant and hard to cure, leprosy
sex, and salty food. In patients with the disease, was probably the major disease. Medical texts of the
acupuncture and moxibustion should not be per- Yi Dynasty referred to leprosy as "big-wind-lepra"
formed for more than 100 days because inflamma- or "big-wind-boil."
tion of the wound could lead to death. The sudden Leprosy was said to result when a "bad wind" got
formation of bad boils in such patients could signal into the body, but the disease was also said to be
imminent death. transmitted from person to person. Records for 1445
in the Yijo Sillok describe outbreaks of leprosy in
Cheju Island. According to the chronicler, the people
Beriberi of Cheju Island abandoned lepers in uninhabited
Several conditions described in the Korean medical areas along the coast because they feared them as
texts suggest a long familiarity with beriberi, also sources of contagion. Another folk belief found in the
known as "kakke." Symptoms described under this historical records for 1613 was based on the idea
heading included swelling of the lower limbs, fol- that when lepers washed their boils, the fish in the
lowed by swelling of the heart and stomach and river or the chickens in the house would acquire the
difficulty in urination, weakness in the feet, dizzi- leprosy. Then when city people ate the contaminated
ness in the head and eyes, and so forth. fish or chicken, they would be infected (Miki 1962).
Although it is likely that beriberi existed in Korea Leprosy was also seen as Heaven's punishment for
since very ancient times, true beriberi was probably criminal acts in this life or past lives.
not distinguished from the various forms of neuritis,
The historical literature also indicates a tradition
heart disease, rheumatism, and other forms of mal-
of relief work and quarantine for leprosy, especially
nutrition. According to the Hyangyak chipsong
on Cheju Island where the disease was most preva-
pang, beriberi was due to the "wind poison" gener-
lent. However, people greatly feared infection, and
ated by wind, cold, hot, and dampness. Later medical
so lepers were abandoned on uninhabited islands
texts attributed the disease to "water dampness."
and there were also many "accidents" in which lep-
Beriberi was most likely to have appeared during
ers fell from the cliffs. Officials did establish "relief
times of famine, but otherwise the disease was proba-
places" and "cure places" and tried to help lepers by
bly somewhat rare in Korea, even during the latter
appointing priests and medical students to give
Yi period, because few people depended on polished
them medicine and help them bathe in the ocean. An
white rice.
entry in the historical records for 1612 states: "Lep-
rosy is the worst disease under the sky" (Miki 1962).
Stroke The ancient medical texts also describe erysipelas,
The Hyangyak chipsong pang and the Tonguipogam carbuncles, dermatitis, furunculosis, inflammations,
describe the main symptoms of stroke, including col- abscesses, tumors, pustules, lymphagitis, and gan-
lapse, loss of speech, paralysis, loss of faculties, and grene, as well as scabies, which probably existed in
inability to move the extremities. Fat people over 50 Korea and China from ancient times. Texts from the
were said to be most susceptible to strokes. Numb- Yi Dynasty described this condition and useful meth-
ness in the thumb and fingers, weakness in the ods of cure, including sulfur poultices. The Tongui
hands and feet, and a numb or tingling sensation pogam says that there are five kinds of scabies: dry,
were considered warning symptoms that a severe damp, sand, insect, and pus.
stroke might occur within 3 years. Treatment was
provided even if the patient was unconscious. When Eye, Ear, Nose, and Throat Diseases
the person could not talk or swallow, medicine could Many forms of deafness and their supposed causes
be boiled so that the patient would inhale the steam. are discussed in the Tongui pogam. The condition
Medicine could also be blown directly into the nose, referred to as earache accompanied by "purulent
but if the patient could not inhale, the case was ear" was probably otitis media. A section on major
judged incurable. and minor nose disease includes symptoms suggest-

ing rhinorrhea, hypertrophic rhinitis, and maxillary philia, infantile tetany, night terrors, chorea minor,
sinusitis. There are also many diseases discussed tics, and fits. •
that were associated with inflammation of the
throat and mouth. Symptoms in the Tongui pogam Insanity and Psychosis
are consistent with tonsillitis, diphtheria, uvulitis, The relationship between Ho Chun's Taoist philoso-
tongue cancer, ranula (sublingual cyst), and various phy and his medical theories are most apparent in
forms of tooth disease. his consideration of mental illness. He based his
Because of their debilitating effect and their direct medical philosophy on the three essences of the Tao-
influence on daily life activities, eye diseases were ist religion: spirit, air, and god. To simplify, we may
readily observed and described. Although eye disor- say that Ho Chun spoke of seven aspects of "mind":
ders caused by problems within the body or peculiar happiness, anger, melancholy, thought, sadness,
diseases inside the eyeballs were hard to detect, con- fear, and fright. Injury to these seven "minds" re-
ditions affecting the surface were described in detail. sults in disease and mental illness.
The Tongui pogam described eye diseases, including The Tongui pogam's section on insanity covers
pterygium and trachoma, in terms of more than 20 symptoms that suggest epilepsy as well as insanity.
symptoms. Liver diseases were thought to cause Psychosis was considered "true madness," and was
problems behind the eyeball, which led to incurable thought to be caused by devils. The discussion in the
loss of vision. Tongui pogam makes it clear that mental disease
was thought to be of two main kinds. The first was
Women's Diseases epilepsy and insanity; the other was psychosis or
Diseases of women discussed in the texts of this era "true madness." In ancient times, however, insanity
include problems of pregnancy and childbirth, was outside the domain of scholarly medicine; treat-
amenorrhea, dysmenorrhea, hypomenorrhea, hyper- ment called for the mudang (Korean shaman) rather
menorrhea, oligomenorrhea, prolapsed and inverted than the physician.
uterus, cancers, and hysteria. Breast cancer is listed
in the Tongui pogam in a discussion of lactation. Miscellaneous
Abnormal conditions in pregnant women seem to The Chinese character for epilepsy used in the Ko-
have included eclampsia, unusual mental condi- rean texts implies both seizure with loss of conscious-
tions, pyelonephritis, dysentery, malaria, and pain ness and insanity. The Tongui pogam discusses a
due to expansion of the heart and chest. After child- similar condition known as "God disease," which is
birth, women were susceptible to five kinds of fever probably equivalent to epilepsy.
due to the following: (1) excessive loss of blood lead- Both the Hyangyak chipsong pang and Tongui
ing to anemic fever; (2) uterine fever; (3) high fever pogam discussed tetanus in connection with strokes.
caused by food poisoning; (4) high fever due to wind However, since the Koryo era, physicians had been
and cold; and (5) fever caused by inflammation of the well aware of the relationship between tetanus and
mammary glands. wounds.
Other symptoms associated with diseases of The medical texts discussed ordinary dog bites,
women suggest painful disorders of the bladder and mad-dog bites, and rabies. Treatment began with
urethra, hernia, ovarian varicocele, and elephantia- washing the bite and cleaning it to remove dirt,
sis vulvae. A condition associated with inflamma- wood splinters, and so forth. The wound was washed
tion, pus, and pain in the urethra and the surround- with water or hot human urine to remove the poison.
ing muscles, said to come from "perverted" sexual Medicines that had cats as their main ingredient
acts, was probably due to gonorrhea. A condition were prescribed. Presumably, the cat in the medicine
called "poisonous urine" was associated with the dis- would scare away the dog poison.
charge of pus and blood. A condition that appears to be polyarthritis was
called "white tiger disease" because the pain was as
Convulsions in Children severe as that of having been bitten by a tiger. The
According to the pediatric sections of the medical Tongui pogam also emphasizes the varying levels of
texts of this era, convulsions were second only to pain associated with arthritis. A condition referred
smallpox as a medical problem characteristic of to as "wind pain" might have been gout, whereas
childhood. Childhood convulsions included all kinds another description suggests the modern diagnosis
of diseases of a nervous nature, such as nervousness, of osteomyelitis or periostitis. A condition described
spasms associated with high fever, epilepsy, spasmo- as a disease caused by a worm eating the synovial

fluid might have been osteomyelitis of a tuberculous
nature. VI.9
Symptoms associated with rickets, including a con- Diseases of the Modern
dition referred to as "turtle chest," appear in the
pediatric section of the Hyangyak chipsong pang. Period in Korea
Osteomalacia, a form of adult rickets, which is far
more common in women than in men, was called
"gentle wind" disease. Medical Missionaries
Lois N. Magner Except for the addition of cholera, the diseases of
Korea of the nineteenth century and the first half of
This publication was supported in part by NIH Grant ROl LM the twentieth century differed little from the ones
04175 from the National Library of Medicine.
prevailing in earlier times. In fact, Westerners who
came to Korea in the 1880s and 1890s thought that
Bibliography the illnesses found in Korea were generally the
Ackerknecht, Erwin H. 1965. History and geography of the
most important diseases. New York.
same as those in North America. George W. Woods,
Cooper, William, and Nathan Sivin. 1973. Man as a medi- for example, a surgeon aboard the U.S.S. Juniata of
cine: Pharmacological and ritual aspects of tradi- America's Asiatic Squadron, reported that he knew
tional therapy using drugs derived from the human of no diseases peculiar to Korea, but he was struck
body. In Chinese science: Explorations of an ancient by the almost universal presence of smallpox and
tradition, ed. Shigeru Nakayama and Nathan Sivin, malaria. Woods, who spent almost 3 months of 1884
203-72. Cambridge, Mass. in Korea, was one of the first Americans to visit the
Fujikawa, Yu 1934. Japanese medicine, trans. John peninsula (Bohm and Swartout, Jr. 1984).
Ruhran. New York. Medical missionaries, upon whose observations
Han Woo-keun. 1970. The history of Korea, trans. Lee we rely for much of this essay, tended to believe that
Kyung-shik, ed. Grafton K. Mintz. Seoul, Korea.
Korean medical knowledge was entirely borrowed
from China and that the history of real medical work
Kim Tu-jong. 1966. Han'guk uihaksa (A history of Korean in Korea began in September 1884, when Horace N.
medicine). Seoul, Korea. Allen of the Presbyterian Mission came to Seoul.
Lee Ki-baik. 1984. A new history of Korea, trans. Edward Medical missionaries soon realized that foreign doc-
W. Wagner. Cambridge, Mass. tors could best establish a claim to medical superior-
Miki, Sakae. 1962. History of Korean medicine and of ity through surgery. Among the operations Allen
disease in Korea. Japan. [In Japanese] performed were excision of the ankle, knee, shoul-
der, and wrist; amputation of fingers, arms, legs,
cancers, and tumors; dissection of scrofulous glands;
enucleation of the eyeball; treatment of cataract and
pterygium; and closure of harelip. One of the most
frequently performed minor surgical operations was
for fistula. One Western physician, Oliver R. Avison,
blamed this apparently common condition on the
Korean custom of sitting on the floor instead of on
chairs (Avison 1897).
After a little more than 3 years of medical work
in Korea, Avison concluded that the kinds of dis-
eases seen in Seoul were about the same as those
seen in Canada, but also that the relative frequency
was different. Avison, founder of Severance Union
Medical College and Hospital, had come to Korea in
1893 in response to H. G. Underwood's call for medi-
cal missionaries. His Korean patients suffered from
all the usual diseases of the major organs, eye dis-
eases, conjunctivitis, ulceration of the cornea,
hernias, various forms of heart disease, hysteria,
epilepsy, paralysis, Bright's disease, asthma, bron-

VI.9. Modern Period in Korea 401
chitis, tuberculosis, whooping cough, diphtheria, ul- Population
cerative tonsillitis, skin diseases, scabies, diarrhea, According to the Korean Repository of 1892, the only
dysentery, intestinal worms, leprosy, syphilis, small- honest answer to the question "What is the popula-
pox, malaria, typhus, and fevers of various sorts. tion of Korea?" was that "a definite figure cannot be
Although he usually wrote with immense confi- reached at present." Estimates varied from 5 million
dence in his own opinions, Avison admitted that "as to 29 million. The Korean census printed under gov-
we do not have the privilege of making autopsies to ernment auspices in 1885 reported the population
correct our diagnoses in case of death, many of our (probably a sizable overestimate) as about 28 million
suppositions . . . may not be correct" (Avison 1897). (15,004,292 males and 13,003,109 females). Accord-
Among the cases seen in the 1920s by Sherwood ing to Woods, the population of Seoul in 1884 was
Hall were the following: gangrene, enlarged spleen about 500,000 inhabitants, but Percival Lowell sug-
due to chronic malaria, enlarged liver due to liver gested that about 250,000 people lived within the 10
abscess, ascites, pleural effusion, edema, distomiasis square miles of the city (Bohm and Swartout, Jr.
due to lung flukes, and many forms of tuberculosis, 1984).
often advanced cases. Hall thought that the use of In 1944, the population was estimated at about 23
unsterilized needles in acupuncture and moxa often million Koreans and about 630,000 Japanese, but by
led to infection and painful inflammation. Among this time epidemic diseases were being tamed by
women patients, Marian Hall encountered abdo- public health work, quarantine regulations, and vac-
mens swollen from enlarged uterine fibroids, tu- cinations against smallpox, typhoid fever, and chol-
mors, and ovarian cysts (Hall 1978). era. Nevertheless, tuberculosis, intestinal diseases,
The early missionaries often fell victim them- venereal diseases, and leprosy (despite isolation of
selves to endemic diseases such as malaria, typhus, lepers) remained as public health problems (Sim-
and dysentery. Some of these deaths were obviously mons et al. 1944).
unnecessary even with nineteenth-century medical
techniques, such as the missionary from Australia Water Supply
who contracted smallpox after only a few months in As in most nineteenth-century cities, the streets of
Pusan, apparently because he had placed his faith in Seoul were "filthy, dirty lanes" flanked by ditches
Providence instead of vaccination. that drained house privies and sewage. Refuse was
Despite the obvious effectiveness of quinine, vacci- poured into the ditches with the hope that it would
nation, and various surgical operations, the medical eventually disappear into the river. Wells were dug
missionaries found that Western medicine was conveniently close to major city lanes, which unfor-
quite powerless before "continued fevers" or, put tunately meant inevitable contamination with sew-
another way, that the mudang (Korean shaman) age from the nearby ditches and, thus, intestinal
was equally as effective as they were. Indeed, the diseases such as diarrhea and dysentery. The sit-
missionaries admitted that in the treatment of uation was similar in small towns and rural com-
many ailments, the results obtained by Korean doc- munities using water from wells, springs, creeks,
tors were comparable to those of the Western doctor and rivers. Both produce and water were generally
(Busteed 1895). contaminated because of the use of night soil as
Studies of Korean village life in the 1940s found fertilizer.
that although people died from many different dis- It follows then that much sickness and death
eases, no adequate accounts of morbidity and mortal- could be attributed to contaminated water, al-
ity patterns were available. Practitioners noted that though most adults were partially immune because
many children died of tuberculosis, whereas many of constant infection. In addition, the custom of
adults died of uncertain maladies of the stomach or drinking tea or water boiled in the rice kettle pro-
intestines, which probably included bacillary dysen- vided some safety.
tery. Among the diseases common in the villages In the twentieth century, the problem began to
were smallpox, typhoid, typhus, cholera, malaria, abate somewhat, and by 1944, the larger cities and
and parasitic worms. Quinine and preventive vac- towns had modern water facilities, and public health
cines did make inroads on malaria, and some of the laboratories were involved in testing food and water
other diseases and health examinations were con- (Simmons et al. 1944). The conditions that had pre-
ducted in the schools where inoculations were given vailed in the nineteenth century, however, created
to students if infectious diseases were found (Osgood fertile soil for not only dysentery but also cholera
1951). and typhoid.

Cholera A second hospital treated 173 cases with a mortality
After escaping its original home in India in 1817, rate of 35 percent (Avison 1895).
cholera began a global migration; by 1820 it had In 1902 when cholera epidemics were reported on
advanced into China and shortly afterward into Ko- the continent, all the harbor towns in Korea estab-
rea and Japan as well. According to Korean records, lished Quarantine Stations; nevertheless, epidemic
the first major cholera epidemic occurred in 1821, cholera once again attacked Seoul, and deaths
and observers were sure that the devastating dis- reached about 10,000. In 1907 it claimed hundreds of
ease, which reached P'yongyang by the end of July victims in outbreaks around Seoul, Pusan, Inchon,
1821, had begun in China. Within 10 days more and P'yangyong. It appeared again in 1908, and in
than 1,000 people had died. The epidemic reached 1909 reached Seoul and Inchon from Manchuria. In
Seoul in August, and by the end of September was in the latter epidemic, 1,775 contracted cholera and
the southern part of the peninsula and all the cities 137 died. During still another outbreak in 1910,
of Kyongsang Province. which also seems to have originated in China, 456
Physicians could neither cure nor prevent the Koreans contracted the disease and 367 died, along
spread of this disease, which terrified observers with 722 Japanese in the country who suffered from
claimed would kill 9 out of every 10 people stricken. the illness (Miki 1962). During the epidemic of
Once the first cases of cholera developed, it appeared 1919-20 there were some 44,000 cases, and then for
to spread instantly to surrounding areas, killing several years no cases were reported. In 1929, only
countless numbers of people. Stunned by its viru- 18 cases were reported, but 15 were fatal, and in
lence, the King appealed to the gods, and the people 1933, 70 cases were reported with 37 deaths.
held feasts and ceremonies to propitiate disease dev- One must consider that official reports may have
ils. Gradually as winter arrived, cholera seemed to underestimated or deliberately concealed cholera
disappear, but in April of the following year it reap- outbreaks. For example, the League of Nations listed
peared around Seoul and once again spread through- Korea as a country in which cholera was epidemic in
out the country. By mid-August, the epidemic had 1937, while the official reports noted only one case
reached Japan (Miki 1962). (Simmons et al. 1944). Indeed, some claimed that
Between 1822 and the 1870s, epidemic cholera cholera was never endemic in Korea and always
made several more invasions, but the records are not came from outside the country, but this was disputed
precise. There are indications of several cholera in- by other authorities.
terchanges between Korea and Japan during this
period, and sometimes the disease spread from Ja- Dysentery
pan to Korea; however, it usually followed the north- Diseases with the characteristic symptoms of dysen-
ern land route from Manchuria along the western tery existed in ancient times in China, Korea, and
coast or across the Yellow Sea. Following the 1870s, Japan, and in modern Korea both bacillary and
cholera epidemics were recorded for the years 1881, amebic dysentery were quite prevalent. Noting that
1885, 1886, 1890, and 1891. Korean patients recovered from amebic dysentery
Modern cholera prevention practices began in better than Japanese patients, Hall concluded that
1880 when the illness spread from Japan to Pusan. dietary habits created different intestinal envi-
Emergency policies included established of Disinfec- ronments. He advised his Japanese patients to in-
tion Stations and Cholera Refugee Hospitals. In clude kimchee in their diet and thought that this
1895, during the Sino-Japanese War, cholera broke improved recovery during later outbreaks (Hall
out in Manchuria. The epidemic slowly but inexora- 1978).
bly crept into Korea, finally attacking Seoul with Adults probably acquired some immunity as a re-
great virulence: At the peak of the epidemic, over sult of repeated infections in childhood, whereas dys-
300 were dying per day. During the 6 weeks of the entery in children was probably confused with com-
epidemic, over 5,000 deaths in Seoul and vicinity mon "summer complaints." Nevertheless, fatality
were counted out of a population of about 220,000. rates during the 1930s were estimated at about 20
The exact number of cases throughout the country is percent of those attacked. Between 1929 and 1937
unknown, but it is estimated that some 300,000 peo- the number of cases reported annually varied from
ple died (Clark 1979). The first cholera hospital orga- about 2,000 to almost 5,000. Amebic dysentery was
nized by Avison in Seoul was closed after the mortal- more common than the bacillary type (Simmons et
ity rate of the first 135 patients reached 75 percent. al. 1944).

Typhoid and Paratyphoid Fevers was said to infect about 95 percent of the people. By
In Korea many people considered typhoid a rather contrast, the pinworm or threadworm, Enterobius
minor disease, perhaps because most adults had yermicularis, and the whipworm, Iricouris trichiura,
been exposed during childhood. Woods's informants seemed to have been comparatively uncommon (Sim-
thought typhoid a rare disease, but he was sure that mons et al. 1944).
it could not be, given the poor sanitary state of Seoul
(Bohm and Swartout, Jr. 1984). Avison also consid- Tuberculosis and Pneumonias
ered Korea to have all the conditions needed for Tuberculosis was "the great enemy of health" in
typhoid fever to flourish, but at the same time he Korea, as in much of the world in the 1890s. Pulmo-
stated that he had never seen a case he could defi- nary tuberculosis was the major form, but physi-
nitely identify as typhoid. cians also saw cases of bone and joint disease, scrof-
Nevertheless, as diagnostic procedures improved, ula, and abscesses of the lymph nodes. Avison (1897)
it became apparent that typhoid fever was the most argued that consumption was even more difficult to
frequent of the enteric diseases in Korea. Between treat in Korea than in Canada, and in fact regarded
1929 and 1937 about 6,000 cases were reported annu- such cases as hopeless, unless they were discovered
ally, with a fatality rate about 17 percent. During very early and the patient was given good food and
the same period, between 300 and 700 cases of attention.
paratyphoid fever were reported annually, with a The disease remained highly prevalent in the
fatality rate of about 7 percent (Simmons et al. 1940s, with pulmonary tuberculosis still the most
1944). common form, but all forms - such as nodular, cuta-
neous, intestinal, bone, and joint - could be found.
Parasitic Infestations Lobar and bronchopneumonia were also common
Intestinal infestations with parasitic worms were so (Simmons et al. 1944).
widespread in early twentieth-century Korea that According to Hall (1978), who founded the first
some public health authorities believed at least 95 tuberculosis sanatorium in Korea, the disease af-
percent of the people were affected. Avison (1897) fected about one out of five Koreans. Almost all
noted a great demand for worm medicine and re- adults produced a positive reaction to the tuberculin
ported seeing round worms and tapeworms of prodi- test. Unsanitary, crowded conditions among factory
gious size. workers in the city contributed heavily to the spread
Infestation with flukes was also widespread be- of tuberculosis from big cities to rural villages and
cause of the preference for eating raw fish and crus- back again along new lines of travel. As elsewhere,
tacea which were often contaminated with the lung an increase in tuberculosis in Korea was part of the
fluke (Paragonimus westermani), the liverfluke(C7o-toll of modernization and communication with the
norchis sinensis), or the intestinalfluke(Metagoni- outside world.
mus yokogawai). Paragonimiasis or pulmonary dis-
tomiasis was most common; it was generally acquired Smallpox
by eating raw crab meat. The developing parasites Smallpox was one of the most feared diseases on the
lodge in the lungs and cause an intense inflammatory peninsula, and almost every person past the age of
reaction that results in the production of rusty-brown 10 years had smallpox scars (Hirsch 1883). In fact,
sputum. Before the etiology and transmission of the children were hardly considered members of the fam-
disease was understood, cases of paragonimiasis num- ily until they survived their bout with this illness.
bered as many as 40,000 per year. Metagonimiasis One woman told Avison that she had given birth to
was also quite frequent, but this disorder was consid- 11 children, but that all of them had died of smallpox
ered mild. Clonorchiasis was rare, but it did cause before reaching the age of 2 years.
severe damage in affected individuals (Miki 1962). It is interesting that most medical missionaries
Ancylostomiasis, or hookworm disease, caused by never mentioned the practice of inoculation and as-
Necator americanus and Ancylostoma duodenale, serted that in Korea there were no methods of pre-
was common during the nineteenth and early twenti- vention or treatment other than magical ceremonies
eth centuries in Korea. Such infestations probably to propitiate the evil spirit that supposedly caused
affected 25 to 30 percent of the people and were the the disease. On the other hand, Woods had no diffi-
cause of much malnutrition and secondary anemia. culty in learning about the Korean method of small-
In addition, Ascaris lumbricoides, the roundworm, pox inoculation during his 3-month visit. In a meet-

ing with an elderly Korean physician the subject of Mosquito-Borne Illnesses
smallpox was the major topic of discussion. Accord- Malaria seems to have been the most common, widely
ing to Woods, smallpox was so common and "appar- distributed disease in Korea. On the Korean penin-
ently so mild in type" that it was considered no more sula, malaria almost always appeared as the "3-day
dangerous than measles. Perhaps he misinterpreted fever" and was most prevalent in areas with numer-
a situation in which mortality from measles made it ous rice fields, which Avison thought "constitute a
almost as dangerous as smallpox. In any case, Woods suitable home for the development of the malarial
noted that Koreans had practiced inoculation for poison." He assumed that all the varieties of malaria
centuries and that vaccination was beginning to dis- would be found in Korea, but most cases were of the
place the ancient methods. tertian or quartan type. The people were familiar
Inoculation was commonly performed by powder- with quinine, and there was a great demand for it,
ing the smallpox scab, placing it on cotton, and intro- especially during the fall and winter months. Unfor-
ducing it into the nostrils. Alternatively, the scab tunately, bogus products were often sold as quinine
was mixed with candy and given to the child. That (Avison 1897). Malaria was still common in the
these methods were not very effective, however, can 1940s, especially in the southern provinces.
be seen by the fact that the disease seemed to leave Filiariasis due to Wunchereria bancrofti was also
its characteristic sign on so many. On one occasion, found in the southern provinces of Korea in the
when surrounded by a crowd of men and boys in 1940s. The principal vectors of this disease were
Seoul, Woods amused himself by counting those who Anopheles hyrcanus sinensis and Culex fatigans.
were pock-marked; he counted 40 with scarred faces It is interesting to note, however, that dengue
among 70 people (Bohm and Swartout, Jr. 1984). fever and yellow fever were not found in Korea de-
The question of smallpox scars was said to have spite the presence of dengue fever in areas that had
determined Queen Min's survival in the palace infrequent intercourse with Korea. This is particu-
trigues of 1882. When King Kojong's father seized larly remarkable because the principal vectors of
power, he condemned the Queen to death. Disguised dengue fever, Aedes aegypti (also the principal vec-
as a peasant, the Queen tried to escape to the coun- tor of yellow fever) and Aedes albopictus, are found
tryside, but she was stopped by guards at the city in Korea.
gate. Because the guards did not know the Queen,
one of them suggested that they examine the Bubonic Plague
woman's face, knowing other members of her family Although devastating epidemics of bubonic plague
to be pock-marked. The Queen's face was perfectly were recorded in China since 1331, the surviving
smooth. Sure that a woman of good complexion could Korean literature does not seem to reflect similar
not be a member of the Min family, the guards let episodes. The bubonic plague outbreaks that oc-
her go free. Eventually the King and Queen were curred in Asia from the 1890s to the 1920s were, of
restored, and the King's father became a state pris- course, watched with great interest by bacteriolo-
oner in Peking (Bohm and Swartout, Jr. 1984). gists and public health workers. Of special concern
Vaccination was increasingly accepted during the to Korea was the epidemic that occurred in north-
early twentieth century. Hall, who was born in Ko- western Manchuria and spread along the newly con-
rea in 1893, noted that smallpox had been very structed railroad lines to various cities of northern
prevalent when he was a boy, but had been practi- China, killing 600,000 people in 1911-12. As the
cally eradicated in the late 1920s (Hall 1978). In 1911 epidemic spread through China, Korea orga-
1909, as many as 4,540 people suffered from the nized preventive teams of personnel and established
disease. In the following year, of the 2,425 Koreans a quarantine line along the northern frontier. Later
who contracted smallpox, 445 died; 36 out of 455 plague epidemics in Manchuria, Mongolia, and
Japanese who also contracted the disease died (Miki northern China also failed to reach Korea.
1962). In 1921, there were 8,321 reported cases, but Human plague was reported in Korea in 1919, but
by 1936 this had been reduced to 1,400, with 371 there were no official reports of the disease between
deaths. In 1937, there were only 205 cases with 44 that year and 1944. Nevertheless, sporadic cases
deaths, but the number of deaths rose again in 1940, may have occurred and some cases may have been
which was reported to have been an epidemic year. imported during World War II. In 1939, Hall was
The fatality rate estimated during the first 40 years summoned to the military hospital wing of the Haiju
of the twentieth century was about 20 to 27 percent Government Hospital for a consultation about a mys-
(Simmons et al. 1944). terious condition spreading among wounded soldiers

returning from Manchuria. It was apparently a type Venereal Diseases

of lung disease that had also attacked medical atten- According to Avison, veneral diseases were about as
dants. The Japanese physician in charge had ruled common in Korea as they had been in England, but
out bubonic plague because the sick had no swelling the syphilitic patients who came to the hospital were
or tenderness of the lymphatic glands in the groin or all in the third stage of the disease. During the
axilla; however, a sudden severe headache was fol- earlier stages the usual method of Korean treatment
lowed by nausea and vomiting. Other symptoms was exposure to the fumes of a mixture containing
were high fever; extreme prostration; rapidly la- mercury. Similar remedies had long been popular in
bored breathing; cough; and expectoration of a wa- Europe, although the benefits were dubious and side
tery, frothy sputum: The afflicted died within hours, effects of mercury poisoning included excessive sali-
almost black with cyanosis. Hall suspected plague vation, ulceration of the gums, and loss of teeth
and found Pasteurella pestis in sputum from the sick. (Avison 1897).
Sworn to secrecy by the Medical Officer, Hall sug- Venereal diseases were still prevalent in the
gested increased precautions to protect the staff and 1940s. The most significant venereal diseases were
an all-out war on rats. Yet, no new cases appeared syphilis, gonorrhea, and chancroid. Lymphogranu-
among hospital patients or staff, and the Chief Medi- loma venereum was occasionally reported, and
cal Officer decided that it was not necessary to alarm granuloma inguinale was quite rare.
the public by instituting rodent control measures
(Hall 1978). Nutritional Diseases
Several conditions described in classical Korean
medical texts suggest long familiarity with beriberi,
Relapsing Fever especially in association with times of famine. How-
Relapsing fever, once considered one of the forms of ever, beriberi was rare in Korea as compared to
typhus, may have appeared in Korea during the other areas in Asia. In the early modern period the
sixteenth century, when epidemics occurred in disease almost never appeared in rural Korea, but it
China and Manchuria. In addition, the epidemic fe- was observed among Japanese students in Korean
ver that appeared in 1886 might well have been cities. In the 1940s the disease was still more preva-
relapsing fever (Miki 1962). Reports from the 1940s lent among the Japanese than Koreans, because the
indicated that this disease was very rare in Korea, Japanese were more likely to consume polished rice.
although ticks that serve as vectors of relapsing During World War II, however, eating white rice
fever are present. became more common, and beriberi was sometimes
observed even in villages.
Typhus Fever Osteomalacia, or adult rickets, a gradual deforma-
Typhus fever was fairly prevalent in the 1890s in tion of improperly calcified bones caused by lack of
Korea, especially among the poor. By the 1940s ob- vitamin D, was fairly common in older women.
servers had detected three types of typhus fever in Scurvy and pellagra were very rare, but nutritional
Korea: the epidemic, or louse-borne type (Rickettsia anemia and anemia secondary to hookworm infesta-
prowazeki); the endemic, orflea-bornetype; and the tion were not uncommon.
mite-borne type caused by Rickettsia orientalis,
known as tsutsugamushi disease or Japanese river Leprosy
fever. The forms of typhus transmitted by mites and Since ancient times, leprosy has been one of the most
lice have the highest fatality rates, but endemic abhorred diseases. According to Korean medical folk-
typhus, sometimes called "Honan fever," was the lore, the disease could be transmitted directly by the
most common form in Korea. Several types of mite sick or through "intermediate hosts" such asfishor
existed in Korea, including Trombicula akamushi, chicken. It was also seen, however, as heaven's pun-
the chief vector of R. orientalis. All three varieties of ishment for sins in this life or in previous lives. Even
human lice were prevalent in Korea. in the modern era, when leprosy appeared, supersti-
Between 1929 and 1937 the annual number of tious people would say "an evil spirit remained in
typhus cases reported varied from 890 to 1,683. The that house and caused disease in the descendants."
fatality rate was estimated as 11 to 13 percent. In the 1890s a few isolated cases of leprosy could
Tsutsugamushi disease was the least frequently re- be found in the general area of Seoul, but most
ported. Body lice were also found to carry Rickettsia patients came from the southern provinces. The dis-
quintana, which causes trench fever. ease generally progressed slowly, but according to

Avison (1897) it appeared in all the forms described polypi were quite common, but surgical removal pro-
in the textbooks. duced good results. The need for tooth extraction
Segregation laws were passed in the early twenti- was quite low, because most people, except for those
eth century, but were not strictly enforced, primarily with congenital syphilis, had very good teeth (Avi-
because facilities for isolation were not available. son 1897).
According to statistics gathered in the 1930s and
1940s, relief stations of an official and a private Miscellaneous Diseases
nature housed about 7,000 lepers, and medical work- In Korea, as in China and Japan, there is no clear
ers estimated the number of lepers living outside historical description of a disease corresponding to
these institutions to be another 7,000. These num- diphtheria until the modern age, perhaps because
bers, however, are probably grossly inaccurate, with diphtheria is not strongly associated with dramatic
the total number perhaps closer to 20,000. In the epidemics of high mortality. Indeed, mild cases are
1940s about 5,000 lepers lived in the government not unusual, and immunity is often quietly acquired
leper colony on Little Deer Island off the southern at an early age. Avison (1897) thought it very
coast, and another 1,500 or so lived in mission- strange that diphtheria was so rare in Korea. He
operated colonies. Gradually, public health policies, had seen a few cases that he was certain were diph-
relief agencies, and improved living standards have theria, but some physicians claimed that the disease
reduced the number of lepers. was not found in Korea.
By contrast, twentieth-century physicians found
diphtheria to be rather common in Korea. In 1937
Scabies there were 2,361 cases, with 608 deaths. The fatality
Scabies probably existed in Korea and China from
rates varied from 21 to 29 percent over a 12-year
ancient times. Since the fifteenth century, Korean period.
doctors treated scabies with remedies that included
Scarlet fever was also quite common in the 1940s.
sulfur poultices and arsenic sulfide. Avison reported
Between 1929 and 1937 reported cases varied from
that scabies was very common among his patients,
937 to 2,190 per year, with fatality rates from 10 to
as were scalp eruptions from head lice, and various
15 percent. Mumps, whooping cough, poliomyelitis,
forms of suppurating sores on other parts of the body
(Avison 1897). The itch-mite, Sarcoptes scabiei, and encephalitis were also reported
in the 1940s
(Simmons et al. 1944).
which causes scabies, is only one of the varieties of
mites found in Korea. During the 1940s, scabies, Outbreaks of cerebrospinal meningitis continued
trichophytous infections, and impetigo were quite to occur in the modern period, with a major epidemic
common. taking place in 1934-5. The disease remained en-
demic in the 1940s, with about 50 to 500 cases re-
ported annually between the years 1929 and 1937.
Eyes, Ears, Noses, Teeth The fatality rate varied from about 50 to 60 percent
According to Woods and Avison, eye diseases were (Simmons et al. 1944).
quite common. Eye disorders included purulent con- Leptospirosis, also known as Weil's disease, or in-
junctivitis, ulceration of the cornea, and complete fectious jaundice, was endemic in Korea. The disease
destruction of the eyeball. Often severe eye disease is spread via food or water contaminated by the
began with simple conjunctivitis following measles urine and feces of infected rats. Rat-bite fever,
or smallpox. Surgical operations for cataract and caused by Spirillum minus, was transmitted by the
pterygium were often successful (Avison 1897). Dur- bite of infected rats.
ing the 1940s, trachoma was frequently the cause of While visiting a drugstore in Seoul with his inter-
the pannus, entropion, trichiasis, and corneal ulcera- preter, Woods (see the first section of this chapter)
tions that caused loss of vision. Other causes of blind- examined many roots and herbs that were all said to
ness were gonorrheal ophthalmia and smallpox. be "good for the stomach!" This suggests, of course,
Hemophilus influenzae (Koch-Weeks bacillus) was that digestive disorders were common. Gastritis
one of the causes of purulent conjunctivitis reported seemed to be the major disease in the category of
in the 1940s (Simmons et al. 1944). stomach diseases, although Avison thought that com-
Ear diseases were quite common: Most cases were mon complaints of chronic indigestion included
the result of smallpox in childhood. Suppuration of many cases of stomach ulcers.
the middle ear often led to destruction of the drum, The Avison family learned that rabies was a fairly
and sometimes there was growth of polypi. Nasal common threat when two of the children were bitten

by a rabid dog. Rabies was still a problem in the taken for typhus. A few sporadic cases of relapsing
1940s because of the large numbers of stray dogs. fever, bacillary dysentery, and smallpox were re-
Andfinally,according to Woods's informants, mid- ported and gonorrhea and syphilis were not uncom-
wifery was practiced by old women, who consulted mon among prostitutes in Seoul and other cities
physicians in difficult cases. Many of the midwives (Summation 1948). However, leprosy remained a
were reportedly skillful and able to perform the ma- public health problem. There were only six leper
nipulations necessary in correcting unnatural pre- clinics in South Korea, and the authorities conceded
sentations (Bohm and Swartout, Jr. 1984). Lack of that it would be impossible to institutionalize all of
cleanliness in the instruments used to cut the umbili- the approximately 31,000 lepers in the country
cal cord was responsible for many cases of neonatal (Summation 1948).
tetanus in infants, even in the 1940s (Simmons et al. A study of mortality in children revealed that
1944). from April to December 1946, 36 percent of all
deaths were of children under 5 years of age. Mea-
Diseases in the 1940s sles, complicated by bronchopneumonia, accounted
Epidemic and endemic diseases were carefully moni- for 18 percent of the child deaths; pneumonia for
tored by the U.S. Army Military Government after 14 percent; and meningitis for 8 percent. Influenza
World War II. Among the communicable diseases and dysenteries followed meningitis in order of
reported in 1946 and 1947 were typhus, smallpox, importance. An epidemic of smallpox was the
relapsing fever, cholera, meningitis, encephalitis, cause of another 4 percent of the deaths. There-
malaria, diphtheria, typhoid, and bacillary dysen- fore, 40 percent of the deaths in children under 5
tery. The Institute for the Prevention of Infectious years could have been prevented by use of peni-
Diseases stocked and dispensed diagnostic tests and cillin, sulfonamides, and vaccination (Summation
vaccines for many of these as well as other diseases. 1948).
Although there were no cases of human plague re-
ported in South Korea, antiplague measures, includ-
ing port quarantine stations and rat control, were Korea in the 1980s
instituted when a case was reported in North Korea The history of disease in twentieth-century Korea
near the Manchurian border (Summation 1946, illustrates the remarkable effect of improved sani-
1947). tary conditions and public health measures. Despite
the devastation caused by World War II and the
By the end of 1947, the communicable disease
Korean War and the repatriation of millions of Kore-
picture was relatively stable. The incidences of
ans from Manchuria, China, and Japan, many of the
many diseases, especially typhus, typhoid, and small-
epidemic and endemic diseases discussed have been
pox, were substantially decreased. In 1946, 117
virtually eliminated. Moreover, Korea's traditional
cases of typhus had been reported, but only 4 were
agrarian Confucian society has been transformed
reported in 1947. Typhoid fever cases were reduced
into one that is highly mobile, urbanized, and well
from 239 to 24 cases, and smallpox cases decreased
educated. The percentage of South Korean citizens
from 41 to 2. When cholera appeared immediately
attending colleges ranks among the highest in the
after World War II, the American occupation forces
world.
were involved in managing the outbreak. Neverthe-
less, in the 1946 cholera epidemic there were 15,748 The population of the Republic of Korea was about
cases with 10,191 deaths. By 1947, however, there 32 million in 1971, giving it a population density
were only 14 cholera cases, with 10 deaths (Summa- ranking about fourth in the world. With improve-
tion 1947). ments in sanitation, public health, and medical fa-
cilities, the population had been increasing at a rate
The general decrease in communicable diseases
of 2.4 percent per year as infant mortality fell, life
was attributed to (1) disease control programs; (2)
expectancy was extended, and endemic and epidemic
educational prevention programs; (3) increased
diseases were brought under control. In the 1980s
availability of preventive inoculations and therapeu-
the population of South Korea was about 42,643,000;
tic drugs; and (4) establishment of clinics and health
one in four Koreans lives in Seoul, the capital city
centers.
(Gibbons 1988).
By 1948, diphtheria, typhus, and typhoid were
Lois N. Magner
about the only major communicable diseases still
reported in South Korea. Typhus was generally the This publication was supported in part by NIH Grant RO1 LM
louse-borne form, but relapsing fever was often mis- 04175 from the National Library of Medicine.

Bibliography
Avison, Oliver R. 1895. Cholera in Seoul. Korean Reposi- VI.10
tory II: 339-44.
1897. Disease in Korea. Korea Repository TV: 90-4,
Diseases of Antiquity in
207-11. South Asia
Bohm, Fred C, and Robert R. Swartout, Jr. 1984. Naval
surgeon in Yi Korea: The journal of George W. Woods.
Berkeley, Cal. South Asia, also known as the Indian subcontinent,
Busteed, J. B. 1895. The Korean doctor and his methods. extends from the Himalayas south to form a huge
Korean Repository II: 189-93. triangle that juts into the Indian Ocean with the
Centennial of modern medicine in Korea (1884-1983), ed. Arabian Sea on one side and the Bay of Bengal on
Medical News Co. Seoul, Korea. [In Korean] the other. India, Bangladesh, Afghanistan, Sri
Clark, Allen DeGray. 1979. Avison of Korea: The life of
Lanka, the Maldives, and the small Himalayan coun-
Oliver R. Avison, M.D. Seoul, Korea.
Gibbons, Boyd. 1988. The South Koreans. National Geo- tries of Nepal and Bhutan are included in this area.
graphic 174: 232-57. South Asia can be divided roughly into three parts,
Hall, Sherwood. 1978. With stethoscope in Asia: Korea. beginning with the triangle-shaped Deccan Plateau,
McLean, Va. moving north to the fertile plain along the Ganges
Hay, Woo-keun. 1970. The history of Korea, trans. Lee and Indus rivers, and finally extending to the north-
Kyung-shik, ed. Grafton K. Mintz. Seoul, Korea. ernmost section at the foot of the Himalayas.
Hirsch, August. 1883. Geographical and historical pathol- Background: The Ancient Indian Texts
ogy, Vol. I, trans. Charles Creighton. London.
Kim Tu-jong. 1966. Han'guk uihaksa (A history of Korean
The Ayurvedic Texts
medicine). Seoul, Korea. Ancient Indian Medicine had close ties with philoso-
Korean Repository, Vols. I-V. 1964. Reprint. New York. phy and religion. The basic texts of Hinduism are
[First edition published in Seoul, 1892-8.] the four Vedas: Rg, Sam, Yajur, and Atharva.
Lee, Ki-baik. 1984. A new history of Korea, trans. Edward Ayurveda, meaning the "science of life," is consid-
W. Wagner. Cambridge, Mass. ered to be the fifth of these texts and as important as
Miki, Sakae. 1962. History of Korean medicine and of the other four. All of the first four Vedas have sec-
disease in Korea. Japan. [In Japanese] tions that deal with healing and the prevention and
Osgood, Cornelius. 1951. The Koreans and their culture. cure of sickness. Yet the approach is usually magical
New York. or by prayer to the deities of the Vedic pantheon.
Simmons, James Stevens, et al. 1944. Global epidemiology: The Ayurvedic texts, by contrast, are of later ori-
A geography of disease and sanitation. Philadelphia. gin and tend to attribute disease to divine causes
Summation of the United States Army military government
activities in Korea. 1946-1948. Commander-in-Chief,
less frequently. The codification of Ayurveda proba-
U.S. Army Forces, Pacific. bly occurred around the sixth century B.C., and the
texts presumably took their defined forms, in which
they are still available, by the sixth or seventh cen-
tury A.D. They were compiled in the northwestern
part of India and in areas that today include Paki-
stan and Afghanistan, although, with the spread of
the Aryans and their culture, Ayurveda came to be
practiced over much of the country. Among other
things this meant that the texts were modified to
take account of the impact on health of geographic
location, climate, water, seasonal variations, and
diet. Indeed, many sections mention diseases due to
these external factors, and one even suggests that
geographic variations cause a difference in general
health, and that certain locations favor epidemic
disease.
The texts are known as the Samhitas - a Sanskrit
term meaning "any systematically arranged infor-

VI. 10. Antiquity in South Asia 409
mational collection of texts or verses." The five course (once in four days), politeness, not being witness or
known Ayurvedic Samhitas are the Sushruta, the guarantor, not going to crossroads, not urinating in the
Caraka, the Astangahrdaya, the Bhela, and the presence of superiors, cows, or against the wind, not sleep-
Kashyapa. Some doubt exists about the authenticity ing during the daytime, and not eating fly-infested food.
of a sixth and incomplete text: the Harita. During epidemics one should not drink water or eat raw
Ayurveda deals with life (human and animal) in all vegetables; one should run away and pray. Lest we smile
at this strange mixture of Indian hygienic measures, we
its aspects including hygiene, ethics, medical educa- might remember that the Indians knew for thousands of
tion, and rules of behavior. Dietetics, geographic pa- years a technique for preventing smallpox, which the Euro-
thology, and even the philosophical basis of existence peans learned from the Turks only during the eighteenth
are also treated. Both the Sushruta and the Caraka century: inoculation.
divide medicine into eight broad areas: (1) Surgery
(Salya); (2) Diseases of the Ear, Nose, Throat, and Eye In the Ayurveda, the balance of bodily health is
(Salakya); (3) Internal Medicine (Kayachikitsa); (4) viewed as being maintained by the healthy function-
Mental Diseases (Bhutavidya); (5) Pediatrics Includ- ing of three dosas - Vayu, Pitta, and Kapha or
ing Pregnancy and Its Complications (Kaumara- Sleshma - which are somewhat akin to the Greek
bhrtya); (6) Chemicals Used in Treatment {Rasa- notion of bodily humors. Disturbances of one or more
yana); (7) Rejuvenation; and (8) Aphrodisiacs of the dosas caused by indiscretions in eating or by
(Vajikarana). The Astangahrdaya also mentions bad personal habits, such as suppression of the de-
eight divisions of the Ayurveda, which are similar sire to defecate or excessive sexual intercourse or
but not identical to the previous sections. male intercourse with a menstruating woman, were
seen as causes of illness. A few diseases could be
triggered by riding on a horse, mule, or camel in an
Caraka and Sushruta ungainly fashion. Others could arise because of ex-
Any discussion of diseases recognized during the ternal influences, such as injuries, whereas still oth-
period under scrutiny must rely heavily on the two ers were due to heredity.
major Ayurvedic texts - Caraka and Sushruta -
because they are the most comprehensive and the After being disturbed, the dosas were believed to
least altered by later authors. These texts consti- lodge in a system of the body in an attempt to be
tute a massive compendium that describes more excreted. While there, however, they produced dis-
than 360 separate diseases. This essay will concen- ease. Thus specific symptoms or signs were gener-
trate on only the more clearly defined of these and, ally viewed as disease, and consequently, the descrip-
when possible, attempt to equate them with modern tions of many conditions are quite similar.
disease entities. The detailed observations of the
ancient Ayurvedic physicians make available a Wounds, Abscesses, Lymphadenopathies,
body of information in which we can find something and Superficial Neoplasms
of a reflection of many of the diseases affecting the The descriptions of wounds and abscesses in the
Indian subcontinent today. texts are detailed and quite complete. The term
In discussing the human being in health and dis- brana, which is often used in the literature and is
ease, the Caraka mentions the necessity of examin- generally taken to mean an ulcer, has to be inter-
ing the following facets: structure, function, causa- preted more liberally as a surgical or traumatic
tion, symptoms, methods of treatment, objectives of wound or even an abscess. A swelling that (1) is
treatment, the influence of seasons and age, the capa- localized to one part of the body, (2) is hard, and (3)
bilities of the physician, the nature of the meditations affects the skin and soft tissues in a particular man-
and appliances used in treatment, and the procedures ner is an inflammatory swelling or shofa. These
to be used and their sequences. swellings were thought to arise from various causes
and were associated with manifestations of imbal-
ance of the particular humors producing the disease.
Concepts of Disease Such inflammatory swellings were described as
Ackerknecht (1982) summarized the ancient Indi- red, yellow, or black in color and increased in size at
ans' concern for disease and health thusly: different rates. They produced local heat, burning,
The ancient Indians put great emphasis on hygiene and and other abnormal sensations and were said to pass
prevention. They recommended toothbrushing, chewing of through the phases of A ma (cellulitis), Pacchyamana
betel leaves, anointing, combing, exercise, massage, bath- (localization), and Pakka (localized abscess).
ing, piety, taking the proper food, sitting idle, sexual inter- The clinical features specifically diagnostic of an

abscess or a wound are also discussed in detail in termed Arbuda, which never suppurated and were
various chapters; for example, an abscess in connec- probably neoplasms. A variant called the Raktar-
tion with a broken bone discharges a mixture of buda reportedly grew rapidly and produced both a
marrow, blood, and often small spicules of bone in a discharge and heaped flesh. Because patients suffer-
fluid resembling clarified butter. Similar diagnostic ingfromRaktarbuda quickly become emaciated and
features of abscesses at various sites are also given the disease was viewed as incurable, the strong sus-
as prognostic signs of danger and curability. The picion is that they were suffering from a malignant
exact timing for the incision of an abscess was neoplasm.
thought to be critical, and dependent upon the clini- Cancer, however, as a specific type of illness was
cal findings. not recognized in the Ayurveda, and the process of
Deep-seated spherical or irregular swellings were metastasis seems not to have been appreciated.
called Vidradhi. Four types were thought to arise Nonetheless some Arbudas were known to produce
from the three disturbed dosas individually or in satellite Arbudas close by.
combination. Two other types mentioned are Agan-
tuka (due to external trauma) and Raktaja (Rakta Fevers (Jvara)
means "blood"). The descriptions of the various Seven types of fevers were viewed as due to various
Vidradhis are often similar. They could develop any- combinations of the dosas, and an eighth was seen as
where in the body, and the overlying skin would the result of external causes. Abhinyasajvara and
have shallow ulcers of varying colors with dis- Ojoniruddhajvara are fevers, both of which were
charges of differing natures - characteristics that thought to occur when all dosas were defective.
identified the dosa responsible. Their symptoms suggest typhoid fever and typhoid
None of the Vidradhi involving the three dosas fever with delirium as well as cerebral malaria. The
were attended with fever, which makes it difficult to Visamajvaras were recurrent fevers with intermis-
accept them as being abscesses (the usual belief). The sions of normal temperature and thus seem to fit the
Sannipataja type — the most serious - resembles the cycles of some of the various types of malaria.
description of a squamous carcinoma more than any-
thing else, and other dosaja Vidradhis could quite Poisons
well have been the same. The texts make it clear that the specialty of toxicol-
Vidradhi arising in the marrow of a bone was ogy (Agadatantra) was well developed in India. Poi-
termed Asthividradhi. This seems clearly to have sons from plants and minerals are discussed, as
been acute osteomyelitis, as the bone was swollen well as the symptoms and effects of insect, reptile,
with acute pain, and the patient had high fever. and animal bites and methods of treatment. In fact,
Finally the abscess discharged outside through the 10 types of poisonous snakes and the effects of their
skin and muscles. venom are discussed together with the appropriate
The two types of Vidradhi where high fever and antidotes.
thirst were prominent, suggesting an infectious ori-
gin, are the Agantuka type (caused by a deep wound Skin Diseases
due to an external agent) and the Rakta Vidradhi, A disturbed Vayu driving Pitta and Kapha dosas
arising in the pelvis of pregnant women following into the skin was thought to bring on some skin
parturition, doubtless in many cases puerperal fever. diseases, whereas other skin diseases were viewed
A variant is the Antarvidradhi or internal as the work of parasites. As a group, skin ailments
Vidradhi, a situation in which one developed on an were generally termed Kustha. The 7 Maha (or ma-
internal organ such as the bladder, spleen, liver, or jor) Kusthas appear to be variants of leprosy, a dis-
heart. Rectal examination and the passage of sounds ease existing in India from ancient times. The 11
into the bladder were common diagnostic techniques minor Kusthas were other skin diseases that are
in these cases. A Vidradhi in the rectum caused more difficult to equate with current cutaneous or-
symptoms suggestive of large intestinal obstruc- ders. However, it would seem that pityriasis versi-
tions, and one on the bladder neck probably indi- color, pemphigus, chilblains, moist eczema, dermati-
cated obstruction of the passage of urine. However, tis, scabies, and leukoderma were all represented.
these symptoms also suggest neoplastic obstruction Leprosy or mahakushtha, as it was known in the
rather than abscess. texts, was understood to be contagious, although it
Disturbed dosas were also thought to produce was also thought to be inherited by offspring of af-
slowly growing, cold, round swellings in the tissues, fected parents.

VI. 10. Antiquity in South Asia 411
Head and Neck Diseases cussed, as is conjunctivitis and glaucoma. The Ayur-
Some Ayurvedic diseases of the mouth would seem to vedic variants of a disease called Adhimantha are
have a recognizably modern counterpart, among actually the progressive stages of glaucoma, produc-
them (1) neoplasms of the lip (when the latter is de- ing a swift loss of vision if untreated.
scribed with raised areas of flesh that ultimately ul- The section on diseases of vision describes cataract
cerate); and (2) herpes labialis, with varicolored mul- and various forms of another disease that resulted in
tiple small swellings. A condition in which the gums disturbed vision - possibly symptomatic of glau-
became spongy, retreated, and bled easily may have coma. Other disturbances of vision included day
indicated scurvy, whereas another in which the gums blindness and night blindness.
and dental roots bled easily and gave off a purulent
exudate may have been pyorrhea or periodontitis. Neurological Disorders
Mahashaushira was a grave and painful condition in Disturbances of Vayu were thought to create many
which teeth became loose in the gums, and the palate neurological diseases. These included Dhanustam-
and the cheek were ulcerated. This seems to have bha (literally a pillar curved like a bow) or tetanus.
been either cancrum oris or buccal carcinoma. Other conditions caused by disturbed Vayu included
Impacted wisdom teeth, dental caries, and a situa- convulsions, the two types of which may well have
tion in which the teeth were so sensitive that even been descriptions of petit mal and grand mal epi-
touch was painful were also described, as were lepsy; paralysis of one lower extremity; paraplegia;
"gravel in the teeth" (tartar), and a condition in sciatica; brachial palsy; and facial palsy. Other dis-
which destroyed teeth took on a blue-black color. eases that we now do not think of as being neuro-
The diseases of the tongue discussed in the texts genic are also ascribed to disturbed Vayu. These
cannot be clearly divided into glossitis and epithelio- include one that appears to be synovitis of the knee
mata, and many symptoms were taken to be disease joint, another that seems suggestive of paresthesias
entities in themselves. Diseases of the throat are of the feet, and still another that seems to have been
generally termed Kantharoga. Among those that ap- bowel obstruction. Dumbness, nasal speech, and in-
pear to be discussed are diphtheria, peritonsillar distinct speech were also seen to stem from the same
abscess, carcinoma of the base of the tongue, laryn- cause.
geal and pharyngeal cancer, acute stomatitis, and
chronic laryngitis. Heart Disease
Specific recognizable afflictions of the nose include Examination of the pulse played an important role in
nasal tumors and nasal polypi, whereas those of the diagnosis and prognosis in Hindu medicine. But the
ear embraced deafness, otalgia, otorrhea, and nature of circulation and cardiac function was not
tinnitus. well understood, which helps to explain the sketchy
In the region of the neck it was thought that Vayu nature of the descriptions of cardiac diseases in the
and Kapha can become vitiated and lodge in the texts. Moreover, the descriptions in the Sushruta and
muscles and fat. The result would be a swelling the Caraka do not exactly correspond. Heart disease
called Galaganda, which did not suppurate, en- due to disturbed Vayu that caused palpitations, pain,
larged slowly, and might produce a vague noise in slowing of the heart rate, fainting fits, and murmur-
the throat. This disease was clearly goiter. The ing sounds in the heart constitutes the only condition
vague noise mentioned may be the stridor of tra- that truly suggests a cardiac disorder. Other diseases
cheal compression, though associated difficulty in of the "heart" seem more like gastrointestinal disor-
breathing is not mentioned. ders in that they could be caused by bad eating habits,
In the hot, dry climate of northwestern India, eye and their symptoms included a sense of heaviness in
diseases have always been common, and thus the the precordium, a bitter or acid taste in the mouth,
sections on eye diseases are among the most detailed tiredness, and belching. Another type of "heart dis-
and remarkable of the Ayurveda. These diseases are ease" was due to parasites arising in putrefied food.
divided into two broad groups: Netrarogas, or dis- Here, the parasites were thought to invade one por-
eases of the eyeball; and Drshtirogas, or disturbances tion of the heart and gradually destroy the rest.
of vision. Seventy -three Netrarogas are described, al-
though some seem to be different manifestations of Respiratory Disorders
the same disease. Four of these, for example, seem to Respiratory problems are discussed under two major
be forms of trachoma and two more forms of sections of the texts: disorders of breathing and of
blepharitis. Various types of corneal ulcers are dis- cough. Hiccough was thought to be a precursor of

respiratory disease which, if left untreated, could variant termed Alashaka, diarrhea is not promi-
help to bring on tuberculosis. Certainly tuberculosis nent, the abdomen distends, the patient has severe
was as common in the past as it now is in the Indian cramps and is very thirsty and nauseated. These
subcontinent. Also apparently described are pulmo- symptoms parallel those of cholera sicca.
nary edema, bronchiectasis, and a number of chronic
pneumonia types. Miscellaneous
Hemorrhoids were clearly distinguished in the text,
Abdominal and Intestinal Disorders and were associated with or seen to be aggravated by
Udara is the anatomical name used in the texts for excessive horseback riding, sitting on hard wooden
the abdomen. The term also signifies generalized seats, and friction with clothes or skin. By contrast,
abdominal disease manifested by enlargement. Most because the anatomy and functions of the kidneys
of the Udara disorders are ascribed to bad eating were not well known, specific diseases due to disor-
habits or to eating spoiled or poisonous food. A few der of renal function are difficult to spy. Tasting the
conditions, however, can be understood by modern urine, however, was an important element in diagno-
medicine. Among them is enlargement of the left sis, and diabetes mellitus appears to have been un-
side of the abdomen because of a large spleen. The derstood as a disease.
symptoms associated with this condition suggest Another disease, Pishta, which translates as "wa-
splenomegaly resulting from malaria or filariasis. ter containing ground rice" and which caused the
Enlargement of the right side of the abdomen was patient to shiver as he or she urinated, may well
the result of involvement of the liver and at times have been Chyluria; this disease, which arises from
must have indicated cirrhosis. A particularly omi- filariasis, is common in India today, and probably
nous situation resulted when all three dosas were was in the past as well. In this vein, Shleepada,
disturbed: The patient turned yellow and suffered which means "elephantiasis," the most prominent
from pain, ascites, and emaciation. This could have symptom of filariasis, was reported to occur most
been either advanced hepatic cirrhosis with liver commonly in areas where stagnant water was
failure or liver or pancreatic cancer. plentiful - a desirable breeding ground for the mos-
A disease called Dakodara was clearly ascites. The quitoes that spread the disease. Schleepada was a
abdomen enlarged with fluid that could be palpated, progressive swelling, generally of the legs and less
the umbilicus was flattened out or everted, and commonly of the hands, lips, ears, nose, and face,
there were enlarged blue veins in the thin abdomi- and in its late stages produced irregularities and
nal wall. Another abdominal distension arose from vesicles on the surface of the skin.
obstruction of the large bowel, and was manifested The dosas could be disturbed by sexual practices
by progressive constipation, gaseous swelling of the that included too much abstinence or too much inter-
abdomen, and crampy pains, all of which provides a course. Syphilis was introduced to India by the Portu-
picture of left colonic cancer or, less commonly, pro- guese, and thus there is no mention of syphilitic chan-
gressive anal stenosis. The latter was ascribed to cres in the older Ayurvedic texts. But at least soft
sharp pieces of food perforating the gut and causing chancre seems to be discussed under diseases of males
continuous thin and liquid anal discharge associated and various forms of vaginitis under the female head-
with vomiting, anorexia, abdominal distension, and ing. In addition, ailments of women such as amenor-
pain. The condition could well have been acute rhea and possibly eclampsia can be discerned.
gastroenteritis, which was, and is still, a common The above sections contain only a fraction of the
disease in the Indian subcontinent. immense corpus of the Ayurveda. Because of the
Among the discernible intestinal disorders are lack of systematic dissection as well as ignorance of
dyspepsia, acute diarrhea, and dysentery with some physiological principles, the descriptions of internal
symptoms of the latter suggestive of amebic dysen- disorders in the Ayurveda are vague. However, dis-
tery. Clearly discernible is cholera, or Vishuchika - eases of the superficial organs and viscera are very
the Ayurvedic term for cholera. The patient vomits, well described and generally can be recognized for
trembles, has continuous watery diarrhea, severe their modern-day counterparts. The detailed obser-
abdominal pain, and hiccoughs. In agonal stages vations of the ancient Ayurvedic physicians have
there is tingling all over the body, and the patient left a body of information in which we can see a
loses consciousness and becomes cyanotic. The voice reflection of many of the diseases affecting the In-
becomes weak, the muscles and joints become lax, dian subcontinent today.
and the eyes retract into the orbital cavity. In a Ranes C. Chakravorty

VI.ll. Premodern Period in South Asia 413
Bibliography most famous medical men from the East and the
Ackerknecht, Erwin H. 1982. A short history of medicine. West were meeting in Baghdad and ushering in a
Baltimore. Renaissance. Indian physicians learned the examina-
Bhisagratna, K. K., ed. 1963. Sushruta Samhita, 3 vols., tion of pulse at Baghdad from Greek and Arab physi-
2d edition. Varanasi, India. cians, who were expert in this sort of diagnosis.
Cockburn, T. Aidan. 1971. Infectious diseases in ancient Knowledge of and interest in alchemy, along with
populations. Current Anthropology 12: 45—62.
the use of opium and many metallic compounds for
Filliozat, J. 1949. La Doctrine classique de la medecine
treatment of various diseases, were also acquired
indienne: Ses origines et ses paralleles grecs. Paris.
Leslie, Charles, ed. 1976. Asian medical systems: A com-
from contact with the Greeks and the Arabs.
parative study. London. The concept of the modern hospital is a Persian
Sastri, K., and G. Chaturvedi, eds. 1979. The Charaka contribution. When the Muslims conquered large
Samhita, 7th edition. Varanasi, India. parts of the Indian subcontinent, they introduced
Shastri, K. A., ed. 1972. Sushruta Samhita, 2 vols., 3d the concept of hospitals along with other institutions
edition. Varanasi, India. and traditions, and since then hospitals have been a
part of city life. One of the 12 commandments issued
by the Emperor Jehangir on ascending the throne in
the seventeenth century was for the establishment
of a hospital in all the larger cities in his domain.
Allauddin II was the earliest Muslim king of the
VI.ll Deccan to build a hospital, Dar-ul-Shifa, at Bidar,
his capital during the fifteenth century where food
Diseases of the Premodern and drugs were provided to patients free of charge.
Period in South Asia The hospitals were mainly staffed by Muslim phy-
sicians well versed in Greek and Arabic (now called
Unani) systems of medicine. Many of them had
Overview Ayurvedic physicians on the staff as well. From the
A geographic notion of South Asia generally in- ninth century, this tradition of having both Hindu
cludes India, Pakistan, Bangladesh, Sri Lanka (Cey- and Muslim physicians in the hospitals continued,
lon), and Nepal. But although these countries may particularly in India.
be thought of as constituting a single region, they
contain a multitude of ethnic groups. Nonetheless, Diseases and Epidemics
during the medieval ages, they had a common medi- The first important Arabic medical treatise that
cal heritage rooted in the Greco-Roman world. At elaborately discussed and summarized the Indian
the extremities of the system, in northern or north- system of medicine of this age is Firdaus-al-Hikmat,
western Europe and along the Russian river system, by Ali ibn Sahl Rabban al-Tabari, who died about
the Greco-Roman medical inheritance was thin. But A.D.855.
in southern Europe and throughout the Muslim- The work of Rhazes, written in this period, deals
Byzantine world, that heritage was rich. The geo- systematically with head, eye, lungs, and digestive
graphic position of the Arabs in Asia Minor close to and circulatory systems, along with diseases of
Greek sources had provided them with the opportu- women and midwifery. The contents of the author's
nity to know the old Greek authors, especially in studies demonstrate his competence and skill in rec-
philosophy and medicine; therefore, the Arabs be- ognizing various diseases, in differentiating similar
came the channels through which Greek influences diseases symptomatically, in making their classifica-
were carried back into the West once more. Many tions, and in adopting methods to treat them.
new observations about diseases and a vast materia Appearing early in the eleventh century, Al-
medica of the available drugs and medicaments in Qanun fi al-Tibb by Avicenna is by far the largest
central Asian countries traveled through channels and most famous medical work of this period. The
containing contributions by the eminent physicians work is divided into five major books. The first book
of the Christian, Jewish, Muslim, and Hindu reli- treats general principles; the second treats simple
gions. Building on Hippocrates and Galen, they all drugs arranged alphabetically; the third deals with
wrote in the common Arabic language, the official diseases of particular organs and members of the
language of the Caliphate. bodyfromhead to toe; the fourth deals with diseases
By the beginning of the ninth century, some of the that, though local and partial in their inception,

tend to spread to other parts of the body; and the civil surgeon of Dacca, for example, found that in the
fifth deals with compound medicines. history of the Tipperah family, between the fifteenth
The Madanul-Shifa i-Sikandar Shahi (Sikandar and eighteenth centuries, 5 out of 16 Maharajahs
Shah's Mine of Medicine), written in 1512 by Mian died from smallpox. According to S. P. James (1909),
Bhowa, discusses the symptoms and treatments of an observer writing in 1767 about the prevalence of
many diseases, including fevers, diarrhea, whooping smallpox in Bengal, said:
cough, dropsy, epilepsy, rheumatism, erysipelas,
heart diseases, gonorrhea, scrofula, elephantiasis, Every seventh year with scarcely any exception, the
small-pox rages epidemically in these provinces during
leprosy, smallpox, measles, and afflictions of chil- the months of March, April and May, until the annual
dren. In all, it discusses 1,167 diseases and the ef- returning rains about the middle of June put a stop to its
fects of various medicaments. fury. On these periodical returns, the disease proves uni-
versally of the most malignant confluent kind,fromwhich
Smallpox few either of the Indians or the Europeans escaped that
Inoculation for smallpox seems to have been known took the distemper in the natural way, commonly dying on
to the Hindus from a very early age. Long before thefirst,second or third day of eruption.
Edward Jenner, certain classes in India, especially
cow herders, shepherds, charans, and the like, had Inoculation against smallpox has been practiced
been in the habit of collecting and preserving the dry in the subcontinent since ancient times, and ac-
scabs of the pustules. They would place a little of counts of the procedure are available in the writings
this material on the forearm, and puncture the skin of several British writers. O. Coult has given an
with a needle. As a result of this inoculation, these account of smallpox inoculation (tikah) as he ob-
classes are purported to have enjoyed a certain served it in Bengal in the year 1731. Edward Ives,
amount of immunity from the disease. who was a naval surgeon on the flagship Kent and
In India, temples in which a deity of smallpox was who was in India in 1754-7, has given further de-
worshipped hint at its presence prior to 1160 B.C. In tails of the method. In Calcutta inoculation was prac-
ancient India, smallpox was, therefore, apparently ticed among certain classes of Europeans as early as
regarded by the Hindus as a manifestation of a 1785, and apparently in 1787 the government estab-
Hindu goddess called Maria-tal, Mari-amma Devi, lished a hospital for smallpox inoculation at Dum
Mata, or Sitala. According to W. A. Jayne (1979), Dum. In 1798, after much experimentation, Edward
"Sitala (the 'Cool-Lady' with a euphemistic allusion Jenner established that prior cowpox inoculation
to the burning fever) was small-pox." The goddess (i.e., vaccination; the Latin word for "cow" being
was worshipped regularly so that she would not cir- Vacca and for "cowpox," Vaccinia) protected the per-
culate among the villages. One could probably find son from getting smallpox, even though he or she
shrines to her in any village or town in ancient was exposed to it. The practice of vaccination was
India, according to O. P. Jaggi (1980). accepted quickly in England, western Europe, and
Russia, and by 1802, only 4 years after this discov-
So it seems that the Indian civilization has faced ery, vaccination was introduced in India.
smallpox epidemics on numerous occasions, yet de-
tails regarding the complete history of the illness in
South Asia remain obscure. The first clinical ac- Cholera
count of the disease appears in the Middle Ages, by The history of cholera began on the subcontinent of
the most competent physician of his age, Rhazes. India. Both literary records and religious practices
Although brief mention of smallpox is made in two suggest that cholera was endemic to the South Asian
medical treatises of the period, the work of Rhazes is region for at least 2,000 years, but it was not until
the first in which the illness is fully treated and in the sixteenth century that European travelers, ex-
which its symptoms are described. Bhowa's medical plorers, traders, and officials provided detailed de-
treatise appearing in 1512 mentioned the disease scriptions of a terrible plague whose symptoms were
smallpox-measles, along with its treatment. Around those of cholera and which was reported to reach
1700, Hakim Mohammed Akbar bin Mohammad epidemic proportions. One authority has identified
Muqin Arzani wrote Mufarreh ul-Qulub, in which 64 separate accounts of cholera in India between
he recorded his own experiments with treatments he 1503 and 1817, and no less than 10 of those refer
adopted to relive the burning and throbbing sensa- specifically to epidemics. The areas of cholera's his-
tion of the vesicles of smallpox. toric endemicity were in South Asia, and especially
The disease attacked the rich and the poor alike. A in the delta regions of east and west Bengal.

VI. 11. Premodern Period in South Asia 415
It is said that the first pandemic of the early The cholera epidemic of 1817-23 gradually disap-
nineteenth century remained geographically in peared from the countries over which it had spread,
Asia, though it approached Europe, and it may and in Bengal little was heard of the disease through-
have touched Africa at Zanzibar. The following sec- out the years 1823-5, except in the endemic areas.
ond, third, and fourth pandemics affected the entire But during the first quarter of 1826, cholera again
world, though with considerable regional varia- erupted throughout the lower Bengal. From there it
tions; the areas of incidence receded significantly in spread to Banaras and extended as far as the Kan-
the fifth and sixth pandemics. pur Division, reaching the stations on the right bank
During the medieval period, court chronicles de- of the Jamna. It was heard of at Hardwar in April
scribed the occurrence of pestilences, though it is and throughout the northwestern frontier provinces
difficult to identify their correct nature in terms of and along the Himalayas before the middle of June.
diseases we now recognize. G. Gaskoin (1867) refers Bombay Presidency, Sind, and the Punjab were as-
to Lendas da India, a publication by a Portuguese saulted by the disease which reached there from the
named Gaspar Correia, who in the spring of 1543 east during the year 1827. It entered Khiva and
witnessed cholera in an epidemic form at Goa. The Herat via Kabul in 1829. The epidemic from Kabul,
local people called it moryxy, and the mortality was Herat, and Persia spread to Russia and Poland in
so great that burying the dead was difficult. In 1563, 1830, to England in 1821-32, to France in 1832, and
Garcia da Orta wrote a vivid description of cholera in the same year to America, where it made its first
as he saw it at Goa, adding that the disease was most appearance, to Cuba and Mexico in 1833, again to
severe in June and July. In the 1600s, more reports Europe from 1835-7, and finally to Africa in 1837.
of epidemic cholera appeared in Madura (1609), Ja- Subsequent cholera epidemics were observed in Eu-
karta (1629), and Goa (1683). Cholera was next re- rope and America (1848-53), in Punjab (1855), in
ported in 1783, when it broke out at Hardwar and, in Persia (1857), and in Arabia (1858-9). It appeared
less than 8 days, killed approximately 20,000 pil- again in Punjab (1861), and traveled from Bengal to
grims. At the same time, the Maratha armies, en- Africa, Arabia, Europe, and America (1863-5).
gaged in war with Tipu Sultan (the Sultan of
Mysore), suffered severely from the disease. In 1787, Plague
there was another account of the disease in India There is uncertainty in attempting to trace the his-
given by an English physician (a Dr. Paisley). Again torical background of plague in South Asian territo-
in 1796, Fra Paolino de S. Bartolomeo penned an ries. According to Jaggi, extant references in Indian
account of cholera in India. history for some pestilences that raged from time to
The appearance of the disease at Fort William in time could indicate epidemics of plague. One proba-
1814 was reported by R. Tytler, Civil Surgeon of ble epidemic attacked the army of Muhammad
Jessore. However, the first full and accurate account Tughlaq in the twelfth century. Again in the year
of epidemic cholera dates from 1817 to 1823. The 1443, a pestilence caused great loss of life in the
earliest notice of this epidemic was given by Tytler army of Sultan Ahmad I. Farishta, a contemporary
in a letter dated August 1817: "An epidemic has of the Mogul emperor Akbar, mentioned the occur-
broke out in the bazaars, the disorder commencing rence of a fatal epidemic similar to that of bubonic
with pain or uneasiness in different parts of the plague in Bihar in 1548. A very devastating
body, presently succeeded by giddiness of the head, plague-like pestilence raged in Gaur, the medieval
sickness, vomiting, griping in the belly and frequent capital of Bengal, in 1573. The great famine of 1590
stools." was followed by a severe epidemic, which may or
While the cholera epidemic spread in the countries may not have been plague. Tuzuk-i-Jahangiri de-
to the west of India, it was also transported to the scribed the occurrence of plague near Agra in 1618.
east. In 1819, Burma and Ceylon were under its influ- The Gujarat plague epidemic of 1812-61 was the
ence. The next year Siam was afflicted, as was Ma- first in India for which a detailed account is avail-
lacca, where the disease was said to have been able. It broke out in 1812 in Kutch and is said to
brought by a vessel from the coast. Shortly after some have destroyed half of the population before spread-
persons with cholera-like symptoms landed from a ing to Kathiawar and Gujarat. According to a state-
vessel, the outbreak began. This outbreak occurred ment given by D. V. Gilder in the Indian Medical
after Dutch vessels coming from Calcutta had an- Gazette near the turn of the century (Nathan 1898):
chored at Malacca. China and the islands of the In tracing the origin of disease in question the natives
Mauritius were also overwhelmed by the disease. agree in referring the period of itsfirstintroduction to the

Hindoo year or Sumwat 1873 (A.D. 1817) three years lages attacked. This disease continued to be reported
subsequent to the dreadful famine, which raged with such in the surrounding regions until 1893.
destructive fury over Gujarat and Kathiawar. The disease In 1896 plague broke out in Bombay, and its diag-
extended to several other areas such as Kutch, Dholera, nosis was confirmed by W. M. Haffkine (Nathan
Peeplee, and Limree, etc., and people roughly distin- 1898) in October of that year. The mortality rate in
guished it by the term Ghaut no roque possessing the Jains at that time was significant, reaching a peak
following symptoms: great and general uneasiness of the of over 100,000 persons. A Plague Research Commis-
frame, pains in the head, lumbar region and joints on the
sion was formed in Bombay in 1905, which worked
day of attack, hard, knotty and highly painful swellings of
the inguinal or axillary glands (whence the name appears) under an advisory committee that was constituted in
in some instances; the parotids are affected in 4 or 5 hours, India and included representation of the Royal Soci-
fever supervenes; these symptoms go on increasing in vio- ety, the Lister Institute, and the India Office. This
lence, attended with great thirst and delirium until the commission continued to work until 1913, and their
third day of the attack, when death closes the scene. studies have formed the basis of our present knowl-
edge of the epidemiology of bubonic plague.
Another British physician also gave an interesting
account of disease spread from Kathiawar, according Malaria
to R. Nathan (1898): Malaria is a parasitic disease that probably tor-
In 1813 the plague was present in Central India and Raj- mented primates long before humankind walked the
putana, Kutch and Kathiawar and was first noticed at Earth. The Indian art and medical classics make it
Kumtakale, and spread throughout Wagar during Janu- clear that malaria had a long history on the subconti-
ary, February and March 1816, and by the end of that year nent area, a history that has been illuminated at
had extended to Sunde where the mortality was great. The various points in the classical medical texts of an-
disease was still prevalent in Central India in 1819, and cient Hindu medicine. Susruta established a vague
disappeared in 1821. Nothing more was heard of the dis- relationship between malaria and mosquito bites.
ease in Central India till July 1836, when it broke out at This mythical savant classified the relevant types of
Pali, a town of Marwar, whence it spread to Jodhpur. It fevers, and linked these with specific types of mosqui-
prevailed at Deoghur, in Meywar, in March 1837, and toes. As in Egypt and Mesopotamia, in the tropical
thereafter extended to Jalia and Ramghat in the district of dampness of the Indian river valleys, malaria
Ajmere. The disease disappeared toward the end of 1837,
reaped a deadly harvest, as it had probably done for
but in November of that year, it again broke out in epi-
demic form at Pali, and continued till February the follow- millennia (1.4 million deaths in British India in
ing year. 1939 alone) (Thorwald 1963).
The existence of a great many diseases in ancient
The same physician also wrote of mahamari (gola or South Asia is reflected in the Vedic books. As might
phutkiya rog), an endemic disease of Kumaun and be expected, fevers predominate because India is
Garhwal in the Himalayas. The first record of the still probably the most malarial country on Earth, as
disease is dated 1823 at Kedarnath, Garhwal. From well as the breeding ground for plague and cholera.
1834, outbreaks in these districts occurred every few But no clear statistics on the early history of malaria
years, except for a long interval between 1860 and are available.
1875, when it appeared to remain quiescent. After The nineteenth-century British medical statistics
1878, the outbreaks were not severe. The disease give some clear indications of the intensity of the
descended to the plains in 1853. In that year it ap- infection. In Bengal, Bombay, and Madras, over the
peared in an epidemic form in towns in the district periods 1847-54 and 1860-75, of 1,110,820 British
Moradabad. According to Nathan (1898), a physician soldiers, 457,088 (or 41.1 percent) were reported as
there concluded that mahamari was identical with malarial cases (McGrew and McGrew 1985). Two
the uncomplicated form of glandular plague of Egypt other nineteenth-century investigations are worthy
and that it could be conveyed by contagion and of mention: (1) In 1845, a surgeon major introduced
spread by endemic causes such as filth, poverty, and the spleen rate as a measure of malarial endemicity
unclean habits of the inhabitants. In 1875, the dis- and used it to map out the incidence of malaria in
ease was prevalent in certain villages in Kumaun villages in the Punjab lying along the course of the
where C. Planck (Jaggi 1980) recorded about 277 old Jammu canal. (2) A great advance in malaria
deaths and confirmed the opinion that it was the therapy was made in 1877 when a method of manu-
pestis or plague in medical terminology; he also re- facturing pure quinine sulfate was discovered at the
corded the first local history of mahamari in 40 vil- government's Sikkim plantation, which resulted in

VI. 11. Premodern Period in South Asia 417
a great reduction in the cost of quinine production Curtis, C. 1807. An account of the diseases of India. Edin-
all over the world. burgh.
Elgood, Cyrill. 1951. A medical history of Persia. Cam-
bridge.
Kala-Azar or Visceral Leishmaniasis Gaskoin, G. 1867. Contribution to literature of cholera.
In India kala-azar has been recognized as a distinct Medico-Chirurgical Review 50: 220—38. London.
clinical entity for over 150 years. A number of epi- Gordon, Benjamin Lee. 1949. Medicine throughout antiq-
demics occurred in Bengal in the mid-nineteenth uity. Philadelphia.
century, and, although it was undoubtedly confused Hamdard Medical Digest. 1962. Karachi.
with malaria, the high treatment failure and mortal- Horder, Lord, ed. 1951. The British encyclopaedia of medi-
ity rates made the physicians of those days realize cal practice, Vol. 7.
Jaggi, O. P. 1980-1. History of science, technology and
that they were dealing with a different illness. More
medicine in India, Vols. 4, 8, 12, and 14. Delhi.
attention was paid to the disease when in 1875 it James, S. P. 1909. Small pox and vaccination in India.
began to invade Assam; kala-azar swept up the Calcutta.
Brahmaputra Valley in three distinct epidemic Jayne, Walter Addison. 1979. The healing gods of ancient
waves between 1875 and 1917. The nature of the civilizations. First AMS edition. New Haven.
disease was clarified in 1903 when the causal organ- Keswani, NandKumar H. 1970. Medical education in India
ism now classified as Leishmania donovani was dis- since ancient times. In The history of medical educa-
covered by William Leishman in the spleen of a tion, ed. C. D. O'Malley. Berkeley and Los Angeles.
soldier who died in England from kala-azar, which Learmont, A. T. A. 1965. Health in the Indian sub-
he had contracted at Dum Dum, a military post just continent 1955-64. A geographer's review of some
outside Calcutta. medical literature. Occasional papers 2. Canberra,
Cutaneous leishmaniasis - or "oriental sore" or Australia.
Delhi boil - is prevalent in the northern and west- Leslie, Charles, ed. 1976. Asian medical systems: A com-
parative study. London.
ern parts of India, especially in the United Provinces
Macnamara, C. 1876. A history of Asiatic cholera. London.
and the Punjab. It is caused by Leishmania tropica, Major, Ralph H. 1954. A history of medicine, Vol. 1. Spring-
which is transmitted by Phlebotomies papatasii in field, 111.
the subcontinent. McGrew, Roderick E., and Margaret P. McGrew. 1985.
Encyclopaedia of medical history. London.
Nathan, R. 1898. The plague in India, 1896, 1897. Simla,
Other Diseases India.
Typhoid, influenza, dysentery, hepatitis, tuberculo- Rabban al-Tahari. 1981. Firdaws al-Hikmat Fi al-Tibb,
sis, as well as illnesses associated with malnutrition, trans. Rasheed Ashraf Nadvi. Pakistan.
are comparatively new diseases in South Asia in the Said, Mohammed, ed. 1966. Hamdard pharmacopeia of
sense that they are newly identified. However, lep- Eastern medicine. Karachi.
rosy and the venereal diseases are quite old, and Siddiqi, Mohammad Zubayr. 1959. Studies in Arabic and
ancient Vedic texts include descriptions of these dis- Persian medical literature. Calcutta.
eases although they are not well sorted out from Sinhjee, Bhagvat. 1927. A short history of Aryan medical
other diseases of the same classes. science, 11th edition. Gondal.
Thorwald, Jurgen. 1963. Science and secrets of early medi-
Hakim Mohammed Said
cine, trans. Richard and Clara Winston. New York.
Transactions of the Medical and Physical Society. 1842.
Bibliography Calcutta.
Ackerknecht, Erwin. 1982. A short history of medicine. Tytler, R. 1817. District ofJessore. Calcutta.
Baltimore. Ullmann, Manfred. 1978. Islamic medicine. Islamic sur-
Balfour, Edward. 1982. Encyclopaedia Asiatica, Vol. 8. veys, Vol. 11. Edinburgh.
New Delhi, India. Walsh, James J. 1920. Medieval medicine. London.
Browne, E. G. 1921. Arabian medicine. Cambridge. Wriggins, W. Howard, and James F. Guyot, eds. 1973.
1962. Arabian medicine, 2d edition. Cambridge. Population, politics, and the future of southern Asia.
Burrows, T. W. 1963. Virulence of Pasteurella pestis and New York and London.
immunity to plague. Ergebnisse der Mikrobiologie
Immunitaetsforschung und Experimentelle Therapie
37: 54-113.
Chakraberty, Chandra. 1983. An interpretation of ancient
Hindu medicine. Reprint of 1923. Delhi.

1918, diseases native to the region (notably smallpox,
VI.12 cholera, and malaria) also contributed substantially
Diseases of the Modern to the period's heavy mortality.
Davis probably exaggerates India's precolonial iso-
Period in South Asia lation. He also neglects its importance as a dissemi-
nator as well as a recipient of epidemic disease. The
five pandemics of "Asiatic cholera" that raged be-
The history of disease in modern South Asia has tween 1817 and 1923 all had their sources in India,
been dominated by epidemic diseases. Smallpox, as did the smallpox epidemics that caused such dev-
cholera, and malaria, along with plague and influ- astation at the Cape of Good Hope in the eighteenth
enza, figured prominently among the leading causes century. Through extensive trading links developed
of sickness and mortality in the region for much of long before the advent of British rule, as later
the period from the eighteenth to the mid-twentieth through the exodus of its laborers and soldiers,
centuries. The recent decline or disappearance of South Asia acted as a source of several major dis-
several of these diseases has correspondingly re- eases. Ancient ties of commerce and conquest with
sulted in a marked fall in overall levels of mortality. the rest of the Eurasian landmass saved the Indian
Although the statistics are unreliable in detail subcontinent from many of the "virgin soil epidem-
(with perhaps a quarter or more of all deaths passing ics" that wrought such human havoc in the Ameri-
unrecorded), the broad trend is clear. From a peak cas and Oceania: Even plague had visited India sev-
mortality of nearly 50 deaths per 1,000 inhabitants eral times before 1896. The critical factor was thus
in British India in the late nineteenth and early not so much the arrival of Europeans or the estab-
twentieth centuries, mortality rates were roughly lishment of British rule as the greater degree of
halved by the 1950s, declining from 42.6 per 1,000 in external contact that resulted from expanding trade
1901-10 and 48.6 in 1911-20, to 36.3 in 1921-30, and improved communications during the nine-
31.2 in 1931-40, and 27.4 in 1941-50 and 22.8 in teenth and early twentieth centuries and the conse-
1951-60. In 1966-70, the figure was 15.3 per 1,000. quent social, economic, and environmental changes
The fall in infant mortality over the same period that facilitated the spread of epidemic diseases,
further confirms this trend. From an annual average whether exotic or indigenous in origin, throughout
of 212 deaths per 1,000 live births between 1911 and the region.
1920, infant mortality in India fell to 176 in 1921-
30, 168 in 1931-40, 148 in 1941-50, and 113 in A second explanation for the twentieth-century
1966-70 (Davis 1951; Chandrasekhar 1972). decline in epidemic mortality focuses on the role of
medical and sanitary intervention. Measures to pro-
tect South Asia from epidemic disease began early
Mortality Levels in the colonial period with the introduction of small-
The reasons underlying this fall in mortality (and the pox vaccination in 1802, and it has been claimed
earlier high levels of mortality) have been much de- that this dramatically reduced the incidence of what
bated. Kingsley Davis (1951) argued that India be- had formerly been one of the region's greatest afflic-
came "the home of great epidemics" only during the tions. Later measures against cholera, plague, and
period of British rule (1757-1947), when it was "ex- malaria - from mass immunization to chemical
posed to foreign contact for the first time on such a spraying - have likewise been identified as decisive
great scale." India's "medieval stagnation" was bro- factors in the eradication or control of these dis-
ken down later than that of Europe and so the region eases. Davis (1956) claimed that by the mid-twen-
fell prey to pathogenic invasions, such as plague, at a tieth century, medical technology had the capacity
later date. But, as in Europe earlier, India's popula- to reduce mortality without waiting for supporting
tion gradually developed an immunity to these dis- advances in socioeconomic conditions. But the limits
eases. Thus, Davis argued, even without medical and of therapeutic intervention have since become appar-
sanitary intervention, India's epidemic diseases be- ent (especially with the resurgence of malaria since
gan to lose much of their initial virulence. However, the 1960s), and recent writers are more skeptical
as Ira Klein (1973) has pointed out, some of the most about its effectiveness as an explanation for earlier
destructive epidemics of the colonial period were not falls in mortality. The low level of colonial (and
exotics but rather diseases long established in the postcolonial) expenditure on medicine and public
region. Although India suffered very severely from health; the paucity of doctors, hospitals, and medical
invasions of plague and influenza between 1896 and supplies relative to the size of the population; and

VI.12. Modern Period in South Asia 419
the enormous technical, social, and cultural obsta- tality, other "competing" causes of debility and
cles in the way of effective medical action — all have death have taken over or have remained largely
been cited as evidence of the limited human capac- unaffected. Mortality has declined since 1900, but
ity to master epidemic disease in South Asia. sickness and death remain all too common.
A third hypothesis draws close parallels with the
European experience. It has been argued that the fall Diseases
in mortality in eighteenth- and nineteenth-century In view of the diverse characteristics of the main
England owed little to medical advances (apart, lat- diseases of South Asia and of the various factors
terly, from vaccination) and derived instead from im- affecting them, it will be helpful to consider the
proved living conditions and diet. A comparable devel- recent history of the most important of them in turn.
opment has been suggested for South Asia, albeit at a
somewhat later date. Despite massive famines that Smallpox
resulted in some 20 million deaths in British India Smallpox was held by nineteenth-century medical
during the second half of the nineteenth century, it is opinion to be "the scourge of India," responsible for
claimed that there was a significant improvement in more deaths than all other diseases combined. En-
economic conditions by 1900. The food supply became demic throughout much of the region, smallpox re-
more dependable, helped by the construction of an turned in epidemic strength every 5 to 7 years. So
extensive rail network and the expansion of irrigated prevalent was the disease between February and
agriculture; famine relief grew more effective in sav- May that it was known in eastern India as basanta
ing lives, and there was a rise in rural incomes roga, the "spring disease." With the onset of the
through the stimulus of an expanding market econ- monsoon season, however, smallpox abated, reach-
omy. Those epidemic diseases most closely associated ing its lowest ebb in October and November. Climate
with famine - smallpox and cholera - declined with might provide a partial explanation for this marked
the disappearance of severe famines from India after seasonality, but social and cultural factors were in-
1908 (apart from the Bengal famine of 1943-4, which fluential, too. In India the dry spring months, a slack
significantly saw a marked recurrence of epidemic period in the agricultural year, were traditionally a
mortality). The high death rate was sustained into time for congregation and travel, for religious fairs,
the 1920s only by epidemics of plague and influenza, pilgrimages, and marriages, all activities that pro-
diseases that (it is claimed) had little connection with vided the close social contact needed for transmis-
rural poverty and hunger (McAlpin 1983). sion of the Variola virus.
This argument has the virtue of singling out fam- In driving large numbers of destitute and under-
ine as a critical determinant of mortality trends in nourished villagers to seek food in relief camps and
South Asia and hence provides a nonmedical expla- cities, famines also created conditions favorable to
nation for the decline of two of the greatest killer the dissemination of the disease. So, too, did the
diseases, smallpox and cholera. But although famine dislocation caused by warfare. Just as Maratha inva-
as such may have disappeared from most of the re- sions may have contributed to an upsurge in small-
gion after 1908, South Asia remained (and remains) pox mortality in eighteenth-century Bengal, so did
afflicted by chronic poverty, with half the population the displacement of millions of refugees in the same
below the poverty line. Malnutrition and over- area during Partition in 1947. Bangladesh's war of
crowded and unsanitary living conditions have re- independence in 1971-2 also occasioned major out-
mained fertile ground for disease and have kept mor- breaks of the disease (Chen 1973).
tality and morbidity at levels far above the norm in In the absence of reliable statistics it is impossible
Western countries. Economic gains have failed to to gauge the full extent of smallpox mortality before
reach most of the people, and per capita foodgrain the late nineteenth century. One demonstration of
availability may even have fallen during the course the disease's long-standing importance was the rev-
of the twentieth century. There thus seems little erence paid throughout South Asia to the Hindu
basis for claiming that socioeconomic change has goddess Sitala (or her counterparts) as the deity
resulted in a healthier population. It would be more credited with the power to either cause or withhold
realistic to argue instead that although the cessa- the disease. A nineteenth-century writer further at-
tion of major famines and the medical targeting of tested to the prevalence of smallpox when he specu-
specific diseases like smallpox and cholera have lated that as many as 95 percent of the 9 million
been responsible for reducing or eliminating some of inhabitants of the north Indian Doab had experi-
the earlier and most conspicuous causes of high mor- enced the disease. So common was it, he claimed,

that "it has become quite a saying among the agricul- Indians, especially of the middle classes, most
tural and even wealthier classes never to count chil- closely associated with them. Compulsory vaccina-
dren as permanent members of the family . . . until tion and the outlawing of variolation began in Bom-
they have been attacked with and recovered from bay city in 1877 and was followed by the Govern-
smallpox" (Pringle 1869). ment of India's Vaccination Act in 1880. However,
As these remarks suggest, smallpox was mainly a the implementation of the acts was piecemeal and
childhood disease, the chronology of smallpox epi- deficient. As late as 1945, primary vaccination was
demics being largely determined by the creation of a compulsory in only 83 percent of towns in British
pool of susceptible infants born since the previous India and a mere 47 percent of rural circles. Compul-
outbreak. Between 60 and 70 percent of fatalities sory revaccination was even rarer (Arnold 1988).
occurred among children under 10 years of age, and Nevertheless, the evidence suggests that vaccina-
of these half died before they were even one year old, tion did contribute to the relatively low levels of
although one of the consequences of the spread of smallpox mortality achieved by the early twentieth
childhood vaccination was to increase the proportion century. The number of vaccinations in India rose
of adult victims. from approximately 4.5 million a year in the 1870s
Smallpox mortality probably reached a peak in to twice that number in the 1900s and exceeded 40
British India in the middle and later decades of the million (nearly three-quarters of them revaccina-
nineteenth century before entering a period of sus- tions) by 1950. Given the heavy death toll smallpox
tained decline. From 1.4 million deaths recorded for had formerly levied among those under 10 years of
the decade 1868-77, and 1.5 million for 1878-87, age, vaccination significantly reduced mortality
smallpox mortality fell to barely 1 million in 1888- among infants and children.
97 and 800,000 in 1898-1907. From 0.8 smallpox Existing methods of smallpox control were, how-
deaths per 1,000 inhabitants in 1878-87, the ratio ever, inadequate to secure the final eradication of
fell to 0.4 in 1908-17 and down to 0.2 in 1937-43, the disease. In 1962, the year in which India
before the Bengal famine and Partition fueled a par- launched its eradication program, the country re-
tial resurgence. Although in epidemic years in the ported 55,595 cases of smallpox and 15,048 deaths
1870s the number of smallpox deaths soared as high from the disease. There were a further 4,094 cases
as 2 per 1,000, by the 1930s there were fewer than and 1,189 deaths in Pakistan (mainly East Paki-
0.5 fatalities per 1,000 of the population (James stan). Five years later, the World Health Organiza-
1909; Hopkins 1983). tion began its own eradication campaign, which con-
Significantly, smallpox mortality began to decline centrated upon early recognition and reporting of
even before the worst famines of the period were the disease, the isolation of cases, and the vaccina-
over, and exactly when medical intervention began tion of contacts. The Bangladesh war of 1971—2 de-
to have an effect on smallpox mortality is unclear. In layed eradication and enabled a fresh epidemic to
Sri Lanka, an island with a small population, vacci- flare up. In 1974 India again suffered a severe out-
nation may have eliminated endemic smallpox early break (showing that Variola major had lost none of
in the nineteenth century; but because of constant its former destructiveness), with 188,003 cases and
reinfection from India, the disease was not finally 31,262 deaths. South Asia was finally freed of small-
eradicated until 1972. pox in 1975.
Although vaccination was introduced into India in
1802-3, its impact there at first was slight. Im- Cholera
ported lymph was unreliable, and local sources of Like smallpox, cholera has had a long history in
supply were not adequately developed until late in South Asia. Reliable accounts of the disease date
the century. The arm-to-arm method of vaccination back to at least the sixteenth century, and it was
was extremely unpopular, and the bovine origin of reported from several parts of India during the late
vaccinia provoked strong Hindu hostility. Vaccina- eighteenth century (MacPherson 1872). But the chol-
tion had, moreover, a popular and well-established era epidemic that erupted in the Jessore district of
rival in variolation (smallpox inoculation), which Bengal in August of 1817 assumed an unprecedented
was considered more effective and culturally accept- malevolence and in barely 2 years it penetrated to
able. Faced with such opposition, the colonial regime almost every part of the subcontinent, including Sri
was disinclined to commit substantial resources to Lanka, before setting out shortly afterward on the
vaccination, and during the nineteenth century it first of its "global peregrinations." Epidemics of chol-
was practiced mainly among Europeans and those era repeatedly swept through South Asia during the

VI. 12. Modern Period in South Asia 421
nineteenth century, and the disease was undoubtedly Whereas in times of good harvests cholera tended
a leading cause of high mortality and (relatively) low to retreat to the low-lying areas where it was en-
population growth in India before 1914. Perhaps from demic, many of the worst epidemics between the
the absence of any existing immunity, mortality rates 1860s and the early 1900s bore some relation with
were particularly high during the 1817-19 epidemic concurrent famine. The disease thus exhibited even
(though not as high as an alarmed Europe was will- more violent fluctuations than smallpox, dying
ing to believe). away in some years, only to return in devastating
The incidence of epidemic cholera in India can be strength once or twice in a decade. In 1874, for exam-
related to a number of factors: The emergence of ple, cholera mortality in India sank to 0.16 per 1,000
Calcutta, the most populous city of British India and of the population; only 3 years later (with famine
an important regional center for trade and adminis- widespread), it reached 3.39 per thousand, before
tration, during the eighteenth and nineteenth centu- ebbing away again to 0.64 in 1880.
ries favored the wide dissemination of the disease In 1900 cholera soared to its highest recorded peak
from its endemic home in the Ganges-Brahmaputra with 797,222 deaths in British India, a ratio of 3.70
delta. As elsewhere in the world, cholera often per 1,000: In this year of sickness and starvation,
moved in the wake of advancing armies. Soldiers cholera accounted for a tenth of all mortality (Rogers
unwittingly helped spread the disease in northern 1928). But, having hovered at around 4 million
and central India in 1817-18 and again during the deaths each decade between 1889 and 1919, cholera
Mutiny campaigns of 1857-8. The seasonal migra- mortality finally began to fall, dropping to 2.2 mil-
tion of laborers and plantation workers may also lion in 1920-9, and 1.7 million in 1930-9, although
have had a comparable effect. They passed through there was a partial resurgence during the 1940s (the
endemic areas, lived in primitive accommodation at decade of the Bengal famine and Partition) to just
the site of their employment, and drew water from over 2 million deaths with 500,000 cholera deaths in
contaminated sources. 1943 alone, nearly 50 percent of them in Bengal.
Of even greater significance was the close associa- From a death rate of 0.74 per 1,000 in 1925-47, and
tion, much remarked upon during the nineteenth 0.17 in 1948-63, the ratio continued to fall to 0.0017
century, between epidemic cholera and Hindu pil- in 1964-8. Epidemic cholera did not disappear en-
grimage. Pilgrims traveled long distances, mainly tirely, however. In 1974, for instance, there were
on foot (before the railway age); they were ill-clothed 30,997 reported cases in India with 2,189 deaths. In
and ill-fed, and crowded in their thousands into in- the same year Bangladesh suffered 5,614 cases and
sanitary towns or into makeshift camps at the main 177 deaths, while Sri Lanka, long the recipient of
fairs and festivals. Cholera not only spread easily epidemics originating on the Indian mainland, had
and rapidly among the pilgrims themselves but also 4,578 cases and 343 deaths.
was carried far afield as they dispersed to their Although various theories were advanced during
homes. Several of the largest epidemics of the nine- the nineteenth century to explain cholera's origins
teenth century were traced to the festival of Rath and spread, it was only in 1883 that Robert Koch
Jatra, held annually at Puri in Orissa, close to the finally identified cholera vibrios in a Calcutta tank.
Bengal cholera zone, and the 12 yearly bathing festi- Even without this knowledge, sanitary measures (as
vals, the Kumbh melas at Hardwar and Allahabad taken in Europe and North America) had had some
on the Ganges (Pollitzer 1959). earlier effect, helping in particular to reduce mortal-
As a mainly waterborne disease, cholera was en- ity among European soldiers who, until the 1870s,
demic in low-lying areas, such as lower Bengal, suffered a high proportion of casualties from the
where the cholera vibrio flourished in village reser- disease. Improved sewers and filtered water less-
voirs ("tanks") and irrigation channels that were ened cholera mortality in several major cities (in-
also used for drinking water. But epidemic cholera cluding Calcutta from 1869); the long-term decline
occurred, too, in conjunction with famine. Although in the disease has also been identified with the cre-
major epidemics could occur (as in 1817-19) in the ation of public health departments in the provinces
absence of famine conditions, the scale of cholera from the early 1920s. But the latter were poorly
morbidity and mortality was greatly magnified by funded, and in India, with a predominantly rural
the migrations of the famine-struck, by their lack of society and a large and growing slum population,
physical resistance to the disease, and by their de- sanitary reform had a more limited impact than in
pendence upon scant sources of water and food that the West.
quickly became contaminated. Cholera inoculation proved a less effective form of

prophylaxis than smallpox vaccination, and the con- Malaria
nection between cholera and Hindu India's pilgrim- Although malaria has undoubtedly been present in
ages and sacred sites made the colonial authorities South Asia for a very long time, it was not recorded
wary for a long time of provoking a religious back- separately from other "fevers" until late in the nine-
lash. But, for all this, anticholera inoculation is teenth century and so is even more difficult than are
likely to have had some success in curbing the explo- smallpox and cholera to trace in recent times. But,
sions of mortality formerly associated with pilgrim- once identified as a distinct disease, malaria was
ages and melas. For many years a voluntary prac- soon recognized as a primary cause of much ill
tice, inoculation for pilgrims became compulsory in health and death. Almost a fifth of the mortality
1954 in time for the Allahabad Kumbh mela, when that occurred between the 1890s and the 1920s
nearly a quarter of a million pilgrims were inocu- (amounting to some 20 million deaths) was attrib-
lated. Combined with intensive medical surveillance uted to malaria. As plague, smallpox, and cholera
and prompt reporting, inoculation contributed to the abated, so malaria gained prominence as the great-
decline of epidemic mortality, although, again, the est single threat to health in South Asia. J. A. Sinton
absence of major famines after 1908 (apart from that estimated in the 1930s that malaria was responsbile
of 1943-4 in Bengal) must also have been a contribu- for 3 or 4 times as many deaths as the 3 other
tory factor. diseases combined. Of 6.3 million deaths in British
In addition, the virulence of the disease may have India between 1924 and 1933, at least 1 million, he
been on the wane by 1914 (or human resistance may believed, were directly attributable to malaria,
have been increasing). The El Tor biotype, which while millions more, weakened by the disease, fell
invaded the region from Southeast Asia in 1964-5, ready prey to other ailments and afflictions. In addi-
proved less fatal than the "classical" form it largelytion, the disease was a frequent cause of abortions
displaced. Immunity acquired early in life, rather and stillbirths.
than inoculation or improved sanitation, possibly As elsewhere, malaria in South Asia has had a
contributed most to cholera's long-term decline. But, close relationship with the environment and with
despite this, cholera remains a recurrent threat to environmental change. During the nineteenth cen-
human health in South Asia. tury, the expansion of irrigation canals and the build-
ing of railway embankments and other major con-
Other Enteric Diseases struction works that interfered with the natural lines
The reasons for the persistence of cholera - insani- of drainage or left patches of stagnant water created
tary living conditions and contaminated water human-made environments in which malaria-bear-
supplies — are also reasons for the continuing impor- ing Anopheles mosquitoes could breed (Klein 1972).
tance of other enteric diseases. Dysentery and diar- South Asia thus failed to experience the beneficial
rhea have long been significant among the major side-effects of the draining of marshlands and
causes of sickness and death in South Asia, and, swamps that contributed so significantly to malaria's
like cholera, greatly swelled mortality during times decline in Europe. The extension of irrigated cultiva-
of famine. Alexander Porter (1889), in his pioneer- tion and the dense settlement it commonly sustained
ing study, reckoned dysentery and diarrhea the in South Asia, combined with the development of new
chief cause of death among famine sufferers in Ma- networks of labor migration and mobility, have also
dras in 1877-8. In the high wave of mortality at tended to create conditions favorable for human trans-
the turn of the century, one death in every seven in mission of the disease.
British India was attributed to dysentery and diar- Until recently, malaria infestation largely pre-
rhea, placing these diseases in third place behind vented agricultural colonization of areas like the
malaria and plague as major killers. But they also Terai in the Himalayan foothills and the hill tracts
accounted for a great deal of the mortality even in along the Andhra-Orissa border. The partial eradi-
nonfamine times, particularly among children. In cation of malaria in the 1950s and 1960s facilitated
1962 in India they were responsible for 179,714 the penetration and settlement of these areas, but
deaths (equivalent to 0.4 per 1,000 population). In its return severely affected immigrant farmers (e.g.,
1974, along with 846,858 cases of gastroenteritis in the Chittagong Hill tracts of Bangladesh) with no
and 333,687 of typhoid (with 3,623 and 924 deaths, inherited or acquired immunity to the disease.
respectively), dysentery, with 4.5 million cases and Like the other diseases so far discussed, malaria
2,182 deaths, stood high among the most commonly has some connections with human hunger. S. R. Chris-
reported illnesses. tophers (1911) showed a close correlation between

VI. 12. Modern Period in South Asia 423
peaks of malaria mortality and morbidity in the Pun- But for all the severity of the disease, plague in
jab between 1869 and 1908, and periods of high food modern India never took as heavy a toll of human
prices, a basic index of widespread poverty and incipi- life as in Europe during the Black Death of 1347-9,
ent famine. But in this instance the decline of famine partly because the deadly pneumonic form of the
was apparently not matched by any corresponding disease was absent. Several areas escaped largely
downturn in malaria morbidity and death. unscathed. Northern and western India bore the
Around 1950 malaria was still killing 500 out of brunt of the epidemic, whereas Bengal, the south,
every 100,000 of the population in South Asia, with and Sri Lanka were far less affected. One possible
India alone suffering 800,000 deaths a year. Al- explanation for this, favored by L. Fabian Hirst, was
though quinine prophylaxis and the mosquito nets that the type offleafound on the rats in western and
and screens have provided limited protection to a northern areas, Xenopsylla cheopis, was a more effi-
small minority (mainly Europeans), the advent of cient vector of the plague bacillus than Xenopsylla
DDT from the end of World War II made a compre- astia, which was more common in southern regions.
hensive assault on malaria possible for the first At the start of the epidemic, in part responding to
time. India launched a National Malaria Eradica- international pressure and the threat of commercial
tion Campaign in 1958, and such was the apparent sanctions by other European powers, the British
success of DDT spraying there and in Sri Lanka that adopted measures of far greater severity than previ-
Davis (1956) was prompted to write of the "amazing ously employed against cholera and smallpox. Sus-
decline" in Third World mortality modern medicine pects and victims of the disease were hospitalized or
made possible. But the triumph soon proved short- put in segregation camps; house searches were made
lived. Increasing anopheline resistance to DDT and to discover concealed cases and corpses; many thou-
the diminishing effectiveness of the drug chloro- sands of travelers were examined, and walls and
quine resulted in a startling recrudescence of ma- roofs pulled down to allow sunlight and fresh air into
laria during the 1960s and 1970s. From a low point dark interiors. At this early stage the role of rat
of 50,000 cases in India in 1961, the number rose to fleas in the transmission of the bacillus was not
1.4 million in 1972 and 1.9 million in 1973. It then understood, and the assumption was that plague
shot up to 3.2 million in 1974 and 5.2 million in was a disease of "filth" or an "acute infectious fever"
1975. Two years later, in 1977, an estimated 30 spread through close human contact.
million people in India were suffering from malaria. But medical intervention on such a scale proved
singularly ineffective. It failed to extirpate the dis-
Plague ease, which continued to spread (in part through
Although not unknown to the subcontinent in previ- people fleeing from such drastic measures), and it
ous centuries, plague arrived in epidemic force in led to evasion and even open defiance in several
1896, when the disease broke out in Bombay city cities. In consequence, the British administration
and then gradually spread to other parts of western soon settled for a less interventionist policy, turning
and northern India. By 1907 close to 2 million down W. M. Haffkine's suggestion of compulsory in-
plague deaths had been recorded, and at its peak in oculation with the antiplague serum he had recently
1904-5 the number of deaths reached 1.3 million in developed. Reliance was placed instead upon volun-
a single year. By 1907-8 plague accounted for more tary segregation and hospitalization, greater use of
than 14 percent of all mortality in British India, and indigenous medical practitioners, and latterly (once
its heavy toll swelled India's great mortality be- the rat flea connection had been established) on the
tween the 1890s and the 1920s. In this third plague trapping and poisoning of rats.
pandemic, India was exceptionally hard-hit. Of 13.2 These measures may have contributed to the de-
million deaths recorded worldwide between 1894 cline of the disease, already marked by 1917; so also
and 1938, 12.5 million occurred in India: Nearly half may the extensive use made of voluntary inocula-
of the deaths in India fell in the period from 1898 to tion (in the long term). It is possible that just as the
1908, with a further third between 1909 and 1918 prevalence of famine in the early years of the epi-
(Hirst 1953). At first mainly a disease of the cities, demic aided the spread of plague, so the later ab-
plague moved steadily into the countryside. The Pun- sence of famine contributed indirectly to its decline.
jab was worst affected, with nearly 3 million fatali- The bulk movement of grain (and with it X. cheopis)
ties between 1901 and 1921; in 1906-7 alone there in times of food shortages may have facilitated the
were 675,307 deaths in the province, equivalent to spread of the disease: There is some evidence for this
27.3 per 1,000 inhabitants. connection in its partial resurgence as a result of the

massive movements of grain triggered by the Bengal India in 1961-2 (equivalent to 0.85 per 1,000), and
famine of 1943-4. Another possibility is that between 100 and 150 out of every 100,000 city-
whereas human susceptibility remained unchanged, dwellers died from this cause. By 1981 an estimated
rats developed a growing immunity to the plague 1.5 percent of the total population of India was af-
bacillus. For whatever reason, plague was in decline fected, placing TB among the leaders of India's many
in India from the early 1920s and, since 1950, has competing causes of death.
been rare, confined to a few isolated pockets, mainly
in the southern Deccan. Miscellaneous
Several other diseases warrant mention, however
Influenza briefly. Tetanus in India has been particularly associ-
Influenza had a much shorter but more devastating ated with childbirth through the use of unsterilized
career than did plague. As with plague, India was implements to cut the umbilical cord. Cases num-
one of the areas of the globe hardest hit by the bered 32,825 in India in 1974, with 4,400 reported
influenza pandemic of 1918-19. In the space of deaths. Hepatitis was widespread, too, with 126,071
barely 3 months it lost between 12 million and 20 cases and just over 1,000 deaths in 1974. In that year
million lives, equivalent to nearly 5 percent of the there were also 206,386 cases of whooping cough
total population of British India, and up to twice as (300 deaths) and 333,697 (924 deaths) from typhoid,
many as had fallen victim to plague during the making these, along with malaria, dysentery,
whole of the previous decade. As with plague, influ- gastroenteritis, and influenza, two of the main iden-
enza entered India through international ports like tifiable causes of morbidity.
Bombay, but then moved with lightning speed from
Leprosy remains strongly entrenched in South
one city to the next along the main lines of transport
and communication. Southern and eastern India Asia. Whereas the census of 1881 counted only
131,618 lepers in British India (surely a gross un-
were again the areas least affected (Davis 1951;
dernumeration), the census of India 90 years later,
Mills 1986).
in 1971, put the figure at 3.2 million. Some experts,
The greatest number of deaths occurred during however, estimate at least 4 million cases of leprosy
October, November, and December 1918, with the in the country. Not only is this a high figure in
major casualties being young adults between the national terms, with 5 to 6 per 10,000 of the popula-
ages of 20 and 40. Connections between influenza tion affected, but it also makes India home to one-
and famine have often been denied, but because the third of the world's leper population. Despite the
epidemic struck at a time of high prices and food availability of modern drug therapies, the socioeco-
shortages in several parts of India and caused dispro- nomic conditions in which leprosy is transmitted
portionate mortality among the poorer classes, (and perpetuated) have so far prevented its effective
grounds exist for arguing that one reason why India eradication.
suffered so severely from the epidemic was precisely
because so large a part of its population was at the
time hungry or malnourished (Klein 1973; Mills Conclusions
1986). As elsewhere influenza died away almost as Several major epidemic diseases of the recent past
quickly as it had come, and though influenza has have been brought under control (or have largely
remained a common affliction in the region, it has disappeared through reasons that may have little to
been responsible for few deaths. In 1974, for exam- do with human intervention). But, so long as poverty
ple, 1,700,000 cases of influenza were reported for remains endemic in the region and levels of public
India, but there were only 87 deaths. health expenditure and provisioning remain low
even by Third World standards, there seems little
Tuberculosis likelihood that the high levels of morbidity and mor-
Tuberculosis was not a disease that attracted much tality that continue to afflict the region will effec-
medical attention before 1945, but it has increased tively disappear.
in importance as other diseases have declined and as David Arnold
the crowded, especially slum, conditions in South
Asian cities have grown. Already at the start of the Bibliography
century, TB and the other respiratory diseases ac- Arnold, David. 1988. Smallpox and colonial medicine in
counted for at least one-seventh of all deaths. Fully India. In Imperial medicine and indigenous societies,
342,391 deaths from the disease were reported in ed. David Arnold, 45-65. Manchester.

VI.13. Antiquity and the Premodern Period in Southeast Asia 425
Chandrasekhar, S. 1972. Infant mortality, population

growth and family planning in India. London. VI.13
Chen, Lincoln C , ed. 1973. Disaster in Bangladesh. New
York.
Diseases of Antiquity and the
Christophers, S. R. 1911. Malaria in the Punjab. Calcutta. Premodern Period in
Davis, Kingsley. 1951. The population of India and Paki-
stan. Princeton, N.J.
Southeast Asia
1956. The amazing decline of mortality in underdevel-
oped areas. American Economic Review 46: 305—18.
Hirst, L. Fabian. 1953. The conquest ofplague. Oxford. In the imaginations of commentators, both Asian
Hopkins, Donald R. 1983. Princes and peasants: Smallpox and European alike, disease and Southeast Asia
in history. Chicago. have long held a close association. For Chinese offi-
James, S. P. 1909. Smallpox and vaccination in British cials posted to the southernmost regions of the T'ang
India. Calcutta. empire, it was a fearful place of miasmas and malar-
Klein, Ira. 1972. Malaria and mortality in Bengal, 1840- ial fevers. To many Europeans, Southeast Asia was,
1921. Indian Economic and Social History Review 9: like tropical Africa, a "white man's grave." In the
132-60. chronicles of the inhabitants of the region, the real-
1973. Death in India, 1871-1921. Journal ofAsian Stud- ity of disease merged with that of other calamities,
ies 32: 639-59.
in a world populated with spirits that held sway over
MacPherson, John. 1872. Annals of cholera from the earli-
est periods to the year 1817. London.
human life. Aside from biomedical considerations,
McAlpin, Michelle Burge. 1983. Subject to famine: Food
there are clearly important political and cultural
crises and economic change in western India, 1860- dimensions to these links between region and dis-
1920. Princeton, N.J. ease. This essay will examine some of the factors
Mills, I. D. 1986. The 1918-1919 influenza pandemic: The that have given disease such a prominent place in
Indian experience. The Indian Economic and Social Southeast Asian history.
History Review 23: 1-40.
Pollitzer, R. 1959. Cholera. Geneva. The Region
Porter, Alexander. 1889. The diseases of the Madras fam- Following Anthony Reid (1988), Southeast Asia will
ine of 1877-78. Madras. here be taken to refer to the area of Asia lying
Pringle, R. 1869. On smallpox and vaccination in India. between the southern regions of China and the north-
Lancet I: 44-5. western extremities of New Guinea. This region en-
Rogers, Leonard. 1928. The incidence and spread of chol- compasses both the land areas of mainland Asia
era in India: Forecasting and control of epidemics.
Calcutta.
draining the eastern Himalayas, characterized by
Sinton, J. A. n.d. What malaria costs India. Delhi.
large rivers and plains, and the many volcanic is-
lands lying between the Pacific and Indian oceans. A
feature of the region is its high temperatures and
monsoonal rainfalls, which, prior to recent times,
supported an abundant flora and fauna.
Human settlement also nourished in this environ-
ment from around 18,000 B.C., when the earliest
hunter-gatherers are thought to have existed in the
region (Higham 1989). Evidence suggests that vil-
lage settlements developed from around the third or
fourth millennium B.C., and more complex, central-
ized polities from the first century A.D. (Coedes
1975; Higham 1989). The larger "city-states" of
mainland Southeast Asia developed from the sixth
and seventh centuries A.D. It is from the time of
the development of these complex polities that the
earliest written records of Southeast Asian peoples
date.
Prior to the nineteenth century, the region was, as
a whole, sparsely populated, the inhabitants concen-
trated mainly in large trading cities and areas of wet

rice cultivation (Reid 1988). With the development paired. The outside world was believed to be popu-
of "city-states" and an increase in commerce and lated by spirits that had the potential to inflict harm
trade both within the region, and with China, India, on humans (Anuman 1962; Endicott 1970; Terwiel
and the Middle East, important changes occurred in 1978). Practices performed in order to strengthen
Southeast Asia. These changes, which affected the the soul, or to propitiate the spirit world, were thus
size and distribution of Southeast Asian popula- common to the region as a whole (Reid 1988).
tions, their occupations, living conditions, and diet, The natural wealth of Southeast Asia, together
were further enhanced by the contact with the West, with its intermediary position between the East and
via both Africa and the Americas, which developed West, has ensured that contact with some of the
from the sixteenth century. This culminated in the world's major civilizations has taken place over a
colonization of much of Southeast Asia by European long period of time. Early contacts with China and
powers, beginning with the establishment of a Portu- India were later followed by Arabs and then Europe-
guese colony at Malacca in 1511. ans. Many features of these civilizations - in particu-
The development of the region was, however, con- lar, religion and writing - were to become important
fined to certain sections of the region and its popula- in Southeast Asian life. However, at least up to the
tion. Until very recently, a considerable proportion of premodern period, as Reid points out, ties within the
the people of Southeast Asia lived much as they had region were generally more important than those
hundreds of years ago. There remain, for example, with peoples beyond it (Reid 1988).
hunter-gatherer communities in remote areas of Bor- This "distancing" from civilizations outside the
neo and Northern Thailand. Even for villagers living region is reflected in the pattern of the adoption of
in rural areas, and the urban poor, many aspects of cultural features. There is strong evidence to sug-
thought and culture continue to reflect traditional gest that aspects of other civilizations were restated
concepts and values. For this reason it is difficult to in terms of the indigenous cultures concerned (the
make a general distinction between "antiquity" on phenomenon termed "localization" by Owen Wolters
the one hand, and the "premodern" and "modern" in 1982) in many of the areas where such borrowing
periods on the other. For the sake of convenience, occurred. It will be argued here that this process of
however, in this essay "antiquity" will be used to adaptation was also prominent in the classification
refer to the period prior to the entry of Europeans into of, and response to, disease.
the Southeast Asian region. The period following the
entry of Europeans into the region, up until the begin- Disease in the Southeast Asian Past
ning of the present century, will be termed the "pre- Knowledge of disease in the Southeast Asian past is
modern era" of Southeast Asian history. severely constrained by some of the same features
The peoples who inhabited the region in antiquity that give the region its uniqueness. Human re-
spoke languages representing a diversity of families, mains, and written records of disease, deteriorate
including Austronesian, Austro-Asiatic, and Tai. rapidly in the acid soils, heat, and humidity that are
However, though there were considerable regional characteristic of this part of the world. This lack of
variations in their customs and rituals, a good many sources would, in itself, constitute a major difficulty
of the peoples of the region were unified by some in the study of the history of disease in Southeast
basic cultural features. Thus, throughout much of Asia. However, the cultural diversity of the region
Southeast Asia, transport was (until recent times) also raises other issues fundamental to the interpre-
mainly by water, dwellings were of wood and bam- tation of the past. For our purposes, paramount
boo, and rice and fish formed the basis of the diet. among these is the question of differing perceptions
Similarly, the custom of betel chewing, and sports of disease.
such as cockfighting and takraw, played with a rat- Following Arthur Kleinman (1987), the term "dis-
tan ball, were common to many peoples. Trade, and ease" will be used here to include a wide range of
the ease of maritime access within the region, proba- explanations or perceptions of illness. Unlike plants
bly facilitated the process of acculturation (Reid and animals, most diseases are not so readily distin-
1988). guishable by common features. Not only do peoples
Beliefs regarding the soul and the spirit world differ in the ways in which they group the various
were also widely shared throughout Southeast Asia. symptoms of illness into diseases, but there may be
It was believed that if the soul, or life-force, con- considerable variation in the types of bodily phenom-
tained within the human body were weakened or ena that constitute symptoms. Conditions such as the
disturbed in some way, then health could be im- enlarged spleen associated with malaria may, among

VI. 13. Antiquity and the Premodern Period in Southeast Asia 427
some populations, be regarded as nonpathological whole of Southeast Asia, the specific illustrations
(Ackerknecht 1946). With other peoples, much em- given in this essay will be taken mainly from main-
phasis is placed on whether symptoms are located in land Southeast Asia. In particular, a good many
the upper or lower part of the body and the time of examples will be drawn from the Thai peoples.
their onset in relation to the phases of the moon There are several reasons for this narrow focus. In
(Ohnuki-Tierney 1981; Mulholland 1987). In some part it reflects this writer's own area of specializa-
cases there may even be little distinction made be- tion, a situation that is unavoidable in approaching
tween disease and the agent that causes it (Schafer such a topic. In addition, however, the history of
1967). As a consequence, available descriptions of disease among the Thai peoples is an appropriate
illness often do not provide the type of information focal point for a study of the disease in Southeast
that is necessary for biomedical diagnoses to be made. Asia. The region of mainland Southeast Asia where
Information on illness in the Southeast Asian past the Thai kingdoms developed in many ways repre-
comes in several forms: In addition to what may be sented a meeting place for the major civilizations of
regarded as indigenous classifications, there are Asia, lying between China to the north, India to the
Indie, Chinese, and early Western systems of classifi- west, and the Austronesian peoples to the south and
cation. It is possible, for example, that a case of east. Originating in the north, the Thai, who were
diarrhea might be seen as "internal heat," "an expan- "syncretizers" par excellence, moved into a region
sion of the heat element," "fluxes," or as a "normal" already occupied by Mon and Khmer peoples. Fur-
phenomenon, depending on the source of the descrip- thermore, although the kingdom of Siam came to
tion. Furthermore, as Norman Owen (1987) has indi- dominate the other Thai "city-states," it was alone
cated, a feature of the Southeast Asians' response to among Southeast Asian countries in remaining
disease was their syncretism. An appropriate diagno- uncolonized by Europeans. On the other hand, it
sis and treatment was selected from among the vari- may be argued that, though not directly colonized,
ous systems available. For this reason, a history of Siam was a de facto colony, in that its development
disease in Southeast Asia is, in part, a history of the during the late nineteenth and early twentieth cen-
ways in which illness has been classified in this turies was mainly in the hands of European and
region of the world. American advisors.
This is not to say that biomedical interpretations Previous historical studies have not, in general,
are not possible. In past accounts one can recognize taken advantage of the opportunities that mainland
many of the diseases that were known in the region Southeast Asia presents for the examination of dis-
until quite recent times and, in a large number of ease. The processes of adaptation, perception, and
cases, are still prevalent in the region today. Ma- response to illness have, for the most part, been
laria, smallpox, dysentery, cholera, typhoid, typhus, examined in the context of the colonized regions of
plague, leprosy, beriberi, goiter, trachoma, respira- insular Southeast Asia. This is to be expected, in
tory diseases, tuberculosis, and parasitic and helmin- view of the ready availability of information on dis-
thic infestations are but a few examples. However, ease, and the size of the populations in these areas,
although it is often possible to interpret accounts of with their concomitant health problems. But in us-
illness in terms of our modern understanding of ing illustrations from uncolonized mainland South-
pathology, this approach reveals only one aspect of east Asia, this chapter seeks to redirect some of the
the history of disease in Southeast Asia. Neglected emphasis in the study of the history of disease.
is the place of disease in the context of extra- and
intraregional dynamics involving trade, warfare, Diseases in the Prehistoric Period
politics, and culture. In short, biomedical interpreta- Our knowledge of the types of diseases suffered by
tions do not show how Southeast Asians perceived the prehistoric inhabitants of Southeast Asia is, of
disease and what it meant to them. necessity, based on the examination of a very limited
Another difficulty in treating the history of dis- range of human remains unearthed in a few sites in
eases in Southeast Asia as a whole is posed by the present-day Thailand, the Malay Peninsula, and
number of different ethnic groups and languages in Sulawesi. The remains represent only the most dura-
the region. This problem is further exacerbated by ble of the body's hard tissues, primarily the skull,
the diversity of languages and methodologies of the mandible, and teeth. Despite such limitations, how-
available secondary sources on the subject. For this ever, they nevertheless reveal a good deal of informa-
reason, although the general features described will tion regarding the diseases suffered by the ancient
relate, in the main, to the history of diseases in the inhabitants of the region.

Skeletal remains, for example, recovered from civilizations in other parts of Asia. Much of the lan-
sites at Ban Chiang, Non Nok Tha, and Ban Na Di in guage used, and the means of recording itself, were
northeastern Thailand suggest that the prehistoric exotic in origin. Originally these descriptions were
inhabitants of these villages suffered many of the made using techniques probably borrowed from In-
same diseases found in these areas today. As might dia or China. Inscriptions were made on stone, or on
be expected from the nature of the source materials, palm leaves trimmed and bound together with cord,
these included a range of diseases primarily affect- or else written on paper. The scripts employed were
ing the skeleton, such as osteoarthritis (or degenera- similarly of Indie or Chinese origin (Guy 1982; Marr
tive joint diseases), and bone infections, possibly in- 1987).
cluding osteomyelitis and tuberculosis of the spine.
There is also evidence for a range of dental pathol-Traditional Medical Texts
ogy, including caries, periodontal disease, abscesses In addition to short references to disease in chroni-
(periapical and alveolar), and excessive tooth wear, cles, or other official records, certain works were
sometimes with pulpal involvement (Pietrusewsky devoted solely to medicine. These appear to have
1974,1982, 1982-3; Houghton and Warrachai 1984). been a feature of almost every major civilization in
Evidence for caries, periodontal disease, and ab- the region, including those of the Burmese, Thai,
scesses has also been found in human remains from Lao, Khmer, Vietnamese, Malay, Javanese, and Bali-
sites at Talaud Island in North Sulawesi, and Gua nese (La Loubere 1691; Sangermano 1833; Macey
Cha in the Central Malay Peninsula (Bulbeck 1982). 1910; Pigeaud 1967; Pham Dinh Ho 1973; Martin
In addition, examination of skeletal remains pro- 1983; Social Research Institute 1986; Lovric 1987;
vides evidence of diseases affecting other organs of Reid 1988). Commonly, the contents of these books
the body. These include tumors, or tumorlike defects consisted of passages relating to theories of illness,
(in a child's cranium from Ban Chiang), and blood lists, and descriptions of diseases, and details of the
disorders. Evidence for the latter comes from a num- methods used in their treatment.
ber of skeletons found in northeastern Thailand, It is likely, however, that such texts provide incom-
which, it has been argued, may indicate thalassemia plete accounts. One reason for this is their perishabil-
or elevated hemoglobin B levels (Pietrusewsky 1982, ity. Being sensitive to decay and insect attack, tradi-
1982-3). tional texts had to be continually recopied in order to
These conditions, both of which are widespread in preserve their contents. Not only did this introduce
the region today, may be associated with resistance the possibility of human error through mistakes in
to malaria, which is common in the area. Indeed the transcription, but, more importantly, there was al-
evidence from the pathology observed in skeletal ways the threat that disruptions caused by warfare
remains has thus been used to argue for the antiq- or other adversity would result in the loss of large
uity of malaria (Pietrusewsky 1982). More recently, numbers of texts. For example, in 1767 the Siamese
however, iron deficiency anemia has been put for- capital of Ayuthaya was sacked by the Burmese, an
ward as an alternative explanation (Houghton and event which, in itself, resulted in the destruction of
Warrachai 1984). This explanation is consistent much of the court's medical library (Koenig 1894).
with the effects of parasitic infestations of the body,Moreover, the loss was compounded by the slowness
which are also prevalent today in this region of of the subsequent recompilation process, which was
Southeast Asia. not completed until some 40 years later, around
1816.
Diseases in Antiquity Another difficulty in the use of traditional texts as
Apart from evidence derived from archeological resource materials is in determining the extent to
search, the earliest available sources of information which their contents reflected diseases actually oc-
on disease in Southeast Asia are references in in- curring in Southeast Asia, and their prevalence. It is
scriptions and accounts appearing in traditional quite possible that accounts of diseases contained in
texts. Khmer inscriptions of the seventh and eighth texts may be largely based on Indie, Chinese, or,
centuries A.D., for example, make reference to lice, later, Arabic medical treatises. This is certainly the
eye impairments, and "dermatitis" or "ringworm" case with other types of texts, such as literary or
(Jenner 1981). It is difficult to date some of these astrological works (Quaritch Wales 1983; Reid
sources, especially texts, but it is clear that by the 1988). On the other hand, evidence suggests that,
time of their appearance there had already been although Southeast Asian medical texts may incor-
considerable contact between Southeast Asia and porate disease terms and concepts derived from tradi-

tions outside the region, they are not simply transla- derived from the other sources discussed above, may
tions of texts belonging to those medical systems. It thus make an important contribution toward our
appears that in the area of disease, as with other understanding of disease in Southeast Asia in an-
aspects of Southeast Asian culture, a process of local- cient times.
ization took place, resulting in the selective empha-
sis of certain concepts of parts of theories, and Indigenous Views of Disease
changes in the meanings of words borrowed from It is clear from the information contained in the
languages outside the region. Some examples of various sources described above that in the past,
these processes will be considered later in this essay. Southeast Asian peoples recognized a large number
of diseases, and classified them in ways that were, in
Travelers' Accounts many cases, quite complex. One feature, which is
A further important source of information on disease immediately striking to an observer familiar with
in Southeast Asia consists of the accounts written by Western concepts, is that conditions that are under-
early travelers to the region. These included the stood to be diseases in modern medicine were not
Chinese Buddhist monk Yi Jing, who passed necessarily viewed as such by Southeast Asians.
through the region on his way to India toward the This is especially evident in the area of diseases
end of the seventh century A.D. (I Tsing 1896), Chou affecting the gastrointestinal tract which, along
Ta-kuan (1951), who accompanied a Chinese ambas- with "fevers," occupy perhaps the most prominent
sador to Cambodia in the thirteenth century, and the place in accounts of illness in the region (see Dam-
later European travelers such as S. de La Loubere pier 1927; Chou Ta-kuan 1951; Schafer 1967; Cook
(1691), and E. Kaempfer (1906). Kaempfer's account 1968).
is of particular interest, because he represented a A number of severe gastrointestinal diseases were
class of scholarly voyagers whose interests often ex- well differentiated by Southeast Asians and elicited
tended to a number of disciplines. As a physician treatment responses. Symptoms and treatments for
and botanist, he took care to record accurately what conditions such as cholera, dysentery, severe diar-
he saw and heard, including indigenous terms and rhea, and certain types of parasitic infestations
descriptions. When compared with accounts ob- were, for example, described in traditional texts
tained from indigenous texts, such information is (Mulholland 1979; Lovric 1987; Terwiel 1987). How-
extremely useful. ever, certain other conditions that biomedicine
would recognize as diarrhea were apparently not
Ethnomedical Studies always considered to be diseases. Recent studies indi-
Modern-day studies of indigenous perceptions of dis- cate, for example, that in certain areas of Southeast
ease in the Southeast Asian region constitute an- Asia infant diarrhea is not necessarily viewed as
other important kind of available information. As pathological. Thus, among some Northeast Thais
well as information on disease appearing in the con- one type of diarrhea (su) may be regarded as a nor-
text of more general anthropological or linguistic mal phenomenon, common to all infants (Earmporn,
studies, a number of specific examinations of indige- Pramote, and Stoeckel 1987). This would also appear
nous medical systems in Southeast Asia have been to be the case for people in parts of northern Thai-
conducted. These include those of insular peoples, as land and Laos. Similar findings have been reported
well as those of mainland Southeast Asia (see, e.g., for the Acehnese and other Indonesian peoples
Frake 1961; Martin 1983; Boutin and Boutin 1987; (Raharjo and Corner 1989).
Bran and Schumacher 1987; Gumpodo, Miller, and It is likely that such poorly defined boundaries
Moguil 1988; Bamber 1989). Although there have between pathological conditions and "normal" bodily
been far-reaching changes in Southeast Asian life, it states are also to be found for other types of disease.
is probable that, until quite recently, for a large Included in these are a number of Southeast Asian
number of people in the region, life was lived in disease categories that are unrepresented in modern
much the same manner as it had been centuries ago medicine. Examples of these that are better known
(Hall 1981). It is thus likely that, for certain sections because of their dramatic expression are the condi-
of the Southeast Asian population, present-day per- tions of amok and latah, Malay behavioral syndromes
ceptions and treatment of disease bear a strong re- that appear to have counterparts in other parts of
semblance to those of the past. An analysis of such Southeast Asia (Westermeyer 1973; Simons 1985).
contemporary "folk" medical beliefs and disease clas- Other conditions, lacking such overt behavioral
sifications, made in conjunction with information symptoms, reflect classifications of illness that are

equally different from those of modern medicine. and exchange (Golomb 1985). These processes would
One such disease is the Thai category saang (chil- have involved not only concepts and terms indige-
dren's disease), which includes a range of symptoms nous to the region but also those originating from
mainly affecting the mouth and skin of young chil- outside Southeast Asia - in Chinese, Indie, or Is-
dren (Mulholland 1987). The onset of this disease lamic medicine. Perhaps the most well-known exam-
has strong links with Thai beliefs regarding "soul ple of the integration and adaptation of foreign con-
loss" (Hanks and Hanks 1955; Hanks 1963). cepts of disease into the Southeast Asian framework
is that of the so-called wind illness.
Shared Disease Terms
It is apparent from a comparison of disease terms in "Wind Illness,"Humoral Theories, and
a number of Southeast Asian languages that certain Therapeutic Practices
categories were widely shared throughout the re- A type of illness common to most of the peoples of
gion. One explanation for this situation is the con- Southeast Asia has been termed wind illness (Hart
tact that resulted from the movement of large popu- 1969). The disease has been reported among Indone-
lations within the region, such as occurred with the sian and Malay peoples, where it is referred to as
establishment of the Tai peoples in the Chaophraya masuk angin, literally "wind enters" (Gimlette
River valley and the Malay Peninsula from the mid- 1939), among Filipinos (Hart 1969), Burmese
eleventh century A.D. (Wyatt 1984). Contact with (Sangermano 1833), Khmer (Headley 1977), Viet-
peoples already established in the region, such as namese (Eisenbruch 1983), and a number of Thai
the Malay, Mon, and Khmer, was reflected in the groups. The conditions represented by wind illness
adoption of disease terms from these languages. vary widely through the region, ranging from symp-
Thus, for example, the Malay disease sawan (convul- toms of the common cold among Indonesians and
sions), which affects small children (Wilson 1985), Malays, to fainting, dizziness, and, more rarely, lep-
also appears, as saphan or taphan, in traditional rosy, among mainland Southeast Asian peoples.
Thai medical texts (Mulholland 1987). Most explanations for the phenomenon have been
A similar though more complex process seems to made in terms of theories derived from the major
have taken place with respect to terms for certain medical systems with which Southeast Asian peo-
types of skin diseases. This may be seen in the case ples have come into contact. In Chinese medicine, for
of the ancient Mon-Khmer term mren, which proba- example, wind illness figures as part of a theory that
bly referred to skin afflictions in general. This term sees disease arising through the entry of wind into
appears to have undergone a change in meaning at the body (Unschuld 1982). Wind illness is similarly
some stage, possibly prior to contact with the Thai, important in the humoral theories of Indie and Is-
to signify ulcer in Khmer, and superficial skin condi- lamic medicine. Here, however, it refers to diseases
tions in Mon (Shorto 1971). of the wind element, one of the four elements (the
Following contact with the Mon and Khmer, the others being earth, fire, and water) of which the
term mren was adopted by the Thai, cognates appear- body is said to be composed (Hart 1969; Ullmann
ing in traditional medical texts as mareng and 1978). According to the Indie version of this theory,
baheng. In this case, however, because in Thai skin the wind element denotes the quality of bodily move-
diseases appear to have been well differentiated ment, or sensation. Any disease that involves an
prior to contact with the Mon and Khmer, there is impairment or abnormality in these faculties would
evidence of an accommodation with existing terms thus be designated as a wind illness. Following from
(Li 1977). Thus in central Thai, which was in close this rationale, wind illness includes a number of
contact with Khmer, mareng came to mean "deep- diseases or conditions, such as paralysis, epilepsy,
seated ulcer" (McFarland 1944). However, in north- and leprosy, which are considered in modern medi-
ern Thai baheng refers to superficial skin diseases, cine to constitute quite separate disease entities
indicating that the term was adopted from the neigh- (Caraka 1949).
boring Mon peoples (Brun and Schumacher 1987). Versions of both these theories are to be found in
These examples also point to the existence of more the Southeast Asian region. The Indie theory of the
complex processes within the Southeast Asian re- four elements is expounded, for example, in Thai
gion which contributed to the sharing and inter- medical texts (Mulholland 1979); Islamic humoral
change of terms and concepts related to disease. theory is widely known in peninsular Malaysia and
Medicine was an area of culture that was particu- Indonesia (Manderson 1986); and beliefs regarding
larly amenable, for a number of reasons, to trade the ill effects of the entry of wind into the body

accompanied Chinese who settled in the region of links with the major civilizations outside of the
(Kwa Tjoan Sioe 1936). However, the wind illness of region meant that different perceptions of disease
Southeast Asia does not alwaysfitneatly with these and therapeutic techniques continued to be intro-
theories. Early writers on Thai medicine com- duced to Southeast Asia, and incorporated into indige-
mented, for example, on the prevalence of wind ill- nous systems (Owen 1987). The result was a matrix of
ness in comparison to diseases affecting the other classifications and strategies that could be brought to
three elements (Pallegoix 1854; Bradley 1967). Thai bear on the experience of illness.
wind illnesses also appear to have encompassed a far
wider range of diseases than one would expect on the Disease in the Premodern Period
basis of Indie theory (Muecke 1979). As noted earlier, from around the beginning of the
Discounting the unlikely possibility that Thais, or sixteenth century, a marked economic and social de-
other Southeast Asian peoples, are predisposed to velopment occurred in most Southeast Asian states.
diseases affecting bodily sensation or movement, it The development of the region had significant ef-
would seem that the Indie concept of wind illness has fects in relation to disease. These included changes
been reinterpreted to accord with indigenous con- in the types of disease suffered by Southeast Asians,
cepts relating to the cause of illness. These concepts their susceptibility, and the ways in which they
probably have more to do with beliefs linking dis- viewed and treated disease. One important feature
ease to soul loss, or the spirit world, than they do of this period was the large-scale intervention of the
with humoral theories (Laderman 1987). The result- state in the control and prevention of disease. This
ing concept of wind illness represents a complex, period saw the initiation of public health measures,
incorporating elements derived from both within the the establishment of hospitals, and the commence-
Southeast Asian region and outside of it. ment of vaccination campaigns. It also saw South-
Similar interactions may be seen throughout the east Asia come to play an important role in the
region in relation to other aspects of disease. For development of Western science. In this section of
example, the etiological concept of hot and cold physi- the chapter, some of these features will be examined
cal states is also widespread in Southeast Asia. Ac- against the background of the cultural and socioeco-
cordingly, certain diseases, foods, and treatment nomic changes that came about at this time.
practices are regarded as heating or cooling (Hart
1969; Manderson 1981). As with wind illness, this Changes in the Types of Disease
concept appears to be the result of an integration of From the medical historian's point of view, one im-
indigenous beliefs with Indie, Islamic, or Chinese portant legacy of the European colonization of South-
theories (Manderson 1981; Marr 1987). east Asia was the propensity of the colonizers to
Therapeutic practices were also shared through- collect statistics, compile reports, and make detailed
out the region. One well-known example is in the observations on illness. These range from simple
ritual ridding of a person, or community, of disease. parish records, as in the Philippines (Owen 1987), to
Among the central Thai this was termed sia kabaan, colonial office records such as those that exist for
and consisted of the symbolic transference of the Java and Malaya (see Gardiner and Oey 1987;
disease to inanimate objects, such as dolls or animal Manderson 1987). Moreover, European interest in
images, which were subsequently floated away on Southeast Asia was not limited to administrative
streams, or otherwise removed from the locale of the concerns; the region was visited by a good number of
patient (Anuman 1958). Similar rituals have been scholars, encompassing a diversity of disciplines,
described for most other Thai groups (Terwiel 1980- and their accounts contain detailed descriptions of
1), and in several other regions of Southeast Asia, the region, its peoples, and history.
with variations according to the local culture Nonetheless, considerable care must be taken in
(Snouck Hurgronje 1893; Skeat 1900; Reid 1988). the interpretation of the sources because they gener-
Often these local variants included elements derived ally reflect European preconceptions, regarding both
from Indie or Islamic tradition. Southeast Asia and disease. Thus whereas figures
The picture that emerges from this brief look at are generally good for foreign communities, the reli-
some of the features of Southeast Asian views of disability of statistics for the indigenous populations is
ease prior to increased contact with the West is one of often questionable (Boomgaard 1987; Gardiner and
a dynamic state. Close contact among peoples within Oey 1987). As has been noted by a number of com-
the region ensured that conceptions of disease and its mentators, there was a strong tendency in Western
treatment were frequently shared. The development sources to emphasize dramatic events such as epi-

demies (Boomgaard 1987; Owen 1987). Epidemics of the Bayon at Angkor, and at Ta Keo (Coedes 1941).
"plague," smallpox, and a number of other diseases The disease was also noted by a Chinese traveler
were indeed a frightening and regular feature of during his stay in Cambodia in 1296 and 1297 (Chou
Southeast Asian life during this period. However, Ta-kuan 1951). Legend also has it that in ancient
insofar as they posed no threat to the health or times, there was a Khmer "leper king" (Coedes 1941;
commercial interests of the European community, Chou Ta-kuan 1951). But other written accounts do
other less dramatic diseases of the region tended to not always permit a fine distinction to be made be-
be neglected in accounts. Yet, in the long run, the tween leprosy and other skin afflictions. In tradi-
toll they took of human life was probably consider- tional Thai medical texts, for example, the term that
ably greater. today is used to denote leprosy, ru'an, also includes a
It is true that references to disease in certain types range of other skin conditions such as tinea. This is
of indigenous sources, such as chronicles, are also also the case in some early European accounts. Thus
often concerned with epidemics. However, these ref- the leprosy which William Dampier reported to be
erences, which occur mainly in connection with ac- widespread in Mindanao and Guam during his 1686
counts of crises, and the performance of state ceremo- visit was probably the same fungal skin disease,
nies, reflect the political or religious function of such possibly tinea imbricata, later reported by John
sources, rather than an attempt to provide balanced Crawfurd in Java (Crawfurd 1820; Dampier 1927).
descriptions of disease. In other indigenous sources, Some of the difficulties mentioned above may be
such as medical treatises, much space is often de- attributed to the complexities of indigenous disease
voted to the description of diseases that do not figure naming, as in the Thai examples, or to the lack of
significantly in either European or official indige- diagnostic expertise of the individual observer, as
nous accounts. was perhaps the case with Dampier. More impor-
A further difficulty in the interpretation of Euro- tantly, however, the examples above point to the fact
pean and indigenous sources alike is that both the that diseases, their incidence, and the ways in which
systems of classification and the illnesses they they were classified, were continually changing.
sought to classify were changing. In the indigenous Thus as diseases were changing in virulence, the
languages of the region it was not uncommon, at susceptibility of the population to disease was also
different times and in different contexts, for a dis- changing. Moreover, new diseases were being intro-
ease to be known under several names. Similarly, duced into the region, and, largely due to the develop-
early European accounts often differentiated poorly ment of Western medical science, changes were oc-
between illnesses, references frequently being con- curring in the understanding of disease. Here, we
fined to such general terms as fluxes, or fevers (see look at some of the factors that were central to these
Dampier 1927; Cook 1968). changes.
The difficulties thus posed for the identification of
illness in modern terms are illustrated by the case of The Development of Cities
the history of cholera in Siam (Terwiel 1987). It is The most important factor concerning disease during
generally agreed that the first major epidemics of this period was probably the redistribution of popula-
cholera in Southeast Asia occurred in the early nine- tions, associated in particular with the development
teenth century as the result of the spread of the of large cities. Whereas in the past the location of
disease from India. Yet in earlier Thai sources chol- cities was primarily determined by strategic consider-
era was known under several names, including ations, which almost certainly would have included
ahiwaat, khai puang yai, and rook long rook. Thus, the provision of secure food and water supplies, trade
owing to both the difficulties in interpreting indige- and industry now became a major determinant.
nous accounts, and the lack of sophistication of early In Southeast Asia major cities, such as Batavia,
Western classifications of the illness, it remains un- Singapore, Manila, and Bangkok, developed in
clear whether a less virulent strain of cholera had coastal or estuarine areas as port cities with their
previously existed in the region (Boomgaard 1987; associated commercial activities. In these areas,
Owen 1987; Terwiel 1987). which were usually low-lying or marshy, drainage,
Similar difficulties are encountered in the identifi- the removal of wastes, and the supply of clean house-
cation of other diseases, as seen in the case of lep- hold water quickly became a problem. The poor, on
rosy, another condition with a long history in South- whose labor the operation of ports and commerce
east Asia. Human figures with features consistent depended, were faced with the additional problems
with leprosy are depicted in Khmer bas-reliefs on of crowded housing and a diet that was often barely

adequate. In addition to the dangers these condi- and wage labor (Robison 1986). Thus under colonial
tions posed for health, the constant port traffic and administrations, the imposition of taxes, to be paid
the linking of Southeast Asia with the rest of the in cash rather than by goods or labor, has been
world meant that the region was increasingly open pointed to as a significant factor in the impoverish-
to the entry of communicable diseases. ment of many (Worth 1985). On the other hand, as
Of the Southeast Asian port cities that emerged Lysa Hong (1984) has pointed out, taxation systems
during this period, Batavia probably had the great- did not necessarily serve to impoverish populations.
est reputation for unhealthiness. The city was re- But when combined with crises such as droughts,
ported to be relatively free from disease for some they could produce extreme hardship. Such was the
years following its establishment in 1619. But its situation in Siam in 1844, when farmers in
growth and the development of an adjacent hinter- Suphanburi, already affected by successive rice crop
land placed such demands on the city's drainage failures, were faced with the added burden of taxes
systems and water sources that from the early eigh- (Terwiel 1989).
teenth century onward disease became a major prob- The many economic changes that produced wide-
lem (Blusse 1985). By the time the explorer James spread poverty meant, of course, that large sections
Cook called at Batavia in late 1770 to take on sup- of the population were placed in situations where
plies and prepare his ship for the journey back to they were more susceptible to disease, through ei-
England, conditions were extremely bad. After a ther direct exposure or poor resistance. Individuals
long voyage heretofore notable for the good health of were also less able to afford the medical care that
its crew, Cook wrote that his ship, the Endeavour, might have promoted recovery from disease. Thus,
left Batavia "in the condition of an Hospital Ship." in addition to famines, and problems directly related
European residents of Batavia were able to insu- to nutritional deficiencies such as beriberi and rick-
late themselves to a large degree from the disease ets, the effects of poverty showed up in a range of
prevalent in the city by moving away from the old other diseases. These included chronic respiratory
areas within the city walls. But the Chinese and disease, tuberculosis, and eye ailments. Infant chil-
Indonesian inhabitants, unable to move, continued dren were one group particularly at risk, and this
to suffer illness at rates that were higher than most was reflected in high infant mortality rates, as in
other towns in Java (Abeyasekere 1987). Although Malaya in the early part of the twentieth century
Batavia provides just one example, this pattern of (Manderson 1987). The conditions of poverty also
disease, related to overcrowded and unsanitary liv- meant that the effects of epidemic diseases, as in the
ing conditions, existed in most other Southeast influenza pandemic of 1918, were considerably more
Asian coastal cities (Lord 1969; Worth 1985; pronounced among the non-European population of
Manderson 1987). Southeast Asia (Brown 1987).
The growth of cities was, of course, not the only
stimulant to disease. Labor, often immigrant, was Changes in Susceptibility
also required to work plantations and mines, under Balancing the deleterious effects of the development
conditions that also posed considerable risks to of the region on health were a number of other fac-
health (Cohen and Purcal 1989). Changes in the tors. It was, after all, in the interests of colonists and
exploitation of the rural environment also created Southeast Asian rulers alike to ensure a supply of
circumstances that led to the spread of disease, as productive labor. By the same token, these economic
seen in the association between wet rice cultivation interests also meant that they often did not do much
and the spread of malaria in Java (Boomgaard more than they had to. As Owen (1987) has put it,
1987). Similarly, plantation agriculture was instru- the colonial system "forced the poorest to the brink,"
mental in the spread of malaria and dengue as well, but it "kept most.. . from toppling over." Yet the
by providing opportunities for mosquitoes to breed, things that kept the majority of the population from
such as in the water trapped in Latex cups and "toppling over the brink" with regard to health were
coconut shells or husks (Wisseman and Sweet 1961). not all attributable to the direct intervention of the
Economic changes in Southeast Asia also contrib- state in the treatment and prevention of disease. A
uted to changes in disease by the creation of a land- number of the changes affecting the susceptibility of
less and impoverished class. In part, this class was individuals to disease occurred at this time, follow-
brought about by the disruption of traditional forms ing from increased contact with the rest of the world.
of agriculture, particularly by the development of Indeed one consequence of prolonged contact be-
plantations, the introduction of money economies, tween Southeast Asian populations and the rest of

the world was the development of disease resistance. use Western medicine to treat the non-European
Thus although initial exposure to diseases previ- population, ulterior motives such as religious conver-
ously unknown to the region resulted in a high mor- sion were often at work (Hutchinson 1933; Worth
tality, long-term exposure produced resistance to 1985). Besides the suspect attitudes and methods of
them. Indeed the openness of the region to trade, it colonists and missionaries, there were other impor-
has been argued, meant that immunity to most seri- tant reasons why Western approaches to the diagno-
ous epidemic diseases was already developed in sis, treatment, and prevention of disease were not
much of Southeast Asia prior to contact with Europe readily adopted by Southeast Asians. For most, lan-
(Reid 1988). Moreover, the existence of some dis- guage and finances also presented practically insur-
eases in the region prior to contact may also have mountable barriers to the acquisition of Western
had some effect in minimizing the impact of intro- medical knowledge. Prominent, too, were indige-
duced diseases. Thus it has been suggested that the nous beliefs regarding illness and the working of the
prior existence of yaws in Southeast Asia was a body, and negative perceptions of the efficacy of West-
factor in limiting the spread of syphilis introduced ern methods. In the latter case although the value of
by the Europeans (Boomgaard 1987). certain aspects of Western medicine, such as the
Probably of even greater significance in keeping medicinal use of opium, had long been recognized in
people away from the brink was the introduction of Southeast Asia, the efficacy of other features was
new foods, habits, and customs which followed the not apparent. Many of the practices introduced by
European presence in the region. A number of food Europeans in the prevention and treatment of ill-
plants, such as the papaya, potato, tomato, and chilli ness were hardly any better than local ones they
pepper, which originated in the New World, came to replaced. These included "cholera drinks," "cholera
Southeast Asia with the Spanish and Portuguese belts" (a broad band of flannel worn while sleeping
and rapidly became an important part of the region's at night to protect the abdominal organs from chill),
cuisine. Footwear also came to be adopted by sec- and dutch wives (cylindrical cushions used to sup-
tions of the population that would have prevented port or protect the body from chills while sleeping at
entry through the skin of parasites such as hook- night) (Bangkok Times 1904; Bangkok Times Weekly
worm. Traditional unhygienic practices relating to Mail 1906; Abeyasekere 1987; Owen 1987). Indeed,
the cutting and treatment of the umbilical cord of some European practices, such as bloodletting, ran
the newborn child, which often produced tetanus, quite counter to local beliefs (Reid 1988; Bamber
also lost favor during this period (Hanks 1963; 1989).
Manderson 1987). Nevertheless, there were occasions when features
of Western medicine appear to have been well ac-
The Adoption of Western Medicine cepted. In some cases, such as in the use of quinine to
Contact with the West also meant contact with West- treat malaria, which became available from the late
ern medical practices, although it is doubtful that eighteenth century, acceptance came as a result of
such medicine had any favorable impact on health the demonstrable pharmacological value of the drug.
prior to the late nineteenth century, when the first In other cases it appears that Western medical prac-
major benefits of medical science came to be felt. In tices were adopted because of a fortuitous coinci-
fact, even then progress was slow. Colonial doctors dence with existing Southeast Asian beliefs. This
and administrators were not, in general, representa- seems to have been responsible in part for the accep-
tive of the most advanced thinking of the age (Owen tance of the treatment of smallpox by vaccination,
1987). Furthermore, the medical and health services which fitted well with local beliefs that substances
introduced were based on European models and inserted beneath the skin could confer magical
were mainly directed at the European populations, power (Reid 1988; Terwiel 1988).
and at the labor force upon whom they depended.
European efforts directed at improving the health Smallpox Vaccination
of indigenous populations were often carried out Smallpox, at least from the time it was recorded in
without regard for local beliefs and customs. In its seventeenth-century accounts, was one of the most
extreme this was seen in measures such as the burn- feared diseases in Southeast Asia (La Loubere 1691;
ing of homes and the desecration of the dead, which Lovric 1987; Reid 1988). Traditional methods of
took place in Java following the outbreak of plague treatment, such as herbal medicines and bathing,
in the early years of the twentieth century (Hull were largely ineffective against epidemics that oc-
1987). Where more sensitive attempts were made to curred regularly throughout the region. Little could

be done by the local inhabitants except to limit the were a feature of the courts of a number of South-
spread of the disease (Reid 1988). But with increased east Asian rulers (Worth 1985; Marr 1987; Bamber
contact with peoples outside the region, different 1989). It is likely, however, that the services of such
methods of prevention became available. One of "hospitals" were largely confined to the elite (Marr
these was inoculation (variolation), involving the 1987; Reid 1988). By the same token, it is unclear
deliberate introduction of smallpox matter into the whether the hospitals that existed in Cambodia dur-
body, usually via the nose, first practiced by the ing the twelfth century under the reign of Jayavar-
Chinese and Indian populations in the region (Ter- man VII were in fact "open to all" as their inscrip-
wiel 1988). This technique was also later employed tions suggested, and whether they can be regarded
by the Dutch in Java around 1780, and appears to as "hospitals" in the Western sense. On this point
have been practiced by Europeans in Siam from the inscriptions are not clear, and could simply
1833 (Boomgaard 1987; Terwiel 1988). At the re- mean dispensaries (Coedes 1941). That this may
quest of the Siamese king, inoculation campaigns have been the case is supported by later accounts
were begun in Bangkok in 1838 (Terwiel 1988). which comment on a reluctance by Southeast Asian
Vaccination, a less dangerous and unpleasant peoples to build or enter hospitals (Hutchinson
form of smallpox prevention, began in Java in 1804, 1933) because of an association of hospitals with
although its spread was limited until the introduc- death. For many Southeast Asians, hospitals were
tion of mass immunization programs (Boomgaard seen as places where one went to die, and in all
1987). The Dutch also introduced regulations in likelihood harbored the spirits of those who had
1820 that ensured that outbreaks were reported and already died there (Chai 1967; Thompson 1967;
contained, which may in fact have contributed more Abeyasekere 1987). The fact that a number of hospi-
to the control of the disease than did the immuniza- tals were originally founded by missionaries as hos-
tion program (Boomgaard 1987). In Siam, largely pices for the care of the victims of epidemics, or
because of problems in obtaining viable vaccine, vac- those suffering incurable illnesses, would have done
cination programs against smallpox did not succeed little to change this view (Yuwadee 1979; Worth
until late in the nineteenth century (Terwiel 1988). 1985).
In Vietnam, smallpox vaccination appears to have Hospitals created by colonial governments were
been initiated in order to protect the French military generally not intended for the use of most non-
and settlers: Free smallpox vaccination campaigns European Southeast Asians but, rather, for the mili-
were introduced among French troops in 1867, and tary and civilian personnel serving the colonial ad-
compulsory vaccination of villagers took place in ministrations. Thus, the health care service provided
1871 when a major epidemic occurred. Further mass by the Dutch East India Company was for company
vaccination campaigns, mainly in the south and cen- servants, as was the hospital system introduced by
ter of the country, were conducted in 1895 and 1896 the British in the Malay states from 1878 (Chai
(Worth 1985; Marr 1987). 1967). In Vietnam hospital facilities were introduced
It may have been the case that methods adopted in the late nineteenth century, largely for the care of
by the colonial administrations in the introduction the colonial army and administration (Worth 1985).
of vaccination were at times heavy-handed. How- Where hospitals were established specifically for
ever, the practice does not, in general, seen to have the benefit of workers, the funding appears to have
met with resistance from the local inhabitants of the come mainly from the groups concerned. For exam-
region. This is suggested by the active interest taken ple, the Chinese Hospital established by the Dutch
by the Siamese, for example, in the pursuit of knowl- in Java was financed by taxes on Chinese residents
edge about vaccination. Where there was reluctance (Abeyasekere 1987). The "paupers" hospitals associ-
to employ the technique, it appears to have arisen ated with mining centers, which were established by
from doubts regarding the viability of the vaccine, the British in Malaya, were also funded by taxing
rather than from the method itself. This was not the Chinese workers (Chai 1967).
always the case in the introduction of other Western The impetus to establish hospitals in Southeast
practices used in the management of disease, particu- Asia did not come solely from colonialists. In the
larly in regard to the establishment of hospitals. case of Siam, for example, the monarch played an
important role in introducing the hospital system.
Hospitals and Public Health On a temporary basis, hospitals had been estab-
State involvement in public health care was not lished in Siam,fromthe early nineteenth century, in
new to Southeast Asia. Departments of physicians order to care for the victims of epidemics (Yuwadee

1979; Muecke and Wichit 1989). In 1855 an offer of in other parts of the colony (Morin 1938; Worth
land and materials for the building of a hospital was 1985). Their purpose was initially military, being
made by the King to an American missionary doctor, intended to carry out research on the diseases — in
but was not taken up (Terwiel 1983). The first state- particular, dysentery and malaria - which severely
financed hospital, Siriraj (Wang Lang), was estab- affected French troops stationed in Vietnam.
lished at the order of the King following the cholera The British also founded research institutes. The
epidemic of 1881, and officially opened in 1888 London School of Tropical Medicine was opened in
(Sanguan 1973). Although it is probable that he was 1899 in order to undertake scientific inquiry into
counseled by the European and American doctors in tropical diseases, and to prepare medical officers for
Siam at the time, the Siamese monarch was well service in the Crown Colonies (Chai 1967). In 1901,
acquainted with Western medicine, having previ- in response to a request from the Resident-General
ously traveled to Singapore and Batavia, and there of the Federated Malay States, a Pathological Insti-
is no reason to doubt that the initiative came from tute, which later became the Institute for Medical
the Court (Yuwadee 1979). Research, was opened in Malaya (Chai 1967).
Medical services were initially staffed, in both colo- In the context of the development of the specialty
nial and noncolonial Southeast Asia, by European or of tropical medicine, the establishment of these in-
American doctors. Some attempts were made to stitutes has been viewed by some writers as "impe-
train local people in medical procedures, for exam- rial arrogance" (Owen 1987). Certainly, by their
ple, the dokter-djawa of Java, who carried out some focus on scientific research into diseases, rather
basic treatments (Boomgaard 1987; Gardiner and than public health measures, they served imperial-
Oey 1987). In general, however, access to a full West- ist ends in several ways (Worboys 1976; Owen
ern medical education was beyond the reach of most 1987). In the short term, it might therefore be ar-
Southeast Asians, and even where entry to medical gued that Southeast Asia did far more for Western
schools was possible, problems remained. For exam- medicine than Western medicine did for Southeast
ple, for some years after its opening in 1890, the Asia. Nevertheless, in the long term, Southeast
Western medical school established in Bangkok suf- Asians came to benefit substantially from the
fered a shortage of Siamese students, probably be- knowledge of disease that was generated by these
cause of the long, difficult nature of the course, its research institutes. The French laboratories in Viet-
expense, and the uncertain prospects facing gradu- nam were, for example, the site for important re-
ates (Yuwadee 1979). In Malaya, positions in the search on plague, smallpox, rabies vaccine. The
Civil Service were closed to non-Europeans and non- Malayan Institute was largely responsible for un-
Malays, thus denying Chinese doctors employment, dertaking the research that established the nutri-
regardless of their qualifications (Chai 1967). tional basis of beriberi, a discovery that was given
wide publicity at the first biennial meeting of the
Southeast Asian Disease and the Development Far Eastern Association of Tropical Medicine. This
of Western Medical Science conference, held in Manila in 1910, was attended by
Closely linked to the development of colonial medi- medical officers from most of the countries of the
cal services was the establishment of research insti- region (Bangkok Times Weekly Mail 1904; Chai
tutes for the study of "tropical diseases." From the 1967). The findings were subsequently dissemi-
standpoint of scientific inquiry, Southeast Asia had nated into areas of Southeast Asia that were out-
long played an important role in Western medicine. side direct colonial control, and otherwise unlikely
The region was an important source of Western ma- to benefit from the work of the research institutes.
teria medica such as cloves, menthol, camphor,
benzoin, and, after 1850, quinine. Southeast Asia The Impact of Western Medicine on Traditional
also figured prominently in the development of bo- Perceptions of Disease
tanical and pathological taxonomy, and a number of Indigenous views of disease were largely disre-
influential figures in the development of Western garded in the introduction of Western medical sys-
natural science traveled to the East Indies as doctors tems (Owen 1987). Even in Siam, where there was a
in the employ of the Dutch. degree of freedom in the adoption of Western-style
The first research institute concerned with tropi- medical education, traditional medicine was offi-
cal medicine, later to become known as the Pasteur cially neglected. In fact, it was originally omitted
Institute, was set up by the French in Saigon in from the curriculum of the medical school when that
1890, and a further three branches were established curriculum was set up under the direction of West-

ern doctors in 1889. Later, however, at the request of environment, its inhabitants, and the world outside.
the king, traditional medicine was included, but In this essay this interaction was examined over two
only as an optional subject; because of differences broad periods of time, the division of which was
between the Siamese and Western doctors engaged marked by the arrival of Europeans in the region.
to teach in the school, it was only in 1907 that How Southeast Asian peoples perceived and re-
courses in Siamese medicine became a compulsory sponded to disease prior to contact with the West
part of the curriculum (Yuwadee 1979). Tellingly, reflects the processes of localization seen in other
one reason for the pressure to introduce traditional aspects of their culture. Perceptions of disease were
medicine into the medical curriculum in Siam came dynamic, integrating features deriving from other
from doctors who had completed the course and gone regions of Southeast Asia, as well as from Chinese,
to work in provincial areas. They complained that Indie, and Islamic civilizations. These processes
they were unable to make use of indigenous medi- (which were evident in the naming of diseases), theo-
cines to treat patients when the scarce supplies of ries of causation, and therapy continued after con-
Western medicines and equipment were exhausted. tact with the West.
The doctors argued that if only they had had some With the development of large, more concen-
basic training in traditional medicine, they could be trated, populations in the region, different types of
of greater value to the provincial population disease became prevalent, most notably epidemics.
(Yuwadee 1979). The prominence of these diseases in accounts proba-
Although Western medicine may have been beyond bly served to enhance the notoriety of the region for
the reach of most Southeast Asians, it nevertheless unhealthiness, among both Asians and Europeans
produced changes in the ways in which those without (Schafer 1967). However, underlying these diseases
direct access perceived disease (Owen 1987). The and the many others that were less dramatic in their
germ theory of disease, for example, was integrated effects and that did not figure prominently in ac-
into indigenous beliefs regarding illness causation. counts were widespread poverty and poor nutrition.
For example, among the Agusan Manobo of Minda- These, rather than miasmas and steaming swamps,
nao there is a belief that disease may result from were the reasons for the prevalence of numerous
germs carried by supernatural agents (Montillo- diseases in the region. Thus, despite the introduc-
Burton 1982). However, in applying germ theory, a tion of public health measures, hospitals, vaccina-
distinction may be made by Southeast Asians be- tion, and eventually some of the other advances
tween diseases endemic to the region and those that made by medical science, what could have the great-
are "foreign." In this case, it is only the foreign dis- est effect on the prevalence of disease in the region
eases that are caused by germs (Montillo-Burton was the relief of poverty. This is still the case.
1982). Scott Bamber
In other cases, there appear to have been semantic
changes in traditional terms for illness in order to
Bibliography
accommodate Western disease categories. An exam- Abeyasekere, Susan. 1987. Death and disease in nine-
ple is the Thai term mareng, which (as discussed teenth century Batavia. In Death and disease in
earlier) in the past signified a "deep-seated ulcer" Southeast Asia: Explorations in social, medical and
and came to refer to cancer. Similarly, wannarok, the demographic history, ed. Norman G. Owen, 189—209.
currently employed Thai term for tuberculosis, for- Oxford.
merly referred to "illnesses involving infections or Ackerknecht, E. H. 1946. Natural diseases and rational
abscesses" (Bamber 1989). In both these cases, the treatment in primitive medicine. Bulletin of the His-
effect has been to emphasize one part of a wide tory of Medicine 19: 467-97.
semantic range, so that the resultant meaning con- Anuman Rajadhon. 1958. The expulsion of evil spirits. In
forms more closely to that of disease categories in Five papers on Thai custom, 5-8. Ithaca.
Western medicine. 1962. The khwan and its ceremonies. Journal of the
Siam Society 50: 119-64.
Bamber, S. 1989. Trope and taxonomy: An examination of
Conclusions the classification and treatment of illness in tradi-
Just as Southeast Asia is not unique in terms of its tional Thai medicine. Ph.D. thesis, Australian Na-
geography, so are its diseases, as seen in biomedical tional University. Canberra.
terms, not unique to this part of the world. The distinc- Bangkok Times. Daily newspaper. Bangkok.
tive profile of disease in the region is more the result Bangkok Times Weekly Mail. Weekly news summary.
of a complex interaction among the Southeast Asian Bangkok.

Blusse, Leonard. 1985. An insane administration and an mortality in Java, 1880-1940: The evidence of the
unsanitary town: The Dutch East India Company and colonial reports. In Death and disease in Southeast
Batavia (1619-1799). In Colonial cities, ed. Robert J. Asia: Explorations in social, medical and demo-
Ross and Gerard J. Telkamp, 65—85. Dordrecht. graphic history, ed. Norman G. Owen, 70-90. Oxford.
Boomgaard, Peter. 1987. Morbidity and mortality in Java, Gimlette, J. D. 1939. A dictionary of Malayan medicine.
1820—1880: Changing patterns of disease and death. London.
In Death and disease in Southeast Asia: Exploration Golomb, Louis. 1985. An anthropology of curing in multi-
in social, medical and demographic history, ed. Nor- ethnic Thailand. Urbana.
man G. Owen, 33-69. Oxford. Gumpodo, Theresa, John D. Miller, and Aloysia Moguil.
Boutin, Michael E., and Alanna Y. Boutin. 1987. Classifi- 1988. Village medical treatment among the coastal
cation of disease among the Banggi of Sabah. Anthro- Kadazan. The Sarawak Museum Journal 39: 149-67.
pological Linguistics 29: 157—69. Guy, J. 1982. Palm-leaf and paper. Melbourne.
Bradley, Dan B. 1967. Siamese theory and practice of Hall, D. G. E. 1981. The making of Southeast Asia. New
medicine, reprint. Sangkhomsat Parithat 5: 103—19. York.
Brown, C. 1987. The influenza pandemic of 1918. In Death Hanks, Jane R. 1963. Maternity and its rituals in Bang
and disease in Southeast Asia: Exploration in social, Chan. Ithaca.
medical and demographic history, ed. Norman G. Hanks, Lucien M., and Jane R. Hanks. 1955. Diphtheria
Owen, 235-56. Oxford. immunisation in a Thai community. In Health, cul-
Brun, Viggo, and Trond Schumacher. 1987. Traditional ture, and community, ed. B. D. Paul, 155-85. New
herbal medicine in Thailand. Berkeley. York.
Bulbeck, F. David. 1982. Continuities in Southeast Asian Hart, Donn V. 1969. Bisayan Filipino and Malayan hu-
evolution since the Late Pleistocene. M.A. thesis, Aus- moral pathologies: Folk medicine and ethnohistory in
tralian National University. Canberra. Southeast Asia. Ithaca.
Caraka. 1949. Caraka samhita. Jamnagar. Headley, R. K. 1977. Cambodian-English dictionary.
Chai Hon-chan. 1967. The development of British Malaya Washington, D.C.
1896-1909. Kuala Lumpur. Higham, Charles. 1989. The archaeology of mainland
Chou Ta-kuan. 1951. Memoires sur les coutumes du Southeast Asia. Cambridge.
Cambodge, trans. Paul Pelliot. Paris. Hong, Lysa. 1984. Thailand in the nineteenth century:
Coedes, G. 1941. L'Assistance medicale au Cambodge a la Evolution of the economy and society. Singapore.
fin du XIIe siecle. Revue MedicaleFrancaise d'Extreme- Houghton, P., and Warrachai Wiriyaromp. 1984. The peo-
orient 19: 405-15. ple of Ban Na Di. In Prehistoric investigations in
1975. The Indianized states of Southeast Asia. Canberra. northeastern Thailand, ed. C. Higham and Amphan
Cohen, Paul, and John Purcal. 1989. The political economy Kijngam, 391-412. Oxford.
of primary health care in Southeast Asia: Problems Hutchinson, E. W. 1933. The French Mission in Siam.
and prospects. In The political economy of primary Journal of the Siam Society 26: 1-72.
health care in Southeast Asia, ed. Paul Cohen and Hull, Terence H. 1987. Plague in Java. In Death and dis-
John Purcal, 159-76. Canberra. ease in Southeast Asia; Explorations in social, medical
Cook, James. 1968. Captain Cook's journal (1768-71). Li- and demographic history, ed. Norman G. Owen, 210-
brary Board of South Australia. 34. Oxford.
Crawfurd, John. 1820. History of the Indian archipelago. I Tsing. 1896. A record of the Buddhist religion as
Edinburgh. practised in India and the Malay archipelago (A.D.
Dampier, William. 1927. A new voyage around the world, 671-695) by I Tsing, trans. Junjiro Takakusu. Taipei.
ed. Sir Albert Gray. London. Jenner, Philip N. 1981. A chrestomathy of pre-Angkorian
Earmporn Thongkrajai, Pramote Thongkrajai, and J. E. Khmer, Vol. 2: Lexicons of the dated inscriptions.
Stoeckel. 1987. Socioeconomic and health program ef- Honolulu.
fects upon the behavioral management of diarrhoeal Kaempfer, E. 1906. The history of Japan, together with a
disease in northeast Thailand. Paper presented at the description of the history of the kingdom of Siam,
Department of Demography, Research School of Social trans. J. G. Scheuchzer. Glasgow.
Science, Australian National University. Kleinman, Arthur M. 1987. Symptoms of relevance, signs
Eisenbruch, M. 1983. "Wind illness" or somatic depres- of suffering: The search for a theory of illness mean-
sion? A case study in psychiatric anthropology. British ings. Semiotica 65: 163-71.
Journal of Psychiatry 143: 323-6. Koenig, J. G. 1894. Journal of a voyage from India to Siam
Endicott, K. M. 1970. An analysis of Malay magic. Oxford. and Malacca in 1779. Journal of the Royal Asiatic
Frake, Charles O. 1961. The diagnosis of disease among Society 26: 58-201.
the Subanun of Mindanao. American Anthropologist Kwa Tjoan Sioe. 1936. De gerzondheidstoestand der
63: 113-32. Chineezen in Nederlandsch-Indie. Koloniale Studien
Gardiner, Peter, and Mayling Oey. 1987. Morbidity and 20(5): 64-77.

Laderman, Carol. 1987. The ambiguity of symbols in the Asia: Explorations in social, medical and demo-
structure of healing. Social Science and Medicine 24: graphic history, ed. Norman G. Owen, 3—30. Oxford.
293-301. Pallegoix, Jean-Baptiste. 1854. Description du royaume
La Loubere, S. de. 1691. Du royaume de Siam. Amsterdam. Thai ou Siam. Paris.
Li, Fang-kuei. 1977. A handbook of comparative Tai. Pham, Dinh Ho. 1973. La Medecine vietnamienne au
Honolulu. XVIIIe siecle, trans. Nguyen Tran Huan. Bulletin de
Lord, Donald C. 1969. Mo Bradley and Thailand. Grand I'ecole frangaise d'extreme-orient 60: 375—84.
Rapids. Pietrusewsky, M. 1974. Non Nok Tha: The human skeletal
Lovric, Barbara. 1987. Bali: Myth, magic and morbidity. remains from the 1966 excavations at Non Nok Tha,
In Death and disease in Southeast Asia: Explorations N£. Thailand. Dunedin.
in social, medical and demographic history, ed. Nor- 1982. The ancient inhabitants of Ban Chiang. Expedi-
man G. Owen, 117-41. Oxford. tion 24: 42-50.
Macey, Paul. 1910. L'Art de guerir au Laos. Revue 1982-3. Pioneers on the Khorat Plateau: The prehis-
Indochinoise 13: 489-502. toric inhabitants of Ban Chiang. Journal of the Hong
Manderson, Lenore. 1981. Roasting, smoking and dieting Kong Archaeological Society 10: 90-106.
in cross-cultural perspective. Social Science and Medi- Pigeaud, T. G. T. 1967. Literature of Java. The Hague.
cine 15B:509-20. Quaritch Wales, H. G. 1983. Divination in Thailand.
1986. Food classification and restriction in peninsular London.
Malaysia: Nature, culture, hot and cold? In Shared Raharjo, Yulfita, and Lorraine Corner. 1989. Cultural atti-
wealth and symbol, ed. Lenore Manderson, 127-43. tudes to health and sickness in public health pro-
Cambridge. grammes: A demand-creation approach using data
1987. Blame, responsibility and remedial action: Death, from West Aceh, Indonesia. Paper presented at the
disease and the infant in early twentieth century Ma- Health Transition Workshop, National Centre for
laya. In Death and disease in Southeast Asia: Explora- Epidemiology and Population Health, Australian Na-
tions in social, medical and demographic history, ed. tional University, May 15-19.
Norman G. Owen, 257-82. Oxford. Reid, Anthony. 1988. Southeast Asia in the age of com-
Marr, David G. 1987. Vietnamese attitudes regarding ill- merce, 1450-1680, Vol. 1. New Haven.
ness and healing. In Death and disease in Southeast Robison, Richard. 1986. Indonesia: The rise of capital.
Asia: Explorations in social, medical and demo- Sydney.
graphic history, ed. Norman G. Owen, 162-86. Oxford. Sangermano, Vincentius. 1883. A description of the Bur-
Martin, Marie A. 1983. Elements de medicine tradi- mese empire, trans. William Tandy. London.
tionelle khmere. Seksa Khmer 6: 135-70. Sanguan Ankhong. 1973. Sing raek nai Mu'ang Thai.
McFarland, George B. 1944. Thai-English dictionary. Bangkok.
Stanford. Schafer, Edward H. 1967. The vermilion bird: Tang im-
Montillo-Burton, Erlinda. 1982. The impact of modern ages of the south. Berkeley.
medical intervention on the Agusan Manobo medical Shorto, H. L. 1971. A dictionary of the Mon inscriptions.
system of the Philippines. Ph.D. thesis. University of London.
Pittsburgh. Simons, R. C. 1985. The resolution of the latah paradox. In
Morin, M. 1938. Les Instituts Pasteur d'Indochine. In The culture-bound syndromes, ed. R. C. Simons and
L'Indochine Francaise: Recueil de notices r&digees a C. C. Hughes, 43-62. Baltimore.
I'occasion du X' congres de la Far Eastern AssociationSkeat, W. W. 1900. Malay magic: Being an introduction to
of Tropical Medicine, 289-413. Hanoi. the folklore and popular religion of the Malay penin-
Muecke, Marjorie A. 1979. An explication of "wind illness" sula. London.
in Northern Thailand. Culture, Medicine and Psychia- Snouck Hurgronje, C. 1893. The Acehnese, trans A. W. S.
try 3:267-300. O'Sullivan. Leiden.
Muecke, Marjorie A., and Wichit Srisuphan. 1989. Born Social Research Institute. 1986. Lanna literature: Cata-
female: The development of nursing in Thailand. So- logue of palmleaf texts on microfilm. Chiangmai.
cial Science and Medicine 29: 643-52. Terwiel, B. J. 1978. The Tais and their belief in khwans.
Mulholland, J. 1979. Thai traditional medicine: Ancient The South East Asian Review 3: 1-16.
thought and practice in a Thai context. Journal of the 1980-1. The Tai of Assam, Vol. 1. Gaya.
Siam Society 67: 80-115. 1983. A history of modern Thailand, 1767-1942. St.
1987. Medicine, magic and evil spirits. Canberra. Lucia.
Ohnuki-Tierney, Emiko. 1981. Illness and healing amongst 1987. Asiatic cholera in Siam: Its first occurrence and
the Sakhalin Ainu: A symbolic interpretation. Cam- the 1820 epidemic. In Death and disease in Southeast
bridge. Asia: Explorations in social, medical and demo-
Owen, Norman G. 1987. Towards a history of health in graphic history, ed. Norman G. Owen, 142—61. Oxford.
Southeast Asia. In Death and disease in Southeast 1988. Acceptance and rejection: The first inoculation

and vaccination campaigns in Thailand. Journal of
the Siam Society 76: 183-201. VI. 14
1989. Through travellers' eyes: An approach to early
nineteenth century Thai history. Bangkok.
Diseases and Disease Ecology
Thompson, V. 1967. Thailand: The new Siam. New York. of the Modern Period in
Ullmann, M. 1978. Islamic medicine. Edinburgh.
Unschuld, Paul U. 1982. Der wind als ursache des
Southeast Asia
krankseins. T'oung pao 68: 91-131.
Westermeyer, J. 1973. On the epidemicity of amok vio-
lence. Archives of General Psychiatry 28: 873-6. Southeast Asia can be visualized as the part of Asia
Wilson, Christine S. 1985. Malay medicinal use of plants. that spills into the sea, comprised of long coasts,
Journal of Ethnobiology 5: 123-33. tidal plains, peninsulas, and islands. There are high
Wisseman, Charles L., and Benjamin H. Sweet. 1961. The mountains, inland plains, plateaus, and upland val-
ecology of dengue. In Studies in disease ecology, ed. leys; nonetheless, to a very large degree, human
Jacques M. May, 15-43. New York. culture has developed with an acute awareness of
Wolters, Owen W. 1982. History, culture and region in water, from the sea, the rivers, and the monsoon
Southeast Asian perspectives. Singapore. rains. It is therefore not surprising that many of the
Worboys, Michael. 1976. The emergence of tropical medi- endemic health problems in the region are related to
cine: A study in the establishment of a scientific spe- water; indeed, since prehistoric times, nearly all ma-
cialty. In Perspectives on the emergence of scientific jor areas of habitation have been exposed to global
disciplines, ed. Gerard Lemaine et al., 75-98. The contact by water transport.
Hague.
Worth, Dooley, 1985. Health as a political decision: Pri- Maritime routes linking the littoral civilizations
mary health care in the Democratic Republic of Viet- of the Eurasian landmass have passed through
nam. Ph.D. thesis, New School for Social Research. Southeast Asia for more than two millennia. We can
New York. accordingly assume that from early times the region
Wyatt, David K. 1984. Thailand: A short history. Bangkok. experienced all of the epidemic diseases familiar to
Yuwadee Tapaneeyakorn. 1979. Wiwatthanakan khong the ancient world. What inhibits discussion of dis-
kanphaet Thai tangtae samai roemton chonthu'ng eases in the earlier historical periods of Southeast
sinsut rachakan Phrabatsomdet Phrachunlachom- Asia is the lack of data. Because of the prevailing
klawchawyuhua. M.A. thesis, Department of History, tropical-equatorial climate, the preservation of writ-
Chulalongkorn University, Bangkok. ten records has, until recently, required greater ef-
fort than most human societies were prepared to
make. Our first information comes from the observa-
tions of Chinese annalists, whose works survived in
the temperate climate of northern China. As the
Chinese moved southward into what is today north-
ern Vietnam, they recorded perceptions of disease
associated with what for them were southern lands.
Most prominent among the health problems en-
countered by ancient Chinese armies in Vietnam
were malaria and other "fevers" associated with the
monsoon rain season. Chinese generals timed their
expeditions into Vietnam to coincide with the dry
season, from November to May. When, in 542, ill-
informed imperial officials ordered a reluctant army
to move into Vietnam during the rainy season, 60 to
70 percent of the army was soon reported dead from
fevers (Taylor 1983). Earlier, the general of a Chi-
nese army encamped in Vietnam during the rainy
season of A.D. 42 described the scene as a kind of
exotic hell: "Rain fell, vapors rose, there were pesti-
lential emanations, and the heat was unbearable; I
even saw a sparrowhawk fall into the water and
drown!" (Taylor 1983).

VI. 14. Modern Period in Southeast Asia 441
It became customary for Chinese generals to ex- Beginning in the late nineteenth century, malaria
plain their failures in Vietnam in terms of "miasmal became a problem on a larger scale than had been
exhalations" by which they associated the heat and previously known because of circumstances associ-
humidity of the area with disease. One of the most ated with the development of colonial and semico-
famous episodes of disease among soldiers was in lonial economies. These included the improvement
605 after a Chinese army successfully plundered a of communication systems, large-scale population
Cham city in the vicinity of modern Da Nang, on movements, the opening of new ricelands, and the
what is today the central coast of Vietnam: The extension of urban settlement. All of these changes
army nearly disappeared when it was struck by an required relatively large-scale construction and engi-
epidemic on its return northward (Taylor 1983). This neering projects that opened new areas congenial to
disease was not malaria, but may have been cholera, certain mosquito species and to epidemics that deci-
smallpox, or possibly even plague. In 627, a promi- mated cattle populations, thereby turning mosqui-
nent Chinese official refused an imperial order to toes toward human beings (Boomgaard 1987).
serve as governor of the Vietnamese territories on In the early 1950s, when the Malayan emergency
the grounds that in Vietnam "there is much ma- resulted in the resettling of large numbers of people
laria; if I go there I shall never return." He ulti- into crowded lowland camps, an observer noted that
mately chose to be beheaded for insubordination the health of the population improved the farther
rather than accept the assignment (Taylor 1983). upriver one went; the same observer argued that
Previously in 136, a Chinese official had argued upland peoples who had been resettled in more
against sending an army to Vietnam because, densely populated areas near the sea experienced an
among other reasons, the anticipated losses to dis- "accentuation of an already existing pattern of dis-
ease would require the sending of reinforcements ease" as a consequence of "the loss of interest in life
who would be disaffected at being ordered into a due to the breakdown of the old culture" (Polunin
pestilential region (Taylor 1983). The failures of Chi- 1952). It may be that any disease ecology must also
nese invasions against Vietnam in 980-1 and 1176- take into account the political and psychological con-
7 were accompanied by large losses of manpower to ditions of a population.
malaria. Another observer has claimed that cultural fac-
Generally, malaria has never been a serious prob- tors can be important in the experience of disease
lem in preurban lowland areas where waterworks and illness, that there is a relationship between dis-
are kept in good repair and the population is at ease and social marginality, and that the incidence
peace (Fisher 1964). Those species of anopheline mos- of disease can operate as a mechanism of social con-
quitoes that breed in the swamps, irrigation canals, trol enforcing respect for authority. In fact, he has
and ricefields of the lowlands tend to prefer the blood written that "the social system tends to precipitate
of animals; and since animals are not susceptible to events which validate the medical beliefs, and this
human malaria and therefore do not provide a reser- in turn affirms the principles upon which the social
voir for the disease, these mosquitoes normally do structure is based" (Feinberg 1979). It is relatively
not carry malaria (Stuttard 1943). On the other easy to discuss this approach in relation to the prac-
hand, those species of Anopheles that breed in the tice of medicine in premodern societies (Lan-Ong
shady, cool water of streams in the foothills and 1972), but contemporary attitudes toward modern
mountainous areas are strongly attracted to human medicine tend to resist this line of analysis.
blood and are dangerous vectors of malaria (Stuttard Beginning in the tenth century, Southeast Asians
1943; Fisher 1964). began to record observations and write annals that
Chinese armies entering Vietnam by land must provide local information, first in Vietnam and
pass through upland areas where malaria is endemic. eventually in Thailand, Burma, Cambodia, and
This fact, along with the desire to achieve the advan- Java. Epidemics are mentioned regularly, particu-
tage of surprise, explains why Chinese generals, hav- larly in times of warfare, though it is very difficult
ing had the luxury of water transport and enough to determine with certainty what diseases were be-
time to lay plans without haste, preferred to invade ing observed. Some modern researchers believe that
Vietnam by sea (Taylor 1983). Malaria became a cholera was absent from Southeast Asia until the
threat in populated lowlands only when warfare or 1820s, and bubonic plague was likewise absent un-
other disorders led to large-scale slaughtering of ani- til 1911. The evidence, however, is ambiguous
mals, a scattered population, and a breakdown of the (Boomgaard 1987; Hull 1987; Terwiel 1987; R«id
water control system (Murphy 1957). 1988). The great outbreaks of cholera and bubonic

plague in the nineteenth and twentieth centuries tion, blood diseases of the tropics, hemoglobinop-
were apparently related to the circumstances of Eu- athies and other genetic factors, as well as snake
ropean colonial expansion in the region and repre- and other venomous bites (South East Asian Re-
sented a more virulent experience of these diseases gional Centre for Tropical Medicine 1967).
than can today be imagined for earlier times. South- In the same year, South Vietnamese disease spe-
east Asia's historic openness to maritime trade and cialists identified malaria and plague as their great-
the global contacts that went with it surely resulted est problems and categorized "endemic infections"
in a measure of immunity being built up in the as follows: bacteriological (cholera, salmonellosis,
population against the diseases common to interna- bacillary dysentery, and typhoid), parasitic (amebia-
tional entrepots. sis, ascariasis, hookworm infections, gnathostomia-
A relatively dispersed village settlement pattern sis, strongyloidiasis, diphyllobothriasis, spargano-
and the Southeast Asian habit of bathing frequently sis, and taeniasis), viral (hemorrhagic fever and
are two other factors that appear to account for what dengue fever, smallpox, infectious hepatitis, Japa-
has been called the "relatively mild epidemic cyle" nese B encephalitis, and rabies), bacterial (leprosy
in premodern times (Reid 1988). The most serious and venereal diseases), and mycotic (cutaneous
epidemic disease, according to Siamese chronicles mycoses) (South East Asian Centre for Tropical
from the fourteenth century and European observers Medicine 1967).
in the sixteenth and seventeenth centuries, was What can be emphasized is that a very large per-
smallpox (Terwiel 1987; Reid 1988). Leprosy and centage of these diseases are waterborne or are trans-
yaws also figured prominently in early European mitted by a parasite that depends upon a water-
perceptions of disease in Southeast Asia, probably dwelling host such as the snail. In a region where a
because of their disfiguring effects (Reid 1988). large part of the population is involved in paddy
Plague, according to French observers in Indochina, agriculture requiring barefoot work infieldscovered
was found only where there were large numbers of with water, where sanitation depends upon the com-
Chinese, namely port cities with a concentration of mon use of rivers and ponds, and where nearly half
ships, large stores of grain, and consequently an of each year is a time of heavy rainfall, such diseases
abundance of rats (Stuttard 1943). In the 1960s, by account for much of the burden of unhealthiness.
which time plague had been eradicated in most of Dysentery, amebic infections, intestinal worms, and
Southeast Asia, outbreaks still occurred in Vietnam skin afflictions are endemic. The linkage between
as a result of wartime conditions (South East Asian health and seasonality is obvious to any observer
Regional Centre for Tropical Medicine 1967). and has been an object of study in recent years. The
From the 1960s, there has been a growing litera- wet season, in addition to providing an environment
ture enumerating and analyzing diseases in South- in which many disease vectors thrive, is also a time
east Asian countries, particularly Thailand. The of food shortages and of a consequent relative in-
category of "tropical diseases" is sometimes used to crease in poverty and decrease in physical well-
emphasize that most of the health problems encoun- being. Women and children are particularly at risk
tered in the region are now seldom seen in temper- during this time (Charles 1979). This writer was in
ate climates. The 1967 syllabus of the "tropical Hanoi in May 1986 during the onset of the rainy
medicine" course at Bangkok's University of Medi- season and saw that within a few days a large part of
cal Science, Faculty of Tropical Medicine, covered the population had become ill with fevers and other
the following illnesses, all identified as "common "flu" symptoms; local people considered this a nor-
diseases": (1) viral, such as smallpox, rabies, mal phenomenon.
dengue, hemorrhagic fever; (2) rickettsial, such as Medically trained observers in Southeast Asia
typhus fever; (3) bacterial, such as typhoid fever, have difficulty in determining mortality statistics.
bacillary dysentery, food poisoning, cholera, leprosy, Such compilation efforts are complicated by the fact
and plague; (4) spirochetal, such as amebiasis, ma- that although death may be occasioned by the onset
laria, kala-azar, and giardiasis; (5) helminthic, such of a particular disease, such as malaria, the person's
as hookworm infection, ascariasis, trichuriasis, en- inability to resist the disease is generally due to
terobiasis, strongyloidiasis, gnathostomiasis, filaria- prior debilitation from a combination of other afflic-
sis, fasciolopsiasis, and paragonimiasis; (6) nutri- tions, such as intestinal parasites and nutritional
tional, such as protein-calorie deficiencies, mineral deficiencies (Institute for Population and Social Re-
and vitamin deficiencies, and food toxicants; and (7) search 1985).
miscellaneous, such as effects of heat, heat exhaus- Beriberi, caused by vitamin B deficiency, was in

VI. 14. Modern Period in Southeast Asia 443
premodern times largely confined to the islands of Bibliography

eastern Indonesia where sago rather than rice was Abeyasekere, Susan. 1987. Death and disease in nine-
the main dietary staple (Reid 1988); recently, how- teenth century Batavia. InDeath and disease in South-
ever, it has become a more general regional phe- east Asia, ed. Norman G. Owen, 189-209. Singapore.
nomenon as a result of the increasing use of polished Boomgaard, Peter. 1987. Morbidity and mortality in Java,
rather than whole-grain rice (Fisher 1964). Beriberi 1820-1880: Changing patterns of disease and death.
In Death and disease in Southeast Asia, ed. Norman
was first reported by the Portuguese in Southeast
G. Owen, 48-69. Singapore.
Asia during the sixteenth century, and the term is of
Brown, Colin. 1987. The influenza pandemic of 1918 in
Malay derivation (Reid 1988). Indonesia. In Death and disease in Southeast Asia, ed.
The ecology of disease in Southeast Asia is cur- Norman G. Owen, 235-56. Singapore.
rently in a period of rapid and significant change, Charles, Robert. 1979. Health, agriculture, and rural pov-
the beginning of which is usually dated around erty: Why seasons matter. Brighton.
1970. For one thing, except for infants and children Feinberg, Richard. 1979. Anutan concepts of disease.
under 5 years, infectious diseases are no longer a Honolulu.
significant threat to health. Tuberculosis remains a Fisher, C. A. 1964. South-east Asia. London.
hazard for the aged population (which has grown), Gardiner, Peter, and May ling Oey. 1987. Morbidity and
and malaria remains endemic in many areas, but, in mortality in Java, 1880-1940: The evidence of the
general, tuberculosis, pneumonia, malaria, diar- colonial reports. In Death and disease in Southeast
rheal diseases, and nutritional deficiencies, along Asia, ed. Norman G. Owen, 70-90. Singapore.
Hull, Terence H. 1987. Plague in Java. In Death and dis-
with other infectious diseases, have declined. On the
ease in Southeast Asia, ed. Norman G. Owen, 210—34.
other hand, death rates for heart-related diseases, Singapore.
cancer, and accidents along with violent deaths have Institute for Population and Social Research. 1985. The
significantly increased (Institute for Population and morbidity and mortality differentials. ASEAN Popula-
Social Research 1985). Increasing attention is being tion Programme Phase III, Thailand: A report on the
given to the problem of infant mortality, for persons secondary data analysis. Bangkok.
under 5 years have benefited least from the overall 1988. The morbidity and mortality differentials. ASEAN
improvement in health. Diseases of pregnancy, deliv- Population Programme Phase III, Thailand, country
ery, and puerperium have also become more promi- study report. Bangkok.
nent of late. In addition, cirrhosis of the liver and Kanchanaraksa, Sukon, ed. 1987. Review of the health
hepatitis have appeared as significant health prob- situation in Thailand, priority ranking of diseases.
lems (Institute for Population and Social Research Bangkok.
1988). Lan-Ong. 1972. Thuong Kinh-Ky-Su. Paris.
Lovric, Barbara. 1987. Bali: Myth, magic and morbidity.
The rise in noninfectious diseases, namely coro- In Death and disease in Southeast Asia, ed. Norman
nary-cerebrovascular diseases and malignant neo- G. Owen, 117-41. Singapore.
plasm (cancer), is primarily a phenomenon of the Manderson, Lenore. 1987. Blame, responsibility and re-
large urban centers such as Bangkok. It is believed medial action: Death, disease and the infant in early
to come not only from improvements in diagnosis twentieth century Malaya. In Death and disease
but also, in the words of a Thai government report, in Southeast Asia, ed. Norman G. Owen, 257—82.
from "real increases in the incidence rate due to Singapore.
various environmental hazards of the present living Marr, David G. 1987. Vietnamese attitudes regarding ill-
conditions" (Kanchanaraksa 1987). ness and healing. In Death and disease in Southeast
Asia, ed. Norman G. Owen, 162-86. Singapore.
Larger proportions of the populations of the South-
Murphy, Rhoads. 1957. The ruin of ancient Ceylon. Jour-
east Asian countries are increasingly concentrating nal of Asian Studies 16:181-200.
in major urban centers. Living conditions in these Owen, Norman G. 1987a. Toward a history of health in
places are increasingly exposed to the chemical envi- Southeast Asia. In Death and disease in Southeast
ronment of modern industry and to the emotional Asia, ed. Norman G. Owen, 3-30. Singapore.
pressures of modern business activity. As Southeast • 1987b. Measuring mortality in the nineteenth century
Asia is integrated into a global system of manufac- Philippines. In Death and disease in Southeast Asia,
turing and markets, we can expect that its disease ed. Norman G. Owen, 91-114. Singapore.
ecology will begin to display characteristics already Polunin, Ivan. 1952. Studies on the diseases of the aborig-
familiar to areas where this system has been in ines and other peoples of the Malay Peninsula. Doctor
place for several decades. of Medicine thesis, University of Oxford, The Queen's
College.
Keith W. Taylor

Reid, Anthony. 1987. Low population growth and its nating Board convened by the government of Thailand
causes in pre-colonial Southeast Asia. In Death and with the cooperation of the Southeast Asian Ministries
disease in Southeast Asia, ed. Norman G. Owen, 3 3 - of Education Secretariat at the Faculty of Tropical
47. Oxford and Singapore. Medicine, University of Medical Science. Bangkok.
1988. Southeast Asia in the age of commerce 1450-1680, Taylor, K. W. 1983. The birth of Vietnam. Berkeley.
Vol. 1: The lands below the winds. New Haven. Terwiel, B. J. 1987. Asiatic cholera in Siam: Its first
Stuttard, J. C , ed. 1943. Indo-China. London. occurrence and the 1820 epidemic. In Death and dis-
South East Asian Regional Centre for Tropical Medicine. ease in Southeast Asia, ed. Norman G. Owen, 142-
1967. Report of the first meeting of the Central Coordi- 61. Singapore.

PART VII
The Geography of Human Disease

VII. 1. Sub-Saharan Africa 447
the continent by at least 40,000 years ago. Scattered

VII. 1 bands of stone-age hunter-gatherers spread lightly
Disease Ecologies of over the entire continent. Signs of permanent settle-
ment by fishermen around lakes and rivers are evi-
Sub-Saharan Africa dent in eastern Africa and places that are now in the
Sahara from about 7000 B.C. Knowledge of stock-
raising diffused from southwest Asia from about
Disease Patterns Before A.D. 1000 5500 B.C., and agriculture followed the same course
The prevalence and distribution of diseases in sub- shortly afterward. The Sahara region did not begin to
Saharan Africa have been determined by the natu- become a desert until about 2500 B.C., so these devel-
ral environment, indigenous living patterns, and the opments first reached peoples in and just south of the
interrelationships between African peoples and new- present Sahara. Here the new ways of life allowed
comers from other continents. The spread of agricul- the gradual development of settled village life, popu-
ture since about 3000 B.C.; the extensive commer- lation growth, the rise of political and economic spe-
cial contacts with the Moslem world from about A.D. cialization, and, in general, the more complex soci-
1000, and with Europe since the fifteenth century; eties associated with the Neolithic "Revolution." Iron
and the establishment of colonial rule in the late technology diffused from the North African coast to
nineteenth century - all have had important conse- what is now the West African savanna by about 300
quences for health conditions in Africa. B.C., giving peoples in the belt south of the desert,
There is little evidence about the disease environ- the ancestors of most modern black Africans, an addi-
ment confronting Africans until fairly recent times. tional advantage over more isolated populations fur-
Literacy dates back to only about A.D. 1000, and ther south.
then only in Ethiopia and some areas of the savanna As of the first or second century B.C., demographic
zone just south of the Sahara desert. Written ac- growth among these iron-age, agricultural groups
counts of conditions on parts of the western and was encouraging them to expand southward against
eastern coasts begin with the Portuguese voyages of weaker, less numerous hunting and gathering peo-
the fifteenth and sixteenth centuries, but literary ples. Peoples ancestral to the modern pygmies proba-
information on most of the vast interior is not avail- bly dominated much of the forest. Further south
able until well into the nineteenth century. Serious were the ancestors of the Khoisans, who once inhab-
medical data collection really began with the colo- ited most of the southern third of Africa, but are now
nial period, but even today knowledge of disease restricted to parts of the Kalahari and bordering
incidence and prevalence is far from adequate. regions. In the west the farming peoples soon
Africa south of the Sahara is a vast area with reached a barrier, the Gulf of Guinea, but members
many different ecological zones. Besides the Sahara of one linguistic group in the borderlands of modern
itself, there are extensive desert regions in the Horn Nigeria and Cameroun had a continent before them.
of northeastern Africa, and the Kalahari in Namibia For roughly 2,000 years these technologically supe-
and Botswana in the southwestern part of the conti- rior peoples have been gradually colonizing half a
nent. Tropical rain forest prevails along most of the continent, driving away, killing, or absorbing most
west coast, in the Zambezi valley of Mozambique, of the indigenous groups. The descendants of these
and in large areas of western equatorial Africa, in- people, speakers of languages of the Bantu family,
cluding much of Gabon, Congo-Brazzaville, and now dominate most of the continent from the equato-
northern Zaire. Forest, however, covers only about rial forest almost to the southern tip.
10 percent of the land area. Rolling grassland, often
called savanna or sudan, predominates between the Disease Patterns from A.D. 1000 to 1500
desert-edge lands and the forest, both north and By about A.D. 1000, most of the better agricultural
south of the equator. The desert and the equatorial lands had been settled by village farmers. There was
forest have always been relatively sparsely popu- still a frontier in the extreme south, and pastoral
lated; most Africans have always lived in coastal groups were important in and near the deserts and in
West Africa or the savanna areas north and south of parts of the East African interior, but the pygmy and
the equatorial forest. Khoisan peoples were increasingly being pushed
Paleontological studies indicate that hominids al- into pockets of marginal jungle or desert - a process
most certainly evolved in Africa, and our species, that has continued until the present. Farming was
Homo sapiens, probably was widely distributed over often of a slash-and-burn type, with villages moving

448 VII. The Geography of Human Disease
to seek new lands at intervals of several years to a equatorial forest, probably had had at least limited
generation or more, but hundreds of people often experience with most of the infectious diseases com-
lived close together in compact, relatively perma- mon to the Eurasian land mass. There was some
nent settlements. Small cities began to develop in attenuation, however, due to distance and relative
response to long-distance trade in parts of the west- isolation, as well as modifications from the tropical
ern Sudan and along the east coast. environment and the fairly low average population
These long, complex processes must have had im- density. The disease mixture would be enriched and
portant implications for health conditions. Hunting- the frequency of outbreaks increased in later centu-
gathering populations were too sparse to support ries as a result of more intensive commercial and
many acute diseases, especially smallpox, measles, other contacts with the Moslem world and with west-
poliomyelitis, chickenpox, and other viral infections ern Europe.
that produce long-lasting immunities. They were mo- We have little direct knowledge of health condi-
bile enough to avoid living for long in close proxim- tions before about 1500, but scattered data and infer-
ity to accumulations of their own wastes. ences from more recent times allow some general, if
Village life, on the other hand, whether based on somewhat speculative, comments. Many Africans
fishing and intensive collecting or on agriculture, suffered from a wide range of intestinal parasites
put much larger numbers of people in close, continu- spread by the fecal-oral route, and from dysentery
ous contact in fixed places. Diseases of crowds, like and other bacterial and viral diseases associated
many of those caused by respiratory transmission of with poor sanitation, although cholera did not exist
common bacterial and viral infections, could be here until it was imported from Asia in the nine-
readily transmitted. Disposal of wastes and contami- teenth century.
nation of water became problems, and failure to Some have argued that there is an old focus of
solve them resulted in much greater opportunities plague in central Africa, but the evidence for this is
for the spread of gastrointestinal infections, such as not compelling, and it is not clear that plague had
dysentery and diarrhea of various etiologies, as well any real importance in Africa before the late nine-
as Ascaris, Trichuris, and other parasitic worms. teenth century. Smallpox was known in Egypt by the
Hookworm, transmitted by fecal contamination of sixteenth century B.C., and may have been epidemic
soil, was also common in many places. Villages and in Ethiopia as early as 570. South of the Sahara,
land cleared for agriculture helped provide breeding smallpox and perhaps also measles were probably
sites for the mosquito vectors of malaria, yellow fe- uncommon and tended to occur in epidemic form at
ver, and filariasis. Animal husbandry also provided long intervals. Respiratory infections like pneumo-
enhanced opportunities for transmission of beef and nia were uncommon, and tuberculosis was rare or
pork tapeworms, anthrax, and other diseases. Ani- absent, except perhaps in trading towns. Cerebrospi-
mal manure attracted disease-carrying flies. In Af- nal meningitis probably did not appear until the late
rica, as elsewhere, the price for the advantages of nineteenth century. Guinea worm and schistosomia-
village life and a more reliable and abundant food sis were, then as now, focal waterborne infections
supply was a dramatic increase in the variety and with high prevalence rates in some localities.
frequency of infectious diseases. Except in the deserts, malaria was ubiquitous. It
Africans gradually developed immunologic and tended to spread in the forest as land clearance for
cultural defenses against many of these diseases, farming created better breeding sites for Anopheles
and population grew, although much more slowly mosquito vectors. The antiquity of falciparum ma-
than in recent decades. Although direct evidence is laria is indicated by the widespread prevalence of
lacking, it is likely that the pool of diseases afflicting sickle cell trait, a costly but effective genetic de-
sedentary populations was especially deadly for in- fense. Most African groups lack Duffy antigen,
digenous hunting-gathering groups beyond the ex- probably another old genetic adaptation, which pro-
panding agricultural frontier. As in the Americas, tects them against vivax malaria. Yellow fever ex-
Australia, New Zealand, and probably also Siberia, isted in forest areas, but attacked mainly children
diseases from what William McNeill has called "civi- and may have caused relatively little harm. Yaws
lized disease pools" helped to pave the way for new- and leprosy were especially prevalent in moister cli-
comers by killing large numbers of the aboriginal mates. Trachoma was more common in arid regions.
populations. Gonorrhea probably had been established by the
By about A.D. 1000 the more densely inhabited first century A.D., at least in the towns of the west-
portions of Africa, or at least those north of the ern Sudan, but syphilis was a post-Columbian im-

VII.l. Sub-Saharan Africa 449
port via Europe and North Africa. Human and ani- Town in 1652, smallpox epidemics introduced by sea
mal trypanosomiasis occurred in places where tsetse in 1713, 1755, and 1767 had serious demographic
flies lived. Then, as now, animal trypanosomiasis consequences for the colonists and were devastating
prevented stock raising in forest areas. Pockets of for the indigenous and already hard-pressed Khoi
savanna bush were infested with flies carrying both pastoralists. On the east coast, it is likely that small-
human and animal pathogens; these places were pox was an early accompaniment of the Indian
generally known and avoided. Ocean trade, but there is little evidence for it in the
pre-European period. The Portuguese recorded a ma-
Disease Patterns of 1500-1900 jor epidemic in 1589. Smallpox diffusion into the
More intensive trade and political contacts with the East African interior probably occurred later than in
outside world, especially Europe, developed from the West Africa because of weaker trade networks; it
sixteenth to mid-nineteenth centuries. These con- may date back only to about 1800.
tacts, accompanied by more extensive long-distance Measles and chickenpox were probably also intro-
trade within Africa and by widespread patterns of duced by traders from time to time, but there is
political centralization, helped to spread many infec- little documentation. Tuberculosis probably reached
tious diseases. coastal West Africa in the early days of contact, but
Europeans and Africans began a long commercial it did not become widespread until after 1900. Vene-
relationship with the arrival of the Portuguese in real diseases were a different story; syphilis and
the fifteenth century. Trade grew rapidly over the gonorrhea were common among coastal groups by
centuries, and came to involve most of the states of the eighteenth century, and these diseases must
western Europe and the Americas and, directly and have spread inland as well. Gonorrhea may well
indirectly, most African groups living within a few have been an indigenous disease whose diffusion
hundred miles of the sea. Coastal African merchants was facilitated by new conditions; syphilis almost
sold slaves, ivory, gold, dyewood, and other commodi- certainly arrived from the outside world.
ties for cloth, guns, metal goods, tobacco, alcoholic Trans-Saharan trade had existed for centuries
beverages, and other manufactured items. African prior to 1000, and no doubt the caravans, like the
products were obtained by trade networks extending sailing ships, sometimes were accompanied by infec-
far into the interior. Negotiations between the tious diseases. Smallpox could well have reached the
coastal middlemen and foreigners were often long Sudanese market towns, either with infected mer-
and complex, providing ample opportunities for ex- chants or in goods. Tuberculosis, measles, and gonor-
changes of pathogens; the trade routes provided rhea no doubt diffused from North Africa with trade,
paths for diseases to spread into the interior. although they may have already existed in the sa-
Among the most important and best documented vanna. Similarly, the extensive pre-European trade
diseases in early African history was smallpox. Al- along the east coast, between the Swahili towns and
though it was widespread in North Africa by the merchants from India, Persia, and Arabia, must
seventh century, and had almost certainly reached have resulted in some disease transmission.
the western Sudan as a by-product of the trans- It is clear, despite the weakness of the data, that
Saharan caravan trade by about A.D. 1000, small- contacts with Europeans and other foreigners had
pox may not have been indigenous to the western serious disease consequences for many African peo-
coast or the southern half of the continent until the ples in the precolonial period, especially those along
seventeenth century. Ships brought infection from the west and east coasts and in the market centers
abroad or carried it from place to place along the for the Sudan. However, although some small groups
coast at irregular intervals, after enough time had may have suffered heavily, there was no postcontact
passed to allow the appearance of a new generation pattern of mass death in Africa similar to what oc-
of susceptibles. An epidemic caused great loss of life curred in parts of the Americas or the Pacific. Afri-
along the Gold Coast in the 1680s, and by at least cans shared enough of the Old World disease pool to
1700 some West African peoples had adopted or in- avoid major demographic disaster. Stronger social
vented variolation techniques. Smallpox epidemics systems of African peoples may also have played a
were frequent in the eighteenth and nineteenth cen- role in their enduring and recovering from great
turies, and a major shipborne outbreak swept the epidemics. Even with the drain of the Atlantic,
whole coast as far south as Gabon and Angola in the trans-Saharan, and Indian Ocean slave traders, Af-
early 1860s. In South Africa, where the Dutch East rica was not depopulated. Disease resistance, strong
India Company had established a colony at Cape local social and political systems, and the introduc-

tion of new food crops like maize and manioc helped the twentieth century. Other African diseases, in-
to sustain populations. cluding onchocerciasis, filariasis, Schistosoma man-
The African disease environment did have very soni infection, and yaws, also became established in
serious consequences for foreigners. We still know American foci.
relatively little about how Moslem traders fared, but Cosmopolitan diseases like dysentery and small-
North African visitors to the Sudan did try to finish pox were frequently introduced into ports along with
their business before the rainy season brought ma- cargoes of slaves. In Brazil, slave imports often rose
larial fevers, and Omani Arabs suffered severely when there was drought and famine in Angola.
from falciparum malaria on the Swahili coast. Drought conditions caused people to migrate in
The fate of Europeans on the west coast is much search of food; they tended to congregate, often as
better documented. "Fevers" and "fluxes" - espe- defenseless, disorganized refugees, in areas where
cially malaria, yellow fever, and the dysenteries - they could find sustenance. Such aggregations en-
took a frightful toll among sailors, soldiers, traders, couraged flare-ups of endemic smallpox as well as
missionaries, explorers, and slavers. Studies of Brit- the depredations of slavers. The virus was often
ish, Dutch, and French experiences have shown that transported by captives, and there is a strong correla-
death rates of 50 percent in a year were not uncom- tion between smallpox epidemics in Brazil and in its
mon. It is possible that Portuguese death rates were Angolan slave supply territory.
somewhat lower, but they too paid a heavy price for In sum, the biological consequences of the African
their African commerce. Mortality prevented any slave trade included millions of deaths in the Ameri-
serious European military activity in most of West cas, among both Europeans and Indians. African la-
Africa; maintaining weak, sickly garrisons in a few bor was crucial in many New World economies, but
coastal forts was all that they could normally do. the demographic costs were enormous for inhabit-
Disease not only helped save West Africans from ants of North and South America and for European
European encroachment, but also gave them a con- sailors on slave ships, as well as for sub-Saharan
siderable commercial advantage. African merchants Africa. Indeed, at least in the United States, the
could, and frequently did, drag out trade negotia- demographic balance was almost certainly unfavor-
tions, knowing that the Europeans were anxious to able. About 300,000 Africans were imported, proba-
complete a deal and leave before the fevers began to bly far fewer than the number of whites who died of
reduce their numbers. The limited Portuguese expan- falciparum malaria, yellow fever, and hookworm in-
sion in northern Angola, although hampered by dis- fection from the eighteenth to the early twentieth
ease, took place in a drier area where malaria was centuries. The period of the European conquest of
not as serious as elsewhere on the western coast. Africa and the consolidation of colonial rule, roughly
European colonization at the Cape was possible only from 1880 to 1920, was the most deadly period
because the Dutch were operating south of the tropi- in history for much of the continent. West Africa,
cal disease environment. perhaps because of its earlier experience with intro-
Africa was more important as a donor than as a duced epidemics, did not suffer as severely as por-
recipient in the post-Columbian exchange of dis- tions of equatorial, East, and central Africa. Intensi-
eases. Falciparum malaria and yellow fever reached fied long-distance trade, warfare, labor demands,
Europe from time to time, but probably did not have and famine characterized this era, as many African
major demographic consequences there. Much more peoples found their relative isolation shattered. Peo-
significant was the transfer of African diseases to ple, pathogens, and vectors all moved, and there
the New World, mostly as a by-product of the slave were radical changes in living conditions. Small-
trade. Falciparum malaria and yellow fever played a pox spread widely, especially in East Africa, where
major role in the population history of the warmer coastal Moslem merchant caravans had begun to
parts of the Americas, from the southern United operate in the interior from the 1830s. Cholera was
States to southern Brazil. Whites suffered severely, introduced several times into East Africa and dif-
and these diseases were leading causes of deaths fused over the trade routes, with an especially de-
among the American Indians, especially in the Ca- structive epidemic occurring in the 1850s. Cerebro-
ribbean basin. The African hookworm, misnamed spinal meningitis epidemics appeared, probably for
Necator americanus, came over in the bodies of en- the first time, in the western Sudan in the 1880s;
slaved Africans, and was a very serious cause of there were several great epidemics there and in
sickness and death in the southern United States parts of the Anglo-Egyptian Sudan and East Africa
and in much of the West Indies and Brazil well into during the twentieth century. On a less spectacular

VII. 1. Sub-Saharan Africa 451
but still important level, even short-distance moves disability, or a loss of digits or limbs. Native to Bra-
might bring people into contact with antigenically zil, the fleas were introduced into the Senegambia
novel strains of familiar organisms, such as the proto- region about 1800, and to the Angolan coast about
zoa that caused malaria and amebic dysentery. 1850. From Angola they spread over central and
Tuberculosis, noted in the coastal towns of West East Africa in a few decades, causing great misery in
Africa around the turn of the century, spread slowly any given place, until people learned how to remove
inland. In the Cape Verde Islands migrants return- them.
ing from the United States facilitated the spread of
infection by the 1880s. The rise of the mining indus- Disease Patterns of 1900-60
try in South Africa and the Rhodesias was dependent The most explosive and most destructive epidemic
on migrant labor. Poor conditions in the mines in the ever to strike Africa was the influenza pandemic of
early twentieth century led to extremely high tuber- 1918-19. Introduced at Sierra Leone in late August
culosis rates and explosion of the disease among the 1918, and to ports around the continent in the next
rural African population as infected miners returned several weeks, the disease spread rapidly inland
to their homes. over the newly constructed colonial roads, railroads,
Besides mining, other development efforts of the and river transport systems. Diffusion was espe-
colonial era often had unexpected and deleterious cially rapid on the southern African rail system and
health consequences. Major infrastructure projects on the river steamers in the Belgian Congo. Indeed,
usually depended on migrant labor and sometimes so quickly did the disease move by these means, that
took a heavy toll in lives. For example, thousands of places in the Congo only 100 miles from the coast
workers conscripted in the savanna country of south- were first attacked by way of the Union of South
ern Chad and Ubangui-Chari died from dysentery, Africa. Almost every inhabited spot on the continent
respiratory ailments, and other diseases during the was struck in a matter of 6 or 7 months, graphic proof
construction of the Congo-Ocean railroad in French that the old isolation was gone forever and that the
Equatorial Africa in the 1920s. Water projects fre- continent was an epidemiological unit closely linked
quently facilitate disease transmission in tropical to the rest of the world. Approximately 2 million
climates. The Gezira irrigation scheme in Sudan, for people - about 2 percent of the population - died dur-
example, as well as the massive Volta Lake in ing the epidemic.
Ghana, has resulted in hyperendemic schistosomia- The demographic balance began to shift by the
sis. On a smaller scale, dam ponds may also become 1920s in much of West and South Africa, and by the
foci for malaria and guinea worm infection, and, in 1930s elsewhere. The harsher aspects of colonial
parts of northern Ghana, dam spillways and bridge rule were being mitigated, famine relief was made
pilings provided breeding sites for the vector of more effective with better transportation, and medi-
onchocerciasis, a worm disease that often causes cal measures began to have some effect. Progress
blindness. was most rapid in the Belgian and British colonies
Venereal diseases also diffused rapidly in the late and in French West Africa; medical services were
nineteenth and early twentieth centuries, as labor slower to develop in Portuguese territories and in
migration and urbanization disrupted social pat- French Equatorial Africa.
terns. Equatorial Africa experienced a very destruc- Colonial medicine had little to offer Africans for
tive gonorrhea epidemic as a direct result of harsh many years, except for surgery, yaws therapy, and
Belgian and French colonial policies; this resulted in smallpox vaccination. But by the 1930s, efforts to
widespread sterility, which is believed to be largely control smallpox, cerebrospinal meningitis, tubercu-
responsible for the very low fertility rates in the losis, louse- and tick-borne relapsing fever, and
region even today. Movements associated with the other epidemic diseases were beginning to have
early colonial period were also apparently responsi- some impact. Plague broke out in several territories
ble for great outbreaks of human trypanosomiasis in in the early twentieth century, but public health
French Equatorial Africa and the Lake Victoria re- measures prevented serious loss of life. Extensive
gion of East Africa in the first decade of the 1900s. efforts to contain trypanosomiasis, primarily by vec-
At least 250,000 died in East Africa alone. tor control in the British colonies and by chemical
On a more trivial but still significant level was the treatment and prophylaxis in the French territories,
rapid spread of the burrowing flea Tunga penetrans had considerable success. The growing cities contin-
(chigoes). This insect invades tissues under the nails ued to function as nodes for the diffusion of infec-
and may result in secondary infections that cause tious diseases into the countryside, but measures to

improve water supplies and waste disposal, control against such major scourges as malaria, onchocerci-
malarial mosquitoes, provide vaccinations, and treat asis, schistosomiasis, trypanosomiasis, and leprosy
patients began to have a positive impact in almost are promising, but high death rates, weak and some-
all urban areas by 1940. Ironically, improved water times declining economic and political systems, and
supplies meant that fewer people were exposed to the AIDS epidemic show that grave problems re-
polio virus as small children when they were most main. More than ever, Africa's disease environment
likely to have mild or asymptomatic cases. Postpone- is determined by its poverty.
ment of infection until adolescence created an in- K. David Patterson
crease in the number of paralytic cases in the post-
World War II period - an unintended by-product of Bibliography
incomplete sanitary reform. Alden, Dauril, and Joseph C. Miller, 1987. Out of Africa:
The advent of sulfa drugs in the late 1930s and The slave trade and the transmission of smallpox
especially the antibiotics in the 1940s provided a to Brazil. Journal of Interdisciplinary History 18:
revolution in the effectiveness and, consequently, 195-224.
the popularity of the colonial medical services. Af- Curtin, Philip D. 1968. Epidemiology and the slave trade.
rica's rapid demographic growth dates from the late Political Science Quarterly 88: 190-216.
Curtin, Philip D., et al. 1978. African history. Boston.
1940s and is partially the result of the success of
Domergue-Cloarec, Danielle. 1986. Politique coloniale
most colonial medical services in lowering death francaise et rkalites coloniales: La sante en Cote
rates from bacterial diseases. Populations are grow- d'lvoire, 1905-1958. Toulouse.
ing at rates that will double the numbers of people in Ford, John. 1971. The role of the trypanosomiases in Afri-
most countries in around 20 years, a situation that is can ecology: A study of the tsetse fly problem. Oxford.
already placing grave strains on medical services Hartwig, Gerald W., and K. David Patterson. 1984. Schisto-
and food supplies. somiasis in twentieth century Africa: Historical stud-
ies in West Africa and Sudan. Los Angeles,
Disease Patterns Since 1960 eds. 1978. Disease in African history: An introductory
Most African states became independent after 1960, survey and case studies. Durham, N.C.
but they have not been able to effect radical improve- Hoeppli, R. 1969. Parasitic diseases in Africa and the West-
ments in health conditions. Colonial medical ser- ern Hemisphere: Early documentation and transmis-
sion by the slave trade. Basel.
vices and their successors in sovereign African coun-
Hopkins, Donald R. 1983. Princes and peasants: Smallpox
tries have tended to stress therapy over prevention, in history. Chicago.
and to favor cities over the rural areas. There has Hughes, Charles C , and John M. Hunter. 1970. Disease
been some real progress. Smallpox has been eradi- and development in Africa. Social Science and Medi-
cated, thanks to a concerted worldwide campaign. cine 3: 443-93.
Vaccines, many developed only after 1960, have be- McNeill, William H. 1976. Plagues and peoples. Garden
gun to make inroads against measles, diphtheria, City, N.Y.
polio, cerebrospinal meningitis, and other common Patterson, K. David. 1979. Infectious diseases in twentieth-
infections, but new vaccines are urgently needed for century Africa: A bibliography of their distribution
other diseases, including malaria and the bacterial and consequences. Waltham, Mass.
and viral agents of childhood diarrheas. The most 1981. Health in colonial Ghana: Disease, medicine, and
urgent need is to improve rural water supplies and socio-economic change, 1900—1955. Waltham, Mass.
sanitation, which would greatly reduce the incidence Patterson, K. David, and Gerald F. Pyle. 1983. The diffu-
of a host of infections. Greater attention to nutrition sion of influenza in sub-Saharan Africa during the
1918—1919 pandemic. Social Science and Medicine 17:
and to infant and child health is also essential.
1299-1307.
Malaria and schistosomiasis are still major causes Patterson, K. David, and Gerald W. Hartwig. 1984. Cere-
of morbidity and mortality, and almost no progress brospinal meningitis in West Africa and Sudan in the
has been made against the common intestinal para- twentieth century. Los Angeles.
sites. Even yaws, which is readily treated with peni- Wiesenfeld, Stephen L. 1967. Sickle-cell trait in hu-
cillin, has reemerged in areas such as Ghana where man biological and cultural evolution. Science 157:
economic distress has curtailed medical services. 1134-40.
Similarly, internal strife and misgovernment in
Uganda have disrupted trypanosomiasis control,
with predictable results. Campaigns sponsored by
the World Health Organization and other groups

VII.2. The Middle East and North Africa 453
The Middle East and North Africa lie roughly

VII.2 between latitudes 20° and 40° north in a transitional
Disease Ecologies of the climatic zone between equatorial and mid-latitude
climates. Because of general atmospheric circulation
Middle East and North Africa patterns, a characteristic of these latitudes is prevail-
ing aridity - the "Mediterranean Rhythm" of winter
rain and summer drought. Only westward-facing
This study of disease ecologies of the Middle East coasts and mountain ranges receive the 250 millime-
and North Africa aims to demonstrate the interrela- ters (about 10 inches) rainfall considered the mini-
tionships of environmental and etiologic factors in mum necessary for cultivation. The lack of cloud
the diseases endemic to that region. In so doing, the cover is a major factor influencing temperature, for
essay surveys the area between Morocco in the west clear skies and intense solar heating of the land
and the Iranian border in the east, including the cause very high temperatures during the day al-
Anatolian Peninsula in the north and the Arabian though temperatures fall considerably at night. An-
Peninsula to the south. other characteristic of the region is scanty water
Conditions before the mid-twentieth century are supply. Except for the Nile, Tigris, and Euphrates,
generally emphasized in this study. The population the majority of rivers are short streams with a rapid
data and some obviously changing current condi- and intermittent course down rugged mountain
tions are, however, pertinent to conditions in the sides. The lack of wooded land is another serious
late twentieth century. The State of Israel is not deficiency. Long occupation has meant prolonged ex-
included in the discussion because of the general ploitation of the land over millennia, almost total
time frame and for other reasons. Israel does not fit deforestation, and removal of ground cover, result-
into most generalizations about the region because ing in uncontrolled water runoff and soil erosion.
of its diversified economy and the comprehensive Aggravated by overcultivation and unrestrained
health-care system created by preindependence set- grazing, especially by goats, soil erosion has led to
tlers. The chapter also will not deal with the region's extensive desiccation and desertification. Hence, at
emerging pattern of the degenerative, metabolic, mid-twentieth century, it was estimated that only 5
and genetic disease concerns of industrialized soci- to 7 percent of the total area is cultivable naturally.
eties. Many of the data are derived from the accumu- The implications of prevailing aridity and great
lation of information assembled by the attempt of expanses of mountainous or desert terrain have been
European nations to deal with epidemics and exotic significant for human survival: Population has been
diseases encountered during the nineteenth century relatively sparse and discontinuous in distribution;
in Africa and Asia. This material is sufficient to until recently, nomadism was widespread; and set-
sketch a tentative disease profile, stressing infec- tled argiculture most often has required irrigation
tious diseases. Moreover, twentieth-century investi- and complex infrastructures to govern the allocation
gations in nutrition have been used to supplement of scarce water resources.
and qualify this information.
Population
Geography, Topography, and Climate The total population in 1984 of countries under con-
The Middle East and North Africa occupy that part sideration in the region, estimated at 257 million,
of the Earth's crust where three tectonic plates con- was about 5.6 percent of the world population, in an
verge, causing great ranges of high-fold mountains area occupying about 10 percent of the Earth's sur-
to be thrust up, notably in western North Africa and face. The largest populations were in Egypt, Turkey,
in the northern tier states of Turkey and Iran. Peaks and Iran, which comprised 52 percent of the inhabit-
in the high Atlas Mountains of Morocco and the ants of the region.
Taurus range in Turkey exceed 12,000 feet, whereas Turkey was the only country in which population
Mount Damavand, in Iran's Elburz mountains, ex- was distributed relatively evenly. Even at the mid-
ceeds 18,000 feet. Running north and south, the twentieth century, about 75 percent of the inhab-
Hijaz, Asir, and Yemen ranges are high escarpments itants lived in small villages scattered over the
in the southwestern Arabian Peninsula, paralleling Anatolian Peninsula, whereas in other states, the
the anticlinal highlands that form the Lebanon and population had already been concentrated along
Anti-Lebanon mountains and the Judean Hills of the seacoast or river banks, on oases, or around the
Palestine. countries' metropolitan centers. Since midcentury,

population pressure on the land has reduced the Egypt, Israel, Syria, and Turkey - no longer con-
percentage of people in agriculture and accelerated form to the typical Third World economic pattern, in
the move to urban centers. By 1984, it was estimated that one-fifth or more of their gross domestic product
that 42 percent of the population of North Africa and is derived from the manufacturing industry. Gener-
53 percent in the Middle East had gravitated to ally, however, the countries of the Middle East and
towns or cities. At the same time, 40 to 45 percent of North Africa belong to the Third World, being still
the populations surveyed were under 15 years. (An heavily dependent upon the export of primary prod-
overall annual growth rate of 2.8 percent means ucts and the import of food, consumer goods, equip-
almost doubling the population in 25 years.) ment, and technology {Oxford Regional Economic
About 93 percent of the people of the region are Atlas 1964; Fisher 1971; Drysdale and Blake 1985).
Muslim and about 57 percent speak Arabic; other
important languages are Turkish, Persian, Hebrew, Disease Patterns
Kurdish, and Berber (Fisher 1971; Drysdale and The foregoing sketch suggests a distinctive ecologi-
Blake 1975). cal disease pattern for the Middle East and North
Africa. Pastoralism and the farmers' reliance on ani-
Economic Life mals for transport, power, fertilizer, and dung fuel
Until very recently, about 60 percent of the popula- have made these occupational groups, living in close
tion cultivated the traditional crops of the Mediterra- proximity to their livestock, vulnerable to zoonoses
nean - cereals and olive and fig trees - whereas date and to insect-borne diseases, some of which infest
palms and sugar cane predominated in the southern domestic or wild animals. Another important disease
deserts. Antiquated and inequitable land-holding complex has developed out of the necessity for irriga-
and tenancy systems have discouraged long-term tion: the widespread incidence of parasitism due to
development by individual farmers, and the tradi- favorable conditions for proliferation of the insect
tional but excessive subdivision of land has worked carrier and an intermediate host where required. At
against cost-effective production. This region still an agricultural conference in 1944, it was reported
must remain vigilant for periodic swarms of destruc- that expanding irrigation in one area of Egypt had
tive locusts, both Saharan and Arabian types, in raised the incidence of both malaria and schistosomi-
addition to the pests that damage crops in other asis from 5 to 45 or even 75 percent of the population
parts of the world. in that area (Fisher 1971). This survey, therefore,
Whereas most lands capable of cultivation have will begin with those ailments most closely related to
been planted with cereals, areas where water and the rural environment: arthropod-borne diseases
good soil are lacking have been left to herders. Sheep and parasitic infestations. Next it shall consider the
are preponderant in all areas; goats also are kept in "crowd diseases," most characteristic of urban soci-
large numbers, especially in steppe and mountain- eties, but also found in crowded villages and oases.
ous areas; and water buffalo have provided most Last it shall sketch the diseases caused by nutri-
animal power in the marshes of Iran and Iraq and tional deficiencies among rural and city people.
the irrigated fields of Egypt. As transport has be- Within those categories, diseases are listed in de-
come increasingly mechanized, the use of the camel scending order of their prevalence or importance as
has declined, but the donkey still carries people and death- or disability-threatening experiences.
commodities everywhere. Neither cattle nor horses
are important economically because of lack of pastur- Major Arthropod-Borne Diseases
age. Mineral resources are limited, with the excep- Because the many species of anopheline mosquitoes
tion of petroleum in some states, and large-scale have adapted to breeding in the widest variety of
extraction has begun only relatively recently. Good- hydrological conditions - from swamps and stagnant
quality coal exists only in northwestern Turkey, but irrigation pools to fast-moving mountain streams,
hydroelectric power and petroleum have been supply- and from freshwater springs to brackish marsh-
ing energy for industrialization in recent decades. land - they are found throughout the region except
The traditional handicrafts and manufactures of in stretches of desert lacking any surface collection
the Middle East and North Africa - metal working, of water. From 9 to 19 species of anopheline mosqui-
glassware, textiles for articles of clothing, and toes exist in each Middle Eastern and North African
woolen carpet-making - have suffered from the com- country, of which 3 or 4 have been identified as vec-
petition of foreign imports, but many countries are tors of malaria.
now promoting them for export. Four countries - Although mosquitoes cannot survive dry, hot

weather, their proliferation in oases in Libya's verely in the sixth-century plague of Justinian, and
Fezzan Desert and in the Arabian Peninsula demon- repeatedly thereafter. Because Procopius had placed
strates their tenacity. One species of Anopheles en- the origin of that pandemic in Egypt, the Nile Val-
demic in southwestern Arabia has caused recurrent ley became identified in Europe's popular and pro-
epidemics of malaria under favorable rainfall condi- fessional imagination as "the cradle of plague."
tions. The last such epidemic was reported in 1950- However, the recurring epidemics of bubonic plague
1, when this species spread inland from Jidda along in this region were initially imported. Infected fleas
the road to Mecca, carried by the increased traffic of on rats infesting the holds of cargo ships transmit-
the Muslims' annual pilgrimage. ted the infection to domestic rats in Mediterranean
Malaria has been reported in all the countries of port cities and established endemic loci for the dis-
the Middle East and North Africa. Since World War ease. Only the coast is naturally vulnerable to
II the World Health Organization (WHO) has carried plague. Inland areas are too hot or too cold, and
out extensive mosquito eradication projects. None- above all too dry to be susceptible to enzootic
theless, malaria continues to break out periodically, plague. However, irrigation systems acted as net-
and in 1950 a public health survey in Morocco re- works for transmitting infective fleas by providing
ported that it was still the most prevalent disease in harborage for rats in the embankments of canals.
the country (Simmons et al. 1954; Nosologie maro- Epidemics flared periodically whenever optimum
caine 1955; Kanter 1967; Benenson 1975). weather conditions - high humidity and moderate
The Aedes Aegypti mosquito that transmits den- temperatures - coincided with an adequate rat-flea
gue fever also is a potential vector of yellow fever, density. After the adoption of quarantine measures
but that infection has not been reported in the Mid- in the southern and eastern Mediterranean in the
dle East and North Africa. Dengue is endemic in the nineteenth century, followed by the discovery of the
eastern Mediterranean area but has not been ob- rat-flea nexus, most areas of the world including
served at heights exceeding 600 meters (2,000 feet) the Middle East and North Africa managed to bring
and has been largely confined to coastal areas. Most plague under control until the epidemic of 1894,
countries in the Middle East have sporadic out- which originated in northern China.
breaks of dengue fever, and a few cases are reported Plague, however, continues to be a potential dan-
in Libya every year; whereas in Morocco, Algeria, ger in the Middle East and North Africa. A reservoir
and Tunisia, the infection has remained only a po- of sylvatic (wild rodent) plague in the mountains of
tential threat (Simmons et al. 1954; Kanter 1967; southwestern Arabia and the Kurdish highlands,
Benenson 1975). shared by Iran, Iraq, and Turkey, may spread infec-
Because early symptoms of Bancroftian filariasis tion by contact with domestic rats. In Libya sporadic
may be simply fever and lymphadenitis, the disease cases transmitted by steppe rodent fleas broke out
was not reported historically until prolonged and almost annually from the time of World War I until
repeated infection caused elephantiasis of the limbs 1940. In Morocco as well, plague recurred sporadi-
or outer genitalia. Today, although the most common cally until 1946, and it was also reported in Tunisia,
mosquito vector of filariasis is abundant throughout Algeria, and Egypt up to the early 1950s (Hirsch
the region, the threat of the disease has remained 1883; Hirst 1953; Pollitzer 1954; Simmons et al.
potential. In Lebanon, filariasis appears occasion- 1954; Nosologie marocaine 1955; Kanter 1967;
ally. There is one focus of infection in the southwest- Benenson 1975; Gallagher 1983).
ern Arabian Peninsula and another in Egypt, where Characteristic of colder climates, typhus is not
the mosquito vector proliferates in numerous brack- common in this region and has occurred chiefly dur-
ish wells in Rosetta (Simmons et al. 1954; Benenson ing the winter among nomads who wear the same
1975). heavy clothing day and night. The human body's
Bubonic plague is transmitted by the bite of humid microclimate provides a favorable environ-
an infective flea, usually Xenopsylla cheopis, and ment for the louse to deposit eggs (nits) that hatch
marked by acute lymphadenitis forming buboes, at into young lice in a few days. Warm dry weather is
the site of the infection; septicemic plague occurs unfavorable for breeding because humans dress
in severe and advanced bubonic plague, causing more lightly, exposing the lice to high temperatures
petechial hemorrhages; pneumonic plague, the most and sunlight. Displacement of people and crowding
infectious and fatal form, is airborne, spread by inha- during World War II contributed to a series of epi-
lation of exhaled droplets from infected patients. demic outbreaks of typhus in North Africa, but
The Middle East and North Africa suffered se- delousing campaigns appeared to eliminate the dis-

ease. Nonetheless, occasional outbreaks have been influenza and is carried by the same phlebotome -
reported in Iran, Iraq, Syria, and Jordan, from con- Phlebotomus papatasii - transmits cutaneous leish-
gested villages and town quarters as well as from maniasis. Sandfly fever reportedly is endemic in
refugee camps (Rodenwaldt 1952; Simmons et al. Syria, Lebanon, Israel, Iraq, Iran, and sporadic in
1954; Nosologie marocaine 1955; Kanter 1967; Jordan and Saudi Arabia (Simmons et al. 1954;
Benenson 1975). Benenson 1975).
Finally, numerous species of flies are abundant
Other Arthropod-Borne Diseases throughout the Middle East and North Africa;
Although foci for endemic tick-borne relapsing fever among the most common of these are species of the
(alternating febrile and afebrile periods) exist Muscidae family, thought to be implicated in the
throughout the region, the disease is rare. Epidemic mechanical transmission of intestinal and eye infec-
louse-borne relapsing fever is more common; be- tions. For example, gastroenteritis causing infantile
tween 1942 and 1945 a series of epidemics spread diarrhea and dehydration, which has been held re-
throughout North Africa from Morocco through sponsible for more than half the infant deaths in
Egypt and extended into Turkey, but it has occurred Egypt, shows a striking peak of incidence during the
only sporadically since then. Boutonneuse fever is a hot, dry, fly season (Labib 1971). Several species
mild to moderately severe febrile illness widely dis- cause myiasis in livestock and occasionally in hu-
tributed in countries adjacent to the Mediterranean, mans, but cases of these invasions are rare (Sim-
Caspian, and Black seas. The disease, which is trans- mons et al. 1954).
mitted by the bite of an infected dog tick, occurs
occasionally in Morocco, Algeria, Tunisia, Libya, Helminth-Transmitted Diseases
and Turkey, and rarely in Israel and Lebanon. Also, Of the four species of blood flukes infecting
another tick-borne disease, tularemia, a plaguelike humans — Schistosoma haematobium, Schistosoma
infection of wild and domestic animals, especially mansoni, Schistosoma intercalatum, and Schisto-
rodents and rabbits, is found only in Turkey soma japonicum - only the first two are endemic in
(Rodenwaldt 1952; Simmons et al. 1954; Benenson the Middle East and North Africa. Persistence of the
1975). disease depends upon the presence of freshwater
Of the three types of leishmaniasis, only cutaneous snails as the intermediate hosts.
leishmaniasis {Leishmania tropica) is common in the The evolution of schistosomiasis probably oc-
Middle East and North Africa. In 1756 Patrick Rus- curred during the period when human populations
sell named the affliction the "Aleppo boil," and today were shifting from hunter-gathering economies to
it is also known as "Baghdad boil" in Iraq and "Jeri- societies based on settled agriculture. Parasitism
cho boil" in Jordan. In Israel it is most common in requires a stable relationship between host and
the Haifa area. It also occurs sporadically in the parasite, such as is available in settlements close to
Arabian Peninsula and in southeastern Turkey, slow-moving water in which snail hosts of the dis-
where it is known as "Urfa sore." In North Africa ease dwell. Vesical or urinary schistosomiasis prob-
cutaneous leishmaniasis is endemic and prevalent ably existed in both ancient Mesopotamia and
in Algeria and Morocco, widespread in Tunisia and Egypt. Babylonian inscriptions and Egyptian pa-
Egypt, but rare in Libya (Russell 1794; Rodenwaldt pyri (Ebers, Kahun) refer to hematuria and pre-
1952; Omran 1961; Kanter 1967; Benenson 1975). scribe remedies. In 1910 Marc Ruffer discovered
Kala-azar, or visceral leishmaniasis, is a chronic ova in Egyptian mummies dating from 1200 B.C.,
systemic infection disease characterized by fever, en- and J. V. Kinnear-Wilson considers the finding of
largement of the liver and spleen, anemia, and pro- shells of the most common host snail, Bulinus
gressive emaciation and weakness. Untreated, it is a truncatus, in the mud brick walls of Babylon evi-
highly fatal disease. Although the vectors of kala- dence that S. haematobium was the cause of
azar are not common in this region, three species of hematuria described in Babylonian texts. French
sandflies are suspected of transmitting visceral leish- soldiers suffered with hematuria during the occupa-
maniasis that appears sporadically in the northern tion of Egypt in 1798-1801, but the causative para-
and western coastal provinces of Turkey, and the site was not identified until 1851 when Theodor
littoral of Algeria and Morocco (Simmons et al. 1954; Bilharz recovered adult worms from the portal sys-
Benenson 1975). tem during an autopsy in Cairo. The life cycles of
Sandfly fever or pappataci fever (phlebotomus the intermediate molluscan hosts were demon-
fever) is a viral 3- or 4-day fever that resembles strated early in the twentieth century.

Studies and clinical records between 1931 and or gallbladder (Simmons et al. 1954; Kanter 1967;
1961 reported schistosomiasis in all the countries of Kinnear-Wilson 1967; Benenson 1975; Sandison
the Middle East and North Africa. However, because 1980).
of prevailing desert conditions, North Africa, except Other worm-related diseases include trichinosis,
for Egypt, has not harbored parasites that require which, because of the Muslim and Jewish prohibi-
surface water or moist soil for survival. A notable tion against pork, is rare in the Middle East and
exception is the Fezzan in Libya, where in some North Africa, and has been reported only in Leba-
oases with shallow wells, up to 86 percent of the non. Taeniasis, an infection with the beef tapeworm,
inhabitants have been infected. However, outside a Taenia saginata - causing anorexia, digestive dis-
relatively small radius the groundwater available to turbances, abdominal pain, and insomnia - occurs
oases has too high a salt content to support the host where the larvae are ingested with raw beef. It is
snail. The highest incidence, up to 100 percent in particularly frequent among herding peoples whose
some villages, has occurred in Iraq and especially in sheep, cattle, and dogs have a high rate of infection,
Egypt where the inhabitants of the Nile Valley have which may be passed to humans. In Libya, for exam-
maintained irrigation systems for millennia. ple, the government hospital at Benghazi reported
The widespread species has been S. haematobium; the existence of the larval form of tapeworm in 20 to
infection with S. mansoni has appeared only in 28 percent of the patients annually between 1960
Egypt and among Yemeni and Iraqi immigrants to and 1963 (Kanter 1967; Benenson 1975).
Israel, although the host snail exists in the Arabian
Peninsula and North Africa (Ruffer 1910; Simmons Zoonoses
et al. 1954; Nosologie marocaine 1955; Malek 1961; The zoonoses that occur in the Middle East-
Farooq 1964; Kanter 1967; Kinnear-Wilson 1967; brucellosis, anthrax, and Q fever - are all occupa-
Benenson 1975; Sandbach 1976; Sandison 1980). tional diseases of herders, farm workers, veterinari-
Ancylostomiasis, or hookworm disease, is probably ans, abattoir workers, and industrial workers who
quite old. A chronic disease of the digestive system process hides, wool, or other animal products. Bru-
described in the Ebers Papyrus of 1550 B.C. has been cellosis, which causes a generalized infection, also
interpreted as hookworm disease. In 1838 Angelo known as undulant fever, has been reported in Mo-
Dubini discovered a worm that he called Ancy- rocco, Algeria, Tunisia, Iran, Turkey, Syria, and
lostoma duodenale, during autopsies in Egypt, and a Lebanon. Anthrax, an infectious disease of rumi-
colleague found the same parasite during autopsies nants, occurs only in Turkey. Q fever rarely infects
in 1845, but neither related them to specific dis- humans in areas where the disease exists enzo-
eases. In 1853, Wilhelm Griesinger identified ancy- otically in animals. Occasional cases, however, have
lostomiasis as the cause of the endemic anemia, been reported in Morocco that were suspected of
called "Egyptian chlorosis," and observed that 25 having been transmitted by tick vectors.
percent of the causes of death were traceable to the Also increasingly rare is rabies or hydrophobia, an
effects of this infestation. acute, almost invariably fatal viral infection of the
Ancylostomiasis occurs in all Mediterranean coun- central nervous system, transmitted to humans by
tries, but the Nile Valley has been a particular locus the bite of a rabid animal. At mid-twentieth century,
of the infection (Khalil 1932; Simmons et al. 1954; James Simmons and colleagues (1954) reported ra-
Nosologie marocaine 1955; Benenson 1975). bies in Iran, Syria, and Jordan; however, most coun-
Ascariasis (infection of the small intestine caused tries in this region have controlled rabies by quaran-
by Ascaris lumbricoides, the large intestinal round- tining and licensing pets and by destroying stray
worm) may cause digestive and nutritional distur- animals (Benenson 1975).
bances. Pictorial evidence demonstrates the presence
of Ascaris in ancient Mesopotamia, and numerous Food- and Waterborne Enteric Diseases
prescriptions for roundworm in the Ebers Papyrus Acute diarrheal disease in early childhood, most
indicate that the ancient Egyptians complained of prevalent after weaning, is important in the Middle
this parasite as well. In the twentieth century, East and North Africa as in all developing countries.
ascariasis has been most common among school chil- Although it may include specific infections, infantile
dren, who may suffer anemia and eosinophilia from diarrhea frequently is a clinical syndrome of uniden-
high infestation. Serious complications among chil- tifiable etiology caused by bacteria, viruses, hel-
dren may include bowel obstruction and occasionally minths, or protozoa. Common in areas of poor sanita-
death due to the migration of adult worms into liver tion and prevailing malnutrition, infant diarrhea

may produce as many as 275 attacks per 100 chil- quarantine regulations during the Second World
dren per year, more than 50 deaths per 1,000 per War. However, since 1961 a new strain of cholera,
year in preschool children. Protein—calorie malnutri- El Tor, has spread extensively from a focus in
tion is commonly associated with acute diarrheal Sulawesi in Indonesia, through most of Asia and
episodes, which may precipitate kwashiorkor. The the Middle East into Eastern Europe and Africa,
highest incidence tends to occur in hot, dry periods, and from North Africa into the Iberian Peninsula
calling for oral rehydration therapy, which has be- and Italy (Hirsch 1883; Simmons et al. 1954;
come a high priority program for the WHO in recent Pollitzer 1959; Kanter 1967; Benenson 1975).
years (Simmons et al. 1954; Benenson 1975).
At mid-twentieth century, Simmons reported "dys- Diseases Transmitted Through the Respiratory
enteries" for all Middle Eastern countries, but pro- Tract
vided no data. All North African countries, includ- Tuberculosis is widespread in the Middle East in the
ing Egypt, reported higher incidence rates for pulmonary form that was known earlier as phthisis
shigellosis then amebiasis, except in Morocco and or consumption. Egyptian wall paintings depict
Libya, where amebiasis was reported more preva- humpbacks typical of bone tuberculosis of the spine,
lent. Between 1900 and 1950 comparative mortality known as Pott's disease, and tuberculous bones have
rates were 8.7 percent for amebic dysentery and 11.8 been found in tombs dating to 3000 B.C. In modern
percent for bacillary dysentery (Rodenwaldt 1952; times, tuberculosis appeared to accompany the rise of
Simmons et al. 1954; Kanter 1967). industrialization and urbanization in the nineteenth
In the Middle East and North Africa, raw fruits century, succeeding smallpox as the most common
and vegetables handled by infected persons are im- affliction in city life. In congested slums tuberculosis
portant vehicles of the transmission of typhoid fever, assumed epidemic proportions because the infection
and flies are often vectors for spreading contamina- is transmitted by exposure to the bacilli in airborne
tion. At mid-twentieth century, the disease was re- droplet nuclei from the sputum of infected persons. In
ported in all countries considered in this survey but the mid-twentieth century, tuberculosis was reported
was reported as rare in Libya (Rodenwaldt 1952; in all Middle Eastern and North African states. War-
Simmons et al. 1954). Paratyphoid infection due to time displacement had caused a steep rise in inci-
Salmonella of all groups except S. typhosa is a gener- dence. In Libya, for example, many uprooted nomads
alized bacterial enteric infection, clinically similar from the Fezzan emigrated to shanty towns on the
to but with a lower fatality rate than typhoid fever; coast. Because food was scarce and sanitary installa-
it occurs only sporadically in this region. tions were nonexistent, tuberculosis spread rapidly
Cholera did not appear in the Middle East and among these desert people in a severe form that was
North Africa until the great pandemics of the nine- often fatal. In the 1950s, the WHO and UNICEF
teenth century that were caused by troop move- supported immunization programs with the result
ments in the lands bordering India, Afghanistan, that tuberculosis in the Middle East has become simi-
and Iran, and by accelerated sea transport linking lar to the European type, milder and chronic (Sim-
Asia with the rest of the world. Six pandemic waves mons et al. 1954; Nosologie marocaine 1955; Kanter
of cholera swept around the world between 1817 1967; Benenson 1975; Sandison 1980).
and 1923, invading all settled communities in Asia, By contrast, pneuomococcal pneumonia was re-
Africa, Europe, and the Americas. Middle Eastern ported to have a significant mid-twentieth-century
and North African countries were vulnerable to in- incidence only in Egypt and Turkey. This may sug-
vasion by the disease because returning Muslim gest susceptibility among the ill-housed, undernour-
pilgrims carried the infection from the holy cities of ished poor inhabiting the overcrowded metropolises,
Arabia, where it was introduced by Muslims from as well as an above-average involvement among the
South Asia. After discovery of the cholera vibrio coal miners in Turkey (Simmons et al. 1954;
and the rationalization of quarantine practices, as Benenson 1975).
well as nineteenth-century sanitary reform pro- Diphtheria typically has been a disease of colder
grams, cholera receded as a major threat. The adop- months in temperate zones. It was reported in
tion of efficient control techniques, particularly Egypt, Israel, Jordan, and Iraq in the mid-twentieth
since the Second World War, has effectively neutral- century; in Morocco it was identified as one of sev-
ized the danger of dissemination from the Muslim eral diseases that accompanied an influx of Europe-
pilgrimage sites. The last major outbreak, which ans during the Second World War (Simmons et al.
occurred in Egypt in 1947, was due to relaxation of 1954; Nosologie marocaine 1955; Benenson 1975).

Meningitis occurs more frequently in children and very high in the Middle East. Egypt was considered
young adults and more commonly in crowded living the principal focus, where about 90 percent of the
conditions. In the mid-twentieth century, meningo- population was reported to have suffered trachoma,
coccal infection was reported in Turkey, Iraq, Leba- often combined with acute bacterial conjunctivitis or
non, and Egypt (Simmons et al. 1954; Benenson occasionally gonococcal conjunctivitis. In Syria,
1975). Lebanon, and Palestine, about 60 percent of the
Smallpox had been a recognized scourge in the Arab schoolchildren and 10 percent of the Jewish
Middle East since the sixth-century epidemic struck children from rural areas were infected with tra-
Ethiopian invaders threatening Mecca. The Islamic choma. In Turkey, 60 percent of the population in
scholar-physician Rhazes, in the tenth century, the southeast steppe area with no forestation was
wrote the classic clinical description of the disease, reported affected. In Iran, the highest incidence also
implying that smallpox was very common and en- was reported in steppe and desert areas near the
demic to the entire Islamic world from Spain to Per- Persian Gulf and in the interior south of Isfahan. In
sia at that time. It is true that plague overshadowed Iraq, the high incidence of trachoma in Baghdad -
smallpox in the Mediterranean for several centuries, 80 percent - was attributed to susceptibility to infec-
but the latter remained widespread and continued to tion from exposure to the loess dust from the Tigris
claim great numbers of victims until the early nine- and Euphratesfloodareas during the hot dry season.
teenth century when Europeans began introducing In Algeria and Morocco about 10 percent, and in
Edward Jenner's vaccination into their colonies in Tunisia 40 percent, of the population were infected
Africa and Asia. Nevertheless, although most coun- with trachoma. According to practitioners in Mo-
tries in the Middle East adopted immunization proce- rocco, trachoma was not an independent nosological
dures during the nineteenth and early twentieth entity; bacterial conjunctivitis accompanied 80 per-
centuries, smallpox continued to break out in all of cent of the cases. In Libya trachoma was most com-
them until systematic vaccination campaigns coordi- mon in the Fezzan oases, where morbidity was es-
nated by WHO eradicated the disease in Libya by timated at 60 percent of the inhabitants. In the
1949 and elsewhere in the region by 1977 (Simmons post-World War II migration of desert people to the
et al. 1954; Kanter 1967; Hopkins 1983; Fenner et coastal cities, incidence ranged from 30 percent to 70
al. 1988). percent in the shanty towns outside Tripoli. In spite
At about midcentury, measles was recorded only of preventive programs, the disease was still wide-
in Egypt, Algeria, and Morocco (Simmons et al. spread in 1963, when 4,126 cases were recorded in
1944; Benenson 1975). Tripolitania Province (Rodenwaldt 1952; Simmons
et al. 1954; Nosologie marocaine 1955; Kanter 1967;
Diseases Transmitted by Human Contact Benenson 1975).
Eye diseases are widespread in the Middle East and Among North Africans, leprosy was believed to
along the Mediterranean littoral. The most serious, have been imported from the eastern Mediterranean
trachoma (earlier called "Egyptian ophthalmia"), is by many peoples. In the ninth century B.C., Phoeni-
a bacterial infection that progresses clinically from cians were blamed for it. Jews driven from Jerusa-
tiny follicles on the eyelid conjunctiva to invasion of lem in A.D. 135 were believed to have reintroduced
the cornea, with scarring and contraction that may it, as were Arab invaders in the eighth century. In
lead to deformity of the eyelids and blindness. It is addition, it was probably periodically reintroduced
often accompanied by acute bacterial conjunctivitis, by Saharan caravans as well. By mid-twentieth cen-
a highly contagious form of conjunctivitis, most of- tury, however, leprosy had effectively disappeared in
ten caused by the Koch-Weeks bacillus, character- North Africa, except among the Berbers, where
ized by inflammation, lacrimation, and irritation, there were an estimated 8,000 cases, and in Egypt
followed by photophobia, purulence, and edema of where 30,000 cases were reported (Rodenwaldt 1952;
the eyelids. Simmons et al. 1954; Nosologie marocaine 1955;
Both trachoma and conjunctivitis are transmitted Kanter 1967; Benenson 1975).
through contact with fingers or articles contami- Finally, in the mid-twentieth century, scabies was
nated by discharges of infected persons. Flies or eye reported in Egypt, Morocco, Iran, Syria, and Jordan,
gnats often spread the infection, and lack of water perhaps aggravated by wartime displacement and
and exposure to dry winds, dust, and sandstorms are crowding, as in refugee camps, with consequent lack
thought to aggravate the problem. of water for bathing (Simmons et al. 1954; Benenson
Between 1928 and 1936, trachoma morbidity was 1975).

Venereal Diseases sent capital to the herdsmen that is not to be wasted
Because leprosy was often confused with venereal by slaughter. Thus, meat contributes only about 2
diseases in antiquity, it is not clear when syphilis percent of the total caloric intake, compared with 21
first appeared in the Middle East and North Africa. percent in the United States. Mutton is the principal
Following the Crusades, however, when all Europe- meat consumed in Muslim countries, and to some
ans were referred to generically as "Franks," syphilis extent beef and goat are also eaten. Like the no-
was associated definitively with Europeans as "il- mads' herds, poultry and eggs provide a livelihood
franji" - that is, the Franks' disease. Gonorrhea refor villagers; they are sold and eaten mainly in
portedly is relatively rare, but occurs fairly fre- towns. Fish as food has been important only among
quently as blennorrhea or gonococcal conjunctivitis the inhabitants of the Black Sea area in Turkey, the
among infants or very young children. In the mid- delta lakes region in Egypt, and the marsh dwellers
twentieth century, nevertheless, venereal diseases of southern Iraq.
were acknowledged public health problems in all the Certain cultural and environmental features re-
countries of the Middle East and North Africa strict diet in both the Middle East and North Af-
(Rodenwaldt 1952; Simmons et al. 1954; Kanter rica. Both Muslims and Jews, for example, are en-
1967; Benenson 1975). joined from eating meat not slaughtered according
to their religious codes, and this ritual slaughter
Nutritional Deficiencies and Disorders adds to the cost. More generally, climatic conditions
The traditional diet of North Africa reflects the geo- and the lack of efficient means of food preservation,
graphic divisions of the area. Each country from the refrigeration, and transport drastically restrict con-
Senegal River to the Nile has a littoral and a desert sumption of fruits, vegetables, milk products, fish,
region that are separated from each other by fertile and meat. The scanty and irregular distribution of
plateaus and arid mountains. Commonly, the littoral rainfall has been a constant factor retarding the
food pattern has been based on cereals and fruit; the development of agriculture. Although production
plateau diet, on cereals, olives, sheep's milk, and has increased in all areas since the Second World
meat; and the desert diet, on dates and camel's milk. War, the low purchasing power of the population,
The dietary patterns of Middle Eastern countries especially in rural areas, as well as the lack of
also reflect geographic and economic conditions. Ex- transport and distribution facilities, has kept con-
cept for Israel and Lebanon, where vegetables and sumption of food low. The result of the foregoing is
fruits abound, cereals provide the major portion of that a significant segment of the population is af-
both the caloric and protein intake in the average flicted with nutritional diseases.
diet. Wheat is the most widely consumed cereal in In Egypt, Iraq, and to a lesser extent in Syria,
all countries; maize is the chief staple in the delta hypochromic microcytic anemia has been attributed
region of Egypt and the Black Sea coast of Turkey; to the prevalence of hookworm infestation in irri-
rice is also popular, but its high cost limits its con- gated farm areas, but there is evidence that para-
sumption to producing areas (mainly Egypt) and the sitic infestation also contributes to the high morbid-
well-to-do; burghul (parboiled wheat sundried and ity of nutritional anemia (May and Jarcho 1961).
crushed) is eaten in Turkey, Syria, and Lebanon as a One investigation in Algeria found that macro-
substitute for rice. Lentils and other legumes are cytic nutritional anemia was common among vari-
consumed widely. ous population groups in the capital, mainly inhabit-
Vegetables such as onions, tomatoes, eggplant, cu- ants of the city slums or rural areas whose diets
cumbers, peppers, squash, and cabbages are univer- were unusually low in protein, fats, fresh fruits, and
sally popular but are consumed in inadequate vegetables. Another survey (May 1967) revealed
amounts. Consumption of fruits shows wide seasonal that a large percentage of children under 1 year of
variations, except for dates, raisins, grapes, and apri- age in Tunisian cities showed signs of nutritional
cots, which can be preserved by drying. The diffi- anemia. And in Morocco it was reported that women,
culty of transporting and preserving fresh milk has especially those pregnant or lactating, showed gross
led to the widespread use of fermented milk, yogurt, evidence of iron deficiency anemia.
and, to a lesser extent, sheep and goat cheese. Kwashiorkor is not as common in the Middle East
Throughout the Middle East, meat is consumed at and North Africa as in sub-Sahara Africa, but it has
a low level, mainly because of its relatively high been reported among the poorest classes in Egypt
cost. Although the animal population in this region and Israel. In Morocco, Algeria, and Tunisia, it re-
is among the highest in the world, livestock repre- portedly has been common following weaning of chil-

dren between 1 and 3 years of age (May and Jarcho anemia and threatening retardation of the physical
1961; May 1967). and mental development of children. Investigators
Xerophthalmia or night blindness due to vitamin A also have suggested that an interaction between
deficiency is common in the Middle East and North Af- poor diet and schistosomiasis may cause pellagra.
rica. Lack of vitamin A also lowers resistance to in- In North African countries and the states of the
fection. For example, keratoconjunctivitis occurring Arabian Peninsula, protein and vitamin deficiencies
in a child deficient in vitamin A increases that child's are reported predominantly among women and chil-
susceptibility to chronic trachoma. Also, in Libya dren, and are not common among men. This observa-
bacterial infections rise during the autumn date har- tion is valid as well for other countries in the region
vest when flies proliferate; combined with vitamin A that share the patriarchal custom of serving the
deficiency, an eye infection may lead to serious father and older sons of the family first, leaving
complications - rupture of the cornea and prolapse of what remains for women and children, which may
the iris - and blindness (Kanter 1967). Night blind- not include meat, fruits, and vegetables.
ness has been reported in Iran and among sedentary In North Africa where the child between 1 and 3
communities of the northern Sahara in North Africa years old is weaned abruptly and then given a diet of
(May and Jarcho 1961; May 1967; Benenson 1975). carbohydrates familiar in family fare, the young
Pellagra, by contrast, has been reported only in may not be able to tolerate the change, which may
the Black Sea area of Turkey and the delta of Egypt then cause dyspepsia, infantile diarrhea, lowered
where maize is the staple grain, and in North Africa resistance to infectious diseases, and kwashiorkor.
during periods of wheat or barley shortage when Nomadic tribespeople of the Sahara south of the
consumption of corn has become necessary. Atlas mountains, however, wean the infant over a
Scurvy is rare in the Middle East and North Africa, 6-month period, introducing it gradually first to cam-
where citrus fruits are usually available, except in el's milk and then to cereals.
Erzerum in northeastern Turkey, which is isolated On the positive side, the high consumption of whole
from food supply lines during winter months. wheat and other cereal products may explain the com-
Rickets, on the other hand, has been observed in parative absence of vitamin B complex deficiencies.
large towns of Iran, Syria, and Egypt where infants Also, traditional dishes that combine cereals with
were swaddled and therefore not exposed to the sun. legumes such as beans, chickpeas, and lentils have
In North Africa rickets was reported in the sunless been demonstrated to be a good source of protein.
slums of coastal cities in Morocco, Algeria, and Tuni- In addition, there are some naturally occurring
sia and among sedentary communities in the north- foods that compensate the inhabitants of unproduc-
ern Sahara. Southern nomads appeared to escape tive areas for the lack of more common foods. In Iraq,
this disease as well as scurvy and xerophthalmia for example, an herb called khoubbaz (Malus ro-
perhaps because of greater exposure to sunlight and tundifolia), which is eaten raw by both rural and
higher milk consumption. Erzerum in northeastern nomadic peoples, has been found to have a high
Turkey has reported seasonal incidence of rickets as ascorbic acid content. And in Libya's Fezzan, two
well as scurvy during long, severe, sunless winters naturally occurring foods have been found to be rich
(May and Jarcho 1961; May 1967; Benenson 1975). in beta-carotene and riboflavin. One, danga, is pre-
pared from an alga growing on salt lakes; the other,
General Observations on Nutrition duda, consists of small crustaceans from the salt
Although malnutrition (overreliance on starch in lakes. Both are kneaded, formed into small cakes,
the diet, with little fat or protein) has been observed, dried in the sun, and later mixed with barley, millet
undernutrition (calorie as well as protein-deficient flour, or dates, and eaten as a main dish in a meal.
diet) has been far more common in the Middle East Lastly, dates, an important food among nomadic and
and North Africa. In most countries, the population seminomadic peoples, are ideal for desert dwellers in
rise has consistently exceeded the increase in culti- that they have a high sugar content, are relatively
vated land. The most dramatic example is Egypt, resistant to contamination with pathological bacte-
where population is increasing by about a million ria, and show long-keeping qualities.
people each year.
In extensively irrigated countries like Egypt and Conclusions
Iraq, and to a lesser extent Syria, there is a synergis- In examining these data on the Middle East and
tic interaction between inadequate diet and parasitic North Africa, I have attempted to connect spatial
infestation, particularly hookworm, causing severe patterns of disease incidence with characteristic fea-

tures of the local environments. The study has indi- Hopkins, Donald R. 1983. Princes and peasants: Smallpox
cated how the geography, topography, and resulting in history. Chicago and London.
climates have been used and misused by humankind Johnson, R. H. 1965. The health of Israel. Lancet 2: 842-5.
over time. The negative aspects of all these factors Kanter, Helmuth. 1967. Libya: A geomedical monograph.
led to low populations in this region until very re- In Studies in geographical medicine, ed. Helmuth
cently. With the introduction of hydroelectric power Jusatz, 1-139. Berlin and Heidelberg.
Khalil, Mohamed. 1932. A century of helminthology in the
and petroleum, the ensuing industrialization has en-
Cairo Medical School. Comptes rendus du congres in-
abled even greater proportions of the populations to ternational de medecine tropicale et d'hygiene 4: 3-25.
live on the seacoast or river banks, and to develop Kinnear-Wilson, J. V. 1967. Organic diseases of ancient
urban centers. Mesopotamia. In Diseases in antiquity, ed. Don
The disease ecologies resulting from the peculiar Brothwell and A. T. Sandison, 191-208. Springfield,
rural environment, mainly with insufficient water; 111.
the specific problems of overcrowded, spatially lim- Labib, Ferdos M. 1971. Principles of public health. Cairo.
ited living areas near water; and the general nutri- Malek, Emile A. 1961. The ecology of schistosomiasis. In
tional deficiencies of poor economies have now been Studies in disease ecology, ed. J. M. May, 261-313.
augmented by increasing population. This phenome- New York.
nal population rise following the establishment of May, Jacques M., ed. 1961. Studies in disease ecology.
post—World War II stability has especially aggra- Studies in medical geography, Vol. 2. New York.
vated conditions of overcrowding, substandard hous- May, J. M. 1967. The ecology of malnutrition in Northern
Africa. Studies in medical geography, Vol. 7. New
ing, and sanitation and poor nutrition in the urban
York.
communities. Although the economic and political May, Jacques M., and Irma S. Jarcho. 1961. The ecology of
patterns of the region vary among the countries, the malnutrition in the Far and Near East. Studies in
interrelationships of many of the other factors re- medical geography, Vol. 3. New York.
main similar. News from the Eastern Mediterranean: Health activities,
LaVerne Kuhnke 1979-80. WHO Chronicle 34: 322-4.
Nosologie marocaine. 1955. Maroc Medical 34: 365-7,
Bibliography 1165-646.
Benenson, Abram S., ed. 1975. Control of communicable Omran, Abdel Rahim. 1961. The ecology of leishmaniasis.
diseases in man. Washington, D.C. In Studies in disease ecology, ed. J. M. May, 331-88.
Brothwell, Don, and A. T. Sandison, eds. 1967. Diseases in New York.
antiquity: A survey of the diseases, injuries and sur- Oxford regional economic atlas: The Middle East and
gery of early populations. Springfield, 111. North Africa. 1964. Oxford.
Cockburn, Aidan, and Eve Cockburn, eds. 1980. Mum- Pollitzer, Robert. 1954. Plague. Geneva.
mies, disease and ancient cultures. Cambridge, U.K. 1959. Cholera. Geneva.
Dols, Michael. 1977. The black death in the Middle East. Rodenwaldt, Ernst, ed. 1952. World atlas of epidemic dis-
Princeton, N.J. eases. Hamburg.
Dorland's illustrated medical dictionary. 1988. Philadel- Ruffer, Marc A. 1910. Note on the presence of bilharzia
phia. maematobia in Egyptian mummies of the 20th dy-
Drysdale, Alasdair, and Gerald H. Blake. 1985. The Mid- nasty (1250-1000 B.C.). British Medical Journal 16:
dle East and North Africa: A political geography. New 177.
York and Oxford. Russell, Alexander. 1794. The natural history of Aleppo,
Farooq, M. 1964. New partnerships in schistosomiasis con- containing.. . an account of the climate, inhabitants
trol. Journal of Tropical Medicine and Hygiene 67: and diseases. London.
265-70. Sandbach, F. R. 1976. The history of schistosomiasis re-
Fenner, Frank, et al. 1988. Small pox and its eradication. search and policy for its control. Medical History 20:
Geneva. 259-75.
Fisher, William B. 1971. The Middle East: A physical, Sandison, A. T. 1980. Diseases in ancient Egypt. In Mum-
social and regional geography. London. mies, disease and ancient cultures, ed. Aidan Cock-
Gallagher, Nancy E. 1983. Medicine and power in Tunisia, burn and Eve Cockburn, 29-44. Cambridge, U.K.
1780-1900. Cambridge, U.K. Simmons, James S., et al. 1954. Global epidemiology: A
Hirsch, August. 1883-6. Handbook of geographical and geography of disease and sanitation, Vol. 2: Africa;
historical pathology, 3 vols., trans. Charles Creighton. and Vol. 3: Near and Middle East. Philadelphia.
London.
Hirst, L. Fabian. 1953. The conquest of plague: A study of
the evolution of epidemiology. Oxford.

VII.3. South Asia 463
neonatal and postneonatal infant care result in

VII.3 very high infant mortality rates and a host of nutri-
Disease Ecologies of South tional disorders. Under such living conditions, and
the highly inadequate nature of the data, discus-
Asia sion of disease ecology of South Asia must remain
broad. In order to understand South Asia's health
context, it is necessary to keep in mind an outline
Disease ecology refers to the intricate human and of some of the essential facts of its physical and
environmental relationships that form the context human environments.
of one or a group of diseases. Diseases are not sim-
ply biomedical entities; rather, they have their
physical, environmental, sociocultural, psychologi- The Physical Environment
cal, and even political parameters. Distinctive hu-
man and biophysical environmental webs form the Topography
context of distinctive groups of human diseases. Ma- The Himalaya and its associated mountain ranges
jor changes in this web, whether brought about by form a physical and cultural divide between South
human intervention, environmental catastrophes, Asia and the lands to the north and east. They rise
or a combination thereof, can result in a new con- in a series of roughly parallel ranges northward
text and possibly a new group of diseases. In devel- from the plains of Bangladesh, India, and Nepal,
oping countries, human control of the environment with each range progressively higher. The much
is limited, basic needs of a healthful life are not lower Sulaiman and Kirthar ranges of western Paki-
met, and, therefore, infectious and communicable stan, with their many passes, have permitted inter-
diseases are the major cause of death. Improve- course with other parts of Asia. Mountains closest to
ments in health conditions will no doubt reduce the the plains have been heavily denuded of their forest
incidence of mortality resulting from infectious discover, and are subject to intense soil erosion.
eases and, in turn, bring about the prominence of South of the world's highest mountain system is
chronic diseases more closely related to life-styles the densely populated alluvial plain of Ganga in
and life stages than to environmental parameters. India and Bangladesh, and the Indus Plain, mostly
South Asia as a geographic region still remains a in Pakistan. Both these plains have extensively de-
region of poverty within which there is a marked veloped systems of irrigation. Canal irrigation is
contrast between the rural and urban genre de vie. particularly well developed in the Indus Plain and
Morbidity and mortality patterns in the rural and the western Ganga Plain. These plains are subject to
urban areas are, therefore, likely to be somewhat periodicfloodingthat is especially heavy and periodi-
different, although paucity and quality of data cally devastating in the eastern part of India and
make generalizations hazardous. Bangladesh.
Ecologically, South Asia is one of the most distinc- The Thar Desert, south of the Indus Plain, is
tive regions of the world. Physiographically well shared by India and Pakistan. Here is a vast arid
demarcated, and climatically distinguished by the region hemmed in from the east by the low Aravalli
monsoonal rainfall regime, South Asian life has a Range. This thinly populated desert region is charac-
rhythm marked by seasonality. Although agricul- terized by shifting sand dunes, large playa lakes,
ture is still the dominant occupation, rapidly swell- salt pans, and, to the southwest, marshlands.
ing cities create air pollution, overcrowding, social South of the Ganga Plain is peninsular India. Com-
stress, and the immense problem of waste disposal. posed of several plateaus, this region, except for the
The dominantly agrarian economic base is being black soils of the Deccan Plateau and the river del-
increasingly supplemented by the diversity of ur- tas, is primarily an area of thin, reddish soils of
ban occupations and modern life-styles. Rapidly medium to poor quality. Part of the peninsula that is
increasing populations on a large numerical base still forested and of marginal quality for agriculture
create an environment of overcrowding, an acute is home to many tribal people. Skirting the penin-
housing shortage, substandard living conditions, sula on the west is the narrow but intensively culti-
and an ever present danger of recurring epidemics. vated and densely populated Malabar coast. On the
Inadequacy of potable drinking water has meant an east the coastal plain is broader. The island nation of
endemicity of various gastroenteric diseases. Un- Sri Lanka is composed of central highlands sur-
dernutrition of pregnant mothers and inadequacy of rounded by a coastal plain.

Climate death rates in the 1980s, infant mortality rates are
South Asia is very hot during the summer; the high- very high: 112 per 1,000 live births in Nepal, about
est temperatures are found in the Thar Desert. Hot 120 in Pakistan, and 138 in Bangladesh. A large
desiccating winds in May and June are frequent in proportion - nearly 40 percent - of the population of
the entire Indus—Ganga Plain and cause substantial South Asia is composed of children under 15 years of
problems of heat stress (Planalp 1971). Tempera- age. Maternal and child health must therefore con-
tures of over 90°F are commonplace. In the moun- sume a large part of the national health budgets.
tainous regions elevation modifies the tempera- Large families, especially of the poor, lead to a high
tures. During winter there is a general temperature incidence of protein-energy malnutrition (PEM). Mi-
gradient from north to south. Temperatures are in gration to urban areas, and life in overcrowded
the 40°F range in the north, reaching well over 75°F houses and hutments mean constant exposure to
in the south. pathogens.
South Asia is characterized by a high degree of
rainfall seasonality, with very uneven geographic Social Realities
distribution, and great variability from year to year. In South Asia, irrespective of religious beliefs, most
In much of India, Bangladesh, Nepal, Bhutan, and of which are expressed in Hinduism, there is a
Pakistan, most of the rainfall is received from June strong concept of social groupings or castes. The
through September. Over the southern part of penin- most important aspect of this system that concerns
sular India, autumn rainfall is significant. On the us here is that the lowest caste groups ("scheduled
southeastern coastal area the predominant season of castes") constitute about 15 percent of India's popula-
rains is autumn.'Most of peninsular India and the tion. They have not only been socially disadvan-
Thar region suffer from high variability of rainfall. taged but also tend to be the poorest. They have
In general, the seasonality of rainfall in the predomi- traditional occupations such as sweeping, cleaning
nantly agrarian societies of South Asia has meant of human waste, skinning animals, and leather
that farming is very dependent upon rainfall despite working, and are spatially segregated in the villages
major developments in irrigation during the twenti- and cities. Although they are not ethnically differ-
eth century. Variability of rainfall, therefore, means ent from the majority population, the hamlets of
that farming communities may suffer from frequent these predominantly landless workers are located
seasonal food shortages, undernutrition, lowered re- separately from the main villages, and their densely
sistance, and higher morbidity. populated clusters of huts are found on the outskirts
Convincing arguments have been made about the of cities along major roads and railway lines. Living
relationship of climatic seasonality to seasonal mor- conditions in their settlements are extremely unhy-
bidity, especially among the poor. Evidence from di- gienic because they lack waste disposal systems.
verse regions of the world, including India/and Ban- Proximity to urban dumps, and pools of stagnant
gladesh, shows that seasonal fluctuations bear more water in construction pits create ideal conditions for
heavily on the poor than on other social groups a very high density offliesand mosquitoes in their
(Chambers, Longhurst, and Pacey 1981). High- settlements.
rainfall regions, especially where humidity is also Tribal cultural groups, collectively termed "sched-
high (e.g., the Malabar coast, Eastern India, and uled tribes," who make up about 3 percent of India's
Bangladesh) are the major endemic areas of infec- population, live mostly in forested, agriculturally
tious diseases such as cholera, typhoid, filariasis, marginal areas of the eastern states, the northeast-
and malaria. ern part of peninsular India, and the degraded for-
ests in Madhya Pradesh, Maharashtra, Rajasthan,
The Sociocultural Environment and Gujarat. Many of these groups practice jhum-
ming, or slash-and-burn agriculture, but others
The Demographic Aspect have migrated to cities and mining areas in search
The South Asian nations are characterized by high of employment. Because virtually all of their tradi-
birthrates, rapidly declining overall death rates, and tional habitat has been isolated, health programs
consequently high natural increases to their already have rarely been extended effectively to them.
large population bases. For example, Bangladesh, at Differential gender valuation is common in South
current rates, will double its population in 25 years, Asia. Male children are valued more than females.
Pakistan in 24, and India in 32 years. The immedi- This tendency is reflected in the actual share of food
ate reality is that in spite of much lowered crude and health care that is available to female children,

who may get a less nutritious diet. When sick, the too poor to rent, must live wherever they can. Thus,
males are more likely than females to receive medi- many semipermanent urban accretions have devel-
cal attention. In general, it would appear that fe- oped. Health conditions in these periurban slums
male morbidity is underreported. are very poor. In fact, these settlements form a vir-
tual ring of high morbidity around growing cities.
General Health Conditions in South Asia Engulfed by rapidly growing suburban housing,
South Asia is home to most diseases of humankind; these shanties are frequently found in close proxim-
surprisingly, yellow fever and some others are ab- ity to outward developing metropolitan areas. City
sent. The major causes of death include infectious governments are constantly trying to "clear" these
and parasitic diseases such as tuberculosis, diar- semipermanent worker settlements (in India called
rhea, malaria, typhoid, gastrointestinal disorders, jhuggies and jhonparies, or simply JtTs), often with
and a variety of childhood diseases such as tetanus, great difficulty. In the meantime, they remain as
pneumonia, whooping cough, diphtheria, measles, centers of high morbidity and infant mortality.
and other preventable diseases (Nyrop 1984). A Expanding cities are also engulfing preexisting
health survey in Pakistan during the mid-1970s re- villages, thus juxtaposing two very different ways of
vealed that nearly 30 percent of the people had ma- life. Demand for milk and meat in the burgeoning
laria, and almost 100 percent had worm or parasitic urban populations has spurred these farming com-
afflictions (Nyrop 1984). Although published data on munities to intensify their farming by growing vege-
many health indicators are lacking or woefully defi- tables, and by keeping dairy cows, buffaloes, and
cient, some indication of health conditions may be chickens. The lower castes raise goats and pigs in
obtained from life expectancy, crude death rates, and these periurban locations. One effect of this urban
infant mortality rates. Death rates in South Asia, as agriculture is that the density of flies and mosqui-
in most developing regions of the world, have de- toes in these areas is very high, thus helping to
clined markedly since the 1970s, although they are maintain endemicity of gastroenteric diseases.
still above the world average. Within South Asia,
Sri Lanka has the lowest death rate (about 6 per Ecology of Selected Diseases in South Asia
1,000), which is lower than most of the European In the space of this essay, it is possible to focus on
countries and the United States (9 per 1,000). Death only a few selected prevalent diseases in South Asia.
rates are higher for India (10 per 1,000) and even Thus, smallpox, in spite of the fact that it was once a
higher for Pakistan (14), Bangladesh (15), Nepal and major killer disease in India, has been omitted be-
Bhutan (17 each). Infant mortality rates, however, cause it has been eradicated. Likewise, although
reveal a grimmer picture of the prevalent health plague has some endemicity, its incidence is now
conditions. Despite official claims to the contrary, very limited. Instead the focus is on diseases of high
infant mortality rates are very high, except in Sri endemicity or prevalence.
Lanka, thanks largely to a very high female literacy
rate compared with other South Asian countries. Cholera
Considering Sri Lanka as the exception, South Asia Although cholera, an acute communicable disease, is
as a whole shows clear signs of environmentally not peculiar to South Asia, there are endemic areas of
related causes of death, especially of infants. cholera in this region from which periodic outbreaks
Sanitation conditions in South Asia are appalling, have occurred (see Map VII.3.1). Cholera etiology is
made worse by the monsoon rains. Most rural inhab- relatively simple, since this disease is caused by the
itants and those living on the outskirts of the cities ingestion of Vibrio cholerae. Two distinct modes of
use fields and any open space as a latrine. Although cholera transmission are usually recognized (Craig
the new "Sulabh" (semiflushing) latrine is gaining 1986). In the "primary" transmission, the vibrio is
ground in Indian cities, human waste disposal re- ingested through vegetables and fish raised in water
mains a serious problem, leading to a variety of that is contaminated with the vibrio. The "secon-
gastrointestinal diseases. Contamination of munici- dary" mode is the fecal-oral transmission. In non-
pal drinking water during the rainy season, includ- immunized persons with relatively lowered stomach
ing cities such as Delhi, results in periodic outbreaks acidity, symptoms of cholera develop rapidly, marked
of hepatitis epidemics. by frequent watery stools, vomiting, and fever. Since
The process of urbanization in South Asia is bring- the vibrio is present in great quantities in the charac-
ing vast numbers of rural unemployed workers to teristic watery stools,fliesmay carry the germ from
the cities. Those unable to find relatives, or who are them to human food. Consumption of this contami-

I Cholera
Malaria - (a) hyper-endemic
(b) endemic
"Kangri Burn" Cancer
Map VII.3.1. General endemicity of N.D. no data
cholera, malaria, and "kangri

burn" cancer. (Based on Misra
1970; Hutt and Burkitt 1986.)
nated food results in the ingestion of the vibrio, thus mulation of cholera germs in pools of water increase,
creating a fecal-oral link, resulting in manifestation putting at risk individuals who use this water for
of the disease. Death occurs as a result of excessive drinking. During the dry season, shrinking pools and
dehydration, electrolyte imbalance, and the pyro- tanks, owing to intense heat, become even more con-
genic endotoxins of V. cholerae. centrated with the vibrio. Fish taken from these
Cholera remains endemic in the delta lands of sources, and vegetables washed with this water, can
Ganga in West Bengal and Bangladesh. Indeed, the transmit cholera. Since most drinking water is nei-
"cholera pandemic that scourged the world in the ther filtered nor boiled, chances for vibrio ingestion
first half of the nineteenth century began in the remain high. During the monsoon season, when heat
Bengali basin and spread as far and as rapidly as and humidity are high, people tend to lose large
man was then able to travel" (Cahill 1976). The rea- amounts of moisture with sweating. Drinking large
sons for cholera's endemicity have to do with a com- quantities of water greatly dilutes the stomach acid-
bination of physical, environmental, and human con- ity. If vibrio-infected food or water is taken under this
ditions. The deltaic region is characterized by heavy condition, the chances for disease manifestation mul-
monsoon rainfall from June through September, re- tiply. This situation happens usually at village fairs,
sulting in frequent and often disastrousflooding.In periodic markets, or other big gatherings in the open.
the aftermath of rains, slow-moving water in the Because the disease has a very rapid course, causing
maze of Ganga's distributaries and stagnant water in vomiting, fever, and passage of watery stools, vibrio
numerous shallow pools characterize the landscape. from such body wastes can be easily conveyed by the
Tanks and wells used as a resource for drinking wa- ubiquitous flies to food items being consumed by
ter are filled with surface flow. Algal infestations of other participants at the fair. Cholera epidemics are
these ponds and tanks greatly increase the alkalinity therefore notorious for their speed and virulence dur-
of stagnant water, and create favorable conditions for ing the summer monsoon season.
the multiplication of V. cholerae (Jusatz 1977). Most From the delta region of the Ganges, cholera has
people defecate outdoors and seek proximity to water often spread in epidemic forms (May 1958; Acker-
for cleaning themselves. Thus, chances for the accu- knecht 1972), although today the death rate is quite

low because of widespread immunization in South defecation increases the chances that the pathogen
Asia. In the past, cholera has also been spread could be carried under the fingernails, and conveyed
through the agency of pilgrims, both Hindu and Mus- to food. Many middle-class South Asian families em-
lim (Misra 1970; Dutta 1985). Hindus visiting their ploy servants as cooks who come from poor families.
sacred places in different parts of India have been Dysentery pathogens may be inadvertently con-
exposed to cholera. The massive Kumbha bathing veyed to the food of these families, even though the
festivals that attract pilgrims from all over India latter may have a high standard of personal hy-
have been the scene of cholera epidemics. Pilgrims giene. Many edible items in stores and shops are
from the endemic areas have inadvertently carried exposed to flies and dust in spite of public health
the cholera germ to sacred centers, where sanitation regulations. It is virtually inevitable that such items
breakdowns have occurred, leading to the exposure of when consumed (without cooking) will carry patho-
pilgrims from nonendemic areas. Muslim pilgrims on gens with them. In cities, where it is easier to en-
hajj to Mecca from Bengal in the past may also force environmental hygiene regulations, and where
have been both carriers of and affected by chol- the modernizing consumers themselves exert suffi-
era. Although these religious convergences remain a cient pressure, store owners do respond by adopting
potential mechanism for the diffusion of cholera, strict hygienic practices. But most of the population
large-scale immunization efforts and improved water of South Asia is rural, and therefore the enforcement
supplies at these religious centers have prevented of public health measures is highly problematic. In
epidemics of cholera. At large pilgrimage congrega- addition, the population - especially the adult rural
tions in India, pilgrims are routinely checked for cer- population - of South Asian countries (Sri Lanka is
tification of cholera immunization at points of entry again the exception) is mostly illiterate, and does
to the designated area of religious fairs. Those with- not effectively demand hygienic practices from food
out a valid certificate are inoculated on the spot be- vendors. Thus, dysentery, a highly preventable dis-
fore proceeding further on their religious journey. ease, persists.
As expected, dysentery shows marked seasonality
Dysentery and Diarrheal Disease in South Asia, because cpnditions for the multiplica-
Intestinal infections of various types are widely tion of flies, a major carrier of dysentery pathogens,
prevalent in South Asia. Cholera has been the focus become ideal during and soon after the rainy season,
of much attention because of its notorious epidemics through summer and early autumn. This is also the
and pandemics; however, it is dysentery (both season when many types of melons, other fruits, and
amebic and bacillary) that generally leads in morbid- vegetables are sold in the open. Thus, even the more
ity in most normal years. Unfortunately, dysentery literate urban populations are placed at risk. Poor
and diarrhea (due to a variety of diseases of the sections of the cities - the slums and the shanties -
alimentary canal) have not been accorded the atten- are particularly vulnerable because of the virtual
tion they deserve because they are predominant lack of sanitation facilities that lead to a very high
among poor rural children. Perhaps as many as 80 density of fly population. Many sanitary systems
percent of rural India's children are infected by para- break down, and wells get polluted. The diffusion of
sitic worms (Nyrop 1986). Tropical diarrhea, mostly tube wells as sources for irrigation and drinking
a traveler's disease, has attracted far more attention water in the rural areas may have had some impact
in-the literature than the killer infantile diarrhea, on the incidence of dysentery. The prevalence of dys-
which is linked to high infant mortality throughout entery in South Asia illustrates the fallacy of consid-
India, Pakistan, Nepal, Bhutan, and Bangladesh. ering disease as only a biomedical entity. It forces us
The causative agent of bacillary dysentery is bacte- to recognize the significance of looking at the web of
ria of the Shigella group, whereas amebic dysentery ecological relationships between people and their
is produced by protozoa. However, both diseases total environment.
manifest after ingestion of the pathogen whether by
food infected byfliescarrying the pathogen, by one's Malaria
own infected hands, or by infected vessels, such as Fevers of many types have been described in the
food containers. Thus, cultural practices, personal ancient Vedic literature of India. Vedic hymns speak
cleanliness, and the nature of the food available of fevers that cause chills and high body tempera-
determine whether the disease will actually develop ture, and torment the sufferer during summer and
in an individual or family. The practice of using autumn (Filliozat 1964). An intermittent fever,
water on bare hands for cleaning the anal area after takman, seems to have been particularly feared by

the Aryans living in the Indus Basin. Their descrip- 5. The western part of the Ganges Delta, and parts
tions indicate characteristics of the fever much re- of the Coromandel coastal region of peninsular
sembling malaria in its seasonality and symptoms. India. The Ganges Delta, of course, has the typi-
Unlike cholera, malaria ecology is complex, since cal monsoon rainfall regime, but the Coromandel
this infection depends upon the life cycles of the coastal region is an area of mostly autumn rain-
parasite Plasmodium and the vector Anopheles mos- fall. These are densely populated, dominantly ag-
quito on the one hand, and human contact with the ricultural areas.
infected vector on the other. This contact has to be
close enough for the infected vector to take a human In addition to these areas of hyperendemicity,
blood meal and, in the process, to inject the pathogen most of India, with over 40 inches of rainfall, was
parasite into the human bloodstream. Repeated in- considered endemic for malaria. Moderate malaria
fections are not uncommon, and once the plasmo- endemicity also was found in the plains of Punjab,
dium parasite is in human blood, fever relapse can especially along the rivers and the irrigation canals.
occur. Characterized by chills, high fever, splenomeg- The rest of India, with rainfall of less than 40 inches,
aly, and debilitation, malaria fever has had a serious suffered from periodic, but severe, epidemics of ma-
impact on economic development by affecting mil- laria. Especially intense "fulminant" epidemics oc-
lions of people. Between 1947, India's year of Inde- curred in the western Ganga Plains and the adjoin-
pendence, and 1953, the year the Malaria Control ing Punjab Plains.
Program was first launched, malaria incidence was
about 75 million, of which nearly 800,000 lives were Malaria Resurgence. A. T. Learmonth (1957,1958),
lost to this disease annually (India 1987). A. K. Dutt, R. Akhtar, and H. Dutta (1980), and later
Learmonth and Akhtar (1984) have added signifi-
Distribution. Geographic distribution of malaria, cantly to our knowledge of malaria ecology in India.
as indeed of several other diseases, has been affected In a series of maps, they bring out the story of ma-
by socioeconomic changes in South Asian countries laria resurgence from 1965 to 1976. Through the
since the 1950s. Before Independence, the major efforts of the government of India, aided by the World
hyperendemic areas (spleen rates over 75 percent) Health Organization (WHO), and the active support
included the following: of the state governments, malaria seemed to have
been brought under control. The success of the Ma-
1. The narrow tarai belt along southern Nepal and laria Control Program, consisting mostly of the
northern Uttar Pradesh. Lying at the foot of the spraying of DDT, encouraged the government of In-
Himalaya Mountain system, this strip was charac- dia to convert this program to malaria eradication,
terized by tall thick grass and sal forest on a which showed spectacular success until about 1965.
relatively thin stony soil. Rainfall in this region In that year, malaria incidence had declined to
decreases toward the west but is generally over 60 100,000 as compared to 70 million in 1947. But two
inches per annum. India-Pakistan wars (1965 and 1970-1), the war of
2. The hills of eastern India up to a height of about Bangladesh's liberation, and later the oil crisis re-
5,000 feet. These forested and poorly accessible sulted in massive disruption of the campaign against
areas have been thinly populated by tribal people malaria. In addition, both the Anopheles vector spe-
who practiced considerable slash-and-burn agri- cies and the pathogen Plasmodium have developed
culture. Rainfall in these areas is very heavy and resistance to antivector and anti-Plasmodium chemi-
is highly concentrated during the months of June cals and drugs, respectively. Thus, hopes of malaria
through September. eradication were replaced by the stark reality of its
3. The Chota Nagpur Plateau and the Eastern Hills recrudescence. From a low of about 100,000 cases in
region of the Indian Peninsula. Covered by for- 1965, a resurgence of malaria developed, with over 5
ests, these regions have poor reddish soils and million cases in 1975. In spite of further malaria
marginal agriculture carried on by tribal people. control efforts, there were still 2 million cases in
Rainfall is well over 40 inches and occurs mostly 1979, only marginally declining to about 1.6 million
in the months of June through September. by 1985. A similar resurgence has occurred in sev-
4. A narrow forested strip along the crest of the eral other countries (Development Forum 1988).
western Ghats. This region receives heavy rain- Geographically, as Learmonth and Akhtar (1984)
fall during the monsoon season, but the rest of the have showed, by 1965 most of India had a low annual
year is quite dry. parasite index (API) (see Map VII.3.2). An API of

196S 1970
Annual parasite Index rate per 1,000
5 and under 20 50 and over
Map VII.3.2. Malaria: annual parasite index (API), per 1,000 population, for selected years.
(Based on Learmonth and Akhtar 1984.)

over 5 per 1,000 existed in the hyperendemic region decade since 1881: insanity, deaf-muteness, blind-
of Eastern Hills, parts of Chota Nagpur Plateau and ness, and leprosy. The last disease is usually of two
northeastern peninsular India, western Vindhyan types - tuberculoid and lepromatous. Tuberculoid
Range, the marshlands of Kachch and western leprosy is usually self-limiting, whereas the leproma-
Gujarat, and the foothill zone of western Uttar tous form is progressive. The causative pathogen of
Pradesh. Relative inaccessibility is a major common leprosy is the bacillus Mycobacterium leprae. Lep-
attribute of all these areas. Their rainfall and soil romatous leprosy is the classic dreaded disease in
characteristics vary widely, but all these areas have which, in advanced cases, loss of digits and other
a high proportion of "scheduled tribes." It needs to be deformities occur. The pathogen is usually thought
stressed that these people have a somewhat different to enter the body through the mucous membrane of
genre de vie than do the nontribal populations of the upper respiratory tract, or through repeated and
India. Formerly much more widespread, the tribal close skin contact, but there is controversy among
peoples now occupy "refuge areas" of marginal agri- leprologists as to the exact mode of transmission
cultural productivity. Malaria control - eradication (Cahill 1976; Sutherland 1977). The incubation pe-
programs of the government of India - seemed to riod is long - 1 to 5 years - making research, early
have been ineffective in these poorly accessible ar- detection, and understanding of the diffusion process
eas. Thus, these areas remained highly endemic ma- very difficult.
larial time bombs. Slackening of the eradication pro- Persons with advanced stages of leprosy are fre-
grams, due to diversion of the national resources to quently found begging at the railway stations, at the
two major wars in the subcontinent, in 1965 and bus stations, and especially at the holy places all
again in 1971, meant a partial reassertion of the over South Asia. Even though legislation against
pre—Malaria Control Program pattern of malaria begging has been frequent, the problem is far from
epidemics. From these focal points, malaria spread solved. Likewise, the stigma attached to leprosy has
again to virtually all parts of India, although as a made early treatment very difficult by discouraging
result of antimalarial drugs and greater availability patients to seek appropriate treatment. Since the
of medical facilities, mortality is now minimal. A disease is considered the greatest misfortune, suffer-
virtually similar process of malaria resurgence oc- ers from it arouse pity rather than understanding.
curred in Bangladesh (Paul 1984). Malaria had been In general, leprosy sufferers are isolated from the
beaten back to the remote tribal areas of Chittagong society either because of their own voluntary re-
Hills, from which it has reasserted itself. sponse or as a result of government policy. India has
The history of malaria control holds a major lesson in place a national leprosy control program under
for all concerned. That lesson is that a disease with a which 434 leprosy control units along with 6,784
complex ecology deserves a multipronged approach. survey, education, and treatment centers, 721 urban
It is necessary to have a well-orchestrated plan of leprosy centers, and 46 leprosy training centers have
action by specialists in various pertinent fields of been developed (India 1987). In neighboring Nepal,
science and bureaucracy, but it is imperative that the National Leprosy Control Program was estab-
the political leadership exercise wisdom. Malaria lished in 1975; now the Leprosy Service Develop-
control, let alone eradication, is possible only under ment Board, it provides treatment and rehabilita-
conditions of political stability, permitting an unin- tive services for leprosy patients.
terrupted commitment of national resources. Cur-
rent interethnic conflicts in Punjab, eastern Indian Geographic Distribution. South Asian countries
states, Bangladesh, and Sri Lanka will surely affect have a medium rate of leprosy, but the very large
malaria control programs adversely. total population base results in a correspondingly
large absolute number of sufferers. In India alone,
Leprosy the prevalence rate of 5.7 per 1,000 population in
Leprosy (Hansen's disease) has been known in South 1986 suggests that the number of leprosy patients
Asian countries since antiquity. Called kustha in the exceeds 4 million, according to government data (In-
Hindu medical literature, it was considered to be dia 1987). Areas of high leprosy prevalence in India
transmittable to the child from parents "when a (over 10 per 1,000) include the following: (1) a belt of
woman and a man have (respectively) the blood and coastal districts of Tamil Nadu, Andhra Pradesh,
sperm vitiated by leprosy" (Filliozat 1964). During and Orissa, which continues into most of West Ben-
the British rule in India, the Census of India (1913) gal and adjoining southern Bihar; (2) western Maha-
collected data on four types of disabilities for each rashtra and the adjoining eastern Andhra Pradesh,

N.D.
Prevalence rate percent
3.00 and over
2.00 • 2.99
1.00-1.99
Less than 1.00
N.D. no data
Map VII.3.3. Leprosy: prevalence

rate percentage, 1974—5. (Based on
Pearson 1984, 1988.)
a substantial part of which was once the princely tions for the diffusion of leprosy. With increasing
state of Hyderabad (all of this area lies in the inte- mobility, the disease could spread without notice. As
rior section of the Deccan Plateau); (3) isolated areas Kevin Cahill (1976) observed, in the "meagerness of
in other parts of India, including the tarai region of our knowledge of the clinical, the bacteriological and
Uttar Pradesh and the far eastern parts of India. the pathological course in the incubational phase of
Surprisingly, Bangladesh reported only 110 cases of leprosy lies the primary reason for the failure of
leprosy in 1979; Pakistan, 3,269; and Sri Lanka, 751 international control and eradication programmes."
(WHO 1981). The longitudinal river valleys of Nepal Peoples along traditional routes of commerce - for
apparently show a high prevalence of endemic example, the river valleys in Nepal - could be espe-
leprosy - over 10 per 1,000 population. cially at risk (Pearson 1984). In spite of the argument
that leprosy is not easily communicable, intrusive
Problems of Leprosy Control. Because leprosy is tourism does place the visitors at risk of carrying the
prevalent in both flat coastal areas and hills and disease from the traditional endemic areas to other
valleys, and in areas of low and high rainfall, any parts of the world.
relationship with broad physical environmental fac- At one time it was hoped that the disease could be
tors seems only tenuous at best (see Map VII.3.3). eradicated because human beings are known to be
Secrecy surrounding earlier phases of the disease the only significant reservoirs of the leprosy patho-
and the victims' fear of social ostracism in the latter gen (Lechat 1988). That this has not occurred seems
stages make control and curative efforts difficult to reason for less optimism, at least in the foreseeable
implement. Slow progression of the disease and the future. However, "multidrug therapy" (MDP), early
necessity for prolonged treatment compound both the identification of cases and at-risk populations, social
preventive and curative problems. It has been found and cultural sensitivity toward the patient, long-
in Nepal that people do not necessarily use the treat- term commitment of the governments, and immuno-
ment facilities located nearest to them, for fear of logic and epidemiological research, can together
being stigmatized in their local community. Patients make a major impact. Immunologic advances, based
seem deliberately to seek treatment at distant facili- upon the cultivation of large quantities of M. leprae
ties (Pearson 1988). This trend has major implica- bacilli in armadillos, and advances in molecular

Map VII.3.4. General distribution

of filariasis and goiter. (Based on
May 1961; Misra 1970; Schwein-
furth 1983; and India, a reference
annual 1987.)
genetics seem to promise positive results, but large- ver, lymphadenitis of the groin, and epididymitis. As
scale confirmatory results are awaited from field the worms multiply, reach adulthood, and die, condi-
trials (WHO 1985). tions such as hanging groins and elephantiasis of
the legs develop. The high prevalence rate of ele-
Filariasis phantiasis of legs on the Malabar coast of India has
Filarial infections, caused by worms such as Wuche- led to the nomenclature "Malabar legs."
reria bancrofti and Brugi malayi, are widespread in The essential components of the filaria ecology in
the tropical climates of Africa, Southeast and South South Asia are the pathogens W. bancrofti and B.
Asia, and the Caribbean. In India alone, over 15 malayi, several species of the mosquito vectors
million people suffer from filariasis, and over 300 (Culex, Anopheles, Aedes), a hot and wet climate
million are at risk (India 1987) (see Map VII.3.4). with high humidity, moist and warm soil, availabil-
Filariasis is endemic in the entire Konkan and ity of stagnant pools of water, and a population of
Malabar coastal areas of western India, the coastal predominantly poor people. Culex and Anopheles
areas of Tamil Nadu, Andhra Pradesh, and Orissa. mosquitoes, both abundant in all parts of South
Its incidence declines rapidly toward the interior Asia, but especially in the high rainfall regions, pick
and the northwestern parts of India. The lowest inci- up microfilaria through a blood meal from infected
dence is found in the Himalaya region. Sri Lanka's human beings, which reach the larva stage in the
major endemic area of filariasis is in the hot, humid, mosquito. These larvae are then introduced to other
and high rainfall areas of the coastal southwest human beings through repeated mosquito bites.
(Schweinfurth 1983). Filariasis is found in both the Filarial larvae reach adulthood in from 1 to 3 years,
rural and urban areas of this coastal region, al- and may produce swarms of microfilariae. Most of
though there are significant differences in the impli- the pathological symptoms are due to larvae and
cated pathogen of the two settings. adult worms (Cahill 1976).
Microfilariae of the worm pathogens entering the More than women, men are susceptible victims
human bloodstream through mosquito bites, circu- because of their outdoor agricultural activities and
late in blood, develop into larvae and, under suitable relatively less protective clothing. There is increas-
conditions, into adult worms. Filariasis leads to fe- ing concern that filariasis is becoming an urban

disease as well. This is happening primarily as a Haryana, S. K. Aggarwal (1986) found that "no
result of the migration of rural males to large cities other factor seems to affect the nutritional status of
in search of jobs. Many of these poor migrants must the children as much as family income." The scien-
live on the outskirts of the cities, where there is an tific concept of balanced diet in South Asia is only of
abundance of stagnant water pools as a result of academic importance; the real concern is dietary
construction activity. These pools serve as breeding sufficiency.
grounds for the urban mosquitoes, which, in turn, The Indian Council of Medical Research found in
become intermediate hosts of the pathogen between its surveys that about 35 percent of children have
new immigrants and the established city popula- protein-calorie malnutrition (Mitra 1985). Earlier
tions. Thus, a disease that at one time was thought emphasis on protein deficiency has given way to the
to be primarily rural is on its way to becoming an more widely acceptable concept of protein-calorie
urban phenomenon as well. U. Schweinfurth (1983) malnutrition (PCM) or protein-energy malnutrition
provides a very interesting case study of filariasis (PEM) (Learmonth 1988). India, Bangladesh, and
infections at the University of Peradenya in Sri Nepal together have a serious problem of malnutri-
Lanka. The beautification of the campus also pro- tion and hunger, even though in recent years agricul-
vided a very good habitat for the breeding of Culex tural production has been rising, especially in India.
vector. Students attending this university from in- The situation in Pakistan and Sri Lanka is, on the
fected areas were the carriers of W. bancrofti in their average, "adequate," but in India, Bangladesh, and
blood. In the beautified university campus, they be- Nepal, less than 90 percent of the average daily
came the source of the pathogen for the mosquito energy requirements are met.
that also found the university campus environment The relationship between food in the market and
conducive for breeding. The vector mosquitoes in its availability to an individual for actual consump-
turn introduced the disease to students from non- tion depends on a host of intervening factors (Aggar-
endemic areas as well. wal 1986). Among these factors are family income,
Difficulty of detection of the disease (microfilariaegender, age, season of the year, government regula-
show no pathogenic symptoms) at the early stage tions, and cultural factors such as dietary restric-
makes preventive measures difficult as well. Sadly, tions, taboos, and preferences. Addressing the role of
filaricidal and larvicidal treatment is available to cultural dietary preferences in disease ecology, A. K.
only about 10 percent of the population in the en- Chakravarti (1982) provides evidence to show that
demic areas of India (WHO 1984). Efforts to intro- existing regional differences do translate into a sig-
duce larvivorousfishin pools of water where mosqui- nificantly higher incidence of diet-related diseases.
toes breed may be helpful as part of a comprehensive These facts were earlier noted by J. M. May (1961).
filaria control program. This strategy, however, may In predominantly rice-eating areas, where highly
be ineffective in the periurban areas where pools of polished rice is preferred, beriberi is preeminent,
water quickly become polluted andfilledwith urban because of thiamine deficiency, which results from
waste. These pools are useless for fish culture, but do the polishing process. Where parboiled rice is widely
invite mosquitoes to breed. employed, however, the incidence of beriberi is
claimed to be significantly lower. Consumption of
Ecology of Nutritional Deficiency Diseases khesari as the basic pulse in eastern Madhya Pra-
Attention to communicable diseases may tend to desh has been associated (Chakravarti 1982) with
mask the prevalence of a great variety of diseases the incidence of lathyrism, which is characterized by
that are the result of undernutrition as well as mal- muscular atrophy, causing the typical "scissors
nutrition. With a very large number of people living gait," incontinence of urine, and sexual impotence
in extreme poverty in South Asia, dietary deficien- (Manson-Bahr 1966).
cies are to be expected. Although "diseases of pov- The impact of malnutrition is not easily mea-
erty" do not constitute a special category in the offi- sured, but some of the effects are well known and
cial International List of Disease Classification, the include anemia, goiter, night blindness, rickets, beri-
international medical community is increasingly beri, and probably permanent damage to the ner-
cognizant of such a class (Prost 1988). M. S. R. Hutt vous system, resulting in mental disorders. The
and D. P. Burkitt (1986) go so far as to say that "most long-term economic, social, and personal impact of
so-called tropical diseases are, in fact, diseases of these dietary deficiencies can only be imagined. In
poverty, rather than of geography." On the basis of addition, undernutrition of pregnant mothers has
his field studies on the nutrition of children in adverse consequences both for them and for their

babies, who are often of low-birthweight. It is a well- lar set of environmental circumstances. Nevertheless,
established fact that low-birthweight is a major some generalizations appear justified. Without question,
correlate of infant mortality. Thus low-income, un- nutritional and infectious diseases account for the largest
dernourished mothers are likely to have a higher percentage of mortality and morbidity in most underprivi-
frequency of low-birthweight babies, and thus con- leged countries, especially in those just becoming industri-
tribute disproportionately to higher infant mortal- alized. . . . In contrast, the toll taken by malnutrition and
infection decreases rapidly wherever and whenever the
ity. Even in the same village infant mortality among living standards improve, but other diseases then become
the poor is twice that of the privileged people (Mitra more prevalent.
1985).
Some of the nutritional deficiency diseases have a South Asian societies are in the process of major
clear regional prevalence. Goiter, for example, has a change, since economic development has become the
high rate of endemicity in a sub-Himalayan belt goal of all the nations (except perhaps Bhutan). In
extending from Arunachal Pradesh and other states pursuit of this goal, national governments have be-
in northeast India through Bhutan, West Bengal, come deeply involved in directing the nature and
Sikkim, Bihar, Nepal, Uttar Pradesh, Himachal pace of change. Against heavy odds, the processes of
Pradesh, Jammu, and Kashmir. Goiter is also found social and economic change are beginning to show
in parts of Gujarat, Madhya Pradesh, and Maharash- their impact. Even in some rural areas of India, a
tra (India 1987). Endemic goiter is primarily due to major reduction in seasonal morbidity of communica-
a dietary iodine deficiency, resulting in enlargement ble diseases has been observed concomitant with ag-
of the thyroid gland. At one time considered only an ricultural prosperity (Bhardwaj and Rao 1988), sug-
unsightly inconvenience, goiter is now known to be a gesting that Western-style development is not a sine
possible precursor of cancer of the thyroid, and is qua non for better health conditions. Sri Lanka,
associated with below normal mental and physical which placed great emphasis on education, has
development. It is also possible that very high infant achieved a high female literacy rate (over 80 per-
mortality in these regions is related to regional io- cent). This has had a major impact on the reduction
dine deficiency (Hutt and Burkitt 1986). The govern- of the birthrate and has helped greatly to reduce the
ment of India in 1983 launched a major program, infant mortality rate, even though Sri Lanka has not
through both private and public channels, of iodiz- become an economically well-developed country. Ne-
ing salt, in an effort to combat iodine deficiency and pal, India, Pakistan, and Bangladesh have not been
decrease goiter incidence. able to accomplish the same for their female popula-
Every culture has some distinctive practices that tion, and consequently their infant mortality rates
may be associated with culture-specific diseases. For are still very high. Female literacy in India varies
example, only in Kashmir do people use an earthen widely between social groups and regions. Where
pot (kangri) containing live coal, nestled in a wicker female literacy is high — for example, in the urban
basket, that hangs by a thread around their neck areas and in the southwest (Kerala) - birthrates and
during the winter season, as a portable personal infant mortality have come down.
body warmer. Heat and irritation from this kangri One of the results of the Green Revolution has
practice is significantly associated with the kangri- been an increased labor demand in the highly irri-
burn cancer, especially among the elderly (Manson- gated areas of western U.P., Punjab, Haryana, and
Bahr 1966). Similarly, cancer of the buccal cavity is Rajasthan. Long-distance agricultural labor migra-
found to be associated with the long-term habit of tions from Bihar and eastern U.P. to the above areas
chewing betel. This habit is common in eastern have now become commonplace. This means that
Ganga Plain and southwestern India. Plasmodium from the eastern part of India has a
greater chance of establishing itself in the farming
Economic Development and Disease communities of northwestern India. Increased avail-
ability of water in the irrigated areas provides an
Ecology expanded habitat for the Anopheles mosquito vector
In his influential book, Man, Medicine, and Environ- as well.
ment (1968), Rene Dubos makes a poignant observa-
tion about disease and development: International migration and tourism, which are
intensifying in South Asia, have been implicated in
Disease presents itself simultaneously with so many dif- the importation of newer diseases; AIDS is only one
ferent faces in any given area that it is usually impossible example (India Abroad, October 26,1990). When the
to attribute one particular expression of it to one particu- first few cases of AIDS were reported in India, the

Indian government was alarmed enough to enforce cultural aspects of food use in India. In India: Cul-
serotesting of foreign students, especially coming tural patterns and processes, ed. Allen G. Noble and
from AIDS endemic areas of sub-Saharan African Ashok K. Dutt, 301-23. Boulder, Colo.
countries. This action immediately aroused the anger Chambers, R., Richard Longhurst, and Arnold Pacey, eds.
of exchange students and strong reactions from sev- 1981. Seasonal dimensions to rural poverty. London.
eral African governments. According to a WHO warn- Craig, Marian. 1988. Time-space clustering of Vibrio chol-
erae 01 in Matlab, Bangladesh, 1970-1982. Social
ing, there may be already over 250,000 HIV-positive
Science and Medicine 26: 5-13.
cases in India with an expectancy of over 60,000 Development Forum. 1988. The malaria comeback. Develop-
AIDS patients by 1995 {India Abroad, October 26, ment Forum 16(2): 16.
1990). The incidence of AIDS is, as yet, reported Dubos, Rene. 1968. Man, medicine, and environment. New
primarily from the major metropolitan areas such as York.
Bombay, Madras, Calcutta, and Delhi, and is cur- Dutt, A. K., Rais Akhtar, and Hiran M. Dutta. 1980. Ma-
rently associated mostly with prostitution. Precisely laria in India with particular reference to west-central
because of this association, however, AIDS will very states. Social Science and Medicine 14D: 317-30.
likely spread into the general population. Since mi- Dutta, M. K. 1985. The diffusion and ecology of cholera in
gration to cities is large, and rural-urban interaction India. In Geographical aspects of health and disease in
is intensifying, the vast rural areas will not be im- India, ed. Rais Akhtar and A. T. A. Learmonth, 91—
mune from AIDS for long. Existing models of AIDS 106. New Delhi.
diffusion strongly suggest this possibility (Shanon Eisenberg, Leon, and Norman Sartorius. 1988. Human
and Pyle 1989). Thus, the context of health is becom- ecology in the repertoire of health development.
World Health Forum 9: 564-8.
ing much wider than imagined under the older health
Filliozat, J. 1964. The classical doctrine of Indian medi-
paradigm in which the physician was considered the cine: Its origins and its Greek parallels. Delhi.
final health authority. L. Eisenberg and N. Sartorius Gopalan, C , et al. 1971. Diet atlas of India. Hyderabad.
(1988) have rightly asserted that "health will have to Hasan, Arif. 1988. Low cost sanitation for a squatter com-
be seen as a state of balance between human beings munity. World Health Forum 9: 361-4.
and their environment. Human ecology can help to Hazara, Jayati. 1989. The changing pattern of diseases in
develop this approach to health and its promotion." West Bengal, India. Singapore Journal of Tropical
South Asian countries have already started to prove Geography 10: 144-59.
the efficacy of such an approach. Hutt, M. S. R., and D. P. Burkitt. 1986. The geography of
non-infectious diseases. Oxford.
Surinder M. Bhardwaj
Hyma, B., and A. Ramesh. 1985. The geographic distribu-
tion and trend in cholera incidence in Tamil Nadu. In
Bibliography Geographical aspects of health and disease in India,
Ackerknecht, Erwin H. 1972. History and geography of the ed. Rais Akhtar and A. T. A. Learmonth, 169-219.
most important diseases. New York. New Delhi.
Aggarwal, Surinder K. 1986. Geo-ecology of malnutrition: India A broad (weekly). October 26, 1990, 19.
A study of the Haryana children'. New Delhi. India, Government of. 1987. India: A reference annual
Akhtar, Rais. 1985. Goitre zonation in the Kumaon region. 1986. New Delhi.
Social Science and Medicine 12D: 152-63. Jusatz, H. 1977. Cholera. In A world geography of human
Akhtar, Rais, and Andrew T. A. Learmonth. 1985. The diseases, ed. G. Melvyn Howe, 131—43. London.
resurgence of malaria in India. In Geographical as- Learmonth, Andrew T. A. 1957. Some contrasts in the
pects of health and disease in India, ed. Rais Akhtar regional geography of malaria in India and Pakistan.
and A. T. A. Learmonth, 107-23. New Delhi. Transactions of the Institute of British Geographers
Bhardwaj, Surinder M., and Bimal K. Paul. 1986. Medical 23: 37-59.
pluralism and infant mortality in a rural area of Ban- 1958. Medical geography in Indo-Pakistan: A study of
gladesh. Social Science and Medicine 23: 1003-10. twenty years' data. Indian Geographical Journal 33:
Bhardwaj, Surinder M., and Madhusudana N. Rao. 1988. 1-59.
Regional development and seasonality of communica- 1988. Disease ecology: An introduction. Oxford.
ble diseases in rural Andhra Pradesh, India. Social Learmonth, Andrew T. A., and Rais Akhtar. 1984. The
Science and Medicine 26: 15-24. malaria resurgence in India 1965-76. Annals, Na-
Cahill, Kevin M. 1976. Tropical diseases: A handbook for tional Association of Geographers, India 4: 23—69.
practitioners. Westport, Conn. Lechat, M. F. 1988. Leprosy: The long hard road. World
Census of India. 1913. Census ofIndia, 1911, India, part 1: Health Forum 9: 69-71.
Report. Calcutta. Manson-Bahr, Philip H. 1966. Manson's tropical diseases:
Chakravarti, Aninda K. 1982. Diet and disease: Some A manual of the diseases of warm climates. London.

May, Jaques M. 1958. The ecology of human disease. New
York. VII.4
1961. The ecology of malnutrition in the Far and Near
East. New York.
Disease Ecologies of East
Misra, R. P. 1970. Medical geography of India. New Delhi. Asia
Mitra, Asok. 1985. The nutrition status in India. In Nutri-
tion and development, ed. Margaret Biswas and Per
Pinstrup-Andersen, 142-62. Oxford.
Nag, Moni. 1988. The Kerala formula. World Health Fo-
East Asian scholars have begun only recently to
rum 9: 258-62. examine Chinese, Korean, and Japanese sources for
Nyrop, Richard E, ed. 1984. Pakistan: A country study. evidence of the history of disease in East Asia. Re-
Washington, D.C. search is at a very early stage: There is much that
1986. India: A country study. Washington, D.C. we do not know, and some of what we think we know
Paul, Bimal K. 1984. Malaria in Bangladesh. Geographi- may turn out to be wrong. At present, scholars dis-
cal Review 74: 63-75. agree about basic facts as well as about how to inter-
Pearson, Maggie. 1984. Leprosy moves along the Nepalese pret them. It is possible, however, to discuss how
valleys. Geographical Magazine 54: 504-9. disease ecologies changed as East Asian civilization
1988. What does distance matter? Leprosy control in developed, and this essay will consider how long-
west Nepal. Social Science and Medicine 26: 25—36. term historical change in East Asia altered the dis-
Planalp, Jack M. 1971. Heat stress and culture in North ease ecologies of this major world region.
India. Alexandria, Va.
Prost, A. 1988. When the rains fail World Health Fo-
East Asia is a large ecological niche bounded on
rum 9: 98-103. all sides by less hospitable terrain. To the north and
Schwartzberg, Joseph E., ed. 1978. A historical atlas of northwest lie the vast steppe lands of Central Asia
South Asia. Chicago. and the virtually impossible Takla Makan Desert.
Schweinfurth, U. 1983. Filarial diseases in Ceylon: A geo- To the west lie the high Tibetan Plateau and the
graphic and historical analysis. Ecology of Disease 2: Himalayan Range with the world's highest moun-
309-19. tains. To the south is the mountainous terrain of
Shanon, Gary W, and Gerald E Pyle. 1989. The origin and southwest China and the jungles of Southeast Asia.
diffusion of AIDS: A view from medical geography. And to the east lies the Pacific Ocean. These formida-
Annals of the Association of American Geographers ble barriers and the great distances between eastern
79: 1-24. and western Eurasia long separated East Asia from
Sri Lanka, Survey Department. 1988. The national atlas the ancient civilizations of the West, and permitted a
of Sri Lanka. Colombo. distinctive culture to develop and to spread through-
Sutherland, Ian. 1977. Tuberculosis and leprosy. In A
out the region with relatively little influence from
world geography of human disease, ed. G. Melvyn
Howe, 175-96. London. the outside.
WHO. 1981. World health statistics annual. Geneva. East Asia can be divided into two major ecological
1984. Lymphatic filariasis; Fourth report of the WHO zones. The northern zone encompasses the steppe
Expert Committee on Filariasis. Geneva. and forest lands that lie north of China's Great Wall
1985. Vaccination trials against leprosy. WHO Research and today includes the modern regions of Inner Mon-
and Training in Tropical Diseases 85.3: 1-15. golia and Manchuria. This vast territory is unsuit-
1986. WHO Expert Committee on Malaria; Eighteenth able for agriculture, and it has long been the home-
report. Geneva. land of nomadic tribes who migrate with the seasons
1987. Multidrug therapy in leprosy control. In World seeking grazing lands for their livestock. The steppe
health statistics annual, 23—4. Geneva. supports relatively few people, and thus has been
1988. Malaria control activities in the last 40 years. In sparsely settled throughout human history. Low
World health statistics annual, 28-9. Geneva.
population density and a pastoral, nomadic way of
life have prevented the buildup of endemic foci of
disease organisms in any one place.
Ecological conditions south of the Great Wall are
altogether different. North China, which includes
the areas drained by the Yellow River and its tribu-
taries, as well as the northern tributaries of the
Yangtze River, has a temperate, semiarid climate
with hot summers and cold winters. Rainfall is lim-

VII.4. East Asia 477
ited and uncertain - about 400 to 800 millimeters The Neolithic Revolution in China was clearly suc-
per year. North China is most suitable for growing cessful. Archeological evidence and early forms of
millet, wheat, and beans, and one or two crops a year Chinese ideographic script reveal an advanced soci-
can be grown in a growing season that lasts from 4 to ety based on labor-intensive agriculture from the
6 months. time of the Shang dynasty (1765-1122 B.C.). The
South China, generally the region from the need for labor led to dense concentrations of people
Yangtze Valley to the coast of southern China, has a and the need for protection to walled cities where
subtropical climate, abundant rainfall (approxi- grain could be stored and defended. These fundamen-
mately 800 to 1,600 mm per year), and temperatures tal changes altered the size, density, and distribution
that are less extreme than those of North China. of populations on the East Asian mainland. The
Rice is the dominant crop in the south, and two or growth of cities brought new problems: Human and
three crops can be grown during 9 to 12 months of animal wastes accumulated, drinking water became
the year. Despite these differences in climate, North contaminated, parasites that thrive in stagnant wa-
and South China have been bound together histori- ter flourished, and people who now lived close to-
cally by a dominant, distinctive culture common to gether in permanent settlements became a reservoir
them both. And in historic times both regions have for microparasites that cause human disease.
supported far greater population densities than the The range of Chinese expansion to the south and
frontier regions north of China's Great Wall. east was virtually unlimited. As indigenous peoples
In prehistoric times Paleolithic humans roamed took up an agrarian way of life, more land was
over all of East Asia. Early hunters and gatherers brought under cultivation and China's population
inhabited the forests and steppes of northeastern grew. From the time of the Shang dynasty to the
Asia, the highlands and plains of North China, the unification of China in 221 B.C., the Chinese people
semitropical and tropical regions of South China, were ruled by great regional lords who controlled
the Korean peninsula, and the Japanese islands. As large territories in North and South China. There are
long as primitive humans moved from place to place no census statistics to serve as benchmarks, but other
in search of food, the disease ecologies of East Asia kinds of evidence indicate that even before unifica-
must have been essentially unchanging. Although tion China had produced a large population. The size
early humans may have been afflicted with mala- of armies increased 10-fold during the Warring States
dies caused by microparasites indigenous to the dif- period (421 to 403 B.C.), and by the fourth century
ferent regions of East Asia, they did not suffer from B.C. each of the leading states of China was able to
many of the diseases with which we are familiar support a standing army of about 1 million men.
today, because the microparasites that cause them In 221 B.C., Shih Huang-t'i, ruler of the state of
require large and concentrated host populations that Ch'in, conquered all of China, unifying the states
did not yet exist. and regions of North and South China. He ordered
The history of changing disease ecologies in East the construction of large-scale public works designed
Asia begins with the emergence of Chinese civiliza- to consolidate political control and to unify China
tion in late Neolithic times. In East Asia, as in other economically. These projects, which included the con-
parts of the world, human society underwent a funda- struction of a national network of roads and the
mental change in the late Neolithic period when the completion of the Great Wall on China's northern
ancestors of the Chinese people began to engage in frontier, offer further evidence of an abundant labor
agriculture and to live in permanent communities. force. The latter project alone required an estimated
This transition from shifting to permanent places of 700,000 laborers to build.
residence occurred in at least two and possibly sev- Long periods of warfare and large public works
eral regions of China about 6,000 years ago. The best projects helped to homogenize the disease environ-
known Neolithic sites are found in the loess region of ment. The amassing of soldiers for battle and the
North China near the juncture of the Wei and Yellow concentration of many thousands of workers pro-
rivers; however, recent excavations in the Yangtze vided an ideal environment for disease organisms to
River delta have turned up evidence of Neolithic propagate. And when the participants returned
communities that may be even earlier than those home, they carried diseases to the towns and vil-
of North China. The historic relationship between lages through which they passed. Hence, the con-
these cultures is not clear, but it was from these core struction of roads and canals, whose function was to
regions that the culture we regard as distinctively strengthen centralized control, promoted the spread
East Asian evolved. of disease throughout the empire.

The Ch'in dynasty was short-lived, but the consoli- disease-causing organisms and nonimmune popula-
dation of political power under centralized imperial tions must have been repeated over and over again
rule continued under the dynasties that followed. in the course of human history as civilizations with
The four centuries of Han rule (202 B.C. to A.D. 220) different disease ecologies came into contact with
were a period of expansion in which the Chinese way one another. Thus it is appropriate to ask whether
of life based upon labor-intensive, irrigated agricul- East Asian populations also suffered major demo-
ture became the dominant culture on the mainland. graphic catastrophes as a result of the introduction
And during the Sui (581-618) and T'ang (618-907) of unfamiliar disease organisms.
dynasties, the completion of the Grand Canal that Undoubtedly there was such a time, but Chinese
connected the Yangtze and Yellow rivers reinforced historians have not denned it as such. A likely time
the links between north and south China. for such an occurrence was around the beginning of
Urbanization was another prominent feature of the Christian era, when growth and expansion of the
social development in the early empire. By T'ang early empire brought China into more frequent con-
times, China had 21 cities with more than a half- tact with neighboring peoples to the south. By the
million inhabitants. The largest urban concentra- first century B.C., a string of populous communities
tion was at the T'ang capital of Ch'ang-an, which stretched from South China to Bengal, and by the
had 2 million registered inhabitants. Even smaller first century A.D., traders and Buddhist missionar-
cities like the southern port of Canton and the bus- ies were traveling overland from northern India to
tling economic center at Yangchow, where the Grand China through Central Asia and by way of Vietnam.
Canal joined the Yangtze River, were centers of hu- Chinese scholars also traveled to India to study at
man density large enough to serve as reservoirs for Buddhist monasteries, and they returned with for-
many human disease pathogens. eign diseases as well as foreign philosophies.
In short, from very early times China had one of One of these foreign diseases, possibly the first to
the world's largest populations and conditions of life be reported in Chinese sources, was smallpox. Small-
that could support many of the density-dependent pox, a prominent, density-dependent disease of the
diseases of civilization with which we are familiar past, is used here as a paradigm for disease in gen-
today. Indeed social, demographic, and environmen- eral, because it was highly visible and because
tal conditions in the early empire were such that changes in its incidence and distribution reflect
China must have had a full range of indigenous changing disease ecologies.
diseases that varied by region according to the cli- It is not clear exactly when smallpox first reached
mate, the available host and vector populations, the China, but at least two early references to it are
density and distribution of human host populations, known. Donald Hopkins (1983) suggests that a dis-
and the sanitary conditions in those regions. But for ease called "Hun pox" that came to China from the
the most part, we do not know what diseases were north around 250 B.C. may have been smallpox. He
present in the early empire. also suggests a second introduction of smallpox from
We do know, however, that many different kinds of the south about A.D. 48, when a Chinese general
human disease existed in China from very early and half his troops lost their lives to a "barbarian"
times, because they were written about on the disease as they were putting down a rebellion in
Shang oracle bones that were used for divination (as southwest China. The first unmistakable descrip-
indicated in Lu and Needham, in this volume, VI. 1). tion of smallpox comes from an account written in
According to these ancient writings, the diseases the fourth century A.D. (Leung, in this volume,
prevalent at the time exhibited many different symp- VI.2). However, given the extent of earlier Chinese
toms and were called by many different names. But contact with India - where it is believed this disease
whether they were caused by pathogenic agents that was known before 400 B.C. - smallpox must have
exist today, by related pathogens, or by unrelated reached China earlier than the fourth century.
pathogens is uncertain. We do not need to know precisely when smallpox
first reached China to understand that early small-
Introduction of New Diseases pox epidemics would have been very costly in terms
The introduction of new diseases to a virgin popula- of human life. Smallpox normally produced a 25
tion can be calamitous. The most celebrated case is percent case-fatality rate, and in virgin-soil epidem-
known as the "great dying" that followed the intro- ics the rate would have been much higher. Thus
duction of Old World diseases to the New World in given China's population size and the links between
the sixteenth century. But contact between virulent many centers of density, we can be certain that the

VH.4. East Asia 479
introduction of smallpox to China caused a demo- were built, and these countries began to be afflicted
graphic crisis of considerable magnitude. with the civilized diseases of China. Contact be-
Population trends for the early empire suggest tween China, Korea, and Japan increased after the
that there were several demographic crises that sixth century, and smallpox and other epidemic dis-
might have been caused by unfamiliar diseases. Peri- eases were spread along with Buddhism and other
ods of population growth alternated with periods of cultural exports.
population decline: From the Warring States period Japanese accounts of smallpox epidemics in A.D.
through the Tang dynasty, China's population fluc- 585 and 735-7 provide excellent early descriptions
tuated, reaching and then retreating from a maxi- of this disease. The smallpox epidemic of 735 came
mum of about 60 million people. The periods of de- from the kingdom of Silla in southern Korea. It
cline during these centuries have been associated began in the part of Kyushu nearest to Korea, and it
with natural disasters and China's periodic wars, spread toward the major population centers in the
but high mortality from disease, undoubtedly exacer- region around the capital at Nara. Although this
bated by war and famine, certainly contributed to was not Japan's first smallpox epidemic, it caused
population decline. high mortality among all age groups in the popula-
After the initial shock waves subsided, however, tion, indicating that smallpox epidemics did not
the demographic characteristics of China's popula- reach Japan very frequently. Wayne Farris believes
tion would have ensured that smallpox became an that high mortality from virulent, imported diseases
endemic disease rather quickly. Hopkins estimates between 645 and 900 caused Japan to suffer a demo-
that a population of less than 300,000 people was graphic setback that had a major impact on Japan's
sufficient to maintain smallpox as an endemic dis- political, economic, and social development in this
ease, because enough new susceptibles would have early period.
been borne each year to sustain the chain of small- Once imported epidemics reached Japan, the di-
pox infection indefinitely. As an endemic disease, rection of spread was invariably from the south-
smallpox would have circulated throughout the em- west - where ports of entry for foreign ships were
pire, appearing most frequently in the larger cities located - to the northeast along routes where Ja-
and least often in the sparse populations of the hin- pan's population was concentrated. Japan had a
terlands. We know that smallpox continued to claim high population density very early in its history,
numerous lives in China for many centuries; how- and as in China, most diseases became endemic
ever, once smallpox and other infectious diseases with little difficulty. Smallpox was clearly endemic
became endemic, the risk of a catastrophic demo- in Japan by the twelfth century and probably well
graphic crisis would have been sharply reduced. before (Jannetta 1987).
The history of smallpox in East Asia reveals a The more sparsely settled and remote areas of
curious chronology in the transmission of this dis- East Asia could still be seriously threatened by se-
ease. Of particular interest is the fact that smallpox vere epidemics as late as the seventeenth century. In
is documented much earlier in the ancient civiliza- Japan, offshore islands, villages in the northeast,
tions of the West. Egyptian mummies 3,000 years and mountainous regions remained vulnerable. In
old have been found with scars that resemble the China it was the dispersed, low-density populations
typical pockmarks left by smallpox; and the people that lived in semiautonomous areas along the enor-
of ancient Greece, as well as the people of India, are mous northern and western frontier that were at
believed to have been afflicted with this disease be- greatest risk of suffering highly disruptive mortality
fore 400 B.C. The much later documentation of small- from epidemics.
pox in China suggests that smallpox spread to east- During the seventeenth and eighteenth centuries,
ern Asia from the West - a journey, if estimates of the dissemination of disease intensified as these pe-
when smallpox reached China are even close to be- ripheral regions were gradually incorporated into
ing correct, that took more than a thousand years. the main networks that operated in East Asia. Sev-
eral factors contributed to this intensification pro-
The Dissemination of Disease Within East cess: East Asian populations increased in size and
Asia density, urbanization accelerated in both China and
By late Han times Chinese culture began to spread Japan, contact between core and periphery in-
to the other regions of East Asia. As the indigenous creased, and activity on China's frontier intensified.
peoples of Korea and Japan began to adopt irrigated, Changes in tribute relations accompanied the con-
wet-rice agriculture, their numbers increased, cities solidation of Tokugawa and Ch'ing power in the sev-

enteenth century, and promoted the dissemination of dispersed and mobile populations north of the Great
disease within East Asia. Between 1637 and 1765, Wall had much less exposure to human pathogens
contacts between China and Korea increased: An than did the densely settled populations to the
average of 3.8 tribute missions a year traveled from south. And because of infrequent exposure they were
Korea to Peking, and in fact Korea and the Ryukyu extremely vulnerable to the civilized diseases of
Islands sent tribute missions to Japan as well. The China.
King of the Ryukyus was regularly required to pay During the late Ming (1368-1644) and early
his respects to the daimyo of Satsuma and on occa- Ch'ing (1644-1911) dynasties, Chinese civilization
sion to the Tokugawa shogun in Edo (Sakai 1968). In began to encroach on territories to the north, and
Japan, the shogunate institutionalized contact be- there was increasing contact between northern Chi-
tween core and periphery with the creation of the nese and the nomadic peoples of the steppe. China's
sankin-kotai system. This system required that traditional policy had been to forbid trade with these
large numbers of retainers travel to Edo from each of barbarian enemies. But as this policy simply encour-
the provinces in alternate years to pay attendance aged invasion raids and seizure of whatever goods
upon the shogun. All of these activities would have were available, at times the Chinese government
increased the rate of disease dissemination in Japan. reluctantly set up official markets to facilitate the
The development of interregional trade in Japan exchange of goods.
also served to disseminate density-dependent dis- The numerous military campaigns of the late
eases throughout the islands. As outlying regions Ming period required large supplies of horses. In the
were drawn into a more widespread market net- second half of the sixteenth century, the Chinese set
work, they were also incorporated into a wider net- up official horse markets on China's northern fron-
work of disease dissemination. Local records show tier, where cloth and grain were exchanged for Mon-
that epidemics became more frequent in the hinter- gol cattle, sheep, mules, and horses. Initially there
lands of Japan during the Tokugawa period. By the were four market locations - at Tatung, Hsuan-fu,
end of the seventeenth century, smallpox epidemics Yen-sui, and Ningsia - where horse fairs were held
were occurring every few years in outlying villages; during the spring and summer months. In time,
by the end of the eighteenth century, smallpox epi- smaller markets were added at other places along
demics had become increasingly frequent on the is- the Great Wall where forts were situated. These
land of Tanegashima, and in the Ryukyu Islands. small markets permitted Mongols who lived near
Even the most isolated islands of the Izu chain south the frontier to come to trade once or twice a month,
of Chiba Prefecture were stricken by smallpox - and the regularization of these markets provided a
reportedly for the first time - in the late eighteenth more dependable supply of goods for Chinese and
century. By the late 1700s density-dependent dis- Mongol alike (Hou 1956). At the same time, more
eases common to the urban centers were afflicting frequent contact between Mongols and Chinese per-
even the most remote regions of Japan (Jannetta mitted the dissemination of the density-dependent
1987). diseases of China to the tribal peoples of the steppe.
On the East Asian mainland, the disease ecology of The disease problems that followed the growth of
China began to expand across the northern frontier. fairs and the border trade in the second half of the
To the north and northwest the range of Chinese sixteenth century are documented in both Chinese
expansion had been sharply limited. The steppes of and Mongol sources. The Mongols were most fearful
Mongolia and Manchuria and the high Tibetan of smallpox, which was rare in Mongolia. The biogra-
wastes had no great river systems from which water phy of Tu T'ung, a military commander in Shensi,
could be drawn to support intensive, irrigated agri- tells of an incident in which men returning from the
culture, and a pastoral society that stood in stark border caught smallpox and died. The incident re-
contrast to that of China had developed on China's sulted in several border clashes, because the Mon-
northern frontier. The steppe had become the home of gols, who were unfamiliar with smallpox, thought
nomadic tribes whose wealth was moveable herds of that the men had been poisoned by the Chinese.
livestock, not land or grain. The Great Wall of China, Chinese contacts constituted the gravest danger
built to keep out the "barbarian" peoples who raided from smallpox for the Mongols, who recognized that
Chinese settlements, marked the frontier between danger and did what they could to contain the dis-
two fundamentally different cultures. ease and prevent further contamination. It was cus-
The Great Wall also marks the frontier between tomary strictly to avoid the stricken person, whether
the two major disease ecologies of East Asia. The a parent, brother, wife, or child:

VII.4. East Asia 481
stead to Jehol for the ceremony. Although some schol-
They provide [the sick] with a Chinese to take care of him;
and if there is no Chinese available, they prepare his food
ars have thought that the code was designed to pro-
and other necessities in a place other than their own and
tect the Chinese from Mongol infections, it is clear
let the person stricken with smallpox take care of him-that its intent was to protect the Mongols who would
self. . .. [T]hey regard China as a house on fire, and they
needlessly be exposed to a grave danger.
refuse to stay there long for fear of contracting smallpox.
These examples illustrate the changes that took
(Serruys 1980) place in East Asia in the early modern period. There
For the Mongols the danger of exposure to small- were real differences between the disease ecologies
pox and other diseases increased during the six- of the East and West, and these differences contin-
teenth century because of increasing contact with ued to be important. Unlike Africa, the Americas,
the Chinese. Not only did they encounter them dur- and many of the more sparsely settled countries of
ing invasion raids and at the border markets and Europe, many density-dependent diseases were al-
fairs, but also after midcentury many Chinese immi- ready endemic in East Asia before the sixteenth
grants settled north of the Great Wall and lived century. Disease ecologies in the West were com-
intermingled with the Mongols. These communities pletely transformed by the discovery of the New
were particularly vulnerable to high mortality from World. The high level of epidemic mortality in the
epidemic diseases. One Chinese observer claimed early modern West may well be related to the un-
that the border communities had grown to 100,000 usual disease exchange that took place between the
by the 1590s, but "luckily" a great epidemic had cut urban centers of Europe and the peripheral primi-
their numbers down by half (Serruys 1980). tive societies with relatively low-density popula-
The Manchus, too, had increasing problems with tions with which they came in contact.
the civilized diseases of China. In Manchuria, as in No such transformation took place in East Asia.
Mongolia, smallpox was a relatively rare disease. There was much greater stability in the high-
The widely scattered populations, often on the move, density populations of China and Japan where many
had prevented the virus from gaining a foothold. diseases were endemic and circulated regularly
However, in the late Ming as Chinese began to settle within a relatively closed system. Thus the arrival of
in Manchuria and as contacts between Manchus and the Europeans in the sixteenth century changed the
Chinese increased, the diseases of China - smallpox disease ecology of East Asia very little.
in particular - became a serious threat. The disease environment of early modern East
An observation relating to the year 1633, when Asia did change, but the reason for change was to-
the Manchu armies were ready to invade China, tally unrelated to new foreign contacts. In East Asia
indicates their awareness of this threat: "Order the dissemination of disease intensified because of
beiles who have already once contracted smallpox to population growth, increasing urbanization, an in-
lead an army from I-p'ien-shih to take Shan-hai- crease in the volume of trade within the region, and
kuan" (Serruys 1980). The order to pick only immu- the integration of more sparsely populated frontier
nized troops for an extended stay in China shows regions into the network of civilized diseases. This
that they understood the great risk of contracting process was affected very little by outside develop-
smallpox there, and they knew that those who had ments. In the modern period, however, when rapid
once had the disease would not get it again. transport began to connect all of the world regions,
Even after China was conquered by the Manchus, East Asia's large, high-density population emerged
Ch'ing legislation for the Mongol bannermen indias a disease center that could disseminate diseases
cates that the Manchu rulers continued to take the to the rest of the world.
problem of smallpox seriously. Proscriptions against Ann Bowman Jannetta
going to the capital when one had not been already
infected with the disease were incorporated into the Bibliography
Ch'ing codes. Two expressions - "those who have al- Chun Hae-jong. 1968. Sino-Korean tributary relations in
the Ch'ing Period. In The Chinese world order, ed.
ready had smallpox" and "those who have not yet
J. K. Fairbank, 90-111. Cambridge, Mass.
had smallpox" - became almost technical terms in Farris, W. W. 1985. Population, disease, and land in early
the Li-fan-yuan code, which was translated into Mon- Japan, 645-900. Cambridge, Mass.
golian. Mongols who inherited a rank within the Fujikawa, Y. 1969. Nikon shippei shi. Tokyo.
administration, and who would normally go to Pe- Hsu Cho-yun. 1980. Han agriculture. Seattle.
king to receive their succession, were excused if they Hopkins, D. R. 1983. Princes and peasants: Smallpox in
had not yet contracted smallpox. They would go in- history. Chicago.

Hou Jen-chih. 1956. Frontier horse markets in the Ming 30,000 years ago that Southeast Asian hunter-
dynasty. In Chinese social history: Translations of se-
gatherers crossed land bridges and narrow channels
lected studies, American Council of Learned Societies.
into New Guinea, Australia, and Tasmania. Inter-
Hucker, C. O. 1975. China's imperial past. Stanford. migration among these landmasses was curtailed
Jannetta, A. B. 1987. Epidemics and mortality in early around 8,000 years ago, when New Guinea and
modern Japan. Princeton. Tasmania became separate islands.
Sakai, R. K. 1968. The Ryukyu (Liu Ch'iu) Islands as a fief
of Satsuma. In The Chinese world order, ed. J. K. A later wave of Malay-type horticulturalists from
Fairbank, 112-34. Cambridge, Mass. islands of Southeast Asia invaded the coasts and
Serruys, H. 1980. Smallpox in Mongolia during the Ming rivers of New Guinea about 6,000 years ago, bring-
and Ch'ing dynasties. Zentralasiatische Studien 14: ing root crops, pigs, chickens, dogs, and polished
41-63. tools. These agriculturalists then spread out through
the islands of Melanesia around 3,000 to 4,000
years ago in their sailing canoes. At this same time,
other Southeast Asian agriculturalists migrated
from the Philippine Islands to Yap and the Mariana
Islands and from Sulawesi to Palau, thus settling
VII.5 the high islands of western Micronesia. After the
voyagers had settled the major islands of Melane-
Disease Ecologies of sia, they pushed north from Vanuatu into Kiribati,
Australia and Oceania thence into the Marshall Islands, and finally into
the Caroline Islands about 2,000 years ago. As Mi-
cronesia was thus being settled, other voyagers ad-
Geography and Demography vanced from Fiji east to Samoa and Tonga around
The islands of Oceania are divided into three large 3,000 years ago. From this cradle, they moved out
geographic areas. Polynesia occupies an enormous through the rest of eastern Polynesia - to the Mar-
triangle in the eastern and central Pacific, stretch- quesas 2,000 years ago and from there to the Soci-
ing from Hawaii in the north, to French Polynesia ety, Cook, and Hawaiian Islands around A.D. 600,
and Easter Island in the east, to New Zealand in the New Zealand around A.D. 750, and Tokelau and
west. Melanesia encompasses the western island Tuvalu and assorted scattered outliers after A.D.
chains that lie south of the equator and extend from 1000.
New Guinea to New Caledonia and Fiji. Micronesia With rare exception, these Pacific Basin island
includes the groups of islands that lie west of Polyne- people were gardeners and fisherfolk, supplement-
sia and north of Melanesia. Although Polynesia is ing their diet with various parts of wild plants, small
spread widely across the Pacific, the physical envi- animals of the beach or bush, or pigs and chickens
ronments — whether volcanic high islands or coral that they raised. Most lived in small hamlets of close
atolls — are all quite similar in being lushly vege- relatives, although sizable villages were to be found
tated and almost all rich in food resources from land especially on the coasts of the larger islands. The
and sea. Melanesia has the greatest variety of physi- Australian aborigines were nomadic within circum-
cal environments: mountain rain forests, grassy pla- scribed territories. Like the aboriginal Australians,
teaus, gorges and valleys, low jungles and allu- the New Zealand Maori were hunters and gatherers
vial plains, mosquito-ridden riverine and coastal without pigs or chickens, yams or taro. Unlike the
swamps, sandy beaches, volcanic fields, and earth- Australians, the Maori lived in large settlements
quake-prone rifts. In western Micronesia, weathered and had sweet potato and fern root as well as a rich
volcanic islands are interspersed among small, lush variety of birds, reptiles, and fish to eat (Oliver
coral atolls. Farther to the east (Marshall Islands 1962).
and Kiribati), the Micronesian atolls are generally Water supplies were often limited throughout
much drier and larger. Except for temperate New most of the region (Henderson et al. 1971). Atoll
Zealand and arid or temperate Australia, the cli- dwellers were without rivers or lakes, and had to
mate of Oceania remains generally hot and humid rely on rain catchment or brackish pools. The vol-
year-round. It is generally accepted that Oceania canic islands generally had freshwater sources, but
and Australia were populated by waves of immi- settlements near them caused pollution, and people
grants initially from Southeast Asia (Oliver 1962; living on ridgetops above them had to transport the
Howe 1984; Marshall 1984). In fact, it was over water over long distances. Water kept near shelters

VII.5. Australia and Oceania 483
was easily contaminated. Lack of abundant fresh- eighteenth century, British explorers first contacted
water for washing resulted in poor hygiene. most of the islands of Polynesia, including New Zea-
land, as well as the Marianas and the east coast of
Australia. At this time, the French were charting
Indigenous Diseases some of the same islands in Polynesia plus groups of
Those European explorers who commented upon the islands off the east coast of New Guinea.
health of the indigenous people they contacted de-
British, French, and American missionaries; Brit-
scribed them as strong, well-shaped, clean, noble,
ish, French, German, and American merchants; and
and generally healthy (Moodie 1973; Howe 1984).
British and American whalers began to move into
Because the weak, ill, or deformed were unlikely to
the Pacific in the late eighteenth century. The Brit-
be among the greeting party, such an appearance
ish established their first permanent settlement in
might be made even if endemic diseases were pres-
eastern Australia in 1788, and claimed sovereignty
ent. Although geographic isolation had protected Pa-
over Australia and New Zealand by 1840. Whaling
cific peoples from the epidemic diseases that had
peaked in the 1850s, but the missionaries and mer-
swept Europe, Africa, and the New World, their con-
chants had become a continuing feature of Pacific
tinued if infrequent contacts with Southeast Asia,
island life in the nineteenth century. In the latter
ever since the initial migrations to Australia and
half of that century, coconut and sugar plantations
New Guinea, exposed them to some of the diseases
were developed on many of the islands, and "black-
extant there (Ramenofsky 1989). Diseases known
birding" sailing ships raided islands in Micronesia
(from explorers' journals or dated skeletal remains)
and Melanesia for indentured laborers to work on
to be present in the region before first contact with
plantations in the islands, in Peru, and in northeast-
Europeans include malaria (restricted to Melanesia
ern Australia. By the late nineteenth century, only
as far south as Vanuatu), respiratory infections, en-
residents of the interior highlands of a few large
teritis, rheumatism and degenerative arthritis, den-
Melanesian islands had escaped extensive experi-
tal wear and decay, eye infections, filariasis, ring-
ence with Westerners.
worm, boils, tropical ulcers, yaws, and a disfiguring
ulceration of the skin. Infant mortality rates were In addition, Chinese, Japanese, and Filipino la-
high, and those who survived could expect to live borers were brought to the plantations of Hawaii,
into their thirties (Howe 1984; Denoon, with Dugan South Asian laborers to Fiji, Southeast Asian labor-
and Marshall 1989). ers to Vanuatu and New Caledonia, and Chinese
traders were prevalent on many of the large islands.
Gold mining operations in the late 1800s led to the
Contact with the Outside World importation of Southeast Asian workers who lived
Early in the sixteenth century, the first Europeans in overcrowded camps and towns in Melanesia un-
ventured into the Pacific, beginning the waves of der worse living conditions than laborers residing
foreigners who reached this region carrying assorted on plantations.
new infectious diseases (Oliver 1962). Magellan's Commerce and communication were somewhat
ships crossed the Pacific from the Americas to South- disrupted in the region by World War I, but the
east Asia, making the initial contact with the Mari- main effects of that war were the shuffling of colo-
anas Islanders. Within a few decades, Guam was a nial powers and the major influx into Micronesia
regular port of call on the Spanish trade route be- and Melanesia of Japanese, Korean, and Oki-
tween Mexico and the Philippines, and Spanish mis- nawan businessmen, fishermen, miners, and mili-
sionaries were proselytizing the Marianas. In the tary. Hong Kong laborers flocked to the phosphate
latter part of the century, Spanish explorers sailed mines of Nauru and Banaba after the war. The
from Peru to the Marquesas and to the islands of discovery of large deposits of gold in northeastern
Melanesia before reaching the Philippines. New Guinea, Fiji, and the Solomons in the 1920s
In the seventeenth century, Dutch traders ex- triggered new interest in these areas and encour-
plored the northern, western, and southern coasts of aged the exploration of New Guinea's central high-
Australia, coastal New Guinea and New Ireland, lands by airplane. This opening up of previously
and island groups in eastern and western Polynesia. impenetrable landscape by air allowed the first con-
British parties during this time period harried the tact between the large populations of highlanders
Spanish galleons in the Pacific Basin and along the and Europeans. Contact among all the islands of
New Guinea coast, calling in at islands as fresh food the Pacific and between the islands and the con-
and water were needed. In the latter half of the tinents bordering the Pacific was greatly facili-

tated by the establishment of transpacific and soil" for these epidemics from the rest of the world or
Australia-New Guinea air routes in the decades even-in the case of malaria in the Papua New
before World War II. Guinea highlands - from circumscribed areas of en-
Pacific islanders suffered greatly during the Sec- demicity within the region.
ond World War. When peace finally returned, the Because it involved translocating large numbers
United States replaced Japan as the colonial pres- of people around the Pacific and concentrating them
ence (U.N.-mandated trustee) in much of Micro- in crowded unhygienic quarters, the labor trade had
nesia, and joined Britain, France, Australia, and a particularly devastating effect on health (Saunders
New Zealand in major disease-eradication projects 1876; Schlomowitz 1987). Laborers not properly
in the region, made possible by the advent of new screened or in a preclinical phase of a disease when
drug therapies. In the subsequent years, towns and recruited could infect the entire ship during the jour-
cities have grown up, opportunities for formal educa- ney. If the pathogen survived in new susceptibles
tion and for travel abroad have increased markedly, until the ship landed, the disease rapidly spread
tourism has replaced plantation produce, and even throughout the labor camp. Moreover, in addition to
the small islands of the Pacific Basin have become introducing infections, the new recruits were particu-
integrated into the world economy and communica- larly susceptible to any diseases present in the
tion network. Yet the diversity in environments and camps. Excessively heavy work, poor shelter, lack of
cultures remains. As in any Third World situation, sanitation, poor diet, impure water, and lack of
many indigenous people in the urban centers face health care meant that many did not survive the
overcrowding, unemployment, poverty, poor sanita- first year.
tion, and easy availability of all sorts of imported Along with internecine warfare and the usual
foods and drugs, while their relatives in the hinter- natural disasters that led to famine and water short-
lands have poor access to any services (including ages, diseases in this region caused extensive loss of
health care) or often even to clean water. Mortality life before preventive or curative methods were suc-
rates and malnutrition are often higher in remote cessful. Endemic diseases regulated fertility and
areas than near the centers, and in most cases the mortality over time; epidemics of new diseases of-
indigenous people in this entire region have inade- ten caused severe depopulation in all age groups
quate housing, poor screening, less pure water, in- when first introduced. The latter were devastating
adequate food storage facilities, poor diet, inade- not just because of their initial toll but also because
quate waste removal, inadequate health services, the loss of mature adults reduced the group's ability
and high birthrates. The greatest value this region to provide food, shelter, and nursing care for itself
now has to major political powers is a strategic one. or to reproduce itself. Pneumonia, diarrheal dis-
In addition to hosting a few military bases, some of eases, and - if present - malaria are still major
the islands have been sites for controversial weap- causes of severe morbidity and mortality for infants
ons storage and nuclear testing by the United and toddlers in the region (Prior 1968; Moodie
States, England, and France. 1973; Marshall and Marshall 1980; Townsend
1985).
Imported Diseases However, as in other regions of the world, infec-
The European explorers and missionaries who first tious diseases have not constituted all of the health
contacted the indigenes brought with them diseases problems in Oceania and Australia. Nutritional defi-
common in their own homelands or in the ports they cits or excesses, either alone or in concert with infec-
had been visiting. However, in the small isolated tious agents or predisposing genotypes, have caused
communities common throughout this region, most a number of important diseases, as have environmen-
diseases could not be maintained indefinitely and tal toxins. Hemorrhage, obstructed labor, and sepsis
needed to be reintroduced through outside contact in childbirth have had fatal consequences in the
after a new pool of susceptibles had developed. Such many areas where specialized care is relatively inac-
reintroductions were accomplished by interisland cessible (Marshall and Lakin 1984). The same has
voyaging, trade among different tribal groups, ex- been true for any trauma leading to hemorrhage or
plorers, merchants, whalers, missionaries, soldiers, sepsis. In addition, since the post-World War II
"blackbirders," Asian laborers on plantations and in years, the chronic life-style diseases (obesity, diabe-
mines, and soldiers from afar. Lacking the immunity tes, cardiovascular disorders, cancers, substance
that develops after centuries of coexisting with abuse) have become common throughout most of the
pathogens, Pacific populations provided a "virgin Pacific.

Diseases of the Region in Time and Space under 3 years of age in some New Guinea communi-
ties may increase resistance to or decrease severity
Arthropod-Borne Diseases of the symptoms of malaria (Lepowsky 1985).
Malaria. Malaria has been a major cause of morbid- Malaria may have indirect effects on child health
ity and mortality at least in the historical period as well. Decreased maternal immunity to malaria
throughout Melanesia, except Fiji, New Caledonia, during pregnancy poses problems for fetal oxygen-
and certain coral atolls. Although the anopheline ation and growth - and consequent infant health -
mosquito vector is present in Micronesia, the in that the unchecked plasmodia clog the placenta,
Plasmodium parasite has not been introduced. Ma- disrupt red blood cells, and induce high fever. Thus,
laria is also absent from Polynesia (Norman-Taylor birth weights in the Solomon Islands increased a few
et al. 1964; Gurd 1967; Willis 1970; Henderson et al. months after initiation of a malaria control program
1971). The disease was endemic in the aboriginal (Taufa 1978).
lands of northern Australia before its eradication in Malaria has been a scourge of settlers, colonists,
1962. Because of the continued presence of Anophe- missionaries, laborers, soldiers, and tourists in
les in Australia, reintroduction from New Guinea or Melanesia, just as it has been of the indigenous
southeast Asia remains a threat (Moodie 1973). people. Symptoms are worse for those adults who
In New Guinea, malaria is hyperendemic in the have not acquired some immunity in childhood or
hot, wet lowlands. As the indigenous people were are malnourished. Nineteenth-century Samoan mis-
"pacified" by colonial administrations and forced to sionaries for the London Mission Society died of ma-
live in larger village units, the resultant proximity laria at various stations in Vanuatu (Howe 1984). In
of large groups of people and numerous small pools World War II, it caused considerable mortality
of mosquito-breeding water facilitated the spread of among the Australian, American, and presumably
malaria (Vines 1970). It did not reach the highlands, Japanese forces, as well as among Melanesians from
however, until the 1930s, as a result of European regions other than the coastal lowlands (Burnet and
road building, airstrip construction, pond and ditch White 1972). Tourists, anthropologists, and Peace
digging, along with increased migration of contract Corps volunteers in Melanesia today regularly take
workers between coastal plantations and highland their weekly antimalarial doses, which are gener-
homes (Riley 1983). In some remote mountain val- ally available over the counter in local pharmacies.
leys, the unstable parasite pool has become nearly
self-sustaining in the 1970s. Plasmodium cannot, Filariasis. Filariasis was indigenous throughout
however, complete its life cycle in Anopheles at alti- the tropical Pacific. Different strains of Wuchereria
tudes above 2,000 meters, where temperatures are bancrofti are transmitted by different mosquito vec-
below 16°C, even though its vector can survive tors in different regions. Culex in Micronesia and
higher up (Nelson 1971; Sharp 1982). Anopheles in some of the Papua New Guinea islands
Although the Polynesian outlier atolls in Papua as well as the Solomon Islands and Vanuatu carry
New Guinea and the Solomon Islands were initially nocturnally periodic strains, whereas daybiting
free from malaria, it was introduced within a decade Aedes transmit nonperiodic strains in Polynesia,
of first European contact in the nineteenth century Tuvalu, Kiribati, Fiji, and New Caledonia (Norman-
to Ontong Java and Sikiana (Bayliss-Smith 1975). Taylor et al. 1964; Iyengar 1965; Gurd 1967; Vines
Malaria control efforts in the 1950s-70s have had 1970; Henderson et al. 1971; Chowning 1989). In the
varying degrees of success (Moodie 1973; Bayliss- first half of the twentieth century, filariasis was
Smith 1975; Taufa 1978). The Institute for Medical highly prevalent in Polynesia except New Zealand
Research in Papua New Guinea has initiated clinical (Iyengar 1965; Henderson et al. 1971; Montgomerie
trials of a malaria vaccine. 1988). In the Cook Islands in 1946, 75 percent of the
In areas of endemic malaria, the disease has its school children were infected (Beaglehole 1957), as
greatest effect on children from 6 months to 5 years was nearly half the Tahitian population in 1949
of age. Before 6 months they are protected by mater- (McArthur 1967). However, in the same time period,
nal antibodies, and after 5 years they have generally the disease was much less common in Papua New
acquired some immunity of their own from repeated Guinea, the Carolines, Marshalls, Marianas, and
infections (Burnet and White 1972). However, in- Kiribati (Kraemer 1908; Hetzel 1959; Maddocks
creased incidence of malaria in Melanesia is not 1973), and the progression to elephantiasis was rare.
necessarily associated with increased infant mortal- In Fiji, adult male plantation workers generally
ity (Van de Kaa 1967). Low-protein diets for children have the highest rates of infection, although equally

high rates are found in women who work near voyagers who landed on the southwestern outer is-
mosquito-breeding areas in pandanus and coconut lands. Since then, cases have appeared in neighbor-
groves. Filariasis is more common on the less devel- ing Yap and in Guam. Aedes was thought to have
oped islands, where screens on windows are often been eradicated in Palau, but seems to have been
absent and mosquito-breeding puddles are plentiful reintroduced from southeast Asia. Signs in an east-
near houses; yet it does not exist on the very small ern Micronesian airport in 1988 warned visitors of
islands in this archipelago. Major mosquito eradica- the danger of dengue spreading from Palau.
tion campaigns in the middle of this century were
fairly successful in Micronesia (Henderson et al. Respiratory Diseases
1971), Marquesas, Tahiti, Samoa, Tonga (Iyengar Respiratory infections, which are extremely common
1965), and Torres Straits islands. in hot humid climates, still constitute a major cause
of mortality everywhere in the Pacific region. Upper
Dengue. Dengue epidemics have occurred for at respiratory infections routinely spread throughout
least a century in Oceania in places where the Aedes villages or whole island populations soon after the
mosquito has been present, generally on lush wet arrival of a ship. Transfer is rapid in the generally
islands where unscreened rain catchment is close to crowded conditions where handwashing is far less
houses. The 1885-6 epidemics in Fiji and New Cale- frequent than personal touching, coughs and sneezes
donia spread eastward into Tahiti, causing miscar- are rarely covered, and flies are plentiful.
riages and excessive mortality in children in south-
ern French Polynesia (McArthur 1967). Wallis and Influenza. Influenza epidemics followed quickly
Futuna experienced an epidemic in 1907, as did upon first contact with Europeans and continued
Torres Straits islands in the early twentieth century, almost annually thereafter. The disease was first
the northern Cook Islands in 1930—1 (McArthur reported in Tahiti in 1772, Fiji in 1791-2, Samoa in
1967), Kiribati in the 1950s, and Fiji in 1943-4 and 1830, the Cook Islands in 1837 (McArthur 1967),
1953 (Wilkinson et al. 1973). Epidemics occurred Pohnpei before 1841, Yap in 1843, the Marshall Is-
infrequently in aboriginal lands in tropical northern lands in 1859, Pingelap in 1871 (Hezel 1983), Papua
Australia, probably arriving from nearby southeast New Guinea in 1889 (Allen 1989), and remote Aus-
Asia (Moodie 1973). tralia before 1890 (Moorehead 1966). The first epi-
Dengue hemorrhagic fever, which is frequently demic in Fiji indirectly brought on a famine because
fatal in children, appears to be a post—World War II of the depletion of food resources by the excessive
phenomenon along major transport routes in south- number of funerary feasts prompted by the heavy
east Asia and the Pacific islands. It has appeared in mortality (McArthur 1967).
Tahiti and elsewhere when at least one other strain Adult mortality was high in the early influenza
of the virus co-occurred with the type 2 strain epidemics in each location. Later, given the wide-
(Chastel and Fourquet 1972; Hammon 1973). In based population pyramid, the very young began to
1971-2, major outbreaks of dengue of varying sever- account for the greater share of mortality, although
ity occurred in coastal Papua New Guinea, Vanuatu, lessened immune responsiveness at both ends of the
New Caledonia, Fiji, Nauru, Kiribati, Tuvalu, West- age spectrum has made influenza a special threat to
ern Samoa, Tonga, Niue, and Tahiti (Pichon 1973; the elderly as well. Certain of the subsequent epi-
Wilkinson et al. 1973; Zigas and Doherty 1973). The demics were particularly severe in the mortality
symptoms were relatively mild in most areas, with a they generated. Among them were those that struck
type 2 strain as the sole causative agent. In Rabaul, New Zealand in 1838 (Owens 1972), Fiji in 1839,
the clinical features of the type 2 infection were Tahiti in 1843, Samoa in 1837 (McArthur 1967),
more severe, but hemorrhage and shock were not Pohnpei in the 1840s, Kosrae in 1856-7, Palau in
seen (Zigas and Doherty 1973). Over half the popu- 1872 (Hezel 1983), Vanuatu in 1863 (Howe 1984),
lation of Tahiti was affected, some of whom de- Wallis and Futuna in 1870 from Fiji, Polynesian
veloped hemorrhagic fever. Severe hemorrhagic outliers in Melanesia around 1900 (Bayliss-Smith
symptoms and high mortality characterized the 1975), Caroline Islands in 1877, 1927, and 1937
Niue outbreak that struck one-third of the popula- (Marshall 1975; Nason 1975), Kiribati in 1915,1935,
tion (Pichon 1973). and 1956, Papua New Guinea in 1957 and 1965 from
Although dengue had ceased to exist in Mi- eastern Australia (Warburton 1973), and Kiribati
cronesia by 1948 (Hetzel 1959), it was reintroduced and Tuvalu in the 1960s (Henderson et al. 1971).
into Palau in the late 1980s by Indonesian drift The influenza pandemic of 1918-19 swept across

most of the Pacific, but spared Papua New Guinea, 1970; Riley 1973; Schlomowitz 1988). Because pneu-
the Marquesas, and Australia, and some remote is- monia is a particular problem for everyone in the
lands in every group. Although the highest mortal- highlands, a vaccine for the common pneumococci
ity rate in the world for that epidemic was in West- has been tested there recently (Riley 1973). In Papua
ern Samoa (25 percent), neighboring American New Guinea, pneumonia is endemic in rural areas
Samoa escaped altogether by quarantining all ships and prevalent among young men who have recently
in its harbor. A single ship from Auckland carried migrated to towns (Hocking 1974). In highland
the disease to Fiji, Tonga, and Western Samoa. How- Papua New Guinea domiciliary smoke has also been
ever, the New Zealand-dependent Cook Islands ma- implicated in the chronic obstructive pulmonary dis-
jor port was infected from Tahiti, where mortality ease (COPD), which is so common there (Vines
was similar to that in Western Samoa. The highest 1970), although its high prevalence on the coast as
mortality throughout the region was among 15- to well suggests repeated acute infections as a more
40-year olds and was generally caused by secondary likely cause (Woolcock, Colman, and Blackburn
bacterial pneumonia (McArthur 1967; Burnet and 1973).
White 1972).
Streptococcal Infections. Sequelae of repeated un-
Diphtheria and Pertussis. Epidemics of diphtheria treated streptococcal throat infections have also been
and pertussis (whooping cough) have been reported a problem in many areas of Oceania. Rheumatic
in various parts of the region since colonial times. carditis is prevalent in Fiji (Gurd 1967), in French
The first diphtheria outbreaks in Australia occurred Polynesia, where it occurs frequently in children
at a time when the disease had intensified in En- under 5 years of age (Houssiaux, Porter, and Fournie
gland and Europe. The disease appeared in south- 1972), and among Australian aborigines (Moodie
east Australia and Tasmania in 1858-9 and in small 1973) and New Zealand Maori (Prior 1968). Post-
scattered settlements in the far west in 1864 (Burnet streptococcal glomerulonephritis is one of the most
and White 1972). Vanuatu experienced an epidemic common causes of death among adult Australian
in the 1860s (Howe 1984). It has since been rare in part-aborigines in south Australia (Moodie 1973).
isolated aboriginal Australian communities (Moodie
1973) and in Papua New Guinea, although epidem- Tuberculosis. Tuberculosis, or "wasting sickness"
ics did occur in the 1950s and 1960s in the highlands as it was called, was introduced into Fiji in 1791 by a
of the latter. After the construction of their jet air- British ship (McArthur 1967). Reports of "consump-
port in 1965, Easter Islanders experienced a diphthe- tion" among the Maori living near missionaries and
ria epidemic. sawyers from England began to increase in the
Pertussis has caused high mortality in the nine- 1820s (Owens 1972). Tuberculosis became common
teenth and twentieth centuries among infants and in much of Polynesia and some of Melanesia and
children in the highlands and islands of Papua New aboriginal Australian lands by the mid-1800s, and
Guinea (Vines 1970; Paine 1973; Lindenbaum 1979), was a major health problem for Australian aborig-
Vanuatu (Howe 1984), Australian aborigines (Moore- ines by the turn of the century (Kuykendall 1966;
head, 1966; Moodie 1973), Kiribati, Fiji, Tonga, West- Moorehead 1966; McArthur 1967; Moodie 1973;
ern Samoa, Tahiti, Leeward and Cook Islands Bayliss-Smith 1975; Howe 1984). Interisland migra-
(McArthur 1967), and New Zealand Maori (Prior tion as well as ships from outside spread it widely
1968). throughout the Pacific during the nineteenth cen-
tury. Although present in even remote areas of the
Pneumonia. Secondary pneumonia usually causes New Guinea islands by the early 1900s (Chowning
the respiratory infection fatalities in this region. 1989), it reached the highlands only decades later.
Pneumonia epidemics have occurred following influ- Travelers from the eastern highlands avoided over-
enza epidemics since first European contact (Mad- night stays in the nearby lowland valleys because
docks 1973). Mortality has been highest among the they feared tuberculosis; this custom also protected
very young, the very old, and those in remote areas them from night-biting anophelines (Riley 1983).
(Allen 1989). Pneumonia was rife in the goldfield Tuberculosis was first introduced into certain popu-
labor camps in the mountains, perhaps because of lous areas of the highlands in 1970, and has occurred
the chilly nights with close contact among the work- only sporadically since (Pust 1983).
ers around smokey fires and the scanty food rations The disease remains an important health problem
which had to be carried in on workers' backs (Vines in the modern Pacific, where crowded households

and extensive sharing of personal articles facilitate reintroduced the disease every year (Gurd 1967; Lep-
spread, and intercurrent infections decrease resis- rosy Review 1973). Shared sleeping mats have been
tance. The 1960s campaigns with screening, immuni- suspect in areas of increasing incidence. Leprosy is
zation, and chemotherapy have been at least some- present throughout Melanesia as well (Gurd 1967;
what successful in most island groups (Henderson et Willis 1970; Leprosy Review 1973; WHO Weekly
al. 1971). 1973). In Papua New Guinea, the highest incidence
Scrofula, characterized by tumors, wasting, neck is in the highlands, although it is also prevalent
swellings, and spinal curvature, was widespread in along the New Guinea coast (Vines 1970; Russell
Polynesia in the early nineteenth century. A number 1973). There are endemic foci among the northern
of authors have equated it with tubercular adrenitis. Australian aborigines, but it is rare in other aborigi-
Said to have been brought to Tahiti by British and nal communities (Moodie 1973). Many cases in rural
Spanish explorers in the eighteenth century, scrof- areas remain undetected, so rates all over the region
ula was carried by Tahitian teachers to the Cook may actually be much higher. Outpatient treatment
Islands in the 1830s, where it spread throughout the has largely replaced the leprosy hospitals built ear-
group in a time of famine, causing many deaths over lier this century (Henderson et al. 1971).
the next 15 to 20 years (McArthur 1967).
Measles. Measles, although present in much of the
Other Infectious Diseases Pacific Rim in 1800, did not reach eastern Australia
until 1828 and Hawaii until 1848. In the 1850s, it
Leprosy. Leprosy was introduced into the region spread throughout Australia, to New Zealand, and
by Asian workers and immigrants in the nineteenth into the islands (McArthur 1967; Cliff and Hagget
century, then spread with interisland migration. Al- 1985). In 1875, a London Mission Society ship car-
though called the "Chinese disease" in Hawaii, the ried measles along the Papuan coast of New Guinea.
actual circumstances of introduction to those is- In the same year, a ship carrying Fijian royalty
lands are unknown. It was present in the 1830s, and home from a visit with the governor of Sydney trans-
numerous cases were reported in 1863, a few years ported the virus to Norfolk Island, the Solomon Is-
before the Molokai leper colony was established to lands, and Vanuatu as well. The effect on Fiji was
isolate the afflicted. Hundreds were sent to Molokai particularly devastating, as over a thousand repre-
over the years, yet many remained in their own sentatives from most of the individual islands had
communities. Hawaiian islanders did not fear the gathered to greet the ill prince and to celebrate for 2
disease and therefore resisted this internment (Kuy- weeks Fiji as a new Crown Colony before dispersing
kendall 1966). Leprosy appears to have entered home. The sudden loss of so many adults in Fiji,
New Zealand in the 1850s, perhaps with Asian trav- Tahiti, and Vanuatu contributed to the heavy mortal-
elers, but was rare until the 1900s (Montgomerie ity, as few remained able to provide food or care
1988). Australian aborigines in the northeast ac- (CliffandHaggettl985).
quired the disease from infected Chinese and Mela- Similar epidemics struck Kiribati in 1890 (Lam-
nesian laborers in the nineteenth century (Moodie bert 1975), and Tonga and Western Samoa in 1893
1973). It was present in New Guinea in 1875 (Mad- (McArthur 1967). Quarantine kept Fiji from all but
docks 1973) and was brought into the northern local port outbreaks until 1903, when measles again
Cook Islands in 1885 by a native son who had spent swept through the group. The 1911 outbreak was
several years in Samoa with a leprosy sufferer from mild on most islands, but severe in those few remote
Hawaii (McArthur 1967). The disease spread to Eas- islands that had escaped earlier. Every epidemic
ter Island (where it is still greatly feared) from thereafter came at shorter intervals, caused fewer
Tahiti, and although widespread in Polynesia in deaths, and affected ever younger children only
1900, it still had not reached the Caroline Islands (Cliff and Haggett 1985). The same pattern-
(Kraemer 1908). sporadic epidemics that become more frequent and
After World War II, leprosy also become wide- less severe - has occurred everywhere in the region
spread in Micronesia west of the Marshall Islands with regular outside contact or large populations.
(Hetzel 1959), but was brought under control - even Small remote islands still have rare epidemics with
in a spot of high incidence — by 1970 (Sloan et al. variable mortality (McArthur 1967; Van de Kaa
1972). In the 1970s, it was still sufficiently prevalent 1967; Brown and Gajdusek 1970; Vines 1970; Willis
in Polynesia (including outliers), Fiji, and Kiribati, 1970; Henderson et al. 1971; Moodie 1973; Linden-
that immigrants to New Zealand from these islands baum 1979; Cliff and Haggett 1985).

Rubella. Rubella epidemics have been recently Asia and South America. In the 1860s, Polynesians
documented for Guam, remote Micronesian atolls, returning to their homes after years of involuntary
Western New Guinea, and Papua New Guinea and servitude in the mines of Peru contracted smallpox
have been associated with excessive hearing impair- on board the ships (McArthur 1967). The first ship-
ment from in utero exposure (Brown and Gajdusek load of plantation workers from India introduced
1970; Stewart 1971; Allen 1989). smallpox and cholera to Fiji in 1879. The need to
train vaccinators locally led to the construction of
Mumps. Mumps was already present in the Cook the Suva Medical School in 1885 (Lander 1989). Can-
Islands when it reached Samoa on a ship from Cali- tonese laborers reintroduced the disease as they
fornia in 1851 (McArthur 1967). The disease subse- slipped undetected into Hawaii in 1881 (Kuykendall
quently spread over much of the region, although it 1967). Before 1900, Javanese laborers for the planta-
did not appear in the New Guinea highlands until tions along the New Guinea coast introduced small-
the 1940s (Lindenbaum 1979). pox as they arrived. It spread into the nearby coastal
mountains, up the Sepik River and across the chan-
Scarlet Fever. Scarlet fever caused deaths among nel to New Britain to remote areas not yet contacted
foreigners in French Polynesia and the Cook Islands by Europeans (Allen 1989; Chowning 1989).
in 1846-7, but remained mild among the islanders
(McArthur 1967). Symptoms are similarly mild Yaws. Yaws was present in the Pacific region prior
among Australian aborigines in recent times (Moodie to outside contact. Before the eradication campaigns
1973). of the mid-twentieth century, yaws was found among
Australian aborigines, and in all of Melanesia, west-
Chickenpox. In the twentieth century, chickenpox ern Polynesia, Micronesia, French Polynesia, and
became more common and is now widespread in the Hawaii. Conversely, it was not present in New Zea-
region. High prevalence was reported from numer- land, Gambier, Easter, or Pitcairn Islands (Hetzel
ous island groups, New Guinea, and Australia in the 1959; Pirie 1971-2; Moodie 1973). It occurred less
1930s (Moodie 1973; Allen 1989). In fact, it has been commonly in particularly dry, cool, or high-altitude
suggested that some of the smallpox reported for areas or in islands settled late.
Australia and Papua was actually chickenpox (Mad- Yaws was usually acquired by children from regu-
docks 1973; Moodie 1973). lar playmates. After recovery from the debilitating
skin lesions, solid immunity to treponeme-caused
Smallpox. Smallpox epidemics in the Pacific re- yaws and to syphilis as well is attained. Incidence of
gion resulted primarily from contact with outsiders. yaws decreased as people washed with soap and cov-
The first reported epidemic was in the Spanish col- ered their bodies with clothes (Pirie 1971-2). After
ony of Guam in 1688 (Carano and Sanchez 1964). A World War II, the disease was virtually eradicated by
century later, within a year of the founding of Port penicillin injections, although antibodies remained
Jackson (now Sydney) in 1788, smallpox erupted in those who had been infected (Norman-Taylor et al.
among the aborigines camped nearby. The immune 1964; Fischman and Mundt 1971; Henderson et al.
settlers were relatively unaffected, but large num- 1971; Davenport 1975). Some pockets of infection
bers of aborigines died (Moorehead 1966). remained after the campaigns in the Marshall Is-
Trade ships and whalers brought the disease to lands (Hetzel 1959) and tropical northern Australia
many islands: Gambier in 1834, Tahiti in 1841, (Moodie 1973).
Pohnpei in the 1840s and in 1854, Hawaii in 1853-4,
the Maori, Palau, and Polynesian outliers in Hepatitis. Hepatitis B has been highly prevalent in
Melanesia in midcentury, Papua in 1865, and the the 1980s in Micronesia and in American Samoa,
New Guinea coast in 1870-90. In many of these where public health posters announce "Hep is not
cases, sick passengers or crew were put ashore and hip." The Australia antigen for identifying the virus
died on the island, passing the disease to any who was isolated in 1967 from the blood of an anemic
helped them. Islanders visiting the port spread the Australian aborigine who had received numerous
virus to their home communities nearby (McArthur transfusions. In the Solomon Islands, the antigen
1967; Kuykendall 1968; Owens 1972; Maddocks was commonly present in those with no clinical
1973; Bayliss-Smith 1975; Nason 1975; Allen 1983, symptoms or predisposing history (Burnet and
1989; Hezel 1983). White 1972).
The labor trade also introduced smallpox from Hepatitis A is endemic in much of island Oceania

and tropical Australia, subclinically infecting most corded soon after regular contact. British and
of the indigenous population under age five (Moodie French explorers in 1767-9 gave each other credit
1973), as might be expected in view of the warm for the syphilis in Tahiti reported by Captain James
climate and casual hygiene among children. Cook in 1769 and spread elsewhere in French Polyne-
sia by explorers over the next few decades. Cook's
Poliomyelitis. Poliomyelitis, being epidemiologi- surgeon wrote that the ship's crew introduced syphi-
cally similar to infectious hepatitis in unvaccinated lis accidentally to Tonga in 1777 and knowingly to
populations, was endemic in tropical Australia and Hawaii in 1779, although other observers stated
the Solomon Islands before World War II, but pro- that the disease was present earlier in Hawaii
vided only rare instances of paralysis (Cross 1971; (Moorehead 1966; McArthur 1967; Pirie 1971-2;
Moodie 1973). Before the massive vaccination cam- Smith 1975; Stannard 1989). Venereal syphilis was
paigns of the 1960s, most Guamanian under 3 years found among the Maori before 1840 and became
of age were already immune (Burnet and White more prevalent but with milder symptoms by 1855
1972). Western and American Samoa experienced an (Pirie 1971-2; Owens 1972). Pohnpei, Kosrae, the
epidemic in 1935 with highest mortality and morbid- Marshall Islands, and Kiribati were also infected by
ity among young adults rather than children. New whalers and traders in the 1840s and 1850s, but a
Guinea and Guam had also been "virgin soil" for century later the disease there had become almost
earlier polio epidemics (Burnet and White 1972). nonexistent (Hezel 1983). Syphilis was unknown in
After World War II and before vaccination, epidem- northern Australia before 1939, but since then has
ics occurred across the South Pacific (Peterson et al. spread among the aborigines around the country
1966; Cross 1971). Vaccination and quarantine fi- (Moodie 1973). Papua New Guinea highlands, where
nally limited the spread (Peterson et al. 1966). yaws had never existed, experienced an epidemic of
syphilis in 1969, after the new highway opened up
Acquired Immunodeficiency Syndrome (AIDS). AIDS access. It was first reported in 1960 and has re-
has surfaced in various indigenous Pacific popula- mained largely confined to the highlands (Linden-
tion in 1988—9. It is now present among urban- baum 1979; Lombange 1984).
dwelling Australian aborigines, as well as among Gonorrhea, often referred to in the region as "vene-
the people of Papua New Guinea, French Polynesia, real disease," was first noted in 1769 in Polynesia
Tonga, Marshall Islands, Guam (Karel and Robey and 1791 in Palau. Whalers, traders, and beachcomb-
1988), Fiji (Pacific Island Monthly 1988), Northern ers passed gonorrhea back and forth with islanders
Marianas, American Samoa (but not Western in the 1830s through 1850s in the Caroline and
Samoa), and Hawaii (information received at the Marshall islands, French Polynesia, and Hawaii,
Hawaii exhibit, Fifth International Conference on which were popular ports of call with more relaxed
AIDS, Montreal). On the other hand, extensive sexual attitudes than in most of western Polynesia
screening in the Solomon Islands and Papua New or Melanesia (Pirie 1971-2; Hezel 1983). Venereal
Guinea found no individuals with the virus (HIV) in disease did reach one frequently visited Polynesian
1985-6. outlier by the 1850s, but has never been present on
its more remote neighbors (Willis 1970; Bayliss-
Venereal Diseases Smith 1975). The first reports of venereal disease on
Syphilis and gonorrhea were brought into the Pacific Papua New Guinea coasts were in 1902-8, but it has
by early explorers and whalers. Because syphilis since become prevalent throughout the country
might have been mistaken for yaws, tropical ulcer, (Pirie 1971-2; Lombange 1984). Thus with rare ex-
scrofula, leprosy, or gonorrhea, confusion exists ceptions, the disease has become ubiquitous in Ocea-
about the circumstances of introduction even though nia, as it has in Australia in the same time period
early ships' logs did comment on the presence of (Moorehead 1966; Moodie 1973).
venereal diseases. In tropical Australia and the wet
islands of the southwestern Pacific, where yaws was Food- and Waterborne Diseases
highly prevalent and promiscuity was not custom- Enteric infections flourish in conditions commonly
ary, syphilis has been a relative newcomer; in cooler found throughout this region (Marshall and Mar-
New Zealand and drier or more recently settled is- shall 1980; Allen 1983; Burton 1983; Reid 1983).
lands of Micronesia and eastern Polynesia where They are often fatal in the very young or in those
yaws was less common and Europeans and island who for any reason quickly become dehydrated in
women often mixed more freely, syphilis was re- the hot climate. Gastroenteritis is ubiquitous, al-

though less common in nomadic or low-density popu- with literally heaps of pork occasionally punctuate
lations (Willis 1970; Reid 1983). the usual highland low-protein, largely sweet potato
diet. Clostridia enter the slaughtered pork as it sits
Cholera. Discrete epidemics of cholera have occa- in the dirt and is handled regularly for about 4 days
sionally occurred. It was reported in Kiribati in before the feast. It is ingested with the meat, colo-
1841, among the Maori in 1838 and after 1840 (Ow- nizes the gut, and produces a toxin that should be
ens 1972), and carried into Fiji by new South Asian inactivated by intestinal trypsin. However, protein
plantation laborers (Lander 1989). Cholera has not deprivation or the presence of trypsin inhibitor from
been documented for either Papua New Guinea or sweet potato (or from the ubiquitous Ascaris) pre-
Australia, even though the easily spread El Tor vents the enzyme from doing so. A vaccine for the
strain was present in neighboring western New toxin became available in the 1980s (Lindenbaum
Guinea and Sulawesi in 1962 (Moodie 1973; Riley 1979; Murrell 1983).
1983). Still a threat in modern times, cholera broke Another clostridial disease, tetanus, occurs widely
out in Kiribati in the late 1970s. An infected in the Pacific islands and Australia, even in areas
crewmember on a Japanese fishing vessel debarked without domestic animals (Gurd 1967; Moodie 1973;
in Truk, causing a major epidemic in 1982-3 which, Lindenbaum 1979). The disease is not found on Eas-
until recently, devastated the tourist trade. ter Island, however, even though horses, cattle,
goats, sheep, Clostridium tetani, and bare feet are
Diarrhea, Dysentery, and Clostridial Diseases. Epi- common. Immunization as part of prenatal care in
demics of the "bloody flux," or bacillary dysentery, Papua New Guinea has reduced mortality from neo-
have plagued Pacific islanders at least since 1792, natal tetanus, which was once very high in rural
when a British explorer brought it to Tahiti. Unlike areas where umbilical cords were cut with contami-
measles, these epidemics did not become more fre- nated objects (Townsend 1985).
quent and less severe with repetition in a given popu-
lation. Severe epidemics of bacillary dysentery were Helminth-Transmitted Diseases
often associated with concurrent civil wars, famines, Intestinal-dwelling nematodes have been very com-
typhoons, droughts, measles, incarceration on labor mon in the Pacific region wherever the soil is moist
vessels, employment on the goldfields in Papua New enough to keep their eggs alive. Generally preva-
Guinea, or ship visitations (McArthur 1967; Prior lence of Ascaris and Trichuris is lower on dry atolls
1968; Bayliss-Smith 1975; Allen 1983; Burton 1983; (e.g., Marshall and northern Cook islands) or in low-
Howe 1984; Schlomowitz 1988). Two notable epidem- land rainforests (as on the New Guinea coast). How-
ics of bacillary dysentery occurred in Papua New ever, the southern Cook and Caroline islands
Guinea during World War II: one introduced by Japa- rainforests have had very high rates, whereas
nese in the course of building an airstrip on the north Ascaris is rare in Vanuatu (Hetzel 1959; Norman-
coast using indigenous labor, and one introduced by Taylor et al. 1964; Vines 1967, 1970). Ascaris is
members of an American military team in the central widely distributed in aboriginal lands in Australia,
highlands. Australian soldiers also brought dysen- but is more common in the cooler drier south (Moodie
tery that they had earlier picked up in North Africa 1973). Enterobius is ubiquitous (Vines 1967).'Hook-
(Allen 1983; Burton 1983). The Marshall Islands worms have had a low prevalence in Kiribati and
have had epidemics of dysentery in recent years soon isolated Pitcairn and Easter islands but are plentiful
after imported chicken has been off-loaded and sold in on wet lowlands. Necator has been far the more com-
local stores. It is endemic in most groups of aborigines mon parasite, although Ankylostoma has replaced it
(Moodie 1973). Typhoid fever and amebic dysentery in Vanuatu. They have been highly prevalent in ab-
have appeared throughout the islands and Australia original lands in Australia, except in the Central
as well (Hetzel 1959; Gurd 1967; McArthur 1967; Desert. They spread outfromthe tropical north with
Burnet and White 1972; Moodie 1973). cattleherders. Eradication campaigns in many is-
The third leading cause of death in the Papua New lands and among the Australian aborigines have had
Guinea highlands is enteritis necroticans, known lo- no enduring effect (Hetzel 1959; Norman-Taylor et al.
cally as pigbel. Peak incidence of this syndrome of 1964; Vines 1967, 1970; Willis 1970; Moodie 1973).
bloody diarrhea, stomach pain, nausea, and vomit-
ing occurs at 4 years of age. Those over 40 years old Zoonoses
generally have developed immunity to the causative Other health problems have arisen as well from the
agent, Clostridium perfringens beta toxin. Feasts close association between humans and various ani-

mals in this region. The disabling or even fatal dog sible for the high prevalence of iron-deficiency ane-
tapeworm is common among Australian aborigines mia among Australian aborigines (Moodie 1973).
who keep dogs closeby in their camps (Moodie 1973). Protein-calorie deficiency does occur, mostly in
Cysticercosis, from pig tapeworm, was first intro- poor remote areas of the New Guinea mainland. Diet
duced into the densely populated pig-raising high- on the smaller islands, while simple, is usually suffi-
lands of Western New Guinea via a gift of infected cient (Vines 1970).
pigs from nearby Bali in 1971. Within 4 years it had Goiter and cretinism have been problems in
spread to the border with Papua New Guinea, and patches in inland Melanesia, where highland people
within 10 years had become a major cause of morbid- have had to trade with coastal people for their sea
ity and mortality in that region, which has been a salt. In 1955, colonial patrols worsened the situation
hotbed of rebellion against the alienation of Papuan in the Papua New Guinea highlands by trading in
lands by Indonesian settlers (Hyndman 1988). noniodized salt, which the highlanders preferred to
Since 1948, epidemics of eosinophilic meningitis their traditional supply. A campaign in the 1960s to
generally attributed to ingestion of rat lungworm, reverse the deficiency with injections of iodized
Angiostrongylus, have been reported in small areas poppyseed oil was successful (Henderson et al. 1971;
dotted across the Pacific: New Caledonia, Pohnpei, Lindenbaum 1979).
Cook Islands, Tahiti, and Hawaii. In some of these
cases, shellfish eaten raw were the intermediaries Diabetes and Obesity. Chronic diseases have in-
(Rosen et al. 1967). creasingly become primary causes of morbidity and
Toxoplasmosis is endemic in much of Oceania and mortality in industrialized societies since the 1950s
Australia, where cats appear to play a critical role in as immunization and chemoprophylaxis have re-
transmission (Wallace, Marshall, and Marshall 1972; duced infectious diseases, as sedentary wage employ-
Moodie 1973). Contact through breaks in the skin ment has become available, and as imported foods
with water or mud contaminated with the urine of constitute an ever-growing share of people's diets.
rats, pigs, or cattle has been responsible for leptospiro- These diseases are distributed unevenly, occurring
sis among Australian aborigines working in sugar- far less regularly in remote rural areas.
cane fields, as swineherds, or as stockmen in tropical Non-insulin-dependent diabetes mellitus (NIDDM)
northeastern Australia. This infection causes inter- is unusually prevalent among certain Pacific soci-
mittent fever and meningitis (Burnet and White eties: Australian aborigines (Moodie 1973), New Zea-
1972). Bubonic plague persisted for 10 years in sea- land Maori (Prior 1968), Cook Islanders (Prior 1968),
port rats in southeastern Australia before eradica- American Samoans (Baker and Crews 1986; Hanna
tion efforts succeeded (Burnet and White 1972). and Baker 1986), Marshall Islanders and I-Kiribati
Scrub typhus mites flourished in grassy clearings (King et al. 1984), Nauruans (Patel 1984; Taylor and
away from human villages in Papua New Guinea and Thoma 1985), Torres Straits islanders (Patel 1984),
northeastern Australia, causing minimal problems Fijian women (King et al. 1984), and residents of
for indigenes but becoming the second leading cause Papua New Guinea's most acculturated urban but not
of death — after malaria - among the foreign soldiers rural or highland areas (Savige 1982; Patel 1984).
cutting through the Bush there in World War II The disease is more common among the wealthy (34
(Burnet and White 1972). percent prevalence in affluent Nauru), the more
acculturated, the urban, and perhaps the female. Its
Diet-Related Diseases meteoric rise in the mortality statistics has paral-
leled increases in dietary refined carbohydrates and
Anemia. Anemia is widespread among women in calories and decreases in exercise and dietary fiber.
Oceania, especially at sea level. The proportion of Obesity even beyond the cultural ideal has also
women having hemoglobin levels below 12 grams- accompanied these changes in all of these areas as
percent is higher than in any other region of the well as in the Marquesas and Solomons (Fried-
world (Wood and Gans 1981; Royston 1982). Anemia laender and Rhoads 1982; Darlu, Couilliot, and
is especially common among children in Vanuatu Drupt 1984). Yet similar dietary changes and de-
and among New Zealand Maori (Norman-Taylor et creased activity level have not led to obesity or
al. 1964; Prior 1968). It has been documented occa- NIDDM on Easter Island. The familial tendency ap-
sionally for Micronesia, less in the western Caro- parent within these populations and the extremely
lines than in the Marianas or Marshalls (Hetzel high rates among certain related island groups sug-
1959). Diet and malabsorption problems are respon- gest a partial genetic basis. According to J. M.

Hanna and P. T. Baker (1986), the metabolic ability phic lateral sclerosis, and Parkinsonism. Occasional
to gain weight rapidly and hold it may have given a cases with similar symptoms have also been found
selective advantage for long interisland voyaging among Caroline Islanders, Filipinos, and Cauca-
with limited space to transport food. Crowding and sians resident in the Marianas. The syndrome has
psychosocial stress in acculturated urban areas may also appeared in Chamorros 30 years after leaving
also play a role in the etiology. Compliance with Guam. Until recently, the Chamorro ate great quan-
treatment regimes (diet, exercise, daily insulin) in tities of the false sago plant seeds, which contain a
the absence of frank clinical symptoms has been low, toxin that causes degeneration of the same motor
especially among men who avoid seeking help un- neurons that disappear in amyotrophic lateral sclero-
less their problem is evident and severe. sis and Parkinsonism. On the other hand, a genetic
Surveys of blood pressure after World War II indi- susceptibility to the effects of such a toxin in this
cated that for most Pacific people, adult blood pres- population has not been ruled out (Mathai 1970;
sures averaged lower than for equivalent age groups Lewin 1987).
in industrialized societies and did not rise with age High incidence of an autosomal recessive congeni-
(Norman-Taylor et al. 1964; Vines 1970; Shaper tal blindness (tapetoretinal degeneration with cata-
1972; Moodie 1973; Gee 1983; Patrick et al. 1983; racts) on a single Carolinian atoll has been attrib-
Ward 1983). However, in recent years hypertension uted to the fact that the island was almost isolated
and age-related increases have become much more in the 2 centuries following the 1780 typhoon that
common in areas where modern wage-earners are killed all but nine of the men on the island (Brody et
concentrated, obesity is obvious, and imported salt al. 1970).
intake is high (Prior 1968; Henderson et al. 1971; Ciguatera, a frequently fatal fish poisoning caused
Moodie 1973; Gee 1983; Patrick et al. 1983; Ward by a curare-like toxin present in certain fish through-
1983; Taylor and Thoma 1985; Hanna and Baker out the region, has been of grave concern in the
1986; Prior 1986). Coronary artery disease is also Pacific islands where fish is the major protein food.
becoming more common in these same situations The source of the toxin appears to be algae that grow
(Hanna and Baker 1986). on submerged World War II equipment or nuclear
testing apparatus and are consumed by the fish. It
Chronic Degenerative Neurological Diseases has been reported in French Polynesia, Guam, Mar-
Certain chronic degenerative neurological diseases shall Islands, and Hawaii, all of which provide appro-
that have close parallels in the industrialized world priate surfaces for the algal growth (Banner et al.
have been highly prevalent in very restricted loca- 1963; Henderson et al. 1971; Bagnis 1972).
tions in Oceania. Kuru, a subacute spongiform cere-
bellar encephalopathy caused by an unconventional Afterword
slow virus, has been present in the Fore area of the Oceania and Australia have been spared many of the
eastern highlands of Papua New Guinea since 1920. major scourges of the tropical Third World: schistoso-
In the 1950s, it was the most common cause of death miasis, trypanosomiasis, onchocerciasis, and leish-
in adult women and in children 5 to 16 years old in maniasis. Yet they have coexisted for millennia with
that area. The unusual age distribution was due to malaria, filariasis, and other troublesome diseases.
the local practice - extant from 1910 to 1955 - of Through contact with Asia and the New World in the
cannibalism. The dead were consumed by female kin past several centuries, they were exposed to all of the
and young children of either sex. The virus entered major epidemic diseases, which have largely become
via cuts in the skin as the flesh and brain were preventable childhood illnesses. The continued lack
prepared. Two to 20 years later, symptoms appeared: of comprehensive public health programs for basic
ataxia, tremoring, pain, slurred speech, loss of sanitation, hygiene, and home screening in the re-
smooth and voluntary muscle control, and pathologi- gion means that the threat of fatal epidemics as in the
cal laughter. Death followed within nine months. past still remains. Lack of refrigeration and transpor-
The number of cases declined progressively after tation problems make it difficult to deliver antibiot-
cannibalism was discontinued (Burnet and White ics and vaccines to those in need.
1972; Gajdusek 1977; Lindenbaum 1979). In the more affluent areas, decreasing infant mor-
Since before World War II, the indigenous Cha- tality rates, a sedentary life-style, and a change in
morro of the Marianas Islands have had an ex- diet have permitted an increasing number of people
tremely high incidence of a syndrome with varying who reach adulthood, and who may be particularly
combinations of Alzheimer-like dementia, amyotro- genetically susceptible, to experience chronic dis-

eases generally more common in industrialized ar- perspective. In Pacific atoll populations, ed. V. Carroll,
eas. Although the recreational drugs of the West 344-416. Honolulu.
became available only after first contact and were Chastel, C , and R. Fourquet. 1972. Responsabilite du vi-
often prohibited to indigenes until recently, sub- rus dengue type 2 dans l'epidemie de dengue de
stance abuse has become a major problem. In recent Taihiti en 1971. Review of Epidemiology 20: 499-508.
years the islanders and Australian aborigines ex- Chowning, A. 1989. The doctor and the curer. In A continu-
ing trial of treatment, ed. S. Frankel and G. Lewis,
posed to experimental radioactive fallout have
217-47. Dordrecht.
shown the world some of the minor health complica- Cliff, A. D., and P. Haggett. 1985. The spread of measles in
tions of nuclear warfare, which would be - for all - Fiji and the Pacific. Canberra.
the final epidemic. Crane, G. G., R. W. Hornabrook, and A. Kelly. 1972.
Leslie B. Marshall Anaemia on the coast and highlands of New Guinea.
Human Biology in Oceania 1: 234—41.
The author is deeply grateful to M. Marshall, D. Denoon,
Cross, A. B. 1971. The rehabilitation of poliomyelitis crip-
H. Hethcote, and G. Rushton for providing essential biblio-
graphic resources. The author also wishes to thank J. Arm- ples in the Solomons. South Pacific Bulletin 21: 32-3.
strong, J. Boutilier, L. Carrucci, J. Fitzpatrick, D. Hrdy, B. Lam- Darlu, P., M. F. Couilliot, and F. Drupt. 1984. Ecological
bert, D. Lewis, M. Maifield, C. Murry, K. Nero, N. Pollock, and cultural differences in the relationships between
U. Prasad, M. Scott, B. Zzferio, and a Hawaii public health diet, obesity and serum lipid concentrations in a Poly-
representative for providing valuable information. nesian population. Ecology of Food and Nutrition 14:
169-83.
Davenport, W. 1975. The population of the outer reef is-
Bibliography lands, British Solomon Islands Protectorate. In Pacific
Allen, B. J. 1983. A bomb, a bullet or the bloody flux? atoll populations, ed. V. Carroll, 64—116. Honolulu.
Journal of Pacific History 18: 218-35. Denoon, D., with K. Dugan and L. Marshall. 1989. Public
1989. Infection, innovation and residence. In A continu- health in Papua New Guinea. Cambridge.
ing trial of treatment, ed. S. Frankel and G. Lewis, 3 5 - Dompmartin, D., E. Drouhet, and L. Improvisi. 1970. As-
68. Dordrecht. pects cliniques et mycologiques de "tinea imbricata"
Bagnis, R. 1972. La Ciguatera: Un probleme original (Tokelau). Bulletin de la Societi Frangaise deDermato-
d'oceanographic medicale. Nouvelle tentative d'expli- logie et de Syphiligraphie 77: 186-90.
cation de sa cause. Medicine de I'Afrique Noire 19: 27— Firth, S. 1987. Nuclear playground. Honolulu.
34. Fischman, A., and H. Mundt. 1971. Test patterns of yaws
Baker, P. T., and D. E. Crews. 1986. Mortality patterns and and antibodies in New Zealand. British Journal of
some biological predictors. In The changing Samoans, Venereal Disease 47: 91-4.
ed. P. T. Baker, J. M. Hanna, and T. S. Baker, 93-122. Friedlaender, J. S., and J. G. Rhoads. 1982. Patterns of
Oxford. adult weight and fat change in six Solomon Island
Banner, A. H., et al. 1963. Fish intoxication: Notes on societies: A semilongitudinal study. Social Science
ciguatera, its mode of action and a suggested therapy. and Medicine 16: 205-15.
SPC Technical Paper No. 141. Gajdusek, D. C. 1977. Unconventional viruses and the
Bayliss-Smith, T. P. 1975. The central Polynesian outlier origin and disappearance of kuru. Science 197: 943-
populations since European contact. In Pacific atoll 60.
populations, ed. V. Carroll, 286-343. Honolulu. Gee, R. W. K. 1983. The epidemiology of hypertension in
Beaglehole, E. 1957. Social changes in the South Pacific. the South Pacific. Papua New Guinea Medical Journal
London. 26: 55-61.
Brody, J. A., et al. 1970. Hereditary blindness among Gurd, C. H. 1967. Health problems in the Pacific Islands.
Pingelapese people of Eastern Caroline Islands. Lan- New Zealand Medical Journal 66: 211-13.
cet 1: 1253-7. Hamblett, E. P. 1968. Tuberculosis in the British Solomon
Brown, P., and D. C. Gajdusek. 1970. Disease patterns and Islands Protectorate (1958-1965). SPC Technical Pa-
vaccine-response studies in isolated Micronesian popu- per No. 157.
lations. American Journal of Tropical Medicine and 1969. Tuberculosis in the Gilbert and Ellice islands col-
Hygiene 19: 170-5. ony (1964-1968). SPC Technical Paper No. 161.
Burnet, M., and D. O. White. 1972. Natural history of Hammon, W. McD. 1973. Dengue hemorrhagic fever: Do
infectious disease, 4th edition. London. we know its cause? American Journal of Tropical
Burton, J. 1983. A dysentery epidemic in New Guinea and Medicine and Hygiene 22: 82-91.
its mortality. Journal of Pacific History 18: 236-61. Hanna, J. M., and P. T. Baker. 1986. Perspectives on health
Carano, P., and P. C. Sanchez. 1964. A complete history of and behavior of Samoans. In The changing Samoans,
Guam. Rutland. ed. P. T. Baker, J. M. Hanna, and T. J. Baker, 419-84.
Carroll, V. 1975. The population of Nukuoro in historical Oxford.

Henderson, J. W., et al. 1971. Area handbook for Oceania. Marshall, L. B., and M. Marshall. 1980. Infant feeding and
Hetzel, A. M. 1959. Health survey of the Trust Territory of infant illness in a Micronesian village. Social Science
the Pacific Islands. U.S. Armed Forces Medical Jour- and Medicine 14B: 33-8.
nal 10: 1199-222. Marshall, M. 1975. Changing patterns of marriage and
Hezel, F. X. 1983. The first taint of civilization. Honolulu. migration on Namoluk atoll. In Pacific atoll popula-
Hocking, B. 1974. Health problems and medical care in tions, ed. V. Carroll, 160-211. Honolulu.
Papua New Guinea. International Journal of Epidemi- Marshall, M., ed. 1982. Through a glass darkly: Beer and
ology 3: 9-13. modernization in Papua New Guinea. Boroko.
Houssiaux, J. P., J. Porte, and L. J. Fournie. 1972. Ou est le Marshall, M. 1984. Structural patterns of sibling classifica-
rhumatisme articulaire aigue en Polynesie franchise? tion in island Oceania: Implications for culture his-
Medecine de VAfrique Noire 19: 93-101. tory. Current Anthropology 25: 597-637.
Howe, K. R. 1984. Where the waves fall. Honolulu. 1987. An overview of drugs in Oceania. In Drugs in
Hyndman, D. 1988. How the west was won. Pacific Islands western Pacific societies, ed. L. Lindstrom, 13-50. Lan-
Monthly 58: 32-4. ham.
Iyengar, M. O. T. 1965. Epidemiology of filariasis in the Marshall, M., and L. B. Marshall. 1975. Opening Pan-
South Pacific. SPC Technical Paper No. 148, Novem- dora's bottle: Reconstructing Micronesians' early con-
ber. tacts with alcoholic beverages. Journal of the Polyne-
Karel, S. G., and B. Robey 1988. AIDS in Asia and the sian Society 84: 441-65.
Pacific. Asian and Pacific Population Forum 2: 1-30. Mathai, K. V. 1970. Amyothrophic lateral sclerosis and
Kerr, A. R. 1972. TB and Polynesians. New Zealand Medi- Parkinsonism dementia in the Marianas. American
cal Journal 76: 295. Journal of Tropical Medicine and Hygiene 19: 151—4.
King, H., et al. 1984. Risk factors for diabetes in three McArthur, N. 1967. Island populations of the Pacific.
Pacific populations. American Journal of Epidemi- Canberra.
ology 119: 396-409. Miles, J. A., et al. 1973. A serological study on the occur-
Kraemer, A. 1908. Die Medizin der Truker. Archiv filr rence of some respiratory infections in Fiji. Human
Schiffs- und Tropen-Hygiene 12: 456-64. Biology in Oceania 2: 79-96.
Kuykendall, R. S. 1966. The Hawaiian kingdom (1854- Montgomerie, J. Z. 1988. Leprosy in New Zealand. Journal
1874), Vol. II. Honolulu. of the Polynesian Society 97: 115-52.
1967. The Hawaiian kingdom (1874-1893), Vol. III. Ho- Moodie, P. M. 1973. Aboriginal health. Canberra.
nolulu. Moorehead, A. 1966. The fatal impact: An account of the
1968. The Hawaiian kingdom (1778-1854), Vol. I. Hono- invasion of the South Pacific (1767-1840). New
lulu. York.
Lambert, B. 1975. Makin and the outside world. In Pacific Murrell, T. G. C. 1983. Pigbel in Papua New Guinea: An
atoll populations, ed. V. Carroll, 212-85. Honolulu. ancient disease rediscovered? International Journal of
Lander, H. 1989. A century of service. Pacific Islands Epidemiology 12: 211-14.
Monthly 59: 20-2. Nason, J. D. 1975. The strength of the land: Community
Lepowsky, M. A. 1985. Food taboos, malaria and dietary perception of population on Etal atoll. In Pacific atoll
change: Infant feeding and cultural adaptation on a populations, ed. V Carroll, 117-59. Honolulu.
Papua New Guinea island. In Infant care and feeding in Nelson, H. E. 1971. Disease, demography and the evolu-
the South Pacific, ed. L. B. Marshall, 58-81. New York. tion of social structure in highland New Guinea. Jour-
Leprosy Review. 1973. Leprosy in the South Pacific. 44: 7. nal of the Polynesian Society 80: 204-16.
Leproux, P., and P. R. Lande. 1972. Profil physiologique de Norman-Taylor, W., et al. 1964. A health survey in the
Tahiti et de ses archipels. Medecine de VAfrique Noire New Hebrides. SPC Technical Paper No. 143.
19: 103-10. Oliver, D. O. 1962. The Pacific islands, revised edition.
Lewin, R. 1987. Environmental hypothesis for brain dis- Cambridge.
ease strengthened by new data. Science 237: 483-4. Owens, J. M. R. 1972. Missionary medicine and Maori
Lindenbaum, S. 1979. Kuru sorcery, Chaps. 2-3. Palo Alto. health: The record of the Wesleyan mission to New
Lombange, C. K. 1984. Trends in sexually transmitted Zealand before 1840. Journal of the Polynesian Society
disease incidence in Papua New Guinea. Papua New 81: 418-36.
Guinea Medical Journal 27: 145-57. Pacific Islands Monthly (PIM). 1988. AIDS in the islands.
Maddocks, I. 1973. History of disease in Papua New 59: 30.
Guinea. In The diseases and health services of Papua Paine, B. G. 1973. Pertussis in the highlands: A clinical
New Guinea, ed. C. O. Bell, 70-4. Port Moresby. review. Papua New Guinea Medical Journal 16: 3 6 -
Marshall, L. B., and J. A. Lakin. 1984. Antenatal health 41.
care policy, services, and clients in urban Papua New Patel, M. S. 1984. Diabetes, the emerging problem in
Guinea. International Journal of Nursing Studies 21: Papua New Guinea. Papua New Guinea Medical Jour-
19-34. nal 27: 1-3.

Patrick, R. C, et al. 1983. Relationship between blood phylaxis: Field trial in three high-prevalence villages
pressure and modernity among Ponapeans. Interna- in Micronesia. International Journal of Leprosy 40:
tional Journal of Epidemology 12: 36-44. 40-7.
Peterson, C. R., et al. 1966. Poliomyelitis in an isolated Smith, H. M. 1975. The introduction of venereal disease
population: Report of a type 1 epidemic in the Mar- into Tahiti: A re-examination. Journal of Pacific His-
shall Islands, 1963. American Journal of Epidemi- tory 10: 38-45.
ology 82: 273-96. Stannard, D. E. 1989. Before the horror: The population of
Pichon, G. 1973. Lutte contre la dengue dans le Pacifique Hawaii on the eve of Western contact. Honolulu.
Sud. Institut de Recherches M6dicales Louis Malarde Stewart, J. L. 1971. Rubella-deafened children in Guam.
et Service des Endemies. Report No. 167/IRM/J.5. South Pacific Bulletin 21: 15-17.
Pirie, P. 1971—2. The effects of treponematosis and gonor- Taufa, T. 1978. Malaria and pregnancy. Papua New Guinea
rhea on the populations of the Pacific Islands. Human Medical Journal 21:197-206.
Biology in Oceania 1: 187-206. Taylor, R., and K. Thoma. 1985. Mortality patterns in the
Prior, I. 1968. Health. In Maori people in the 1960s, ed. modernized Pacific island nation of Nauru. American
E. E. Schwimmer, 270-87. New York. Journal of the Public Health 75: 149-55.
Pust, R. E. 1983. Clinical epidemiology of tuberculosis in Townsend, P. K. 1985. The situation of children in Papua
the Papua New Guinea highlands. Papua New Guinea New Guinea. Boroko.
Medical Journal 26: 131-5. Van de Kaa, D. J. 1967. Medical work and changes in
Radford, A. J. 1973. Balantidiasis in Papua New Guinea. infant mortality in Western New Guinea. Papua New
Medical Journal of Australia 1: 238-41. Guinea Medical Journal 10: 89—94.
Ramenofsky, A. F. 1989. Another perspective on accultura- Vines, A. P. 1967. Intestinal helminthiases in the South
tion and health in highland New Guinea. Current Pacific area. South Pacific Commission Seminar on
Anthropology 30: 67-8. Helminthiases and Eosinophilic Meningitis, Noumea,
Reid, J. 1983. Sorcerers and healing spirits. Canberra. New Caledonia. June, SPC/SHEM/WP.3.
Riley, I. D. 1973. Pneumonia in Papua New Guinea. Papua 1970. An epidemiological sample survey of the high-
New Guinea Medical Journal 16: 9—14. lands, mainland, and islands regions of the Territory
1983. Population change and distribution in Papua New of Papua and New Guinea. Port Moresby.
Guinea: An epidemiological approach. Journal of Hu- Wallace, G. D., L. Marshall, and M. Marshall. 1972. Cats,
man Evolution 12: 125-32. rats, and toxoplasmosis on a small Pacific island.
Rosen, L., et al. 1967. Studies on eosinophilic meningitis: American Journal of Epidemiology 95: 475-82.
Epidemiologic and clinical observations on Pacific is- Walzer, P. D., et al. 1973. Balantidiasis outbreak in Truk.
lands and the possible etiologic role of Angiostrongy- American Journal of Tropical Medicine and Hygiene
lus cantonensis. American Journal of Epidemiology 22: 33-41.
85: 17-44. Warburton, M. F. 1973. Epidemiology of influenza in Aus-
Royston, E. 1982. The prevalence of nutritional anemia in tralia and Papua New Guinea. Medical Journal of
women in developing countries. World Health Statis- Australia 1 (special supplement): 14-18.
tics Quarterly 2: 52-91. Ward, R. H. 1983. Genetic and sociocultural components of
Russell, D. A. 1973. Leprosy in Papua New Guinea. Papua high blood pressure. American Journal of Physical
New Guinea Medical Journal 16: 83-5. Anthropology 62: 91-105.
Saunders, K. 1976. The Pacific Islander hospitals in colo- WHO Weekly Epidemiology Record. 1973. Leprosy
nial Queensland. Journal ofPacific History 11: 28-50. (B.S.I.P.). 48: 229-30.
Savige, J. 1982. Diabetes mellitus in the Tolais of the Wilkinson, P. J., et al. 1973. The 1971-1972 dengue epi-
Gazelle Peninsula, New Britain. Papua New Guinea demic in Fiji. Otago, N.Z.
Medical Journal 25: 89-96. Willis, M. F. 1970. The Takuu islanders: Health and social
Schlomowitz, R. 1987. Mortality and the Pacific labor change in an atoll population. South Pacific Bulletin
trade. Journal of Pacific History 22: 34—55. 20: 39-42.
1988. Mortality and indentured labor in Papua (1885- Wood, C. S., and L. P. Gans. 1981. Hematological status of
1941) and New Guinea (1920-1941). Journal of Pa- reproductive women in Western Samoa. Human Biol-
cific History 23: 70-9. ogy 53: 268-79.
Shaper, A. G. 1972. Cardiovascular disease in the tropics: Woolcock, A. J., M. H. Colman, and C. R. B. Blackburn.
Blood pressure and hypertension. British Medical 1973. Chronic lung disease in Papua New Guinea and
Journal 3: 805-7. Australian populations. Papua New Guinea Medical
Sharp, P. T. 1982. Highlands malaria: Malaria in Enga Journal 16: 29-35.
Province of Papua New Guinea. Papua New Guinea Zigas, V, and R. L. Doherty. 1973. An outbreak of dengue
Medical Journal 25: 253-60. in the Rabaul community. Papua New Guinea Medical
Sloan, N. R., et al. 1972. Acedapsone in leprosy chemopro- Journal 16: 42-5.

VII.6. The Caribbean 497
its Neolithic revolution. This was before Old World
VII.6 hunter-gatherers with stone tools (which the pio-
Disease Ecologies of the neers were) became sedentary farmers with metal
tools, and settled down to domesticate plants and
Caribbean animals and, not incidentally, to propagate disease.
The animals that gave these Old World farmers
milk, eggs, meat, and hides also passed on bacteria
The Pre-Columbian Period and viruses and helminthic parasites that flourished
The belief that the American Indians were indige- in the new environment, which humans were creat-
nous persisted until relatively recently. But today it ing for them. Unlike hunter-gatherers who were al-
is generally accepted that the first Americans were ways on the move, sedentary farmers stayed put to
actually wandering Asians who took advantage of pass those pathogens back and forth among them-
the prevailing ice age to cross the Bering Straits selves through fouled water supplies, mounting hu-
from Siberia to Alaska and enter a continent devoid man garbage, and filthy housing that harbored in-
of human life. Then, perhaps 10,000 years ago most sects, rodents, and other assorted pests adept at
of the large ice caps melted and seas rose, inundat- spreading illness. Moreover, no sooner did one group
ing the land bridge and sealing off the Asian pio- develop immunities to local ailments than human
neers in what would later be called the New World. migration and trade brought them into contact with
They were hunter-gatherers, these pioneers, with another group and new diseases, or new and deadly
a nomadic way of life, which meant that when a strains of old diseases.
band became too numerous to function efficiently, a The later construction of cities also saw the con-
part would break off and move on to new lands. struction of a near perfect pathogenic paradise to
Gradually this hiving out took them southward, and provide a last crucial step in the immunologic tem-
archeological remains tentatively suggest that some pering of Old World peoples. Crowded together as
9,000 years ago the southerly thrust finally came to they were, spitting, coughing, and breathing on one
an end as they reached the southern tip of South another, surrounded by the excrement of humans
America. and animals alike to contaminate all they consumed
It seems to have been much later, however, that with the aid of swarms of flies buzzing about, the
the first humans settled the islands of the Carib- city peoples were natural targets for epidemic dis-
bean, although there is neither afirmdate nor agree- ease. But their growing numbers meant that dis-
ment on the mainland from which those first to eases once epidemic soon became endemic and thus
arrive came. For example, the northern Antilles, became childhood diseases to be endured as a kind of
Cuba, is a short sailing distance from both southern a rite of passage that would ensure immunity
Florida and the Yucatan Peninsula, whereas on the against them as adults.
other end of the island chain, to the southeast, lies By extreme contrast, New World populations expe-
Trinidad, just off the South American continent. rienced very little of this sort of immunologic prepa-
When the first Spaniards reached the Caribbean, ration. Rather, their pioneering ancestors had left
they found at least four Indian cultures whose bear- home before the Old World Neolithic Revolution had
ers had apparently arrived at different times, with begun. Thus, they came without animals with whom
the levels of those cultures reflecting the stage of to share diseases, while those humans who were sick
human development on the mainlands when the mi- or weak would have been summarily weeded out by
grations occurred. There is some evidence to indicate the hardship and cold inflicted on them in their
that one of these peoples may have come from Flor- passage to Alaska. The result was that the salubri-
ida, although this is in dispute. Most, however, came ous environment of the Americas remained rela-
from the northeast of South America. Because of tively disease-free despite human invasion.
these various migrations it is probably safe to as- One says "relatively," because by 1492 a New
sume that the Caribbean Indians carried most of the World Neolithic Revolution had been under way for
same kinds of pathogens as their mainland counter- some time. Many had settled into sedentary agricul-
parts, meaning that they too were blessed with a ture, some animals had been domesticated, and
freedom from illnesses that had been denied to most some complex civilizations such as the Mayas, Incas,
of the rest of the world's peoples for millennia. The and Aztecs had long before constructed large cities.
pioneers who had crossed into the Americas made Thus, some kinds of tuberculosis had developed, at
that crossing before the Old World was caught up in least among the city dwellers, and they were tor-

mented by ailments that derived from their water their blood, bowels, and hair, and on their breaths
and food such as intestinal parasites and hepatitis. and skin. Disease-bearing insects and rodents
In addition, pinta seems to have been endemic winged their way and scampered ashore, while cat-
among those in warmer climates whose dress was tle, horses, and especially hogs wobbled down gang-
sufficiently scanty to permit ready skin-to-skin planks on stiff legs to begin munching and tram-
transmission. Whether they had venereal syphilis pling their way across the fragile flora of the islands,
has long been a matter of dispute, with one of the reproducing wildly as they went with no natural
reasons for that dispute being that pinta would have predators to thin their numbers.
provided some cross-immunity against syphilis. The long-run consequence of this Old World inva-
There is little question, however, that the New sion is that today the islands are truly artificial; only
World Indians were "virgin soil" peoples for the host their limestone, volcanic rock, coral, and the underly-
of diseases about to descend on them from Eurasian ing mountain ranges upon which they rest are of this
and African Old Worlds. In the words of Alfred hemisphere. The plants that grow on them, along
Crosby (1986), "They seem to have been without any with the animals and humans that inhabit them, are
experience with such Old World maladies as small- practically all Old World immigrants.
pox, measles, diphtheria, tracoma, whooping cough, Of the pre-Columbian island inhabitants, the hu-
chicken pox, bubonic plague, malaria, typhoid fever, mans were the first to depart, and their disappear-
cholera, yellow fever, dengue fever, scarlet fever, ance unfortunately was accomplished very quickly.
amebic dysentery, influenza and a number of They left behind them little more than a few artifacts
helminthic infestations." and the unanswered question of how numerous they
The diet of the Indians of the hemisphere, in con- were prior to the arrival of Columbus so that the
trast, was apparently considerably more varied than magnitude of the demographic disaster that befell
their diseases. In the Caribbean, the principal nutri- them can be measured. There has been a tendency to
ment of those engaged in sedentary agriculture disregard early Spanish estimates as excessive and to
came from manioc (yucca), which they grew in culti- portray the West Indies as sparsely populated. More
vated fields and processed into a bread, which the recently, however, considerably more respect has
Spaniards called "cassava." Corn was not the impor- been accorded the earlier estimates, and the size of
tant staple that it was elsewhere in the Americas, pre-Columbian populations is being revised sharply
but it did supplement some West Indian diets as did upward. For example, S. F. Cook and W. W. Borah
white and sweet potatoes, beans, pumpkins, and pea- (1971, 1974, 1979) have calculated that the island of
nuts. With no domesticated animals save for a kind Hispaniola (today the Dominican Republic and Haiti)
of dog (sometimes eaten), animal protein was served contained close to 4 million Indians; they suggest
up mostly in the form of fish along with certain that by 1508 that population had dwindled to less
reptiles and insects. than 100,000, thereby providing us with at least a
Fishing, however, appears to have been more a glimpse of the holocaust of disease the islands had
leisurely activity than an industry, and it would become.
seem that animal protein played a fairly minor role Another glimpse comes from Cuba, which was con-
in the diet. This essentially vegetable diet based quered in 1511. Just a few short years later, Fran-
largely on manioc, which is notorious for its lack of cisco Lopez de Gomara could write that this island
important nutrients, coupled with the Spanish obser- "was once heavily populated with Indians: today
vation that the Indians ate very sparingly, suggests there are only Spaniards." This of course was an
that they probably suffered from some nutritional impression only, and the Cook and Borah estimate,
deficiencies, and these, in combination with the Indi- although based on an array of evidence and in-
ans' lack of disease immunities, would have ren- formed demographic reasoning, remains an estimate
dered them even less able to ward off the Old World only. Yet knowledge of what specific diseases have
illnesses about to arrive. done to immunologically defenseless peoples lends a
good deal of plausibility to theories that urge the
European Diseases existence of much larger pre-Columbian populations
Perhaps no other region on the globe has ever experi- than previously believed.
enced such a sudden and devastating ecological as- Francisco Guerra (1988) argues convincingly that
sault as the islands of the Caribbean with the ar- the first epidemic disease unleashed on the Indians
rival of the Europeans. Ship after ship arrived to was swine influenza; it reached the West Indies in
disgorge humans bearing Old World pathogens in 1493 with swine brought by Columbus from the Ca-

VH.6. The Caribbean 499
nary islands on his second voyage. Certainly some trap for the remaining original Americans as well as
disease began sweeping the islands shortly after the for the white newcomers who up to this point had
discovery and long before smallpox apparently made found the islands reasonably healthful.
its Caribbean debut. There were reports of massive
die-offs not just in Hispaniola but in Cuba and the African Diseases
Bahamas as well. Vivax malaria probably arrived in the blood of the
Typhus had surfaced in Spain during the war with first Europeans and, although a relatively benign
Granada and doubtless also reached the islands (and form of the disease, nonetheless joined in the slaugh-
the Indians) even before smallpox began its relent- ter by claiming its share of Indian lives. As the
less assault on Hispaniola in 1518, and on Cuba the Indian die-off progressed, the'Spaniards found them-
following year. There ensued a decade during which selves forced to look elsewhere for hands to put to
dozens of other diseases were probably introduced, work colonizing the Americas, and they chose the
before the next reported epidemic, measles, which black African. By 1518 the transatlantic slave trade
struck in 1529. was under way, which almost immediately opened a
Swine influenza has been known on occasion to conduit for the transatlantic flow of a much more
precipitate mortality levels as high as 20 to 25 per- deadly form of the disease: falciparum malaria.
cent of a population, and smallpox has killed upward The circumstances surrounding the introduction
of 40 percent of a people experiencing it for the first of yellow fever from Africa are less clear: Although
time; measles, a relatively benign disease for Europe- it is now generally accepted that the anopheline
ans, has thinned the ranks of "virgin soil" peoples by mosquitoes that spread malaria were on hand in the
25 percent; whereas typhus has historically pro- New World to do just that, the Aedes aegypti vector of
duced mortality for between 10 and 40 percent of yellow fever most probably was not. Thus both vec-
those ill with the disease. tor and virus had to be imported and to reach human
Clearly then, with maladies capable of producing populations dense enough to support them. A case
these high levels of mortality, conceivably the pre- has been made that all of these conditions were met
Columbian populations of the Caribbean could have by 1598 at San Juan, Puerto Rico, and there is abso-
been much larger than heretofore believed. This lutely no question that they were met by 1647 when
also ignores mortality generated by other illness yellow fever launched assaults on Barbados and Gua-
such as chickenpox, diphtheria, scarlet fever, ty- deloupe, before continuing on to Cuba and the Gulf
phoid, whooping cough, and bubonic plague, all of coasts of Mexico and Central America.
which were also introduced from Spain. No wonder The slaves had lived with both of these tropical
then, that by 1570 most of the Indians of the region killers for eons and in the process had developed a
had vanished. Only the Caribs still survived in the relative resistance to them. But in addition, they
eastern Caribbean - an area not yet much fre- were also accustomed to most of the other Old World
quented by the Europeans. illnesses that had proven so devastating to the Indi-
It is important to note, however, that all of these ans. The ironic result of this ability to resist disease
maladies struck equally hard at mainland popula- was that it made blacks even more valuable as
tions. But although they also experienced massive slaves. The Indians died of European and African
die-offs, the survivors slowly built immunities, and diseases, the whites died of African diseases, but the
after a century or two those populations began to blacks were able to survive both, and it did not take
grow once again. But this was not the case in the the Europeans long to conclude that Africans were
West Indies. Part of the reason was that the Carib- especially designed for hard work in hot places.
bean was a corridor through which all Europeans This view was not limited to the Spaniards, al-
had to pass to reach various parts of the mainland; though they had been the first to discover the blacks'
therefore, those in the corridor had more exposure to durability. Other Europeans had begun trickling
disease than those outside it. But the main reason into the Caribbean, impelled from their mother coun-
was that the West Indian Islands became the target tries because of wars, religion, politics, crimes com-
of still another wave of disease - this time from Af- mitted, or just outright lust for adventure and
rica. The most deadly of these diseases were riches. They settled first on the islands of the east-
mosquito-borne and seldom reached up into the ern Caribbean, which had been left relatively un-
cooler elevated regions of the mainlands, which were touched by the Spaniards, and brought disease to,
home for so many Indians, but they turned the low- and ultimately an end to, the surviving Caribs.
lying areas of the West Indies into one huge death If at first these new arrivals grew any "cash

crops," they grew tobacco in small plots, which the in the West Indies, the bulk of them to this pair of
Dutch, by then ubiquitous in West Indian waters, tropical killers. Much of that mortality had been
marketed for them. All this changed abruptly, how- sustained during the British invasion of San Dom-
ever, when the Dutch, who had moved into Brazil, ingue, where the slaves were revolting against
were driven out, taking with them the secrets of French masters. Because of their ability to resist the
sugar production. These they gave to the small plant- disease, the ex-slaves had a strong ally in yellow
ers of the eastern Caribbean along with financial fever, as the disease counterattacked the British
assistance, and the sugar revolution was under way. with deadly effect.
Tobacco growers became sugar planters, small to- Next came the French attempt to retake San Dom-
bacco plots were consolidated into large sugar planta- ingue. Briefly they met with success. Then they met
tions, and the demand for black labor soared. The with yellow fever and within 10 months of landing
Dutch met that demand with their slave ships, had lost some 40,000 men including 1,500 officers
which brought African pathogens as well as Afri- and their commander, Napoleon's brother-in-law.
cans, both of which had heretofore only trickled into Yellow fever nourished in the Caribbean wherever
the Caribbean and now began to pour in. the virus discovered a sufficient number of nonim-
In addition to yellow fever and falciparum malaria mune persons to host it, for the A. aegypti is a domes-
came the filarial worm, also carried by mosquitoes, to ticated mosquito that lives close to and feeds on
create the infamous disease "Barbados leg." It seems humans and breeds in rain-filled gouges humans
to have broken out on that island first, but soon was have made in the earth or in any of the discarded
widespread throughout much of the Caribbean, al- accoutrements of civilization that hold water. Anoph-
though always strangely absent in Jamaica. The Afri- eline mosquitoes that carry malaria, however, are
cans also carried with them the misnamed hookworm not so tied to humankind and consequently are not
Necator americanus, which found the West Indian spread evenly across the Caribbean. Thus August
sugarcane fields an especially favorable habitat. Hirsch (1883-6) identified Cuba, Jamaica, Santo Do-
That dracunculiasis was rife among them could be mingo, Guadeloupe, Dominica, Martinique, St. Lu-
noted as Guinea worms poked their heads out of slave cia, Grenada, Trinidad, and Tobago as the places
legs to be patiently wound on a stick by the victim where the disease was most prevalent. He termed
until all of the worm was removed. In addition, yaws malaria "rare" in the Bahamas, Antigua, St. Vin-
blossomed on the bodies of slave youngsters, leprosy cent, and Barbados, where today we know that for a
assaulted the adults, and onchocerciasis invaded the variety of reasons anopheline mosquitoes had diffi-
eyes of both. Indeed, even smallpox began arriving culty in breeding successfully.
from African rather than European reservoirs, and It should be stressed that, although yellow fever
the Caribbean was transformed practically overnight and malaria were the chief killers of whites in the
into an extension of an African, as opposed to a Euro- West Indies, the victims were generally newcomers.
pean, disease environment. Old residents, by contrast, usually suffered from yel-
Paradoxically, the increasing dangers of such an low fever while quite young, at an age when the
environment paralleled the increasing value of the malady is relatively gentle with its victims, and in
West Indian Islands in the eyes of the capitals of the process earned a lifetime of immunity against
Europe. As colonies that sustained a slave trade, another visitation. Similarly, resistance to malaria
purchased products from mother countries, and sup- was gained by repeated bouts with the disease al-
plied sugar for processing to those countries, the though this was not so perfect an immunity as that
islands fit marvelously into - indeed helped to acquired against yellow fever.
shape - the prevailing mercantilist philosophy, a Blacks, on the other hand, although remarkably
part of which prescribed grabbing as many more resistant to these diseases, suffered greatly from
islands as possible from European competitors. other illnesses that generally bypassed whites, and
The political consequence was that Europe's wars their resulting experience with disease was so differ-
of the seventeenth and eighteenth centuries were ent from that of whites that physicians were moved
fought out in the islands as well as on the continent. to write whole books on the subject. They identified
The epidemiological consequence was the slaughter one of the most fearful diseases of slave infants as
of tens of thousands of nonimmune soldiers and sail- the "9-day fits," which today would be diagnosed as
ors sent to do that fighting who died, not from battle, neonatal tetanus triggered by an infected umbilical
but from yellow fever and malaria. During the years stump. Another example of a presumed black dis-
1793-6, for example, the British lost 80,000 troops ease came from the same source. Plantations were

littered with the droppings of horses and oxen con- the mal d'estomac in some islands and hatiweri or
taining tetanus spores, so the almost always fatal cachexia Africana in others. Physicians first thought
illness struck hard at slaves with open wounds re- that the lack of energy, breathlessness, and nerve
sulting from frequent accidents with machinery, and problems including an unsteady, high-stepping
because almost all went barefoot. gait - the symptom constellation of mal d'estomac —
Poor nutrition, however, was probably the biggest were caused by dirt eating; later investigators have
destroyer of slave life, either directly because of nu- suspected that the cause was hookworm disease. But
tritional diseases or indirectly because it left slaves because, as will be discussed shortly, blacks of West
less able to combat other ailments. Their basic diets African origin are very resistant to the ravages of
of very little salted fish (jerked beef in Cuba) and hookworm infection, dry beriberi remains the best
lots of manioc and other root crops, plantains, rice, explanation for this particular ailment.
and corn produced symptoms of frank beriberi (re- Another disease that remained a mystery at least
lated to thiamine deficiency) and pellagra (related to until recently, and which struck white troops as well
niacin deficiency) among slaves all across the Carib- as slaves, was the "dry belly ache." But research by
bean. Of the two, beriberi had the greatest demo- Jerome Handler, Arthur Aufderheide, and others
graphic impact because thiamine deficiency is (1986) has made it clear that this ailment was actu-
passed along from mother to infant in her milk, and ally lead poisoning; the lead being ingested in non-
infantile beriberi has proved historically to be al- aged rum made with distilling equipment contain-
most invariably fatal. ing the metal and from molasses and sugar whose
Another major disease of the slave young was production also involved the leaching of lead from
protein-energy malnutrition (PEM) brought on by a some of the equipment.
lack of whole protein in the diet. Slave infants were The successful slave revolution in San Domingo
nursed by their mothers for about 3 years and were brought ruin to one major sugar-producing area of
thus safe from the disease, which struck after they the Caribbean, whereas the abolition of the British
were weaned to a diet of pap almost totally devoid of slave trade in 1807, and then of British slavery in
good-quality protein. Some developed marasmus, a 1833, severely damaged most other sugar islands.
symptomatic pole of PEM in which the child simply This left the field to Cuba, which developed a flour-
wastes away. More often, however, they developed ishing contraband slave trade, and became the new
the swollen bellies of kwashiorkor, which are evi- focus of such African diseases as filariasis, leprosy,
dent in physicians' descriptions of slave children. and yaws while at the same time achieving the un-
The prevalence of PEM in Barbados can be assumed happy distinction of becoming the nineteenth-
from the conclusions of an investigation of the teeth century yellow fever capital of the hemisphere.
of excavated slave skeletons, which revealed consid- Other diseases also became prevalent during this
erable nutritional stress at the time of weaning period. Typhoid, for example, was an increasingly
(Handler and Corruccini 1986). serious health problem in the West Indies through-
The term dropsy was very frequently recorded as out the century, although in part this trend doubt-
the cause of slave deaths, and doubtless when a child less reflects nothing more than better diagnosis as
died of kwashiorkor, this was called dropsy. Simi- physicians learned to untangle typhus and typhoid
larly, the fluid accumulations of wet beriberi would from each other and both from the whole bundle of
have been called dropsy. Other dropsy cases were fevers that bedeviled the region. Because the fouled
probably the work of hypertensive heart disease. water supplies that brought typhoid were serious
Apparently in the largely salt-free environment of problems everywhere, it was predictable that the
sub-Saharan Africa, black bodies had developed an islands would pay a steep price for this condition
ability to retain the mineral that is crucial to life when the pandemics of Asiatic cholera reached
itself (Wilson 1986). In the West Indies, however, them. This first occurred in Cuba where, during the
slaves received an abundance of the mineral in their years 1833-6, the disease wiped out at least 8 per-
salted fish or beef, and in addition, were issued a cent of the slave population.
great deal more as a condiment. For a people with The 1850s, however, were the real cholera years
the knack for retaining salt, this must have pro- for the Caribbean during which as many as 34,000
voked much fluid accumulation and frequently slaves in Cuba perished, between 40,000 and 50,000
proved deadly. individuals died in Jamaica, another 20,000 to
Dry beriberi's symptoms are remarkably similar 25,000 lives were lost in Barbados, and at least
to those of a mysterious illness of the slaves called 26,000 succumbed in Puerto Rico. Cholera returned

a final time to Cuba in 1867, where it claimed a few The Twentieth Century
thousand more lives before leaving the region for- The twentieth century has been a time of a tremen-
ever. In its wake, however, it left a far greater per- dous mortality decline in the Caribbean as it has in
centage of black than white victims. Because there much of the rest of the underdeveloped world. Im-
is no racial predisposition to cholera, the best expla- proved nutrition, great strides in public health and
nation for this lies in the impoverished circum- sanitation, and the increasing sophistication of mod-
stances of blacks on the one hand and lesions of ern medicine have all played significant roles.
nutrition that deprived them of gastric acid to fight Yellow fever's Caribbean career came to a close
cholera vibrios on the other (Kiple 1985). during the occupation of Cuba by the United States
The fact that tuberculosis waited until the nine- when the theory of Cuban physician Carlos Finlay
teenth century to fall on blacks with the fury that it that the disease was mosquito-borne was proved cor-
did is less easy to explain. Tuberculosis was not one rect by a Yellow Fever Commission headed by Wal-
of the Euroasian diseases that blacks had experi- ter Reed. Ensuing mosquito control measures were
enced in Africa, and they proved to be extraordi- successful in throttling the long-dreaded malady in
narily susceptible to it when exposed. That such Cuba, and, armed with this new epidemiological un-
exposure was so long delayed suggests that the plan- derstanding of the disease, William Gorgas was able
tation probably served as a kind of quarantining to eliminate yellow fever in Panama where the canal
device. After slavery, however, the disease exploded was under construction. The disease flared up one
among them as many impoverished blacks crowded last time in Cuba in 1905 but, after that, retreated
into the cities. In Havana, for example, the disease from the whole of the Caribbean.
generated mortality rates approaching 1,000 per The public health activities of the U.S. Army also
100,000 population. brought sweeping sanitary reforms to Cuba, which
Nonetheless, although tuberculosis continued to in Havana resulted in a decrease of "close to 30
rage, it was during the last half of the nineteenth percent in the crude death rate in that city by 1902"
century that much of the region began to experience (Diaz-Briquets 1983). Similarly the annexation of
a significant decline in mortality. Certainly some of Puerto Rico, and the occupation of the Dominican
the decline was due to nothing more than the end of Republic and Haiti by the United States, although
slavery. But empirical observation also played a con- deplorable, nonetheless brought important health
siderable role. Cholera had drawn attention to the benefits to these countries in the form of cleaner
dangers of bad water, and the last decades of the water supplies, adequate sewage disposal systems,
century witnessed important efforts to improve wa- mosquito control, and medical treatment.
ter supplies, with a resulting decrease in the preva- Just at the time when one African disease, yellow
lence of typhoid and dysentery. Empirical observa- fever, was conquered, however, another African mal-
tion had also established once and for all the efficacy ady was revealed. In Puerto Rico, the Puerto Rico
of quinine against malaria, and its regular use also Anemia Commission discovered a hookworm prob-
brought important mortality reductions. lem estimated to be causing one third of all deaths
Cuba, however, was largely exempted from the on the island. War was declared on this disease, as
mortality decline enjoyed elsewhere during this pe- well as on malaria and yaws, in much of the Carib-
riod. No sooner had the contraband slave trade come bean by the Rockefeller Sanitary Commission and
to an end, capping the pipeline of disease from Af- later by the Rockefeller International Health Board.
rica, and no sooner had cholera receded than the Ten The Rockefeller physicians in the West Indies and in
Years' War (1868-78) erupted. Soldiers arrived from the southern United States discovered that black
Spain to extinguish the rebellion only to introduce people were resistant to hookworm disease although
smallpox and be extinguished themselves by that not to hookworm infection, whereas pockets of poor
disease in tandem with yellow fever and malaria. A whites and Asians in the West Indies living side by
few years later, this pattern was repeated as Spain side with blacks suffered severely from the disease.
once more sent soldiers to Cuba to quell the rebellion Tuberculosis receded among Caribbean blacks as
that began in 1895. In both instances, yellow fever mysteriously as it had appeared, and it had ceased to
and malaria claimed far more lives than did bullets, be much of a health problem long before the end of
with war and disease slashing Cuba's population World War II when medicine finally got its "magic
from about 1.8 million in 1895 to 1.5 million in bullet" against the malady. Yet the greatest gains in
1899 - fully a 15 percent reduction in less than 5 reduced mortality have taken place among the very
years. young. Infant mortality rates, which were as high as

303 per 1,000 live births in Barbados earlier in the able than that enjoyed by those in most other devel-
century, have plummeted in most places to rates of oping nations.
20 per 1,000 or below. Exceptions are the Dominican Yet it is ironic that today the greatest threat to the
Republic and especially Haiti, where age-old prob- health of West Indian people is their own relatively
lems of neonatal tetanus, malaria, yaws, and other good health. With the tremendous strides made in
African diseases still linger. reducing infant and child mortality, populations
Less satisfactory have been improvements in the have mushroomed in alarming fashion. In the past,
nutrition of the young, and it is quite possible that much of the excess population of the region migrated
fully half the deaths that have taken place among to Great Britain or to the United States; that safety
the age group 1 to 4 years in Hispaniola and Jamaica valve has been shut down by the recent restrictions
in recent years are the result of PEM — the same both of these countries have placed on immigration
disease that proved so devastating to the slave from the islands. And they are islands, which by
young of yesterday. Other problems or potential prob- definition means a limited area of land. If, as is the
lems left over from the disease ecology of that period case in so many of them, land is put into sugar
also remain. Yellow fever is still very much alive in instead of foodstuffs, then the latter must be im-
its jungle form in the treetops of South America and, ported. Thus, swelling populations can only threaten
with the present lax mosquito control measures, the level of their nutrition while placing perhaps
could easily return to the Caribbean as it in fact impossible pressures on the ability of governments
attempted to do in Trinidad during 1954. Indeed the to continue to deliver essential medical and sanitary
ever increasing number of dengue epidemics that services.
have taken place of late in the region show just how Kenneth F. Kiple
vulnerable the West Indies are to yellow fever, be-
cause the same mosquito spreads both diseases.
Bibliography
Similarly the pockets of falciparum malaria that Ashburn, P. M. 1947. The ranks of death: A medical history
still exist may also suddenly expand, as happened in of the conquest of America. New York.
Cuba during the 1920s when tens of thousands of Ashcroft, M. T. 1965. A history and general survey of the
Haitian and Jamaican laborers entered the country helminth and protozoal infections of the West Indies.
bringing the illnesses with them. Haiti, in particu- Annals of Tropical Medicine and Parasitology 59:
lar, remains a focus of the infection, as an epidemic 479-93.
there in 1963 so vividly demonstrated by assaulting Cook, S. E, and W. W. Borah. 1971, 1974, 1979. Essays in
some 75,000 individuals. population history: Mexico and the Caribbean, 3 vols.
Filariasis has not been completely eradicated. In Berkeley.
fact, the people of Puerto Rico were found to have a Crosby, A. W. 1972. The Columbian exchange: Biological
surprisingly high rate of infection during a survey in and cultural consequences of 1492. Westport, Conn.
1986. Ecological imperialism: The biological expansion
the 1960s. In Barbados, however, where the disease
of Europe, 900-1900. New York.
was once notorious, the malady (or at least its most Curtin, P. D. 1989. Death by migration: Europe's encounter
notable symptoms) has become rare. Schistosomiasis with the tropical world in the nineteenth century. New
may still be found in some of the Lesser Antilles, and York.
small endemic foci have been located in the Domini- Dobyns, H. F. 1983. Their numbers become thinned: Native
can Republic as well, and intestinal parasites remain American population dynamics in eastern North Amer-
widespread across the Caribbean region. In addition, ica. Knoxville.
another new, seemingly African disease - AIDS - Diaz-Briquets, S. 1983. The health revolution in Cuba.
has surfaced in Haiti, although the extent to which Austin.
this threatens the rest of the Caribbean remains to be Dirks, R. 1978. Resource fluctuations and competitive
seen. transformations in West Indian slave societies. In Ex-
tinction and survival in human populations, ed.
One of the greatest assaults of late mounted on
C. Laughlin and I. Brady. New York.
remaining health problems in the region has taken Guerra, F. 1988. The earliest American epidemic: The
place in Cuba, where the government of Fidel Cas- influenza of 1493. Social Science History 12: 305-25.
tro has made improved health a top priority. The Handler, J., and R. S. Corruccini. 1986. Weaning among
extension of health services to the countryside, West Indian slaves: Historical and bioanthropological
mass vaccination campaigns, and important ad- evidence from Barbados. William and Mary Quarterly,
vances in sanitation have allowed the Cuban people 3d ser, 43: 111-17.
to attain a life expectancy considerably more favor- Handler, J., et al. 1986. Lead contact and poisoning in

Barbados slaves: Historical, chemical, and biological coherent view. General trends are perceptible in clas-
evidence. Social Science History 10: 399—425. sical times, and very sketchy numbers can be offered
Hirsch, A. 1883-6. Handbook ofgeographical and histori- for population in the late medieval period. Modern
cal pathology, 3 vols., trans. C. Creighton. London. times have, of course, brought masses of statistics,
Hoeppli, R. 1969. Parasitic diseases in Africa and the West- but these as often confuse as enlighten. Still, it is
ern Hemisphere: Early documentation and transmis- possible, at least, to discern some of the impact of
sion by the slave trade. Basel.
disease upon demography and to infer some aspects
Kiple, K. F. 1976. Blacks in colonial Cuba. Gainesville,
Fla. of the influences that played upon certain diseases.
1984. The Caribbean slave: A biological history. New Because it is so difficult to identify diseases in the
York. past, I confine myself largely to the specific diseases
1985. Cholera and race in the Caribbean. Journal of of plague, leprosy, tuberculosis, and smallpox. Other-
Latin American Studies 17: 157-77. wise, the influence of epidemic disease of unknown
Sheridan, R. B. 1985. Doctors and slaves: A medical and type will be the other main consideration, along
demographic history of slavery in the West Indian Is- with some presumed diseases of childhood. There is
lands, 1680-1834. New York. at least some reason to feel that the four specific
Wilson, T. W. 1986. Africa, Afro-Americans, and hyper- diseases may be identified as factors in human de-
tension: An hypothesis. Social Science History 10: mography in the past, as can epidemic and endemic
489-500. diseases whose exact nature is unidentifiable.
All human populations share some common fea-
tures, and European populations carry some particu-
lar features, which can help us at least conjecture
about factors influencing the expression of disease.
For example, about 105 males are born per 100 fe-
VII.7 males (Russell 1977). Although malnutrition can
Disease Ecologies of Europe cause disease, major population losses do not neces-
sarily reflect malnourishment (Wilson 1957; Wrig-
ley 1962; Rotberg and Rabb 1983). Certainly the
We can consider the ecology of disease to be the sum diseases of postindustrial society are those of an
total of all the influences on pathogens and their abundance of food. Despite the fascination since an-
hosts and, because of the interdependence of the two cient times with food as a cause, predisposing factor,
for disease expression, the internal structures and and therapeutic agent in disease, very little is actu-
systems of both that bear upon a disease question. ally known about the relationship between food and
Thus we are clearly considering a structure of rela- health beyond the effects of some vitamin-deficient
tions whose complexity surpasses all comprehen- states, and full-blown protein-energy malnutrition.
sion. Such may also be said of a single disease. No The ability of human populations to replenish
one has yet fully defined all that constitutes the themselves is limited. A birthrate above 50 per 1,000
expression of even one disease, and such an explana- population per year is truly exceptional, and above 30
tion would be its ecology. To describe the disease is quite uncommon (Wrigley 1962). There are well-
ecology of Europe is a task at first so daunting as to known age and sex predilections for a variety of dis-
admit no possibility. Still, there are a few aspects of eases, but they are as etiologically obscure as they are
the ecology of disease in Europe that can be de- epidemiologically well documented (Wilson 1957).
scribed, if without claim to completeness or ultimate For example, although infants are extremely suscepti-
value, at least with an eye to creating a target for ble to tuberculosis, children between the ages of 5 and
more detailed studies and criticism. 15 exhibit a relative immunity to the disease. Then a
With such cautions in mind, I should like to offer a sex predilection occurs, with women much more com-
few general comments on human disease and its monly the victims from about 25 years up to around
expression, and then set forth a very limited number age 45, at which time men are the predominant vic-
of aspects of the totality of my subject, which I feel tims of the disease until late in life (Wilson 1957).
can be discussed. For most of the sojourn of human- These observations are based on data gathered
kind on Earth, we have only skeletal remains upon mainly in the British Isles during the nineteenth
which to build any concept of disease in the past. century, but no one knows the extent to which they
Even after the advent of agriculture and the earliest represent the result of metabolic versus environmen-
civilizations, we have little upon which to develop a tal factors in pathogen and host. It is also generally

VH.7. Europe 505
felt that societies tended to have more males than unrealistic. Host-parasite relations vary from non-
females among adults because more women than specific, in which multiple species support the organ-
men die between the ages of 25 and 45 (Russell 1977). ism, to those in which the organism is dependent
This generalization, however, is based to a very great upon a single host. In the second case, it is felt that
extent on the perceived epidemiology of tuberculosis, the organism has lost the ability to synthesize its
a disease neither universal nor of equal importance own essential nutrients to an extreme degree (Lovell
in all societies. 1957). Leprosy is an example of an organism that
In Europe, several generalizations are usually ac- cannot be cultured in an ordinary fashion and is
cepted regarding human populations. Since classical highly host dependent (and even specific to certain
times until the Industrial Revolution, cities have cells in the host). This characteristic suggests that
harbored more women than men. Cities have also the susceptible tissues contain some chemical or pro-
been unable to replenish their own populations, at vide some enzymatic function (or possibly something
least from medieval times until the nineteenth cen- entirely different) that cannot be provided in culture
tury, because of the unfavorable disease climate of media (Wilson 1957). If we consider virulence to be
urban life (McNeill 1976; Russell 1977). Before the the property that permits an organism to cause
nineteenth century, the vast majority of humans in death or damage to the body parts invaded, we are
Europe lived in villages or on farms, with only a left with a multitude of factors to consider. An in-
very small fraction residing in cities (Guillaume and crease in virulence toward one species may decrease
Poussou 1970; Russell 1977). The total population of that strain's virulence to others (Wilson 1957), indi-
preindustrial societies contained at least one-third cating the intimacy of the relationship to a given
children, of whom less than half lived to adulthood host. The same strain of Mycobacterium tuberculosis
from medieval until modern times (Flinn 1985). is generally much more virulent when entering the
Humans also affect their environment and in turn host via the respiratory route as opposed to the gas-
affect their own disease ecology. Practices we take trointestinal tract, but with bovine tuberculosis the
for granted, such as the domestication of animals, situation is the opposite. Such information, however,
change another species' disease environment, and offers little practical guidance in the history of dis-
the interaction of domesticated animals with hu- eases, for the specificity of an organism toward hu-
mans has often led to human disease (Lovell 1957). mans (e.g., organisms causing leprosy, meningo-
An example of a disease that became of at least coccal meningitis, typhoid fever, and smallpox) only
minor importance among humans primarily in this tells us that if the disease is present, so are humans,
way is brucellosis, usually introduced to humans which is rarely in question.
through goats. During the Crimean War, for exam- In general, organisms are tissue specific. Clos-
ple, Malta became an endemic area for brucellosis; tridium tetani, for example, is harmless to intact
in 1906 the means of human infection was described skin, but can be deadly when in contact with
(Alausa 1983). abraided or necrotic tissue (Wilson 1957). The longer
Disease in turn may alter the character of human an organism is in contact with the environment and
populations. After major epidemics of infectious dis- outside a host, the likelier it will be damaged. Organ-
ease associated with high mortality, a period of mark- isms that affect the gastrointestinal tract, such as
edly reduced mortality generally begins. It is felt Salmonella typhi, are able to withstand environmen-
that such epidemics "weed out," at least in some tal pressures longer than those not waterborne or
cases, the weaker elements in a population, leaving foodborne (as a generalization) (Wilson 1957). Insect
a healthier one behind (Wrigley 1962). On the other vectors may result in significant effects on the ex-
hand, diseases such as plague and some rickettsial pression of disease. Arthropod vectors are more im-
infections often kill the healthy. portant, generally, in parasitic infections than in
If we limit our generalizations about humans in bacterial ones (Wilson 1957), but plague and typhus
Europe, our knowledge of their pathogens is even are notable exceptions.
sketchier. The whole question of virulence among Despite the staggering complexity of host-patho-
various bacteria is extremely complicated, and, gen relationships, the presence of certain diseases
since it is not well understood in modern infections can reveal important aspects of human populations.
and since organisms can mutate, virulence can be Measles is a human disease only and requires at least
assessed only by effect. The effect of an organism in a population of some hundred thousands in some con-
turn is related to host, pathogen, and environment, tact to remain endemic (Bailey 1954, 1957; Bartlett
so that any comments about organisms in the past is 1957,1960; Becker 1979; Smith 1983). Diseases such

as measles and smallpox (another human disease Europe to late twentieth-century society. I have very
whose pathogen needs a fairly large population to little to say about medicine, because I do not believe it
remain active) tend to become childhood diseases (Mc- has had a significant effect on the ecology of disease
Neill 1976; Smith 1983). Thus the first observation of except in very limited circumstances.
measles would tell us when a communicating popula- Geographically, I define "Europe" as extending as
tion of humans reached a certain level. Unfortu- far east as western Poland down through Greece, as
nately, we do not know when this occurred in Europe far north as Scandinavia (but excluding Iceland), as
because we do not know when measles first appeared. far west as the British Isles, France, and Spain, and
The clinical expression of a given disease can also tell as far south as Greece, Italy, and Malta.
us about genetic factors in a population. Susceptibil-
ity to leprosy, in both its polar forms (although more Prehistoric Europe
in tuberculoid leprosy), is in part genetically medi-
ated (Smith 1979; Eden et al. 1980; Keyu et al. 1985). Hunting-Gathering Societies and the Neolithic
When measles and TB have fulminant courses with Revolution
high and dramatic mortality, they are present in a It is often observed that hunter-gatherers are
previously unexposed population (Wilson 1957; Mc- healthier than their supposedly more "civilized" con-
Neill 1976). The same may have been the case when temporaries. This anthropological observation of
syphilis appeared in Europe at the end of the fifteenth the still-extant human groupings that practice
century, but this is hardly an undisputed subject. It is hunting-gathering has been extrapolated into the
also becoming apparent that some resistance to par- past to suggest that, because of a meat-rich diet,
ticular diseases reflects prior exposure to others that very low population density, natural birth control
confer cross-immunity (Ell 1984a). through lactation, and a variety of other factors,
Characteristics of childhood diseases, especially hunter-gatherers innately enjoyed more healthful
measles, have become the subject of mathematical circumstances than did other preindustrial soci-
modeling. Birthrate has been shown to be an impor- eties. There is, however, little evidence of any kind
tant factor in determining whether or not a disease to support such claims. Skeletal remains have been
like measles can remain endemic and in predicting used to claim a life expectancy similar to that of the
interepidemic periods (Bailey 1957; Bartlett 1957; rural poor of the nineteenth century (Birdsell 1957;
Becker 1979). Unfortunately, such models, although McNeill 1976). (What is less obvious is that skeletal
of great theoretical and some practical interest, can- remains from the very distant past will tend to
not explain much of what occurs in a given epidemic. support this hypothesis because the skeletons of
They are based on populations of constant size and children and infants neither weather as well nor
without immigrants - factors from which deviation were often buried as carefully as those of adults.)
has been crucial in many other epidemics (Siegried Although it is true that hunter-gatherer groups do
1960; Biraben 1975). This mathematical modeling is not have enough population to support measles,
of very limited value in considering the disease ecol- they do have diseases exquisitely adapted to their
ogy of Europe in the past. Too many of the factors are circumstances. An example of this phenomenon is
unknown (population size, birthrate), and the effect kuru, a slow virus that afflicts cannibal aborigines.
of social customs has not proved very susceptible to There is no reason to imagine that hunting-
quantification. Further, in this chapter we perceive gathering peoples of the past did not experience
childhood mortality as a nearly constant back- diseases equally consonant with their particular
ground factor for much of the time period discussed, patterns of life. There is no real foundation for the
with major epidemics, which have proved resistant claim that the hunter-gatherers of prehistoric Eu-
to neat equations, the more influential factors. rope were healthier than people from the Neolithic
In the following pages, I try to discern, within what and pre-Industrial periods. We simply lack any evi-
is known about the demographic history of Europe, dence to support a conclusion of any type.
the effects of disease on that history. Partly because Likewise, we do not know much about the changes
war has been an invariable aspect of human behav- in disease ecology occasioned by the development of
ior, and partly because it reflects so much else about a agriculture and the first numerically more substan-
society, I focus often on military strategy, on the com- tial groupings of persons. Observations about re-
position and size of armies, as well as on the direct maining societies that mirror Neolithic times, or
effects of disease upon armies. The time frame consid- even about remaining hunting-gathering peoples,
ered extends from the hunter-gatherers of prehistoric are suspect simply because the groups' mere sur-

VII.7. Europe 507
vival indicates something not generalizable about The Peloponnesian War also saw the famous
them. Of the population of Europe before historical Plague of Athens. In Thucydides' description of this
times, it would be difficult to frame a convincing plague, there is no sense of epidemic disease on this
argument for a number with an order of magnitude scale being any part of ordinary Greek life. To that
error included. author, the epidemic was one of the main factors in
It is felt that parasitic, especially helminthic infes- Athens' ultimate loss because it bore away Pericles
tations are among the oldest of diseases (Smith whom Thucydides clearly felt could have led his
1983), but beyond noting the claim, we can do noth- people to victory (Thucydides 1958).
ing to confirm it. The prehistory of Europe is just The exploits of Alexander the Great resulted in
that; to impose a demographic and disease structure the Hellenization of parts of Asia and Africa. The
upon it is folly. army of Alexander was able to campaign for 12
years in Asia without suffering a significant loss to
Bronze Age Civilizations disease. Fresh recruits from Macedonia and Greece
The civilizations of Mycenaean Greece and of arrived mainly to replace those retiring or lost in
Minoan Crete are discoveries of the last century. battle. The whole concept of a campaign like that of
Before excavations at the site of Troy and among the Alexander, which lacked temporal and spatial goals,
Greek cities of Homeric renown, along with Crete, would be either unthinkable or pure folly in an envi-
the period covered by the Homeric epics was an ronment similar to that found in Renaissance Eu-
unknown. Scholarship has translated much, in- rope wherein plague could easily defeat both oppos-
ferred much, and given us striking impressions of ing armies. The size of the armies of the Persian
these lost societies. From the point of view of dis- king, Darius III, although beyond the scope of the
ease, we have little to offer. Mycenaean civilization ecology of Europe, also bespeaks a very heavily popu-
seems to have fallen to outside invaders. There is no lated realm (Bosworth 1988).
evidence to support disease as a major factor in the Although no social custom so complex and deeply
decline of either mainland Greek or Minoan civiliza- rooted in Greek society as the exposure of infants
tion. The latter may plausibly be linked to a natural (Veyne 1987) can admit an easy explanation, the
disaster. The disease history of these fascinating cul- practice still argues for significant population pres-
tures remains beyond our grasp. sure. In response to most severe epidemics, the birth-
rate rises, probably partly consciously to repopulate,
Classical Antiquity but also because many epidemics remove weaker
elements from the population (Wrigley 1962; Ner-
The Golden Age audau 1984). The deliberate abandonment of infants
The time limits of classical antiquity are as protean in places where their survival would depend on some
as all artificial periodization. For the purposes of other adult's desire for a child being strong enough
this discussion, I shall concentrate on Greece from to rescue them presents a picture of children as an
the sixth century B.C. through the Western Roman apparently significant economic liability. This is
world into the second century A.D. Overall, the dis- rarely the perception when epidemic disease makes
ease picture here suggests societies with significant day-to-day life totally unpredictable and when an
overpopulation expanding into new territories and outbreak can destroy entire family lines. The Greek
experiencing few major epidemics, until a point was myths arefilledwith tales that bear on the abandon-
reached when exposure to infectious epidemic dis- ment of infants, of which the story of Oedipus is but
ease began a process of demographic decline and the most famous. Many others involve the abandon-
cultural retraction. ment of children by the poor.
If one considers classical Greece, the former part of There is reason to believe that children were an
this process can be seen in full swing. The settlement economic liability in fact as well as in perception. A
of Magna Graecia by colonists from the Greek main- worker in Periclean Athens could earn enough to
land speaks clearly of population pressure. The live comfortably, if he did not marry. Once married,
Greeks also colonized the coast of what is now Turkey. he could still afford food and shelter. But each child
The Italian and Sicilian settlements became major added significant strain to that ability (Austin and
sources of grain for mainland Greece, and the need for Vidal-Naquet 1977; Finley 1981). The mindset of
reliable grain sources has been linked plausibly to past societies cannot reliably be reconstructed, but it
the Athenian military debacle in Sicily during the seems reasonable to imagine that persons exposing
Peloponnesian War (Guillaume and Poussou 1970). children had little reason to suppose that the family

was at significant risk of being decimated by dis- tory are impressive. No army of medieval or Renais-
ease. Classical Greece seems to offer the picture of a sance Europe could have approached the size of the
society at the limits of its population potential, but army Rome could have mustered from its Italian
which perceived and experienced minimal risk of population alone. Losses such as those sustained at
epidemic disease altering the tenor of life. Trasimeno and Cannae would likewise have left
The Hellenistic Age shows little difference in this even many early modern states without the man-
regard. Greek became the lingua franca of much of power even to consider continuing a war. The Roman
the Mediterranean world, and Alexandria, an Egyp- Senate judged that a similar number of men were
tian city founded by Alexander, became one of the not worth ransoming to help fend off an incredibly
intellectual (and population) centers of the world. skilled opponent; rather, the image of what a Roman
Greek influence is clearly to be found in sculpture soldier should be was more important.
native to India during this period, a measure of how If the early course of the war argues for abundant
extensive Greek expansion and culture became. population and little risk or heed of epidemic dis-
It is said that as he spent his last months of life ease, the remainder of the conflict shows the same
in Babylon, Alexander the Great considered the features. Hannibal was able to campaign in Italy for
conquest of Rome, a state just then beginning to nearly 2 decades, with only minimal reinforcements.
become prominent in Mediterranean affairs (Bos- He was never defeated on Italian soil. When Rome
worth 1988). Alexander died short of his thirty- finally produced a general capable of opposing the
third birthday without having affected Rome other Carthaginian commander, the strategy employed
than through the latter culture's admiration of him. again indicates the same picture with regard to epi-
Rome then began perhaps the most impressive ex- demic disease.
pansion in all of world history. In order to gain Scipio Africanus the Younger took his army to
some insight into the disease ecology of the Roman Africa to threaten Carthage, reasoning that Hanni-
world, it is instructive to consider the Second Punic bal would be obliged to return and defend his home-
War, which established Rome as the most impor- land. This he did, and Scipio defeated the Carthagin-
tant power in the western Mediterranean. This war, ian master at the battle of Zama in 202 B.C. Once
fought at the end of the third century B.C. (ending in again, in moving the most important Roman army to
202 B.C.), gives glimpses of both a very highly popu- Africa as a strategic ploy, we see no fear of an epi-
lated Italy and a military strategy that excluded any demic destroying Rome's greatest chance to end the
significant impact secondary to epidemic disease. war. Indeed, the relative ease with which armies
Hannibal invaded Italy (with his elephants, as traversed great distances during this war argues for
every Western schoolchild used to know), command- a relatively uniform environment in terms of disease
ing an army of around 40,000 mercenaries. These and one that had little to frighten an adult. Hanni-
men had marched through Spain, across southern bal's army operated on two continents, yet never
France (for convenience, I refer to places by their experienced significant loss to disease. In 1630, the
modern names, insofar as is possible), over the Alps Venetian army met that of the Hapsburgs at Man-
and into northern Italy. According to contemporary tua. At a fraction of the distance from home tra-
sources, Rome could have put an army in thefield20 versed by the armies of the Second Punic War,
times the size of that of Hannibal. Rome could call plague caused so much mortality that neither the
upon a reserve of 700,000 foot and 70,000 cavalry victorious Hapsburgs nor the beaten Venetians
(figures sometimes adjusted to 580,000 and around could even reorganize their forces (Lane 1973).
60,000) (Caven 1980). Rome replied more cautiously The Mediterranean world in the centuries before
but, using smaller armies, lost 15,000 and 5,000 men the first emperor of Rome appears to have been an
in the first two major encounters with Hannibal. At environment abundantly populated, but relatively
Cannae, a larger Roman force left around 25,000 free of at least major epidemic disease. Of the fate of
men on the field and a similar number prisoner children, we know much less. The Romans continued
(Caven 1980). Yet Rome refused to ransom the pris- the practice of exposure or abandonment of infants.
oners, even though Hannibal offered. (It may have The head of a Roman household decided on the fate
also been good strategy to keep Hannibal's soldiers of any infant born into that household. Once again,
busy guarding prisoners.) there are complex cultural phenomena at work, but
The Roman reserve of soldiers, the losses sus- children were definitely an expendable commodity
tained, and the disdain for ransoming prisoners in (Veyne 1987).
one of the darkest hours of Republican Roman his- All of this speaks of the great classical civilization

VII.7. Europe 509
being largely spared devastating epidemics of infec- strategy had in position soldiers in the hundreds of
tious disease. Of the disease background we know thousands, the soldiers over time also became colo-
little. The writings of the Hippocratic corpus, in par- nists and were defending their own land. Hadrian's
ticular, describe many illnesses (it is felt by some Wall across England is an example of this phase of
that brucellosis is described therein), but putting strategy. Its sophistication and effectiveness speak
modern names to them is another matter. No one has for themselves. It was perhaps no longer so safe to
successfully identified the disease that caused the move armies to strange countries. Recall that Mar-
Plague of Athens. Background causes of morbidity cus Aurelius died near Vienna while on a frontier
and mortality are simply beyond reach. At a time campaign. In fact, the "plague" epidemic of the end
when fever was considered a disease and not a symp- of the second century has been seen by Robert Lopez
tom or sign, there is no realistic way to translate (1967) as perhaps the most important of the myriad
most diseases from Ancient Greek or Latin into a of factors in the subsequent decline of the empire. In
modern equivalent. any case, after the second century, the empire was
Some generalizations seem reasonable, nonethe- obliged to develop new and increasingly risky mili-
less. There was probably a surplus of men among the tary strategies to maintain itself.
adult population because more women died in the
25- to 45-year age group. Much of this is probably A.D. 200-1000: The West Reaches Its Nadir
attributable to death associated with childbirth. If
this period had the attributes common to most prein- The Barbarians, c. A.D. 200-600
dustrial societies, about 30 to 40 percent of the total When it was no longer feasible for Rome to defend
population was composed of children. What is singu- the frontiers from the barbarians who lurked upon
larly lacking is a sense of what the probability of a the eastern side of the Rhine-Danube frontier, the
child at birth growing to adulthood was. This is both empire enlisted them to defend what they coveted.
the most important factor in determining life expec- Given land in the empire, the barbarians were par-
tancy at birth (much of the spectacular change in tially Romanized and, in return for their land, were
this parameter in modern times is the result of de- asked to defend the frontier. At this point, the third
creasing childhood mortality). phase of the tripartite strategy comes into play. Be-
cause armies were not available in sufficient size to
The Tide Begins to Turn guarantee the immense frontier of the empire, and
As we have seen, military strategy in the early Ro- because the colonized barbarians themselves might
man Empire again depended upon abundant man- decide to sack a nearby town or two, a "defense in
power and low risk of epidemics. A controversial but depth" approach was developed. Strongly fortified
compelling reassessment of Roman strategy over positions were built, which could be supplied and
time has divided the military strategy of the empire manned to hold out for a long time in the rear of an
into three phases (Luttwak 1976): First was the use enemy encroachment. These fortifications gave the
of client or buffer states to separate Rome from poten- Romans a foothold in areas that could only too easily
tial enemies. These states, such as those along the be overrun. These strongholds could shelter and de-
Asian border of the empire, could be paid or other- fend the frontier population until adequate military
wise induced to mediate or simply physically sepa- strength could be massed to counter the incursion. A
rate Rome from potential enemies. If attacked, such strategy of this type clearly depends upon a much
states also buffered the conflict to give Rome the smaller population. For a stronghold to house more
time necessary to concentrate forces and plan a cam- than a token population, the frontier population had
paign against the opponent. Such a strategy could to be small in the first place. This is further attested
operate only when the empire could confront any by the fact that the forts were victualed for long
enemy on the battlefield with an army that might be campaigns. Generally such fortifications were set
gathered from many regions and transported a long upon natural defensive positions, minimizing the
distance, while the buffer state was itself strong and manpower necessary to defend them.
populous enough to hold off the enemy at least for Even if this picture of the strategy of the empire is
enough time for the Romans to make their military incorrect, there are too many other signs of popula-
reply. tion decline and of the increasing importance of local
The second strategy was that of fixed frontiers. environments to deny convincingly that the demo-
Perhaps here is the first inkling that the population graphic and disease picture had not changed im-
situation was not so favorable. Even though this mensely. The empire itself, which had dominated the

Mediterranean world, divided itself up into two selves. The first wave of barbarian invasions ended
main units, with a "second Rome" emerging in the with western Europe in the hands of barbarian king-
form of Constantinople. By the fourth century it had doms and the East still a state with considerable
become two major territories, each usually with its territory and the ability to defend itself.
own emperor. No longer could armies feasibly be Cities, the cornerstones of classical antiquity, de-
moved around so effortlessly as in the Punic Wars. clined. In a famous example, the inhabitants of one
The Greek and Latin empires drifted apart. The city declined to the point where they lived in the city
Latin Empire was increasingly the prey of barbari- stadium. Effective government collapsed and local
ans. Peoples on the borders of the empire in the strongmen became the only powers that affected
West, whether under population pressure of their most of the population. In this decline of cities in
own or because of pressure from more remote peo- particular, plague may have had a major role. In
ples, invaded and often settled in the lands that had general, plague favors city over rural populations.
comprised the empire. Often, they tried to revive Barbarians came from nonurban civilizations, but
Roman government and customs, as with the typically settled in the Roman cities they conquered.
Ostrogoths, only to fall prey to more aggressive and As epidemic followed epidemic (or, in the case of the
less civilized peoples such as the Lombards. Matters Plague of Justinian, continued well into the seventh
were further complicated by the advent of Christian- century), succeeding waves of barbarians probably
ity, as if the empire was not experiencing enough profited from their predecessors' disease experience.
travails. Certainly there is reason to believe that the Huns
The Christian religion arose (and was seen so to were displaced by another tribe that was experienc-
arise by divine plan by Augustine) in the empire. Its ing overpopulation.
appeal was undeniably greatest to people who found Aside from the Plague of Justinian, we can iden-
the world they lived in unsatisfactory. Again so com- tify few of the epidemics that afflicted Europe. The
plex a subject as the change in the overall concept of practical knowledge that permitted the Romans to
the cosmos cannot be related to something as simple drain swamps to lessen malaria was replaced by
as disease, but there is little question that Christian- superstition and senseless violence. When an epi-
ity denigrated the world, as human beings lived in demic threatened the lives of the children of one of
it, in favor of a life that would come after death. St. the Frankish kings, he decided that he was being
Augustine died while the Vandals besieged the city punished by God for taxing the people. He burned
of which he was bishop. It would be an incredible the tax rolls, Gregory of Tours (1905) tells us, and
oversimplification to attribute the fact that the City his children survived. Again a single incident has
of God could not exist in this world, to the world much to tell us. First, unlike the societies that ex-
Augustine lived in, but the religions of classical an- posed children, we see a king terrified that his chil-
tiquity with few exceptions (and those exceptions dren will die. Partly this is a difference in religion
became the rule as the situation of the empire wors- and culture - barbarian Christian versus classical
ened) saw this life as real life and what came after as Greek - but partly there is a background of epidemic
a shadow thereof. diseases that pose terrifying threats. There is also a
What diseases weakened the empire? Did the Ro- population on the edge of disaster, low in number,
mans come in contact with a distant disease pool, as and barely managing to subsist. There are enemies
has been suggested by William McNeill (1976)? We everywhere in the form of humans, diseases, and the
have essentially no hope of knowing the details. supernatural (the term dates from the fourteenth
Nonetheless, epidemic diseases played an increasing century).
role in the fate of the empire. In the sixth century, Among the myriad factors that have been argued
Justinian made a supreme effort to reunite the two to have contributed to Rome's fall, the unfavorable
halves of the empire. He might have succeeded had epidemic disease picture, as opposed to the threat of
not a monstrous epidemic (in this case identifiable the barbarians, is a factor that cannot be discounted.
as plague) wreaked such mortality that the prospect
was not entertained again for centuries. The Early Middle Ages, c. A.D. 500-1000
The barbarians who occupied Roman lands first However influential the Plague of Justinian was,
were almost invariably displaced by others who obvi- once its century-long devastation of Europe ended,
ously had the manpower and freedom from epidem- plague did not recur in western Europe again until
ics to oust their rivals, who in their turn seem to 1347. Why this is so is totally obscure. Even if cities
have suffered much the fate of the Romans them- and overall population density declined, plague is

VII.7. Europe 511
primarily a zoonosis and, once established, counts an unfavorable disease climate were not enough, the
humans as incidental victims. It seems likely that experience of the Romans was about to be mimicked
the plague never established an enzootic focus in by their inheritors. The comparatively settled bar-
Europe, or if it did, that focus died out quickly. This barian kingdoms had by 800 coalesced (largely by
pattern has been documented in recent years for force of arms, to be sure) into the Empire of Charle-
Hawaii (Ell 1984a; Tomich et al. 1984). In such magne. What the future of this empire left to itself
places, a few susceptible animal strains allowed the might have been, we will never know. A storm of
disease an enzootic foothold, but could not sustain it new invaders fell mercilessly on western Europe,
indefinitely. and a near parody of what had gone before occurred.
Despite the temporary absence of plague, the Evidence from Scandinavia suggests that that re-
Early Middle Ages saw its share of disease. Chroni- gion was overpopulated (Musset 1971). Again, for
cles rarely covered more than a few years before unclear reasons, peoples outside what was left of the
noting some outbreak of epidemic disease. Roman Empire seem to have enjoyed a much more
Although charges of abandoning children, suffocat- favorable disease ecology and significant population
ing them in their sleep, and so forth, remained part growth. In 796, the first Viking raid sacked the
and parcel of medieval lore, children were certainly monastery at Lindisfarne. A little over two centuries
not subjected to a formal decision on survival at later, a Dane ruled England. Until very recently, the
birth. We can read little or nothing into this as English Book of Common Prayer contained the
regards population dynamics, however, because we phrase "God protect us from the fury of the North-
are in the world of Christianity and Germanic cus- men." William the Conqueror was the descendant of
tom rather than classical practice. the Viking conquerors of Normandy.
If the barbarians started their careers in a favor- The north was not the only battleground. For more
able demographic position relative to the Romans, obscure reasons, the Magyars, fierce horsemen from
this situation seems to have lasted a very short time, central Europe, began to press the eastern borders of
as suggested above. Despite the influx of barbarians the old Carolingian domains. Their depredations
into western Europe, cities contracted further, and destabilized the precarious hold of the young Ger-
secondary waves of barbarians overwhelmed earlier man monarchy, which finally crushed them at the
arrivals. The best example of this phenomenon is the Battle of Lechfeld in 955.
primacy of the previously obscure Franks, who were In the south, Islam entered one of its periodic
the only barbarian tribe that by chance had not expansionist phases and threatened Europe. Pirates
converted to what was rapidly perceived as a hereti- and small armies made every locale anywhere near
cal form of Christianity. the Mediterranean coast unsafe. No single engage-
There was certainly little enough to favor popula- ment or event ended this incursion, but it ebbed
tion growth. The Roman governmental apparatus away almost completely by the year 1000.
was among the most elaborate the world has ever The wave of barbarian invasions ended differently
seen and certainly surpassed anything to be seen in from the first. Despite high cost, the existing institu-
Europe at least until the Renaissance (and then on a tions proved capable of driving off or absorbing the
much smaller scale). When the barbarians tried to invaders. More importantly, the second wave of bar-
take over this system, the results were indeed barbarian invasions was the last. By 1066, Europe was
baric. Roads were not repaired. Tax rolls were not free to develop politically without outside threat.
updated, so that someone living in a given place The weak had begun to grow strong again.
might legally be someone long dead and owe the
latter's taxes. The newly risen landowners might The High Middle Ages, 1000-1348
live a life unencumbered with taxes, while identifi-
able units from the past were asked for money they Renewal
could not pay. War, which was the king's truest busi- A marginal agricultural surplus began to be pro-
ness and accounted for much of his revenue, contrib- duced by at least the tenth century, and by the year
uted little to this already bleak picture. Every 1000 the demographic profile of western Europe be-
spring, the Frankish kings reviewed their armies gan to improve dramatically. Whenever the actual
and went off to war. Since war generally increases improvements in agricultural techniques began is
epidemic disease, the annual royal endeavor again unclear, but so long as Europe was under the siege of
would be likely to worsen the disease situation. the second wave of barbarians, such improvements
As if political ineptitude, gratuitous violence, and were unlikely to have a significant effect. Once a

period of relative peace ensued, the small agricul- Leprosy in medieval Europe has produced an im-
tural surplus then available provided the basis for mense literature. (Probably the most complete and
one of the great periods of population growth in the most extensive bibliography to date is Brody
European history (Duby 1981). Other factors were 1974.) In recent years, it has become possible to
also at work, including better government and proba- speak of medieval leprosy as the same disease we
bly the abatement of a now unidentifiable series of know today, at least from around the year 1200 on
epidemics. In any case, for the next 300 years, west- (arguments summarized in Ell 1986). This state-
ern Europe enjoyed very favorable demographic cir- ment is based mainly on the results of excavations of
cumstances. Indeed by the year 1300, parts of rural skeletal remains from the cemeteries of leprosaria
Italy enjoyed population densities that would not be (after the Fourth Lateran Council of 1215, a leprosy
reached again until the nineteenth century (Herlihy patient could not be buried in the same cemetery as
1968). The results of this growth in population were a person not suffering from the disease), coupled
spectacular. with the writings of contemporary physicians (Ell
Huge amounts of land were brought under cultiva- 1986,1989b). In particular, the works of Theodoric of
tion for the first time. Improvements in plows and Cervia in the thirteenth century and Guy de
crop rotations boosted agricultural yields (White Chauliac in the fourteenth show a clear acquain-
1962; Duby 1968). Gothic architecture arose at the tance with a disease that is readily recognizable as
hands of Suger of St. Denis and cast its magic light leprosy (usually the lepromatous, or low-immunity
over Europe (Duby 1981). Partly because less effort type). Many claims made by these authors and dis-
was required for daily life, persons of means turned missed by several generations of more modern com-
hungrily toward knowledge and found it on the inter- mentators can be shown to have a basis in fact, often
face of Christianity and Islam, mainly in Spain and fact that has only recently been rediscovered (Ell
Sicily. The vast storehouse of classical literature, 1984b, 1986, 1989b).
along with the brilliant commentaries and original It has been claimed that leprosy was the most
works of the great minds of Islam, was translated for common disease in Europe before plague. Unfortu-
the Latin world (Southern 1966; Lindberg 1978; nately, there is absolutely no ground for supporting
Stock 1978). This fueled one of the most exciting such a claim. Very tentative and speculative work
intellectual flowerings in Western history. The uni- using skeletal remains, and a regression analysis of
versity, which arose from the cathedral school, dates bone loss in the anterior maxilla as related to dura-
from the High Middle Ages and remains a foundation of lepromatous leprosy, have suggested that
tion of intellectual life. part of southern Denmark experienced an incidence
For the first time, western Europe began to expand of 20 cases per 1,000 population between the years
against its neighbors. In Urban IPs call for the First 1250 and 1550 (Ell 1988). It is unrealistic at the
Crusade, there is an overt reference to an overpopula- current time to extrapolate any aspect of this study
tion of knights, who were creating internal violence. to the rest of Europe, and it is well to remember that
Thus aside from its religious content, the First Cru- Scandinavia was probably the highest-incidence
sade was seen as a partial solution to overpopulation. area in Europe, and clearly the area in which the
This adventure involved not only knights but also disease persisted longest.
thousands of peasants, who attempted to make their If the study cited above is correct, however, the
way to the Holy Land, only to perish en route. The incidence in that region of Denmark was in the high-
Germanic kingdom began to expand to the East, and est range classified today (Sansaarico 1981). Not
in Spain the reconquista to drive out the Moors was only is it risky to extrapolate the proposed incidence
accelerated. in this part of Denmark to the rest of Europe, but it
The recovery of classical and Islamic medical writ- is well known that the incidence of the disease may
ings permits, along with contemporary Western vary significantly within a small geographic region.
works, the identification of at least a few diseases. This pale glimpse of the possible prevalence of one
Smallpox and chickenpox were separated, and small- disease in a small region is both speculative and
pox can occasionally be identified. Like most endemic isolated, for we have no information at all on other
diseases of humans that require direct contact, small- diseases. Tuberculosis, frequently mentioned in dis-
pox was a major killer of children (Hopkins 1983). cussions of medieval disease history, cannot readily
Plague made its reappearance only to mark the end of be identified beyond the point of stating that the
the High Middle Ages, but leprosy was a near obses- disease was present in medieval Europe, but at what
sion in western Europe. level and significance we have no idea.

VH.7. Europe 513
Premonitions of Disaster Keyser 1938; Mols 1954-6; Baratier 1961; Herlihy
Thomas Aquinas, the greatest philosopher of the 1967; Acsadi and Nemeskevi 1970; Russell 1971,
High Middle Ages and one of the greatest synthesiz- 1977). It has been suggested that infant mortality
ing authors of all time, when asked who would carry was lower in medieval Europe than in early indus-
on to completion his reconciliation of classical and trial Europe, because there was less crowding and
Christian sources, is reputed to have replied, on his somewhat superior living conditions (Russell 1977).
deathbed, that the work could not be done. Aquinas This is a reasonable argument, but no more than
died on the eve of one of the greatest demographic that; there is not a shred of evidence to support this.
disasters in the history of Europe, the Plague of Plague left Europe, indeed most of the world, in a
1348, but his remark, apocryphal or not, shows a catastrophic state. In Venice 75 percent of the nobil-
changing mood in western Europe. ity was dead (Archivio 1348; Ell 1980). Cities rou-
High medieval thought and activity abound with tinely lost over 50 percent of their populations
optimism. Intoxicated with new knowledge and in- (Carpentier 1962a, 1962b). Strange heresies arose,
creasing material abundance, the prevailing expec- such as the Flagellants, who traveled about, beating
tations of the future were very high. Around 1300, themselves unconscious with whips to repent the
this mood began to change, and it changed in many sins that had brought the epidemic. Medicine, as
areas. Major defaults by important Italian banks, usual, was powerless to do anything to stop the dis-
famines reappearing in a population freed from ease. More damning, the Church failed to offer much
them for two centuries, overcrowded and over- real comfort or practical relief. Infant mortality and
worked farmland - all these reverses changed the the loss of elderly adults are most easily absorbed by
mood of the fourteenth century to one of anxiety any society; however, plague tends to affect young
and foreboding. Although Dante would die in 1330, adults and children over 5 years old (Ell 1984a,
18 years before plague struck the city in exile from 1985). Yet careful local studies have not always
which he composed the greatest work of the Middle borne out such a pattern in European plague epidem-
Ages, he wrote, "Io non averei creduto che morte ics of this period. The exact epidemiology remains
tanta n'avesse disfatta" ("I would not have believed unclear, or perhaps varied from place to place. When
death had undone so many" - author's translation plague left infants and the elderly relatively un-
of a 1981 edition of Dante). This line might stand as touched, but decimated the rest, it could destroy the
the motto for what was to come. Whatever stance productive and reproductive present and future of
historians may take regarding an economic depres- whole societies. This phenomenon has been well
sion in the fourteenth century, it is clear that Eu- documented for Orvieto (Carpentier 1962b). Plague
rope was in demographic decline before the plague did not visit Europe once and then disappear, as did
struck. the Plague of Justinian. Rather, Europe became a
site of recurrent epidemics, none as ghastly as the
The Later Middle Ages first, but even in 1630-1 Venice still lost a third of
In 1347, the plague began its journey through Eu- its population to the disease (Ell 1989a). It is diffi-
rope. When the pandemic ended in 1350, a third of cult to give a sense of what this level of loss is like.
the population of Europe was dead. The population The worst-hit countries in World War II lost 10 per-
of Europe on the eve of the epidemic has been esti- cent of their population. Venice lost 7.5 times that
mated at 75 million. Although life expectancy at percentage in about one-twentieth the time.
birth was only around 30 years, the very high infant No argument can be made for a hypothesis that the
mortality rate artificially lowered this relative to epidemic was triggered by population density. As
the life expectancy of a person who reached adult- noted, population was already in decline, and plague
hood. Women tended to fare worse, probably as a returned many times after the population density
result of childbirth, although some authors also cite had plummeted. It is also clear that the pattern these
tuberculosis and malaria (Russell 1977). Before the epidemics took does not fit the classical rat-flea
year 1000, no city in medieval Europe had a popula- model of transmission. In fact, the European experi-
tion exceeding 20,000. In 1340, the largest European ence of plague does not fit the general model derived
cities were Venice, Paris, Florence, and Genoa, each from India and China by the British Plague Commis-
with populations around 100,000. Closely behind sion around the turn of the century. According to that
were cities such as London, Barcelona, Bologna, model, animal foci or reservoirs of plague are estab-
Brescia, Ghent, and Cordoba, each of which had lished among wild rodents, which can harbor the
populations over 50,000 (Beloch 1937, 1940, 1961; infection indefinitely, either only among themselves

or, as is now more often recognized, among multiple The conventional pillars of Christian faith and
species. The natural history of such foci is that they doctrine began to change to new, more startling
enlarge. For example, the focus in the United States, views. People turned away from the belief that rea-
which was established in the first decade of the twen- son could lead them to God. Radical nominalism
tieth century, now extends over almost the entire developed, and left an indelible mark upon subse-
western half of the country (Ell 1980). It is consider- quent philosophy. The Doctrine of Double Truth also
ably more reasonable to postulate that there was emerged. According to this view, individuals could
never an enzootic focus of plague in Europe but, by reason arrive at certain conclusions, but only
rather, that the disease was repeatedly reintroduced, revelation was the source of ultimate truth. Aquinas
most likely through trade or travelers. The observed had tried to keep the comprehension of truth in this
epidemiology is much more compatible with in- world and available to reason. Postplague Europe
terhuman transmission via the humanfleathan with made truth something separate from and unattain-
either rat—flea or pneumonic spread (Ell 1984). able from this world.
Whatever historiographic stance one takes with For totally unclear reasons, leprosy had begun to
regard to the points discussed above, the recurrent decline in much of western Europe by 1300 and
plague epidemics undeniably mark a major change definitely before plague struck. There is no known
in the ecology of disease in Europe. For the first explanation. It is claimed that the climate of Europe
time, in an institutionalized way, European govern- became colder. It is indeed true that climate can
ments began to try to alter disease ecology. In 1486 affect the epidemiology of disease as well as much
Venice made permanent the Provveditori alia else in human society. A change of 1°C average tem-
Sanitd, a public health board that had first been perature over a year can change the growing season
established in 1348 and was re-formed in response to by 2 weeks in England, for example. It is known that
each epidemic. The invention of the quarantine is figs were grown in England in the time of Charle-
credited to Venice, which first tested it in the Vene- magne. The climatic cooling of the fourteenth and
tian colony of Ragusa in 1379. Measures such as fifteenth centuries has been called the "Little Ice
quarantine are not always useful against plague, Age" (Russell 1977). Such a shift in climate would
with its complicated transmission pattern, but were certainly affect crops and food supplies, as well as
valuable against other infectious diseases. More im- some diseases (e.g., influenza is largely a disease of
portantly, such measures introduced the concept cold weather, whereas enteric fevers tend to occur in
that human and particularly governmental actions summer). Although climatic cooling has been cred-
could modify the expression of disease. When plague ited for the decline of leprosy, the fact that the dis-
appeared, city-states, which traditionally were at ease thrived in Scandinavia renders this argument
odds with one another, exhibited a high degree of at best incomplete and probably irrelevant. What-
cooperation, as elegantly documented by Carlo Ci- ever the cause, half the previously occupied beds in
polla (1981). Much of the future of European disease leprosaria in England were empty in 1300 (Richards
ecology would follow from this none too successful 1977). The argument that plague killed an inordi-
attempt to control plague, and humans would begin nate number of leprosy victims is not supportable in
increasingly to modify disease. Yet much of what a direct way because leprosy is considered to confer
plague brought was considerably less positive. immunity to plague. Indirectly, through the deaths
Artistic and literary styles in the immediate wake of those who looked after leprosaria patients, plague
of the epidemic of 1348 were profoundly world-weary may have hastened the decline of leprosy in much of
and pessimistic. The concept of the macabre arose in Europe, but it neither initiated nor finished the
this period. The so-called transit tomb style, in change (Ell 1987).
which the deceased is sculpted both in his well- Although it itself is highly speculative, let us con-
dressed idealized appearance and as a rotting corpse, sider another possible cause of leprosy's decline in
being devoured by vermin, is one of the most strik- much of Europe. The elaborate rituals and merciless
ing elements of this deep cultural pessimism. This rules by which leprosy patients were excluded from
was a society in which the young and healthy adult contact with normal society have been described ex-
could die in a few hours without warning or reason. tensively (Brody 1974; Richards 1977). If we con-
It is likely that such an atmosphere could produce sider the fact that Japan completely rid itself of
behavior of so careless or dangerous a nature that leprosy early in this century by strictly separating
mortality from other diseases increased, but we have contagious cases from the population (Saikawa
no real evidence to back up such an argument. 1981), it seems possible that the less scientific, but

VH.7. Europe 515
still powerful apparatus of medieval Europe may for example, the Polynesian peoples were exposed to
have produced the same end. This hypothesis, how- measles. Smallpox was probably the most disastrous
ever, like so many others, cannot explain the persis- disease for the post-Columbian Indians.
tence of the disease in Scandinavia. One difference, Within a few years of Columbus's discoveries, Eu-
however, lies in the possibility that the organism is rope perceived itself to be plagued by two new dis-
found in parts of Scandinavia outside a human host eases, namely syphilis and typhus. The debate over
(in fact, in a type of moss), which would provide a syphilis has raged for many years, with some claim-
reservoir of the organism able to survive irrespec- ing that it was an import from the Americas, and
tive of what happened to patients with the disease others claiming that it was either first recognized as
(Huang 1980; Job 1981). a disease entity at the end of the fifteenth century or
was a new disease — the result of a mutation. When
It is often argued (e.g., by Russell 1977) that tuber-
culosis became the most important infectious dis- one considers the fact that skeletal evidence may
ease during this period. Tuberculosis is simply too show the existence of syphilis in pre-Columbian
protean to be identifiable in the Middle Ages and America, whereas no skeleton from Europe before
Renaissance, except in rare instances. Its perceived 1495 has ever shown osseous changes, the first hy-
effects on human demography are reasonable, but pothesis seems more reasonable.
again real evidence is lacking. Typhus was also seen as new. Here the question is
more difficult. First, it is not clear at this time
The Renaissance whether recognition of typhus preceded the discov-
No two dates for the Renaissance ever seem to coin- ery of the New World. In any case, Europe's ties with
cide. If we judge from art and literature, Giotto and new trading partners very likely caused typhus to
Dante would place the starting date in the four- appear in western Europe. Furthermore, typhus was
teenth century. If we follow the reasoning of Hans not conclusively differentiated from typhoid fever
Baron that the Renaissance is a reflection of a civic until the nineteenth century, and thus the question
image, the date shifts to 1405. Probably everyone of recognizing a new disease is extremely difficult.
would agree that Michelangelo and Leonardo da Nonetheless, it was perceived as new, and that in
Vinci belong in the Renaissance, but if we turn to itself is of some importance.
science the greatest change comes with Galileo, who In the case of syphilis and typhus, the perception
lived after the Reformation! Very artificially, let us of new diseases helped to end the rather static medi-
put this period at 1400 to 1550. cal models of the time. They stimulated considerable
Two changes in European disease ecology stand written discussion and, of course, the poem from
out strongly. Both result from the new trade and which the name syphilis comes. The perception of
exploration involving the Far East and the Ameri- these diseases as "new" aspects of the human disease
cas. On the one hand, Europe became a major ex- experience is perhaps most significant, but it is not
porter of its endemic diseases to the Americas and clear at what point this perception began. Plague
appears to have acquired two diseases in return. was known, at least in writing, from centuries past
It has become increasingly apparent in recent when it struck again in 1347, but syphilis and ty-
years that the role of the introduction of European phus were perceived as new. Probably the most im-
diseases such as smallpox into the Americas was a portant aspect of the diseases in Europe is the fact
factor in the ability of the tiny European armies to that the quality of Renaissance thought permitted
conquer empires inhabited by millions of persons. observation to allow what mindset would have pro-
Since it appears that the native American popula- hibited in the past.
tion had no previous exposure to such pathogens, the Syphilis seems to have had a much more fulmi-
results were disastrous, and estimates have gone so nant course than would be expected now. This again
far as to suggest that in the century after the estab- suggests a new disease in a previously unexposed
lishment of contact with the Americas, up to 95 society. As time passed, the pressure of the dis-
percent of the population of the major centers of ease probably altered European population genetics
American civilizations had perished. In part, the toward genetic makeups capable, in most cases, of
shift from ruler to ruled (or, in effect, enslaved) staving off the organism or coexisting with it.
probably worsened the situation, as did the forced From the point of view of disease ecology, the Re-
adoption of European religion, language, and cus- naissance marks the era of new diseases in two
toms. Europe's extensive prior experience with infec- senses. The following years would see more and
tious diseases was to prove catastrophic later when, more precise and, to modern physicians, identifiable

descriptions of diseases that had no doubt been ex- primarily searches for trade routes and later for
tant for many years. Medicine did not, except in indigenous wealth to be returned to Europe, more
exceedingly rare instances, prove capable of com- and more colonists left Europe for the New World. At
batting them, but at least it differentiated them. first, the settlers were primarily Spanish and Portu-
The second sense of new diseases lies in the Euro- guese, but the British and French soon followed.
pean export of diseases to previously unexposed peo- Behind this one assumes a favorable turn in the
ples. F. Braudel (1979) has argued convincingly that, disease ecology of Europe, allowing populations to
of the great civilizations of around the year 1500, increase. The gradual cessation of plague epidemics
Europe excelled only in its shipping. That shipping cannot have been the only factor. Leprosy main-
made it richer and more powerful, and permitted it tained a foothold primarily in Scandinavia. What
to devastate the Americas and, later, other lands had been a European disease became a largely re-
with its own combination of infectious diseases. Al- gional one. Plague pandemics gave way to much
though the appearance of cycles of epidemic dis- more local epidemics, with those more widely spaced
eases, often from elsewhere, mark the history of in time.
ancient Greece, Rome, and the medieval world, the Even medicine, in a practical way, began to offer
Europe of the Renaissance and later tended to be a some help. The discovery of quinine for use against
potent exporter of disease. malaria made life less risky in the tropics and even
in those parts of Europe where malaria remained.
Early Modern Europe, 1550-1800 The discovery of the use of citrus fruit to prevent
What began in the Renaissance continued and accel- scurvy allowed sea voyages to be longer without the
erated in Early Modern Europe, except that new risk of that peculiar ailment, only understood in
diseases were not a significant factor within Europe. near completeness in the twentieth century. Vario-
The population recovered surprisingly quickly from lation and later vaccination began to bring the long
plague epidemics. Some of the Italian city-states reign of smallpox to an end. Smallpox was a perfect
made grants of citizenship easier to obtain, so as to disease to attack by vaccination. The causative virus
repopulate. Plague gradually became less common. is not known to mutate, and is antigenically similar
Venice enjoyed more than half a century without an to the much less virulent virus that produces cow-
epidemic before the outbreak of 1630. By the eigh- pox. This explanation was beyond the state of medi-
teenth century, plague was rare indeed. cal knowledge of the time, but many other positive
Cities remained unhealthy places, however. It is contributions in medicine also have arisen pragmati-
unclear if major cities could maintain their own cally, whereas theory has often led to adverse treat-
population or continued to demand an influx from ments. In actual fact, medicine had only a very small
the countryside. Smallpox was probably the single impact on disease overall. The hospital, a medieval
worst childhood killer, although a variety of uniden- invention, remained for the most part a charitable
tifiable diseases took their toll. Among adults, it is rather than medical institution. In eighteenth-
assumed that tuberculosis was on the rise, although century France, 63 percent of all hospital beds were
again evidence to support this contention is precari- used to look after the needy, not to treat disease
ous. Many diseases can imitate tuberculosis, and (Joerger 1980). In this period, those engaged in child-
tuberculosis can imitate many other diseases. Be- birthing care in Provence, France, underwent a
cause the diagnosis became very reliable in the nine- change from older women serving simply as mid-
teenth century and because tuberculosis was then a wives, to younger, stronger women who could exert
severe problem, it is assumed that the same was the the strength sometimes necessary in dealing with
case in Early Modern Europe. It may well have been. difficult labor. An eighteenth-century tract on obstet-
The countryside remained healthier than the city. rics comments on 600 difficult cases, in which 78
Country homes for the wealthy city noble or mer- mothers and 230 infants died (Laget 1980), hardly a
chant probably owe much to this fact. It is interest- testimony to medical progress in this vital area.
ing to speculate how many of the magnificent villas Even the combination of all these effects seems
along the Brenta near Venice would be there if inadequate to explain the growth of Europe's popula-
plague had not so often threatened their owners' tions. Still, demographic balance is often precarious.
lives in the city. The population remained predomi- Slight shifts in even a small number of diseases can
nantly rural, and there are clear signs of population mean the difference between population growth and
pressure for the first time since before 1300. decline. Clearly the population of Europe was in-
Although the first voyages to the Americas were creasing and had been since some point, not clearly

VII.7. Europe 517
identified, when plague no longer killed off as many was replaced in Europe by a demography of indolent
as had been born and survived childhood. growth. This change seems to have been a directly
It was during this period that Europe as an ex- voluntary effect. Contraception - however primitive
porter of diseases proved spectacularly lethal. Mea- the means - became the rule rather than the excep-
sles, introduced into some of the South Pacific is- tion. Although the explosive growth begun in Europe
lands, resulted in essentially 100 percent mortality. during the Industrial Revolution continues, it does so
In one sense, there is nothing more fittingly sym- primarily in the Third World, where agricultural
bolic of the growing power and influence of Europe progress and decreases in infant mortality allow im-
than the ability accidentally to kill off an entire poverished populations to expand continuously.
population. Europe avoided this fate, and proceeded with a
Just as the greatest generals of the ancient world relatively stable population. Decreases in infant
gave insights into disease demography, so also does mortality caused average life expectancy to double,
the career of Napoleon Bonaparte, with which we and more sanitary living conditions coupled with
may end this brief discussion of the eve of the Indus- abundant food added still more years to the average
trial Revolution. At the time of Napoleon, we again life-span. Medicine played a major role in decreas-
see armies in thefieldnumbering in the hundreds of ing infant mortality, once the germ theory of dis-
thousands of men. Rome also produced armies of ease had been accepted and infants were delivered
such magnitude (even if they were not concentrated under conditions conducive to their survival. But at
in one place), but a very long interval elapsed before the other end of the life spectrum, medicine has not
this phenomenon repeated itself. contributed much. The diseases of modern societies
are not primarily infectious. Atherosclerosis, inter-
Industrial and Post-Industrial Civilization estingly enough the commonest radiographic find-
The most characteristic change in disease ecology ing when the royal mummies of ancient Egypt were
relating to the Industrial Revolution and post- X-rayed, has come to the fore as the most signifi-
Industrial society is an almost complete exchange of cant cause of adult mortality. Myocardial infarc-
the diseases of importance. Although medicine has tions, fatal arrhythmias, and cerebrovascular acci-
claimed credit for the eradication of infectious dis- dents, respectively, are some of the major causes of
eases, it has been convincingly demonstrated that death in modern society. This is a strikingly post-
every major infectious disease of earlier times was Industrial phenomenon. As late as the end of the
already sharply in decline when medical cure be- nineteenth century, upper-class Englishmen ate a
came available, with only very few exceptions. Tu- diet as rich in fats and cholesterol as the world has
berculosis is an excellent example. The tuberculosis known. Obesity was the rule, not the exception. Yet
epidemic in England and Wales can be seen to have myocardial infarction was almost unknown. For all
become very significant in the eighteenth century. It the pretensions of modern medicine, the ecology of
peaked around 1810 and then began to decline (Lov- disease is still wrapped in mystery, particularly
ell 1957). Effective antibiotic therapy was well over when it comes to the appearance and disappearance
a century away. T. McKeown (1976) has shown that of individual diseases.
the introduction of antibiotic therapy lies in the as- Cancer, certainly known for as long as there have
ymptotic portion of the curve of incidence. been medical writings, but a rare cause of death in
The impact of the Industrial Revolution is difficult antiquity, has also become one of the commonest
to overestimate. It produced profound changes in a causes of death in modern society. Genetics plays
nation's gross national product, patterns of raw mate- some role. Some carcinogens have been convincingly
rial usage and consumption, and real incomes that in identified, such as tobacco and asbestos. Yet the inci-
turn led to improved living standards. All of these dence of some cancers continues to rise, whereas the
helped to permit explosive population growth (Wrig- incidence of a commoner cancer of early industrial
ley 1962). For example, the population of England times (and still common today in parts of the Ori-
and Wales was under 10 million in 1800, but in 1990 ent), namely adenocarcinoma of the stomach, is in
is approaching 50 million; world population took un- decline. Diet is assumed to play a major role, but it is
til 1830 to reach one billion and had quadrupled by sobering to recall that diet has historically been
1975 (McKeown 1988). Yet another unique feature of implicated whenever it was unclear why a disease
the Industrial Revolution is that explosive popula- behaved as it did.
tion growth, which the exponential increase in If we examine the length of the disease history of
wealth probably could have supported for a long time, Europe, it is striking that patterns of disease experi-

ence, once identifiable, did not change significantly Carpentier, E. 1962a. Autour de la peste noire: Famines et
until the Industrial Revolution. In these terms, it is epid6mies dans l'histoire du XlVe siecle. Annales:
probably appropriate to divide history into post- Economies, Society, Civilizations 17: 1062-92.
Neolithic and post-Industrial only. In any case it is 1962b. Une Ville devant la peste: Orvieto et la peste noire
clear that the Industrial Revolution changed the de 1348. Paris.
disease ecology of Europe almost totally. Medicine Caven, B. 1980. The Punic Wars. New York.
Cipolla, C. M. 1981. Fighting the plague in seventeenth
has perfected the cure of the diseases that were in
century Italy. Madison, Wis.
the process of disappearing anyway, but has grap- Duby, G. 1968. Rural economy and country life in the
pled with only very limited success with the diseases medieval West, trans. C. Postan. Columbia, S.C.
of the new age (McKeown 1988). It remains for fu- 1981. The age of the cathedrals, trans. E. Levieux and
ture historians to determine whether or not humans B. Thompson. Chicago and London.
will be able to alter the disease ecology they have Eden, W. van, et al. 1980. HLA segregation of tuberculoid
produced by industrialization. leprosy: Confirmation of the DR2 marker. Journal of
Stephen R. Ell Infectious Diseases 141: 693-701.
Ell, S. R. 1980. Interhuman transmission of medieval
Bibliography plague. Bulletin of the History ofMedicine 54:497-510.
Acsadi, Gy., and J. Nemeskevi. 1970. History of human life 1984a. Immunity as a factor in the epidemiology of
span and mortality. Budapest. medieval plague. Reviews of Infectious Diseases 6:
Alausa, O. K. 1983. Brucellosis in Nigeria: Epidemiology 866-79.
and practical problems of control. In Human ecology. 1984b. Blood and sexuality in medieval leprosy. Janus
and infectious diseases, ed. N. A. Croll and J. H. Cross, 71:153-64.
312-31. New York and London. 1985. Iron in two seventeenth-century plague epidem-
Archivio de Stato di Venezia. 1348. Provveditori alia ics. Journal of Interdisciplinary History 15: 445-57.
Sanita: Rubbrica delle Leggi, Vol. 2, Folio 194. 1986. Leprosy and social class in the Middle Ages. Inter-
Austin, M. M., and P. Vidal-Naquet. 1977. Economic and national Journal of Leprosy 54: 300—5.
social history of ancient Greece, trans. M. M. Austin. 1987. Plague and leprosy in the middle ages: A paradoxi-
Berkeley. cal cross-immunity? International Journal of Leprosy
Bailey, N. T. J. 1954. A statistical method of estimating the 55: 345-50.
periods of incubation and infection of an infectious 1988. Reconstructing the epidemiology of medieval lep-
disease. Nature 154: 139-40. rosy: Preliminary efforts with regard to Scandinavia.
1957. The mathematical theory of epidemics. London. Perspectives in Biology and Medicine 31: 496-506.
Baratier, E. 1961. La Demographie provencale du Xllle au 1989a. Three days in October of 1630: Detailed examina-
XTVe siecle. Paris. tion of mortality during an early modern plague in
Bartlett, M. S. 1957. Measles periodicity and community Venice. Reviews of Infectious Diseases 11: 128-39.
size. Journal of the Royal Statistical Society, Ser. A, 1989b. Three times, three places, three authors, and one
120: 48-70. perspective on leprosy in Medieval and Early Modern
1960. The critical community size for measles in the Europe. International Journal of Leprosy 57: 823-33.
United States. Journal of the Royal Statistical Society, Finley, M. I. 1981. Economy and society in ancient Greece.
Ser. A, 123: 37-44. London.
Becker, N. G. 1979. The uses of the epidemic models. Flinn, M. W. 1985. The European demographic system,
Biometrics 35: 295-305. 1500-1800. Baltimore.
Beloch, J. 1937, 1940, 1961. Bevolkerungsgeschichte Gregory of Tours. 1905. Historia francorum. Monumenta
Italiens. Berlin. Germaniae historica. Scriptores rerum merovingica-
Biraben, J.-N. 1975. Les Hommes et la peste en France et rum, Book 5, Chapter 34.
dans les pays europiens et miditerraneens, Vol. 1. Guillaume, P., and J.-P. Poussou. 1970. Dimographie
Paris. historique. Paris.
Birdsell, J. B. 1957. Some population problems involving Herlihy, D. 1967. Medieval and Renaissance pistoia. New
Pleistocene man. Cold Spring Harbor Symposium of Haven, Conn.
Quantitative Biology 20: 47-69. 1968. Santa Maria impruneta: A rural commune in the
Bosworth, A. B. 1988. Conquest and empire: The reign of late middle ages. In Florentine studies, ed. N. Rubin-
Alexander the Great. Cambridge and New York. stein, 242-71. Evanston, 111.
Braudel, F. 1979. The structures of everyday life: Civiliza- Hopkins, D. R. 1983. Peasants and princes: Smallpox in
tion and capitalism, 15th-18th century, Vol. 1, 402-7. history. Chicago and London.
New York. Huang, C. L.-H. 1980. The transmission of leprosy in man.
Brody, S. N. 1974. The disease of the soul: Leprosy in International Journal of Leprosy 48: 309-18.
medieval literature. Ithaca and London. Job, C. K. 1981. Leprosy - the source of infection and its

VII.8. North America 519
mode of transmission. Leprosy Review 52 (Suppl. 1): transmitted human infections. In Human ecology and
69-76. infectious diseases, ed. N. A. Croll and J. H. Cross,
Joerger, M. 1980. The structure of the hospital system in 332-52. New York and London.
France in the ancien regime, trans. E. Forster. In Southern, R. 1966. The making of the Middle Ages. New
Medicine and society in France, ed. R. Forster and Haven, Conn.
0 . Ranum, 104-36. Baltimore. Stock, B. 1978. Science, technology, and economic progress
Keyser, E. 1938. Bevolkerungsgeschichte Deutschlands. in the Early Middle Ages. In Science in the Middle
Leipzig. Ages, ed. D. Lindberg, 1-51. Chicago and London.
Keyu, X., et al. 1985. HLA-linked control of predisposition Thucydides. 1958. The Peloponnesian war, trans. R. Craw-
to lepromatous leprosy. International Journal of Lep- ley. Garden City, N.Y.
rosy 53: 56-63. Tomich, P. Q., et al. 1984. Evidence for the extinction of
Laget, M. 1980. Childbirth in seventeenth and eighteenth plague in Hawaii. American Journal of Epidemiology
century France: Obstetrical practices and collective 119: 261-73.
attitudes. In Medicine and society in France, ed. Veyne, P. ed. 1987. A history of private life: From Rome
R. Forster and O. Ranum, 137-76. Baltimore. to Byzantium, trans. A. Goldhammer. Cambridge,
Lane, F. 1973. Venice: A maritime republic. Baltimore. Mass., and London.
Lindberg, D. 1978. The transmission of Greek and Arabic White, L. 1962. Medieval technology and social change.
learning to the West. In Science in the Middle Ages, Oxford.
ed. D. Lindberg, 52-90. Chicago. Wilson, G. S. 1957. The selective action on bacteria of
Lopez, R. 1967. The birth of Europe. New York and Phila- various factors inside and outside the body, with par-
delphia. ticular reference to their effect on virulence. In Micro-
Lovell, R. 1957. The biological influences of man and ani- bial ecology, 338-59. Cambridge.
mals on microbial ecology. In Microbial ecology, 315- Wrigley, E. A. 1962. Population and history. New York and
27. Cambridge. Toronto.
Luttwak, E. N. 1976. The grand strategy of the Roman
Empire. Baltimore.
McKeown, T. 1976. The modern rise of population. New
York.
1988. The origins of human disease. Oxford. VII.8
McNeill, W. H. 1976. Plagues and peoples. Garden City,
N.Y.
Disease Ecologies of North
Mols, R. J. 1954-6. Introduction d la dimographie America
historique des villes de I'Europe du XTVe au XVIIIe
siecle. Gembloux.
Musset, L. 1971. Les Invasions: Le second assaut contre America north of the Rio Grande, that life zone some-
I'Europe chrttienne VIe-XIe siecles. Paris.
times referred to as the Nearctic region, presents the
Neraudau, J.-P. 1984. Eire enfant a Rome. Paris.
scholar of history and geography of disease with nu-
Richards, P. 1977. The medieval leper and his northern
heirs. Totowa, N.J.
merous challenges. These include such questions as
Rotberg, R. I., and T. K. Rabb. 1983. Hunger and history: the following: What potential disease-causing agents
The impact of changing food production and consump- existed in the hemisphere before the comparatively
tion patterns on society. Cambridge. recent arrival of human beings? How effective was
Russell, J. C. 1971. Medieval regions and their cities. New- the "cold screen" (Stewart 1960) in ensuring the
ton Abbot. health of the migrants crossing the link from Eurasia
1977. Population in Europe. 500-1500. In The Fontana to the New World? Given the isolation of this popula-
economic history of Europe, Vol. 1: The Middle Ages, tion, how varied was it in a genetic sense, and how
ed. Carlo Cipolla, 25-70. London and Glasgow. well adapted did it become to North American ecolo-
Saikawa, K. 1981. The effect of rapid sosio[sic]-economic gies? Were native North Americans indeed "far more
development of the frequency of leprosy in a popula- healthy than any others of whom we know" (Ashburn
tion. Leprosy Review 52 (Suppl. 1): 167-75.
1980)? Just what was the impact of the "Columbian
Sansaarico, H. 1981. Leprosy in the world today. Leprosy
Review 51 (Suppl. 1): 1-15.
exchange" (Crosby 1972)? Did these invaders receive
Siegried, A. 1960. Itineraires des contagions: Epidemies et the country "from the hands of nature pure and
ideologies. Paris. healthy" (Rush 1786)? What relative contribution to
Smith, D. G. 1979. The genetic hypothesis of susceptibility ill health and disease did the European group provide
to lepromatous leprosy. Human Genetics 50: 163-77. compared to that of the enslaved African popula-
Smith, D. M. 1983. Epidemiology patterns in directly tions? What were the dimensions and timing of the

"epidemiologic transition" in North America (Omran ships ecologists have led us to expect. Birds and mam-
1977)? How real have urban and rural differences in mals must have had their parasites, and, it is as-
health experience been through time? How serious is sumed, sylvan cycles of infection and death took
the threat today of "life-style" diseases? place. To identify these in the lack of any, as yet, hu-
Clearly all of these and other equally intriguing man presence is difficult, but insofar as today's known
questions arise. This brief discussion can only hope zoonoses cycles in North America have been elu-
to touch on some of them and to review a portion of cidated, some endemic conditions can be postulated.
the work by persons from biochemists to medical These would include the bacteria known to cause
historians, from archaeologists to medical geogra- tularemia, botulism, relapsing fever, anthrax, and
phers, who have applied their learning to the fasci- pasteurellosis (Cockburn 1971; Meade, Florin, and
nating question of human well-being through the Gesler 1988) as well as the highly localized Babesia
ages in North America. microtia of ticks infesting rodents on Nantucket
Island. Additionally, Rickettsia rickettsii of the tick
The Ecological Region Ixodes infested small mammals, and possibly Rick-
North America, which is separated from the Old ettsia typhii was carried by the fleas on native ro-
World by major oceans (apart from the Bering Strait, dent species already present (Newman 1976). More
now a mere 85 kilometers wide), encompasses an certainly, the viral encephalitis group is nidal in
area of just over 19 million square kilometers. It the region (MacLean 1975), as are a number of hel-
stretches across 136° of longitude, from 52° west at minthic conditions such as the tapeworm Diphyl-
Cape Spear in Newfoundland to 172° east longitude lobothrium pacificum, whose definitive host is the
at Attu Island in the western extremity of the Aleu- Pacific seal (Patrucco, Tello, and Bonavia 1983), the
tians, but its latitudinal extent of 64°, from 83° north pinworm Enterobius vermicularis, and the thorny-
at Ellesmere Island to the Florida Keys, is all north headed worm Acanthocephala; all are parasites of
of the Tropic of Cancer. Nevertheless, tropical influ- wild animals (Fry, Moore, and Englert 1969; Fry
ence is not unknown in the region, as the continent and Moore 1970). The parasitic flatworm of migra-
is open to climatic incursions along the Gulf coast tory waterfowl, whose intermediate host is the
penetrating across the interior Mississippian low- snail, is endemic among the bird populations of the
lands northward to the Great Lakes. In essence, this North American flyways, and has probably been so
means that extratropical cyclones develop along the for eons before unfortunate humans encountered
jet stream and migrate from west to east and, in so the cercariae and experienced "swimmers' itch" (Du-
doing, draw up hot humid air in summer, and lead to Four 1986).
incursions of freezing air masses as far south as Other organisms associated with water and the
Florida in winter. faunal population include Leptospira (although the
Throughout the eastern and central sections then, agent of Weil's disease was not present until the intro-
seasonal contrasts are marked, especially when com- duction of its natural host, the brown rat - Rattus
pared to those of northwestern Europe. The moun- norvegicus) and a number of Salmonella organisms
tains of the West modify these conditions, giving rise carried by seagulls and other sea-living animals in-
to wet Pacific coastlands in the north and semiarid cluding oysters and fish (Ffrench 1976). Further-
rainshadow valleys on the eastern lee with sub- more, the free-living amebaNaegleriaflowleri, inhab-
humid areas extending over more and more exten- iting soil, water, and decaying vegetation (but only
sive areas toward the southwest. The natural vegeta- entering medical literature as a disease agent in
tion mirrors the climatic conditions. It ranges from 1965), along with other similar organisms, has long
luxuriant forests of the Northwest through scrub been in the environmental complex of Nearctica
and grasses of the semiarid plains and the evergreen (Craun 1986).
boreal forests of the northlands, to the deciduous Still another group of organisms associated (in at
forests of the East fringed on the southeast coast by least 27 cases) with a free-living existence in soil
marshlands, with each presenting its own niches for and water is the mycobacteria (Runyon 1971). As is
life forms from buffalo to mosquito. well known, some species of the genus Mycobac-
terium are associated with human tuberculosis and
Indigenous Disease Agents of North leprosy. Others, however, called "environmental,"
America vary in frequency, depending upon locale, soil condi-
Within this varied habitat a myriad of organisms tions, and climate; and modern American studies
lived and died with the usual range of interrelation- have shown that human exposure to these is quite

common (Steinbock 1987). Furthermore, Myco- over by the Beringia transmigrants, and claims
bacterium bovis and occasionally Mycobacterium that it would be more likely to arise de novo in the
avium produce disease in humans that is clinically Western Hemisphere.
identical to that caused by Mycobacterium tuberculo- But what of the "cold screen" or, perhaps more
sis. Native Nearctic guinea pigs, mice, bison, and correctly, the cold filter? T. D. Stewart (1960), argu-
birds may well have harbored these varieties. Thus ing that New World populations were relatively free
organisms capable of causing human tubercular le- of Old World pathogens, stated that "the cold of the
sions were almost certainly in the New World before Far North has been characterized as a screen serving
the advent of humans (Anderson et al. 1975). in past times to prevent the flow of many pathologi-
cal germs along with the movements of their human
Prehistoric Incidence of Disease hosts," a position that has become widely accepted in
According to L. E. St. Hoyme (1969): "[I]t is easy the literature (Jarcho 1964; Hare 1967; Dunn 1968;
enough to explain why few diseases entered the New St. Hoyme 1969; Crosby 1972, 1986; Newman 1976;
World with man; it is far harder to explain the origin Martin 1978; Dobyns 1983). Thus it has been
of those diseases that man acquired in the New World claimed that
before the coming of Columbus." The entry of humans
into the Nearctic realm through the land bridge of the [n]ot only did very few people of any origin cross the great
oceans, but those who did must have been healthy or they
Bering Straits area up to 35,000 years ago (Yi and
would have died on the way, taking their pathogens with
Clark 1985) has been assumed to have been sporadic, them. The indigenes were not without their own infec-
small scale, and across a harsh environment. More tions, of course. The Amerindians had at least pinta, yaws,
recently, the founding groups have been seen as lim- venereal syphilis, hepatitis, encephalitis, polio, some vari-
ited to between 300 and 500 and possibly associated eties of tuberculosis (not those usually associated with
with but three waves of migration - the so-called Am- pulmonary disease), and intestinal parasites, but they
erind, Na-Dene, and the Aleut-Eskimo - none older seem to have been without any experience with such Old
than 15,000 B.C.; the order of chronology, however, World maladies as smallpox, measles, diphtheria, tra-
remains uncertain (Greenberg, Turner, and Zegura choma, whooping cough, chicken pox, bubonic plague, ma-
1986). Given this general scenario, it is claimed that laria, typhoid fever, cholera, yellow fever, dengue fever,
the numbers would be far too small to sustain a scarlet fever, amebic dysentery, influenza, and a number of
human-to-human mode of infection (Cockburn 1963; helminthic infestations. (Crosby 1986)
St. Hoyme 1969). However:
The aborigines, then, seem to have been relatively
As man wandered around the world, he would take many disease-free, as a result of their isolated and limited
of his parasites with him. Those such as the louse, the populations initially, and the harsh climate. More-
pinworm, herpes virus, typhoid bacillus, and others that over, given the nature of the immigrant economy,
were closely attached to him would not have great trouble and the paucity of animal domesticates, only the
in travelling in this fashion. Others that required trans- guinea pig, turkey, and South American cameloids
mission by a specific intermediate host would die out once served along with the dog in the New World as reser-
the territory of the necessary intermediate hosts was left voirs for horizontal transfer of disease (Newman
behind. (Cockburn 1963) 1976). Thus we have an image of human beings in a
Moreover, it now seems possible that human tuber- nearly ideal state of physical health, removed from
culosis made the voyage as well, in that one or the main channels of human disease (Dubos 1968).
more of the Bering Strait migrants may have had a However, B. Trigger (1985) has rightly warned:
childhood primary infection that, like 5 percent of
Scholars should not succumb to the temptation of believ-
cases today, developed into chronic destructive tu-
ing that in prehistoric times illnesses had not been preva-
berculosis (Myers 1965; Steinbock 1987). The predis- lent or of concern to native people [for] [t]he extraordinary
posing factors for this transformation (any condi- levels of mortality and other misfortunes that followed
tion that impairs acquired cell-mediated immunity) European contact must have caused them to idealize ear-
include poor nutrition, diabetes, or an acute infec- lier times as a halcyon age of physical health, economic
tion possibly from a traumatic incident. All of these prosperity, and social harmony.
could have occurred in a band of hunter-gatherer
adventurers in spite of the "cold screen." At least Alfred Crosby (1986) maintains that the spiro-
one scholar (Klepinger 1987), however, denies that chetal diseases of pinta, yaws, and venereal syphilis
there is any evidence of the disease being carried were present in pre-Columbian America. A great

deal has been written regarding Treponema pal- causes of death, reflecting the new relationship be-
lidum (the organism causing venereal syphilis) and tween human and land (Martin 1978; Dobyns 1983).
its virulent expression in Europe following the dis-
covery of Nearctica (Cockburn 1971; Crosby 1972). The Native American and Disease Ecology
However, it appears now that like many other organ- The long-term result of the development of North
isms this one spirochete has adapted over time to American peoples in the absence of contact with oth-
present different clinical patterns under different ers was a healthy population adjusted to its environ-
climatic and sociological regimes (Hudson 1963, mental niches. Humankind had multiplied from the
1965, 1968). Moreover, C. J. Hackett (1963, 1967) founding stock and by the late fifteenth century num-
has argued that pinta was brought into the Ameri- bered somewhere between 4.4 million (Ubelaker
cas by the founding groups and has "a long duration 1976) and 9.8 million (Dobyns 1966). Within this
of infectiousness which would maintain it in small total, a degree of variety had arisen in the human
population groups, even in families, which suggests populations of Nearctica in the course of some 600
that it is the early human treponematosis." generations, reflecting the historical and environ-
Additionally, there is some suggestion that the mental conditions (Brues 1954; Szathmary 1984).
treponematosis that causes yaws produced depres-
sions in some prehistoric Indian crania, which may The genetic characteristics of American Indian popula-
tions are sufficiently similar to one another and different
indicate a northern extension of yaws in earlier
from those of other continental groups to permit (as a first
times up the Mississippi into the Midwest (St. approximation) of their description as a "distinct" sub-
Hoyme 1969). On the other hand, as recently as group of the human species. . . . Closer analysis of genetic
1967, it was argued that there was no osteological affinities reveals that over larger areas the genetic conti-
proof of pre-Columbian yaws and that the tradi- nuity takes the modified form of gradients or clines. Thus
tional view that it had been introduced by African thefrequencyof the gene for blood group A decreases from
slaves was still acceptable (Stewart and Spoehr north to south, that for the allele for the Diego factor and
1967). In addition, recent reports (Rothschild and the M gene increases from north to south. (Weiner 1971;
Turnbull 1987) of syphilis in a Pleistocene bear see also Suarez, Crouse, and O'Rourke 1985)
skeleton in Nebraska have been discounted, as no
Throughout the region the B gene is singularly
authenticated treponemal infections have been
lacking, with almost all Amerindian groups belong-
found in a nonprimate (Neiburger 1988).
ing to the O blood group. This situation may ex-
In summary, sparse populations of indigenes plain a particular susceptibility to smallpox on its
would be fairly free of diseases transmitted from introduction (Mourant, Kopec, and Domaniewska-
other humans, although their contact with game, Sobczak 1958). Not all scholars agree even on this
and especially their ingestion of raw meat and of point, however:
water, would bring them into contact with some inva-
sive pathogens (Fenner 1970). Their necessarily mo- The role of the blood groups in the resistance of certain
bile hunting-and-gathering life-style would protect infections or parasites has been controversial. If it was
them from a degree of self-contamination, but fail- demonstrated, its importance would be significant in ac-
ure of the hunt would periodically stress them and counting for the repetition of certain factors . . . [I]n the
accidents would traumatize some. region of pestilential or variolic endemic diseases, the
plague would be worse and more frequent among people
As the sedentary maize-based cultures spread
with type O, and smallpox, among those with type A.
north from Mexico, villages appearing after 7000 (Bernard and Ruffle 1966, trans. Graham)
B.C. and, later, larger settlements (possibly as large
as 40,000 as at Cohokia, Illinois) created other This interpretation is based on the discovery that
health problems, among them those of sanitation Pasteurella pestis possesses an antigen similar to the
(Heidenreich 1971; Crosby 1986). Furthermore, the H antigen, whereas the variola virus has an antigen
invasion of settlements by rodents and fleas would similar to the A antigen. As people with blood group
have led to human contact with the illnesses of na- O are not able to produce any anti-H antibody
tive animals (Dobyns 1983). One can only speculate (which corresponds to the H antigen of P. pestis),
as to the impact of these concomitant aspects of they have a very poor prognosis when infected (Vo-
agriculture; but while the carrying capacity of local gel, Pettenkofer, and Helmbold 1960; Matsunage
areas, and hence their population densities, grew, 1962, 1982). Although anthropologists and others
there is no firm evidence that morbidity declined. have used these studies to support theories of ge-
Rather, there may well have been a shift in the netic distance and purity of Amerindian stock (Post,

Neel, and Schull 1968; Roberts 1976; Szathmary rise to the realization that Europeans — and in the
1984), the consensus on the theory of genetic suscep- south, Africans - entered what Francis Jennings
tibility to disease is that the case is unproven in the (1975) has called a "widowed" land. This interpreta-
context of the exposure of these peoples to the im- tion, in contradistinction to that of the "Black Leg-
ported Old World infections (Newman 1976; Ward end" (Newman 1976), which blamed the decline of
1980; Joralemon 1982). native populations on the cruelty and warfare of the
There is, however, increasing evidence in genetic invading peoples, views the role of accidentally intro-
epidemiology that certain conditions are related to duced disease as critical. "Virgin soil" disease ecolo-
genotype—environment interactions. In the case of gists argue that persons having no previous contact
contemporary North American native peoples, these with the larger pathogen pool of humanity are immu-
conditions include inflammation of the inner ear nologically defenseless. And so the Amerindians
(Gregg, Steele, and Holzheuter 1965), gallbladder who had not before encountered Old World bacteria
disease (Burch, Comess, and Bennett 1968), diabetes and viruses succumbed in large numbers to ailments
(Miller, Bennett, and Burch 1968), and alcoholism that scarcely touched the immune Europeans
(Broudy and May 1983; Social Biology 1985). Indeed, (Hauptman 1979; Joralemon 1982; Dobyns 1983;
it has been claimed that at the present time Curtin 1985; Hader 1986). M. T. Newman (1976),
however, warns:
Many Amerindian peoples are experiencing a major epi-
demic of a series of diseases which include a tendency to There is mounting evidence that American Indians were
become obese at an early adult age, adult onset of diabetes no more susceptible to most of these infectious disease
mellitus, the formation of cholesterol gallstones. [T]his imports than other populations where these diseases had
epidemic . . . seems to be due to an interaction between not struck within the lifetime of the people — none of
susceptible Amerindian genotype(s) and some recently whom therefore had acquired specific immunities.
changed aspect of the environment, probably involving
dietary components. (Weiss, Ferrell, and Hania 1984) For this reason Newman quotes W. R. Centerwall
(1968), who called for "a reevaluation . . . with re-
It would seem, then, that there is evidence of an spect to the primary susceptibility of the Indian
ecology of disease specifically associated with the to . . . diseases of civilization, such as pertussis
continent's native peoples, one of the three major (whooping cough), smallpox, and tuberculosis"; and
human stocks presently inhabiting the region. Centerwall concluded that "during the conquest, cul-
tural disruption should be added to the impacts of
The Columbian Impact the new pathogens, compounded by the force of Euro-
Although evidence of varying quality exists for hu- pean arms and the later ill-treatment of slavery."
man penetration of Nearctica prior to the arrival of Numerous other scholars have also implicated psy-
Columbus in 1492 (Boland 1961), that event and chological, economic, and social factors stemming
the almost simultaneous arrival of Africans were to from introduced disease in the high mortality and
be catastrophic in terms of the disease ecology of even decimation of Amerindian populations (Crosby
the continent (Ashburn 1947; Crosby 1972, 1976;' 1976; Dobyns 1976,1983; Meister 1976; Miller 1976;
McNeill 1976). Europeans and Africans represented Trigger 1985). In any event, the indigenes went into
a totally different set of disease foci and introduced decline as their battle with disease resulted gener-
pathogens that initially devastated the native ally in high death rates - up to 90 percent has been
Americans. The age of contagious or infectious dis- mentioned in some smallpox outbreaks, with case
ease had dawned in America. There were two basic fatalities of 74 percent in others (see Fenner 1970;
reasons for this, beyond the obvious one of disease Joralemon 1982; Hader 1986).
importation. The first involved the zoonoses in- This kind of die-off, of course, did not occur simul-
troduced as a result of the transfer of animals pre- taneously or uniformly across the continent (Meister
viously unknown to the continent; the second re- 1976). Pertussis, smallpox, pulmonary tuberculosis,
lated to the colonization that led to communities measles, diphtheria, trachoma, chickenpox, bubonic
having threshold populations that could sustain plague, malaria, typhus, typhoid fever, cholera, scar-
infection. let fever, influenza, and a number of intestinal infec-
In the initial period, European diseases spread tions arrived with the Europeans at various times
rapidly into the interior, outdistancing the newcom- over 5 centuries. Of these, smallpox has generally
ers who had brought them, while decimating native been seen as the most dramatic (Ashburn 1947) and
populations (Dobyns 1983). This fact, in turn, gave was one of the earliest to arrive. In Espafiola it made

1507
16th and 17th Centuries 18th Century
Map VII.8.1. Diffusion of smallpox among native

Americans. (After Heagerty 1928.)
SCALE
500 1000 1500 2000
19th Century
its appearance by 1519 (Crosby 1986), and was pres- demic on the Great Plains, which decimated about
ent in North America prior to the middle of the half the remaining natives there (Hearne 1782,
century, spreading northward from Mexico (Dobyns quoted in Innis 1962; Crosby 1976).
1983; Trigger 1985). As a new disease moving with- Maps VII.8.1 and VII.8.2, based on J. J. Heagerty
out an intermediary vector, from person to person, it (1928) and H. F. Dobyns (1983), respectively, summa-
hit those of all ages, although the mortality of young rize in a stylistic manner the history and geography
males in many populations was especially devastat- of these outbreaks and illustrate that full elucida-
ing (Ray 1974). tion of these events awaits an in-depth study based
Most Europeans had experienced smallpox in on original accounts, documents, and interpreta-
childhood, and hence were protected, but this was tions. Thus the hypothesized lower susceptibility, of
not true for the Amerindians or, for that matter, those with a dominance of blood group O, noted
many of the blacks in America. Repeated introduc- above, is not borne out by the historical evidence. On
tions along the East Coast and up the St. Lawrence the other hand, the anomalous group of the Black-
led to further outbreaks from the seventeenth to the foot Indians, with their A blood group, certainly
nineteenth century, including an outbreak that dra- suffered very severely; over two-thirds or some 6,000
matically influenced the population decline in Hu- Blackfoot were decimated in the smallpox outbreak
ronia in 1639-40 (Trigger 1985), and the 1837 epi- of 1837 (Bradley 1900; Ewers 1958).

1520
16th and 17th Centur 18th Century
Map VII.8.2. Diffusion of smallpox among native

Americans. (After Dobyns 1983.)
SCALE
500 1000 1500 2000
km
19th Century
The Europeans, however, were not all immune to epidemics and affected a larger number of adults in
smallpox, as population growth in the colonies in- the New World. Only late in the colonial period,
creased the number of susceptibles. Thus, in Boston with population clusters in excess of 500,000, could
a 10 percent death rate from this scourge was re- measles or, for that matter, smallpox become estab-
corded for 1721, and in each of the years 1702, 1730, lished as endemic in America (Black 1966; Fenner
and 1752 over 6 percent of the population of that city 1970; Cliff et al. 1981). When and where this first
died from this one disease (Dobson 1987). occurred is not known, but it was probably not until
Measles was also introduced in the seventeenth the nineteenth century (Cartwright 1972). The fact
century from Europe, and as early as 1635 the Jesu- that the pair of diseases was confused in the records
its reported an outbreak among the French and does not help in establishing this important turning
Indians (Duffy 1972). The disease was very conta- point.
gious, and a series of epidemics such as those of Unlike the two diseases just discussed (and other
1713-15 spread inland from the seaports. Indeed, purely human diseases such as scarlet fever and
in 1772 measles was a leading cause of death in diphtheria), vectored diseases and zoonoses required
Boston (Duffy 1972) and was claimed to be more infective agents to become established in the New
often fatal in America than in England as in the World. Just two of these - plague and malaria — will
former it took the form of a series of introduced be discussed. Plague was one of the earliest diseases
to be introduced from Europe (Williams 1909; Posey but malaria was more often a predisposing condition
1976). Rats infested every ship that crossed the At- rather than a fatal disease once the milder vivax
lantic, though only occasionally was the rat-human malaria (introduced from Europe) became estab-
relationship as close as that described by Colonel H. lished in the Mississippian west. For Europeans
Norwood (n.d.) in the mid-seventeenth century. "The (who may have been exposed to the vivax variety in
infinite number of rats that all the voyage had been England), falciparum malaria was deadly wherever
our plague, we now were glad to make our prey to it had been introduced to the local mosquitoes by
feed on." No doubt, however, those that survived slaves along the marshlands of the Atlantic and Gulf
landed and by 1612-19 in Florida and New England, coasts (Childs 1940; Savitt 1978).
these newcomers and their fleas had given rise to
Although a variety of strains and perhaps even both major
human plague (Dobyns 1983). As D. A. Posey (1976)
species may have been introduced by diverse carriers at a
explains, "Once the rodent carriers were transported fairly early date, a more probable model, given the flow of
to this virgin territory, the plague would have immigration and the prevalence of vivax in Europe and
spread as wild native rodent populations became falciparum in Africa, would have strains of the former
reservoirs of the dreaded disease . . . and few, if any entering during the first half of the [seventeenth] century,
animals, except the louse were more common in In- followed by the gradual establishment of areas of stable,
dian and colonial camps." low-level endemicity. The shattering of this picture would
Thus, the conditions were present for plague occur as blacks in numbers began arriving from a variety
long before the first fully documented case was re- of African areas, bringing with them new strains of...
corded in 1899 as having come from Japan into falciparum. ... [A] qualitative change occurred sometime
in the second half of the century as falciparum entered the
San Francisco (Link 1953; Schiel and Jameson
colony... . [T]he benign vivax was prevalent in the 1670's
1973). Three views of plague in the hemisphere but was supplanted by the more virulent falciparum in the
can be sustained on the basis of present knowl- 1680's. (Rutman and Rutman 1976)
edge. One view is that it has long existed, even
from prehistoric times as a sylvatic cycle disease Further vivax introductions from African sources
in rodents. The remaining two, more probable, would be strictly limited because of the absence of
views entail its introduction from Europe, followed the Duffy blood group determinants Fya and Fyb in
by possible extinction in eastern locations, and the most individuals of African descent, which prevents
documented transpacific reintroduction in the late them from hosting the disease (Mourant, Kopec, and
nineteenth century. Certainly this third route has Domaniewska-Sobczak 1976).
given rise to endemic plague from the Mexican bor- The transmission, of course, depended on the trans-
der to Alberta primarily among ground squirrels mission of infection to Anopheles mosquitoes from
and their fleas (Hubbard 1947). Unfortunately, do- those suffering with malaria parasites. Unfortu-
mestic animals from time to time pick up these nately, Nearctica was already amply provided with
fleas and transport them into Western homes potential vectors (Freeborn 1949), and these mosqui-
where occasional human infections are contracted, toes became instrumental in spreading the infection
the annual incidence rate being 3.4 cases per year, from the south and east right up the Mississippi
1927-69 (Canby 1977). Valley as far as Canada, where seasonal transmis-
Falciparum malaria, dysentery, smallpox, intesti- sion took place among the native peoples and set-
nal worms, yaws, guinea worm, schistosomiasis, and tlers locally into the 1940s (Drake 1850/1954; Moul-
yellow fever were contributed by the African slave ton 1941; Ackerknecht 1945). Furthermore, malaria
(Ashburn 1980; Dunn 1965). Of these African dis- was widespread in the nineteenth century in the
eases, malaria and yellow fever were the most sig- Pacific Northwest of the continent (Boyd 1985; see
nificant (McNeill 1976), but their impact differed also Map VII.8.3). Indeed, infection and even death
among the major population groups involved (Postell from this imported disease still take place in North
1951; Duffy 1972; Kiple and Kiple 1977). In the case America, although changed environmental and so-
of malaria, the African slaves usually had been pre- cial conditions led to its retreat to the South. By the
viously exposed, or had blood anomalies to protect 1950s, malaria - "the United States disease of the
them. Malaria among this group was generally a late 19th century" (Meade, Florin, and Gesler
childhood disease in terms of mortality, though recur- 1988) - had been eradicated. Much of the resurgence
rence in later years was debilitating. On the other of the South and its development as the "Sun Belt"
hand, among native Amerindians mortality from ma- are related to this aspect of disease ecology.
laria could be as high as 75 percent (Dobyns 1983), The nineteenth-century social and economic condi-

0 100 200 300 400

km
Map VII.8.3. Malarial disease deaths per 1,000 population, 1870. (Based on Ninth U.S. Census; assembled by author.)
tions, together with improved communication and ered the microorganism Vibrio cholerae in 1883. In
ever increasingflowsof immigrants, opened the con- the pandemics of 1831-2, 1848-50, 1853-4, and
tinent to further invasions of disease. Indeed, immi- 1866, North America was not spared. Entering at
grants, poverty, and disease were almost synony- port cities such as New York, Quebec, and New Or-
mous in many circles in this period. Most dramatic leans, the disease spread with the migrants and cre-
of these imported epidemics were those of cholera, ated terror but eventually catalyzed the develop-
with its ability to kill an estimated 40 to 60 percent ment of meaningful public health reporting and
of its victims within hours (Morris 1976) and an treatment networks (Bilson 1980). This result would
etiology that was unknown until Robert Koch discov- perhaps have taken much longer to achieve than it

Deaths per 1,000

<25 •
25-55 •
55-90
90-140 •
140-200
>200
Map VII.8.4. "Consumption" deaths per 1,000 population, 1870. (Based on Ninth U.S. Census; assembled by author.)
actually did had not this one condition had such a It came to "transcend all maladies in the total num-
powerful effect on the population as a whole. ber of its victims and the cost to society" (Ashburn
The other great scourge of the nineteenth century 1947; see also Map VII.8.4).
was pulmonary tuberculosis, also known as the That Amerindians had little experience with epi-
"white plague." As previously noted, mycobacteria demic tuberculosis prior to contact with Europeans
had long been present in the Western Hemisphere, (Clark et al. 1987) is borne out by the dramatic
but it was only in the nineteenth century, with ur- susceptibility of Indians after exposure. For exam-
banization (crowding of masses of people, often in ple, R. G. Ferguson (1934) wrote:
poor-quality housing and lacking good nutrition),
that this person-to-person infection assumed epi- A most disastrous epidemic appeared among the tribes
demic proportions (Ashburn 1947; Cockburn 1963). settled on the reservations and within a few years [after

• or ALNWICK Location. Whar* Caaaa of Laproay War* Raportod

• Laiaratto
County Boundary
SOUT
euro*: John J. Haagorty,

Map VII.8.5. Leprosy area of New
Uadlol
» JACKVILLE
Hlatorv In Canada ....
Brunswick, predominantly in the
\ 2 Vola.. Toronto. 1029
nineteenth century. (From
Heagerty 1928.)
1879] the general death rate among them was varying modern times. (Among Europeans, it had been intro-
from 90 to 140 deaths per 1,000, two-thirds of these due to duced [Heagerty 1928] but never became estab-
tuberculosis. lished, except for a brief period in the Florida Keys.
In 1928 the U.S. Bureau of the Census reported Only a handful of persons — for instance, in New
that 11.6 percent of Amerindian deaths were due to Brunswick - are recorded as having had the disease;
tuberculosis, as compared to 5.5 percent of Negro see Map VII.8.5; Losier and Pinet 1984).
deaths and 5.6 percent of all white deaths (Ashburn
1947). The Present and the Past
As far as blacks are concerned, some suggest that Writing in 1963, A. Cockburn claimed that "tubercu-
tuberculosis was rare among slaves (Postell 1951), losis had not displaced malaria as the world's num-
though all agree that during Reconstruction it be- ber one problem in infectious disease," but like ma-
came a major cause of ill health and mortality, as laria, it has become rare and under control in
social and economic conditions for most blacks de- Nearctica.
clined markedly (Savitt 1978). As for other myco- Like other so-called developed areas, North Amer-
bacteria, leprosy is said to have been introduced ica has undergone both demographic and epidemio-
with the slave population (Ashburn 1947) and re- logical transitions (Omran 1977): from high birth
mained an endemic disease in small numbers into and death rates to low birth and death rates, and

from the predominance of infectious diseases in caus- white segment of the population. Thus there are now
ing death, to a preeminence of degenerative diseases fewer deaths from fevers and tuberculosis and infant
(heart disease and cancers) in causing death (Dubos mortality is declining, but both are still much higher
1968). Genes replace "germs" as the significant vari- among blacks than among white Americans (Bouv-
ables in these societies (Ward 1980). Having said ier and Van der Tak 1976). The result is that the
that, one can question just how and when these national mortality rates for the United States for
transitions took place. Almost certainly they did not many ages and causes are inflated by inclusion of
occur simultaneously for each of the three groups the relatively disadvantaged black minority, and the
discussed here. The Amerindians survived an initial full impact of lower birth and death rates has not yet
period of adjustment on entering the continent, been seen for this group.
when adaptation would bring great stress but infec- White Americans, like the blacks, experienced an
tions as such would be rare. They then grew in initial seasoning period upon arriving in Nearctica.
numbers and, with the development of agriculture Thereafter they grew rapidly in numbers, experienc-
and sedentary villages, attained densities that gave ing more healthful conditions than those currently
rise to self-contamination, in addition to the hazards prevailing in Europe (Duffy 1972; Dobson 1987).
of the field and hunt. However, as St. Hoyme (1969) They did, however, have higher mortality rates in
observed, "At the time of the conquest, Indians suf- the southern colonies and continually in the coastal
fered less from contagious diseases than from arthri- towns into which disease was constantly brought
tis, nutritional and metabolic disturbances, and non- from overseas. Thus, urban areas acted as reservoirs
specific infections associated with traumata." of infection that periodically broke out to cause sud-
At this point, the era of exotic contagions dawned, den devastation in the new generation of suscepti-
with death rates threatening extinction. This did not bles in the smaller settlements and countryside (Dob-
happen uniformly or necessarily (Meister 1976). son 1987). Prophylactic measures, notably improved
Thus, some areas experienced rapid population de- sanitation and standard of living, enabled this group
cline, and others growth. Gradually white newcom- to enjoy the full benefits of the transition model.
ers and, to a lesser extent, blacks, as well as Amerin- Thus,
dians, all adjusted to the new disease environment,
as a result of the ensuing rise in economic standards,
and populations recovered, only to encounter new diseases associated with toiling for food and coping with
hazards as a result of environmental moves from natural disasters have been supplanted by those which
traditional homelands. spring from the complexities of our technological age, in
Today, however, most Amerindian groups con- which man's connection with the soil has become less
tinue to have high infant mortality rates and high direct. (Furness 1970)
rates of infectious disease. The blacks, too, like the
Amerindians prior to contact, were in a state of The Present and the Future
health homeostasis when rudely plucked from Af- Although all three population groups have seen dra-
rica and transported to the New World, with a terri- matic improvements in their health, disease eco-
ble toll being paid en route (Pope-Hennessy 1967; logies continue to evolve. Today virus infections
Kiple 1984). Once in America they suffered a large remain as serious public health problems, acting
number of infections that, according to William differentially on the genetic variation present on the
Postell (1951), continent. Often forgotten in this context is that
perplexing virus, influenza. It is perplexing because
may have been caused by dietary deficiency. The great of its mutational history, with each strain - "Asian,"
number of dental caries, sore eyes, sore mouths, sore feet "Hong Kong," "swine," and so forth - being distinct
and legs, and skin lesions is suggestive of pellagra . . . for immunologically, and ever dangerous in light of the
it is suspected that the slave received an improperly bal-
still readily recalled devastation caused by the
anced diet, particularly during the winter months [and]
suffered greatly from cholera, pneumonia, dysentery .. . 1918-20 pandemic. Recent work by Gerald Pyle, a
and probably to a lesser extent than his white master, medical geographer, epitomizes the promise of the
from yellow fever and malaria. application of geographic modeling to public health
problems of tracing the diffusion of diseases such as
Respiratory complaints or "pleuretical disorders" this (Pyle 1986). The acquired immune deficiency
were particularly fatal to them (Duffy 1972). Since syndrome (AIDS) has established itself as of prime
the days of slavery, conditions have improved for concern and appears to be following much the same
black Americans, but much more slowly than for the pattern of spread as the earlier urban-centered epi-

Table VII.8.1. Incidents of serious contamination in U.S. work sites and residential areas
Location Chemicals Health effects Cause of incident

Southern mirex Causes cancer in mice. Mirex was sprayed over several of the
United States" Toxic to crabs and shrimp. southern states in order to control fire
Detected mirex in fatty tissue of 25% of ants.
people living in area sprayed. Its use was phased out in 1978 owing to
health effects.
Mirex stays in the environment longer
than DDT.
St. Louis Park, creosote Severe skin reaction from handling Reilly Tar and Creosote Manufacturer
Minn.* creosote-bearing soil. had an 80-acre site where waste was
dumped.
Nearby wells were contaminated by the
site.
Hopewell, Va.c kepone June 1975: A worker became ill with diz- The Life Science Products Corporation
ziness and trembling due to high concen- produced the pesticide kepone and em-
tration of kepone in his blood. ployed the people affected.
State official investigations found 7
workers ill enough to require immediate
hospitalization. Over 100 people, includ-
ing wives and children, had kepone in
their blood, and 30 more people were
hospitalized with tremors and visual
problems.
Some people may be permanently ster-
ile, and all are threatened with possible
development of liver cancer.
Tyler, Tex.c asbestos 25-40 of 900 workers have died from The asbestos plant closed in 1972.
breathing asbestos.
The death toll is expected to reach 200
workers.
Chattanooga, nitrogen Exposed persons are more susceptible to TNT plant located nearby.
Tenn.c dioxide respiratory disease, colds, bronchitis, Levels of exposure up to 500 grains/
croup, and pneumonia. billion have been shown.
Times Beach, dioxin Effects of dioxin exposure appeared al- Man was hired to spread oil on dirt
Mo.c [TCDD] most immediately. roads; oil residues plus other wastes
(300 ppb) In 10 days hundreds of birds and small that remained in the containers were
and others animals died; kittens were stillborn, mixed into the oil.
and many horses died. Dioxin in the form TCDD as high as 300
ppb (1 part per billion is the maximum
dose deemed safe).
Times Beach, dioxin Miscarriages, seizure disorders, liver im- EPA purchased every piece of property
Mo.c [TCDD] pairment, and kidney cancer. in the town and ordered its evacuation.
Sources: "Gould (1986, 28-9); *Epstein, Brown, and Pope (1987, 75); 'Getis, Getis, and Feldman (1981).
demies of alien origin. Immigrants continue to intro- health effects of contamination are not always dra-
duce new potential pathogens and are the source of matic, but as Table VII.8.1 shows, the results can
reintroduction of others to which the resident popu- be very real.
lation may have lost herd immunity (Kliewau Perhaps because of the shorter time lapse involved,
1979). Urban wastes as well as technologies con- the monitoring of birth defects and infant mortality
stantly tend to poison the environment (Greenberg provides an important measure of these new hazards
1978), and through disposal efforts and acid rain, (Puffers and Serrano 1973). Although improvements
virtually the whole population is exposed. The in infant survival rates encourage the belief that a

new homeostasis is being reached, any marked Boyd, R. T. 1985. Infections among the Northwest Coast
change for the worse and any increase in congenital Indians 1770-1870. Ph.D. dissertation, University of
anomalies need to be treated very seriously. Washington, Seattle.
Bradley, J. H. 1900. Affairs at Fort Benton 1831-69. Mon-
Much remains to be learned about the natural history of tana Historical Society Contributions, Vol. 3. Helena.
health and disease in the Americas. . . . We do not know Broudy, D. W, and P. A. May. 1983. Demographic and
why diseases occur or do not occur at a given time and epidemiologic transition among the Navajo Indians.
place. Even less do we know what conditions and circum- Social Biology 30: 1-16.
stances cause them to spread within a country and be- Brues, A. M. 1954. Selection and polymorphism in the A -
tween countries in the Hemisphere. Indeed, accurate B-0 blood groups. American Journal of Physical An-
knowledge of the etiology of a specific disease does not tell thropology 12: 559-97.
us about the sequence of events that produce it. Today we Burch, T. A., L. J. Comess, and P. H. Bennett. 1968. The
accept the fact that multiple causes are involved in the problem of gall bladder disease among Pina Indians.
development of disease. (Horwitz 1973) In Biological challenges presented by the American
Indian. Pan American Health Organization. Scien-
These causes include those of nature, inherited in tific Publication No. 165. Washington, D.C.
infancy from the genetic stream, predisposing in all Canby, T. Y. 1977. The rat: Lapdog of the devil. National
probability to a number of conditions from hyperten- Geographic 152: 20-87.
sion in black North Americans to schizophrenia and Cartwright, F. F. 1972. Disease and history. New York.
beyond. The triggers creating recognizable diseased Centerwall, W. R. 1968. A recent experience with measles
individuals, however, often appear to remain envi- in a "virgin-soil" population. In Biological challenges
ronmental and related to poverty. The comprehen- presented by the American Indian. Pan American
sive evaluation of these links of nature and nurture Health Organization, Scientific Publication No. 165,
remains the challenge of a historically based medi- 77-81. Washington, D.C.
cal geography of the Americas. Childs, St. J. R. 1940. Malaria and colonization in the
Carolina low country 1526—1696. Johns Hopkins Uni-
Frank C. Innes
versity Studies in Historical and Political Science, Ser.
The support, advice, and editorial assistance of Dr. Robert Doyle, LVIII: 1.
Department of Biology, was invaluable. Student assistance of Clark, G. A., et al. 1987. The evolution of mycobacterial
Lydia Stam-Fox and Amanda James and cartography by Ron disease in human populations. Current Anthropology
Welch together with a grant from University of Windsor Research 28:45-62.
Board made this contribution possible. Cliff, A. D., et al. 1981. Spatial diffusion: An historical
geography of epidemics in an island community. Cam-
Bibliography bridge.
Ackerknecht, G. H. 1945. Malaria in the Upper Missis- Cockburn, A. 1963. The evolution and eradication of infec-
sippi Valley 1760-1900. Bulletin of the History of tious diseases. Baltimore.
Medicine, Suppl. No. 4. Baltimore. 1971. Infectious diseases in ancient populations. Cur-
Anderson, D. H., et al. 1975. Pulmonary lesions due to rent Anthropology 12: 45-62.
opportunistic mycobacteria. Clinical Radiology 26: Craun, G. F , ed. 1986. Waterborne diseases in the United
261-9. States. Boca Raton, Fla.
Ashburn, P. M. 1980. The ranks of death: A medical history Crosby, A. W. 1972. The Columbian exchange: Biolog-
of the conquest of America, 4. Philadelphia. ical and cultural consequences of 1492. Westport,
Bernard, J., and J. Ruffie. 1966. Himatologiegiographique Conn.
ecologie humaine caracteres hereditaires du sang, Vol. 1976. Virgin soil epidemics as a factor in the aboriginal
1: 333. Paris. depopulation in America. William and Mary Quar-
Bilson, G. 1980. A darkened house. Toronto. terly, 3d ser., 23: 289-99.
Black, F. L. 1966. Measles endemicity in insular popula- 1986. Ecological imperialism: The biological expansion
tions: Critical community size and its evolutionary of Europe, 900-1900. Cambridge.
implications. Journal of Theoretical Biology 11: 207- Curtin, P. D. 1985. Cross cultural trade in world history.
11. Cambridge.
Boland, C. M. 1961. They all discovered America. New Dobson, M. J. 1987. From old England to New England:
York. Changing patterns of mortality. Research Paper No.
Bourque, B. J., and R. H. Whitehead. 1985. Torrentines 38, School of Geography, Oxford.
and the introduction of European trade goods in the Dobyns, H. F. 1966. Estimating aboriginal American popu-
Gulf of Maine. Ethnohistory 32: 327-41. lation: An appraisal of techniques with a new hemi-
Bouvier, L. E, and J. Van der Tak. 1976. Infant mortality - sphere estimate. Current Anthropology 7: 395-416,
progress and problems. Population Bulletin 31: 3032. 425-45.

1976. Brief perspective on a scholarly transformation: Greenberg, M. R. 1978. Public health and the environment:
widowing the "virgin" land. Ethnohistory 23: 95-104. The United States experience. New York.
1983. Their numbers became thinned: Native American Gregg, J. B., J. P. Steele, and A. M. Holzheuter. 1965.
population dynamics in eastern North America. Knox- Roentgenographic evaluation of temporal bones from
ville. South Dakota Indian burials. American Journal of
Drake, D. 1850/1954. A systematic treatise on the principal Physical Anthropology 23: 51-61.
diseases of the interior valley of North America, Vols. Hackett, C. J. 1963. On the origin of the human
1-2. Cincinnati. treponematoses. Bulletin of the World Health Organi-
Dubos, R. 1968. Man, medicine and environment. New zation 29: 7-41.
York. 1967. The human treponematoses. In Disease in antiq-
Duffy, J. 1972. Epidemics in colonial America. Port Wash- uity: A survey of the diseases, injuries and surgery of
ington, N.Y. early populations, ed. D. Brothwell and A. T.
DuFour, A. P. 1986. Diseases caused by water contact. In Sandison, 152-69. Springfield, 111.
Waterborne diseases in the United States, ed. G. F. Hader, J. M. 1986. The effects of epidemic illnesses on the
Craun, 23-42. Boca Raton, Fla. American Indians. Western Canadian Anthropologist
Dunn, F. L. 1965. On the antiquity of malaria in the 3: 19-34.
Western Hemisphere. Human Biology 4: 241-81. Hare, R. 1967. The antiquity of disease caused by bacteria
1968. Epidemiological factors: Health and disease in and viruses: A review of the problem from a bacteriolo-
hunter-gatherers. In Man and hunter, ed. R. B. Lee gist's point of view. In Diseases in antiquity: A survey
and I. DeVore, 221-8. Chicago. of the diseases, injuries and surgery of early popula-
Epstein, S., L. Brown, and C. Pope. 1987. Hazardous waste tions, ed. D. Brothwell and A. T. Sandison, 115-31.
in America. San Francisco. Springfield, 111.
Ewers, J. D. 1958. The Blackfoot, raiders of the Northwest- Hauptman, L. M. 1979. Smallpox and the American In-
ern Plains. Norman, Okla. dian. New York State Journal of Medicine 79: 1945-9.
Fenner, F. 1970. The effects of changing social organiza- Heagerty, J. J. 1928. Four centuries of medical history in
tion on the infectious diseases of man. In The impact Canada and a sketch of the medical history of New-
of civilization on the biology of man, ed. S. V. Boyden, foundland, 2 vols. Toronto.
49-68. Canberra. Heidenreich, C. G. 1971. Huronia: A history and geogra-
Ferguson, R. G. 1934. A study of tuberculosis among Indi- phy of the Huron Indians, 1600-1650. Toronto.
ans. Transactions of the American Clinical and Clima- Horwitz, A. 1973. Foreword to Patterns of mortality in
tological Association, 1—9. childhood: Report of the inter-American investigation
Ferguson, R. G. 1934. Some light thrown on infection, of mortality in childhood, ed. R. R. Puffer and C. V.
resistance and segregation by a study of tuberculosis Serrano. Pan American Health Organization, Scien-
among Indians. Transactions of the American Clinical tific Publication No. 262. Washington, D.C.
and Climatological Association, 18-26. Hrdlicka, A. 1909. Tuberculosis among certain Indian
Ffrench, G. 1976. Water in relation to human disease. In tribes. Bureau of American Ethnology Bulletin 42: 1-
Environmental medicine, ed. G. M. Howe and J. A. 48.
Lorraine, 40-71. London. Hubbard, C. A. 1947. Fleas of western North America.
Freeborn, S. B. 1949. Anophelines of the Nearctic region. Ames.
In Malariology, ed. M. F. Boyd, 379-98. London. Hudson, E. H. 1963. Treponematosis and anthropology.
Fry, G. F., and J. G. Moore. 1970. Enterobius vermicularis: Annals of International Medicine 58: 1037—48.
10,000-year-old infection. Science 166: 1620. 1965. Treponematosis and man's social evolution. Ameri-
Fry, G. F, J. G. Moore, and J. Englert. 1969. Thorny- can Anthropology 67: 885-901.
headed worm infections in North American prehis- 1968. Christopher Columbus and the history of syphilis.
toric man. Science 163: 1324-5. Acta Tropica 25: 1-15.
Furness, S. B. 1970. Changes in non-infectious diseases Innis, H. A. 1962. The fur trade in Canada. Toronto.
associated with the processes of civilization. In Impact Jarcho, S. 1964. Some observations on disease in prehis-
of civilization on the biology of man, ed. S. V. Boyden. toric North America. Bulletin of the History of Medi-
Canberra. cine 38: 1-19.
Getis, A., J. Getis, and J. Feldman. 1981. The Earth science Jennings, F. 1975. The invasion of America: Indians, colo-
tradition. Dubuque. nialism, and the cant of conquest. Chapel Hill, N.C.
Gould, Jay, M. A. 1986. Quality of life in American neigh- Joralemon, D. 1982. New world depopulation and the case
borhoods, ed. A. T. Marlin, Boulder, Colo. of disease. Journal of Anthropological Research 38:
Greenberg, J. H., C. G. Turner, II, and S. L. Zegura. 1986. 108-27.
The settlement of the Americas: A comparison of the Kiple, K. F. 1984. The Caribbean slave: A biological his-
linguistic, dental and genetic evidence. Current An- tory. Cambridge.
thropology 27: 477-97. Kiple, K. F., and V. H. Kiple. 1977. Black yellow fever

immunities, innate and acquired, as revealed in the Omran, A. R. 1977. Epidemiologic transition in the United
American South. Social Science History 1: 419-36. States. The health factor in population change. Popu-
Klepinger, L. A. 1987. Comment on The evolution of lation Bulletin 32: 1-42.
mycobacterial disease in human populations, by G. A. Patrucco, R., R. Tello, and D. Bonavia. 1983. Parasito-
Clark, M. A. Kelley, J. M. Grange, and M. C. Hill. logical studies of pre-Hispanic Peruvian populations.
Current Anthropology 28: 45-62. Current Anthropology 24: 393-4.
Kliewau, E. W. 1979. Factors influencing the life expec- Pope-Hennessy, J. 1967. Sins of the fathers. London.
tancy of immigrants in Canada and Australia. PhD. dis- Posey, D. A. 1976. Entomological considerations in south-
sertation, University of British Columbia, Vancouver. eastern aboriginal demography. Ethnohistory 23:
Link, V. B. 1953. A history of plague in the United States. 147-60.
Public Health Monographs No. 26. Washington, D.C. Post, R. H., J. V. Neel, and W. J. Schull. 1968. Tabulations
Losier, M. J., and G. Pinet. 1984. Children of Lazarus. of phenotype and gene frequencies for 11 different
Fredericton, N.B. genetic systems studied in the American Indian. In
MacLean, D. M. 1975. Group A mosquito-borne arbo- Biomedical challenges presented by the American In-
viruses, primarily in the Western Hemisphere. In Dis- dian. Pan American Health Organization Scientific
eases transmitted from animals to man, ed. W. T. Publication No. 165, 131-3, Washington, D.C.
Hubbert, W. F. McCulloch, and P. R. Schnurrenberger, Postell, W. D. 1951. The health ofslaves on southern planta-
968-83. Springfield, 111. tions. Baton Rouge.
Martin, C. 1978. Keepers of the game: Indian-animal rela- Puffers, R. R., and C. V. Serrano. 1973. Patterns of mortal-
tionships and the fur trade. Berkeley. ity in childhood. In Reports of the inter-American in-
Matsunaga, E. 1962, 1982. Selection mechanisms operat- vestigation of mortality in childhood. Pan American
ing on ABO and MN blood groups with special refer- Health Organization Scientific Publication No. 262.
ence for prezygotic selection. Social Biology 29: 291-8. Washington, D.C.
McNeill, W. H. 1976. Plagues and peoples. Oxford. Pyle, G. 1986. The diffusion of influenza: Patterns and
Meade, M., J. Florin, and W. Gesler. 1988. Medical geogra- paradigms. Totowa, N.J.
phy. New York. Ray, A. J. 1974. Indians in the fur trade: Their role as
Meister, C. W. 1976. Demographic consequences of Euro- trappers, hunters, and middlemen in the lands south-
American contact on selected American Indian popula- west of Hudson Bay, 1660-1870. Toronto.
tions and their relationship to the demographic transi- Roberts, D. F. 1976. The geography of genes. In Environ-
tion. Ethnohistory 23: 161-72. mental medicine, ed. G. M. Howe and J. A. Lottaire,
Miller, M., P. H. Bennett, and T. A. Burch. 1968. 238-53. London.
Hyperglycemia in Pima Indians: A preliminary ap- Rothschild, B. M., and W. Turnbull. 1987. Nature 329:61-2.
praisal of its significance. In Biomedical challenges Runyon, E. H. 1971. Whence mycobacteria and mycobac-
presented by the American Indian. Pan American terioses? A nnals of Internal Medicine 72: 467-8.
Health Organization Scientific Publication No. 165, Rush, B. 1786. An enquiry into the cause of the increase of
89-93. Washington, D.C. bilious and intermitting fevers in Pennsylvania with
Miller, V. 1976. Aboriginal Micmac population: A review hints for preventing them. Transactions of the Ameri-
of the evidence. Ethnohistory 23: 117-27. can Philosophical Society 2.25: 206-12.
Morris, R. J. 1976. Cholera 1832: The social response to an Rutman, D. B., and A. H. Rutman. 1976. Of agues and
epidemic. London. fevers: Malaria in the early Chesapeake. William and
Moulton, F. R., ed. 1941. A symposium on human malaria. Mary Quarterly, 3d sen, 23: 31-60.
American Association for the Advancement of Science St. Hoyme, L. E. 1969. On the origins of New World
No. 15. paleopathology. American Journal ofPhysical Anthro-
Mourant, A. E., A. C. Kopec, and K. Domaniewska- pology 31: 295-302.
Sobczak. 1958. The ABO blood groups. Oxford. Savitt, T. C. 1978. Medicine and slavery, the diseases and
1976. The distribution of the human blood groups and health care of blacks in antebellum Virginia. Chicago.
other biochemical polymorphisms, 2d edition. Oxford. Schiel, J. B., and W. C. Jameson. 1973. The biogeography
Myers, J. A. 1965. The natural history of tuberculosis in of plague in western United States. In Proceedings of
the human body: 45 years of observation. Journal of the American Association of Geographers, 240-5.
American Medical Association 194: 184—90. Washington, D.C.
Neiburger, E. J. 1988. Syphilis in a Pleistocene bear? Na- Social Biology [special issue]. 1985. Genetics and the hu-
ture 333: 603. man encounter with alcohol. 32: 3, 4.
Newman, M. T. 1976. Aboriginal new world epidemiology. Steinbock, R. T. 1987. Commentary on The evolution of
American Journal ofPhysical Anthropology 45:667-72. mycobacterial disease in human populations by G. A.
Norwood, Col. H. n.d. [ca. 1650]. A voyage to Virginia. In Clark et al. Current Anthropology 28: 56.
Force, Tracts III: 10. Stewart, T. D. 1960. A physical anthropologist's view of

VII.9. South America 535
the peopling of the New World. Southwest Journal of

Anthropology 16: 259-73. VII.9
Stewart, T. D., and A. Spoehr. 1967. Evidence on the
paleopathology of yaws. In Diseases in antiquity: A
Disease Ecologies of South
survey of the diseases, injuries and surgery of early America
populations, ed. D. Bothwell and A. T. Sandison, 307-
19. Springfield, 111.
Suarez, B. K., J. D. Crouse, and D. H. O'Rourke. 1985. Pre-Columbian Peoples
Genetic variation in North American populations: The natural environment of the continent of South
The geography of gene frequencies. American Journal
of Physical Anthropology 67: 217-32.
America is overwhelmingly diverse and thus has
Szathmary, E. J. E. 1984. Peopling of northern North
posed special problems of physiological adaptation to
America: Clues from genetic studies. Acta Anthropo- its indigenous populations, as well as later to Euro-
genetica 8: 79-109. pean, African, and Asian intruders. Indeed, because
Trigger, B. 1985. Natives and newcomers: Canada's "He- of the harsh environments of much of the continent,
roic Age" reconsidered. Kingston and Montreal. there are but few places in which people can flourish
Ubelaker, D. H. 1976. Prehistoric New World population without great effort and skillful labor. In much of
size: Historical review and current appraisal of North the continent's vast interior, even communication
American estimates. American Journal of Physical and transportation would be impossible without the
Anthropology 45: 661-5. river systems of the Amazon and the Parana-
Vogel, F., H. J. Pettenkofer, and W. Helmbold. 1960. Ueber Paraguay along with the smaller rivers of Colombia
die populationsgenetik der ABO blutgruppen. II. Acta and Venezuela, the Magdalena and the Orinoco, and
Genetica 1.00: 267-94. the Sao Francisco of northeastern Brazil.
Ward, R. H. 1980. Genetic epidemiology: Promise or com-
promise? Social Biology 27.2: 87-100.
One of the most formidable environments is that
Weiner, J. S. 1971. The natural history of man. New York. of the Andes Mountains, which range from western
Weiss, K. M., R. E. Ferrell, and C. L. Hania. 1984. A New Venezuela to the tip of the continent, with snow-
World syndrome of metabolic disease with a genetic capped peaks at more than 20,000 feet in altitude
and evolutionary basis. Yearbook of Physical Anthro- and with populations perched at 10,000 and 13,000
pology 27: 153-78. feet. At such altitudes, scarcity of oxygen has led to
Williams, H. V. 1909. The epidemic of the Indians of New physiological adaptations in the bodies of the indige-
England, 1616-1620, with remarks on native Ameri- nous peoples of Peru and Bolivia that permit them to
can infections. Johns Hopkins Hospital Bulletin 20: perform hard physical labor in the thin air.
340-9. The Andes break the westerly movement of rain-
Yi, S., and G. Clark. 1985. The "Dyuktai culture" and New fall from the Amazon basin, and rain falls in profu-
World origins. Current Anthropology 26: 1-13.
sion on the eastern slopes, where lush tropical for-
ests shelter the people of the Upper Amazon from
outside invaders. On the opposite side of the Andes,
a lack of rainfall creates the semiarid coastal low-
lands intersected by small rivers flowing through
the desert to the ocean.
As early as 13,000 B.C., people settled in camps
along the coast of Peru and Chile. They fished and
hunted the marine life of the Humboldt current that
sweeps up from Antarctica, and planted crops along
the rivers. Some 3,000 to 5,000 years ago, they built
temples and monumental structures in "U" shapes
along the northern coast (Stevens 1989). They would
later construct massive irrigation complexes, cities,
and states, the greatest of which was the Kingdom of
Chimu, conquered first by the Incas and then by the
Spaniards.
From these earliest beginnings in the coastal des-
erts, civilizations evolved and spread to the highlands

at Chavin de Huantar in the Andes and the great had migrated to the Brazilian coast and farmed in
grasslands around Lake Titicaca in the high plain the tropical forests along coastal rivers. The vast
(altiplano) of Peru and Bolivia, where stone monoliths grassland of the pampas housed nomads who hunted
recall the civilization of Tiwanaku, whose wealth was a "humpless camel" and large flightless birds. Other
based on enormous herds of llamas, alpacas, and vicu- hunters and gatherers followed their prey to the
nas. In Colombia the golden chiefs of "El Dorado" barren, windswept lands on the edge of Antarctica,
ruled confederations of chiefdoms from their towns where they occupied the rocky outcrops of the Straits
and villages, while the powerful empire of the Incas of Magellan.
governed large cities from Ecuador to northern Argen- The Spanish, who, following Columbus, landed at
tina and Chile, and embraced both coastal deserts and Trinidad off the coast of Venezuela in 1498, would
mountain valleys. Great armies swept along the Inca confront sophisticated civilizations that had mas-
roads, sometimes spreading a mysterious disease, tered difficult environments from lowland tropical
which may have been typhus (Guerra 1979). rain forests and deserts without rainfall to high
While large cities and empires evolved in the mountain valleys. As settled agriculturalists living
Andean world, large towns also arose along the Ama- in villages, towns, and cities, they raised a variety of
zon River and its tributaries, where many people foodstuffs, giving many of them an excellent diet,
lived before 1500. In fact, Donald Lathrup views the and traded surpluses to neighbors in different locali-
central Amazon and its chiefdoms as the "cradle" of ties. Only nomadic hunters and gatherers had uncer-
civilization in South America (Stevens 1989). They tain food supplies by 1500. On the eve of the con-
were in touch with the Andean world. They traded quest, the pre-Columbian populations of South
with it, and their armies (along with "fevers") re- America were among the best-fed peoples of the fif-
pelled Incan armies that tried to conquer them. teenth century, which in turn had an impact on the
When the Spanish under Francisco de Orellana pene- quality of their health and nutritional status, and
trated the Amazon in the 1540s, they encountered hence resistance to disease.
"very large cities" whose armies attacked them as In the Andean highlands, the staples were maize,
they explored the river to its mouth. Civilization white potatoes (often stored as freeze-dried chufiu),
thus extended all the way to Santarem at the and the "Andean rice" quinoa, which were supple-
Tapajds river (where mound builders sculpted fanci- mented by guinea pigs and llama meat. Warehouses
ful ceramics) and to Marajd Island at the mouth of built as early as 3,800 years ago stored food against
the Amazon (where another group of mound build- times of famine. In the coastal deserts, farmers
ers, the Marajoara, buried their ancestors in large raised corn, beans, squashes, peanuts, and sweet
funeral urns) until about A.D. 1300, when the people potatoes, and caught fish, hunted birds, or raised
there mysteriously disappeared (Roosevelt 1989). guanacos in Chile. The peoples of the Amazon spe-
Those who lived along the Amazon River raised cialized in the root crops, such as manioc, peanuts,
maize on the floodplain of the river, or root crops and sweet potatoes, as well as maize, and hunted
such as manioc on marginal soils. They traded with deer and tapirs, fished in the great rivers, and gath-
one another, held large fiestas in which maize beer ered nutritious wild fruits and nuts. Only away from
was drunk, and worshiped their ancestors. In other the rivers were food resources precarious for no-
words, the Amazon region was populated and even madic hunters and gatherers. Some of these popula-
"civilized" on the eve of the conquest. tions, as well as the coastal Tupi of Brazil, supple-
Between the rivers, nomadic hunters and gather- mented their diet with human victims acquired in
ers roamed as far south as the semiarid savanna wars and eaten in religious rituals.
region (the cerrado) of central Brazil or occupied the On the whole, diets were largely vegetarian - low
great swampland (the pantanal) of western Mato in animal fats but rich in vitamins and vegetable
Grosso and Bolivia. Either too little water for 6 protein from beans, peanuts, and amaranth — with
months in the cerrado or too much in the pantanal some animal protein from fish, birds, and animals.
during the rainy season forced people to migrate The lack of dairy cattle and goats, however, often
with the changing seasons. meant calcium deprivation in weaned babies and
Further south more propitious conditions for set- children and osteomalacia in adult women who had
tlement existed along thefloodplainsof the Parana- multiple pregnancies. In fact, ceramic figurines from
Paraguay rivers, where the Guarani lived a settled western Mexico and the west coast of South America
agricultural life-style in small towns and villages. that depict bed-ridden females with "deformities and
Linguistically related to them were the Tupi, who bowing of the lower extremities" may document cal-

cium deprivation in pre-Columbian women (Weis- Evidence for the presence of treponematoses (vene-
man 1966). Otherwise, limited skeletal analysis real syphilis, yaws, endemic syphilis, and pinta) also
from Peru suggests that the pre-Columbian people exists for Peru and northern South America. Al-
as a group were healthy and diedfromaccidents and though the debate on the origin of venereal syphilis
war injuries, old age, and ritual sacrifices rather continues unabated, skeletal remains suggest that
than from frequent epidemic diseases. There is, how- some type of treponemal disease existed in South
ever, some evidence from bone scars for a severe America before 1500 (see Buikstra in this volume,
childhood febrile illness among the coastal cultures V.8). Some deformations in bone surfaces in skele-
of Paracas, Nazca, and lea (Allison, Mendoza, and tons and a skull from Paracas in coastal Peru sug-
Pezzia 1974). All this would change with the arrival gest venereal syphilis (Cabieses 1979). Sixteenth-
of the Europeans and their African slaves, who century chroniclers in Peru also described bubas (a
would alter both the diet and disease environment of word used for syphilis and yaws) in Spanish con-
South America. quistadores, such as Diego de Almagro, who had
had sexual intercourse with Indian women. Further-
Pre-Columbian Diseases more, in sixteenth-century Chile more Spaniards
On the eve of the European arrival, there are only a than Indians suffered from bubas (Costa-Casaretto
limited number of diseases that can be documented 1980), which may suggest that the Indians had a
for South America. The best evidence survives for longer experience with a treponemal disease than
Peru in the ceramics of the Moche and Chimu, who did the Spaniards. At that time it was a "seem-
accurately depicted diseases, ulcers, tumors, and con- ingly venereal ailment that produced genital se-
genital or acquired deformities in their portrait pots, cretions" (Cabieses 1979). According to Francisco
and in the remains of mummies and skeletons pre- Lopez de Gomara, "all Peruvians" suffered from
served in the coastal deserts and at high altitudes in bubas (Cabieses 1979). The problem, however, is
the Andes (Perera Prast 1970; Home and Kawasaki that bubas is such a vague term used for skin sores
1984). or ulcers that it could refer to verruga (Carri6n's
Because so many ancient Peruvians lived in disease) and yaws, whereas Cabieses (1979) believes
crowded towns and cities, it is hardly surprising that that bubas descriptions resemble Nicolas—Favre dis-
paleopathologists have found evidence for tuberculo- ease (lymphogranuloma).
sis, a disease so often associated with urban popula- Another treponemal disease, pinta (also carate),
tions (Cabieses 1979). In a study of 11 mummies from was called ccara by the Incas (Guerra 1979) and is
Chile and Peru, two dating from A.D. 290 had "cavi- now endemic in Colombia. Descriptions of pinta in
tary pulmonary lesions from the walls of which acid- Colombia date from the arrival of the Spanish, who
fast bacilli were recovered." According to William adopted the Indian name for the disease: carate. The
Sharpe, two of these mummies have "diagnoses of Jesuit Juan de Velasco often observed the disease,
tuberculosis about as solidly established as paleo- and it seems to have been a common skin disease in
pathologic techniques will permit" (Sharpe 1983). slaves (Chandler 1972). Colombia is also one of the
A second disease for which convincing evidence few countries in which yaws, pinta, and venereal
survives is arthritis. According to Fernando Cabieses syphilis occur together (Hopkins and Fl6rez 1977).
(1979), Peruvian museums have many vertebrae and Possibly confused with treponemal diseases that
bones that reveal "typically rheumatic injuries." cause skin changes was bartonellosis (Carri6n's dis-
While examining these remains, A. Hrdlicka discov- ease, Oroya fever, Peruvian verruga). Characterized
ered a type of arthritis of the hip in adolescents, by high fever, anemia, and a warty eruption on the
which modern experts identify as Calve-Perthes dis- skin, it severely afflicted Francisco Pizarro's soldiers
ease (Cabieses 1979). Another specific study on bone when they invaded Peru (Hirsch 1885). In one area
lesions in skeletons from Chancay, in coastal Peru, of Ecuador, Spanish soldiers died of it within 24
documents osteoarthritis in the skeletal remains hours or suffered from warts "as large as hazelnuts,"
(Berg 1972), and Jane Buikstra (in this volume, V.8) whereas the Indians experienced less severe forms of
reports a "convincing case of juvenile rheumatoid the disease (Cabieses 1979). Pre-Columbian ceram-
arthritis in an adolescentfromthe Tiwanaku period." ics depict the warty eruptions of the disease,
A mummy of a young girl of the Huari culture exhib- whereas a case of Carrion's disease in the warty
its "one of the earliest known cases of collagen dis- phase has been documented in a mummy of the
ease" with "many aspects compatible with SLE" (sys- Tiwanaku culture (Allison et al. 1974b). On the ba-
temic lupus erythematosus) (Allison et al. 1977). sis of this evidence, as well as the high Spanish

mortality in verruga areas in the Andes, there is ceus), which means wild fire in English and is en-
little doubt that this endemic disease was of great demic in central Brazil along the Tocantins and Pa-
antiquity in the Peruvian Andes (Herrer and Chris- rana rivers and their tributaries. In 1902—3,
tensen 1975). Caramuru Paes Leme reported it among the Indians
Another old Peruvian disease is uta, a type of living along the Araguaia River of central Brazil,
leishmaniasis (Herrer and Christensen 1975). The whereas another good description of the disease from
Spanish called it the "cancer of the Andes," since it 1900 dates from Bahia, a state near the Tocantins
left ulcers on the nose and lips and often destroyed River. Apparently, fogo selvagem was limited in inci-
the septum. Pedro Pizarro may have described it dence as long as the Brazilian interior was sparsely
when he reported that "those who entered the jungle settled or people avoided living along the rivers.
contracted a 'disease of the nose' very similar to Since the construction of Brasilia and the opening of
leprosy for which there was no cure" (Cabieses the interior to the landless poor, the disease has
1979). Ceramic evidence of mutilated noses and lips spread to Acre, Amazonas, and Rondonia, where it
also documents the existence of uta in the pre- was once unknown, as well as to neighboring coun-
Columbian period for Colombia and Peru. A pre- tries (Diaz et al. 1989).
Columbian ceramic from Cundinamarca, Colombia, Since many of the pre-Columbian peoples in the
where leishmaniasis is now endemic, depicted "muti- Andes raised animals for food and wool or kept them
lated nasal tissue" on an Indian's face (Werner and as pets, intestinal parasites may have been common.
Barreto 1981). Some parasite remains have been recovered in autop-
In contrast to uta and Carri6n's disease, American sies on mummies from Chile and Peru. An examina-
trypanosomiasis (Chagas' disease) is difficult to docu- tion of the body of a young boy revealed Trichuris
ment before the sixteenth century. It is, however, trichiura ova as well as those for head lice (Home
unquestionably of New World origin, because the and Kawasaki 1984). According to chroniclers, the
vectors and the disease do not exist outside of the poor in the Inca Empire had to "pay tribute in the
Americas. Now one of the most important vector- form of small containers of lice." Not surprisingly,
borne diseases in South America, Chagas' disease typhus was "a very common disease in ancient Peru"
extends throughout much of the interior of South (Cabieses 1979). Evidence of pinworms from Chile
America, but especially from northeastern Brazil to and hookworm from Brazil has been collected in
north central Argentina in a wide savanna corridor fossilized feces (Parasitologista 1986), whereas a
sandwiched between the coastal forests and the tropi- mummy of the Tiwanaku culture yielded hook-
cal rain forests of the Amazon (Bucher and Schofield worms from around A.D. 900 (Allison et al. 1974a).
1981; Schofield, Apt, and Miles 1982). Because this Tunga penetrans, the chigger that burrows into the
region was remote from the Incas or coastal Euro- feet where it lays its eggs and causes painful foot
pean settlements, historians know little about the ulcers, was native to Brazil. In the nineteenth cen-
disease before 1500. The earliest descriptions of tury it spread to Africa (Crosby 1986) and thus was
Chagas' disease symptoms were made in sixteenth- one of the few New World vectors to migrate to the
century Brazil, whereas those for the vectors Old World.
(triatomine bugs) date from the sixteenth century On the eve of the conquest, the people of South
for Chile, Argentina, and Peru and the seventeenth America had a limited number of diseases: tuberculo-
century for Bolivia, where the illness is still endemic sis, arthritis, and one or more treponemal diseases -
(Buck, Sasaki, and Anderson 1968; Guerra 1970; Carri6n's disease, uta, Chagas' disease, endemic goi-
Schofield et al. 1982). Charles Darwin was attacked ter, and hookworm infestation. In addition, many
by triatomine bugs - what he termed "Benchuca" - doubtless suffered from nonlethal diarrheas caused
when he traveled through endemic areas in 1835 by other worms and parasites as well as from foot
(Schofield et al. 1982). Because of the way in which ulcers caused by the chigger. Unspecified fevers,
Chagas' disease causes facial edema, it was some- such as typhus, also caused ill health; and viruses
times confused with endemic goiter, which often oc- have even been found in a well-preserved mummy
curred in the same regions because of the lack of salt from near Santiago, Chile (Home and Kawasaki
in the diet (Guerra 1970). The Incas identified goiter 1984). Not all diseases existed everywhere, however,
as coto (Guerra 1979). because of known environmental limitations, par-
Another disease of the Brazilian interior that may ticularly of the vectors. Carrion's disease, for exam-
have existed among "the aborigines of Brazil" (Silva ple, occurs only where the sandfly lives, whereas
1971) is fogo selvagem (endemic pemphigus folia- Chagas' disease follows the range of the triatomine

insects. Thus, prior to 1500, diseases were limited to respiratory diseases, which early missionaries and
specific environments (tuberculosis in the cities and miners inadvertently encouraged by gathering Indi-
towns) or vectors, and few deadly epidemics deci- ans into mission villages and mines, where influ-
mated populations. enza and the common cold could sweep from person
to person with lethal impact. Pneumonia, tuberculo-
Old World Diseases sis, and bronchitis also preyed on the survivors. Peru-
Which of the new diseases brought to the New World vian Indians forced to work in the mines died of
by the Europeans first touched South America is pneumoconiosis and silicosis (Munizaga et al. 1975);
unknown, but the best documented disease in terms only by fleeing the missions, mines, and European
of its progression is smallpox. In 1514 smallpox may settlements could Indians survive. In the 1990s,
have arrived in Panama with a group of Spanish their descendants still confront, and die of, the same
colonists (Hopkins 1983). Because of frequent trade diseases.
and communication between the isthmus and Peru, Because so many Indians could and did flee into
smallpox preceded the Spanish into the Inca Empire. the interior, the impact of European diseases in
A devastating illness of the mid-1520s, character- sixteenth-century South America was uneven and
ized by "fever, rash, and high mortality," struck the possibly less catastrophic in some regions than in
Inca and his imperial court in Quito and killed the Mexico. Population decline in the southern high-
Inca, Huayna Capac; it also killed many in the capi- lands of Peru, for example, was not as precipitous as
tal of Cuzco. Henceforth, smallpox would sweep in coastal Peru (Cook 1981) or central Mexico. None-
ahead of the Spanish conquistadores and claim thou- theless, all peoples would eventually suffer depopula-
sands of victims before they arrived. By 1554 it had tion as a result of flight, disease, forced labor, war-
reached as far south as Chile, where it attacked the fare, and the massive disruptions in indigenous food
Araucanians. A year later it appeared at Rio de supply and consumption that accompanied the Euro-
Janeiro among a group of French Huguenots, who pean conquests. In other words, although environ-
spread it to the coastal Indians. They in turn fled mental diversity blunted the catastrophe that so
into the interior, where they passed it on to others quickly overtook the Caribbean and Mexican popula-
living far from the coast. By the 1590s it was deci- tions in the sixteenth century, it also prolonged the
mating the Indians of Paraguay (Luque 1941). Jesuit trauma of the impact of disease through the centu-
missionaries unwittingly took the contagion as far ries until the present.
inland as the Upper Amazon, and from the seven- On the other hand, much of South America's en-
teenth century on, smallpox epidemics reappeared vironment facilitated the establishment of new
in even the most remote parts of the interior. The mosquito-borne diseases in the tropical lowlands of
continuous arrival of ships from Portugal, Spain, northern South America, the Amazon basin, and
and Africa would renew the epidemics, and, because coastal Brazil. These diseases came from Europe and
control measures were often ineffective, smallpox from Africa aboard slave ships and in the bodies of
would continue to ravage South America until it was the African slaves forcibly imported into South
finally eradicated in Brazil in 1971 (Hopkins 1983; America.
RuffiS and Sournia 1984; Lanning 1985; Alden and The first of these great killers was malaria; when
Miller 1987). and where and in what form its parasites and vec-
Less easily traced but often as virulent in its im- tors entered the continent has long been debated
pact on the Indians was measles, which often accom- (Dunn 1965). Malaria may have been indigenous
panied smallpox epidemics or was confused with the and hence may have been the reason ancient Peruvi-
disease. It arrived in Peru in 1530-1 (Ruffi6 and ans built their houses far from the rivers (Cabieses
Sournia 1984), settled in among all population 1979); it also might have been one of the "fevers"
groups, exacted a high cost in lives among mission that attacked the Inca armies as they invaded the
Indians and Africans in the slave trade, and re- Upper Amazon (Cabieses 1979). On the other hand,
appeared in frequent epidemics throughout the cen- this seems unlikely, given population densities
turies (Luque 1941). It continued to attack isolated achieved in the Upper Amazon before the conquest.
Indians as late as the 1980s, as road builders and Prevailing opinion is that malaria was an im-
settlers opened up the Amazon region to migrants ported disease, and one or more strains of malarial
and their children from endemic-measles areas. parasites were undoubtedly introduced into the
Next to smallpox and measles, possibly the major Americas in the sixteenth century from endemic ar-
killers of the Indians, past and present, were the eas in Europe and Africa (and, as a matter of fact, as

late as 1930 when an epidemic spread by A. gambiae public health programs in coastal cities of South
erupted with particular virulence in Brazil) (Marks America has led to the reappearance of the vector A.
and Beatty 1976). Sixteenth-century Jesuits re- aegypti in cities such as Rio de Janeiro and sporadic
corded attacks of fever throughout the tropics; and a outbreaks of yellow fever. Most cases continue to be
century later Europeans discovered the treatment reported in the Amazon region or other parts of
for these fevers, cinchona bark (the source of quina rural, tropical South America. As James Ward con-
or quinine), but did not use it very effectively (Luque cluded in 1972, "Yellow fever is not a disease of the
1941; Dunn 1965; McCosh 1977). In the eighteenth past" but rather "a disease of the present" in South
century, malaria was known as sezoes in the Brazil- America.
ian interior, and by the nineteenth century as inter- A third tropical fever is dengue, which attacked
mittent or pernicious fever (Documentos 1942; Lima, Peru, in 1818 and northern South America in
Karasch 1987). More recently, scientists identified the 1820s. By the 1840s it had reached Rio de Ja-
and classified the parasites and vectors as causal neiro (Hirsch 1883). Since that time, dengue is often
agents, and widespread spraying with insecticides difficult to trace because of its confusion with other
followed, retarding malarial incidence until the fevers. With the eradication of its vector, A. aegypti
1980s, when it once again became a serious problem (which also carries yellow fever), in twentieth-
of health. A chloroquinine-resistant strain of para- century coastal cities, dengue retreated until the
site, and massive deforestations in Rondonia and 1980s, when it again swept urban, southeastern
other parts of the Amazon have led to significant Brazil - wherever the vector had reestablished itself
outbreaks of malaria among miners, Indians, and owing to faltering public health campaigns. By 1990
settlers in the region. it was in the Amazon region as far inland as Iquitos,
Urban yellow fever is more easily traced than Peru.
malaria in historical sources, owing to the distinc- Next to the tropical fevers in virulence were other
tive bloody (black) vomit and high mortality with diseases that reached South America from Africa.
which it is associated (Goodyear 1978). One of the As long as the slave trade with Africa existed, so too
first unmistakable descriptions of the disease dates did epidemics associated with Africans and the trade
from 1623, when Aleixo de Abreu, who had served in (Karasch 1987). Thus, until the effective abolition of
Brazil and Africa, wrote his Treatise of the Seven the slave trade to Brazil in 1850, smallpox and mea-
Diseases in which he described a "disease of the sles attacked slave ships and port cities or wherever
worm" marked by blood vomit. The disease, hence- infected Africans were unloaded for sale. Dysentery
forth to be called bicha or os males (the evils), took (Hirsch 1886; Karasch 1987) preyed on those con-
epidemic form in Pernambuco in the northeast of fined to slave ships and the great slave markets of
Brazil between 1685 and 1694 (Rosa and Franco Cartagena, Salvador, Buenos Aires, and Rio de Ja-
1971) and then apparently disappeared until it at- neiro. From the markets it often spread to kill un-
tacked Salvador and Rio de Janeiro in 1849 (Ward told victims in the coastal cities and neighboring
1972; Cooper 1975). Indian missions. Intestinal parasites infested most
The first good descriptions of sylvan or jungle yel- slaves, and sometimes led to wormy ulcers in the
low fever date from 1898-9 from the interior of Sao rectum, the malady known as bicho or maculo in
Paulo when the authorities encountered cases of yel- Brazil and Africa (Guerra 1970). Schistosomiasis (S.
low fever "in full virgin forest" (Franco 1969). Since mansoni) settled into coastal Brazil (Silva 1983),
the mid-nineteenth century, yellow fever (in both its Suriname, and Venezuela (WHO 1985), whereas lep-
urban and sylvan forms) has swept through tropical rosy reached into the interior of the continent to as
and subtropical South America (Henschen 1966). Be- far as Goias in the eighteenth century and the tropi-
cause of successful twentieth-century eradication cal lowlands of Colombia. Filarial worms (filariasis)
programs that began with the efforts of Osvaldo found congenial breeding grounds in the swampy
Cruz in Brazil in 1903, yellow fever was eliminated lowlands of Brazil and northern South America, and
from many parts of the continent. It has, however, soon the bodies of their human hosts swelled to "ele-
resumed the offensive in the 1980s as settlers have phantine size." The African disease ainhum, which
moved into areas of sylvan yellow fever or built led to the loss of toes, was observed in slaves in
towns in the Amazon region that created optimal Brazil (Peixoto 1909). Blinding eye diseases of con-
breeding conditions for A. aegypti, the most promi- junctivitis and trachoma (ophthalmia) accompanied
nent vector of the disease, and thus for the transmis- slave ships and attacked coastal cities and planta-
sion of urban yellow fever. Indeed, the breakdown in tion areas. Onchocerciasis found new vectors in

northern South America and settled into the river 1986). It also attacked Argentina and appeared in a
valleys of Colombia's Pacific lowlands (Trapido, major epidemic during the Paraguayan War (1864-
D'Alessandro, and Little 1971), Venezuela, and 70), where it claimed both civilian and military lives
northern Brazil (Pan American 1974). The Guinea (Reber 1988). Cholera continued to reappear in epi-
worm arrived in the bodies of Africans, along with a demics throughout the continent until twentieth-
variety of other worms and parasites. The sarna, or century public health campaigns brought it under
"itch," caused epidemics of itching on ships and in control.
ports, whereas scurvy, pellagra, and beriberi, as well Another Asiatic disease that has settled into
as other nutritional diseases, affected slaves fed South America is the bubonic plague. How it came to
manioc or corn with beans and a little dried beef. survive in countries as far distant as Brazil and
Yaws swept through slave quarters and settled down Ecuador is still uncertain. In 1899 the plague broke
among blacks in coastal Colombia, where it is still out in Rio de Janeiro and Santos (Vianna 1975).
endemic (Chandler 1972). In blacks it was often con- About 9 years later, in 1908, merchant ships intro-
fused with syphilis. Once the slave trade ended, the duced the plague into the port of Guayaquil and
most lasting legacy of these waves of epidemics was coastal Ecuador, from which it spread to the high-
the establishment of the African diseases as endemic land populations, among whom it was still endemic
diseases in tropical South America. in the 1930s (Jervis 1967). Most cases of plague,
The diseases of the slave trade were followed by a however, occurred in Brazil, especially in the region
new wave of diseases in the nineteenth century, as of the Northeast. In 1903 an epidemic of plague
European and Asian immigrants replaced the Afri- broke out in Maranhao and Para, and the disease
cans. German colonists brought epidemics of typhus was well established in the interior of Pernambuco
to southern Brazil, whereas severe outbreaks of by the 1920s (Oliveira 1975; Vianna 1975). In 1973
diphtheria and scarlet fever, probably accompany- Brazil registered 35 percent of the cases of plague
ing the Europeans, attacked southern South Amer- reported to the World Health Organization (Marks
ica (Hirsch 1883; Karasch 1987). This was, how- and Beatty 1976). Over 10 years later, from 1984 to
ever, not the first time diphtheria had appeared in 1986, epidemics of bubonic plague erupted in
South America. In 1614 it struck Cuzco, Peru, and Paraiba and Minas Gerais, but isolated cases occur
reportedly touched every household (Marks and every year in the states of Ceara and Bahia. Only
Beatty 1976; Cook 1981). As once small towns grew rapid medical intervention prevents a high mortal-
into densely crowded cities with slums lacking ity (Peste 1986).
clean water or sewer systems, the incidence of ty- In most of the twentieth century, public health
phoid fever increased and hepatitis worsened. programs and massive immunization projects, com-
Tuberculosis attacked the black slaves and the bined with the removal of mosquitoes and their habi-
poor of the growing cities with exceptional viru- tats, led to the control of many epidemic diseases.
lence. Indeed after the late nineteenth century, pos- Exceptions are the great influenza epidemic of 1918-
sibly more died of tuberculosis in cities like Rio de 19, which exacted the same high cost in lives in South
Janeiro than of the "great tropical killers" as a America as elsewhere in the world, and the AIDS
result of swamp removals and public health cam- epidemic of the 1980s, which rages unchecked in the
paigns against mosquito habitats. As so many rural heterosexual population of Brazil. In the 1960s mod-
migrants crowded into urban slums with precarious ern medicine and scientific technology had seemed to
food, water, and health care, the frequency and viru- be victorious over epidemic disease, but in the 1980s
lence of these "urban" diseases increased dramati- the deteriorating economies of South America have
cally. stifled public health and immunization programs.
These urban slum populations would be among Children's diseases such as measles, chickenpox, and
those to fall prey to a new disease that appeared in pertussis once more prey on the nonvaccinated,
South America for the first time in the nineteenth whereas polio cripples children and meningitis
century: Asiatic cholera. This Asian import was first sweeps through the slums of Brazil. Diarrhea and
reported among sailors coming from Europe to Bra- dehydration kill infants, and intestinal parasites
zil in 1855. The first Brazilian case occurred in plague the poor. Schistosomiasis saps their strength,
Belem in 1855 with the next in Salvador about a and Chagas' disease extends its range as deforesta-
month later, followed by cases in Rio de Janeiro. tion changes habitats and people continue to live in
This first great epidemic of 1855-6 may have thatched-roof houses, where the vector hides. Ma-
claimed up to 200,000 lives in Brazil alone (Cooper laria, yellow fever, and dengue have once more re-

sumed the offensive as a result of the environmental Berg, Ed. 1972. Paleopathology: Bone lesions in ancient
changes in the Amazon region and the reestablish- peoples. Clinical Orthopaedics and Related Research
ment of vectors in the towns and cities. While the 82: 263-7.
ancient Peruvian fevers still attack and disfigure the Bowers, John Z., and Elizabeth F. Purcell, eds. 1979. As-
rural poor, unknown but deadly fevers have erupted pects of the history of medicine in Latin America. New
in settlers along the Trans-Amazon Highway. Viral York.
Bucher, E. H., and C. J. Schofield. 1981. Economic as-
hemorrhagic fevers, for example, whose victims died
sault on Chagas' disease. New Scientist, October 29,
of massive bloody hemorrhages, erupted in the 1970s 321-4.
and 1980s. Even cholera reappeared in South Amer- Buck, Alfred A., Tom T. Sasaki, and Robert I. Anderson.
ica in the early 1990s. 1968. Health and disease in four Peruvian villages:
The combination of population growth, environ- Contrasts in epidemiology. Baltimore, Md.
mental devastation, and deteriorating public health Cabieses, Fernando. 1979. Diseases and the concept of
services due to a debt crisis and capital outflows have disease in ancient Peru. In Aspects of the history of
led to severe setbacks in the modern campaigns to medicine in Latin America, ed. John Z. Bowers and
contain epidemic disease in South America. As the Elizabeth F. Purcell, 16-53. New York.
number of rural and urban poor increase, so too does Campos, Hermenegildo Lopes de. 1909. Climatologia
the frequency of disease, since so many diseases, such medica do estado do Amazonas, 2d edition. Manaus.
as Chagas', hepatitis, and typhoid, are often linked to Chandler, David L. 1972. Health and slavery: A study of
health conditions among Negro slaves in the viceroy-
low socioeconomic standards of living. Thus, al-
alty of New Granada and its associated slave trade,
though once isolated from the onslaught of Old World 1600-1810. Ph.D. dissertation, Tulane University,
diseases, the South American continent now suffers New Orleans.
from all those illnesses that international travelers Cook, Noble David. 1981. Demographic collapse: Indian
carry with them from the urban coastal cities to the Peru, 1520-1620. Cambridge.
most remote parts of the Amazon region. Unless eco- Cooper, Donald B. 1975. Brazil's long fight against epi-
nomic and political strategies are developed to im- demic disease, 1849-1917, with special emphasis on
prove public health in the 1990s, the diseases of both yellow fever. Bulletin of the History ofNew York Acad-
the Old and the New World will continue to flourish emy of Medicine 51: 672-96.
and grow in virulence in South America. 1986. The new "Black Death": Cholera in Brazil, 1855-
Mary C. Karasch 1856. Social Science History 10: 467-88.
Costa-Casaretto, Claudio. 1980. Las enfermedades vene-
reas en Chile desde el descubrimiento hasta la co-
Bibliography lonia. Revista Medica de Chile 108: 969-76.
Ackerknecht, Erwin H. 1965. History and geography of the Crosby, Alfred W. 1986. Ecological imperialism: The bio-
most important diseases. New York and London. logical expansion of Europe, 900-1900. Cambridge.
Alden, Dauril, and Joseph C. Miller. 1987. Unwanted car- Diaz, Luis A., et al. 1989. Endemic pemphigus foliaceus
goes: The origins and dissemination of smallpox via (Fogo Selvagem): II. Current and historic epidemio-
the slave trade from Africa to Brazil, c. 1560—1830. In logic studies. Journal of Investigative Dermatology 92:
The African exchange: Toward a biological history of 4-12.
black people, ed. Kenneth F. Kiple, 35-109. Durham Documentos relativos ao Brasil. 1942. Boletim do Arquivo
and London. Histdrico Militar 12: 232.
Allison, Marvin J., et al. 1974a. A case of hookworm infes- Dunn, Frederick L. 1965. On the antiquity of malaria in
tation in a Precolumbian American. American Jour- the Western Hemisphere. Human Biology 37: 385-93.
nal of Anthropology 41: 103-6. Franco, Odair. 1969. Hist6ria da Febre-Amarela no Brasil.
1974b. A case of Carrion's disease associated with hu- Revista Brasileira de Malariologia e Doencas Tropi-
man sacrifice from the Huari culture of southern cals 21: 315-511.
Peru. American Journal of Physical Anthropology 41: Gache, Samuel. 1895. Climatologie midicale de la Repu-
295-300. blique Argentine at des principales villes d'AmArique.
Allison, Marvin J., Daniel Mendoza, and Alejandro Pezzia. Buenos Aires.
1974. A radiographic approach to childhood illness in Gajardo Tobar, Roberto. 1979. Las enfermedades de los
Precolumbian inhabitants of southern Peru. Ameri- aborigenes y el cataclismo que siguio a la conquista.
can Journal of Physical Anthropology 40: 409-15. Revista Medica de Chile 107: 182-4.
Allison, Marvin J., et al. 1977. Generalized connective Goodyear, James D. 1978. The sugar connection: A new
tissue disease in a mummy from the Huari culture perspective on the history of yellow fever. Bulletin of
(Peru). Bulletin of the New York Academy of Medicine the History of Medicine 52: 5-21.
53: 292-301. Guerra, F. 1970. American trypanosomiasis: An historical

and a human lesson. Journal of Tropical Medicine and Peste bubonica mata dois de uma mesma familia na
Hygiene 72: 83-104; and 73: 105-18. Paraiba. 1986. Jornal do Brasil, October 16.
Guerra, Francisco. 1979. Pre-Columbian medicine: Its in- Reber, Vera Blinn. 1988. The demographics of Paraguay:
fluence on medicine in Latin America today. In As- A reinterpretation of the Great War, 1864-70. His-
pects of the history of medicine in Latin America, ed. panic American Historical Review 68: 289-319.
John Z. Bowers and Elizabeth F. Purcell, 1-15. New Rodrigues, Bichat A. 1975. Smallpox eradication in the
York. Americas. Pan American Health Organization Bulle-
Henschen, Folke. 1966. The history and geography of distin 9: 53-68.
eases, trans. Joan Tate. New York. Roosevelt, Anna. 1989. Lost civilizations of the lower Ama-
Herrer, Aristides, and Howard A. Christensen. 1975. Impli- zon. Natural History 2: 76-82.
cation of Phlebotomus sand flies as vectors of bar- Rosa, Joao Ferreira da, and Odair Franco. 1971. A febre
tonellosis and leishmaniasis as early as 1764. Science amarela no seculo XVII no Brasil. Rio de Janeiro.
190: 154-5. Ruffle, Jacques, and Jean-Charles Sournia. 1984. Les
Hirsch, August. 1883—6. Handbook of geographical and epidemies dans I'histoire de I'homme. Paris.
historical pathology, 3 vols., trans. Charles Creighton. Salterain, Joaquin de. 1884. Contribucion al estudio del
London. desarrollo y profilaxia: Epidemicas en Montevideo.
Hopkins, Donald R. 1983. Princes and peasants: Smallpox Montevideo.
in history. Chicago. Sasa, Manabu. 1976. Human filariasis: A global survey of
Hopkins, Donald R., and Daniel Florez. 1977. Pinta, yaws, epidemiology and control. Baltimore.
and venereal syphilis in Colombia. International Jour- Schofield, C. J., W. Apt, and M. A. Miles. 1982. The
nal of Epidemiology 6: 349-55. ecology of Chagas' disease in Chile. Ecology of Dis-
Home, Patrick D., and Silvia Quevedo Kawasaki. 1984. ease 1: 117-29.
The prince of El Plomo: A paleopathological study. Sharpe, William D. 1983. Essay-Review. Transactions and
Bulletin of the New York Academy of Medicine 60: Studies of the College of Physicians of Philadelphia,
925-31. Ser. 5(5): 278-81.
Jervis, Oswaldo. 1967. La peste en el Ecuador de 1908 a Silva, J. Ramos e. 1971. Id6ias gerais sobre o penfigo sul-
[sic] 1965. Boletin de la Oficina Sanitaria Panameri- americano; Seu hist6rico no Brasil; Conceituagao
cana 62: 418-27. atual do grupo penfigo. Revista Brasileira de Medicina
Karasch, Mary C. 1987. Slave life in Rio de Janeiro, 1808- 28: 611-15.
1850. Princeton, N.J. Silva, Luiz Jacintho da. 1983. Sobre a antiguidade de
Lanning, John Tate. 1985. The royal protomedicato: The alguns focos de esquistossomose do estado de Sao
regulation of the medical professions in the Spanish Paulo. Revista Brasileira de Malariologia e Doencas
Empire, ed. John Jay TePaske. Durham, N.C. Tropicais 35: 73—8. Rio de Janeiro.
Luque, Pedro Leon. 1941. Apuntes histdricos sobre Stevens, William K. 1989. Andean culture found to be as
epidemiologia Americana con especial referenda al old as the great pyramids. New York Times, October 3.
Rio de la Plata. Cordoba. Strong, Richard P., et al. 1915. Report of first expedition to
Marks, Geoffrey, and William K. Beatty. 1976. Epidemics. South America 1913. Cambridge.
New York. Trapido, H., A. D'Alessandro, and M. D. Little. 1971.
McCosh, Fred. 1977. Malaria and goitre in South America Onchocerciasis in Colombia: Historical background
one hundred and fifty years ago. Central African Jour- and ecologic observations. American Journal of Tropi-
nal of Medicine 23: 254-8. cal Medicine and Hygiene 20: 104—8.
Munizaga, Juan, et al. 1975. Pneumoconiosis in Chilean Van Thiel, P. H. 1971. History of the control of endemic
miners of the 16th century. Bulletin of the New York diseases in the Netherlands Overseas Territories. An-
Academy of Medicine 51: 1281-93. nales de la Societe Beige de Midecine Tropicale 51:
Oliveira, Valdemar de. 1975. No tempo de Amaury. Recife. 443-57. Antwerpen.
Pan American Health Organization. 1974. Research and Vianna, Arthur. 1975. As epidemias no Pard, 2d edition.
control of onchocerciasis in the Western Hemisphere. Belem.
Proceedings of an international symposium. Scientific Ward, James S. 1972. Yellow fever in Latin America: A
Publication No. 298. Washington, D.C. geographical study. Liverpool.
Parasitologista estuda doengas pre-colombianas. 1986. Weisman, Abner 1.1966. Pre-Columbian artifacts portray-
Jornal do Brasil, August 17. ing illness. Bulletin of the Menninger Clinic 30: 39—44.
Peixoto, Afranio. 1909. Climat et maladies du Bresil. Rio Werner, J. Kirwin, and Pablo Barreto. 1981. Leish-
de Janeiro. maniasis in Colombia, a review. American Journal of
Perera Prast, D. Arturo. 1970. Las representaciones Tropical Medicine and Hygiene 30: 751—61.
patol6gicas en la ceramica precolombiana del Peru. WHO Expert Committee. 1985. The control of schis-
Anales de la Real Academia Nacional de Medicina 87: tosomiasis. WHO Technical Report Series No. 728.
403-8. Geneva.

PART VIII
Major Human Diseases
Past and Present

VIII. 1. Acquired Immune Deficiency Syndrome (AIDS) 547
biological and geographic origins of the organism

vni.i remain obscure, the AIDS epidemic appears to mark
the first time this organism has spread widely in
Acquired Immune Deficiency human populations. There is no evidence for casual
Syndrome (AIDS) transmission of HIV.
Following the identification of HIV-1, tests to de-
tect antiviral antibodies to the virus were devised in
Acquired immune deficiency syndrome (AIDS), first 1984. Although these tests do not detect the virus
identified in 1981, is an infectious disease character- itself, they are generally effective in identifying in-
ized by a failure of the body's immunologic system. fection because high levels of antibody are produced
As a result, affected individuals become increasingly in most infected individuals. The enzyme-linked
vulnerable to many normally harmless microorgan- immunosorbant assay (ELISA), followed by Western
isms, eventually leading to severe morbidity and blot testing, has made possible the screening of do-
high mortality. The infection, spread sexually and nated blood to protect the blood supply from HIV, as
through blood, has a high fatality rate, approaching well as testing for epidemiological and diagnostic
100 percent. Caused by a human retrovirus known purposes.
as HIV-1, AIDS can now be found throughout the
world - in both Western industrialized countries and
also the developing nations of Africa and Latin Distribution and Incidence
America. Although identified only in 1981, AIDS can now be
Although precise epidemiological data remain un- found throughout the world. Spread by sexual con-
known, public health officials throughout the world tact, by infected blood and blood products, and
have focused attention on this pandemic and its po- perinatally from mother to infant, AIDS had been
tentially catastrophic impact on health, resources, reported in 138 countries by July 1988, according to
and social structure. Treatments for the disease the World Health Organization. Since HIV infection
have been developed, but there is currently no cure precedes the development of AIDS, often by as many
or vaccine. as 7 to 11 years, the precise parameters of the epi-
demic have been difficult to define. Estimates sug-
Etiology and Epidemiology gest that worldwide between 5 and 10 million indi-
Beginning in the late 1970s, physicians in New York viduals were infected with the virus by the end of
and California reported the increasing occurrence of 1988. At that time, in the United States more than
a rare type of cancer, Kaposi's sarcoma, and a variety 80,000 cases of AIDS had occurred, and nearly
of infections including pneumocystis pneumonia 50,000 of these individuals had died. Projections by
among previously healthy young homosexual men. the U.S. Public Health Service Centers for Disease
Because of the unusual character of these diseases, Control estimate that between 1.5 and 2.0 million
which are typically associated with a failure of the Americans are infected with HIV but are currently
immune system, epidemiologists began to search for asymptomatic. Although the "cofactors" that may
characteristics that might link these cases. AIDS was determine the onset of symptoms remain unknown,
first formally described in 1981, although it now ap- all current evidence suggests that HIV-infected indi-
pears that the virus that causes the disease must viduals will eventually develop AIDS.
have been silently spreading in a number of popula- Researchers have identified three epidemiological
tions during the previous decade. Early epidemio- patterns of HIV transmission, which roughly follow
logical studies suggested that homosexual men, geographic boundaries. Pattern I includes North
recipients of blood transfusions and blood products America, Western Europe, Australia, New Zealand,
(especially hemophiliacs), and intravenous drug us- and many urban centers in Latin America. In these
ers were at greatest risk for the disease. For this industrial, highly developed areas, transmission
reason, research focused on a search for a common has been predominantly among homosexual and bi-
infectious agent that could be transmitted sexually or sexual men. Since the introduction of widespread
through blood. This research led to the identification blood screening, transmission via blood now occurs
in 1983, in French and American laboratories, of a principally among intravenous drug users who
previously undescribed human retrovirus. Officially share injection equipment in these areas. Although
named HIV-1 for human immunodeficiency virus, there is no evidence of widespread infection among
this organism is an RNA retrovirus. Although the the heterosexual population in these countries, het-

548 VIII. Major Human Diseases Past and Present
erosexual transmission of the virus from those in- tory of infection with this agent remains unclear, as
fected via intravenous drug use has increased, lead- does its prevalence.
ing to a rise in pediatric cases resulting from
perinatal transmission. Immunology
Within the United States the distribution of AIDS HIV cripples the body's immunologic system, mak-
cases has been marked by a disproportionate repre- ing an infected individual vulnerable to other
sentation of the poor and minorities. As the principal disease-causing agents in the environment. The
mode of transmission has shifted to intravenous drug most common of these opportunistic infections in
use, AIDS has increasingly become an affliction of AIDS patients has been pneumocystis pneumonia,
the urban underclass, those at greatest risk for drug an infection previously seen principally among pa-
addiction. Serum surveys reveal that 50 percent or tients receiving immunosuppressive drugs. In addi-
more of the intravenous drug users in New York City tion to pneumocystis, AIDS patients are prone to
are infected with HIV. Blacks and Hispanics, who other infectious agents such as cytomegalovirus
comprise 20 percent of the U.S. population, accounted (CMV), Candida albicans (a yeastlike fungus), and
in 1988 for more than 40 percent of all AIDS cases. Toxoplasma gondii (a protozoan parasite). There is
Women, who account for more than 10 percent of new also evidence that infection with HIV makes indi-
AIDS cases, are typically infected by intravenous viduals more vulnerable to infection with tuberculo-
drug use or by sexual contact with a drug user; in 70 sis. A resurgence of tuberculosis has been reported
percent of all infected newborns, transmission can be in nations with a high incidence of AIDS.
traced to drug use. By 1991, between 10,000 and Immunologic damage occurs by depletion of a spe-
20,000 children in the United States are expected to cific type of immune cell, a white blood cell known as
have symptomatic HIV infections. a helper T4 lymphocyte. Destruction of these cells
In pattern II countries, comprised of sub-Saharan accounts for the vulnerability to many normally
Africa and, increasingly, Latin America, transmis- harmless infectious agents. In some cases, infection
sion of HIV occurs predominantly through heterosex- of the central nervous system with HIV may cause
ual contact. In some urban areas in these countries, damage to the brain and spinal column, resulting in
up to 25 percent of all sexually active adults are severe cognitive and motor dysfunction. In its late
reported to be infected, and a majority of female manifestations, AIDS causes severe wasting. Death
prostitutes are seropositive. In addition, transfusion may occur from infection, functional failure of the
continues to be a mode of transmission because uni- central nervous system, or starvation.
versal screening of blood is not routine. Unsterile
injections and medical procedures may also be con- Clinical Manifestations and Treatment
tributing to the spread of infection. In these areas, HIV infection has a wide spectrum of clinical mani-
perinatal transmission is an important aspect of the festations and pathological abnormalities. After in-
epidemic; in some urban centers at least 5 to 15 fection, an individual may remain free of any symp-
percent of pregnant women have been found to be toms for years, perhaps even a decade or longer.
infected. Some individuals do experience fever, rash, and mal-
Pattern III countries, which include North Africa, aise at the time of infection when antibodies are first
the Middle East, Eastern Europe, Asia, and the Pa- produced. Patients commonly present with general
cific, have thus far experienced less morbidity and lymphadenopathy, weight loss, diarrhea, or an oppor-
mortality from the pandemic. Apparently, HIV-1 tunistic infection. Diagnosis may be confirmed by
was not present in these areas until the mid-1980s; the presence of antibodies for HIV or by a decline in
therefore, fewer than 1 percent of all cases have been T4 helper cells. Most experts now agree that HIV
found in pattern III countries. Infection in these infection itself should be considered a disease regard-
areas has been the result of contact with infected less of symptoms.
individuals from pattern I and II countries, or impor- Research efforts to develop effective therapies
tation of infected blood. The nature of world travel, have centered on antiviral drugs that directly attack
however, has diminished the significance of geo- HIV, as well as drugs likely to enhance the function-
graphic isolation as a means of protecting a popula- ing of the immune system. Because the virus be-
tion from contact with a pathogen. comes encoded within the genetic material of the
In 1985, a related virus, HIV-2, was discovered in host cell and is highly mutable, the problem of find-
West Africa. Although early reports have suggested ing safe and effective therapies has been extremely
that HIV-2 may be less pathogenic, the natural his- difficult, requiring considerable basic science and

clinical knowledge. Studies are currently being con- could not be sustained. Once a sizable reservoir of
ducted to determine the anti-HIV properties of many infection was established, however, HIV became pan-
drugs, but the ethical and economic obstacles to clini- demic. As with other sexually transmitted diseases,
cal trials with experimental drugs are formidable. such as syphilis, no country wished to be associated
Given the immediacy of the epidemic, it is difficult with the stigma of the "origin" of the virus.
to structure appropriate randomized clinical trials, The epidemic began at a moment of relative com-
which often take considerable time, to assess the placency, especially in the developed world, concern-
safety and efficacy of a drug. At present, the U.S. ing epidemic infectious disease. Not since the influ-
Food and Drug Administration has licensed only one enza epidemic of 1918-20 had an epidemic appeared
drug for the treatment of HIV infection, AZT with such devastating potential. The Western, devel-
(azidothymidine) which, according to clinical stud- oped world had experienced a health transition from
ies, delays but does not prevent death. Since the the predominance of infectious to chronic disease
beginning of the epidemic, clinical reasearch has and had come to focus its resources and attention on
refined the treatment of opportunistic infections. Re- systemic, noninfectious diseases. Thus AIDS ap-
cent studies, for example, have demonstrated the peared at a historical moment in which there was
effectiveness of aerosolized pentamidine, an antibi- little social or political experience in confronting a
otic, in preventing the development of pneumocystis public health crisis of this dimension. The epidemic
pneumonia. Despite these advances, expected sur- fractured a widely held belief in medical security.
vival currently (as of 1988) averages 2 years after Not surprisingly, early sociopolitical responses
the onset of symptoms. With anticipated improve- were characterized by denial. Early theories, when
ments in antiviral treatments, length of survival is few cases had been reported, centered on identifying
likely to increase. particular aspects of "fast track" gay sexual culture
that might explain the outbreak of cases of immune-
History and Geography compromised men. Additional cases among individu-
In its first decade, AIDS has created considerable als who had received blood transfusions or blood prod-
suffering and has generated an ongoing worldwide ucts, however, soon led the U.S. Centers for Disease
health crisis. During this brief period, the epidemic Control to the conclusion that an infectious agent was
has been identified and characterized epidemio- the likely link among these individuals. Neverthe-
logically, the basic modes of transmission have been less, in the earliest years of the epidemic, few wished
specified, a causal organism has been isolated, and to confront openly the possibility of spread beyond
effective tests for the presence of infection have been these specified "high-risk" groups. During this pe-
developed. In spite of this remarkable progress, riod, when federal and state interest and funding
which required the application of sophisticated lagged, grassroots organizations, especially in the
epidemiological, clinical, and scientific research, the homosexual community, were created to meet the
barriers to controlling AIDS are imposing and relate growing needs for education, counseling, patient ser-
to the most complex biomedical and political ques- vices, and in some instances, clinical research. Agen-
tions. AIDS has already sorely tested the capabili- cies such as the Gay Men's Health Crisis, founded in
ties of research, clinical, and public health institu- New York City in 1982, and the Shanti Project, estab-
tions throughout the world. lished in San Francisco in 1983, worked to overcome
Because HIV is related to other recently isolated the denial, prejudice, and bureaucratic inertia that
primate retroviruses such as simian T lymphotropic limited governmental response.
virus (STLV)-III, which has been isolated in wild As the nature and extent of the epidemic became
African green monkeys, there has been considerable clearer, however, hysteria sometimes replaced de-
speculation that HIV originated in Africa. Anti- nial. Because the disease was so powerfully associ-
bodies to HIV were discovered in stored blood in ated with behaviors characteristically identified as
Zaire dating back to 1959, and it seems likely that either immoral or illegal (or both), the stigma of those
evidence of the organism will be identified in even infected was heightened. Victims of disease were of-
earlier specimens. According to Robert Gallo and ten divided into categories: those who acquired their
Luc Montagnier, who have been credited with the infections through transfusions or perinatally, the
identification of HIV, it is likely that the virus has "innocent victims"; and those who engaged in high-
been present for many years in isolated groups in risk, morally condemnable behaviors, the "guilty per-
central Africa. Because outside contacts were mini- petrators" of disease. Since the early recognition of
mal, the virus was rarely spread, and an epidemic behavioral risks for infection, there has been a ten-

dency to blame those who became infected through mission appear to be some years away, the principal
drug use or homosexuality, behaviors viewed as "vol- public health approaches to controlling the pandemic
untary." Some religious groups in the United States rest upon education and behavior modification.
and elsewhere saw the epidemic as an occasion to Heightened awareness of the dangers of unprotected
reiterate particular moral views about sexual behav- anal intercourse among gay men, for example, has
ior, drug use, sin, and disease. AIDS was viewed as led to a significant decline in new infections among
"proof" of a certain moral order. this population. Nevertheless, as many public health
People with AIDS have been subjected to a range officials have been quick to note, encouraging the
of discriminatory behavior including loss ofjob, hous- modification of risk behaviors, especially those relat-
ing, and insurance. Since the onset of the epidemic, ing to sexuality and drug use, present no simple task,
incidents of violence against gays in the United even in the face of a dread disease.
States have risen. Despite the well-documented The burden of AIDS, in both human suffering and
modes of HIV transmission, fears of casual transmis- its demands on resources, is likely to grow in the
sion persist. In some communities, parents protested years ahead. Projections now estimate expenditures
when HFV-infected schoolchildren were permitted to totaling nearly $70 billion per year in the United
attend school. In one instance, a family with an HIV- States by 1991. Ensuring quality care for those in-
infected child was driven from a town by having fected will become even more difficult, especially in
their home burned down. the epidemic's epicenters, where those infected are
By 1983, as the potential ramifications of the epi- increasingly among the minorities and poor. In the
demic became evident, national and international developing world, AIDS threatens to reverse ad-
scientific and public health institutions began to vances in infant and child survival in recent de-
mobilize. In the United States, congressional appro- cades. The epidemic is likely to have a substantial
priations for research and education began to rise impact on demographic patterns. Because the dis-
significantly. The National Academy of Sciences isease principally affects young and middle-aged
sued a consensus report on the epidemic in 1986. A adults, 20 to 49 years of age, it has already had
presidential commission held public hearings and tragic social and cultural repercussions. Transmit-
eventually issued a report calling for protection of ted both horizontally (via sexual contact) and verti-
people with AIDS against discrimination and a more cally (from mother to infant), the epidemic has the
extensive federal commitment to drug treatment. potential to depress the growth rate of human popu-
The World Health Organization established a Global lations, especially in areas of the developing world.
Program on AIDS in 1986 to coordinate interna- In this respect, the disease could destabilize the
tional efforts in epidemiological surveillance, educa- work force and depress local economies.
tion, prevention, and research. AIDS has clearly demonstrated the complex rela-
Despite the growing recognition of the signifi- tionship of biological and behavioral forces in deter-
cance of the epidemic, considerable debate continues mining patterns of health and disease. Altering the
regarding the most effective public health responses course of the epidemic by human design has already
to the epidemic. Although some nations such as proved to be no easy matter. The lifelong infectious-
Cuba have experimented with programs mandating ness of carriers; the private, biopsychosocial nature
the isolation of HIV-infected individuals, the World of sexual behavior and drug use; and the fact that
Health Organization has lobbied against the use of those at greatest risk are already stigmatized - all
coercive measures in response to the epidemic. have made effective public policy interventions even
Given the lifelong nature of HIV infection, effective more difficult. Finally, the very nature of the virus
isolation would require lifetime incarceration. With itself- its complex and mutagenic nature - makes a
the available variety of less restrictive measures to short-term technological breakthrough unlikely.
control the spread of infection, most nations have The remarkable progress in understanding AIDS
rejected quarantine as both unduly coercive and un- is testimony to the sophistication of contemporary
likely to achieve control, given current estimates of bioscience; the epidemic, however, is also a sobering
prevalence. Traditional public health approaches to reminder of the limits of that very biotechnology. Any
communicable disease including contact tracing and historical assessment of the AIDS epidemic must be
mandatory treatment have less potential to control considered provisionary. Nevertheless, it already has
infection because there are currently no means of become clear that this epidemic has forced the world
rendering an infected individual noninfectious. to confront a new set of biological imperatives.
Because biomedical technologies to prevent trans- Allan M. Brandt

Bibliography Keniston, Kenneth. 1989. Introduction to the issue. Daeda-

Anderson, R. M., R. M. May, and A. R. McLean. 1988. lus 118: IX-XXXII.
Possible demographic consequences of AIDS in devel- Macklin, R., and G. H. Friedland. 1986. AIDS research:
oping countries. Nature 332: 228-34. The ethics of clinical trials. Law, Medicine, and
Bayer, Ronald. 1989. AIDS, privacy, and responsibility. Health-Care 14: 273-80.
Daedalus 118: 79-99. Mann, Jonathan M., et al. 1988. The international
Bloom, David E., and Geoffrey Carliner. 1988. The eco- epidemiology of AIDS. Scientific American 259: 82-9.
nomic impact of AIDS in the United States. Science May, Robert M., Roy M. Anderson, and Sally M. Blower.
239: 604-10. 1989. The epidemiology and transmission dynamics of
Christakis, Nicholas A. 1989. Responding to a pandemic: HIV AIDS. Daedalus 118:163-201.
International interests in AIDS control. Daedalus Nelkin, Dorothy, and Stephen Hilgartner. 1986. Disputed
118: 113-34. dimensions of risk: A public school controversy over
Cotton, Deborah. 1988. The impact of AIDS on the medical AIDS. Milbank Quarterly 64: 118-42.
care system. Journal of the American Medical Associa- Nicholas, Eve K. 1989. Mobilizing against AIDS. Cam-
tion 260: 519-23. bridge, Mass.
Curran, James W., et al. 1988. Epidemiology HIV infection Osborn, June E. 1988. AIDS: Politics and science. New
and AIDS in the United States. Science 239: 610-16. England Journal of Medicine 318: 444—7.
Fauci, Anthony S. 1983. The acquired immune deficiency 1989. Public health and the politics of AIDS prevention.
syndrome: The ever broadening clinical spectrum. Daedalus 118: 123-44.
Journal of the American Medical Association 249: Panos Institute. 1988. AIDS and the Third World: Update.
2375-6. Washington, D.C.
1988. The human immunodeficiency virus: Infectivity Piot, Peter, et al. 1988. AIDS: An international perspec-
and mechanisms of pathogenesis. Science 239:617—22. tive. Science 239: 573-9.
Fineberg, Harvey V. 1988. Education to prevent AIDS: Presidential Commission on the Human Immunodefi-
Prospects and obstacles. Science 239: 592-6. ciency Virus Epidemic. Report. 1988. Washington,
1988. The social dimensions of AIDS. Scientific Ameri- D.C.
can 259: 128-34. Ron, Aran, and David E. Rogers. 1989. AIDS in the United
Fox, Daniel M. 1986. AIDS and the American health pol- States: Patient care and politics. Daedalus 118: 41—58.
icy: The history and prospects of a crisis of authority. Rosenberg, Charles E. 1989. What is an epidemic? Daeda-
Milbank Quarterly 64: 7-33. lus 118: 1-17.
Fox, Daniel M., Patricia Day, and Rudolf Klein. 1989. The Shilts, Randy. 1987. And the band played on. New York.
power of professionalism: Policies for AIDS in Britain, U.S. Office of Technology Assessment. 1985. Review of the
Sweden, and the United States. Daedalus 118:93-112. public health services response to AIDS: A technical
Friedland, Gerald H. 1989. Clinical care in the AIDS epi- memorandum. Washington, D.C.
demic. Daedalus 118: 59-83. Winkenwerder, William, Austin R. Kessler, and Rhonda
Friedland, G. H., and R. S. Klein. 1987. Transmission of M. Stolec. 1989. Federal spending for illness caused by
the human immunodeficiency virus. New England the human immunodeficiency virus. New England
Journal of Medicine 317: 1125-35. Journal of Medicine 320:1598-603.
Friedman, Samuel, et al. 1987. The AIDS epidemic among Zalduondo, Barbara O. de, Gernard Iddi Msamanga, and
blacks and Hispanics. Milbank Quarterly 65 (Suppl. Lincoln C. Chen. 1989. AIDS in Africa: Diversity in
2): 455-99. the global pandemic. Daedalus 118: 165-204.
Gallo, Robert, and Luc Montagnier. 1988. AIDS in 1989.
Scientific American 259: 48.
Gostin, Larry. 1986. The future of communicable disease
control: Toward a new concept in public health law.
Milbank Quarterly 64: 79-96.
Hamburg, Margaret A., and Anthony S. Fauci. 1989.
AIDS: The challenge to biomedical research. Daeda-
lus 118:19-58.
Haseltine, William A. 1989. Prospects for the medical
control of the AIDS epidemic. Daedalus 118: 1-21.
Heyward, William L., and James W. Curran. 1988. The
epidemiology of AIDS in the U.S. Scientific American
259: 72-81.
Institute of Medicine. National Academy of Sciences.
1988. Confronting AIDS. Washington, D.C.

VIII.2
African Trypanosomiasis
(Sleeping Sickness)
African trypanosomiasis, or sleeping sickness, is a

fatal disease caused by a protozoan hemoflagellate
parasite, the trypanosome. It is transmitted through
the bite of a tsetse fly, a member of the genus
Glossina. Sleeping sickness is endemic, sometimes
epidemic, across a wide band of sub-Saharan Africa,
the so-called tsetse belt that covers some 11 million
square kilometers. Although the disease was not Figure VIII.2.1. Glossina palpalis.
scientifically understood until the first decade of the
twentieth century, it had been recognized in West two large blocks of lowland rain forest in western
Africa from the fourteenth century. and central Africa as well as the fringing gallery
The chemotherapy to combat trypanosomiasis has forests along waterways, which extend into neighbor-
remained archaic, with no significant advances ing savanna regions. The morsitans group, or sa-
made and, indeed, very little research done between vanna tsetse, is the vector for T. b. rhodesiense, the
the 1930s and the 1980s. Most of the victims are cause of the rhodesiense form of sleeping sickness; it
poor, rural Africans, which has meant that there is includes Glossina morsitans (see Figure VIII.2.2),
little or no economic incentive for pharmaceutical Glossina pallidipes, and Glossina swynnertoni,
firms to devote research resources to the disease which live in the savanna woodlands of eastern and
(Goodwin 1987). However, in the mid-1980s field southern Africa (see Maps VIII.2.1 and VIII.2.2).
trials of a promising new drug, Dl-alpha-difluoro- Although tsetse flies are not easily infected with
methylornithine (DFMO), demonstrated the drug's trypanosomes, once infected they remain vectors of
efficacy in late-stage disease when there is central the disease for life.
nervous system involvement. In addition, there have After being bitten by an infected fly, most victims
been exciting recent developments in the field of experience local inflammation, or the trypanosomal
tsetse eradication with the combined use of fly traps chancre; and parasites migrate from this site to mul-
and odor attractants (Hall et al. 1984). And, the tiply in blood, lymph, tissue fluids, and eventually
World Health Organization's Special Program on the cerebrospinal fluid. The blood trypanosome
Tropical Disease is trying to overcome the research count oscillates cyclically, with each successive
problem resulting from the reluctance of pharmaceu- wave, or parasitemia, manifesting different surface
tical firms to get involved. antigens. In this manner, trypanosomes evade anti-
bodies raised by the host to their previous surface
coats. (This antigenic variability has helped to make
Etiology
There are two forms of human sleeping sickness in
Africa. An acute form caused by Trypanosoma
brucei rhodesiense with a short incubation period of
5 to 7 days occurs in eastern and southern Africa.
The chronic form, Trypanosoma brucei gambiense, of
western and central Africa can take from several
weeks to months or even years to manifest itself.
Both diseases are transmitted by tsetse flies. There
are many species of Glossina, but only six act as
vectors for the human disease. Thepalpalis group, or
riverine tsetse, is responsible for the transmission of
T. b. gambiense disease. Riverine tsetse include
Glossina palpalis (see Figure VHI.2.1), Glossina
fuscipes, and Glossina tachinoides; these inhabit the Figure VIII.2.2. Glossina morsitans.

VIII.2. African Trypanosomiasis 553
-20
Distribution of species of Distribution of species of

the palpalis group the morsiians group
-30
Map VIII.2.1 Distribution of African sleeping sickness Map VIII.2.2 Distribution of African sleeping sickness
(palpalis group). (From A. M. Jordan. 1986. (morsitans group). (From A. M. Jordan. 1986.
Trypanosomiasis control and African rural development. Trypanosomiasis control and African rural development.
Essex: Longman House, by permission of the publisher.) Essex: Longman House, by permission of the publisher.)
the trypanosome one of the most researched patho- humans, parasites, tsetse flies, wild and domesti-
genic parasites and a particular favorite with mo- cated animals, and the ecological setting that they
lecular biologists today [Warren, personal communi- share. Although foci remain at varying levels of
cation].) Eventually, all organs are invaded, with endemicity, increasing population movements have
central nervous system involvement ultimately lead- complicated the epidemiology (Lucasse 1964; Ruppol
ing to death. and Libala 1977). Moreover, disease incidence is not
necessarily related to fly density. Research has
Epidemiology shown that a small number of flies with good
The epidemiology of African sleeping sickness is far human-fly contact can sustain an endemic, even as
from being fully understood (Jordan 1986). A com- epidemic, incidence.
plex epidemiology makes it most difficult to analyze The average life-span of tsetsefliesis 1 to 6 months,
and predict, thereby necessitating analysis of the during which they require shade, humidity, and a
total context of the disease pattern. In addition, the temperature range between 20° and 30°C. Tsetse spe-
epidemiological pattern varies considerably from cies have varying food preferences, ranging from the
place to place. Nevertheless, two features are well- blood of wild and domestic animals to that of humans,
recognized. First, trypanosomiasis is exceptionally but they require a daily blood meal, thereby making a
focal, occurring at or around specific geographic loca- singleflypotentially highly infective.
tions; and second, the number of tsetsefliesis appar- Gambiense sleeping sickness is classically a dis-
ently not as important for disease incidence as is the ease of the frontier of human environment, where
nature of the human-fly contact. human-created habitat meets sylvan biotope. Hu-
The focal nature of sleeping sickness means that mans are the principal reservoir of T. b. gambiense,
the ecological settings in which it occurs are of vital and they maintain the typical endemic cycle of the
importance for understanding its epidemiology. disease. It is now known, however, that some ani-
Seemingly impossible to destroy, many historical mals, including domestic pigs, cattle, sheep, and
foci tend to flare up in spite of concentrated efforts even chickens, can act as reservoirs. The key to
since the 1930s on the part of surveillance and pre- understanding the gambiense form is its chronicity
vention personnel (Duggan 1970; Janssens, personal and the fact that there are usually very low numbers
communication). This means that very often the vil- of parasites present in the lymph and other tissue
lages and regions that were affected decades ago fluids. Gambiense disease can be maintained by a
remain problem areas today. The disease involves mere handful of peridomesticflies—that is, those

that have invaded bush or cultivations near human ungulate herds became trypo-tolerant, with few ex-
settlements. This is known as close human—fly conceptions domestic cattle still succumb to the dis-
tact. Cultivation practices such as the introduction ease, and the vast majority of research and funding
of banana groves, shade trees, new crops like tobacco has been aimed at solving the problem of animal -
and lantana hedges, or the creation of new farms can not human — sleeping sickness.
provide fresh ecological niches into which tsetse flies In evolutionary terms, the presence of trypano-
may spread, introducing sleeping sickness through somes in Africa may perhaps have precluded the
peridomestic transmission. development of some ground-dwelling faunas, thus
Riverine G. palpalis are most commonly found encouraging certain more resistant primates, includ-
near the low-level brush bordering smaller water- ing the early ancestors of humankind, to fill the
ways and pools; during dry seasons, when humans empty ecological niches (Lambrecht 1964). If so,
and flies are brought together through their shared then humans were exposed to the possibility of
need for water, the flies become particularly infec- trypanosomal infection at the time of their very re-
tive. Activities such as fishing, bathing, water collec- mote origin. The parasites are, on the whole, poorly
tion, and travel bring humans into daily contact adapted to humans, which accounts for the variety of
with the insects, and in this way an endemic level of clinical symptoms and ever-changing epidemio-
the disease can be maintained over long periods. logical patterns. The fact that the parasitism of hu-
Other common foci for the disease are sacred groves, man beings is still evolving helps us to understand
which are often small clearings in the forest where the unpredictable nature of the disease. A perfectly
the high humidity allows the flies to venture farther adapted parasite does not kill its host - at least in
from water sources. the short run.
The virulent rhodesiense form of the disease is a
true zoonosis maintained in wild animal reservoirs Distribution and Incidence
in the eastern African savannas. In the case of T. b. An estimated 50 million people in 42 countries are
gambiense, humans are probably the normal mam- at risk for trypanosomal infection (Molyneux and
malian hosts, with wild and domestic animals as Smith, personal communication), while it is esti-
adventitious hosts, whereas in the case of T. b. mated that only about 5 to 10 million people have
rhodesiense the usual mammalian hosts are wild access to some form of protection against or treat-
ungulates, with humans as adventitious hosts. ment for the disease (World Health Organization
Transmission of rhodesiense disease is more haphaz- 1985). Sleeping sickness is endemic across the wide
ard and directly relates to occupations such as band of sub-Saharan Africa known as the "tsetse
searching forfirewood,hunting, fishing, honey gath- belt" lying roughly between 20° north and 20° south
ering, poaching, cultivation, cattle keeping, and be- of the equator (see Maps VIII.2.1 and VIII.2.2),
ing a game warden or a tourist. Whereas the where it can attain epidemic proportions for a vari-
gambiense form of the disease is site related, the ety of natural and sociopolitical reasons.
rhodesiense form is occupation related, which helps The actual numbers of cases will never be known,
to explain why the latter characteristically affects as it is a disease of remote rural areas, and even
many more men and boys than women and girls. today people in such places often die undiagnosed
However, when a community moves near bush in- and uncounted. Most national statistics are grossly
fested with infected flies, the entire population is at underreported, with the World Health Organization
risk. being notified of about only 10 percent of the new
The wild and domestic animal reservoir of cases. Based upon data from reporting countries, the
trypanosomes is an important factor in the epide- current estimate of incidence is 20,000 to 25,000
miology and history of sleeping sickness. The cases annually, which is alarming because most of
paleogenesis of human trypanosomiasis has been the victims are concentrated in Zaire, Uganda, and
much studied, and it is well established that the southern Sudan, the most important foci of the dis-
trypanosomiases are ancient in Africa. Indeed, it is ease in the 1980s. In 1987, Busoga (Uganda) re-
conjectured that the presence of sleeping sickness ported around 7,000 new cases, whereas the same
may explain why the ungulate herds of the African region reported 8,500 to 9,000 cases in 1979-80.
savanna have survived human predators for so Some villages had infection rates of up to 25 percent
long; the wild-animal reservoir of trypanosomes (Smith, personal communication). In the late 1970s
firmly restricted the boundaries of early human and 1980s, severe outbreaks occurred in Cameroon,
settlement (McNeill 1977). Although the wild Angola, Central African Republic, the Ivory Coast,

Tanzania, as well as the Sudan, Zambia, Uganda, of asymptomatic carriers. During gambiense infec-
and Zaire. tion, trypanosomes multiply, and, with increased
parasitemia, the victim suffers fever after which the
Clinical Manifestations and Pathology parasitemia recedes in apparent response to the pro-
Although trypanosomiasis has been studied for over duction of antibodies. Soon the parasites again multi-
80 years, much is still unknown about the pathology ply, but this generation produces antigenic material
of the disease. Three phases follow the bite of an against which the previous antibodies are ineffec-
infected fly: first the chancre itself; then the tive. It is this phenomenon of "antigenic variation"
hemolymphatic or "primary stage"; and finally the that greatly reduces the prospect of producing an
meningocephalitic or "secondary stage." On aver- effective vaccine, and at present very little research
age, people infected with T. b. gambiense live 2 or 3 is underway on vaccine development (Boothroyd
years before succumbing, although there are re- 1985).
corded cases of infection spanning as much as 2
decades. In contrast, infection with the more viru- History and Geography
lent T. b. rhodesiense, if untreated, usually leads to The history of sleeping sickness in Africa is long and
death within 6 to 18 weeks. complex, stretching across millennia to threaten mil-
The disease manifests a bewildering, sometimes lions today. The complicated ecology of the trypanoso-
startling, array of clinical symptoms, which can vary miasis, involving the human host, trypanosome,
from place to place. Progressing through the two tsetsefly,wild and/or domestic animal reservoir, cli-
stages, there is increasing parasitemia with eventual mate, and geography has dramatically affected demo-
involvement of the central nervous system. Clinical graphic patterns in sub-Saharan Africa. The parame-
symptoms can include fever, headache, and psychiat- ters and density of human settlement have been lim-
ric disorders such as nervousness, irascibility, emo- ited in many regions until the present time, while
tionalism, melancholia, and insomnia, which reflect the trypanosomiasis have prevented cattle-keeping
neuronal degeneration. Other symptoms include loss across vast regions of the continent, thereby seriously
of appetite, gross emaciation, sleep abnormalities, affecting the nutrition of entire populations.
stupor, and the characteristic coma from which sleep- The "African lethargy," or "sleepy distemper," was
ing sickness derives its name. Some of the initial well known to Europeans in West Africa from as
symptoms of sleeping sickness are also characteristic early as the fourteenth century, through good de-
of early malaria, which can make differentiation be- scriptions given by Portuguese and Arab writers.
tween the two diseases difficult in the field. A com- For centuries slave traders rejected Africans with
mon, easily recognizable symptom is swelling of the characteristic swollen cervical glands, for it was
lymph nodes, especially those of the cervical, common knowledge that those with this symptom
subclavicular, and inguinal regions. Another com- sooner or later died in the New World or North Af-
mon symptom is called "moon face," an edema caused rica (Hoeppli 1969). In 1734 an English naval sur-
by leaking of small blood vessels. A most common geon described the disease along the Guinea coast,
complication during trypanosomiasis is pneumonia, and in 1803 another English doctor described the
which is a frequent cause of death. A disturbing as- symptom of swollen cervical glands, which came to
pect of the chronic gambiense form can be its long be called "Winterbottom's sign" (Atkins 1735; Win-
period of development, sometimes as long as 15 years terbottom 1803). As European exploration and trade
after the victim has left an endemic area. along the West African coast increased between
1785 and 1840, the disease was reported in Gambia,
Immunology Sierra Leone, and western Liberia, whereas between
The prospect of a vaccine for human trypanoso- 1820 and 1870, it was also commonly noted along
miasis is bleak. This pessimism is occasioned in part the Liberian coast.
by the trypanosome's ability to alter rapidly surface
antigens, apparently to evade the host's humoral Colonial Period
immunity. Nevertheless, immune mechanisms may Certainly the disease was an important factor in the
be involved in several aspects of the disease. This is history of colonial Africa. In the beginning, colonial
probably the case for endemic gambiense disease in administrators were concerned mainly with the
western and central Africa, where sleeping sickness health of Europeans and those few Africans in their
is known to be an ancient disease, and where early service. But the threat of epidemics of sleeping sick-
field workers sometimes observed the phenomenon ness eventually forced colonial authorities to take

much more seriously the health of entire African cially designed to investigate the exotic diseases of
populations. warm climates. The British, for example, opened
For many Africans the disease occasioned their schools of tropical medicine at Liverpool and London
first, often traumatic, encounters with their new in 1899, while other such schools came into being in
political masters, while epidemics enabled many co- Germany, Belgium, France, Portugal, and the
lonial authorities to increase their political hege- United States. This new field of scientific endeavor,
mony through public health measures. In those colo- tropical medicine ("colonial medicine" for the
nies affected by sleeping sickness, medical services French), offered the opportunity for bright young
often developed in direct response to this one dis- men to gain international acclaim and a place in the
ease, which resulted in the development of "vertical" history of medicine. According to John L. Todd of the
health services — programs aimed at controlling a Liverpool School of Tropical Medicine in 1903,
specific disease, while neglecting other crucial pub- "Tryps are a big thing and if we have luck, I may
lic health issues. Although the colonial powers have make a name yet!" (Lyons 1987).
departed, as recently as the 1970s the World Health It should be noted that sleeping sickness was not
Organization urged developing countries to move the only disease to receive such attention as Europe-
toward "horizontal" health services that take into ans sought to establish themselves permanently in
account the multifactoral nature of disease and regions of the globe where health conditions were
health. difficult and mortality was high (Carlson 1984; Brad-
ley 1986). There were major discoveries by Manson,
Research in Parasitology and Tropical Medicine. who was the first to demonstrate insects as vectors of
Sleeping sickness, along with malaria and yellow human disease (filariasis); and by Ronald Ross, who
fever, played an important role in the development found that the malaria parasite was transmitted by
of the new specialties of parasitology and tropical the Anopheles mosquito. Yet, despite the fact that
medicine. In 1898, Patrick Manson, the "father of endemic malaria was probably the cause of far more
tropical medicine," published the first cogent discus- morbidity, the trypanosome and trypanosomiases at-
sion of the new scientific discipline. He explained tracted much attention in the new field of tropical
that tropical diseases, those present in warm cli- medicine for the next 2 or 3 decades. Indeed, obses-
mates, were very often insect-borne parasitical dis- sion with it dominated the first issue of the Transac-
eases, the chief example being trypanosomiasis tions of the Society of Tropical Medicine and Hygiene
(Manson 1898). in 1907.
Trypanosomiasis at the time was very much on Quite literally, sleeping sickness captured the colo-
the minds of colonial officials. In the decade between nial imagination (Martin 1923). International meet-
1896 and 1906, devastating epidemics killed over ings were convened to discuss sleeping sickness, be-
250,000 Africans in the new British protectorate of ginning with one at the British Foreign Office in
Uganda, as well as an estimated 500,000 residents of 1907. As the number of "tryps" specialists increased,
the Congo basin. Understandably, the new colonial sleeping sickness became a key factor in the interna-
powers, including Britain, France, Germany, Portu- tional exchange of researchfindingsin tropical medi-
gal, and King Leopold's Congo Free State, perceived cine. The Sleeping Sickness Bureau was opened in
sleeping sickness to be a grave threat to African London in 1908 to facilitate communication of re-
laborers and taxpayers, which in turn could dramati- searchfindingson all aspects of the disease. Its work
cally reduce the utility of the new territories. More- continues to the present time as the important Tropi-
over, the fears were not limited to the continent of cal Diseases Bulletin.
Africa; the British also speculated that sleeping sick- After World War I and the formation of the League
ness might spread to India, the "jewel" of their em- of Nations' Health Organization (the antecedent of
pire (Leishman 1903). the World Health Organization), two major confer-
Thus ensued one of the most dramatic campaigns ences in 1925 and 1928 were convened to focus on
in the history of medicine, as scientific research African sleeping sickness. These conferences, follow-
teams were dispatched to study sleeping sickness. ing the pattern of the nineteenth-century sanitation
They began with the Liverpool School of Tropical and hygiene conferences, sought international col-
Medicine's expedition to Senegambia in 1901 and laboration and cooperation in implementing public
the Royal Society's expedition to Uganda in 1902; health solutions. In Africa, special research centers
other expeditions followed until World War II. on tsetse flies and sleeping sickness appeared in
Many of these were sent by new institutions espe- many colonies including Uganda, Kenya, Tangan-

yika (now Tanzania), Belgian Congo (Zaire), Nige- volves many factors. The declaration of an epidemic
ria, Ghana, and French Equatorial Africa (Chad, is most often made by an authority with the sanction
Central Africa Republic, Congo-Brazzaville, and of the state. Epidemics are social and political, as
Gabon). Sleeping sickness thus became an impor- well as medical, events and their declaration can
tant catalyst for cooperation among the colonial pow- serve a variety of needs (Stark 1977). Early in the
ers in Africa, which in turn aided the rapid growth of twentieth century, the declaration of an epidemic
tropical medicine as afield.In fact, sleeping sickness could provide a pretext by which to control unruly
early in the twentieth century attracted interna- populations suffering the traumas of colonial con-
tional attention to Africa with an urgency that was quest. For example, in response to threatened epi-
repeated in the early 1980s with AIDS (Kolata demics of disease, African populations could be recog-
1984). nized and relocated for ease of political control and
Response to the disease occurred within the pri- administration. On the other hand, declarations of
vate sector as well. Concerned at the possible loss of sleeping sickness epidemics also enabled public
increasingly important African markets, the Euro- health and medical service personnel to implement
pean business and commercial community encour- measures designed to contain the incidence and
aged and sometimes initiated research into tropical spread of the disease.
diseases. For example, the principal founder of the Medical experts at the turn of the nineteenth cen-
Liverpool School of Tropical Medicine in 1899 was tury tended to favor the theory of circumstantial
the influential and powerful capitalist Alfred Lewis epidemiology, which held that diseases were spread
Jones, chairman of a Liverpool-based shipping line mainly through human agency within specific sets
that plied a lucrative trade along the West African of circumstances. Lacking effective treatments, the
coast (Morel 1968). He was also a personal friend of principal methods of control of epidemic disease con-
the notorious King Leopold of the Congo Free State. sisted of segregation or isolation and disinfection
The businessman shared the imperialist's dismay at with acrid smoke or strong fumes such as sulfur and
the potential devastation that could be caused by vinegar. Disease was perceived as an invader to be
sleeping sickness, and together they were keen to demolished. This view accounts for much of the imag-
support attempts to prevent the decimation of Afri- ery and idiom of war used in early public health
can populations. campaigns. A major adjunct to this theory was the
belief that once the circumstances had been identi-
Politics and Epidemiology. The politics of colonial- fied, most diseases in Africa could and would be
ism often reflected contemporaneous perceptions of controlled, even eliminated, with techniques and
the epidemiology of sleeping sickness. By 1900, for technology developed in Europe. The European colo-
example it was widely accepted that the disease had nials assumed that they would succeed where Afri-
been endemic in West Africa for centuries but had cans had failed and that they would transform the
only recently begun spreading into the Congo basin continent by conquering the problems of tsetse and
and eastward. H. H. Johnston, the English colonial the trypanosome, among others. Most colonists be-
expert, popularized this view by arguing that sleep- lieved that much of the backwardness they saw in
ing sickness had been spread eastward across the African society was attributable, at least in part, to
Congo basin in 1888-9 by H. M. Stanley's Emin endemic diseases such as sleeping sickness that
Pasha Relief Expedition (Morris 1963; Lyons 1987). could, they thought, help to explain the lack of the
From the earliest days of colonial settlement, it use of the wheel and the attendant need for human
was not uncommon to blame sleeping sickness for porterage, as well as the lack of animal-powered
the abandoned villages and depopulated regions plows, mills, and the like.
that Europeans encountered during their push into Powerful notions of the potential of Western tech-
the interior. It usually did not occur to the intruders nology for solving health problems in Africa, sleep-
that in many cases Africans were withdrawing from ing sickness among them, have survived until quite
areas because of the brutal nature of colonial con- recently. Rarely, if ever, did colonial authorities con-
quest, and half a century would pass before research- sider the possibility that Africans not only possessed
ers began to examine the deeper socioeconomic and some ideas about the ecology of sleeping sickness but
political causes of the dramatic changes in the Afri- had gained fairly effective control of their environ-
can disease environment that had resulted in the ment. An example of one such African strategy was
spread and increased incidence of sleeping sickness. the warnings to early European travelers not to
The word "epidemic" is a relative term that in- travel through certain regions during daylight

hours when tsetse flies were active and might infect years researching sleeping sickness, was one of the
their transport animals. Moreover, throughout the first to challenge this "classical view" of the pacifica-
tsetse-infested regions, there were instances of Afri- tion of Africa and the spread of the disease. He argued
can residence patterns that allowed coexistence with that it was not the pacific character of European
the ubiquitous tsetse flies yet avoided population colonization but, on the contrary, its brutal nature,
concentrations conducive to epidemic outbreaks. It that greatly disrupted and stressed African popula-
was, according to John Ford (1971), tions (Kjekshus 1977). In particular, the balanced
ecological relationships among humans, tsetse flies,
a curious comment to make upon the efforts of colonial and trypanosomes were disrupted by European activi-
scientists to control the trypanosomiases, that they almost ties with the result that endemic sleeping sickness
entirely overlooked the very considerable achievements of flared into epidemic proportions. Vivid examples of
the indigenous peoples in overcoming the obstacle of the results of such ecological upheaval were the sleep-
trypanosomiasis to tame and exploit the natural ecosys-
tem of tropical Africa by cultural and physiological adjust- ing sickness epidemics in Uganda and the Congo
ment both in themselves and [in] their domestic animals. basin that had killed hundreds of thousands.
European colonizers, by contrast, often dis- Public Health Initiatives. Epidemics continued
rupted - or destroyed — indigenous practices and sur- throughout much of the colonial period, especially
vival strategies with the result that endemic sleep- prior to World War II when there were serious out-
ing sickness spread and sometimes became epidemic breaks in both West and East Africa, which occa-
with disastrous effects. For example, from the late sioned a great deal of morbidity and mortality
1880s through the 1920s, the Belgians forced (Duggan 1970). Public health regulations prolifer-
Congolese individuals to spend ever-increasing ated to control the disease that affected other areas
amounts of time searching farther and farther afield of administration such as taxation, labor supply, and
for sources of wild rubber with which to meet tax freedom of movement across international frontiers.
demands. In northern Zaire, rubber vines prolifer- In some colonies, sleeping sickness programs be-
ated in the gallery forests, and such galleries were, came so extensive and bureaucratic that they came
and remain, superb ecological niches for the vector into conflict with other colonial departments, exacer-
of gambiense sleeping sickness, G. palpalis. bating competition for scarce staffing and financial
The colonial powers, however, held their own ver- resources within colonial administrations. In addi-
sion of the history of sleeping sickness and its evolution, sleeping sickness regulations were often respon-
tion (Morris 1963; Burke 1971). Prior to their ar- sible for confrontations between the private and
rival, ancient, intractable foci of the disease had state sector as members of the former found them-
existed in West Africa and in the Congo basin selves increasingly hindered in their attempts to
around which, from time to time, the disease would exploit the people and resources of Africa.
flare into epidemic proportions. Colonials believed Two major patterns emerged in the colonial cam-
that it really began to spread only after the Euro- paigns against sleeping sickness. In one, the focus
pean newcomers had suppressed local wars and was on tsetse eradication, whereas in the other, the
slave raiding among African peoples and established focus was on the medicalization of victims. Both
law and order. This in turn allowed many Africans, approaches, however, involved varying degrees of
for the first time ever, to move freely and safely brush clearance as a prophylactic measure, and in
away from their home regions. Protected by Pax reality, most campaigns were a combination of fea-
Brittannica, Belgica, and the like, the increased tures from each approach. For instance, it was point-
movements of Africans carried sleeping sickness less to think of successfully destroying tsetse habitat
from old endemic foci to new populations. There was in the rainforest conditions of the Congo basin or
some basis for this hypothesis, especially in West much of French Equatorial Africa. Nevertheless, in
Africa such as in Ghana and Rukuber of Nigeria (cf. some areas combined campaigns of brush clearance,
Duggan 1970). This widely accepted notion of the resettlement, and medicalization were carried out.
spread of sleeping sickness had an important conse- Within this framework, national variations
quence in the enormous effect expended by the Euro- emerged in the colonial campaigns. The British
peans in trying to regulate African life at every took a more broadly ecological approach to control
level, and especially to limit strictly any freedom of of the disease, whereas the French and the Belgians
movement. took a more "medical" approach to the problem of
Ford, the British entomologist who spent over 25 human infection. British policy was to break the

chain of sleeping sickness transmission by separat- 1932 there were five such teams operating annually
ing people from flies. Thus, while British adminis- in northern Congo alone. Admirable as it was for its
trators implemented social policies aimed to protect sheer scale of organization, the policy of mass medi-
people from disease, the scientific community, espe- calization did not affect the fundamental ecology of
cially the new entomologists, searched for solutions the parasites; indeed, this approach had the effect of
to the "tsetse fly problem" in Africa (Ford 1971). removing the store of antibodies from humans that
The compulsory mass resettlement of Ugandans, had been built up through long contact with the
which probably helped save lives, from lakeshore parasites (Lyons 1987).
communities in Buganda and Busoga in 1908, and Sterilization of the human reservoir was made
the huge Anchau (northern Nigeria) scheme begun possible in 1905 when the first trypanocidal drug
in 1936 are good examples of breaking transmission became available in the form of an arsenical com-
chains. Likewise, in some regions where it was eco- pound, atoxyl. Discovered by the German chemist
logically feasible, Belgians resettled groups of peo- Paul Ehrlich, and adapted for use with sleeping sick-
ple such as those along the Semliki River in eastern ness by Wolferstan Thomas of the Liverpool School
Congo. of Tropical Medicine, atoxyl, alone or in combination
Unfortunately, in the context of recently con- with other compounds, remained the only chemother-
quered and colonized Africans, who had rural subsis- apy for 2 decades. Atoxyl was toxic for 38 percent of
tence economies, and whose culture and tradition patients, with dreadful side effects suffered by those
were intricately linked to locale, compulsory reloca- whom it did not kill outright, among them the blind-
tion sometimes had calamitous effects on those it ing of 30 percent of those injected. By the early
was meant to protect. In the Belgian Congo an extra- 1920s, new drugs - suramin (1916-20) and tryparsa-
ordinary amount of legislation and effort was di- mide (1919-25), and later in the early 1940s,
rected at the control of populations in relation to pentamidine - were in use for early-stage rhode-
sleeping sickness. In some places people found them- siense and gambiense disease. Melarsoprol, a most
selves forbidden to go near rivers that were desig- problematic arsenical with serious side effects, in-
nated "infected" with the disease. They could not cluding up to 5 percent mortality, was and is used for
fish, cross the rivers, use their rivercraft, or even second-stage disease. Together with suramin and
attend to cultivations along the banks. It is not sur- pentamidine, these three have remained the drugs
prising that many Africans regarded sleeping sick- of choice since the 1940s.
ness as the colonial disease because of the sometimes
overwhelming amount of administrative presence it Postcolonial Period
elicited (Duggan, personal communication; Lyons In the early 1960s, which saw independence for
1985). many African territories, colonial rulers concurred
French and Belgian efforts were directed chiefly that human sleeping sickness was under control in
at "sterilizing the human reservoir" of trypanosomes Africa. But political upheavals in many countries
through mass campaigns of medicalization, or injec- following independence, accompanied by the break-
tions. To achieve this, they conducted systematic down of medical infrastructures and large-scale
surveys of entire populations, hoping to locate, iso- population displacements, once again seriously af-
late, and treat all victims. Eugene Jamot, a French fected the epidemiology of sleeping sickness. Some
parasitologist, developed this method in Ubangui- countries - Zaire, Uganda, Sudan, and Ivory Coast,
Chari (French Equatorial Africa), and later intro- for instance - witnessed epidemics of sleeping sick-
duced it to affected parts of Cameroon and French ness, and it has been estimated that by 1969 there
West Africa (Jamot 1920). In 1916, he organized an were up to 1 million sleeping sickness victims in the
ambitious sleeping sickness campaign based upon Congo alone (Mulligan 1970).
mobile teams, which systematically scoured the Sleeping sickness continues to afflict unknown
country for victims of the disease to be injected. numbers of Africans. Epidemics occurred in the
A grid system was devised to ensure complete 1980s in old, well-known foci located in those re-
surveys, and the mobile teams worked with true gions of Africa experiencing disorder and decay of
military efficiency. Between July 1917 and August public service brought about by socioeconomic and
1919, over 90,000 individuals had been examined, political conditions. In fact, some areas are experi-
and 5,347 victims were identified and treated. encing a disheartening replay of events earlier this
Jamot's design for a sleeping sickness service was century, while other areas are experiencing the intro-
soon adopted by the Belgians in the Congo, and by duction of the disease for the first time.

Tsetse flies and the trypanosomes that cause sleep- Kjekshus, Helge. 1977. Ecology control and economic devel-
ing sickness will continue actively to shape the future opment in East African history: The case of Tangan-
of humankind in Africa. Because the most effective yika, 1850-1950. London.
means of control is continual and thorough surveil- Kolata, Gina. 1984. Scrutinizing sleeping sickness. Sci-
lance and treatment with available chemotherapy, ence 226: 956-9.
present-day health planners and administrators Lambrecht, Frank. 1964. Aspects of evolution and ecology
of tsetse flies and trypanosomiasis in prehistoric Afri-
must be aware of the history of this disease and the
can environment. Journal of African History 5: 1-23.
ease with which that history can repeat itself. Leishman, W. B. 1903. On the possibility of trypanoso-
Maryinez Lyons miasis in India. British Medical Journal 2: 1252-4.
Lucasse, C. 1964. Control of human sleeping sickness at
Bibliography present times. Annales de la Sociiti Beige du
Atkins, John. 1735. Voyage to Guinea, Brasil, and the Medecine Tropicale 44: 285-94.
West-Indies: In His Majesty's ships, the Swallow and Lyons, Maryinez. 1985. From "death camps" to cordon
the Weymouth. London. sanitaire: The development of sleeping sickness policy
Balfour, Andrew, et al. 1923. Interim report on tuberculosis in the Uele district of the Belgian Congo, 1903-1914.
and sleeping sickness in equatorial Africa. Geneva. Journal of African History 26: 69-91.
Behrman, Jack N. 1980. Tropical diseases: Responses of 1987. The colonial disease: Sleeping sickness in the so-
pharmaceutic companies. Washington, D.C. and Lon- cial history of northern Zaire, 1903-1930. Ph.D. the-
don. sis, University of California, Los Angeles.
Boothroyd, John C. 1985. Antigenic variation in African 1988a. Sleeping sickness policy and public health in the
trypanosomiasis. Annual Review of Microbiology 39: early Belgian Congo. In Imperial medicine and indige-
475-502. nous societies, ed. David Arnold, 105—24. Manchester.
Bradley, David J. 1986. Tropical medicine. In The Oxford 1988b. Sleeping sickness, colonial medicine and imperi-
companion to medicine, Vol. 2, ed. John Walton, Paul alism: Some connections in the Belgian Congo. In
B. Beeson, and Ronald Bodley Scott, 1393-9. Disease, medicine and empire, ed. Roy M. McLeod and
Burke, Jean. 1971. Historique de la lutte contre la maladie Milton Lewis, 242—56. London.
du sommeil au Congo. Annales de la Societe Beige du McKelvey, John M. 1973. Man against tsetse: Struggle for
Medecine Tropicale 51: 65-482. Africa. Ithaca, N.Y.
Carlson, Dennis. 1984. African fever: A study in British McNeill, William. 1977. Plagues and people. Oxford.
science, technology, and politics in West Africa, 1787— Manson, Patrick. 1898. Tropical diseases: A manual of the
1864. New York. diseases of warm climates. London.
Domergue, D. 1981. La Lutte contre la trypanosomiase en Martin, Gustave. 1923. Interim report on tuberculosis and
Cote d'lvoire, 1900-1945. Journal of African History sleeping sickness in equatorial Africa. Expert Commit-
22: 63-72. tee of the League of Nations. Health Committee.
Duggan, Anthony J. 1970. An historical perspective. In Matzke, G. E. 1988. Sleeping sickness control strategies in
The African trypanosomiases, ed. Hugh W. Mulligan, Tanzania. In Health and disease in tropical Africa:
xli—lxxxviii, London. Geographical and medical viewpoints, ed. Rais Akhar,
Eyidi, Marcel Beby. 1950. Le Vainqueur de la maladie du 359-72. London.
sommeil: LeDocteurEugene Jamot, 1879—1937. Paris. Maurice, G. K. 1930. The history of sleeping sickness in
Ford, John. 1971. The role of the trypanosomiases in Afri- the Sudan. Journal of Royal Army Medical Corps 55:
can ecology. Oxford. 161-241.
Goodwin, Leonard G. 1987. Chemotherapy and tropical Molyneux, D. H., and R. W. Ashford. 1983. The biology of
disease: The problem and the challenge. In Chemo- Trypanosoma and Leishmania, parasites of man and
therapy of tropical diseases, ed. M. Hooper, 1-18. domestic animals. London.
Chichester. Morel, E. D. 1968. E. D. Morel's history of the Congo reform
Hall, D. R., et al. 1984. A potent olfactory stimulant and movement, ed. William R. Louis and Jean Stengers.
attractant for tsetse isolated from cattle odors. Insect Oxford.
Science and Its Application 5: 335—9. Morris, K. R. S. 1963. The movement of sleeping sickness
Hoeppli, R. 1969. Parasitic diseases in Africa and the West- across Central Africa. Journal of Tropical Medicine
ern Hemisphere. Basel. and Hygiene 66: 159-76.
Jamot, Eugene. 1920. Essai de prophylaxie m6dicale de la Mulligan, Colonel H. W. 1970. The African trypanoso-
maladie du sommeil dans 1'Oubangui-Chari. Bulletin miases. London.
de la Societi de Pathologie Exotique et de Ses Filales Musambachime, Mwelwa. 1981. The social and economic
13: 340-76. effects of sleeping sickness in Mweru—Luapula, 1906—
Jordan, Anthony M. 1986. Trypanosomiasis control and 1922. African Economic History 10: 151-73.
African rural development. London. Ruppol, J. F., and K. Libala. 1977. Situation actuelle de la

VTII.3. Ainhum 561
lutte contre la maladie du sommeil au Zaire. Annales disposition has not been ruled out (Curban and
de la Societe Beige du Medecine Tropicale 57: 299-314. Moura 1965). Surgery is the mainstay of therapy, for
Stark, E. 1977. Epidemic as a social event. International in most cases prompt amputation may allow the
Journal of the Health Sciences 74: 681-705. patient to escape pain and infection.
Winterbottom, Thomas. 1803. An account of the native Donald B. Cooper
Africans in the neighbourhood of Sierra Leone to
which is added an account of the present state of medi-
cine among them. London. Bibliography
World Health Organization. 1985. African trypanoso- Browne, S. G. 1965. True ainhum: Its distinctive and differ-
miases. In Tropical disease research, 7th Programme entiating features. Journal of Bone and Joint Surgery
Report. Geneva. 47B(1): 52-5.
1986. Trypanosomiasis control manual. Geneva. Burgdorf, Walter H. C , and Robert W. Goltz. 1987. Ain-
hum and other forms of constricting bands (pseudo-
ainhum). In Dermatology in general medicine, 3d edi-
tion, ed. Thomas Fitzpatrick et al., 1031-2. New York.
Cole, C. J. 1965. Ainhum: An account of fifty-four patients
with special reference to etiology and treatment. Jour-
VIII.3 nal of Bone and Joint Surgery 47B(1): 43-51.
Ainhum Curban, Guilherme V., and J. B. Athayde Moura. 1965.
Ainhum: Consideragoes sobre o conceito nosologico.
Revista do Hospital das Clinicas: Faculdade de Me-
dicina da Universidade do Sao Paulo 20: 225—34.
The name ainhum is derived from a word in the Silva Lima, J. F. da. 1867. Estudo sobre o "Ainhum"-
Nagos language of East Africa meaning "to saw." It mol6stia ainda nao descrita, peculiar a raca ethi6-
describes the development of constricting bands pica, e afetando os dedos minimo dos pes. Gazeta
about digits, almost always the fifth, or smallest, Medica da Bahia 1: 146-51, 172-6.
toe, which ultimately undergoes self-amputation.
Typically the disease is bilateral (i.e., affecting both
small toes).
Ainhum is ordinarily a disease of middle-aged
black Africans of both sexes accustomed to going
barefoot. The disease is common in Nigeria and East VIII.4
Africa, and has been reported less frequently in Alzheimer's Disease
other tropical areas, including India, Burma, Pan-
ama, the Antilles, and Brazil (Burgdorf and Goltz
1987). In 1906, Alois Alzheimer first described a neurologi-
Ainhum was noticed frequently among slaves in cal disorder of the brain associated with global dete-
Brazil and was first described in detail in 1867 by rioration of cognitive functioning and resulting in
Brazilian doctor J. F. da Silva Lima who also named severe social impairment. Once thought rare, senile
the disease. Silva Lima's description is outstand- dementia of the Alzheimer's type is the most com-
ingly accurate, and has not been bettered. In one monly acquired progressive brain syndrome. Alz-
case he wrote that the toe had taken the shape of a heimer's disease begins with insidious intellectual
small oval potato; the covering skin had become and memory loss as the brain becomes shrunken from
"coarse and scabrous, and very tender to touch. As nerve cell loss and advances over 5 to 15 years to a
the disease progressed, wrote Silva Lima, a strong chronic vegetative state. Progressive cognitive, psy-
constriction appeared at the base of the toe, and, as chological, and social dysfunction has a profound ef-
the blood flow to the toe was impeded, the bones fect on family and friends. Alzheimer's disease is
ceased to exist. In time, spontaneous amputation of associated with significant morbidity, and it may be
the toe occurred (Cole 1965; Silva Lima 1867). the fourth leading cause of death in the United States
The cause of ainhum is unknown. According to (Katzman 1976). D. K. Kay and colleagues (1964)
Walter Burgdorf and Robert Boltz, chronic trauma, showed the average survival for demented men to be
infection, hyperkeratosis, decreased vascular supply, 2.6 years after the diagnosis of illness, whereas the
and impaired sensation may alone or in combination survival period for nondemented men of the same age
produce excessivefibroplasia,and lead to ainhum. It was 8.7 years. However, there is great variability in
is an acquired condition, although a hereditary pre- survival statistics from different studies.

Although Alzheimer's disease is the leading cause cits may predominate initially. Spatial relationship
of dementia, its etiology remains unknown, and impairment is common early. The patient may also
treatment is supportive. The illness is a major prob- complain of word-finding difficulty or demonstrate
lem among the elderly. Approximately 4 percent of mild problems in speaking and understanding. In
the population over the age of 65 is affected, and by cases where damage to the frontal lobes of the brain
age 80, prevalence reaches 20 percent (Brodie 1982). predominates, the patient presents with judgment
As the elderly population of the United States in- problems.
creases, the number of persons with Alzheimer-type
dementia will also increase. Alzheimer's disease ex- Diagnosis
ists in the presenium, but it has been difficult to Diagnosis of Alzheimer's disease remains a diagno-
document a bimodal distribution with regard to age. sis of exclusion. In the absence of biological markers
Even though pathological changes in presenile and for the illness, it is not surprising that clinical diag-
senile forms of the illness are similar, there is evi- nosis may be less than accurate and, in fact, may be
dence that early- and late-onset Alzheimer-type de- correct in as few as one-half of Alzheimer-type senile
mentia differ clinically (Seltzer and Sherwin 1983). dementia cases (Alafuzoff et al. 1987). Not only do
cognitive changes associated with normal aging over-
Clinical Manifestations and Diagnosis lap those found in the early stages of dementia, but
also a wide spectrum of conditions may produce de-
Clinical Manifestations mentia. In any given patient, several conditions lead-
Alzheimer-type senile dementia is associated with ing to progressive cognitive decline may occur simul-
behavioral signs and symptoms that divide into corre- taneously. Even neuropathologists may encounter
sponding stages. In the early stage, subjective mem- diagnostic difficulty and may be reluctant to make
ory deficit may be difficult to differentiate from be- the diagnosis without the proper clinicopathological
nign senile forgetfulness. However, elderly persons correlation (Khachaturian 1985).
with benign forgetfulness are unable to recall unim- The clinical diagnosis of Alzheimer-type senile de-
portant details, whereas patients with Alzheimer- mentia always requires documentation of progres-
type senile dementia forget important and unimpor- sion (McKhann et al. 1984). Reports from family and
tant information randomly (Krai 1962). friends provide the most valid measures of cognitive
Typically, patients with Alzheimer's disease forget decline in elderly persons and support the clinician's
where things are placed, become lost easily, and judgment that global intellectual deterioration has
have difficulty remembering appointments. Both re- occurred.
cent and remote memory are affected, which may be
documented by neuropsychological testing. When pa- Clinical Staging and Evaluation
tients recognize their cognitive and social losses, Progression is usually gradual but with fluctuation
many develop feelings of hopelessness and despon- of symptom severity. The patient may react very
dency. As Alzheimer-type senile dementia pro- dramatically to changes in the living situation, to
gresses, the patient enters a confusional phase with losses of friends or relatives, or even to admission to
more global impairment of cognitive functioning the hospital for evaluation. These acute changes
(Schenk, Reisberg, and Ferris 1982). Changes in probably represent withdrawal of orienting stimuli
higher cortical functions, such as language, spatial and emotional distress rather than progression of
relationships, and problem solving, become more ap- the disease process.
parent. A number of clinical staging strategies have been
During the confusional phase, obvious denial be- developed, but there is no entirely satisfactory tech-
gins to replace anxiety, and cognitive deficits are nique as yet. Simplified rating scales (such as the
noticeable to family and friends. In the final phase, Folstein Mini-Mental) may be efficiently adminis-
the patient becomes aimless and may hallucinate or tered, but only identify the presence or absence of
be restless and agitated. Language disorders such as cognitive impairment. Other cognitive scales are
aphasia occur in late stages. Abnormal neurological more accurate, but they are also more complex and
reflexes, indicative of loss of higher neural inhibi- may take an hour to administer. The Blessed Scale
tion, are common. Not all patients with Alzheimer- (Blessed, Tomlinson, and Roth 1968) obtains infor-
type senile dementia demonstrate the classic evolu- mation from collateral sources and has the advan-
tion of symptoms. Although almost all patients have tage of documented correlation with pathological le-
some memory impairment, other focal cortical defi- sions at autopsy. Unfortunately, it provides little

VTII.4. Alzheimer's Disease 563
information about cognitive performance. Other be- tors for stroke should be evaluated and controlled
havioral scales rely solely on the interviewer's inter- when possible in every patient with early dementia.
pretation of the patient's performance on several J. L. Cummings and D. F. Benson (1983) suggest
activities (Salzman, Kochansky, and Shader 1972). that all forms of dementia other than Alzheimer's
Psychometric tests may be useful in delineating and Pick's disease show signs of subcortical dysfunc-
patterns of cognitive deficit at various stages of se- tion in addition to more obvious cortical signs. This
verity and in identifying the qualitative aspects of is especially true of dementia associated with basal
performance deficit. Although laboratory tests are ganglia disease, which regularly produces the char-
sometimes used to support the diagnosis of Alz- acteristic subcortical pattern of slowed thinking, at-
heimer's disease, the laboratory is actually more tention deficit, memory impairment, and apathy.
useful in excluding other causes of cognitive deterio- Subcortical dementia occurs in 20 to 40 percent of
ration. Atrophy of the cerebral cortex is often seen patients with Parkinson's disease (Marttila and
on computed tomography, but it is frequently Rinne 1976) and is also observed in progressive su-
overinterpreted. There is a poor correlation between pranuclear palsy, Huntington's chorea, and Wilson's
size of the brain ventricles, widened cerebral sulci, disease. Symptomatic treatment of basal ganglia dis-
and severity of dementia (Fox, Topel, and Huckman ease occasionally improves the associated dementia.
1975). Attempts have been made to correlate demen- Antidepressants may improve cognition as well as
tia with brain density (Albert et al. 1984). Unfortu- any associated depression (Albert, Feldman, and Wil-
nately, results have been inconsistent, and there is a lis 1974).
pressing need for quantitative computed tomo- Depression is the most common treatable illness
graphic studies that correlate the scanning images that may masquerade as Alzheimer-type senile de-
with clinical and pathological findings. mentia. Cognitive abilities return to baseline levels
when depression is treated. Because some patients
Differential Diagnosis with early dementia have secondary depression, de-
Alzheimer's disease may be difficult to distinguish mentia and pseudodementia may be difficult to dif-
from other untreatable progressive dementias, which ferentiate. The depression that occurs in the early
include Pick's disease, demyelinating diseases, slowly stages of Alzheimer-type senile dementia tends to
progressive brain tumors, inflammatory diseases, ar- resolve as the disease progresses. Pseudodemented,
teriosclerotic vascular diseases, toxic exposures, re- depressed patients are apt to have poor attention,
peated metabolic insults, deficiency diseases, late se- inconsistent cognitive changes, absence of cortical
quelae of head trauma, Creutzfeldt-Jakob disease, signs, weight loss, sleep disturbance, guilt, poor self-
and viral and fungal infections. Dementia is common esteem, a past personal family psychiatric history,
in patients with terminal cancer and may result from and a more rapid onset.
a variety of causes. In contrast, patients with cortical dementia of
The evaluation of a patient presenting with de- Alzheimer-type often show insidious onset, slow pro-
mentia often reveals untreatable causes, but treat- gression, early loss of insight, amnesia for remote
able dementia is discovered in 20 to 25 percent of and recent events, spatial disorientation, reduction
such patients (Wells 1977). in spontaneous speech, and occasionally aphasia.
Treatable causes of dementia include pernicious Agnosia, apraxia, increased muscular tension, and
anemia, thyroid disorders, chronic central nervous abnormal neurological reflexes may also be present
system infections, toxic exposures, surgically correct- (Gustafson and Nilsson 1982).
able mass lesions, inflammatory vascular disease,
certain forms of arteriosclerotic vascular disease, Epidemiology and Etiology
and normal-pressure hydrocephalus. Occasionally, Alzheimer's disease is ultimately a neuropatho-
iatrogenic dementia, related to the inappropriate logical diagnosis. A wide variety of gross morphologi-
use of medication or to idiosyncratic drug effects, is cal and microscopic changes occur in the brain of
identified. Multi-infarct dementia may be the most patients with Alzheimer's disease. Unfortunately,
difficult progressive dementia to differentiate from many of these changes are difficult to distinguish
Alzheimer's disease despite the fact that specific di- from alterations that occur in the brain of normal
agnostic criteria for each have been promulgated in elderly persons, who also show some atrophy of
the official nomenclature. There is an obvious need white matter and, to a lesser extent, gray matter.
for a valid and reliable set of clinical criteria to Neurochemically, Alzheimer's disease has been as-
distinguish the two conditions. Nonetheless, risk fac- sociated with a decrease in the activity of the en-

zyme choline acetyltransferase, which synthesizes of chromosome 21 (St. George-Hyslop et al., 1987).
acetylcholine (Coyle, Price, and DeLong 1983). Recent data favor the hypothesis of a genetically
Acetylcholine is the neurotransmitter most involved induced overproduction of amyloid protein as a fac-
in memory circuits. Levels naturally decrease with tor in the cause of Alzheimer's disease.
age, but in patients with Alzheimer-type dementia, When families request genetic counseling, one can
choline acetyltransferase may decline to 20 percent only explain what is known about the genetic fac-
of that in age-matched control subjects. Other tors. In a family with a single Alzheimer victim, the
neurochemical changes associated with Alzheimer's lifetime risk for a close relative also to develop de-
disease include a decrease in gamma-aminobutyric mentia is approximately 10 percent. Since most de-
acid, substance P, and somatostatin-like activity in mentia develops over the age of 70, this is a rela-
the brain of patients with Alzheimer-type dementia. tively small probability. In families with dementia
The significance of these findings is unclear. occurring over several generations, an autosomal
Although it is generally recognized that genetic dominant inheritance is probable, and the risk for
influences are important in Alzheimer's disease, the children of an affected parent may approach 50 per-
exact nature of these genetic influences also remains cent. In these families, optimum health manage-
unclear. There are some families that have a large ment indicates the suspicion of dementia in every
number of members with the clinical or pathological elderly person with altered environmental-social in-
diagnosis of Alzheimer's disease (Cook et al. 1979). teractional skills, multiple physical complaints in
The most important practical point regarding these the absence of objective disease, or vague and un-
kindreds is that most of them meet criteria for au- clear history. Autopsy can be suggested to confirm
tosomal dominant inheritance. Penetrance of the diagnosis to trace the pedigree more accurately.
gene exceeds 90 percent in most of these families. As Environmental causes for Alzheimer's disease
a result, the children of an affected person have a 50 have also been suggested. Some investigators have
percent risk of developing dementia if they survive linked focal intranuclear accumulation of aluminum
to the age at which dementia begins in that family. to the presence of neurofibrillary degeneration in
The exact proportion of familial cases is unknown, hippocampal neurons. The relationship of aluminum
but they may account for as many as 10 percent of to Alzheimer-type senile dementia, however, is not
all cases of Alzheimer-type dementia (Kokmen well accepted (Markesbery et al. 1981). General de-
1984). There is some familial clustering in families cline of immunologic competence with aging suggests
without dominant inheritance. It would appear that an autoimmune mechanism. Although elevated lev-
concordance for dementia is somewhat higher in els of brain antibody have been demonstrated in
monozygotic versus dizygotic twins, suggesting ge- Alzheimer's disease, antineuronal antibodies have
netic factors. On the other hand, concordance is not not been demonstrated in the central nervous system
100 percent, so environmental factors must have a (Watts, Kennedy, and Thomas 1981). Serum protein
role. Since age of onset varies within a twin pair, it abnormalities have been demonstrated, notably
may be difficult to be certain whether a given pair is changes in haptoglobin functions. Finally, a viral
truly discordant. cause has been proposed but not substantiated
An association has been shown also between Alz- (Wisniewski 1978).
heimer's disease and families that produce children
with Down syndrome (Heston and Masri 1966). Fur- Treatment
ther support for a link between Down syndrome Although the cause of this disease remains unclear,
and Alzheimer's disease is provided by the fact that good clinical management is nonetheless critical.
patients with Down syndrome tend to demonstrate Every effort should be made to maintain the pa-
neuropathological findings consistent with Alz- tient's independence within the limits of safety. Mea-
heimer-type senile dementia if they live to adult sures to maintain orientation, such as memory aids,
life. Since Down syndrome represents a disorder of eyeglasses, hearing aids, calendars, diaries, ade-
chromosome 21, a point of origin for the search for quate lighting, and organization of the patient's per-
the genetic determinants of Alzheimer's disease is sonal items, are helpful (Eisdorfer and Cohen 1981).
suggested. The amino acid sequence for the amyloid Appropriate locks to prevent unsafe wandering, and
that accumulates in the brains of patients with Alz- suitable safeguards on dangerous household appli-
heimer's disease is called the A4 beta-pleated ances must be utilized. Of course, the patient should
amyloid. The gene for the precursor has been identi- not be permitted to drive.
fied, cloned, and mapped to the proximal long arm Providing quality care, however, requires an un-

VIII.4. Alzheimer's Disease 565
derstanding of the health care delivery system in decades focused on whether it was an inevitable
which physicians and patients find themselves. Psy- product of aging, or rather an actual disease. Emil
chosocial management is based on enhancing the Kraepelin, one of the founders of modern psychiatry,
function of the care system that surrounds the pa- pointed out the difficulty in separating normal senil-
tient. This usually involves several family care- ity from senile dementia. In applying the new tech-
givers, who should receive accurate information con- nique of silver staining, Alzheimer, his student, iden-
cerning the disease and the prognosis. Caregivers tified a new neuropathological marker of dementia
must take care of themselves and may benefit sub- in the brain of a patient who had died at age 55 after
stantially from referral to a support group of the a 4-year illness. This marker was the neurofibrillary
Alzheimer's Disease and Related Disorders Associa- tangle, which he speculated was the marker of a
tion. Caregivers should be made aware of the factor dead cell. Alzheimer thus made the first correlation
that most insurance does not cover either commu- between clinical characteristics of dementia in a pa-
nity services or long-term care in nursing homes. A tient and pathological lesions in the brain. Kraepe-
competent legal adviser and appropriate financial lin later named the illness Alzheimer's disease in
counselor can be of substantial help. Even though honor of his former pupil.
many families want to keep elderly individuals in The question then became one of determining if
the home, in-home support services are expensive this disease was the same as senile dementia. It
and often not available. revolved around the ancient problem of what patho-
Alzheimer's disease remains a major challenge logical changes can be attributed to aging as opposed
not only to modern medicine but also to the health to other causes. Kraepelin had emphasized the
care delivery system, and to society at large. Not presenile nature of Alzheimer's disease, yet because
only is further research necessary in the diagnosis of its similarity to senile dementia some investiga-
and management of the disease itself, but also major tors suggested that Alzheimer's disease might be
changes are necessary in the health care delivery caused by "a premature onset of the aging process"
system if patients afflicted with this illness are to (Beach 1987). Also confusing the picture was the
get the care that they need. nineteenth-century notion which extended also into
the twentieth century: that cerebral arteriosclerosis
History might be the cause of senile dementia. By the late
Although Alzheimer's disease only recently "has ex- 1920s, there had been a sufficient accumulation of
ploded into public and scientific consciousness" case descriptions of dementia among the elderly that
(Rabins 1988), it doubtlessly has a long history un- statistical analysis could be brought to bear on the
der such rubrics as "senility," "hardening of the ar- problem. It was found that most of the cases did in
teries," and "dementia," to name but a few. Cer- fact occur between the ages of 50 and 60, sustaining
tainly senility and dementia are conditions that the notion of its presenile nature. In 1955 Martin
have been recognized for millennia. The Assyrians, Roth showed that mental changes could be triggered
Greeks, and Romans all knew and described them. by a variety of both "functional" and "organic" dis-
Peter V. Rabins (1988) credits J. E. D. Esquirol, eases, and by the 1960s two major groups of research-
however, for the first modern description, in 1838, of ers were at work on Alzheimer's disease. One,
what seems to have been Alzheimer's disease. headed by Robert Terry, was based at Albert Ein-
Esquirol wrote of a "senile dementia" that increases stein University, and the other, headed by Bernard
with age (Beach 1987). Seven years later, Wilhelm Tomlinson, Gary Blessed, and Roth, was located at
Griesinger published a textbook on mental disease Newcastle-upon-Tyne. From their work and from
that clearly recognized the condition of "presenile other studies, it became apparent, among other
dementia" caused by brain atrophy found at autopsy. things, that the changes in the brain found in cases
Neither of these reports, however, seems to have had of presenile dementia were the same as those in
much influence on investigators at the time (Wis- senile dementia (Katzman 1986; Vannoy and Greene
niewski 1989). 1989).
It was during the latter half of the nineteenth The discovery broadened the definition of Alz-
century that public as well as scientific concern for heimer's disease and thereby increased enormously
problems of the elderly increased considerably. With the number of individuals viewed as victims of it. It
that concern came the birth of the field of geriatrics also created major semantic problems. Previously
and increasing attention paid to dementia in the the presenile nature of Alzheimer's disease was a
elderly (Beach 1987). Much of the effort during these defining factor. Now the illness shown to be a major

affliction of the elderly population was called senile almost 1:4 chance of developing Alzheimer's disease
dementia of the Alzheimer type (SDAT), which psy- or a related disorder, estimates suggest that the num-
chiatrists call "primary degenerative dementia." Se- ber of these victims will increase from some 2.5
nile dementia (SD) has been used to mean either million in the late 1980s to about 4 million by the
SDAT or Alzheimer's disease (AD), but it may also turn of the century. As the 1990s began, it was fur-
refer to other forms of dementia in the elderly ther estimated that fully half of all nursing home
(Reisberg 1983). In addition, Alzheimer's disease patients in the United States are Alzheimer victims.
and senile dementia were often lumped together as The implications of the growing number of these
senility or as cerebral arteriosclerosis. This latter victims for health care delivery systems are stagger-
concept proved to be so tenacious that even as late as ing. In 1967 a White House conference on aging
the middle 1970s it was called "probably the most resulted in the creation of the National Institute on
common medical misdiagnosis" of the cause of men- Aging, which greatly facilitated research on Alz-
tal deterioration in the elderly (Beach 1987). heimer's disease. In 1983, a Task Force on Alz-
In the early 1980s, Alzheimer's disease was denned heimer's Disease was created by the Department of
as an "age-associated cognitive decline of gradual Health and Human Services, which has emphasized
onset and course, accompanied by Alzheimer-type the need for increased research and increased re-
neuropathologic brain changes" with "no distinction search funding, and in 1987 the journal Alzheimer's
with respect to age of onset" (Reisberg 1983), and was Disease and Associated Disorders -An International
thought to be responsible for 50 percent or more of all Journal was founded to report such research. As
dementias (Vannoy and Greene 1989). more and more resources are brought to bear, the
This definition is essentially the working one as outlook for breakthroughs in understanding the
we enter the last decade of the twentieth century. causes of Alzheimer's disease and treating it are
Experts at a 1990 conference on the illness believe more optimistic than in former times. But at the
that Alzheimer's disease is being diagnosed cor- time of writing, it remains a devastating disease
rectly in about 80 percent of cases, even though such whose etiology is unknown.
diagnoses can be confirmed only after death, and Joseph A. Kwentus
even though the etiology and epidemiology of the
disease remain obscure.
It may well be determined that Alzheimer's dis- Bibliography
ease is not a single disease but, rather, many differ- Alafuzoff, I., et al. 1987. Histopathological criteria for
ent diseases with multiple causes ranging from ge- progressive dementia disorders: Clinical pathological
netics to exogenous toxins. The extent to which age correlation and classification by multivariate data
and aging will rank among those causes remains a analysis. Ada Neuropathologica 74: 209-25.
subject of debate. Reports of the condition among Albert, M. T., R. G. Feldman, and A. L. Willis. 1974. The
subcortical dementia of progressive supranuclear
individuals in their 30s have been used to support
palsy. Journal of Neurology, Neurosurgery and Psy-
the contention that the disease is unrelated to aging. chiatry 37: 121-50.
On the other hand, there is a rising prevalence with Albert, M. T., et al. 1984. CT density numbers in patients
age, such that by age 85 and over, some 20 percent or with senile dementia of the Alzheimer type. Archives
more are demented. If, of course, Alzheimer's disease of Neurology 41: 1264-9.
is a specific disease or diseases (as opposed to an Bartus, R. T., et al. 1982. The cholinergic hypothesis of
inevitable product of the aging process for some 5 to geriatric memory dysfunction. Science 217: 408-17.
7 percent of the population over age 65), then, of Beach, Thomas G. 1987. The history of Alzheimer's dis-
course, there is hope for a cure. ease: The debates. Journal of the History of Medicine
The question, however, of why Alzheimer's disease and Allied Sciences 42: 327-49.
has been called the disease of this century - one that Blessed, G., B. E. Tomlinson, and M. Roth. 1968. The
association between quantitative measures of demen-
has only recently burst upon the developed world in
tia and of senile change in the cerebral grey matter of
epidemic proportions - is certainly bound up with elderly subjects. British Journal of Psychiatry 114:
advancing age for many and with the demographic 797-811.
changes that this has wrought. In 1900, there were Brodie, J. A. 1982. An epidemiologist views senile demen-
only 3 million Americans aged 65 or older. Today tia facts and fragments. American Journal of Epide-
there are 27 million, and it has been estimated that miology 115: 115-62.
in the year 2030 there will be 50 million. Given the Christie, J. E., et al. 1981. Physostigmine and arecoline:
fact that an individual who lives to be 80 has an Effects of intravenous infusions in Alzheimer pre-

VIII.4. Alzheimer's Disease 567
senile dementia. British Journal of Psychiatry 138: 1986. Alzheimer's disease. New England Journal of
46-50. Medicine 314: 964-73.
Cohen, E. L., and R. J. Wurtman. 1976. Brain acetylcho- Kay, D. W. K., P. Beamish, and M. Roth. 1964. Old age
line: Control by dietary choline. Science 191: 561-2. mental disorders in Newcastle-upon-Tyne. British
Cook, R. H., et al. 1979. Studies in aging of the brain: IV. Journal of Psychiatry 110:146-8.
Familial Alzheimer disease: relation of transmissible Khachaturian, Z. S. 1985. Diagnosis of Alzheimer's dis-
dementia, aneuploidy, and microtubular defects. Neu- ease. Archives of Neurology 42: 1097-105.
rology 29: 1404-12. Kokmen, E. 1984. Dementia: Alzheimer type. Mayo Clinic
Coyle, J. T., D. Price, and M. R. DeLong. 1983. Alzheimer's Proceedings 59: 35-42.
disease: A disorder of central cholinergic innervation. Krai, B. A. 1962. Forgetfulness: Benign and malignant.
Science 219: 1184-9. Canadian Medical Association Journal. 86: 257—60.
Cummings, J. L., and D. F. Benson. 1983. Dementia: A Markesbery, W. R., et al. 1981. Instrumental neutron acti-
clinical approach. London. vation analysis of brain aluminum in Alzheimer's dis-
Devanand, D. P., H. A. Sackeim, and R. Mayeux. 1988. ease and aging. Annals of Neurology 10: 511—16.
Psychosis, behavioral disturbance, and the use of Marttila, R. J., and U. K. Rinne. 1976. Dementia in Parkin-
neuroleptics in dementia. Comprehensive Psychiatry son's Disease. Acta Neurologica Scandinavica 54:
29: 387-401. 431-41.
Eisdorfer, C , and D. Cohen. 1981. Management of the Mayeux, R., Y. Stern, and S. Spanton. 1985. Clinical het-
patient and family coping with dementing illness. erogeneity in patients with dementia of the Alz-
Journal of Family Practice 12: 831-7. heimer type: Evidence for subgroups. Neurology 35:
Folstein, M. E, S. E. Folstein, and P. R. McHugh. 1975. 453-61.
Mini-mental state: A practical method for grading the McKhann, G., et al. 1984. Clinical diagnosis of Alz-
cognitive state of patients for the clinician. Journal of heimer's disease: Report of the NINCDS-ADRDA
Psychiatric Research 12: 189-98. ADRDA Work Group under the auspices of Depart-
Fox, T. H., J. L. Topel, and M. S. Huckman. 1975. Use of ment of Health and Human Services Task Force on
computerized tomography in senile dementia. Journal Alzheimer's disease. Neurology 34: 939—44.
ofNeurology, Neurosurgery and Psychiatry 38:948-53. Morris, J. C , et al. 1988. Consortium to establish a regis-
Gustafson, L., and L. Nilsson. 1982. Differential diagnosis try for Alzheimer's disease. Psychopharmacology Bul-
of presenile dementia on clinical grounds. Acta Psychi- letin 24: 641-52.
atrica Scandinavica 65: 194-209. Mundy-Castle, A. C , et al. 1953. The electroencephalo-
Harner, R. N. 1975. EEG evaluation of the patient with gram in the senile psychosis. Electroencephalography
dementia. In Psychiatric aspects of neurologic disease, and Clinical Neurophysiology 6: 245-52.
ed. D. F. Benson and D. Blumer, 63-82. New York. Nuwer, M. R. 1988. Quantitative EEG: II. Frequency
Haxby, J. V., et al. 1986. Neocortical metabolic abnormali- analysis and topographic mapping in clinical settings.
ties precede nonmemory cognitive defects in early Journal of Clinical Neurophysiology 5: 45-85.
Alzheimer's-type dementia. Archives of Neurology 43: Rabins, Peter V. 1988. Science and medicine in the spot-
882-5. light: Alzheimer's disease as an example. Perspectives
Hersch, E. L. 1979. Development and application of the in Biology and Medicine 31: 161-9.
extended scale for dementia. Journal of the American Reisberg, Barry. 1983. Alzheimer's disease. New York and
Geriatrics Society 27: 348-54. London.
Heston, L. L., and A. R. Masri. 1966. The genetics of Reisberg, B., et al. 1982. The Global Deterioration Scale
Alzheimer's disease: Associations with hematologic (GDS): An instrument for the assessment of primary
malignancy and Down's syndrome. Archives of Gen- degenerative dementia. American Journal of Psychia-
eral Psychiatry 34: 976-81. try 139: 1136-9.
Hughes, C. P., et al. 1982. A new clinical scale for the Reisberg, B., et al. 1983. The Brief Cognitive Rating Scale
staging of dementia. British Journal of Psychiatry (BCRS): Findings in primary degenerative dementia.
140: 566-72. Psychopharmacology Bulletin 19: 47-50.
Johnson, K. A., et al. 1987. Comparison of magnetic reso- Reynolds, C. F, et al. 1983. Electroencephalographic sleep
nance and roentgen ray computed tomography in de- aging, and psychopathology: New data and state of
mentia. Archives of Neurology 44: 1075-80. art. Biological Psychiatry 18: 139-55.
1988. Single photon emission computed tomography in Salzman, C , G. E. Kochansky, and R. I. Shader. 1972.
Alzheimer's disease: Abnormal iofetamine I123 uptake Rating scales for geriatric psychopharmacology — a re-
reflects dementia severity. Archives of Neurology 45: view. Psychopharmacology Bulletin 8: 3—50.
392-6. Schenk, N. K., B. Reisberg, and S. H. Ferris. 1982. An
Katzman, R. 1976. The prevalence in malignancy of overview of current concepts of Alzheimer's disease.
Alzheimer's disease: A major killer (editorial). Ar- American Journal of Psychiatry 139: 165-73.
chives of General Psychiatry 33: 217-18. Seltzer, B., and I. Sherwin. 1983. A comparison of clinical

features in early and late-onset primary degenerative Wisniewski, H. M. 1978. Possible viral etiology of
dementia: One entity or two? Archives of Neurology neurofibrillary changes and neuritic plagues. In
40: 143-6. Alzheimer's disease: senile dementia and related disor-
Sharp, P., et al. 1986. Application of iodine-I123 labeled ders, ed. R. Katzman, R. D. Terry, and K. L. Beck,
isopropylamphetamine imaging to the study of demen- 355-8. New York.
tia. Journal ofNuclear Medicine 27: 761-8. 1989. Alzheimer's disease and related disorders. New
Sojdel-Sulkhowska, E. M., and C. A. Marotta. 1984. York.
Alzheimer's disease brain: Alterations in RNA levels Wurtman, R. J., M, J. Hirsch, and J. Growdon. 1977. Leci-
and in a ribonuclease—inhibitor complex. Science 225: thin consumption raises serum free-choline levels.
947-9. Lancet 2: 68-9.
Spor, J. E., and R. Gerner. 1982. Does the dexamethasone
suppression test distinguish dementia from depres-
sion? American Journal of Psychiatry 139: 238-40.
St. George-Hyslop, P. H., et al. 1987. The genetic defect
causing familial Alzheimer's disease maps on chromo-
some 21. Science 235: 885-90.
VIII.5
Stern, Y., M. Sano, and R. Mayeux. 1988. Long-term ad- Amebic Dysentery
ministration of oral physostigmine in Alzheimer's dis-
ease. Neurology 38: 1837-41.
Summers, W. K., et al. 1986. Oral tetrahydroamino- Amebiasis is an infection of the colon caused by a
acridine in long-term treatment of senile dementia parasitic protozoan, the ameba Entamoeba histoly-
Alzheimer's disease. New England Journal of Medi- tica. Several species of ameba inhabit the large intes-
cine 315: 1241-5.
tine. Most are harmless commensals or minor para-
Terry, R. D., et al. 1981. Some morphometric aspects of the
brain in senile dementia of the Alzheimer type. An- sites, usually causing little or no clinical damage.
nals of Neurology 10: 184-92. The closely related species Entamoeba coli and
Thai, L. J., et al. 1983. Oral physostigmine and lecithin Entamoeba hartmanni are commensals, and infec-
improve memory in Alzheimer's disease. Annals of tion with E. histolytica is also often asymptomatic.
Neurology 13: 491-6. E. histolytica is probably a species complex, with a
Tierney, M. C, et al. 1988. The NINCDS-ADRDA Work number of morphologically similar forms with vary-
Group criteria for the clinical diagnosis of probable ing degrees of invasiveness. E. hartmanni, formerly
Alzheimer's disease: A clinicopathologic study of 57 believed to be a "small race" of E. histolytica, is now
cases. Neurology 38: 359-64. recognized as a separate nonpathogenic species.
Tomilson, D. E., G. Blessed, and M. Roth. 1968. Observa- Pathogenic amebas cause light to severe intestinal
tions on the brains of non-demented old people. Jour- damage (amebic dysentery) and sometimes spread to
nal of the Neurological Sciences 7: 331—56. the liver, lungs, brain, and other organs.
1970. Observations on the brains of demented old peo-
ple. Journal of the Neurological Sciences 11: 205—32.
Vannoy, John E, and James A. Greene. 1989. Alzheimer's Etiology
disease: A brief history. Journal of the Tennessee Medi- The parasite exists in two forms during its life cycle.
cal Association 82: 15—17. Active adults, trophozoites, multiply in the lumen of
Visser, S. L., et al. 1976. Visual evoked response in senile the colon. They frequently live there harmlessly,
and presenile dementia. Electroencephalography and feeding on the contents of the intestine. Some
Clinical Neurophysiology 40: 385-92. strains are generally commensal; others are highly
Volicer L., and L. R. Herz. 1985. Pharmacologic manage- pathogenic. Under conditions of stress, lowered host
ment of Alzheimer-type dementia. American Family resistance, or when a particularly pathogenic strain
Physician 32: 123-8. is involved, amebas invade the intestinal wall and
Watts, H., P. G. E. Kennedy, and M. Thomas. 1981. The cause abscesses. As they pass lower into the large
significance of antineuronal antibodies in Alzheimer's intestine, the drier environment stimulates them to
disease. Journal of Neuroimmunology 1: 107-16. form a cyst wall. The original cell nucleus divides
Wells, C. E. 1977. Dementia. Philadelphia. twice, producing four daughter nuclei. Cysts are
1979. Pseudodementia. American Journal of Psychiatry
passed with the feces and are infective when swal-
136: 895-900.
Wettstein, A., and R. Spiegel. 1984. Clinical trials with the lowed. Excystation takes place in the small intes-
cholinergic drug RS86 in Alzheimer's disease (AD) tine, and the young trophozoites, four from each
and senile dementia of the Alzheimer's type (SDAT). cyst, are carried in the fecal stream to the large
Psychopharmacology 84: 572-3. intestine. When dysentery occurs, trophozoites are

VIII.5. Amebic Dysentery 569
swept out too rapidly to encyst. Even though huge rier rate is between 2 and 5 percent; 31 amebiasis
numbers of amebas may be passed, they die quickly deaths were recorded from 1962 to 1971.
and are not infective. Persons with mild or no symp- Asymptomatic and clinical amebiasis is much
toms produce infective cysts, and it is they, not the more common in Third World countries. Surveys
patients with dysentery, who spread the disease. have shown prevalence rates of from 2 to 60 percent,
reflecting real differences as well as technical diffi-
Epidemiology culties. It is clearly a major public health problem in
Infection is by the fecal-oral route. Direct infection much of South and Southeast Asia, China, Africa,
can take place in circumstances of extreme crowding and parts of Latin America. Mexico appears to have
among children, as well as inmates of institutions for an unusually high prevalence. In the early 1980s it
the mentally retarded and insane, and among male was estimated that 5 to 6 milliom;linical cases and
homosexuals. Indirect spread, however, by fecal con- 10,000 to 30,000 deaths took place annually in a
tamination of food and water, is more common. Water- population of some 70 million. Men in their 20s and
borne epidemics of amebic dysentery are not so fre- 30s were most likely to die. In 1981, it was estimated
quent as those of bacillary dysentery, but the former that there were about 480 million infected people in
do occur when sewage contaminates wells or water the world: 290 million in Asia, 80 million in Africa,
pipes. Fruits and vegetables can become covered with 90 million in the Americas, and remarkably, 20 mil-
cysts when human feces are used as fertilizer, or lion in Europe. Serious disease struck 10 million in
when fruits are washed in contaminated water or are the Americas, 15 to 30 million Asians, 10 million
handled by a symptomatic or asymptomatic carrier. Africans, and few if any Europeans. The global
Flies and cockroaches can mechanically transmit death toll was between 40,000 and 110,000.
cysts from feces to food. The disease thus nourishes in
poor sanitary conditions but is rare where good per- Diagnosis, Clinical Manifestations, and
sonal hygiene is practiced and where water and Pathology
sewer systems function properly. Dogs, cats, and mon- Diagnosis depends on microscopic examination of
keys can be infected in the laboratory, but there is nostools, serologic tests, and clinical symptoms. The
evidence that animal reservoirs have an epidemiolog- classic method, discovery of trophozoites or cysts in
ical significance. stools, is tedious and requires considerable skill,
even with modern equipment and staining tech-
Distribution and Incidence niques. Trophozoites remain active only in fresh
Infection with E. histolytica occurs around the world, specimens and must be distinguished from commen-
although both commensal and pathological amebia- sal species and white blood cells. Preserved fecal
sis is more common in poor, tropical countries. Preva- specimens may be concentrated and stained, but de-
lence rates vary greatly, as does the proportion of tecting the adults and cysts and identifying them
infections that result in clinical disease. accurately are still difficult procedures. Further-
Amebiasis, especially clinical disease, is rare to- more, since trophozoites and cysts are not continu-
day in developed countries and is confined largely to ally passed, more than one sample must be exam-
specific groups such as residents of institutions, ined. Three or more specimens collected on separate
male homosexuals, travelers, and immigrants. In days will find 80 to 90 percent of infections; fewer
the United States from 3,000 to 4,000 cases were will be needed in symptomatic cases, as trophozoites
reported annually in the 1960s through the late are most readily detected in bloody patches in stools.
1970s. However, a spurt to roughly twice that level Serologic tests also have limitations. Antibodies do
occurred in 1979-84. The disease was concentrated not form unless amebas reach the bloodstream. It
in Texas and California and was probably due to has been estimated that antibodies circulate in 85 to
increased immigration from Mexico and Southeast 90 percent of patients with liver abscess but in only
Asia. 50 to 80 percent of those with severe dysentery.
On the other hand, cases may be significantly Serologic tests detect antibodies from recovered as
underreported. One recent estimate suggests that well as active cases, which further limits the use of
the real annual total probably exceeds 100,000, and, such methods in prevalence surveys.
in a 1970 study, 4 percent of military recruits had Amebas cause disease when they invade the
positive serologic tests. As recently as the early mucosal and submucosal layers of the large intes-
1950s, infection rates of 10 to 20 percent were found tine, producing characteristic flask-shaped lesions.
in some rural southern counties. In Britain the car- In severe cases the lesions become large and conflu-

ent, resulting in substantial tissue destruction, History
bleeding, loss of fluids, and sloughing of patches of Little is known of the early history of amebiasis. The
mucosa. Damage to the intestinal wall reduces wa- disease probably did not become a serious problem
ter absorption, and loose stools with blood and mu- until people began to adopt a sedentary, agricultural
cous are passed. In addition to severe and perhaps way of life. Dysentery has been described in the
fatal damage to the gut, amebas sometimes pene- early medical writings of Europe and Asia, and out-
trate through the muscular coat of the bowel, where breaks were frequent in military units, on slave
they enter the bloodstream and are carried to other ships, and in prisons. It is generally impossible, how-
organs, especially the liver. Intestinal perforation ever, to determine whether amebic or bacillary dys-
may result in fatal peritonitis. Large abscesses may entery was involved in any particular outbreak of
form in the liver, with grave and sometimes fatal the "flux."
consequences. Amebas may also migrate from the British doctors in India provided good clinical ac-
liver through the diaphragm to the lungs and cause counts of amebiasis in the early nineteenth century.
new abscesses there. Brain abscesses are rare, but In 1828 James Annesley published an important
lethal. Very destructive skin ulcerations can also study, based on clinical and pathological work,
occur, especially around the anus. which clearly linked the intestinal and hepatic as-
Clinical symptoms of intestinal amebiasis range pects of the disease. The pathogen was described in
from mild diarrhea and abdominal discomfort to fre- 1875 by a Russian physician, Fedor A. Losch. Losch,
quent loose stools with blood mucus, severe pain, working in St. Petersburg with a patient from north-
emaciation, and prostration. Onset is generally in- ern Russia, noted the clinical course of the disease,
sidious. Liver involvement may develop without evi- identified the ameba, and was able to produce simi-
dence of intestinal disease. Symptoms include se- lar lesions in dogs by feeding them ameba-rich stools
vere, continuous pain, enlarged and tender liver, from his patient. Losch, however, believed that some-
fever, and weakness. Diagnosis is by biopsy or serol- thing else initially caused the disease and that the
ogy. Chronic amebiasis, both intestinal and hepatic, ameba merely "sustained" it. Technical problems,
is sometimes very difficult to identify. especially in identifying amebas and determining
Differential diagnosis must rule out bacillary dys- which were pathogenic and which were harmless,
entery. Amebic dysentery tends to be a chronic dis- greatly impeded further research.
ease with a gradual onset and little or no fever. The Stephanos Kartulis kept interest in the subject
stools tend to be more abundant but less frequent alive in the 1880s. Working in Cairo, he established
and not to be bright red with blood, as is common in that an ameba was the probable cause of tropical
bacillary dysentery. Amebic dysentery has a longer dysentery and managed to transmit infection to kit-
incubation period, 20 to 90 days or more, compared tens. Then in 1890, a Canadian, Henri Lafleur, and
to 7 days or less for the bacillary form. Finally, with an American, William Councilman of Johns Hop-
its shorter incubation period and greater probability kins, published a definitive study of the pathology of
of water transmission, bacillary dysentery is more the disease. Two German investigators, H. Quincke
likely to occur in dramatic epidemics. and E. Roos, distinguished between a pathogenic
and a commensal ameba of humans, on clinical and
Prevention morphological grounds, as well as by infection ex-
Prevention is achieved with improved sanitation, periments on kittens. Still, the situation remained
especially good water and sewer systems and proper confused, as ameba identification and taxonomy was
washing of fruits, vegetables, and hands. Routine controversial and many research results could not be
chlorination of water does not destroy cysts. A Brazil- replicated. Doubts about the significance of patho-
ian root, ipecacuanha, and its active ingredient, genic amebas were widespread in the early 1900s,
emetine, have been given orally to treat dysentery despite painstaking studies like those of Leonard
since the seventeenth century. It was first given by Rogers in Calcutta. Even Sir Patrick Manson, per-
injection in 1912 and, despite its toxicity, is some- haps the single most important figure in tropical
times still employed for both intestinal and ex- medicine, expressed skepticism about the role of
traintestinal amebiasis. Safer drugs, such as metro- amebas in dysentery as late as 1909. Ernest L.
nidazole, are usually employed but must be given Walker (1913), an American scientist working in the
over 10- to 20-day periods and relapses are frequent. Philippines, established the basic outline of the life
Infection does not produce immunologic protection cycle of E. histolytica and cleared some of the confu-
against reinfection with the same or another strain. sion about nonpathogenic forms with a series of feed-

VIII.6. Anemia 571
ing experiments on volunteer Filipino convicts. The
discovery of methods to raise amebas in culture in VIII.6
1925 has contributed to further clarification. Many Anemia
mysteries still remain, however, as to distinctions
between pathogenic and nonpathogenic strains, and
factors such as diet, stress, and concomitant infec- Anemia, an insufficiency of red blood cells (RBC)
tions that trigger invasiveness in longstanding, and hemoglobin for oxygen-carrying needs, results
asymptomatic infections. from a variety of disease processes, some of which
K. David Patterson must have existed since ancient times. It was de-
fined in quantitative terms in the mid-nineteenth
Bibliography century, but before that the evidence of anemia is
Foster, W. D. 1965. A history of parasitology. Edinburgh. found in the descriptions of pallor or in the occur-
Kean, B. H., Kenneth E. Mott, and Adair J. Russell, eds. rence of diseases that we now know cause anemia.
1978. Tropical medicine and parasitology: Classic in- For example, lead poisoning decreases RBC produc-
vestigations, Vol. I, 71-168. Ithaca and London.
tion and was apparently widespread in Rome. Intesti-
Parasitic Diseases Programme, World Health Organiza-
nal parasites cause iron deficiency anemia and were
tion. 1986. Major parasitic infections: A global review.
World Health Statistical Quarterly 39: 145-60.
known to exist in ancient times. Parasites found in
U.S. Public Health Service. Centers for Disease Control. paleopathological specimens include Ascaris lumbri-
1986. Summary of notifiable diseases, United States, coides, Trichiuris trichiuria, and various species of
1986. Athens. Taenia (ovis, globosa, solium, and saginata), all of
Walker, E. L. 1913. Experimental entamoebic dysentery. which can cause intestinal blood loss and anemia.
Philippine Journal of Science 8: 253-371. Diphyllobothrium latum, which leads to malabsorp-
Walsh, Julia A. 1986. Problems in recognition and diagno- tion of vitamin B12 and a megaloblastic anemia, has
sis of amebiasis: Estimation of the global magnitude been found in mummies in Prussia and Peru.
of morbidity and mortality. Reviews of Infectious Dis- Congenital abnormalities in RBC metabolism, in-
eases 8: 228-38. cluding glucose 6-phosphate dehydrogenase (G6PD)
Wilcocks, Charles, and P. E. C. Manson-Bahr. 1972. Man-
deficiency and various forms of thalassemia and
son's tropical diseases. London.
World Health Organization. 1980. Parasite-related diar-
sickle-cell disease, were probably present also in an-
rheas. Bulletin of the World Health Organization 58: cient times. Thalassemia protects against malaria,
819-30. and the incidence of the relatively mild, hetero-
Wright, Willard H. 1955. Current status of parasitic dis- zygotic form of thalassemia (thalassemia minor)
eases. Public Health Reviews 70: 966-75. probably increased in the Mediterranean region af-
ter the appearance of falciparum malaria, the most
fatal form of the disease.
Iatrogenic anemia was also common throughout
most of recorded history, because bleeding was con-
sidered therapeutic from Greek and Roman times
until the mid-nineteenth century.
Quantitation of Hemoglobin
The first quantitation of blood elements is attributed
to Karl Vierordt of Tubingen, who published his
method for counting RBC in 1852. The method was
laborious, however, requiring some 3 hours, and
other methods for diluting the blood and the use of
pipets and counting chambers were subsequently
developed. George Hayem of the University of Paris
introduced a diluting solution in 1875. (It was the
same saline solution he used intravenously to treat
cholera.) Hayem observed that the average size of
erythrocytes in chlorosis was smaller than normal (6
[Am vs. 7.5 \im in diameter) and that the amount of

hemoglobin per RBC was decreased in chlorosis patients with pernicious anemia, he fed them 100 to
(Wintrobe 1985). 240 grams of liver a day. He observed that the
The quantitation of hemoglobin specifically was in- reticulocytes (an index of bone marrow activity)
troduced in 1899 by Theodur W. Tallquist of Finland. started to rise 4 to 5 days after the liver diet was
The results, reported as percentages of "normal," had begun. In fact, patients showed a consistent rise in
a wide margin of error, but the method was used well RBC count and hemoglobin levels whenever they
into the mid-twentieth century. Other physicians had consumed liver in adequate amounts. In the at-
measured the hematocrit in centrifuged, anticoagu- tempt to purify the protein in liver, it was found
that extracts were effective, and subsequently,
lated blood, or had used the size of red blood cells and
a color index as measures of hemoglobin concentra- cyanocobalamin - vitamin B12 - was identified. It
tion. In 1903 the "volume index" was introduced. It was purified in 1948 and synthesized in 1973 (Cas-
was clear that in various forms of anemia, the red celltle 1980; Wintrobe 1985).
size and concentration of hemoglobin in the red blood The possible role of the stomach in PA was pointed
cells varied (Wintrobe 1985). out by Austin Flint in 1860, only 5 years after Addi-
son's description of the ailment appeared. In 1921, P.
Classification Levine and W. S. Ladd established that there was a
There are many conditions or deficiencies that result lack of gastric acid in patients with PA even after
in anemia. This section will identify several types of stimulation. William B. Castle established that gas-
anemia prevalent today. tric juice plus beef muscle was effective in treating
pernicious anemia, although either alone was not.
Pernicious Anemia (PA) An autoimmune basis for development of pernicious
Awareness of this type of anemia appears in the anemia has been established in recent years
second half of the nineteenth century. Thomas Addi- (Doniach, Roitt, Taylor 1963; Castle 1980).
son of Guy's Hospital described a severe, usually
fatal form of anemia in 1855. Macrocytes were recog- Iron-Deficiency Anemia
nized by Hayem in 1877; he also noted a greater Iron-deficiency anemia is by far the most common
reduction of hemoglobin than of red blood cells in cause of anemia in every part of the world today
pernicious anemia. In 1880, Paul Ehrlich found (Davidson and Passmore 1969). It undoubtedly ex-
large nucleated RBC in the peripheral blood contain- isted in ancient times as well. In this condition,
ing dispersed nuclear chromatin; he called them fingernails develop double concave curvature, giv-
megaloblasts, correctly concluding that they were ing them a spoon shape (koilonychia). A Celtic tem-
precursors of Hayem's giant red cells that had es- ple at Nodens, in Gloucestershire, England, built in
caped from the marrow (Castle 1980). Ascelpian style after the Romans had left Britain in
In 1894, T. R. Fraser of Edinburgh became the the fourth century A.D., contains a votive offering of
first physician reported to have fed liver to patients an arm fashioned crudely proximally but with in-
with PA. Although he achieved a remission in one creasing detail distally; it shows characteristic
patient, others could not immediately repeat his suc- koilonychia (Hart 1980).
cess (Castle 1980). But in 1918, George H. Whipple Pallor, the hallmark or cardinal sign of anemia, is
bled dogs and then fed them canned salmon and seen especially in the face, lips, and nails, often
bread. After the dogs became anemic, he needed to imparting a greenish tint to Caucasians, a present-
remove very little blood to keep the hemoglobin low, ing sign that led to the diagnosis of chlorosis or the
although when the basal diet was supplemented, he "green sickness" in the sixteenth century. In the
found that he needed to bleed them more often. It seventeenth century, pallor became associated in the
turned out that liver was the most potent supple- popular mind with purity and femininity, and
ment, but it was not until 1936 that hematologists chlorosis became known as the "virgin's disease"
realized that the potency of liver was due to its iron (Hart 1980). Constantius I, father of Constantine the
content (Whipple and Robsheit-Robbins 1925). Great, was called Constantius Chlorus, because of
George Richards Minot of Harvard University be- his pale complexion (Hart 1980), and it seems most
came interested in the dietary history of his pa- likely that he had a congenital form of chronic ane-
tients following the first reported syndromes due to mia. (He came from an area known today to have a
deficiency of micronutrients. He focused attention relatively high frequency of thalassemia.)
on liver after Whipple's observations in dogs; in Preparations containing iron were used therapeu-
trying to increase the iron and purines in the diet of tically in Egypt around 1500 B.C. and later in Rome,

VIII.6. Anemia 573
suggesting the existence of iron deficiency. In 1681, ited to blacks; it is found among Sephardic and Kurd-
Thomas Sydenham mentioned "the effect of steel ish Jews, Sardinians, Italians, Greeks, Arabs, and in
upon chlorosis. The pulse gains in strength and fre- the Orient among Filipinos, Chinese, Thais, Asiatic
quency, the surface warmth, the face (no longer pale Indians, and Punjabis. It has not been found among
and death like) a fresh ruddy coulour. . . . Next to North American Indians, Peruvians, Japanese, or
steel in substance I prefer a syrup . . . made by steep- Alaskan Eskimos.
ing iron or steel filings in cold Rhenish wine. . . ." In The first documented report of drug-induced (as
1832 P. Blaud described treatment of chlorosis by opposed to fava bean-induced) hemolytic anemia ap-
use of pills of ferrous sulfate and potassium carbon- peared in 1926 following the administration of the
ate that "returns to the blood the exciting principle antimalarial drug pamaquine (Plasmoquine). Dur-
which it has lost, that is to say the coloring sub- ing World War II, after the world's primary sources
stance" (London 1980). of quinine were captured by the Japanese, about
Children have increased needs for iron during 16,000 drugs were tested for antimalarial effective-
growth, as do females during menstruation, preg- ness. In 1944, an Army Medical Research Unit at the
nancy, and lactation. Chronic diarrhea, common in University of Chicago studying these potential
the tropics where it is often associated with parasit- antimalarial drugs encountered the problem of
ism, decreases iron absorption whereas parasitism drug-induced anemia. Research by this group over
increases iron losses. Estimates indicate that the the next decade elucidated the basic information on
needs of pregnant and lactating women in tropical G6PD deficiency (Keller 1971).
climates are about twice those of women in temper- Pamaquine was found to cause hemolysis in 5 to
ate zones. In the tropics high-maize, low-iron diets 10 percent of American blacks but only rarely in
are common, and soils are iron deficient in many Caucasians, and the severity of the hemolysis was
areas (Davidson and Passmore 1969). observed to be dependent on the dose of the drug
(Keller 1971; Beutler 1980). Although similar sensi-
Glucose 6-Phosphate Dehydrogenase (G6PD) tivity to the related drug primaquine and many
Deficiency other related drugs was demonstrated, the term
Favism, or hemolytic anemia due to ingestion of fava "primaquine sensitivity" came to be used to desig-
beans, is now known to occur in individuals deficient nate this form of hemolytic anemia. It was subse-
in G6PD. The Mediterranean type of G6PD defi- quently demonstrated that the hemolysis was due to
ciency is found in an area extending from the Medi- an abnormality in the erythrocytes of susceptible
terranean basin to northern India, an area corre- individuals and that it was self-limited even if ad-
sponding to Alexander's empire. Sickness resulting ministration of primaquine was continued (Dern et
from ingestion of beans was probably recognized in al. 1954). Several biochemical abnormalities of the
ancient Greece, forming the basis for the myth that sensitive red cells, including glutathione instability,
Demeter, Greek goddess of harvest, forbade mem- were described. In 1956, Paul E. Carson and col-
bers of her cult to eat beans. Pythagoras, physician leagues reported that G6PD deficiency of red cells
and mathematician of the fifth century B.C. who had was the common denominator in individuals who
a great following among the Greek colonists in south- developed hemolysis after one of these drugs was
ern Italy, also seems to have recognized the disorder, administered, and the term G6PD deficiency became
since he, too, forbade his followers to eat beans. It is synonymous with primaquine sensitivity (Carson et
in that area of southern Italy that the incidence of al. 1956). It was soon found that this deficiency was
G6PD deficiency is highest (Hart 1980). genetically transmitted (Beutler 1980).
In 1956, the basis for many instances of this type
of anemia was recognized as to a hereditary defi- Sickle-Cell Disorders
ciency of the enzyme glucose-6-phosphate dehydroge- Sickle-cell disorders have existed in human popula-
nase within the red cell. Inheritance of G6PD is now tions for thousands of years. However, the discovery
recognized to be a sex-linked characteristic with the of human sickle cells and of sickle-cell anemia was
gene locus residing on the X chromosome. first announced in the form of a case report by James
It is estimated that currently over 100 million Herrick at the Association of American Physicians
people in the world are affected by this deficiency. in 1910. In 1904, Herrick had examined a young
Nearly 3 million Americans carry the trait for G6PD black student from Grenada who was anemic; in the
deficiency; about 10 to 14 percent of black American blood film he observed elongated and sickle-cell-
males are deficient in G6PD. The defect is not lim- shaped RBC (Herrick 1910).

By 1922 there had only been three cases of this homozygous sickle-cell cases came to medical atten-
type of anemia reported. But in that year Verne R. tion because of a high infant mortality rate from
Mason, a resident physician at Johns Hopkins Hospi- that disease. This was demonstrated in Leopoldville
tal, described the first patient recognized to have when J. and C. Lambotte-Legrand found that only
that disease at that institution. He entitled his re- two cases of sickle-cell anemia had been reported
port "Sickle Cell Anemia," thus introducing the among adults in the Belgian Congo although
term that would become the standard designation sickling occurred in about 25 percent of the black
(Mason 1922). population. They subsequently followed 300 infants
In 1923 C. G. Guthrie and John Huck performed with sickle-cell anemia. They found that 72 died
the first genetic investigation of this disease and before the end of the first year of life, and 144 had
developed a technique that became an indispensable perished by the age of 5 (Lambotte-Legrand and
tool for the identification of sickle trait in later inves- Lambotte-Legrand 1955).
tigations, population surveys, and genetic studies Subsequent research by others, however, estab-
(Guthrie and Huck 1923). lished the fact that sickle-cell anemia patients who
Virgil P. Sidenstricker, of Georgia, recorded many did survive to adolescence came from the higher
of the clinical and hematologic features of sickle-cell social groups, and that the standard of living, the
disease. He introduced the term "crisis," was the prevalence of infection and nutritional deficiency,
first to suggest that the anemia was hemolytic, and and the level of general health care were the princi-
reported the first autopsy describing the typical le- pal factors affecting the mortality rate from sickle-
sions of the illness including a scarred, atrophic cell anemia in young children. By 1971, as improved
spleen. He was also the first to describe sickle-cell health care became available, the course of the dis-
anemia in childhood, noting the peculiar susceptibil- ease was altered; and, at the Sickle Cell-Hemoglo-
ity of victims to infection with a high mortality rate binopathy Clinic of the University of Ghana, it was
(Sidenstricker et al. 1923). reported that 50 percent of the patients with sickle-
The first case of sickle-cell anemia to be reported cell anemia survived past age 10 (Conley 1980).
from Africa was described in 1925 in a 10-year-old Geographic distribution of sickle-cell gene fre-
Arab boy in Omdurman, and the first survey of the quency was mainly charted by the mid-twentieth cen-
frequency of sickle-cell trait in the African popula- tury. The prevalence of sickling in black populations
tion was reported in 1944 by R. Winston Evans, a of the United States was well established by 1950.
pathologist in the West African Military Hospital. In Numerous studies performed in central and South
a study of almost 600 men of Gambia, the Gold Africa also revealed that although the frequency of
Coast, Nigeria, and the Cameroons, he found ap- sickling varied, the occurrence of the gene that
proximately 20 percent to have the trait, a sickling caused it was confined mostly to black populations.
rate about three times that in the United States In Africa, after World War II, surveys established
(Evans 1943-4). that across a broad belt of tropical Africa, more than
In East Africa, E. A. Beet found a positive test for 20 percent of some populations were carriers of the
sickling in 12.9 percent of patients in the Balovale sickle-cell trait. Significantly, a high frequency of
district of Northern Rhodesia. He also reported strik- sickle trait was also found among whites in some
ing tribal differences in the prevalence of sickle-cell areas of Sicily, southern Italy, Greece, Turkey, Ara-
trait. By 1945 H. C. Trowell had concluded that bia, and southern India. Yet by contrast, sickling
sickle-cell anemia was probably the most common was virtually absent in a large segment of the world
and yet the least frequently diagnosed disease in extending from northern Europe to Australia. These
Africa. He noted that in his own clinic in Uganda no observations led to several hypotheses about where
cases had been recognized before 1940, but 21 cases the mutant gene had had its origin and how such
were seen within the first 6 months of 1944 when he high frequencies of a deleterious gene are main-
began routine testing for sickling (Trowell 1945; tained (Conley 1980).
Beet 1946). Hermann Lehmann presented evidence that sick-
For many years, it was thought that sickle-cell ling arose in Neolithic times in Arabia, and that the
anemia was rare in Africa in contrast to the greater gene was then distributed by migrations eastward to
prevalence observed in America, and some thought India and westward to Africa. He and others have
that interbreeding with white persons brought out speculated that the frequency of the gene increased
the hemolytic aspect of the disease. It was not until significantly in the hyperendemic malarial areas of
the mid-1950s that it was understood that few Africa and spread northward across the Sahara

VIII.6. Anemia 575
along ancient trade routes, particularly along the sickle-cell anemia, proposed earlier by James Neel -
routes that led to Mecca in Arabia. Since the eastern that the person with sickle-cell trait is a hetero-
and western Arabian types of sickle-cell disease are zygous carrier of the sickling gene - and supplied a
different, spread must have occurred along sea trade direct link between defective hemoglobin and mole-
routes, accounting for similarities in sickle-cell ane- cules and the pathological consequences (Pauling et
mia in eastern Africa, eastern Arabia, and southern al. 1949).
India (Lehmann and Huntsman 1974).
Obviously then, there was much interest gener- Thalassemia
ated in the cause of the very high frequency of the Thalassemia, an inherited form of anemia, results
sickle-cell gene in Africa. In 1946, Beet in Rhodesia from the deficient synthesis of a portion of the globin
noted that only 9.8 percent of sicklers had malaria,
molecule and is thought by some also to have stabi-
whereas 15.3 percent of nonsicklers were affected lized in the face of malaria. A variety of forms exist,
(Beet 1946). P. Brain, of Southern Rhodesia, sug- based on the chain and site within a specific chain at
gested that RBC of sicklers might offer a less favor- which the genetically determined defect exists. It
able environment for survival of malarial parasites has been suggested that thalassemia originated in
(Brain 1952). In 1954, J. P. Mackey and F. Vivarelli Greece and spread to Italy when it was colonized by
suggested that "the survival value [of the trait] may Greeks between the eighth and sixth century B.C.
lie in there being some advantage to the hetero- At present, it is most frequent in areas where an-
zygous sickle cell individual in respect of decreased cient Greek immigration was most intense: Sicily,
susceptibility of a proportion of his RBC to parasiti- Sardinia, Calabria, Lucania, Apulia, and the mouth
zation by P. falciparum" (Mackey and Vivarelli of the Po (Ascenzi and Balistreri 1977).
1954).
A relationship between sickle-cell trait and
falciparum malaria was reported by A. C. Allison in Skeletal Changes in Anemia: Porotic
1954. He noted that the frequency of heterozygous Hyperostosis
sickle-cell trait was as high as 40 percent in some Chronic anemia from any cause results in bone
African tribes, suggesting some selective advantage changes, which can be recognized in archaeological
or else the gene would be rapidly eliminated because specimens. These changes, called porotic or symmet-
most homozygotes die without reproducing. He de- rical hyperostosis, result from an overgrowth of bone
cided that a high spontaneous mutation rate could marrow tissue, which is apparently a compensatory
not account for the high but varying frequencies of process. The cancellous zone between the cortical
the gene, and postulated that sickle-cell trait occurs layers or tables of the skull is enlarged and the
as a true polymorphism and that the gene is main- trabeculae become oriented perpendicular to the in-
tained by selective advantage to the heterozygous. ner table, giving a radial pattern described as "hair
Comparing the distribution of falciparum malaria standing on end." The inner table is unchanged, but
and sickling, Allison found that high frequencies of the outer table is displaced externally and may be
the trait were invariably found in hyperendemic ma- thinned or completely atrophied and often has a
larial areas. He also found that people with sickle- spongy appearance. The process varies in location in
cell trait suffer from malaria not only less frequently different individuals; frontal, parietal, temporal,
but also less severely than other persons, and con- occipital, and maxillary bones can be affected. A
cluded that where malaria is hyperendemic, chil- similar process is also seen in the metaphysical ends
dren with the sickle-cell trait have a survival advan- of long bones and anterior superior and acetabular
tage (Allison 1954). areas of the ilium.
Previously in 1979, Linus Pauling and Harvey Today porotic hyperostosis is seen classically in X-
Itano had reported the aberrant electrophoretic mo- rays of patients with congenital hemolytic anemias,
bility of sickle hemoglobin, and ascribed the altered as well as in children with chronic iron deficiency
hemoglobin of patients with sickle-cell anemia to a anemia. This is especially the case when the iron
change in the globin portion of the molecule. It was deficiency occurs in premature infants or is associ-
shown that the red cells of sickle-cell anemia pa- ated with protein malnutrition or rickets (Lanz-
tients contain the abnormal hemoglobin almost ex- kowksy 1968).
clusively, whereas those with sickle-cell trait con- Porotic hyperostosis has been observed in archaeo-
tain other normal and abnormal components. These logical specimens from a variety of sites, including
findings supported the theory of the genetic basis of areas of Greece, Turkey, Peru, Mexico, the United

States, and Canada. In most areas, the findings are Beet, E. A. 1946. Sickle cell disease in the Balovale dis-
considered evidence of iron-deficiency anemia, al- trict of Northern Rhodesia. East African Medical Jour-
though thalassemia was apparently responsible in nal 23: 75-86.
some areas. Around the shores of the Mediterra- Beutler, E. 1980. The red cell: A tiny dynamo. In Blood
nean, malaria was probably the most frequent cause pure and eloquent, ed. M. W. Wintrobe, 141—68. New
of chronic anemia at certain times. York.
Brain, P. 1952. Sickle cell anemia in Africa. British Medi-
Archaeological specimens from the Near East cal Journal 2: 880.
show an incidence of anemia of only 2 percent in Carson, Paul E., et al. 1956. Enzymatic deficiency in
early hunters (15,000-8000 B.C.) who ingested a lot primaquin-sensitive erthrocytes. Science 124: 484—5.
of animal protein and thus took in reasonable Castle, W. B. 1980. The conquest of pernicious anemia. In
amounts of dietary iron. By contrast, farming popula- Blood pure and eloquent, ed. M. W. Wintrobe, 171—
tions of 6500 to 2000 B.C. showed an anemia inci- 208. New York.
dence of 50 percent. Conley, C. Lockhart. 1980. Sickle-cell anemia. In Blood
Many New World natives whose diet consisted pri- pure and eloquent, ed. M. W. Wintrobe, 319-71. New
marily of corn (maize) and beans had a diet deficient York.
in iron and protein. Moreover, when cooked in water . Davidson, S., and R. Passmore. 1969. Human nutrition
for long periods of time, the food in the diet was also and dietetics. Baltimore.
low in ascorbate and folate. Ascorbate helps convert Dem, R. C , et al. 1954. The hemolytic effect of primaquin.
I. The localization of the drug-induced hemolytic de-
dietary ferric to ferrous iron, which is more easily
fect in primaquin-sensitive individuals. Journal of
absorbed; therefore, deficiency of this vitamin in- Laboratory and Clinical Medicine 43: 303-9.
creased the problem of deficient dietary iron. A high Doniach D., I. M. Roitt, and K. B. Taylor. 1963.
incidence of iron deficiency has been demonstrated Autoimmune phenomena in pernicious anemia: Sero-
by modern studies of infants and children in popula- logic overlap with thyroiditis, thyrotoxicosis and sys-
tions living on a diet consisting mostly of maize and temic lupus erythematosus. British Medical Journal
beans (El-Najjar and Robertson 1976). It is not sur- 1:1374-9.
prising then, in North America, that porotic El-Najjar, M. Y., and A. Robertson. 1976. Spongy bones in
hyperostosis was found in 54 percent of skeletons in prehistoric America. Science 193: 141-3.
the canyons of northern Arizona and northern New Evans, R. W. 1943-4. The sickling phenomenon in the
Mexico, among a population that ate little meat and blood of West African natives. Transactions of the
subsisted mainly on maize. By contrast, plains dwell- Royal Society of Tropical Medicine and Hygiene 37:
ers in southern Arizona and southern New Mexico, 281-6.
who used more animal foods, had an incidence of Guthrie, C. G., and J. G. Huck. 1923. On the existence of
more than four isoagglutinin groups in human blood.
only 14.5 percent. Absence of evidence for malaria or Bulletin of the Johns Hopkins Hospital 34: 37-48.
hemoglobinopathies in the New World before the Hart, Gerald D. 1980. Ancient diseases of the blood. In
arrival of the Europeans argues against these possi- Blood pure and eloquent, ed. M. W. Wintrobe, 33-56.
ble causes of porotic hyperostosis (Hart 1980). New York.
Alfred Jay Bollet and Audrey K. Brown Herrick, J. B. 1910. Peculiar elongated and sickle-shaped
red blood corpuscles in a case of severe anemia. Ar-
Bibliography chives of Internal Medicine 6: 517—21.
Allison, Anthony C. 1954. Protection afforded by sickle- Keller, Dan. 1871. G-6-PD deficiency. Cleveland.
cell trait against subtertian malarial infection. Brit- Lambotte-Legrand, J., and C. Lambotte-Legrand. 1955. Le
ish Medical Journal 1: 290-4. Prognostic de l'anemie drapanocytaire au Congo
Angel, J. Lawrence. 1975. Paleoecology, paleodemography Beige (A propos de cas de 150 dec6des). Annales de la
and health. In Population, ecology and social evolu- Societe Belgique de Medecine Tropicale 35: 53—7.
tion, World Anthropology Series, 167-90. Chicago. Lanzkowsky, Philip. 1968. Radiological features of iron
1977. Anemias of antiquity: Eastern Mediterranean. In deficiency anemia. American Journal of Diseases of
Porotic hyperostosis: An enquiry, ed. E. Cockburn, Children 116: 16-29.
Paleopathology Associates Monograph No. 2,1-5. De- Lehmann, Hermann, and R. G. Huntsman. 1974. Man's
troit. hemoglobin. Oxford.
Ascenzi, A., and P. Balistreri. 1977. Porotic hyperostosis London, Irving. 1980. Iron and heme: Crucial carriers and
and the problem of the origin of thalassemia in Italy. catalysts. In Blood pure and eloquent, ed. M. W.
In Porotic hyperostosis: An enquiry, ed. E. Cockburn. Wintrobe, 171-208. New York.
Paleopathology Associates Monograph No. 2, 5-9. Mackey, J. P., and F. Vivarelli. 1954. Sickle cell anemia.
Detroit. British Medical Journal 1: 276.

VIII.7. Anorexia Nervosa 577
causes many anorectics to develop osteoporosis, a

Mason, Verne, R. 1922. Sickle cell anemia. Journal of the
American Medical Association 29: 1318-20. loss of bone density that is usually seen only in
Pauling, Linus H., et al. 1949. Sickle cell anemia, a molecu-
postmenopausal women (Garfinkel and Garner
lar disease. Science 110: 543-8. 1982).
Sidenstricker, Virgil P., W. A. Mulherin, and R. W. By the time the anorectic is profoundly under-
Houseal. 1923. Sickle cell anemia. Report of 2 cases in
weight, other physical complications due to severe
children with necropsy in one case. American Journal
malnutrition begin to appear. These include brady-
of Diseases of Children 26: 132-54.
cardia (slowing of the heartbeat), hypotension (loss
Trowell, H. C. 1945. Sickle cell anemia. East African Medi-
cal Journal 22: 34-45. of normal blood pressure), lethargy, hypothermia,
Whipple, George H., and F. S. Robsheit-Robbins. 1925. constipation, the appearance of "lanugo" or fine
Blood regeneration in severe anemia. II. Favorablesilky hair covering the body, and a variety of other
metabolic and systemic changes.
influence of liver, heart and skeletal muscle in diet.
American Journal of Physiology 72: 408-18. In addition to the physical symptoms associated
Wintrobe, M. W. 1985. Hematology, the blossoming of a with chronic starvation, anorectics also display a
science. Philadelphia. relatively consistent cluster of emotional and behav-
ioral characteristics, the most prominent of which
grows out of the anorectic's distorted perception of
food and eating. Unusual eating habits may include
monotonous or eccentric diets, hoarding or hiding
VIII.7 food, and obsessive preoccupation with food and cook-
ing for others.
Anorexia Nervosa Emotionally, anorexic patients are often described
as being perfectionistic, dependent, introverted, and
overly compliant. Although studies have failed to
Anorexia nervosa is a psychophysiological disorder find a consistent psychiatric symptom pattern for
especially prevalent among young women and is the disorder, frequently reported neurotic traits in-
characterized by prolonged refusal to eat or to main- clude obsessive compulsive, hysterical, hypochon-
tain normal body weight, an intense fear of becom- driacal, and depressive symptoms. A decrease in or
ing obese, a disturbed body image in which the ema- disappearance of sexual interest is also a frequent
ciated patient feels overweight, and the absence of concomitant of anorexia nervosa, according to the
any physical illness that would account for extreme 1987 Diagnostic and Statistical Manual (DSM) of
weight loss. The term anorexia is actually a misno- the American Psychiatric Association.
mer, because genuine loss of appetite is rare, and A distorted body image is an almost universal char-
usually does not occur until late in the illness. In acteristic of anorectics, with many patients insisting
reality, most anorectics are obsessed with food and that they are overweight even when their bodies are
constantly struggle to deny natural hunger. extremely emaciated. As a result, most individuals
with anorexia nervosa deny or minimize the severity
Clinical Manifestations and Pathology of their illness and are thus resistant to therapy. The
In anorexia nervosa, normal dieting escalates into a anorectic's refusal to acknowledge her nutritional
preoccupation with being thin, profound changes in needs, and her steadfast insistence that nothing is
eating patterns, and a weight loss of at least 25 wrong, make anorexia nervosa one of the most recalci-
percent of the original body weight. Weight loss is trant disorders in contemporary medicine.
usually accomplished by a severe restriction of calo-
ric intake, with patients subsisting on fewer than Distribution and Incidence
600 calories per day. Contemporary anorectics may Once considered to be extremely rare, the reported
couple fasting with self-induced vomiting, use of incidence of anorexia nervosa has more than dou-
laxatives and diuretics, and strenuous exercise. bled during the 1970s and 1980s (Herzog and Cope-
The most consistent medical consequences of an- land 1985). The disorder is especially prevalent
orexia nervosa are amenorrhea (ceasing or irregular- among adolescent and young adult women. Indeed
ity of menstruation) and estrogen deficiency. In most 90 to 95 percent of anorectics are young and female,
cases amenorrhea follows weight loss, but it is not and as many as one in 250 females between 12 and
unusual for amenorrhea to appear before noticeable 18 years of age may develop the disorder. Onset of
weight loss has occurred. The decrease in estrogens anorexia nervosa occurs almost exclusively during

the teens, although some patients have become sociocultural causes of anorexia nervosa has linked
anorectic as early as age 11 and others as late as the the increased incidence of anorexia nervosa and
sixth decade of life. Patients are typically from other eating disorders with the tremendous cultural
middle- or upper-class families. attention given to dieting and food, standards of
Anorexia nervosa is comparatively rare in men: beauty increasingly based on thinness, and the fit-
Approximately 5 to 10 percent of anorectics are ness movement (Chernin 1985; Schwartz, Thomp-
male. The clinical picture for male anorectics is also son, and Johnson 1982; Orbach 1986). Yet sociocul-
much different from that for women. In general, tural variables alone cannot explain why some
male anorectics tend to display a greater degree of women but not others move from chronic dieting to
psychopathology, are often massively obese before anorexia nervosa. Therefore, other individual fac-
acquiring the disorder, are less likely to be affluent, tors must be implicated in the final development of
and are even more resistant to therapy than their the illness.
female counterparts (Garfinkel and Garner 1982). Brumberg's model of anorexia nervosa relies on a
Among American blacks, Chicanos, andfirst-and second stage - career or acclimation - to correct the
second-generation ethnic immigrants, there are few shortcomings of sociocultural explanations of the dis-
reported cases. However, this racial and ethnic distri- order. During the career phase, specific biological
bution reflects socioeconomic status rather than ra- and psychological features determine which indi-
cial characteristics (Herzog and Copeland 1985). viduals develop the full-blown psychopathology of
Similarly, anorexia nervosa is confined to the United anorexia nervosa. In order to explain the transition
States, Canada, Western Europe, Japan, and other between the recruitment and career phases of an-
highly industrialized areas. The absence of the disor- orexia nervosa, Brumberg relies on recent research
der in developing nations, and its high incidence in the biological and social sciences that has sought
among affluent social groups in Westernized coun- to uncover the unique physiological and psychologi-
tries have led many clinicians to classify anorexia cal characteristics of anorexic patients.
nervosa as a "culture-bound" syndrome (i.e., a disor- Since the early 1900s, a number of different endo-
der that is restricted to certain cultures primarily crinological and neurological abnormalities have
because of their distinctive psychosocial features) been postulated as underlying biological causes of
(Prince 1985). anorexia nervosa: hormonal imbalance, dysfunction
in the satiety center of the hypothalamus, lesions in
Etiology and Epidemiology the limbic system of the brain, and irregular output
Although the etiology of anorexia nervosa is an area of vasopressin and gonadotropin (Herzog and Cope-
of intense investigation, researchers have yet to land 1985). The search for a biomedical cause of
reach a consensus about the origin of the disorder. anorexia nervosa is made difficult, however, by the
The most sophisticated thinking on the subject re- fact that chronic starvation itself produces extensive
gards anorexia nervosa as a disorder that involves changes in hypothalamic and metabolic function.
an interplay of biological, psychological, and cul- Researchers in this area have yet to find a common
tural factors. Advocates of this model view these biological characteristic of the anorectic population
three etiologic factors as reciprocal and interactive, that is unmistakably a cause rather than a conse-
and believe that it is simplistic to isolate one compo- quence of extreme weight loss and malnutrition
nent as the single underlying cause of the disorder (Brumberg 1988a).
(Garfinkel and Garner 1982; Brumberg 1988a; A more satisfactory explanation of the biological
Brumberg and Striegel-Moore 1988). factors that contribute to the "career" phase of an-
Joan Brumberg (1988a) has developed a multi- orexia nervosa is the "addiction to starvation" model
determined etiologic model based on a two-staged proffered by the British psychiatrists George I.
conceptualization of anorexia nervosa, which delin- Szmukler and Digby Tantum (1984). According to
eates the relative impact of sociocultural influences Szmukler and Tantum, patients with fully developed
and individual biological and psychological vari- anorexia nervosa are physically and psychologically
ables in precipitating the disorder. In the first dependent on the state of starvation. Much like alco-
stage - the "recruitment" phase of the illness - holics and other substance abusers, anorectics find
sociocultural factors play the dominant role. During something gratifying or tension-relieving about the
this period, cultural assumptions that associate thin- state of starvation, and possess a specific physiologi-
ness with female beauty lead certain women into a cal substrate that makes them more susceptible to
pattern of chronic dieting. Indeed, research on the starvation dependence than individuals who merely

engage in chronic dieting. Szmukler and Tantum lation between eating disorders and depression. How-
add, however, that starvation dependence is not the ever, the association between anorexia nervosa and
total explanation of anorexia nervosa. Rather, they other psychiatric disorders remains controversial
believe that starvation dependence acts in conjunc- (Garfinkel and Garner 1982; Herzog and Copeland
tion with a range of sociocultural, psychological, and 1985).
familial factors that encourage certain individuals
to use anorexic behavior as a means of expressing History
personal anguish.
Current psychological models of anorexia nervosa Pre-Eighteenth Century
fall into three basic categories: psychoanalytic, family The existence of anorexia nervosa in the past has
systems, and social psychology. In both the psychoana- been a subject of much historical debate. Some clini-
lytic and family systems models, anorexia nervosa is cians and medical historians have postulated that
seen as a pathological response to the development anorexia nervosa was first identified in 1689 by the
crisis of adolescence. Orthodox psychoanalysts, draw- British doctor Richard Morton, physician to James II
ing on the work of Sigmund Freud, view the anorec- (Bliss and Branch 1960; Silverman 1983). The medi-
tic as a girl who fears adult womanhood, and who eval historian Rudolph Bell has dated the origins of
associates eating with oral impregnation (Brumberg anorexia nervosa even earlier, claiming that certain
1988a). Family systems theory, however, offers a more medieval female saints, who were reputed to live
complex explanation of the relationship between ado- without eating anything except the eucharist, actu-
lescence and anorexia nervosa. On the basis of clinical ally suffered from anorexia nervosa (Bell 1985).
work with anorectics and their families, family sys- Other historians, however, have argued that at-
tems therapists have found that the majority of an- tempts to label all historical instances of food refusal
orexic patients are "enmeshed," meaning that the nor- and appetite loss as anorexia nervosa are simplistic,
mal process of individuation is blocked by extreme and maintain that the historical record is insuffi-
parental overprotectiveness, control, and rigidity. An- cient to make conclusive diagnoses of individual
orexia nervosa is therefore seen as a form of adoles- cases (Bynum 1987; Brumberg 1988a). Although
cent rebellion against parental authority (Minuchin, these historians agree that the final physiological
Rosman, and Baker 1978; Bruch 1988). stage of acute starvation may be the same in contem-
Research in social psychology and thefieldof per- porary anorectics and medieval ascetics, the cultural
sonality has devised several psychological tests to and psychological reasons behind the refusal to eat
distinguish the psychological characteristics of ano- are quite different. Thus, to reduce both to a single
rectics from others in their age group. One study has biomedical cause is to overlook the variety of social
shown that whereas many of the psychological traits and cultural contexts in which certain individuals
of anorectics and other women are indistinguishable, have chosen to refuse food.
anorectics display a markedly higher degree of inef-
fectiveness and self-esteem. Other studies have pro- Nineteenth Century
posed that anorectics have actual cognitive problems The modern disease classification of anorexia
with body imaging, whereas others suggest a relation- nervosa emerged during the 1860s and 1870s, when
ship between anorexia nervosa and sex-role socializa- the work of public asylum keepers, elite British phy-
tion (Garfinkel and Garner 1982). sicians, and early French neurologists partially dis-
Finally some researchers have attempted tofitan- tinguished anorexia nervosa from other diseases in-
orexia nervosa within other established psychiatric volving loss of appetite (Brumberg 1988a). In 1859,
categories such as affective disorders and obsessional the American asylum physician William Stout
neurosis. Many anorectics in fact display behavior Chipley published the first American description of
patterns associated with obsessive-compulsive disor- sitomania, a type of insanity characterized by an
ders: perfectionism, excessive orderliness and clean- intense dread or loathing of food (Chipley 1859).
liness, meticulous attention to detail, and self- Although Chipley found sitomania in patients from
righteousness. This correlation has led a number of a broad range of social and age groups, he identified
researchers to suggest that anorexia nervosa is itself a special form of the disease that afflicted adolescent
a form of obsessive-compulsive behavior (Rothenberg girls. Chipley's work was ignored by his contempo-
1986). Depressive symptoms are also commonly seen raries, however, and it was not until the 1870s, when
in many patients with anorexia nervosa. Various fam- two influential case studies by the British physician
ily, genetic, and endocrine studies have found a corre- William Withey Gull (1874) and the French alienist

Charles Lasegue (1873) were published, that physi- ciency as the cause of anorexia nervosa. Research
cians began to pay significant attention to anorexia conducted at the Mayo Clinic in Rochester, Minne-
in girlhood. Gull's primary accomplishment was to sota, during the period between the two world wars
name and establish anorexia nervosa as a coherent established a relationship between thyroid function
disease entity distinct from either mental illnesses and body weight, and led many physicians to regard
in which appetite loss was a secondary feature, or anorexia nervosa as a metabolic disorder caused by a
physical "wasting" diseases such as tuberculosis, dia- deficiency in thyroid hormone. Throughout the
betes, or cancer. Despite widespread acclaim for 1920s and 1930s, insulin, antuitrin, estrogen, and a
Gull's work with anorectic patients, however, clini- host of other hormones were also employed in the
cians during the late nineteenth century generally treatment of anorexia nervosa (Brumberg 1988a).
rejected the conception of anorexia nervosa as an The second major approach to anorexia nervosa in
independent disease. Instead, they conceptualized it the early twentieth century grew out of the field of
either as a variant of hysteria that affected the gas- dynamic psychiatry, which emerged during the
trointestinal system, or as a juvenile form of neuras- 1890s and early 1900s. Beginning in the last decade
thenia (Brumberg 1988a). of the nineteenth century, practitioners in dynamic
Nineteenth-century physicians also tended to fo- psychiatry increasingly focused on the life history of
cus on the physical symptom of not eating, and ig- individual patients and the emotional sources of ner-
nored the anorectic patient's psychological reasons vous disease. Two of the leading pioneers in this new
for refusing food. An important exception was field - Freud and Pierre Janet - were the first to
Lasegue, who was the first to suggest the signifi- suggest a link between the etiology of anorexia
cance of family dynamics in the genesis and per- nervosa and the issue of psychosexual development.
petuation of anorexia nervosa. Because of the so- According to Freud, all appetites were expressions of
matic emphasis of nineteenth-century medicine, libido or sexual drive. Thus, not eating represented a
however, most nineteenth-century medical practitio- repression of normal sexual appetite (Freud 1918-
ners disregarded Lasegue's therapeutic perspective. 59). Similarly, Janet asserted that anorectic girls
Instead, they directed medical intervention toward refused food in order to retard normal sexual develop-
restoring the anorectic to a reasonable weight and ment and forestall adult sexuality (Janet 1903;
pattern of eating rather than exploring the underly- Brumberg 1988a).
ing emotional causes of the patient's alleged lack of Because of the enormous popularity of endocrino-
appetite (Brumberg 1988a). logic explanations of disease, the idea of anorexia
nervosa as a psychosexual disturbance was gener-
Early Twentieth Century ally overlooked for more than 30 years. By the
In the twentieth century, the treatment of anorexia 1930s, however, the failure of endocrinologic models
nervosa changed to incorporate new developments to establish either a predictable cure or a definitive
within medical and psychiatric practice. Before cause of anorexia nervosa, the growing reputation of
World War II, two distinct and isolated models domi- the Freudian psychoanalytic movement, and in-
nated medical thinking on anorexia nervosa. The creased attention to the role of emotions in disease
first approach was rooted in late-nineteenth-century led a number of practitioners to assert the value and
research in organotherapy, a form of treatment importance of psychotherapy in the treatment of an-
based on the principle that disease resulted from the orexia nervosa. Although biomedical treatment of
removal or dysfunction of secreting organs and the disorder continued, most clinicians realized that
glands (Brumberg 1988a). Between 1900 and 1940, a successful, permanent recovery depended on uncov-
variety of different endocrinologic deficiencies were ering the psychological basis for the anorectic's be-
proposed as the cause of anorexia nervosa. In 1914, havior. Following on the work of Freud and Janet,
Morris Simmonds, a pathologist at the University of orthodox psychiatrists during this time postulated
Hamburg, published a clinical description of an ex- that refusal to eat was related to suppression of the
treme cachexia due to destruction of the anterior sexual appetite, and claimed that anorectic women
lobe of the pituitary. Because patients with anorexia regarded eating as oral impregnation and obesity as
nervosa and those with Simmonds' disease shared a pregnancy (Brumberg 1988a).
set of common symptoms, many clinicians assumed
that a deficiency in pituitary hormone was the cause Post-World War II
of both conditions (Brumberg 1988a). After World War II, a new psychiatric view of eating
Other researchers implicated thyroid insuffi- disorders, shaped largely by the work of Hilde

Bruch, encouraged a more complex interpretation of orexia nervosa: Its history, psychology, and biology.
the psychological underpinnings of anorexia ner- New York.
vosa. Although Bruch agreed that the anorectic was Bruch, Hilde. 1973. Eating Disorders: Obesity, anorexia
unprepared to cope with the psychological and social nervosa, and the person within. New York.
consequences of adulthood and sexuality, she also 1978. The golden cage: The enigma of anorexia nervosa.
stressed the importance of individual personality for- New York.
1988. Conversations with anorexics, ed. Danita Czyzew-
mation and factors within the family to the psy-
ski and Melanie A. Suhr. New York.
chogenesis of anorexia nervosa. Here, Bruch revived Brumberg, Joan Jacobs. 1988a. Fasting girls: The emer-
Lasegue's work on the role of family dynamics in gence of anorexia nervosa as a modern disease. Cam-
anorexia nervosa. According to Bruch, the families bridge, Mass.
of most anorectic patients were engaged in a dysfunc- 1988b. From fat boys to skinny girls: Hilde Bruch and
tional style of familial interaction known as the popularization of anorexia nervosa in the 1970s.
"enmeshment": Such families are characterized by Paper presented at the 1988 American Association for
extreme parental overprotectiveness, lack of privacy the History of Medicine meetings.
of individual members, and reluctance or inability to Brumberg, Joan Jacobs, and Ruth Striegel-Moore. 1988.
confront intrafamilial conflicts. Although superfi- Continuity and change in the symptom choice: An-
cially these families appeared to be congenial, said orexia nervosa in historical and psychological perspec-
Bruch, this harmony was achieved through exces- tive. Unpublished paper available from authors.
sive conformity on the part of the child, and under- Bynum, Caroline Walker. 1987. Holy feast and holy fast:
The religious significance of food and medieval
mined the child's development of an autonomous
women. Berkeley, Cal.
self. Anorexia nervosa, according to Bruch, was Chernin, Kim. 1985. The hungry self: Women, eating and
therefore a young woman's attempt to exert control identity. New York.
and self-direction in a family environment in which Chipley, William S. 1859. Sitomania: Its causes and treat-
she otherwise felt powerless (Bruch 1973, 1988). ment. American Journal of Insanity 26: 1—42.
Bruch was also primarily responsible for the tre- Freud, Sigmund. 1918-59. From the history of an infan-
mendous growth in the popular awareness of an- tile neurosis. In Collected papers, Vol. 3. New York.
orexia nervosa and other eating disorders in the Garfinkel, Paul E., and David M. Garner. 1982. Anorexia
1970s and 1980s. Through her book, The Golden nervosa: A multidimensional perspective. New York.
Cage: The Enigma of Anorexia Nervosa (1978), Gull, William. 1874. Anorexia nervosa (apepsia hysterica,
which sold over 150,000 copies, and numerous arti- anorexia hysterica). Transactions of the Clinical Soci-
ety of London 7: 22-8.
cles in popular magazines, Bruch brought anorexia
Herzog, David B., and Paul M. Copeland. 1985. Eating
nervosa into common American parlance (Brumberg disorders. New England Journal of Medicine 313:
1988b). 295-303.
At the same time that the American public was Janet, Pierre. 1903. Les Obsessions et la psychasthenie.
becoming increasingly aware of anorexia nervosa, New York.
the number of reported cases of the disorder grew Kaye, W. H., et al. 1986. Caloric consumption and activity
tremendously. This phenomenon has led some clini- levels after weight recovery in anorexia nervosa: A
cians and social commentators to suggest that the prolonged delay in normalization. International Jour-
popularization process itself may promote a "sympa- nal of Eating Disorders 5: 489-502.
thetic host environment" for the disorder (Striegel- Lasegue, Charles. 1873. De L'Anorexie hysterique. Ar-
Moore, Silberstein, and Rodin 1986; Brumberg chives gin&rales de medecine 1: 385—7.
1988b). As Bruch (1988) herself observed: Minuchin, Salvador, Bernice L. Rosman, and Lesley
Baker. 1978. Psychosomatic families: Anorexia ner-
Once the discovery of isolated tormented women, it [an- vosa in context. Cambridge, Mass.
orexia nervosa] has now acquired a fashionable reputa- Morton, Richard. 1689. Phthisiologia, seu exercitationes de
tion, of being something to be competitive about.. .. This phthisi. London.
is a far cry from the twenty-years-ago anorexic [sic] whose Orbach, Susie. 1986. Hunger strike: The anorectic's strug-
goal was to be unique and suggests that social factors may gle as a metaphor for our age. New York.
impact the prevalence of the disorder. Prince, Raymond. 1985. The concept of culture-bound syn-
' Heather Munro Prescott drome: Anorexia nervosa and brain-fag. Social Sci-
ence and Medicine 21: 197-203.
Bibliography Rothenberg, Albert. 1986. Eating disorder as a modern
Bell, Rudolph. 1985. Holy anorexia. Chicago. obsessive-compulsive syndrome. Psychiatry 49: 45-53.
Bliss, Eugene L., and C. H. Hardin Branch. 1960. An- Schwartz, Donald M., Michael G. Thompson, and Craig L.

Johnson. 1982. Anorexia nervosa and bulimia: The during World War II. This is of prime importance for
socio-cultural context. International Journal ofEating
the eipdemiology of the disease because it is rarely
Disorders 1: 20-36. spread directly from animal to animal, but almost
Silverman, Joseph. 1983. Richard Morton, 1637-1698: always through ingestion of contaminated food, ei-
Limner of anorexia nervosa: His life and times. Jour-
ther by grazing or, in cooler climates, through im-
nal of the American Medical Association 250: 2830-2.ported winter foodstuffs. Humans are accidentally
Striegel-Moore, Ruth, Lisa R. Silberstein, and Judith Ro-
infected either by contact with infected animals or
din. 1986. Toward an understanding of risk factors in
bulimia. American Psychologist 41: 246-63. by contaminated animal products. The infectivity of
Szmukler, George I., and Digby Tantum. 1984. Anorexia the anthrax bacillus for people is low, and therefore,
nervosa: Starvation dependence. British Journal of even where large numbers of spores and bacilli are
Medical Psychology 57: 303-10. found in an industrial environment, only relatively
few cases occur.
The nonindustrial type of anthrax in humans af-
fects those in professions such as veterinary sur-
gery, pathology, farming, butchery, and the like and
takes the form of malignant pustule - a lesion due
VIII.8 to contamination of the skin with material from
Anthrax infected animals. The industrial type may present
as either malignant pustule or pulmonary disease
and is acquired in the woolen industries especially
Anthrax is an acute zoonotic disease, primarily of through contaminated air. The disease approached
herbivorous animals, which is transmissible to huan epidemic situation in the late eighteenth and
man beings. The causative organism is Bacillus nineteenth centuries in France and in England in
anthracis, often referred to in earlier, and especially factories processing imported horsehair and sheep's
in French, texts as bacteridie, the name first be- wool.
stowed on it by Casimir Davaine in 1863. Humans
are infected only secondarily through contact with Distribution and Incidence
animals or animal products, and thus the disease in Anthrax is widely distributed throughout the world,
human beings must be considered in relation to an- but there are distinct differences in incidence and in
thrax in animals. species affected among the various continents and
The species of domestic animals most commonly countries. Outbreaks in animals in Europe (mainly
affected are cattle, sheep, and goats; pigs, dogs, and cattle) and in Asia (sheep and goats) heavily out-
cats are less susceptible. Since an enlarged spleen is weigh those in the United States and Africa,
a classic observation in animals with anthrax, the whereas Australia and Canada are rarely affected.
disease has also been known as splenic fever or Extensive enzootic areas with a constant presence of
splenic apoplexy. In humans the cutaneous form is infection include China, Ethiopia, and Iran, and, in
known as malignant pustule, and the pulmonary or the Americas, Mexico and some South American
intestinal, industrial type, as woolsorters' disease or countries. Available data suggest an annual average
industrial anthrax. In French the equivalent of total of some 10,000 outbreaks throughout the
splenic fever is sang de rate, in German Milzbrand; world; for Great Britain the annual total between
other French synonyms include charbon and pustule the two world wars ranged from 400 to 700, mostly
maligne. very minor outbreaks. Since then there appears to
have been a gradual reduction in incidence, helped
Etiology and Epidemiology in Great Britain by the introduction in 1919 of the
Because B. anthracis produces resistant spores in Anthrax Prevention Act, forbidding importation of
suitable soils, the disease has long been endemic in certain types of potentially contaminated material.
many areas throughout the world, with a majority of Since World War II the number of fatal cases in
the outbreaks occurring in Europe and Asia. The human beings has been substantially reduced follow-
Americas, Africa, and Australasia are less affected. ing the introduction of antibiotic therapy.
Once contaminated with anthrax spores, an area can In countries such as Italy and Russia, a close corre-
be extremely difficult to clear, as has been demon- lation has existed between the seasonal incidence of
strated on the island of Gruinard off the west coast of the disease in people and in animals, with a rise
Scotland, which was experimentally contaminated during the hot summer months reflecting the sea-

VIII.8. Anthrax 583
sonal changes in temperature, humidity, and vegeta- ings include hemorrhages in the lung, hemorrhagic
tion favoring spread and reproduction of the bacillus. mediastinitis and lymphadenitis, and sometimes
hemorrhagic meningitis.
Immunology
The immunogenic behavior of the anthrax bacillus
History and Geography
is complex, and it is not certain whether or to what
In the past, outbreaks of anthrax (along with other
extent immunity develops in cases of recovery from
epizootic diseases) among animals have undoubtedly
infection. The existence of an extracellular toxin
helped to prepare the way for major outbreaks of
produced by B. anthracis, which in part determines
epidemic disease in human beings. When anthrax
its virulence was demonstrated only during the
has decimated herds of cattle or sheep, for example,
1980s. Certain strains of certain animal species
human populations have faced starvation which, in
possess a high degree of natural resistance, a fact
turn, has lowered their ability to resist those epidem-
that introduced confusion and fed much of the contro-
ics. Anthrax has been known from antiquity, al-
versy surrounding the early work on the etiology of
though until relatively recently it was not clearly
and immunity in anthrax. The live attenuated vac-
separated from other diseases with similar manifes-
cines used by Louis Pasteur have undergone contin-
tations. Possibly sudden death of animals at pasture,
ued development and improvement over the years,
blamed by Aristotle (and subsequently by his follow-
but early results claiming reductions in incidence
ers over the centuries) on the shrewmouse and its
and fatality rates following their use were not
"poisonous bite," may in many cases have been due
readily sustained. Thus, the early vaccines have
to the peracute form of anthrax commonly referred
gradually been replaced by spore-based vaccines and
to as splenic apoplexy.
methods combining active and passive immuniza-
tion using prepared antiserum. Until recently, vac- Nineteenth-century authors speculated that the
cines have not been considered safe for use in human fifth and sixth plagues of the Egyptians as described
beings, but serum treatment has been used exten- in Exodus, which struck their herds and the Egyp-
sively for prophylactic and therapeutic purposes. tians themselves, might have been anthrax. Evi-
dence that this may have been the case centers on
For occupational reasons women are less liable to the Israelites, who were installed on sandy ground
exposure than men, but the disease, when estab- above the level of the Nile. They escaped the
lished, is more commonly fatal in females. plagues, whereas those who did not lived in areas
Clinical Manifestations and Pathology subject tofloodingby the rising of the Nile, which
In its principal animal hosts, anthrax may take one could have provided perfect conditions for growth of
of three forms: (1) aperacute type (splenic apoplexy), the anthrax bacillus. Three decades before the birth
where sudden death occurs almost simultaneously of Christ, Virgil, in the Georgics, vividly described
with the first symptoms; (2) an acute type character- an animal plague that had much in common with
ized by an acute fever, usually followed by death anthrax, and warned against its transmission to peo-
after 2 to 12 days; and (3) a subacute type often ple through contact with infected hides.
followed by recovery. Classical signs include fever, Through the centuries since Biblical times there
stupor, spasms, convulsions, intestinal disturbances, are many records of animal plagues that almost cer-
and respiratory or cardiac distress. Death follows tainly were anthrax but were often confused with a
septicemia and accompanying severe toxic manifes- number of other complaints. By 1769, when identifica-
tations. Characteristic enlargement of the spleen is tion of epidemic diseases of animals and human be-
reflected in the name of splenic fever. ings had become more precise, Jean Fournier in Dijon
Anthrax in people may take the form of a malig- classified a number of different lesions as a single
nant pustule (cutaneous anthrax), where the bacilli disease entity (anthrax), which he called charbon
enter through the skin, producing a primary lesion malin. More importantly, he recognized the transmis-
developing into a characteristic area of inflammation sion of the disease to people, and drew attention to
surrounding a dark necrotic center; or it may take cases occurring in workers who handled raw hair and
the form of the pulmonary or - less commonly - the wool, a theme developed in several accounts pub-
intestinal type, which follows inhalation of dust con- lished in France during the following decade. These
taining anthrax spores, as has occurred in the woolen were all concerned with workers who had contracted
industries. Monkeys exposed to artificially gener- anthrax while opening and sorting bales of horsehair
ated aerosols of anthrax spores develop symptoms imported from Russia. From the mid-nineteenth cen-
mimicking woolsorters' disease. Postmortem find- tury, the disease became a problem in English facto-

ries as well, and subsequently in those of Scotland. At Cunningham, William. 1976. The work of two Scottish
about the same time, the woolen industries began medical graduates in the control of woolsorters' dis-
experiencing the problem as wool and hair from the ease. Medical History 20: 169-73.
East were introduced to the British trade. Wool- Fleming, George. 1871. Animal plagues: Their history,
sorting, until then considered a particularly health- nature and prevention. London.
ful occupation, suddenly began to show an alarming Lincoln, Ralph E., et al. 1964. Anthrax. Advances in Veteri-
nary Science 9: 327-68.
increase in the number of deaths and the extent of
Page, Cecil H. W. 1909. British industrial anthrax. Jour-
disease among the workers. The workers themselves nal of Hygiene 9: 279-315; 357-98.
suspected an association between the disease and the Theordorides, Jean. 1968. Un grand medecin et biologiste:
growing proportion of wool and hair imported from Casimir-Joseph Davaine (1812-82). In Analecta
the East. By the late 1870s, concern in the Yorkshire medico-historica, 4. Oxford.
factories was acute, but by then the new bacteriology Wilson, Graham, and Geoffrey Smith. 1983-4. Anthrax.
had led to the identification of the cause of anthrax. In Principles of bacteriology, virology and immunity,
J. H. Bell in Bradford had demonstrated that both 7th edition, Vol. 3, Chap. 54, 102-12. London.
woolsorters' disease and malignant pustule in hu- Wyatt, Vivian. 1978. Maladie de Bradford - after 100
mans derived from anthrax in animals. years. New Scientist 79: 192-4.
Bell's work had been made possible by the work of
Davaine and that by Robert Koch in the 1860s and
1870s. During the nineteenth century, the study of
anthrax and the use of animal models in its pursuit
had become an important part of the framework for VIII.9
the emergence of bacteriology as an academic disci-
pline. In France, Eloy Barthelemy established the Apoplexy and Stroke
transmissibility of anthrax in feeding experiments
with horses in 1823. From 1850 onward, study of the
putative agent was pursued by workers in Germany Apoplexy
and in France, beginning with the results obtained by The old, very popular and quite international term
Aloys Pollender, then by Pierre Rayer, andfinallyby apoplexy (or its equivalents apoplectic attack, attack,
Davaine who, during extensive work with guinea apoplectic ictus or ictus) today generally means
pigs in the 1860s, bestowed xon it the name of stroke. The word "apoplexy" comes from the Greek
bactiridie, which survived in the literature for a long apoplexia, which is derived from the verb apoples-
time. From 1876 onward, the anthrax bacillus be- sein, meaning, respectively, "stroke" and "to strike."
came a cornerstone of both Koch's theories and his To define apoplexy is therefore to relate the history
development of pure culture methods; in the late of the word and of its different successive significa-
1870s, W. S. Greenfield at London's Brown Institu- tions. The history of apoplexy, from the Greeks to the
tion and H. Toussaint in Lyons published the first twentieth century, will be presented first, followed
studies of acquired immunity against anthrax in ani- by the medical details of stroke.
mals, before Pasteur took over thefieldand was able
to demonstrate, at Pouilly-le-Fort in 1881, that immu- History
nity could be produced through vaccination of sheep. In the Hippocratic corpus, "apoplexy" appears as an
In Great Britain, industrially acquired anthrax obviously clinical term. For many centuries after
became a notifiable disease in the Factory and Work- Galen's-writings of the second century A.D., it was
shops Act of 1895; the incidence was reduced when thought that apoplexy involved brain matter,
the Anthrax Prevention Act of 1919 prohibited im- whereas epilepsy represented a disturbance of brain
portation of certain types of potentially contami- function. From the invention of the printing press to
nated material. Since World War II, following the the late nineteenth century, several hundred mono-
introduction of antibiotic therapy, the number of fa- graphs were devoted to apoplexy. Indeed the medical
tal human cases has been substantially reduced. history of A. Dechambre (1866) listed some 150 such
Lise Wilkinson references between 1611 and 1865.
Thefirstautopsies involving postmortem examina-
Bibliography tions of the brain were performed in the seventeenth
Brachman, Philip S. 1980. Inhalation anthrax. Annals of century. Many more were done, however, after the
the New York Academy of Science 353: 83-93. publication of De Sedibus, et Causis Morborum per

VIII.9. Apoplexy and Stroke 585
Anatomen Indagatis, Libri Quinque by Giovanni tumor, uremia, or vascular obstruction. A. Trous-
Battista Morgagni in 1761. Morgagni reported nu- seau, a professor in Paris, however, had attacked
merous cases of postmortem examinations of apo- this problem of confusion in his famous Clinique
plexy cases, which he separated into serous apoplexy medicale de I'Hotel-Dieu de Paris (1865), and the
(apoplexia serosa) and sanguineous apoplexy (apo- French neurologist J. M. Charcot later (1881) empha-
plexia sanguinea). sized that apoplexy was a clinical syndrome that
In his 1820 treatise On Apoplexy, John Cooke con- unfortunately had often been used synonymously
sidered that hemorrhagic lesions were commonest with cerebral hemorrhage.
and that the other types of lesions (e.g., tumors, Thus, Trousseau and Charcot, along with individu-
suppuration, cysts) were questionable cases of apo- als such as Dechambre (1866), E. Bouchut and A.
plexy. In his volume Cases of Apoplexy and Lethargy Despres (1889), and J. Dejerine (1914), concluded
with Observations upon the Comatose Diseases pub- that apoplexy could arise from conditions other than
lished in 1812, John Cheyne thought that apoplexy intracerebral hemorrhage, and that the use of the
might be "serous" or "sanguineous," but he was skep- term should be restricted to the clinical syndrome
tical of the former entity. The periodic apnea, now that involved a "sudden and simultaneous loss of all
known as the Cheyne-Stokes respiration, was first the brain functions, consciousness, feeling and move-
described by Cheyne in an 1818 article. "A case of ment, without conscpicuous change of respiration
apoplexy in which the fleshy part of the heart was and blood circulation" (Dejerine 1914). Surprisingly,
converted into fat." For John Abercrombie, writing in 1921, J. Lhermitte, in his well-known Traite de
on Pathological and Practical Research on Diseasespathologie medicale, nonetheless persisted in the use
on the Brain and Spinal Cord in 1828, the cerebral of apoplexy as a synonym for hemorrhage and op-
lesion of apoplexy might be either a hemorrhage or a posed the "hemiplegy of the apoplexy" and "the
serous effusion, but sometimes there seemed to be no hemiplegy of the infarctus."
apparent anatomic lesions. The term "apoplexy" has since become obsolete
In his well-known L'Anatomie pathologique du and disappeared from the indices of most contempo-
corps humain . . ., Jean Cruveilhier, professor of mor- rary textbooks of neurology and neuropathology and
bid anatomy in Paris, used the word "apoplexy" as a from the usual vocabulary of the modern physician.
synonym for "hemorrhage" (in its anatomic, patho- Nevertheless, it remains widely used in popular lan-
logical meaning). He distinguished "apoplexy with- guage and literature. Its proper use, however should
out loss of consciousness" from "apoplexy with loss of be restricted to the field of the history of medicine,
consciousness" and wrote of pontine or spinal apoplex- from Hippocrates to the beginning of the twentieth
ies as well as cerebral ones. This pathological point of century. In the present medical vocabulary, the term
view was strengthened by Richard Bright who, in his "apoplexy" must be replaced either by "stroke" or by
book Diseases of the Brain and Nervous System "hemorrhage" according to the context.
(1831), described and illustrated under the term "apo-
plexy" several cases of cerebral hemorrhage. Stroke
This association of apoplexy with hemorrhage in According to World Health Organization diagnostic
the central nervous system led gradually to the use criteria, a stroke consists of "rapidly developing clini-
of apoplexy as a synonym for hemorrhage and to the cal signs of focal (at times global) disturbance of
creation of expressions such as "spinal apoplexy" (in cerebral function, lasting more than 24 hours or
place of "spinal hemorrhage"), "pulmonary apo- leading to death with no apparent causes other than
plexy" (in place of "hemorrhagic pulmonary in- that of vascular origin." "Global" refers to patients
farct"), "abdominal apoplexy" (in place of "massive in deep coma and those with subarachnoid hemor-
abdominal hemorrhage"), "renal apoplexy" (in place rhage (SAH). This definition excludes transient isch-
of "renal hemorrhage"), "splenic apoplexy" (in place emic attacks (TLA), a condition in which signs last
of "hemorrhage of the spleen"), and so forth. less than 24 hours.
From the second half of the nineteenth century to
the beginning of the twentieth century, the semantic Distribution and Incidence
confusion between apoplexy and hemorrhage contin- Strokes are the most common life-threatening neuro-
ued. J. Russell Reynolds, for example, in his Diagno- logical disease and the third leading cause of death,
sis of Diseases of the Brain, Spinal Cord, Nerves and after heart disease and cancer, in Europe and the
Their Appendages (1866), stated that an apoplectic United States. Death rates from strokes vary with
attack could result from congestion, hemorrhage, age and sex; for example, in the United States, the

rates for males are 11.9 per 100,000 for those aged sists long enough. In most cases, ischemia is caused
40 to 44, and 1,217 per 100,000 for those aged 80 to by occlusion of an intracerebral artery by a throm-
84. For females the rates are 10.9 (aged 40 to 44) and bus or an embolus arising from extracranial artery
1,067 (aged 80 to 84). In France, in the 30- to 34- disease or cardiac source. The main cause of isch-
year-old group, fully 2^ times more men than women emic strokes (40 to 56 percent of the cases) is
die of the disease. The differential, however, declines atherosclerotic brain infarction, the result of either
progressively with increasing age so that at over age intracerebral artery thrombosis or embolism aris-
84 the sex ratio is equal. Large differences in ing from stenosed (narrowed or restricted) or oc-
cerebrovascular disease (CVD) mortality have been cluded extracranial arteries. Lacunar infarction (14
noted among races. For example, in the United percent of the ischemic strokes) is a small, deep
States, mortality is 344 per 100,000 for nonwhites infarct in the territory of a single penetrating ar-
but just 124 per 100,000 for whites. Among countries tery, occluded by the parietal changes caused by
differences in mortality due to stroke ranged from 70 hypertensive disease. Cerebral embolism from a car-
in Switzerland to 519 per 100,000 in Japan. Within diac source accounts for 15 to 30 percent of ischemic
the same region, mortality from stroke is higher in strokes. The main cause is atrial fibrillation related
Scotland than it is in England and Wales. to valvular disease or ischemic heart disease. Other
Decline in CVD deaths has occurred in all devel- causes of cerebral infarction are multiple, resulting
oped countries since 1915, and the decline has acceler- from various arterial diseases (fibromuscular dys-
ated during the last two decades. The acceleration plasia, arterial dissections, arteritis), hemopathies,
seems related to decline in incidence, because 30-day systemic diseases, or coagulation abnormalities.
case fatality rates were unchanged over this 20-year However in 20 percent of the cases, the cause of
period. Interestingly, this decrease in incidence was cerebral infarction, despite efforts to arrive at a
demonstrated in a Rochester study (Schoenberg 1978). diagnosis, remains undetermined.
The incidence in Rochester, New York, in 1983 Intracranial hemorrhages (ICH) account for 37 per-
was 103 per 100,000. The 3-week mortality rate was cent of strokes. The main cause of ICH is the rupture
within the range of 25 to 35 percent. But strokes are of miliary aneurysms that have developed in the
more disabling than lethal: 20 to 30 percent of survi- walls of interior arteries because of hypertensive dis-
vors became permanently and severely handi- ease (72 to 81 percent of the ICH). Nonhypertensive
capped. Moreover, recurrent strokes have been ob- causes of ICH are numerous and include substance
served in 15 to 40 percent of stroke survivors. abuse, cerebral amyloid angiopathy, intracerebral tu-
mors, and coagulation abnormalities.
Risk Factors
Apart from age, the most important risk factor for Clinical Manifestations and Classification
CVD is arterial hypertension. Control of severe and Clinical manifestations of strokes depend on both
moderate, and even mild, hypertension has been the nature of the lesion (ischemic or hemorrhagic)
shown to reduce stroke occurrence and stroke fatal- and the part of the brain involved. In the early
ity. Cardiac impairment ranks third, following age 1960s, a classification of strokes according to their
and hypertensive disease. At any level of blood pres- temporal profile was proposed to promote the use of
sure, people with cardiac disease, occult or overt, common terminology in discussion of natural history
have more than twice the risk of stroke. Other risk and treatment programs.
factors are cigarette smoking, increased total serum The term incipient stroke (TIA) was defined as
cholesterol, blood hemoglobin concentration, obesity, brief (less than 24 hours), intermittent and focal
and use of oral contraceptives. neurological deficits due to cerebral ischemia, with
the patient normal between attacks. The term "re-
Etiology and Pathology versible ischemic neurological deficit" (RIND) was
Strokes are a heterogeneous entity caused by cere- coined for entirely reversible deficits occurring over
bral infarction or, less commonly, cerebral hemor- more than 24 hours.
rhage. Cerebral infarction accounts for the majority The term progressing stroke (stroke-in-evolution)
of strokes (63 percent, as documented by the New is applied to focal cerebral deficits observed by the
York Neurological Institute, in 1983-4). When physician to progress in the severity of the neurologi-
perfusion pressure falls in a cerebral artery below cal deficit over a period of hours or, occasionally, over
critical levels, brain ischemia (deficiency of blood) a few days.
develops, progressing to infarction if the effect per- The term completed stroke is used when the neuro-

VIII. 10. Arboviruses 587
logical signs are stable and no progression has been

noted for 18 to 72 hours. Major stroke is a term ap- VIII. 10
plied when immediate coma or massive neurological
deficit occurs. In these cases, hope of recovery and of
Arboviruses
effective treatment are minimal. Minor stroke, by con-
trast, is a term applied to cases where the deficits Arbovirus is a truncated term for arthropod-borne
relate to only a restricted area of a cerebral hemi- viruses, all of which require multiplication in their
sphere, or where the symptoms experienced are of vectors for transmission. Arboviruses diseases may
only moderate intensity. With minor strokes, diagno- be simpler to understand when viewed solely from
sis and institution of treatment should be rapidly com- the position of the end product, which is disease in
bined to avoid further deterioration and, if possible, humans or other vertebrates. The diseases fall into a
facilitate the regression of deficit. few recognizable sets: (1) encephalitides; (2) diseases
These definitions contain some obvious uncertain- with fever and rash, often fairly benign; (3) diseases
ties, particularly in categorizing a stroke during the with hemorrhagic manifestations, often fatal; and
early hours. However, they underscore the fact that (4) mild fevers, quite undiagnosable except through
the management of a stroke often depends more on laboratory study. A common feature of all of these is
its temporal profile and on the severity of the neuro- periodic outbreaks, with dozens, hundreds, or thou-
logical deficit than on the nature of the lesion. sands of cases. A second common feature is lack of
Jacques Poirier and Christian Derouesni specific treatment. In addition, only for very few of
the diseases do vaccines exist. Possibility of disease
control is real, however, and is based on a knowledge
Bibliography
Alperovitch, A., et al. 1986. Mortality from stroke in
of the epidemiology of arbovirus infections in gen-
France. Neuroepidemiology 5: 80—7. eral, the role that vectors play, and the particular
Barnett, H. J. M., et al., eds. 1986. Stroke: Patho- features in regard to the transmission of the specific
physiology, diagnosis, and management, 2 vols. New disease in question.
York.
Bouchut, E., and A. Despres. 1889. Dictionnaire de
midecine et de tMrapeutique midicale et chirurgicale, Etiology
ed. Felix Alcan. Paris. Arboviruses, numbering at latest count 512 separate
Charcot, J. M. 1881. Clinical lectures on senile and chronic and identifiable agents, are placed in 11 families,
diseases. London. with a few as yet unclassified agents. Table VIII. 10.1
Dechambre, A. 1866. Dictionnaire encyclopidique des sci- presents a listing of family and subfamily groupings,
ences midicales, Vol. V. Paris. limited to those viruses of major importance in hu-
Dejerine, J. 1914. Simiologie des affections du systeme man and veterinary diseases.
nerveux. Paris.
Derousn6, C. 1983. Pratique neurologique. Paris.
It is evident from the table that there is no simple
Escourolle, R., and J. Poirier. 1978. Manual of basic
delimiting definition of an arbovirus on a taxonomic
neuropathology, 2d edition. Philadelphia. basis, or even on a biochemical basis. There are 511
Jaccoud, ed. 1865. Nouveau dictionnaire de midecine et de RNA viruses, and then there is African swine fever
chirurgie pratiques. Paris. virus (ASF), a DNA virus. ASF belongs to the
Lhermitte, J. 1921. Les Lesions vasculaires de 1' enc§phale Iridoviridae and is the only Iridovirus (so far as is
et de la moelle epiniere. In Traiti de pathologie midi- yet known) with an arthropod vector and a verte-
cale et de thirapeutique appliquie, Vol. VI, ed. E. brate host. There are numerous Iridoviridae, inciden-
Sergent, L. Ribadeau Dumas, and L. Babonneix, 195. tally, with arthropod vectors and plant or arthropod
Paris. hosts.
Malmgren, R., et al. 1987. Geographical and secular Viruses must qualify in several important points in
trends in stroke incidence. Lancet 2:1196—9.
order to be considered as arboviruses. The life cycle of
Schoenberg, B. S., ed. 1978. Neurological epidemiology.
New York.
an arbovirus involves an arthropod (usually insect,
Spillane, John D. 1981. The doctrine of the nerves: Chap-
tick, or mite) that is capable of becoming infected
ters in the history of neurology. Oxford. itself when it imbibes the virus from an infected host.
Stehbens, W. E. 1972. Pathology of the cerebral blood ves- The arthropods serve as vectors of the virus, from an
sels. St. Louis. infected vertebrate host to an uninfected one. The
Trousseau, A. 1865. Clinique midicale de I'Hdtel-Dieu de virus must multiply in the arthropod, a process re-
Paris, Vol. 2, 2d edition. Paris. quiring several days, and reach a concentration suffi-

Table VIII.10.1. 512 recognized arboviruses listed by family and subcategories, with totals
Antigenic groups No. of viruses in Total no. arbovs. in

Virus family Genus within genus groupings family
Bunyaviridae 251
Bunyavirus 17 128
Nairovirus 6 24
Phlebovirus 1 38
Uukuvirus 1 6
Hantavirus 1 4
Bunyavirus-"like" 10 25
Ungrouped 26
"bunya"
Reoviridae 72
Orbivirus 14 61
Ungrouped 11
Rhabdoviridae 64
Lyssa virus 1 2
Other groupings 9 39
Ungrouped 23
Togaviridae 98
Alphavirus 1 28
Ungrouped alpha 1
Flavivirus 1 68
Ungrouped flavi 1
Rubivirus—measles 1 not arboviruses
Corona viridae 2
Corona virus 1 2
Herpesviridae 1
Ungrouped 1
Nodaviridae 1
Nodavirus 1 1
Orthomyxoviridae 2
Thogoto 1 1
Ungrouped 1
Paramyxoviridae 2
Paramyxovirus 1 1
Poxviridae 4
Salanga 1 1
Ungrouped 3
Iridoviridae 1
African swine fever 1 1
Unclassified to 14
family
Nyamanini 1 1
Somone 1 1
Ungrouped 12
Grand total 512
Source: Modified from U.S.P.H.S. Centers for Disease Control, Center for Infectious Diseases (1988)

VIII. 10. Arboviruses 589
cient to be passed, in a later feeding, to the host, and Structurally, some entire groupings of viruses are
to induce an infection in that host. The host, in turn, enveloped, some are not. There are other differential
must have a viremic phase in order to pass the virus characteristics, as indicated in the table. Again, the
back to a biting or sucking arthropod. common bond is biological transmission by arthro-
This rigid definition gives rise to confusion (e.g., pod to vertebrate. How, in the evolution of viruses,
recent misconceptions about putative arthropod vec- this ability to exploit two phyla of living creatures
tors of measles, hepatitis B virus, and human arose again and again in such widely different taxa,
immunodeficiency (HIV) virus), but the definitions is not known.
are uncompromising. The confusion is compounded Virus morphology is not totally explicated by refer-
when it is realized that although an arthropod, with ence to arboviruses subsumed in such groups as al-
mouth parts freshly contaminated by feeding on an phaviruses, flaviviruses, bunyaviruses, rhabdovi-
infected host, may possibly transmit virus mechani- ruses, orbivirus (see Table VIII. 10.1). More detailed
cally, a defined vector must be capable of multiply- references (e.g., Theiler and Downs 1973; Field
ing the virus internally over a period of several days 1985) must be consulted for further information. Al-
and of transmitting it by then biting a susceptible most the entire grouping of arboviruses consists of
host in later feedings. This is referred to as the RNA viruses that are readily degradable by lipid
biological transmission cycle. Mechanical transmis- solvents, ribonucleases, or heat and freezing (at tem-
sion must be quite unusual and with respect to peratures above — 70°C). The viral agents can be
arboviruses has never been observed in nature, but vacuum-desiccated satisfactorily, permitting greatly
has been achieved in the laboratory under controlled lengthened periods of storage with minimal loss in
conditions. In the case of HIV (not an arbovirus), titer. Wet or desiccated material in glass-sealed am-
mechanical transmission by needle is thought to be poules can be stored in dry-ice containers or, better
a dominant mode of transmission in the subset of yet, in liquid nitrogen containers for long periods of
drug users in some societies. The malaria parasite time.
similarly can be transmitted by infected needle.
Again, from the point of view of the virus, it must Epidemiology
be capable of multiplying in one or more vertebrate When the science of epidemiology of the nineteenth
hosts, usually over a period of several days, reaching century was applied to the study of yellow fever, the
a level in the bloodstream adequate to infect a forag- epidemiologist was hampered by a lack of knowledge
ing vector. of infectious agents and of vector arthropods in the
The above considerations define (1) the interval transmission cycle. Consequently, there was great
between the arthropod ingestion of infected blood confusion and an endless diatribe surrounding vari-
and the ability to transmit virus biologically, again ous hypotheses on how infection could travel so mys-
by biting, to a susceptible host (the extrinsic incuba- teriously from place to place, with infections occur-
tion period), and (2) the period, in the host, before ring in people who apparently never had had contact
the viremia level rises to a height necessary to infect with a case. With Theobald Smith's demonstration
the biting arthropod (the intrinsic incubation pe- in cattle of transmission of the Texas redwater fever
riod). The minimum interval between infection in organism by ticks, Ronald Ross's demonstration of
one vertebrate host and acquisition of infection by transmission of the parasite of malaria by mosqui-
the next vertebrate host is the sum of the extrinsic toes, and Walter Reed's demonstration of transmis-
and intrinsic incubation periods. It is frequently sion of the virus of yellow fever by mosquitoes, came
about a week or more, and the maximum interval the dawn of modern epidemiological studies on
from one infection to the next may be weeks or arthropod-transmitted diseases.
months. As can be seen in Table VIII. 10.3, a mysterious
specificity exists between certain feeding arthropods
Virus Morphology, Size, Structure, and and certain viruses; furthermore, a preferential feed-
Characteristics ing of certain arthropods (mosquitoes, for example)
Arboviruses from selected families or subgroupings on certain food sources is shown. Some vertebrates
that contain viruses of importance to humans or react to a specific virus with severe disease. Yellow
other vertebrates are compared in Table VIII. 10.2. fever, for example, produces severe illness in hu-
Size varies considerably; shapes range from spheri- mans, laboratory white mice, rhesus monkeys, and
cal to rhabdoform (bullet-shaped) to icosahedral. Alouatta monkeys. On the other hand, yellow fever

Table VIII. 10.2. Size, morphology, structure, and composition of selected virus families or genera that
contain arboviruses
Family Genus Size Morphology Composition Structure
Bunyaviridae 80-120 run spherical RNA Lipid bilayer or enve-
lope that anchors
external surface pro-
jections of 5-10 nm,
arranged regularly
Uukuniemi has hex-
agonal arrays of sur-
face structure
Togaviridae
Alphavirus 60-65 nm spherical RNA Enveloped; symmetri-
cal surface fila-
ments, 6-10 nm;
icosahedral with
42-subunit symme-
try
Flavivirus 43 nm (mean diam.) spherical RNA Enveloped with sur-
face projections
Reoviridae
Orbivirus 50-65 nm (inner spherical RNA Double-protein capsid
core) shell; nonenveloped;
icosahedral symme-
try
Rhabdoviridae 60-85 nm wide; "bullet shape" RNA Enveloped; intri-
approx. 180 nm long cate internal struc-
(animal rhabs) ture
Corona viridae 100-150 nm spherical RNA No envelope; 20-nm
surface projections
Iridoviridae
African swine fever 175-215 nm icosahedral DNA Capsid has dense
outer shell; central
nucleoid, 72-80 nm
Source: In part based on Theiler and Downs (1973); Field (1985); and Monath (1988).
may infect dogs, cats, Cebus monkeys, cows, and human beings, but are of cardinal importance in the
horses without producing overt disease. Among the design of specific serologic tests for virus identifica-
encephalitides, eastern equine encephalitis (EEE) tion. With the advent of cell culture techniques, lead-
virus (endemic strains) can produce severe disease ing to the preparation of monoclonal antibodies to
and death in human beings, laboratory mice, certain specific portions of a virus genome, identification
other vertebrates, and very specifically equines. But work has been greatly broadened in scope and much
cattle do not develop illness with this agent, nor do narrowed in specificity, often providing in a matter
sheep, goats, dogs, or cats. By contrast, the South of hours identification of a virus that would have
American EEE strain that kills horses produces no required days or weeks for identification using older
illness in human beings but does produce detectable techniques.
antibodies. Modern techniques, founded on studies carried out
The resistance of various vertebrates to various over a period of half a century, involving basic labora-
arboviruses can be of use to the investigator because tory techniques of complement fixation, precipita-
it permits the production of large quantities of im- tion, electrophoresis, centrifugation, hemagluti-
mune sera in such vertebrates. Such immune sera nation inhibition, and virus neutralization, have
are of minimal importance in treating disease in been extended by later advances such as "tagged"

VHI.10. Arboviruses 591
Table VIII. 10.3. Twenty-nine selected arboviruses important in causing human and/or animal diseases, with
data on vectors, hosts, and geographic distributions
Virus Principal host(s)

Family Subfamily or group (abbr.) Vector(s) involvement Geographic range
Togaviridae Alphaviridae EEE mosquito equines, birds, hu- Americas
mans
WEE mosquito equines, birds, hu- Americas
mans
VEE mosquito equines, small mam- Americas
mals, humans
CHIK mosquito humans Africa, Asia
RR mosquito humans Australasia, Pacific
MID mosquito large vertebrates, Africa
humans
Flaviviridae YF mosquito monkeys, humans tropical, Americas
and Africa
DENs mosquito humans, monkeys pantropical and sub-
tropical
SLE mosquito birds, humans, Americas
horses, dogs
JBE mosquito birds, humans, pigs, Asia, Southeast
horses Asia
MVE mosquito birds, humans Australia, New
Guinea
ROC mosquito humans Brazil
RSSE tick small mammals, hu- northern Eurasia
mans
KFD tick monkeys, humans India (Mysore
State)
POW tick small mammals, hu- USA, Canada
mans
Bunyaviridae California gp LAC mosquito small mammals, hu- midwest USA
mans
Phlebovirus gp SFS Phlebotomus humans Mediterranean re-
gion
SFN Phlebotomus humans Mediterranean re-
gion
RVF mosquito sheep, cattle, hu- tropical Africa,
mans Egypt, RSA
Simbu serogroup ORO Culicoides humans Trinidad, South
America
Nairovirus gp CHF tick cattle, humans Middle East, Africa,
s. Russia
NSD tick, Culicoides sheep, humans Africa
Hantaan gp HAN mites small animals, hu- worldwide, seaports
mans
Rhabdoviridae Rabies (not an
arbovirus)
Vesiculovirus gp VSI mosquito bovines, humans
PIRY marsupials, hu- Brazil
mans
CHP Phlebotomus humans Asia, Africa

Table VIII.10.3. (cont.)
Virus Principal host(s)

Family Subfamily or group (abbr.) Vector(s) involvement Geographic range
Orbiviridae Colorado tick CTF tick small mammals, hu- western USA
fever gp mans
Changuinola gp CHAN Phlebotomus humans Panama, South
America
Iridoviridae African swine fever ASF tick swine, warthog Africa, Europe,
Cuba
Abbreviations: ASF = African swine fever; CHP = Chandipura; CGL = Changuinola; CHIK = Chikungunya; CTF =
Colorado tick fever; CHF = Crimean hemorrhagic fever; DENs = dengues (1,2,3,4); EEE = eastern equine encephalitis;
HAN = Hantaan (Korean hemorrhagic fever); JBE = Japanese encephalitis; KFD = Kyasanur Forest disease; LAC =
LaCrosse; MID = Middelburg; MVE = Murray Valley encephalitis; NSD = Nairobi sheep disease; ORO = Oropouche;
PIRY = Piry; POW = Powassan; RVF = Rift Valley fever; ROC = Rocio; RR = Ross River; RSSE = Russian spring/
summer encephalitis; SFN = Naples sandfly fever; SFS = Sicilian sandfly fever; SLE = St. Louis encephalitis; VEE =
Venezuelan equine encephalitis; VSI = Vesicular stomatitis (Indiana); WEE = Western equine encephalitis; YF =
yellow fever.
Sources: Based in part on Calisher and Thompson (1985); Evans (1984); and Karabatsos (1975), among others.
antibodies - that is, the use of monoclonal anti- has of recent years established itself in other coun-
bodies in combination with "tagged probes" in elec- tries such as the United States, with as yet unknown
tron microscopy. Such new techniques, involving the potential for involvement in the life cycles of still
use of specific "probes," are presently a fertile area of other viruses such as yellow fever. There are also
research, from which is emerging a more rational other aedine vectors of dengue in Polynesia. The
and complete knowledge of the virus particle itself dengues are placed in four serotypes, one or more of
and its interactions with vertebrate and inverte- which are associated with often fatal manifestations
brate hosts. of dengue hemorrhagic fever and dengue shock syn-
drome. These are important causes of mortality in
Dengue small children in countries of Southeast Asia, scat-
Geographic distribution of viruses and disease is tered cases being seen elsewhere. It is hypothesized
determined by the characteristics of the vectors, that sequential infections in the same individual by
rather than by the characteristics of the viruses. different serotypes of dengue may lead to these seri-
Taking dengue viruses (Flavivirus genus) as an ex- ous complications.
ample, the limits of their distribution are defined by
the limits of the distribution of the principal vector, Yellow Fever
Aedes aegypti. This mosquito, originally found in Yellow fever, a Flavivirus serologically related to the
Southeast Asia, spread worldwide, traveling wher- dengues, is also capable of being transmitted from
ever humans traveled and established itself in tropi- human to human by A. aegypti and can maintain
cal and subtropical and often temperate regions, but itself endemically in a human population by such
not in Arctic and Antarctic polar extremes. The means. This mode of transmission occurred a cen-
dengue viruses moved with the vectors and became tury and more ago but has not been observed re-
established worldwide, particularly in tropical and cently. The virus is found in Africa, south of the
subtropical regions. The viruses may have had, in Sahara, and in the equatorial South American jun-
their original territories of Southeast Asia, cycles gle regions. In both Africa and South America (here
involving A. aegypti and/or Aedes albopictus and including Central America, and the West Indies),
subhuman forest primates, but as the virus left their and even in the United States, Spain, France, Gi-
original home, they adapted to a vector-human- braltar, and England, periodic outbreaks of the
vector cycle, allowing them to exist in endemic form disease, often explosive and devastating, have been
wherever humans exist, and to appear in epidemic observed since A. aegypti may establish itself in sub-
form at intervals. tropical and even temperate locales. Although A.
The other Southeast Asian vector, A. albopictus, aegypti (and A. albopictus) is prevalent in Asia and

VIII.10. Arboviruses 593
Australia, yellow fever has never established itself themselves have a basic vertebrate cycle in birds or
in these regions. With vectors present, as well as small mammals. Certain of the viruses, such as Vene-
millions of nonimmune humans, there is a continu- zuelan equine encephalitis, eastern equine encepha-
ing threat of its introduction. litis, and western equine encephalitis, can escape
A reason yellow fever has been able to maintain from the mosquite-small vertebrate-mosquito cycle
and spread like wildfire in one or another of the
itself in tropical South America and Africa is that the
larger vertebrates, causing widespread mortality,
virus can utilize a different set of vectors: the forest
canopy-frequenting Haemagogus mosquitoes of the and humans may be thus involved. These epidemics
New World, as well as A. aegypti and Aedes africanus, are sporadic and unpredictable. The endemic cycles
Aedes simpsoni, Aedes taylori, Aedes furcifer, and are present continuously, but unobserved unless spe-
other aedines in Africa, often with and often without cifically sought for. Others of the viruses are associ-
A. aegypti. Using the endemic Haemagogus or Aedes ated particularly with birds and mosquitoes. These
species, the virus remains established as an endemic viruses include St. Louis encephalitis virus of the
virosis in various subhuman primates of these re- Americas, Japanese encephalitis virus of the Orient,
gions. This maintenance cycle is referred to as "syl- Murray Valley encephalitis of Australia and New
van" or "jungle" yellow fever. The sylvan Haemago- Guinea, Ilheus virus of South America and Trinidad,
gus or Aedes can and often does bite humans, and Rocio virus of southeast Brazil, and West Nile virus
thus can transfer the virus out of the mosquito- of Africa, the Middle East, and India. The viruses
monkey-mosquito cycle into a mosquito-human- are often very prevalent in a region, in birds, with
mosquito cycle. An infected forest worker in the earlythe disease usually being uncommon in human be-
stage of illness (and circulating virus in high titer)ings, but sometimes occurring in large epidemics.
can migrate to an urban setting infested with A. Heron rookeries and pig farms in the Orient have
aegypti and establish the dreaded urban mosquito- been shown to be Japanese encephalitis virus-
human-mosquito cycle. Recently, several large out- amplifying localities, providing opportunities for in-
breaks of this type have occurred in Africa and in fection of large numbers of mosquito vectors and
South America, some of them involving the deaths of thus facilitating large-scale transmission of virus to
thousands of people such as in the Nigeria epidemic human beings. Immunity rates in populations are
in 1986. often high (bespeaking inapparent infections), and
A completely effective attenuated yellow-fever vac-encephalitis rates low.
cine (17D) has been available since 1935, but govern- In the central United States, a recent arrival on
ments in regions where yellow fever is endemic have the virus scene, La Crosse virus, a member of the
as yet failed to react adequately in getting the popula-
California virus group, has established its position
tion at risk immunized. The blame for this rests not as the commonest arboviral cause of encephalitis.
on technical failure (the vaccine itself), nor on diffi-
This endemic disease has some unusual features. It
culties in administration of same, but in the inability
is transmitted by woodland aedine mosquitoes, and
of governments to establish adequate bureaucratic- has as vertebrate hosts certain small mammals of
administrative procedures to protect the health of the region. It has been further established that the
the people. Aedes control projects, often employed forvirus can be transmitted transovarially (TOT) from
disease control, again suffer from a bureaucratic in- mosquito to mosquito, vertically, through the egg,
ability to maintain effective programs at a high leveland laterally, from female to male or from male to
of efficiency over periods of years. female during copulation. This mechanism has been
hypothesized to explain the long persistence of virus
Encephalitides in a vector, serving to carry it over periods of inclem-
Another group of the arboviruses, the encephalitides ent weather or drought. Similar TOT has been
(Venezuelan, eastern, western, St. Louis, Japanese, shown for dengue, Japanese encephalitis, and yellow
Murray Valley, Russian spring-summer encephali- fever.
tis), present mechanisms quite different from the Tick-borne encephalitis (Russian spring-summer
dengue or yellow fever models. The vectors in encephalitis, RSSE) in the Eurasian continent and
question — mosquitoes or ticks - are of themselves Powassan virus encephalitis in America are delim-
geographically delimited, and therefore, the specific ited by the range of specific tick vectors; these vi-
viruses associated with specific vectors are geo- ruses are endemic in small mammals and present
graphically delimited, with little chance of spread themselves in humans as sporadic cases, often not
beyond natural ecological barriers. The viruses distinguished from encephalitis caused by other vi-

ruses or of unknown etiology except by special labo- ticularly treatment of shock (maintaining fluid and
ratory studies. electrolyte balance) may be life-saving in dengue-
Epidemiology of arboviruses can be conceptual- shock syndrome cases.
ized as a huge, multidimensional matrix, involving Vector control is applicable in certain situations.
many viruses on one axis, many vectors on another, Fred Soper and co-workers in the 1930s eradicated A.
many vertebrate hosts on another, and yet another aegypti from all of Brazil, thus eliminating the risk of
axis for ecological, ethological, meteorological, cul- urban yellow fever. The mosquito has reinvaded
tural, and edaphic influences impinging on vectors much of the territory formerly freed, and the threat of
and hosts. yellow fever has returned. Short-term vector control
is widely practiced, particularly when epidemics
Clinical Manifestations and Diagnosis threaten. This may include airplane spraying of insec-
The early days of onset of most arboviral infections ticides, treatment of interior walls of buildings with
are usually accompanied by fevers, aching, and gen- residual insecticides, insecticide treatment of mos-
eral malaise, and cannot be distinguished from early quito breeding places, destruction or drainage of mos-
stages of other very common diseases such as influ- quito breeding places, screening of dwellings, use of
enza, malaria, measles, pneumonias, meningitis, insecticidal fogs in and around dwellings, use of in-
other respiratory afflictions, and even Lassa fever sect repellents, and wearing of protective clothing.
and smallpox. As diseases progress in their course, The attenuated live yellow fever virus vaccine
specific later manifestations may provide aid in dif- (17D) has been used for over 50 years in the success-
ferential diagnosis. Such specific manifestations in- ful immunization of millions of people. A live attenu-
clude rashes, eruptions, nausea and vomiting, diar- ated dengue virus vaccine is being tried. A killed
rhea, cough, and encephalitis. Japanese encephalitis virus vaccine is given to mil-
Sporadic cases in a population may be quite impos- lions of people in the Orient. A killed RSSE virus
sible to diagnose specifically. But as epidemics prog- vaccine is used extensively in parts of the former
ress, specific features may appear and provide the Soviet Union. Killed virus vaccines against eastern
clue to diagnosis. Malaria in the tropics and influ- equine encephalitis, western equine encephalitis,
enza in temperate regions and the tropics serve as Venezuelan equine encephalitis, and Rift Valley fe-
"coverup" or "umbrella" diagnoses that often block ver virus are used primarily to protect livestock.
out recognition of arbovirus illness. Laboratory workers studying these viruses are rou-
Definitive diagnosis demands the assistance of ex- tinely immunized.
perienced virologists working in adequate laboratory Wilbur G. Downs
diagnostic facilities. There exist only a few dozen
such facilities in the world, supported by the World
Health Organization, governments, armed forces Bibliography
military establishments, and, in a few instances, pri- Barber, T. L., and N. M. Jochim, eds. 1985. Bluetongue and
vate philanthropy. Such laboratories usually com- related Orbiviruses. New York.
Beneson, A. S., ed. 1985. Control of communicable diseases
bine laboratory diagnostic methodology and facilities
in man, 14th edition. New York.
for carrying out field epidemiological studies. Calisher, C. H., and W. H. Thompson, eds. 1985. California
Specific diagnosis can only rarely benefit the pa- serogroup viruses. New York.
tient, but is of vital importance in alerting health Evans, A. S., ed. 1984. Viral infections of humans, 2d
departments of the presence of a potentially threat- edition. New York.
ening epidemic. Appropriate control procedures di- Fenner, F., and A. Gibbs. 1988. Portraits of viruses. New
rected at the vectors can then be applied on an emer- York.
gency basis. In the special case of yellow fever, mass Field, B. N., ed. 1985. Virology. New York.
immunization of exposed populations can success- Fraenkel-Conrat, H., and R. R. Wagner, eds. 1979. Com-
fully halt an epidemic in its tracks. Such an immuni- parative virology. New York.
zation campaign is usually combined with emer- 1987. The viruses. New York.
Gear, J. H. S., ed. 1988. Handbook of viral and rickettsial
gency mosquito control.
hemorrhagic fevers. Boca Raton, Fla.
Karabatsos, N., ed. 1975. International catalogue of arbo-
Treatment and Control viruses including certain other viruses of vertebrates.
Aside from provision of nursing care, and maintain- Washington, D.C.
ing nutrition and fluid balance, there are no specific Klingberg, M. A., ed. 1979. Contributions to epidemiology
remedies for infections. Nonspecific measures, par- and biostatistics, Vol. 3. New York.

Vni.ll. Arena viruses 595
Lennette, E. H., and N. J. Schmidt, eds. 1979. Diagnostic meningitis (LCM). Six of the viruses - Junin,
procedures for viral, rickettsial and chlamydial infec- Machupo, Pichinde, Tacaribe, Lassa, and LCMs —
tion. New York. have infected laboratory workers. (Because Lassa
Lennette, E. H., E. H. Spaulding, and J. P. Truant, eds. fever is covered elsewhere in this work, it will not be
1974. Manual of clinical microbiology, 2d edition. treated here in any detail.)
Washington, D.C.
Monath, T. P., ed. 1980. St. Louis encephalitis. New York.
1988. Arboviruses: Epidemiology and ecology, 5 vols.
Virus Morphology, Size, and Structure
Boca Raton, Fla. Electron micrographic studies of infected cells re-
Pan American Health Organization. 1985. Proceedings of veal round, oval, or pleomorphic budding particles
an international conference on vesicular stomatitis. with mean diameters of 110 to 130 nanometers. The
New York. envelopes, which have spikes, are derived from the
Schlesinger, R. W., ed. 1980. The togaviruses: Biology, plasma membranes of the host cell by budding. The
structure, replication. New York. interior contains variable numbers of electron-dense
Scott, H. H. 1939. A history of tropical medicine, 2 vols. granules measuring 20 to 25 nanometers and resem-
Baltimore. bling ribosomes. These sandy grains gave rise to
Strode, G. K., ed. 1951. Yellow fever. New York. the name Arenavirus because arena means "sand"
Theiler, Max K., and Wilbur G. Downs. 1973. The (Rowe et al. 1970). The exact composition of this core
arthropod-borne viruses of vertebrates: An account of material and its derivation are as yet uncertain.
the Rockefeller Foundation virus program. New Haven.
The virions are enveloped RNA-containing nucleo-
U.S. Public Health Services Centers for Disease Control.
Center for Infectious Diseases. 1988. Arthropod-borne
capsids. The genome consists of two single-stranded
virus information exchange, June 14. Atlanta. RNA molecules (Lehmann-Grube 1988).
World Health Organization. 1986. Prevention and control
of yellow fever in Africa. Geneva. History
The first arenavirus to be discovered was the one
Yunkers, Conrad., ed. 1987. Arboviruses in arthropod cells
in vitro, 2 vols. Boca Raton, Fla. causing LCM in mice and monkeys; it was reported
in 1934 by C. Armstrong and R. D. Lillie. Later
studies showed that the virus was present in feral
Mus musculus (the common house mouse) and ac-
counted for a scattering of human cases annually in
Europe and America. More commonly, those cases
VIII.ll were seen in personnel who were handling labora-
Arenaviruses tory animals, particularly white mice and hamsters.
The agent itself was characterized morphologically
by electron microscopy, and later investigated in
The Arenaviridae are a small group of viruses, con- serologic, biochemical, and biophysical studies. No
taining several of considerable importance as hu- serologic relatives were found, and over several de-
man disease agents. They are listed in the Catalogue cades, only scattered cases and outbreaks have been
of Arthropod-Borne Viruses, not because they are reported in America and Europe.
arboviruses but because they have been discovered In 1957, a virus named Tacaribe was recovered
in large part by arbovirologists, working on details from a fruit-eating bat in Trinidad, West Indies
of arthropod-transmitted viruses. Most of the 14 (Downs et al. 1963). This agent remained unclassi-
members of the group have rodents as reservoir fied. Meanwhile a disease was observed among field
hosts, but they occasionally infect humans who im- workers in the northern provinces of Argentina that
bibe or ingest the virus when accidentally consum- occurred at harvest time and caused considerable
ing rodent-contaminated food and drink, or are other- mortality. A virus subsequently named Junin
wise in contact with an environment contaminated (Parodi et al. 1958) was recovered from these pa-
by rodent excreta. At least one of the viruses, how- tients, and the disease was named Argentinian hem-
ever, Lassa virus, can pass directly from person to orrhagic fever (AHF). Cases occur annually, and
person. This happens particularly in hospital set- there have been epidemics of the disease over the
tings. Other Arenaviruses important in human dis- past 30 years.
ease are Junin (Argentine hemorrhagic fever), A particularly virulent infection broke out in the
Machupo (Bolivian hemorrhagic fever) from South small town of San Joaquin, Beni Department, in the
America, and the virus causing lymphocytic chorio- Amazonian lowlands of Bolivia. In due course it was

called Bolivian hemorrhagic fever (Johnson et al. ral cycle of transmission in rodents but, as previ-
1965). The outbreak was checked, however, once the ously mentioned, can spread from human to human.
rodent host of the Machupo virus that caused the
disease was implicated and rodent control mecha- Epidemiology (and Phylogenetic
nisms were instituted. Since then Machupo virus Considerations)
has "gone underground"; no further outbreaks have Table VIII. 11.1 lists the 16 members of the
been reported and little further epidemiological Arenaviridae, their known vertebrate hosts' geo-
work is being done on the disease. graphic distribution, date of first finding, and au-
In January 1969, another of the arenaviruses was thor(s) and dates offirstdescription. Four of these are
forcefully brought to the attention of Western medi- important agents in human disease: LCM, Junin,
cine, with an outbreak among medical personnel in Machupo, and Lassa. In addition, 10 other members
Lassa, northeastern Nigeria (Buckley, Casals, and of the group are apparently nonpathogenic (for hu-
Downs 1970). At least seven more outbreaks of the man beings). Epidemiological information about
disease subsequently named Lassa fever have taken these is scanty, although several — particularly
place since then, involving about 450 patients and Tacaribe and Pichinde — have been studied inten-
almost 125 deaths. The virus appears to have a natu- sively in the laboratory.
Table VIII.il.1. History and natural occurrence of arenaviruses

Natural Occurrence
First Geographic
Virus finding Principal host distribution First description
LCM 1933 Mus musculus America, Europe Armstrong and
Lillie 1934
Quaranfil 1953 Bubulcus ibis: pigeon Argas ticks Egypt, S. Africa, Taylor et al. 1966
Afghanistan, Ni-
geria
Tacaribe" 1956 Artibeus literatus Trinidad, West Downs et al. 1963
Artibeus jamaicensis Indies
Junin 1958 Calomys laucha Argentina Parodi et al. 1958
Akodon azarae
Amapari 1964 Oryzomys sp. Brazil (Amazonas) Pinheiro et al. 1966
Neacomys guianae
Araguari 1964 opossums Brazil USPHS 1988
Johnston Atoll 1964 Ornithodorus capensis Johnston Atoll Taylor et al. 1966
(Pacific)
Machupo 1965 Calomys callosus lowland Bolivia Johnson et al. 1965
Parana 1965 Oryzomys buccinatus Paraguay Webb et al. 1970
Tamiami 1965 Sigmodon hispidus Florida (U.S.A.) Calisher et al. 1970
Pichinde 1965 Oryzomys albigularis Colombia Trapido and
Thomasomys lugens Sanmartin 1974
Latino 1965 Calomys callosus Brazil, Bolivia Webb et al. 1973
Lassa 1969 Praomys natalensis Nigeria, Liberia Buckley et al. 1970
Sierra Leone
Flexal 1975 Oryzomys bicolor Edo. de Para, Brazil Pinheiro et al. 1977
Mopeia ca.1976 Praomys natalensis Southeast Africa Wulffetal. 1977
Mobala ca.1982 Praomys jacksoni Central African Gonzalez et al. 1983
Republic
Note: Three of these viruses are already named in the International Catalogue of Arboviruses (1975 and 1988 update):
Araguari, Quaranfil, and Johnston Atoll are considered possible Arenaviridae, the latter two on basis of electron
microscopic studies (Zeller, personal communication, 1989). None of these three viruses has rodent hosts.
a
The isolation of Tacaribe from mosquitoes is considered doubtful, and due to a possible laboratory numbering error
(Downs et al. 1963).

VIII. 11. Arenaviruses 597
In regard to the Tacaribe group viruses, beginning Immunology

with LCM, and continuing with other members of The various arenaviruses have been shown to be
the group, a rodent association is usually found. related principally via complement fixation reac-
Exceptions are Tacaribe, a virus isolated several tions to the glycoprotein gp44 in the viral envelopes.
times from bats in Trinidad in 1957 (and never The nucleoproteins of the viruses demonstrate rela-
reisolated there or elsewhere), and the two recently tionships through virus neutralization tests. The fa-
associated agents, Quaranfil and Johnston Atoll, tal infection induced in adult mice experimentally
found in birds and tick ectoparasites of birds inoculated with LCM has been shown to be associ-
(learned from personal communication with wife of ated with a T cell-mediated immune response. Stud-
H. Zeller in 1989). ies of the several viruses of the Tacaribe group have
A fascinating feature is the geographic-ecolog- extended knowledge of this phenomenon. When new-
ical-natural host range of the Arenaviridae. Each born mice are infected intracerebrally with LCM,
rodent species involved with an individual virus has their immune response is deficient, and they go into
its ecologically determined range, and thus delimits a lifetime chronic carrier state. This same response
the territory of distribution of the virus. As can be can be induced in adult mice that have been
seen in Table VIII. 11.1, the exception to the limited- immunosuppressed.
host-range rule is the house mouse, M. musculus. The
genus Mus is an Asiatic and European genus. Mus Clinical Manifestations, Diagnosis,
musculus is well adapted to the human environment Treatment, and Control
and now has worldwide distribution but is found par-
ticularly in the temperate regions of America, Eu- Lymphocytic Choriomeningitis (LCM)
rope, and Asia. It moves where humans move, and LCM has been found in the Americas, Europe, and
communication by sea has opened the world to it, Asia, but not in Africa or Australia. Outbreaks are
although in the tropics it has remained more re- sporadic and often associated with experimental ani-
stricted to coastal or riverine settlements. mal colonies. The disease in humans is usually be-
Praomys natalensis, the multimammate mouse, is nign, with symptoms resembling influenza. Inap-
also very common; commensal with humans, it is parent cases (determined by serologic changes) are
widely distributed in Africa, and is associated with frequent during outbreaks. Meningitis (with 90 to 95
Lassa virus and Mopeia virus. Praomys jacksoni, percent lymphocytes in the cerebrospinal fluid) may
another member of the genus, which holds 14 spe- occur as a primary symptom of disease, or more usu-
cies, is associated with Mobala virus in the Central ally as a relapse several days after apparent recovery
African Republic. The literature is confusing be- from the acute illness. In some cases there may be
cause Praomys is often referred to as Mastomys. Cur- meningoencephalitic signs and symptoms, with re-
rently, however, Mastomys, Myomys, and Myomys- flex changes, paralyses, cutaneous anesthesias, and
cus are all considered to be synonymous with somnolence. Fatal cases are rare. When infections
Praomys (Honacki, Kinman, and Koeppl 1982). occur in pregnancy, complications of encephalitis,
Praomys is placed in the rodent family Muridae. hydrocephaly, and chorioretinitis in the fetus and the
The New World rodents associated with arenavi- newborn may be seen. Treatment is limited to sup-
ruses are all placed in the family Cricetidae, with portive care. Control is limited to control of mouse
several genera involved. It is likely that there have populations in houses and to vigilant supervision of
been many opportunities for virus dispersal as well laboratory colonies of mice and hamsters.
as adaptation of viruses to new rodent hosts, when
one considers (1) the number of viruses, such as Argentine Hemorrhagic Fever (Junin)
LCM, Lassa, Junin, Machupo, and others; (2) the The disease occurs in the heavily agricultural moist
diversity of rodents; and (3) the rise (and later enor- pampas provinces to the west of Buenos Aires. It is
mous development) of intracontinental and intercon- seen in the rural regions, mostly in farm workers,
tinental traffic; and (4) the recently recognized pair including migrant workers. Several hundred cases
of viruses Quaranfil and Johnston Atoll (provision- are seen annually, occurring mainly in the harvest
ally placed in the Arenaviridae on the basis of elec- season between April and July. Infection in humans
tron microscopic studies), which are associated with resultsfromcontact withfieldrodents. The incubation
birds that disperse widely. Thus it seems evident period is from 10 to 14 days, with an insidious onset
that the whole world is at risk for species radiation beginning with malaise, fever, chills, head and back
of Arenaviridae. pains, nausea, vomiting, and diarrhea or constipation.

In progressive cases, hemorrhagic manifestations be- Bibliography
gin about the fourth day of illness, and may proceed to Acha, Pedro N., and Boris Szyfres. 1987. Zoonoses and
death (in about 10 percent of confirmed cases). In some communicable diseases common to man and animals,
cases, neurological symptoms may predominate. 2d edition, 289-97, 297-301, 392-6. Pan American
Laboratory findings include leukopenia, thrombo- Health Organization Scientific Publication No. 503.
cytopenia, albuminuria, and cylindruria. Serologic Armstrong, C , and R. D. Lillie. 1934. Experimental
testing is an aid to diagnosis, but as is the case with lymphocytic choriomeningitis of monkeys and mice
produced by a virus encountered in studies of the 1933
many virus diseases, virus isolation and identifica-
St. Louis encephalitis epidemic. Public Health Re-
tion are recommended. Convalescence lasts several ports, Washington 49: 1019-27.
weeks after severe illness, and recovery is then usu- Auperin, D. D., and J. B. McCormick. 1989. Nucleotide
ally complete. There are no proven specific antiviral sequence of the Lassa virus (Josiah strain) genome
agents; but there are recent reports of successful RNA and amino acid sequence of the N and GPC
treatment with immune plasma. When it has been proteins to other arenaviruses. Virology 168: 421—5.
given before the eighth day of illness, marked reduc- Benenson, A. S., ed. 1985. Control of communicable dis-
tion in mortality has been observed. Rodent control eases in man, 14th edition, 16-18. American Public
would appear to be an obvious prevention measure, Health Association. Chicago.
but it is not practical, given the vast areas where the Buckley, S. M., J. Casals, and W. G. Downs. 1970. Isolation
virus is endemic. Much attention has been given to and antigenic characterization of Lassa virus. Nature
development of a vaccine, and at present a live at- 227: 174.
tenuated vaccine shows promise of becoming useful Calisher, C. H., et al. 1970. Tamiami virus, a new member
of the Tacaribe group. American Journal of Tropical
in preventing disease in human beings. Another vac- Medicine and Hygiene 19: 520-6.
cine possibility being explored utilizes the avirulent Casals, Jordi. 1979. Arenaviruses. In Diagnostic proce-
Tacaribe virus to induce immunity against Junin. dures for viral and rickettsial and chlymadial infec-
tions, eds. E. H. Lennette and N. J. Sather, 5th edi-
tion, 815-41. American Public Health Association.
Bolivian Hemorrhagic Fever (Machupo) Chicago.
This disease is localized to several provinces of the Compans, R. W., and D. H. L. Bishop. 1984. Segmented
Department of Beni, in the Amazonian lowlands, negative strand viruses: Arenaviruses, bunyaviruses
and is endemic in the local rodent (Calomys) popula- and orthomyxoviruses, 51-64,109-16,193-216, 3 4 1 -
tions. Exposed human beings have an incubation 7. New York.
period of about 2 weeks. Patients have a high fever Downs, W. G., et al. 1963. Tacaribe virus, a new agent
for at least 5 days; myalgia, headache, conjunctivi- isolated from Artibeus bats and mosquitoes in Trini-
tis, cutaneous hyperesthesia, nausea, and vomiting dad, West Indies. American Journal of Tropical Medi-
are features of the illness. Hemorrhagic manifesta- cine and Hygiene 12: 640-6.
tions occur in some 30 percent of patients, and there Fuller, J. G. 1974. Fever. New York.
may be serious bleeding. Hypotension in the second Gear, J. H. S., ed. 1988. Handbook of viral and rickettsial
hemorrhagic fevers. Boca Raton, Fla.
week of illness is seen in about 50 percent of pa-
Gonzalez, J. P., et al. 1983. An arenavirus isolated from
tients, and in many patients it proceeds to hypo- wild-caught rodents (Praomys sp.) (Praomys jacksoni,
volemic shock and death. Symptoms indicative of sic) in the Central African Republic (Mobala). In-
central nervous system involvement, among the tervirology 19: 105-12.
tremors of tongue and extremities, convulsions, and Honacki, J. H., K. E. Kinman, and J. W. Koeppl. 1982.
coma, appear in almost half the patients. The death Mammal species of the world: a taxonomic and geo-
rate in several epidemics has been about 25 percent. graphic reference, 542—4. Lawrence, Kans.
Convalescence is protracted. Laboratory findings in- Johnson, K. M., et al. 1965. Virus isolations (Machupo)
clude leukopenia, hemoconcentration, and protein- from human cases of hemorrhagic fever in Bolivia.
uria. Pathological findings include generalized ade- Proceedings of the Society ofExperimental Biology and
nopathy and focal hemorrhages in various organs. Medicine 118: 113-18.
No specific therapy is known. Treatment is limited Karabastos, N., ed. 1985. International catalogue of
to supportive measures. Rodent control in homes arenaviruses, including certain other viruses of verte-
brates. American Society of Tropical Medicine and
and villages has proven to be an effective means of
Hygiene, Subcommittee on Information. (Looseleaf)
controlling epidemics, and also of preventing spo-
Lehmann-Grube, F. 1988. Arenaviruses. In Portraits of vi-
radic cases of disease. ruses, ed. F. Fenner and A. Gibbs. Basel, Switzerland.
Wilbur G. Downs Oldstone, M. B. A. 1987. Arenaviruses. Current Topics in

VIH.12. Arthritis (Rheumatoid) 599
Microbiology and Immunology 134: 5-130, 145-84,
211-39. VIII. 12
Parodi, A. S., et al. 1958. Sobre la etiologia del brote
epidemico de Junin. Dia Medica 30: 2300-2.
Arthritis (Rheumatoid)
Pinheiro, F. P., et al. 1966. A new virus of the Tacaribe
group from rodents and mice of the Amapa Territory,
Brazil. Proceedings of the Society ofExperimental Biol- Rheumatoid arthritis, the major crippling illness
ogy and Medicine 122: 531—5. among chronic rheumatic disorders, is a systemic
1977. Studies on arenaviruses in Brazil (Flexal). disease that affects many joints with an inflamma-
Medecina (Buenos Aires) 37: 175-81. tory reaction lasting months or years. Frequently,
Rowe, W. P., et al. 1970. Arenaviruses: Proposed name for the small joints of the hands and feet are affected
a newly described virus group. Journal of Virology 5: first, although often the larger peripheral joints of
651-2. the wrists, hips, knees, elbows, and shoulders are
Taylor, R. M., et al. 1966. Arboviruses isolated from Argas involved as well. Some remissions do occur, but the
ticks in Egypt: Quaranfil, Chenuda and Nyamanini. illness progresses to produce damage and deformity.
American Journal of Tropical Medicine and Hygiene There is no known etiology.
15: 75-86.
In 1961, the American Rheumatism Association
Trapido, H., and C. Sanmartin. 1974. Pichinde virus, a
new virus of the Tacaribe group from Colombia.
developed a set of eight diagnostic criteria for rheu-
American Journal of Tropical Medicine and Hygiene matoid arthritis suitable for epidemiological sur-
20: 631-41. veys. They are as follows:
U.S. Public Health Service. Centers for Disease Control.
Center of Infectious Diseases. 1988. Arthropod-borne
1. Morning stiffness
virus information exchange. June 24. 2. Pain on motion or tenderness in at least one joint
Webb, P. A., et al. 1970. Parana, a new Tacaribe complex 3. Swelling (soft tissue) of at least one joint
virus from Paraguay. Archives fur die gesammte Virus- 4. Swelling of at least one other joint
forschung 32: 379-88. 5. Symmetrical joint swelling
1973. Behavior of Machupo and Latino viruses in 6. Nodules under the skin, typically on the surface of
Calomys callosus from two geographic areas of Bo- muscles that extend or stretch the limbs
livia. In Lymphocytic choriomeningitis virus and other 7. Observable changes identified by X-rays, typi-
arenaviruses, ed. F. Lehmann-Grube, 313-22. Berlin. cally erosions of bone
World Health Organization. 1975. International Sympo- 8. Positive serologic test for rheumatoid factor
sium on Arenaviral Infections, 14-16 July 1975. Bulle-
tin of the World Health Organization 52: 381-766. In a given patient, a definite diagnosis of rheuma-
Wulff, H., et al. 1977. Isolation of an arenavirus closely toid arthritis would depend on the presence of at
related to Lassa virus. Bulletin of the World Health least five of these criteria and the absence of evi-
Organization 55: 441-4. dence for other rheumatic conditions.
Distribution and Incidence

When using the above definition, a number of re-
searchers have indicated that rheumatoid arthritis
is worldwide, affecting all ethnic groups. A sum-
mary of prevalence data in rheumatoid arthritis has
been provided by P. D. Utsinger, N. J. Zvaifler, and
E. G. Ehrlich (1985). Fifteen studies were cited from
countries such as the United States, United King-
dom, Finland, Puerto Rico, Canada, Japan, Bul-
garia, and Jamaica. The authors have concluded
that the prevalence of rheumatoid arthritis, as de-
fined above, is consistently between 1 and 2 percent
of the adult population in all parts of the world. In
general, females suffer the illness about two and a
half times more frequently than males; however,
prevalence increases for both females and males
over age 35, making it normally a disease of the

middle years. The number of new cases per 1,000 ited function and instability. Signs of systemic in-
population per year ranges from 0.68 to 2.9. The volvement may also be seen, for example, nodules at
prevalence of chronic arthritis in children among the elbows, cutaneous degeneration at the fingertips
Caucasians is 5 percent that of adults. The mode of (which appear as small, 1- to 2-millimeter infarcts in
onset in children may vary more than that in adults, the nail fold) or at the elbow tip, pulmonary fibrosis,
in that the simultaneous involvement of four or inflammation of the sac enclosing the heart, anemia,
more joints — seen in 93 percent of the adult cases - fever, rash and peripheral ulcers in the lower limbs,
occurs in only 30 percent of those children in whom disease of the nervous system, and wrist weakness
diagnosis of rheumatoid arthritis is subsequently occasioned by the carpal tunnel syndrome. In addi-
established. tion, there is usually a gradual weight loss as well as
the loss of muscle volume and power.
Epidemiology and Etiology
Despite the years of intensive study of endocrine,
Treatment
metabolic, and nutritional factors as well as geo-
Although there is no cure, the principles of treat-
graphic, occupational, and psychological variables,
ment are, first, to minimize the swelling, pain, and
the etiology of rheumatoid arthritis has not been
damage; and second, to maintain joint function as
elucidated. A genetic predisposition is suspected (be-
closely to normal as possible. To this end, a number
cause certain histocompatibility markers are found
of medical and surgical modalities are available to
frequently); however, bacterial and viral infections
manage patients over the course of their disease.
are often associated with acute polyarthritis in hu-
Drug therapy is an important part of this manage-
mans, and thus an infection followed by an altered
ment as it is directed toward controlling the destruc-
or sustained immunologic response could be instru-
tive inflammatory processes within the joint.
mental for development of the disease. Certainly,
immunologic abnormalities appear to play a role in The antiinflammatory agents commonly used for
both the aggravation and perpetuation of the inflam- this control include aspirin and similar compounds
matory process. Cellular and humoral immunologic referred to as nonsteroidal antiinflammatory agents.
reactions occur at the local site (joints) and often Whereas some symptoms and signs of the disease can
systemically. The production of antiimmunoglobu- be improved by these drugs, additional agents may be
lins or rheumatoid factors occurs initially in the required for those patients who have continuing pro-
inflammatory tissue of the joint and can subse- gressive damage. This treatment might include gold
quently be detected in the serum of 80 percent of the salts and antimalarial, antitumor, and immunosup-
patients treated for the condition. Those patients pressive agents. Corticosteroid derivatives are recog-
with rheumatoid arthritis who are seropositive for nized to be potent antiinflammatory agents with
rheumatoid factor show a more marked progression some immunomodulating effect. Although they may
of the disease than do those who are seronegative. dramatically improve the most troublesome symp-
toms, they have not been proven to alter significantly
the progression of the disease. Moreover, the side
Clinical Manifestations and Diagnosis effects of these drugs may be hazardous over the
The onset and course of rheumatoid arthritis are many years needed to treat chronic conditions such as
particularly variable. Usually, fatigue, weight loss, rheumatoid arthritis.
and generalized aching and stiffness, especially on
awakening in the morning, precedes localization of
symptoms and the development of joint swelling. History and Geography
These symptoms at times develop explosively in one The clinical term "rheumatoid arthritis" was first
or more joints, but more often there is progression to introduced in the medical literature by A. B. Garrod
multiple joint involvement. The disease may remit in 1859. It was not in common usage until "officially
spontaneously in the first year or diminish in inten- recognized" in the United Kingdom by the Depart-
sity, only to recur in the same or additional joints at ment of Health in 1922 and by the American Rheuma-
intervals. The more troublesome cases usually con- tism Association in 1941. Until recent times many
tinue to affect many joints with sustained inflamma- names were used to describe what we currently recog-
tory reactions for months or years. In these latter nize as rheumatoid arthritis: rheumatic gout, chronic
cases, marked bone and joint damage often develop, rheumatic arthritis, goutte asthenique primative,
with drift of the ulna (outer bone of the forearm) and rheumatismus nodosus, and rheumatoid osteoarthri-
consequent deviation of the fingers, leading to lim- tis. Broader terms such as gout, arthritis, and rheu-

VIII. 12. Arthritis (Rheumatoid) 601
matism would also have encompassed rheumatoid absence of currently applied diagnostic criteria
arthritis as well as numerous other conditions. based on skeletal X-rays and serologic information
Evidence for the existence of rheumatoid arthritis does not absolutely exclude a diagnosis of polyartic-
in earlier times, however, must be gleaned from lit- ular gout or some other erosive joint disease in an
erature, from art, and from paleopathological stud- otherwise very suggestive report.
ies of ancient bones, and to date that evidence has In the thirteenth century, a less complete descrip-
been far from overwhelming. Indeed the lack of tion was written in Britain by Bartolemeus Anglicus
early descriptions of this disease led authors such as who, after describing several types of arthritis,
E. Snorrason (1952) to suggest that the disease is stated that "one form of the disease is worse for it
recent in origin (i.e., since the seventeenth century) draws together tissues and makes the fingers shrink
and is evolving to develop a peak incidence during and shrivels the toes and sinews of the feet and of
the twentieth century before ultimately disappear- the hands."
ing (Buchanan and Murdoch 1979). Perhaps the earliest known description suggestive
By contrast, other arthritic disorders such as of rheumatoid arthritis is in the Eastern literature
ankylosing spondylitis, osteoarthritis, and spinal (India) and discussed in the Caraka Samhita, writ-
hyperostosis have been recognized in skeletons thou- ten about A.D. 123. In this work, the disease in
sands of years old and appear to be unchanged from question was said to manifest itself as swollen, pain-
the present condition. In fact, given the lack of evi- ful joints initially in the hands and feet and then
dence of the existence of rheumatoid arthritis until affecting the whole body. The ailment was reported
relatively recent times, L. Klepinger (1979) and oth- to be protracted, difficult to cure, and associated
ers have suggested that rheumatoid arthritis has with anorexia. Although ultimate proof is lacking,
evolved from ankylosing spondylitis. Suffice it to say these descriptions may represent the earliest writ-
that the uncertainty about the antiquity of rheuma- ten record of rheumatoid arthritis.
toid arthritis is at least partly due to the methods by
which we have examined the evidence of a disease Art
whose current definition includes a combination of Although there is no unequivocal illustration of sym-
clinical, radiological, and serologic criteria. Nonethe- metrical polyarthritis, attention has been drawn to
less, a search for evidence of rheumatoid arthritis in some presentations of deformities of the hands in
the literature, art, and bones of the past is an intrigu- the Flemish painters (1400-1700) who otherwise
ing one. painted the ideal, unaffected limb with considerable
accuracy (Klepinger 1979). Some works of Peter
Literature Paul Rubens show changes typical of rheumatoid
In 1800, A. J. Landre-Beauvais wrote an account of arthritis, suggesting to T. Appelbloom and col-
a disease that is today universally accepted as rep- leagues (1981) that Rubens, who himself suffered
resenting rheumatoid arthritis. Earlier European from rheumatoid arthritis, painted the progressive
descriptions of rheumatoid arthritis, which C. L. phases of his own disease in the hands of his sub-
Short (1974) and the present authors find convinc- jects during the years 1609-38.
ing, were written by Thomas Sydenham in 1676, W.
Heberden in 1770, and B. Brodie in 1818. These Paleopathology
observers each described long-term, chronic, debili- Of the thousands of mummies and whole skeletons
tating diseases affecting multiple joints, which in- from the distant past that have been observed, there
cluded descriptions of typical hyperextension defor- are surprisingly few specimens that show features
mity of the interphalangeal joints of the fingers. compatible with rheumatoid arthritis. The reader
Before these dates, there are several descriptions of will recall that the definition of the disease requires
disease that could represent certain phases of rheu- a symmetrical pattern commonly affecting the small
matoid arthritis, ranging from the acute explosive joints. This poses a problem when the determination
attack to one of chronic sustained disability. This is of symmetry is not possible because one or more long
particularly so in the case of the Emperor Constan- bones are absent or because the small bones of the
tine IX (ca. 980-1055) who, at the age of 63, suf- hands and feet are frequently lost.
fered from polyarthritis in the feet, and subse- Although rheumatoid arthritis, at the present
quently the hands, shoulders, and knees, leading to time, is a major cause of symmetrical erosive
a nodularity and residual deformity in the fingers, polyarthritis, other causes do exist, and thus it
and flexion and swelling of the knees. However, the seems appropriate to employ the term "erosive joint

disease," which may or may not have been rheuma- Estudio prospective de 100 casos. Archivos del Insti-
toid arthritis when describing the arthritis seen in tute de Cardiologia de Mexico 57: 159-67.
ancient bones. Buchanan, W. W., and R. M. Murdoch. 1979. Hypothesis:
The description by W. P. May (1897) of an Egyp- That rheumatoid arthritis will disappear. Journal of
tian mummy 5,500 years old indicates a case of Rheumatology 6: 324-9.
possible rheumatoid arthritis: a male, 50 or 60 Caughey, D. E. 1974. The arthritis of Constantine IX.
Annals of the Rheumatic Diseases 33: 77-80.
years of age with hands, wrists, elbows, and knees,
Garrod, A. B. 1859. The nature and treatment of gout and
and feet affected. Particular note was made of the rheumatic gout. London.
fingers — "small joints of the hands are swollen and Klepinger, L. 1979. Paleopathological evidence for the evo-
fusiform" - while the metatarsophalangeal joints lution of rheumatoid arthritis. American Journal of
were markedly involved with some peripheral fu- Physical Anthropology 50: 119-22.
sion. The author emphasized the unequal symme- May, W. P. 1897. Rheumatoid arthritis (osteitis deformans)
try, and no erosions were described. Studies by J. affecting bones 5,500 years old. British Medical Jour-
Rogers and colleagues (1981) and A. K. Thould and nal 2: 1631-2.
B. T. Thould (1983) in the United Kingdom have Ortner, D., and C. S. Utermohle. 1981. Polyarticular in-
identified only two or three cases of erosive arthri- flammatory arthritis in a pre-Columbian skeleton
tis compatible with rheumatoid arthritis in some from Kodiak Island, Alaska. American Journal of
816 skeletons dating from the Saxon to Roman and Physical Anthropology 56: 23-31.
British medieval times. Rogers, J., P. Dieppe, and I. Watt. 1981. Arthritis in Saxon
and medieval skeletons. British Medical Journal 283:
A detailed analysis of a well-preserved 34-year-old 1668-70.
female Eskimo mummy from the Kodiak Islands is Rothschild, B. M., R. J. Woods, and K. Turner. 1987. New
described by D. Ortner and C. S. Utermohle (1981); World origins of rheumatoid arthritis (abstr). Arthri-
in this instance evidence of erosive inflammatory tis and Rheumatism 30 (Suppl.) S61: B29.
polyarthritis compatible with juvenile rheumatoid Short, C. L. 1974. The antiquity of rheumatoid arthritis.
arthritis is clearly presented. More recently, reports Arthritis and Rheumatism 17: 193-205.
of erosive polyarthritis occurring in ancient bones Snorrason, E. 1952. Landre-Deauvais and his goutte
ranging from 5,000 years to 1,000 years old in North asthenique primative. Acta Medica Scandinavica 142
America have been identified by B. M. Rothschild's (Suppl.): 115-18.
group (1987). In fact, Rothschild and colleagues have Thould, A. K., and B. T. Thould. 1983. Arthritis in Roman
speculated that rheumatoid arthritis could have had Britain. British Medical Journal 287: 1909-11.
a viral origin in North America and then migrated Utsinger, P. D., N. J. Zvaifler, and E. G. Ehrlich, eds. 1985.
Rheumatoid arthritis. Philadelphia.
to Europe in the post-Columbian period, where it
manifested itself as a more severe disease in subse-
quent centuries. This, they argue, might account for
the apparent relative infrequency of the disease in
Europe prior to the seventeenth century.
Today the disease is identified in most ethnic
groups and in all parts of the world. Thus only de-
tailed studies and precise reports on skeletal re-
mains can establish whether erosive arthritis, which
may have been rheumatoid arthritis, was more
prevalent in the past than it is presently. These
findings could impact considerably upon our under-
standing of the pathogenesis of the disease and per-
haps also suggest whether it is likely to disappear as
some have argued.
Howard Duncan and James C. C. Leisen
Bibliography
Appelbloom, T., et al. 1981. Rubens and the question of the
antiquity of rheumatoid arthritis. Journal of the
American Medical Association 245: 483—6.
Badui, E., et al. 1987. El corazon y la artritis reumatoide.

VIII. 13. Ascariasis 603
tries, although improved sanitation has greatly re-

vni.13 duced prevalence in recent decades. During the
Ascariasis 1960s, surveys conducted in school children and
other groups showed infection rates of 2.5 to 75 per-
cent in Italy, 21 percent in Spain, 40 to 80 percent in
The giant intestinal roundworm, Ascaris lumbri- Portugal, 18 percent in Romania, 2 to 5 percent in
coides, is a very common parasite with a worldwide urban Japan, and up to 20 percent in the Japanese
distribution. The adult worms are 15 to 35 cm (6 to countryside. Foci still exist in some rural areas in
14 inches) long and reside in the lumen of the small the southern United States.
intestine. Sometimes, however, they are passed in
the feces and, if vomited into the oral cavity, may Clinical Manifestations, Diagnosis,
exit from the host's mouth or nostrils; thus they Treatment, and Control
have been known to medical observers for millennia. Symptoms of ascariasis vary widely. As is often true
Female worms produce up to 200,000 fertilized eggs for helminthic infections, low worm loads may cause
daily, which are passed in the feces. Eggs incubate in few or no symptoms. Large numbers of larvae in the
the soil for at least 2 to 3 weeks to produce an lungs may produce ascaris pneumonitis, with symp-
infective larval stage within them. The eggs are toms resembling pneumonia. Allergic reactions can
very resistant to chemicals, desiccation, and ex- cause asthma attacks. Larvae can reach atypical
treme temperatures, but they mature or "em- (ectopic) sites such as the brain, eye, or kidney, where
bryonate" most rapidly in warm, moist, shady condi- they may produce grave, life-threatening conditions,
tions in clay soils. People become infected by eating but such events are fortunately rare. Adult worms in
embryonated eggs in food or water contaminated the intestine can cause fever, abdominal discomfort,
with feces; or, in the case of toddlers, infection occurs diarrhea, and allergic reactions to their proteins. Fe-
by direct ingestion of eggs with dirt. Poor rural sani- ver may induce worms to wander to the larynx, where
tation and the use of human feces for fertilizer obvi- they can cause suffocation, or to exit the mouth or
ously favor transmission. Mature eggs hatch in the nostrils. Heavy infections rob the host of nutrients,
small intestine, and the larvae then undergo a re- and tangled masses of worms can result in fatal intes-
markable series of migrations in the host. They pene- tinal obstruction if not treated promptly. Intestinal
trate the intestinal wall and are carried in blood or ascariasis is especially serious in young children. A
lymph vessels to the liver and heart, and then the study in Kenya showed that ascariasis produced
lungs. Here they break out into the air sacs, develop, signs of protein-energy malnutrition in many chil-
and molt for about 3 weeks, and then climb up the dren and often retarded their growth; similar results
trachea to the throat, where they are subsequently have been reported from other Third World countries.
swallowed to establish themselves as adults in the Even if severe effects occur in only a small percentage
small intestine. of cases, the ubiquity of the worm makes it an impor-
tant cause of morbidity in many countries.
Diagnosis is made by detecting eggs in micro-
Distribution and Incidence scopic examination of the feces. Drug treatment is
This nematode was known to ancient writers in usually safe and effective, but care must be taken to
China, India, Mesopotamia, and Europe, and was keep the adult worms from wandering about in re-
present in pre-Columbian America. The World sponse to therapy. Intestinal obstruction is treated
Health Organization estimated in the early 1980s by inducing vomiting or by surgery. Preventive mea-
that between 800 and 1,300 million people harbored sures include sanitary latrines, composting feces to
an average of six worms each. The true figure may be used as fertilizer, and careful washing of fruits
be even higher. Surveys have demonstrated infec- and vegetables that are eaten raw. Mass treatment
tion in more than 50 percent of sampled populations may also reduce the danger of continued reinfection.
in such countries as Bangladesh, Brazil, China, Co- K. David Patterson
lombia, India, Iran, Kenya, Mexico, Tanzania, and
Vietnam, and the rate approaches 100 percent in Bibliography
many rural areas. In China, it was estimated that Jeffery, G. M., et al. 1963. Study of intestinal helminth
the 1947 Ascaris population produced 18,000 tons of infections in a coastal South Carolina area. Public
eggs a year; they may be even more productive to- Health Reports 78: 45-55. -^
day. The worm is also common in developed coun- Kean, B. H., Kenneth E. Mott, and Adair J. Russell, eds.

1978. Tropical medicine and parasitology: Classic in- gienic practices are especially dangerous; proper
vestigations, Vol. II, 346-59. Ithaca and London. handwashing after defecation is a simple but effec-
Latham, L., M. Latham, and S. S. Basta. 1977. The nutri- tive preventive measure. Crowding and poor sanita-
tional and economic implications of ascaris infection tion favor transmission, and outbreaks are common
in Kenya. World Bank Staff Working Paper No. 277 in jails and institutions for the retarded and men-
(September). Washington, D.C. tally ill.
Pawlowski, Z. S. 1984. Strategies for the control of
ascariasis. Annales de la Societe Beige de Medecine
Epizootics have been reported in colonies of cap-
Tropicale 64: 380-5. tive primates, and two species have been isolated
Stoll, N. R. 1947. This wormy world. Journal of from dogs, but animal reservoirs have no known
Parasitology 33: 1-18. epidemiological significance.
World Health Organization. Parasitic Diseases Pro-
gramme. 1986. Major parasitic infections: A global Distribution and Incidence
Shigellosis occurs worldwide, but is especially com-
review. World Health Statistics Quarterly 39: 145-60.
mon in countries with poor water and sewage sys-
tems. The virulent S. dysenteriae is mostly confined
to the tropics and East Asia; a much less pathogenic
form, S. sonnei, is the most abundant species in the
VIII. 14 United States. All age groups are vulnerable, but
severe disease is most common in children and
Bacillary Dysentery among the elderly. There appears to be no racial or
ethnic immunity, although populations can acquire
considerable resistance to locally prevalent strains.
Bacteria from several genera, including Campylo- Travelers may become ill when they encounter unfa-
bacter, Salmonelle, and Yersinia, as well as some miliar strains. Accurate incidence rates are impossi-
strains of the common intestinal bacillus Escheri- ble to obtain, but shigellosis is a serious health prob-
chia coli, can invade the mucosa of the large intes- lem in most underdeveloped countries and a major
tine and cause dysentery, but members of the genus cause of infant and child mortality. The disease is
Shigella are by far the most important agents. commonly endemic in poor countries, but great epi-
Shigellosis is a common disease that occurs world- demics can also take place. During World War II,
wide and afflicts persons of all races and age groups. acute dysentery, apparently introduced by Japanese
In addition, Campylobacter appears to be an emerg- and/or Allied troops, attacked many indigenous
ing pathogen, at least in the United States. It lives groups in western New Guinea, causing thousands
in the small intestine and produces a dysentery-like of deaths despite the efforts of Australian authori-
condition that is usually self-limiting. ties. In 1969 an epidemic of S. dysenteriae caused
110,000 cases and 8,000 deaths in Guatemala.
Etiology and Epidemiology Shigellosis is also a constant threat in developed
Four species or subgroups of Shigella cause human countries, especially when sanitary standards are
disease. Shigella dysenteriae (subgroup A), the first weakened. For example, two important S. sonnei
to be discovered, is the most virulent. Shigella flex- outbreaks occurred in the United States in 1987.
neri (B), Shigella boydii (C), and Shigella sonnei are One took place among Orthodox Jews in New York,
less dangerous. More than 40 serotypes are recog- New Jersey, Ohio, and Maryland, with the majority
nized and are useful in tracing the spread of out- of cases occurring among small children in religious
breaks. schools. Patterns of spread were consistent with
Shigella organisms are passed in the feces and person-to-person transmission among religious com-
spread from person to person by the fecal-oral route. munities in the four states. The first outbreak was
Bacteria are excreted during the illness and for in New York City, where 132 cases were reported
about 4 weeks after recovery, but some asympto- and at least 13,000 were suspected. Smaller epidem-
matic individuals may act as carriers for a year or ics in upstate New York and other states appeared
more. Contaminated food and water are the most to be linked with Passover visits to relatives in the
common modes of transmission. Direct fecal contami- city. The second epidemic began with the annual
nation or mechanical carriage by flies can introduce meeting of a counter-culture group, the Rainbow
bacteria into food, milk, or water. Sick, convalescent, Family, in a national forest in North Carolina in
or even healthy food handlers who have poor hy- early July. Poor hygiene and inadequate latrines

VIII.14. Bacillary Dysentery 605
allowed infection to spread among the campers, inadequate sanitation, avoidance of raw foods and
who caused at least four clusters of cases in Mis- use of bottled water can help to protect the traveler.
souri and Pennsylvania when they dispersed. Patients may require rehydration and replace-
Shigellosis rates in the United States ranged from ment of lost electrolytes, as well as symptomatic
about 5 to 11 per 100,000 from 1955 to 1986; the care for cramps and discomfort. Bed rest is impor-
disease is almost certainly seriously underreported. tant. After a day or two of fasting, soft, easily digest-
ible food should be given in small, frequent meals. In
most cases, such supportive therapy is sufficient. A
Diagnosis, Clincial Manifestations, and variety of antibiotics can be effective against various
Pathology Shigella species, but drug resistance is a growing
Diagnosis is by clinical signs, cultivation of Shi- problem. Many strains of S. sonnei in the United
gella or other bacteria from tissue swabs and feces, States have developed resistance to ampicillin and
and serologic tests to determine species and strains. tetracycline; thus, in cases where drug therapy is
Differential diagnosis must exclude other agents of essential, newer agents must be employed.
dysentery, including other bacteria, viruses, and
amebas. History
Bacteria invade the mucosa of the large intestine, Medical writers have described dysentery or "the
where they cause mucus secretion, edema, and, usu- flux" since ancient times, but the bacterial form of
ally, superficial ulceration and bleeding. The watery the disease was not clearly distinguished until late
diarrhea is probably caused by a toxin that increases in the nineteenth century. Dysentery ravaged Per-
the secretions of the cells of the intestinal wall. sian armies invading Greece in 480 B.C., and the
The incubation period is from 1 to 4 days. Onset is disease has always been a companion of armies, of-
sudden in children, with fever, drowsiness or irrita- ten proving much more destructive than enemy ac-
bility, anorexia, nausea, abdominal pain, tenesmus, tion. This disease was, and remains, common among
and diarrhea. Blood, pus, and mucus appear in the both rural and urban poor people around the world.
diarrheal stools within 3 days. Increasingly frequent An epidemic of what must have been shigellosis
watery stools cause dehydration, and death can oc- swept France in 1779, causing especially severe dam-
cur as early as 12 days. If the patient survives, age in some rural areas of the western part of the
recovery usually begins after about 2 weeks. In country. Troop movements for a planned invasion of
adults, there is usually no fever, and the disease England helped spread the disease. At least 175,000
generally resolves itself after 1 to 6 weeks. Symp- people died, with some 45,000 deaths in Brittany
toms in both children and adults may vary from alone. Children constituted the majority of the fatali-
simple, transient diarrhea to acute dysentery and ties. During the U.S. Civil War, Union soldiers had
death. annual morbidity rates of 876 per 1,000 from dysen-
It is not always possible to differentiate amebic tery, and annual mortality rates of 10 per 1,000.
and bacillary dysentery on clinical grounds, but Dysentery outbreaks were problems for all belliger-
shigellosis generally has a more sudden onset and ents in World War I, especially in the Gallipoli and
more acute course, is more likely to occur in explo- Mesopotamian campaigns.
sive epidemics, and is not a chronic disease. Tenes-
Bacterial dysenteries took a heavy toll among in-
mus is a much more common symptom in shigellosis,
fants and young children in Western countries until
and the stools are generally less abundant and con-
very recent times. During the late nineteenth and
tain more bright red blood than in typical cases of
early twentieth centuries, the decline in breast feed-
amebic dysentery.
ing and the growing use of cows' milk in European
and American cities exposed infants and toddlers to
Control and Treatment a variety of bacterial and other agents of dysentery
Sanitary measures are crucial for the prevention of and diarrhea. As milk is an excellent growth me-
bacillary dysentery and other diseases that are dium for Shigella and many other pathogens, con-
spread by fecal-oral route. Proper waste disposal, taminated milk and lack of refrigeration led to espe-
postdefecation handwashing, and safe water sup- cially high death rates in hot weather. Milk-borne
plies are essential. Chlorination of water kills shigellosis was a significant contributor to the "sum-
Shigella and other bacterial agents of dysentery. mer complaint," which took thousands of young lives
Sanitary food preparation, control of flies, and pas- annually in cities like Paris and New York. Infant
teurization of milk are also important. In areas with health movements, public health education, and pas-

teurization of milk largely eliminated the problem
in western Europe and North America by about VIII. 15
1920. Shigellosis, however, still contributes to the
"weanling diarrhea," which afflicts tens of millions
Beriberi
of Third World children every year.
The Japanese bacteriologist Kiyoshi Shiga iso- Beriberi is a disease caused by a deficiency of thia-
lated S. dysenteriae in 1898, and confirmed its role mine, or vitamin Bj, that is expressed in three major
as a pathogen by showing that the organism reacted clusters of symptoms, which vary from person to
with sera of convalescing patients. The other species person. It involves edema, or swelling, of the legs,
were discovered early in the twentieth century, and arms, and face. The nerves may be affected, causing,
much research has been directed to immunologic first, a loss of sensation in the peripheral nerves and,
studies of various strains. The role of Campylobacter later, paralysis. The cardiovascular system may be
species as common human pathogens has been recog- involved, evidenced by enlargement of the heart and
nized only since the 1970s. extremely low diastolic blood pressure. Beriberi may
K. David Patterson be chronic and so low-grade that it cannot be de-
tected by clinical examination; in its chronic form, it
Bibliography may alternatively result in disability for months or
Bulloch, William. 1938. The history of bacteriology. Oxford. years; or it may be acute and result in death in a few
Burton, John. 1984. A dysentery epidemic in New Guinea weeks. Until major tissue damage occurs, it is cur-
and its mortality. Journal of Pacific History 18: 336- able and reversible by consumption of thiamine.
61. The name "beriberi" derives from a Sinhalese
Lebrun, Francois. 1981. La Grande dysenterie de 1779. word, meaning weakness. As kakke, it has been
L'Histoire 39: 17-24. known in Japan since antiquity and is described in
Rosen, George. 1958. A history ofpublic health. New York. the earliest Chinese medical treatises. The several
Smith, David T., and Norman F. Conant. 1960. Zinsser
forms of beriberi have often been considered as sepa-
microbiology, 12th edition. New York.
U.S. Public Health Service. Centers for Disease Control. rate diseases. In "wet" beriberi, swelling and heart
1987. Morbidity and Mortality Weekly Report 36 (July complications occurred, although often with loss of
17): 440-2, 448-50; (October 2): 633-4. the sense of touch, pain, or temperature. In "dry"
1988. Campylobacter isolates in the United States, beriberi, there was little swelling, but instead a pro-
1982-1986. In CDC Surveillance Summaries (June), gressive loss of those senses and then of motor control
1-13. followed by atrophy of the muscles of the paralyzed
limbs and a general wasting syndrome. Today it is
thought that dry beriberi was partly due to a defi-
ciency of vitamin B2. Shoshin beriberi was a term
used to denote a fulminating, or acute form with se-
vere heart complications. "Infantile" beriberi was the
last form to be recognized; in addition to swelling,
heart enlargement, and other cardiovascular compli-
cations, indicative of beriberi, suckling infants also
had such symptoms as loss of voice and gastrointesti-
nal disturbances, neither of which occurred in adults.
The discovery that beriberi was caused by a nutri-
tional deficiency led to the identification and study
of vitamins. The isolation and later synthesis of thia-
mine led to the enrichment of key foods as a public
health intervention. Beriberi was not only a cause of
enormous human suffering and death, but also one
of the most important diseases in the development of
medical science.
Etiology and Epidemiology

Thiamine is vital to every living thing, both plant
and animal. It is an essential component of dozens of

VIII. 15. Beriberi 607
enzymes that metabolize food. In particular, thia- more of the caloric energy. When the hull is removed
mine is necessary to derive energy from glucose, the with a mortar and pestle at home, enough bran re-
preferred food of nerve cells, and from other carbohy- mains on the rice to provide the necessary thiamine.
drates. It is more indirectly involved in the metabo- When the rice is milled efficiently in modern plants,
lism of the amino acids isoleucine, leucine, and however, it is polished into white rice and thiamine
valine. is almost entirely eliminated.
An enzyme is a catalyst for chemical reactions. It Cooking methods are also important in the etiol-
consists of a protein and a coenzyme that attaches to ogy of the disease. In northern China, Korea, and
the target substance, activates the chemical change, Japan, the rice hulls were traditionally removed be-
and then detaches to be ready again for the target fore shipment in order to reduce bulk. When the rice
substance. In its most important role, thiamine, as reached the cities, it was so crawling with weevils
thiamine pyrophosphate, is the coenzyme ofcarboxy- that the subsequently highly-milled rice was cov-
lase. Among other things, it causes carboxyl ered in weevil juices and thus often treated with
(COOH) groups to be oxidized into carbon dioxide talc. Cooking procedures called for the rice to be
and water, releasing energy to body cells. Because it thoroughly washed several times. The first washing
functions as part of a reusable enzyme catalysis sys- alone removed half of the thiamine. In Burma and
tem and is not an integral part of tissue structure other parts of Southeast Asia, the custom has been
itself, thiamine is needed in only small amounts of 1 to cook rice with excess water and throw away the
to 3 micrograms a day. water that is not absorbed, which contains most of
Thiamine is a water-soluble vitamin that is found the thiamine. Other peoples either cook the rice so
widely in foods. It is most concentrated in whole as to absorb all the water, or use the extra water for
grains, yeast, and legumes; in liver, heart, and kid- drinking purposes or for other cooking. In the lower
neys of most mammals; and in oysters. It is available Ganges Valley in India, in Bihar and Bengal, the
also in most green vegetables and pork. An antagonis- custom has been to parboil rice. Steaming the rice
tic enzyme produced by bacteria - thiaminase - is for partial cooking before drying it and then milling
found in a few diverse foods such as raw fish and tea. it for distribution preserves most of the thiamine in
The symptoms of beriberi are caused by a deficiency white rice, and is protective against beriberi. How-
of thiamine, which may be slight or severe, tempo- ever, the labor or costs required in the process and
rary or long term. The deficiency usually results from the different taste and texture produced have not
the shortage of thiamine in a restricted and monoto- been widely acceptable among other peoples in Asia.
nous diet, but it can sometimes be exacerbated by the Numerous cultural beliefs and practices are in-
consumption of large amounts of foods high in volved in the regional etiology of beriberi. In north-
thiaminase. eastern Thailand and Laos, for example, people usu-
The epidemiology of beriberi follows from the role ally steam their glutinous variety of rice - a protec-
of thiamine in energy metabolism and its deficiency tive behavior. But, unlike other people in Thailand,
in restricted diets. The population at highest risk for they have very limited supplies of fresh fruit or
beriberi have been (1) people engaged in heavy la- vegetables or of meat for consumption. They eat
bor, such as farmers plowing their fields and soldiers fish, most of which is in the form of a fermented
and construction workers; (2) pregnant women; and raw paste and is high in thiaminase, the destroyer
subsequently, (3) their nursing infants. The popula- of thiamine. Throughout the region, rice is so cen-
tions in which beriberi has been most prevalent tral to the cultures that it is synonymous with food
have been of two kinds: people confined to institu- itself. One result is that invalids, weanlings, and
tions, such as prisons, asylums, and naval ships, who other susceptible people may eat nothing except
are limited to monotonous and restricted diets such rice. As milling spreads throughout the region,
as bread and water or fish and rice; and people who beriberi has resulted.
derive a large portion of their calories from rice from
which milling has removed most of the bran in Other At-Risk Groups
which the thiamine is found. There is now indication that in eighteenth- and
nineteenth-century Brazil, the disease was endemic
Rice Cultures among slaves and members of the working classes.
Beriberi is in large part a disease of rice culture. The deficiency was usually the result of diets consist-
When rice is the staple food, it is eaten in very large ing mainly of manioc flour and a little dried meat.
quantities and commonly provides 80 percent or This flour actually contains less thiamine than does

milled rice, and the preparation of the lean dried in west Africa, and Venezuela, northwestern Argen-
meat not only eliminated most of its natural thia- tina, and Brazil.
mine but also increased the body's need for the vita- The true contemporary incidence of beriberi can-
min (Kiple 1989). not be determined. Since it is so easily treated upon
A new population at risk has recently been recog- detection by the administration of thiamine, it has
nized. In urbanized and industrial countries, beri- almost ceased to be fatal. As a nutritional deficiency,
beri occurs most frequently among alcoholics. At the it is rarely reportable at any governmental statisti-
same time that chronic alcohol consumption impairs cal level. At the subclinical level, however, it proba-
the absorption of thiamine by the intestine and its bly still occurs widely. In a study in Australia, one in
storage and utilization in the liver, it increases the five healthy blood donors and one in three alcoholics
metabolic rate and requires relatively enormous at a hospital were found by biochemical assay to be
amounts of thiamine for metabolism of the alcohol. deficient in thiamine (Wood and Breen 1980).
When the alcoholic substitutes alcohol for other There was an epidemic of beriberi in the decades
foods in his or her diet and curtails consumption of following World War II. Before the war, hand milling
thiamine, Wernicke's encephalopathy and other of rice was universal except for the largest cities.
neuropsychiatric disorders may occur, involving loss With independence and economic development,
of motor coordination, loss of feeling in the hands power milling spread along the railroads and, via
and feet, and inability to remember or learn. new highways, to the rural hinterland and eventu-
There are a few other specific groups of individually even to the remote hill country. In the late
als at risk of beriberi. These include people suffering 1950s, beriberi was thought to be responsible for a
from renal failure and under long-term dialysis, and quarter or more of the infant mortality in parts of
people under long-term intravenous feeding. Burma and the Philippines (Postumus 1958) and to
Because beriberi is a deficiency disease, it is en- be the tenth highest cause of overall mortality in
tirely preventable by the consumption of adequate Thailand (May 1961). Enrichment of rice at the
amounts of thiamine. In the United States, enrich- mills has greatly reduced clinical beriberi, but even
ment of white bread - replacing the thiamine that in southern China it still occurs (Chen, Ge, and Liu
had been removed in the milling and bleaching of 1984).
wheat — caused clinical disease virtually to disap-
pear except among alcoholics. More recently, rice Clinical Manifestations and Pathology
enrichment has also proved beneficial. The beriberi clinical triad consists of edema and
neurological and cardiovascular manifestations. The
Distribution and Incidence complex of symptoms resulting from thiamine defi-
Within recent centuries, beriberi has occurred ciency, however, has often been confused by the com-
among institutionalized populations and military mon occurrence of other vitamin deficiencies at the
forces all over the world. Although the disease has same time. Thus, some of the symptoms that distin-
afflicted poor Americans subsisting mainly on white guished "dry" beriberi were indicative of riboflavin
bread and poor Europeans consuming a monotonous deficiency. A diet deficient in thiamine would usu-
diet of potatoes without meat or vegetables, beriberi ally be deficient in other B vitamins as well. Some of
is and has been most prevalent among the large the differences in the manifestation of thiamine defi-
Asian populations who consume white rice. In the ciency disease among laboring adults, suckling in-
first decade of the twentieth century, mortality from fants, and alcoholics are due to such complications.
beriberi in Japan averaged 20 per 100,000, and in A person with beriberi classically entered the
1920 reached 70 per 100,000 among the urban popu- medical system when he or she developed symptoms
lation (Shimazono and Katsura 1965). In that same of the weakness that gave the disease its name.
first decade, an estimated 120 per 1,000 people in There was malaise, a heaviness in the lower limbs,
the Straits Settlements (what is now Malaysia and loss of strength in the knee joint and wrist, and
Singapore) had beriberi, and in the Philippines, 120 usually some loss of sensation. There was tightness
per 1,000 of Filipino military scouts were admitted in the chest, palpitations, restlessness, loss of appe-
to a hospital for the disease (Williams 1961). Jacques tite, and often a full feeling in the epigastrium. In-
May (1977) reported that in recent times beriberi fants also vomited, had diarrhea, and had difficulty
still occurred in southern China, Vietnam, the Phil- breathing.
ippines, Indonesia, parts of Burma, southern India, Edema is one of the important signs and is always
Sri Lanka, Madagasgar, central Africa, local areas present in the early stages. Edema, or dropsy, com-

VIII.15. Beriberi 609
monly progresses until the lower extremities and among troops and institutionalized people around
the face are swollen. Pain and sensitivity in the calf the globe. What appeared to be epidemics occurred
muscles is an early sign as muscles begin to swell, on British ships in the Bay of Bengal, Dutch ships in
degenerate, and atrophy. Swelling of the lining of the East Indies, Norwegian whalers, ships plying
the intestines can also congest them. Edema of the the China trade in the Sea of Japan, and ships bring-
lungs often causes sudden respiratory distress and, ing "coolies" home to India from labor in the French
with heart failure, death. Antilles (Hirsch 1885). The broader epidemiology
Heart palpitations, even at rest, and a diastolic was very puzzling.
blood pressure below 60 millimeters of mercury are
usually diagnostic. There is enlargement of the The Search for the Etiology
heart, particularly the right ventricle. A heart mur- August Hirsch (1885) noted many contradictions as
mur may be heard. An EKG may be normal in a he described the changing pattern of beriberi in the
mild case but shows abnormal waves of sinus origin latter half of the nineteenth century. In a few places,
in advanced ones. notably Japan and the Malay archipelago and the
First the autonomic, then the sensory, and finally state of Minas Gerais in Brazil, the disease was
the motor nerves are affected. On autopsy, there is endemic. The disease had first appeared in Bahia in
proliferation of Schwann's cells in the sciatic nerves. Brazil in 1866, and then had spread to Sao Paulo
In chronic beriberi, there is progressive degenera- and Rio Grande do Sul by 1874, along the Brazilian
tion of nerve fibers. There is loss of coordination, seacoast, and into the interior provinces and on into
sometimes even of the eyes. Sensibility to tactile Paraguay. Similarly, the disease had been known on
stimulation, then to pain, andfinallyto temperature the coast of Japan, but had now spread into interior
is lost. The motor nerves are next affected, with towns. Earlier opinion had held that a distance of 40
paralysis beginning in the lower extremities. Then to 60 miles from a seacoast or great river was
the fingers are affected, the hand drops limp at the enough to give immunity, but the disease now oc-
wrist, and the fingers contract into a claw hand. curred hundreds of miles into the interior of Burma
Eventually, even the intercostal muscles, dia- and India as well as Brazil. Its appearance in new
phragm, and speech control muscles are affected. places showed that it was not caused by climate,
Other symptoms that commonly occur include a which had not changed, and yet it was associated
full sensation or cramping of the epigastrium, heart- with the rainy season and hot, humid weather. It
burn, constipation, and mental confusion. B. Wood seemed associated with a period of acclimatization,
and K. J. Breen (1980) define clinical thiamine defi- since people from the interior who moved to the
ciency to consist of beriberi heart failure and coast as well as new troops usually did not develop
Wernicke's encephalopathy. The latter is a dysfunc- the disease for 8 months to a year. It afflicted people
tion of the brain that is characterized by confusion in the prime of life, and wealth and high position did
and by a loss of coordination and independent move- not grant immunity. People who led sedentary lives,
ment of the eyes that is commonly found in alcohol- such as scholars and teachers, were prone to the
ics. Thiamine reverses most of the symptoms, but disease but so were soldiers and laborers. Tainted
many patients are left permanently with an inabil- water was contraindicated. Clearly people who lived
ity to form new memories (Korsakoff's psychosis). in crowded and poorly ventilated quarters were at
In classic beriberi, death results eventually from risk. The evidence for a dietary cause was confusing.
severe disturbances of the circulatory system and There seemed to be an association with insufficient
paralysis of the respiratory muscles ending in heart diet, especially lack of fat and albumin, and with
failure. preponderance of rice and dried fish in the diet.
Rice, however, was eaten widely in places where
History and Geography beriberi did not occur, and cases had been observed
Most historical studies of beriberi have been con- in Borneo where troops eating beef and eggs con-
cerned not with its occurrence or impact, but with tracted the disease whereas laborers on a diet of rice
the developments in medical science that led to an and fish did not. Hirsch concluded from the global
understanding of its etiology, treatment, and preven- evidence that the cause of beriberi was sui generis, a
tion. The geography of the disease has been closely peculiar and specific poison and not the climate,
bound to the rice-eating peoples of Asia, although weather, soil, manner of living, or diet. It is instruc-
the disease has never been limited to them. tive to contemplate the complexity of the disease,
In the nineteenth century, beriberi was common which was not clarified until the concept of a nutri-

tional deficiency, lack of a vitamin, (or mineral) was 1885, as surgeon general of the Japanese navy, he
developed and replaced the idea of a positive poison, altered the diet on the ship where sailors had previ-
in the twentieth century. Then three factors could ously been much afflicted with beriberi, and in so
explain Hirsch's observations quite simply: the mo- doing provided convincing evidence of beriberi's nu-
notonous, restrictive diets of certain populations tritional etiology. He subsequently ordered the pro-
such as prisoners, troops, and coolies; the metabolic tein ration increased for all naval personnel, and
needs of heavy labor; and, notably, the spread of barley was added to their diet.
steam-driven milling to supply the urban grain By the late nineteenth century, the Dutch in Indo-
needs. The power mills, first established along nesia had also become convinced that diet was some-
coasts and at great ports, then spread along trans- how to blame for beriberi. Experiments were carried
portation routes through the urban system. They out among the penitentiaries of Java in which lo-
intensified and spread an ancient problem in East cally hand-milled rice was substituted for white rice,
Asian populations, and introduced it to plantation and beriberi almost disappeared among the prison-
societies and booming cities in Latin America and ers. In 1890, Christian Eijkman, a Dutch officer in
Africa. Power milling practices continued to widen Java, discovered that a paralytic disease with nerve
and to cause beriberi in Asia especially until into damage characteristic of beriberi could be induced in
the 1970s. chickens fed polished rice. He and his successor, Ger-
Ship beriberi was serious among the fishing fleets rit Grijns, demonstrated in 1900 that this condition
of New England, Norway, Great Britain, and Can- could be prevented or cured by feeding rice bran.
ada. There were epidemics in the asylums of Arkan- Later Grijns extracted the water-soluble factor from
sas, and among convicts in South Carolina. It was the bran and used it to treat people.
reported along the entire coast of South America These Dutch efforts were the first experimental
from Venezuela to Argentina, but was especially seri- characterization of nutritional deficiencies, and they
ous in Panama City and among the Brazilian navy. developed an animal model that was essential for
In Africa, where there was little rice consumption, it later nutritional work. Their immediate impact was
affected troops in Senegal, Sierra Leone, Gabon, the limited, however, because American and Japanese
Congo, and Angola. Seven epidemics along the Ivory physicians did not read Dutch. The belief continued
Coast killed 80 percent of 1,100 known afflicted. It across much of the globe that beriberi must be due to
afflicted especially those who ate diets based on ba- some toxin or microbe, although none could be
nanas, corn, and yams. found, or to food spoilage. After the work of Louis
Robert R. Williams (1961) has best described the Pasteur, the assumption was that every disease
importance of the disease as he first encountered it must have a positive etiology, an active cause.
in the Philippines in 1910 (25 years after Hirsch's
description) by summarizing some of the numerous Isolation of the Active Factor
papers and presentations of Edward B. Vedder. In In 1910 in the Philippines, Vedder, a U.S. Army
Asia, beriberi was one of the leading causes of death. captain, began treating beriberi cases with an ex-
In what is now Malaysia, British doctors estimated tract from rice bran, and enrolled the efforts of Wil-
that in 20 years they had treated 150,000 hospital- liams, a new scientist at the Bureau of Science in
ized cases, of whom 30,000 had died out of a total Manila, to isolate the active factor. A Filipino doctor,
population of 1,250,000. In the hospitals of Kuala Jose Albert, was then able to identify infantile
Lumpur between 1895 and 1910, 8,422 admissions beriberi: Recognizing that in Europe, breast feeding
out of 33,735 were for beriberi; 20 percent died (Wil- was protective compared to artificial feeding of ba-
liams 1961). In Japan, where white rice was popular, bies, but that in the Philippines two-thirds of the
mortality increased from 20 per 100,000 to over 30 mortality occurred in breast-fed infants, he made
per 100,000 in the early 1920s (Shimazono and the connection linking the mothers' eating habits to
Katsura 1965). General morbidity among the Japa- the disease.
nese population is not known, but in the Russo- In 1911, Casimir Funk at the Lister Institute in
Japanese War of 1904—5 more than 20,000 cases London isolated a crystalline substance, which he
among the troops made beriberi "the only ravaging erroneously thought was the active antiberiberi fac-
epidemic." tor and called it a "vitamine" after its amine func-
There were early suspicions that diet was responsi- tion. In 1926, two Dutch chemists in Java, B.C.P.
ble. K. Takaki observed as a student in Europe the Jansen and W. F. Donath, succeeded in isolating and
low incidence of beriberi among European navies. In crystallizing the active substance from rice bran.

VIII. 15. Beriberi 611
They mischaracterized it, however, by missing its an epidemic following the spread of power rice mill-
sulfur atom, and other scientists were unable to re- ing and development, the United Nations and its Food
peat the isolation. and Agriculture Organization continued to ignore ef-
Williams, now a chemist at Bell Laboratories forts at rice enrichment. Finally, in the 1970s the
working on marine cables, continued on his own government of Thailand undertook heavy invest-
time and money at home to isolate the active factor ments, and others followed their example until the
and succeeded in 1933. He and those working with agencies of the United Nations became supportive. It
him characterized it chemically, andfinally,in 1936, was difficult to treat rice grains with synthesized vita-
completely synthesized it and proved their active mins (locally deficient) and seal them with a protec-
synthetic material to be biologically and chemically tive coating against washing and excess cooking wa-
identical to the antiberiberi factor. Williams named ter, let alone to distribute tons of the enriched rice to
it thiamin, to which research councils later added a be mixed with deficient rice at thousands of small
final e. Taking out a patent whose royalties funded mills extending into the most remote areas, and then
the Williams-Waterman Fund for the Combat of to regulate and enforce the system. Nonetheless the
Dietary Disease, Williams interested Merck & Com- success of recent efforts portends that, although mar-
pany in developing a commercial process. Produc- ginal and subclinical beriberi may persist forever, the
tion of thiamine increased from 100 kilograms in scourge of beriberi is ended.
1937 to 200,000 in 1967 (Gubler 1984) until, as Wil- Melinda S. Meade
liams remarked with satisfaction, synthetic thia-
mine was cheaper than that which could be ex-
tracted from any natural source (Williams 1961). Bibliography
Chen, Xue-Cun, Ke-you Ge, and Ling-Fen Liu. 1984. Stud-
ies in beriberi and its prevention. Journal of Applied
Prevention of Beriberi Nutrition 36: 20-6.
In the final stage, from his position on the Food and Gubler, Clark J. 1984. Thiamin. In Handbook of vitamins,
Nutrition Board of the National Academy of Sci- ed. Lawrence J. Machlin, 245—97. New York.
ence's National Research Council, Williams pio- Hirsch, August. 1885. Handbook of geographical and his-
neered and supported the enrichment of grain with torical pathology, Vol. II, trans. Charles Creighton,
synthetic thiamine. Russell M. Wilder led the effort 569-603. London.
to enrich flour, which General Mills supported, and Kiple, Kenneth K. 1989. The nutritional link between
in 1941, the first definitions and standards for en- slave infant and child mortality in Brazil. Hispanic
richment were established. The principle espoused American Historical Review 69: 677-90.
was to raise thiamine to "high natural levels" in the Leevy, Carroll M., and Herman Baker. 1968. Vitamins and
milled flour. Because it was a standard and not a alcoholism. American Journal of Clinical Nutrition
requirement, enrichment of bread in the United 21: 1325-8.
States was not fully accomplished until a popular May, Jacques M. 1961. The ecology of malnutrition in the
Far and Near East. New York.
movement was organized during World War II.
1977. Deficiency diseases. In A world geography of hu-
Other methods of preventing beriberi had been man diseases, ed. G. Melvyn Howe, 535—75. New
practiced for decades in Asia. There was considerable York.
success in both Japan and Indonesia in limiting the Postumus, S. 1958. Beriberi of mother and child in Burma.
extent of milling so that bran remained on the rice. Tropical and Geographical Medicine 10: 363-70.
These efforts involved the large, central mills of ma- Shimazono, Norio, and Eisuke Katsura, eds. 1965. Review
jor cities rather than isolated rural enforcement. Pro- ofJapanese literature on beriberi and thiamine. Tokyo.
fessionals involved in public health generally be- Thomson, A. D., M. D. Jeyasingham, and D. E. Pratt.
lieved in the importance of educating the public and 1987. Possible role of toxins in nutritional deficiency.
improving diet to prevent beriberi. Williams, who re- American Journal of Clinical Nutrition 45: 1351-60.
peatedly traveled to Asian countries campaigning for Wilcocks, C. 1944a. Medical organization and disease of
the prevention of beriberi, noted that there was oppo- Burma before the Japanese invasion. Tropical Disease
Bulletin 41: 621-30.
sition on the part of British nutritionists and their
1944b. Medical organization and disease of Indochina
Asian pupils to any artificial enrichment of cereals before the Japanese invasion. Tropical Disease Bulle-
because of a viewpoint that "any commercial intent is tin 41: 887-98.
suspect with respect to any public health measure" 1944c. Medical organization and disease in the Nether-
(Williams 1961). The result was that even as beriberi land East Indies before the Japanese invasion. Tropi-
spread through the Southeast Asian countryside as cal Disease Bulletin 41: 983-96.

1944d. Medical organization and disease of Thailand plague is enzootic in various populations of wild
before the Japanese invasion. Tropical Disease Bulle-
rodents. From there it was supposed to have spread
tin 41: 791-802. along the Mongol trade routes east to China, south
Williams, Robert R. 1961. Toward the conquest of beriberi.
to India, and west to the Kipchak Khanate, the Cri-
Cambridge, Mass. mea, and Mediterranean. Recently, however, John
Wood, B., and K. J. Breen. 1980. Clinical thiamine defi-
Norris (1977) has contested this account, pointing
ciency in Australia: The size of the problem and ap-
out that the sources describing Chinese epidemics of
proaches to prevention. Medical Journal of Australia
1: 461-4. the 1330s and 1340s and the inscriptions on the
graves at Issyk Kul (1388-9), south of the Aral Sea,
World Health Organization. 1958. Fifth report of the Joint
FAO/WHO Expert Committee on Nutrition. Geneva. are too vague to allow us to identify the disease(s) in
1980. Peripheral neuropathologies. W.H.O. Technicalquestion as plague, and that there are no reliable
Report Series No. 654, Geneva. records of Indian epidemics in the mid-fourteenth
century. Although Norris's own theory that the Black
Death originated to the south of the Caspian in
Kurdistan or Iraq is highly speculative (Dols 1978;
Norris 1978), he is certainly correct that much more
vm.16 work needs to be done with Chinese and Mongol
sources before we can say anything definite about
Black Death the course of the Black Death before 1346 and its
eastern geography and chronology after that date.
The "Black Death" is the name given by modern The epidemic's westward trajectory, however, is
historians to the great pandemic of plague that rav- well established. It reached the Crimea in the winter
aged parts of Asia, the Middle East, North Africa, of 1346-7 and Constantinople shortly afterward.
and Europe in the middle of the fourteenth century. From there it followed two great, roughly circular
Contemporaries knew it by many names, including paths. The first swirled counterclockwise south and
the "Great Pestilence," the "Great Mortality," and east through the eastern Mediterranean and the
the "Universal Plague." This epidemic was the first Middle East. The Black Death reached lower Egypt
and most devastating of the second known cycle of in the autumn of 1347 and moved slowly up the Nile
widespread human plague, which recurred in waves, over the next 2 years. By early 1348, it had also hit
sometimes of great severity, through the eighteenth Cyprus and Rhodes, and during the late spring and
century. Some of the later and milder "plagues" in summer it moved through the cities of the Mediterra-
this period seem to have also involved other dis- nean littoral and Palestine - Gaza, Jerusalem, Da-
eases, including influenza, smallpox, and dysentery. mascus, Aleppo - and then east to Mecca, Armenia,
Nonetheless almost all historians agree, on the basis and Baghdad, where it appeared in 1349.
of contemporary descriptions of its symptoms, that The second circle described by the plague was
the Black Death should be identified as a massive greater in length and duration and moved clockwise,
epidemic of plague, a disease of rodents, caused by west and north and finally east again, through the
the bacillus Yersinia pestis, that can in the case of western Mediterranean and Europe. According to
massive epizootics be transmitted to human beings Italian chroniclers, Genoese ships brought the dis-
by fleas. Although the Black Death manifested itself ease to Sicily from the Black Sea in the autumn of
most commonly as bubonic plague, it also appeared 1347, at about the same time it appeared in Alexan-
at various times and places in its primary pneu- dria. From there it spread to Tunisia, the Italian
monic and septicemic forms. mainland, and Provence. By the summer of 1348 it
had moved westward into the Iberian peninsula and
History and Geography as far north as Paris and the ports of southern En-
The geographic origins and full extent of the Black gland. During 1349 it ravaged the rest of the British
Death are still unclear. The earliest indisputable Isles and northern France, parts of the Low Coun-
evidence locates it in 1346 in the cities of the Kip- tries and Norway, and southern and western Ger-
chak Khanate of the Golden Horde, north and west many. In 1350 it was in northern and eastern Ger-
of the Caspian Sea. Until recently, most historians many, Sweden, and the Baltics, and in 1351, in the
have claimed, based on Arabic sources, that the epi- eastern Baltics and northern Poland. During the
demic originated somewhere to the east of the Cas- following 2 years, it attacked Russia, reaching as far
pian, in eastern Mongolia or Yunnan or Tibet, where east as Moscow in the summer of 1353.

VIII. 16. Black Death 613
Although the Black Death lasted in all at least 7 dents from port to port, where they could infect the
years, from its first clearly recorded appearance in local rat population, and that sick rats also traveled
the Caspian area to its final devastation of Moscow, overland hidden in shipments of cloth arid grain.
no single city or region suffered for more than a Some also emphasize the autonomous role of the
small fraction of that period. The plague moved like oriental rat flea, Xenopsylla cheopis, which could
a wave through the Middle East and Europe, and the survive independently and be transported in cloth
average duration of the epidemic in any given place and bedding. Others add to that the role of the hu-
seems to have been about 5 to 6 months. The reasons man flea, Pulex irritans, arguing that in severe epi-
for this are complicated. The ecology of plague demics such as the Black Death with a high inci-
means that it is a seasonal phenomenon; in its domi- dence of septicemic plague, fleas could transmit the
nant, bubonic form, it flourishes in warm weather, disease between humans with no need for a rodent
whereas its rarer, primary pneumonic form is most intermediary (Biraben 1975; Ell 1980). In addition,
common in winter. Thus the Black Death was above on the basis of detailed contemporary descriptions, it
all a disease of spring, summer, and early autumn, is now almost universally accepted that in both Eu-
typically receding in the last months of the year. For rope and the Middle East, the Black Death also
this reason, areas first affected in early spring, like included numerous pockets of primary pneumonic
Tunis or the cities of central Italy, in general suf- plague, a highly contagious airborne disease. It
fered longer and more severely than those, like seems likely that all of these forms of transmission
northern France and Flanders, affected in August or were involved, although their relative importance
September. The most unfortunate regions were varied according to local conditions.
those such as Lower Egypt, the Veneto, Provence, or It is difficult to judge mortality rates during the
Ireland, which experienced successive pneumonic Black Death with any precision, except in a few
and bubonic epidemics (lasting as long as 9 or 10 areas. Contemporary chroniclers tended to give im-
months, spanning both winter and summer) or were possibly high estimates, whereas other records-
reinfected in successive years. necrologies, testaments, hearth taxes, and so forth -
are incomplete or reflect only the experience of par-
Transmission and Mortality ticular groups or require extensive interpretation.
There is considerable debate over the ways in which Nonetheless, historians generally agree that death
the Black Death was transmitted from person to rates most commonly ranged between about 30 and
person and place to place. Plague is an ecologically 50 percent in both Europe and the Middle East, with
complex disease, depending on the mutual interac- the best records indicating a mortality in the upper
tion of bacilli, rodents,fleas,and humans; the lack of end of that range. Some areas are known to have
detailed evidence about the experience and behavior suffered more than others. It is frequently claimed
of animals and insects in the mid-fourteenth century that central Italy, southern France, East Anglia, and
forces us to rely on indirect and therefore ambiguous Scandinavia were most severely affected, although
evidence derived from the speed and pattern of the the evidence for this claim is uneven. Clearly, how-
epidemic's spread. ever, certain regions were relatively fortunate; Mi-
The disease was clearly propagated by humans; lan, for example, Bohemia, and parts of the Low
rather than moving slowly across fields and forests Countries seem to have experienced losses of less
from one group of rodents to another, it progressed than 20 percent, whereas Nuremberg, for some rea-
quickly along major routes of trade and communica- son, escaped entirely. In general, however, the trend
tion, traveling faster by sea than by land. Thus in in recent research is to move the estimated mortal-
virtually every area in which its trajectory is known ity rates upward. It now appears that many remote
(the Black Sea, the Mediterranean, the North Sea, and rural areas suffered as much as the larger cities
the Baltic), it appeared first in ports and then spread and that a number of regions previously thought
more slowly along roads and rivers to inland cities largely to have escaped the epidemic, such as parts
and from there into the surrounding countryside. A of the Low Countries, were in fact clearly affected.
number of extremely remote areas, including parts of The Black Death seems to have been more universal
the Pyrenees, the central Balkans, and the sub-Atlas and more virulent than many historians a genera-
region, seem to have escaped largely or entirely. tion ago believed.
Historians differ, however, about the ways in Some groups also suffered more than others, even
which humans acted to spread the plague. Virtually within a single city or region. A number of contempo-
all agree that ships carried colonies of diseased ro- rary observers in various parts of Europe com-

mented on the relatively high death rates among the morally neutral event: Drawing on traditional teach-
poor. These assertions are plausible; the poor lived ings concerning sin and penance, Christians on ev-
in crowded and flimsy houses, which would have ery level of society interpreted the plague as a mark
allowed the easy transmission of plague from rats to of divine wrath and punishment for sin and, in some
humans and from person to person, and they did not cases, even as a sign of the approaching apocalypse.
have the luxury of fleeing, like the rich, to plague- In many Italian cities, private individuals engaged
free areas or to their country estates. Conversely, in acts of piety and charity in an attempt to ensure
death rates seem to have been somewhat lower than the safety and salvation of themselves and their com-
average among the high European aristocracy and munities, while public authorities released poor pris-
royalty, who lived in stone buildings and were rela- oners and passed temporary laws against concubi-
tively mobile. People whose occupations brought nage, swearing, sabbath-breaking, and games of
them into contact with the sick, such as doctors, chance. But public reaction often took more extreme
notaries, and hospital nurses, appear to have suf- forms - among them, groups of flagellants, who pro-
fered disproportionately, at least in some areas, as fessed publicly, whipping themselves and preaching
did people who lived in large communal institutions, repentance, in order to ward off God's wrath and the
such as the Mamluks of Egypt and Syria or members Black Death. This movement seems to have begun in
of Christian religious orders. For all these groups, Italy, where it drew on thirteenth-century prece-
the main factor seems to have been increased expo- dents, but it reached its height in northern and cen-
sure rather than susceptibility. tral Europe, in Austria, Thuringia, Franconia, the
Rhineland, and the Low Countries. In Thuringia it
Attempts at Control and Prevention was associated with a radical critique of ecclesiastical
The Black Death was in many ways a completely authorities, which led Pope Clement VI to condemn
unprecedented experience for those who suffered the practice as heretical.
through it. Plague had virtually disappeared from The most extreme and shocking example of Chris-
the Middle East and Europe during the centuries tian religious reaction to the Black Death, however,
between the end of the first pandemic in the eighth was directed against Jewish communities in Pro-
century and the beginning of the second pandemic, vence, Catalonia, Aragon, Switzerland, southern Ger-
and although the first half of the fourteenth century many, and the Rhineland. Jews in these areas were
had been marked by a number of epidemics of other accused of spreading the plague by poisoning Chris-
diseases, none approached the Black Death in de- tian springs and wells. This kind of scapegoating was
structiveness and universality. Contemporaries re- not unprecedented - earlier fourteenth-century epi-
acted vigorously against the disease, attempting to demics had provoked similar accusations against lep-
halt its spread, mitigate its virulence, and alleviate ers, foreigners, and beggars as well as Jews - but the
the suffering it provoked. For the most part, how- violence of the popular reaction was extraordinary, in
ever, their responses took traditional forms: Rather some places resisted and in some places abetted by
than developing new strategies for managing the rulers and municipal governments.
crisis, they fell back on established measures, Despite the protests of the pope, hundreds of Jew-
though in many cases they applied these with un- ish communities were completely destroyed in 1348
precedented rigor. and 1349, their members exiled or burned en masse,
For those who could afford it, the most common while the residents of many others were imprisoned
reaction sanctioned by established medical authori- and tortured, with their property confiscated. The
ties was flight; even in the Islamic world, where destruction was great enough to shift the center of
religious authorities inveighed against the practice gravity of the entire European Jewish population
and exhorted believers to accept the mortality as a significantly eastward. Like the flagellant proces-
martyrdom and a mark of divine mercy, people aban- sions, with which they were occasionally associated,
doned infected cities in search of more healthful many of these pogroms had a prophylactic intent;
territory. Those who remained sought spiritual reme- some of the most violent episodes took place before
dies. In both Islamic and Christian countries, reli- the plague had actually reached the areas in ques-
gious leaders organized prayers, processions, and tion. There is no evidence for practices of this sort in
special religious services, supplicating God to lift the Islamic communities, which could boast both a long
epidemic. The European reaction, however, had a tradition of religious pluralism and tolerance and a
unique perspective, which was lacking for the most less morally loaded theological interpretation of the
part among Muslims for whom the epidemic was a epidemic.

VIII. 16. Black Death 615
A second set of defensive reactions belonged to the receive the sick and isolate them from the rest of the
realm of medicine and public health. Although both community.
Muslims and Christians identified Divine Will as These measures against contagion were unprece-
the ultimate cause of plague, most accepted that God dented in the context of both contemporary medical
worked through secondary causes belonging to the theory and municipal practice; they seem initially to
natural world, and this allowed them to interpret have been a response to the experience of pneumonic
the epidemic within the framework of contemporary plague, which ravaged the cities of Italy and south-
medical learning. Both societies shared a common ern France in the winter and spring of 1347-8. The
medical tradition based on the works of Greek writ- ecology of plague and problems of enforcement made
ers such as Hippocrates and Galen, which explained such measures largely ineffective, although it is
epidemics as the result of air corrupted by humid striking that Milan, which applied anticontagion
weather, decaying corpses, fumes generated by poor practices most drastically, was the least affected of
sanitation, and particular astrological events. Thus all major Italian cities. Nonetheless, such measures
both Muslim and Christian doctors recommended represent the beginnings of large-scale public health
(with some differences in emphasis) a similar set of organizations in Europe; succeeding epidemics saw
preventive and curative practices that included a their elaboration and their spread to other parts of
fortifying diet, rest, clean air, and moderate bloodlet- the continent, where they eventually became the
ting for the healthy, together with salves, internal basis for widespread practices such as quarantines
medication, and minor surgery for the sick. and cordons sanitaires.
Where Europe and the Islamic world clearly di- Katharine Park
verged was in their attitudes toward public health.
There is little evidence that Islamic communities
(where theological teachings combined with the clas-
sical medical tradition to deemphasize contagion as
Bibliography
Biraben, Jean-Noell. 1975. Les Hommes et la peste en
a cause of infection) engaged in large-scale social France et dans les pays europeens et me'diterrane'ens, 2
measures to prevent plague, beyond religious cere- vols. Paris.
monies and occasional public bonfires to purify the Bowsky, William, ed. 1971. The Black Death: A turning
air. From the very beginning of the epidemic, how- point in history'? New York.
ever, the populations of a number of European Bulst, Neithard. 1979. Der Schwarze Tod: Demograph-
cities - above all, in central and northern Italy, ische, wirtschafts- und kulturgeschichtliche Aspekte
which boasted a highly developed order of municipal der Pestkatastrophe von 1347-1352. Bilanz der neu-
and medical institutions - reacted aggressively in a eren Forschung. Saeculum 30: 45—47.
largely futile attempt to protect themselves from the Callic6, Jaime Sobreque's. 1970—1. La peste negra en la
disease. Initially they fell back on existing sanitary peninsula ib6rica. Anuario de Estudios Medieuales 7:
legislation, most of it dating from the thirteenth and 67-101.
Campbell, Anna Montgomery. 1931. The Black Death and
early fourteenth centuries; this emphasized street
men of learning. New York.
cleaning and the control of particularly odoriferous Carabellese, F. 1897. La peste del 1348 e le condizioni delta
practices like butchery, tannery, dyeing, and the sanita pubblica in Toscana. Rocca San Casciano.
emptying of privies. As the plague moved closer, Carpentier, Elisabeth. 1962a. Autour de la Peste Noire:
however, a number of Italian governments insti- Famines et 6pid6mies dans l'histoire du XlVe siecle.
tuted novel measures to fight contagion as well as Annales: Economies, Societes, Civilisations 17: 1062—
corrupt and fetid air. They imposed restrictions on 92.
travel to and from plague-stricken cities and on the 1962b. Une ville devant la peste: Orvieto et la Peste Noire
import and sale of cloth from infected regions and de 1348. Paris.
individuals. They passed laws against public assem- Dols, Michael W. 1977. The Black Death in the Middle
blies and regulated the burial of the dead. They East. Princeton.
hired doctors to study the disease and treat its vic- 1978. Geographical origin of the Black Death: Com-
tims (many physicians had fled the cities along with ment. Bulletin of the History of Medicine 52: 112-13.
others of their class), and they appointed temporary Ell, Stephen R. 1980. Interhuman transmission of medi-
eval plague. Bulletin of the History of Medicine 54:
boards of officials to administer these measures. In
497-510.
Milan the ducal government boarded up the houses Hatcher, John. 1977. Plague, population and the English
of plague victims, and in Avignon, the pope created a economy, 1348-1530. London.
settlement of wooden huts outside the city walls to Kieckhefer, Richard. 1974. Radical tendencies in the Fla-

gellant movement of the mid-fourteenth century. Jour- "fatal dust" in the first century. In the sixteenth
nal of Medieval and Renaissance Studies 4: 157-76. century, Agricola observed that miners, physicians,
Lerner, Robert E. 1981. The Black Death and western and engineers were aware of shortness of breath and
European eschatological mentalities. American His- premature death. In the early nineteenth century,
torical Review 86: 533-52. pathologists observed that some miners in Scotland
Meiss, Millard. 1951. Painting in Florence and Siena after had black lesions on the lung at autopsy. The term
the Black Death. Princeton.
pneumoconiosis appears to have been invented in
Norris, John. 1977. East or West? The geographic origin of
1867. Brown lung seems to have been named by
the Black Death. Bulletin of the History of Medicine
51: 1-24. analogy with black lung, apparently in the 1960s.
1978. Response to Michael W. Dols. Bulletin of the His- The contemporary, imprecise medical synonym for
tory of Medicine 52: 114-20. black lung is coal workers' pneumoconiosis (CWP).
Williman, Daniel, ed. 1982. The Black Death: The impact CWP occurs in two forms: simple CWP and progres-
of the fourteenth-century plague. Binghamton, N.Y. sive massive fibrosis. Both forms have characteristic
Ziegler, Philip. 1969. The Black Death. New York. lesions. Agencies awarding compensation for disabil-
ity usually use the designation "black lung" as a
rough synonym for pathologically defined CWP and
for obstructive airways disease among coal miners.
Most medical authors, epidemiologists, and agen-
cies awarding compensation usually use "brown
VIII. 17 lung" as a popular synonym for byssinosis or chronic
Black and Brown Lung dust-induced respiratory disease (CDIRD). The pa-
thology in these descriptions resembles that of
Disease chronic bronchitis.
The rich literature on the history and geography
of black and brown lung cannot be summarized in
Black and brown lung are the names given by work-
conventional terms. Many authors have attempted
ers in the coal and textile industries, respectively,
to describe the history of these conditions, but they
and by some physicians and public officials, to symp-
have almost invariably done so on the basis of the
toms of respiratory distress associated with dusty
precise definition of symptomatology accepted at the
work. Most physicians and epidemiologists have,
time they were writing. The reported geography of
however, preferred to categorize these symptoms as
the conditions is consistent with the distribution of
they relate to findings at autopsy and studies of
industries in which dust is a by-product, but the
pulmonary function and to name their appearance
perception of the conditions in particular places (and
in particular patients as, respectively, coal workers'
by later observers) has determined what is said, in
pneumoconiosis and byssinosis. The terms "black
retrospect, about their geography.
lung" and "brown lung" are historical legacies of
intense negotiations about the causes of respiratory
distress and mortality among workers in the coal Distribution and Incidence
and textile industries of Europe and North America, Each condition has been described among workers
especially since the nineteenth century. (For the con- exposed to coal dust (CWP) and cotton dust
ventional medical definitions of the pathology sub- (byssinosis). Perhaps 1 million workers worldwide
sumed under the terms black lung and brown lung, are currently exposed to both coal and cotton dust.
see the extensive bibliographies in papers by Fox The most reliable statistical accounts of the condi-
and Stone [1981] and Corn [1980]). tions, both contemporary and historical, are avail-
able in British and American sources. The historical
and geographic incidence of each condition (and of
History and Geography the particular diseases defined at each time of writ-
For many centuries, medical observers, and workers ing) has been influenced by public policy and regula-
and their employers, have recognized respiratory dis- tions for dust suppression, by the characteristics of
tress and its consequences as an occupational hazard the mining and manufacturing process (and, for
among underground miners and employees of indus- black lung, by the type of coal itself), by the workers'
tries that generate considerable dust (notably refin- general state of health, and by their exposure to
eries, foundries, and the manufacturing of cotton, other causes of respiratory disease, notably cigarette
flax, and hemp). Pliny described the inhalation of smoke, and by the availability of publicly supported

VIII.17. Black and Brown Lung Disease 617
programs of disability compensation and medical lungs; yet the syndrome seems extremely rare in the
care. United States, dispite the high incidence of both dust
Opinions about the distribution and incidence of exposure and arthritis among miners.
the conditions have been linked to competing views For byssinosis, areas of uncertainty include the
about their clinical manifestations and pathology. following: (1) the substance in cotton dust that
For many years and in many communities, physi- causes respiratory distress; (2) lack of clear evidence
cians did not differentiate the symptoms of black linking levels of dust exposure to findings indicative
and brown lung from those of other common respira- of clinically defined disease; and (3) the absence of
tory disorders. In the early stages of both diseases, widely agreed upon findings from clinical and patho-
workers are frequently asymptomatic and without logical examinations that are sufficiently specific to
functional impairment. For black lung denned medi- permit a diagnosis of disease.
cally as CWP, the progression of symptoms often Nevertheless, the contemporary literature on both
includes chronic cough and phlegm, shortness of conditions is widely regarded as offering consider-
breath, and then functional impairment; but some able guidance for public action. Most investigators
workers with lesions of CWP at autopsy remained agree that the relatively high incidence of respira-
free of symptoms. The initial symptoms of byssinosis tory distress in mining and textile workers is evi-
are tightness in the chest, dyspnea, and a cough dence of exposure to toxic agents in industrial dust.
following a return to work after a weekend or holi- Many authors have hypothesized mechanisms by
day. Later symptoms extend to other workdays and which these agents could operate in the lung. There
include a chronic stage, with severe continuous is considerable agreement about clinical manifesta-
dyspnea, chronic cough, and permanent ventilatory tions and pathology. And there is overwhelming con-
insufficiency. sensus that reducing dust levels in the workplace
contributes to reducing the incidence of both black
Epidemiology and Etiology and brown lung and the symptoms, signs, and find-
Both black and brown lung (and their medically ings defined by medical scientists as diseases among
named partial synonyms) have been the focus of workers in dusty industries.
many studies - and are highly controversial. Early Throughout their histories, black and brown lung
epidemiological studies established an association have been matters of controversy involving people
between occupation and respiratory disease. Studies and institutions beyond the medical profession. The
of both conditions in the United States were, in gen- definitions of the conditions have been matters of
eral, initiated later than those in Britain for reasons intense political concern. Generalizations about
that include the political roles of manufacturers and their incidence and distribution depend on how they
unions and the structure of public regulation as well are defined, and defining them has long been contro-
as different perceptions of the relative importance of versial. Etiology and epidemiology remain in dis-
silica and coal dust and the amount of dust that pute in part because of scientific uncertainty but
constituted a dangerous exposure in textile manufac- also because involved as well are significant
turing. Moreover, many epidemiological, clinical, amounts of money and fundamental issues about the
and pathological investigations have yielded uncer- relationship between employers and employees and
tain results. the public interest in workplace health and safety.
Aspects of coal miners' lung distress that remain Laws and regulations are often more important
controversial include the following: (1) the mecha- sources than medical texts for understanding what
nisms by which coal dust acts on the lungs; (2) the clinical manifestations and pathological findings
significance of the correlation, or lack of it, between mean for treatment, compensation, and control of
clinical evidence of respiratory impairment and X- the environment of the workplace.
ray findings; and (3) the absence, in some studies, of Daniel M. Fox
strong, independent correlations between respira-
tory disorders in mining communities and work in
Bibliography
the mines. Caplan's syndrome is an example of the
Benedek, Thomas G. 1973. Rheumatoid pneumoconiosis:
complexity and controversy surrounding coal min- Documentation of onset and pathogenic consider-
ers' lung conditions. This syndrome, first described ations. American Journal of Medicine 55: 515-24.
among Welsh coal miners in 1953, appears to be a Corn, Jacqueline Karnell. 1981. Byssinosis — an historical
consequence of the interaction of characteristics of perspective. American Journal of Industrial Medicine
rheumatoid arthritis with a residue of silica in the 2: 331-52.

Elwood, P. C, et al. 1986. Respiratory disability in ex- lation of blood - that is, by its transformation from
cotton workers. British Journal ofIndustrial Medicine a fluid to a gel-like state. Uncontrolled bleeding
43: 580-6. and its antithesis, thrombosis (the formation of a
Fox, Daniel M., and J. F. Stone. 1980. Black lung: Miners' clot within a blood vessel), are important patho-
militancy and medical uncertainty, 1968—72. Bulletin genetic factors for human disease, including a large
of the History of Medicine 54: 43-63. variety of hereditary disorders.
Judkins, Bennett M. 1986. We offer ourselves as evidence:
Toward workers' control of occupational health. West- The basic structure of both the occlusive clots that
port, Conn. halt blood loss and pathological intravascular clots
Kilburn, Kaye H. 1986. Byssinosis. In Maxcy—Rosenau (or thrombi) is a meshwork offibrousprotein {fibrin)
public health and preventive medicine, ed. John M. that entraps blood cells. Plato and Aristotle both
Last et al., 12th edition. Norwalk, Conn. described the fibers found in shed blood. When the
Merchant, James A. 1986. Coal workers' pneumoconiosis. blood vessel wall is disrupted, whether by trauma or
In Maxcy—Rosenau public health and preventive medi- disease, a soluble plasma protein, fibrinogen (factor
cine, 12th edition, ed. John M. Last et al. Norwalk, I), is transformed into the insoluble strand of fibrin.
Conn. Fibrin formation takes place through three steps:
Salvaggion, John E., et al. 1986. Immunologic responses to First, a plasma proteolytic enzyme, thrombin,
inhaled cotton dust. Environmental Health Perspec- cleaves several small peptides from each molecule of
tives 66: 17-23. fibrinogen. Molecules of the residue, called fibrin
Smith, Barbara Ellen. 1987. Digging our graves: Coal monomers, polymerize to form the fibrin strands.
miners and the struggle over black lung disease.
Philadelphia.
Finally, these strands are bonded covalently by a
Wegman, David H., et al. 1983. Byssinosis: A role for plasma transamidase, fibrin-stabilizing factor (fac-
public health in the face of scientific uncertainty. tor XIII), itself activated by thrombin, increasing
American Journal of Public Health 73: 188-92. their tensile strength.
Thrombin is not found in normal circulating
plasma, but evolves after vascular injury from its
plasma precursor, prothrombin (factor II), via either
or both of two interlocking series of enzymatic
events, the extrinsic and intrinsic pathways of
VIII. 18 thrombin formation. The steps of the extrinsic path-
way begin when blood comes into contact with in-
Bleeding Disorders jured tissues (such as the disrupted vascular wall).
The tissues furnish a lipoprotein - tissue thrombo-
plastin or tissue factor (factor III) — that reacts with a
The existence of a hereditary tendency to excessive
plasma protein, factor VII. Factor VII then converts
bleeding was recognized in the second century A.D.
a plasma proenzyme, Stuart factor (factor X), to its
by Rabbi Judah, who exempted from circumcision
active form. Thus activated, Stuart factor (factor
the son of a woman whose earlier sons had bled to
Xa), acting in conjunction with a nonenzymatic
death after this rite. But only in this century has
plasma protein, proaccelerin (factor V), releases
expanding knowledge of the physiology of hemosta-
thrombin from prothrombin, and in this way initi-
sis — the arrest of bleeding - made evident the di-
ates the formation of fibrin.
verse nature of inherited bleeding disorders. In addi-
tion, only recently has it been recognized that a The intrinsic pathway of thrombin formation is
tendency to thrombosis might likewise be due to an launched when vascular disruption brings plasma
inherited hemostatic defect. into contact with certain negatively charged sub-
stances, such as subendothelial structures or the oily
sebum layer of skin. Exposure to negative charges
Physiology of Hemostasis changes a plasma protein, Hageman factor (factor
The mechanisms by which blood loss in mammals is XII), to an enzymatic form, activated Hageman fac-
stopped after vascular disruption are complex. tor (factor XHa), that participates in both clotting
Small vascular injuries are sealed by platelets that and inflammatory reactions. In the latter role, acti-
adhere to the site of damage, where they attract vated Hageman factor converts a plasma proen-
other circulating platelets, so as to form an occlu- zyme, prekallikrein, to kallikrein, an enzyme that
sive aggregate or plug that can close small gaps. releases small peptides from a plasma protein, high
Larger defects in vessel walls are occluded by coagu- molecular weight kininogen. These peptides, notably

VIII. 18. Bleeding Disorders 619
bradykinin, increase vascular permeability, dilate sues but not in plasma. Heparin cofactor II, a protein
small blood vessels, and induce pain. distinct from antithrombin III, also inhibits clotting
The role of activated Hageman factor in the intrin- in the presence of heparin. Cl esterase inhibitor (Cl-
sic pathway is to initiate a series of proteolytic reac- INH) originally detected as an inhibitor of the acti-
tions that lead ultimately to the release of thrombin vated form of the first component of the immune
from prothrombin. These reactions involve the se- complement system (Cl), also blocks the activated
quential participation of several plasma proteins, forms of Hageman factor and PTA as well as plasmin.
including plasma thromboplastin antecedent (PTA, Alpha-1 -antiproteinase (alpha-1 -antitrypsin) is an in-
factor XT), high molecular weight kininogen, plasma hibitor of activated PTA. Protein C, when activated
prekallikrein, Christmas factor (factor IX), antihemo- by thrombin, blocks the coagulant properties of
philic factor (factor VIII), Stuart factor (factor X), antihemophilic factor (factor VIII) and proaccelerin
and proaccelerin (factor V). Of these various pro- (factor V), an action enhanced by protein S; proteins
teins, PTA, plasma prekallikrein, Christmas factor, C and S both require vitamin K for their synthesis.
and Stuart factor are the precursors of proteolytic Activated protein C also enhances the conversion of
enzymes, whereas high molecular weight kininogen, plasminogen to plasmin. Alpha-2-macroglobulin is
antihemophilic factor, and proaccelerin serve as an inhibitor of plasma kallikrein, and plasmin can be
nonenzymatic cofactors. The ultimate product, acti- inhibited by several plasma proteins, notably by
vated Stuart factor (factor Xa), releases thrombin alpha-2-plasmin inhibitor.
from prothrombin through the same steps as those of Human disorders due to the functional deficiency
the extrinsic pathway. Hageman factor also en- of each of the factors needed for the formation of a
hances clotting via the extrinsic pathway by aug- clot have been recognized and extensively studied.
menting the activity of factor VII, whereas factor In some instances, the patient's plasma appears to
VII in turn can directly activate Christmas factor. be deficient or totally lacking in a specific clotting
Thus, the steps of the extrinsic and intrinsic path- factor or inhibitor. In others, plasma contains a non-
ways are intertwined. functional variant of the normal plasma protein.
Certain steps of both the extrinsic and intrinsic
pathways require the presence of calcium ions and Classic Hemophilia
phospholipids, the latter furnished, in the extrinsic
pathway, by tissue thromboplastin and, in the intrin- Clinical Manifestations
sic pathway, by platelets and by plasma itself. The best known of all the bleeding disorders is clas-
Antihemophilic factor (factor VIII) is of peculiar sic hemophilia (hemophilia A, the hereditary func-
interest as it circulates in plasma loosely bound to tional deficiency of factor VIII), which is the proto-
another plasma protein, von Willebrand factor type of an X chromosome-linked disease, limited to
(vWf), which fosters hemostasis by promoting adhe- males but transmitted by female carriers. Necessar-
sion of platelets to injured vascular walls. The ily, all daughters of those with the disease are carri-
plasma proteins participating in coagulation are syn- ers, as are half the daughters of carriers. In turn,
thesized at least in part by the liver, except for von half the sons of carriers inherit the disease. A typical
Willebrand factor, which is synthesized in vascular family history of bleeding inherited in the manner
endothelial cells and megakaryocytes. described is found in about two-thirds of cases; in the
Synthesis of certain of the plasma clotting rest, the disorder appears to arise de novo, either
factors - namely prothrombin, factor VII, Stuart fac- because a fresh mutation has occurred or because
tor (factor X), and Christmas factor (factor IX) - is cases were unrecognized in earlier generations.
completed only in the presence of vitamin K, fur- Classic hemophilia varies in severity from family
nished by leafy vegetables and by bacterial flora in to family. In the most severe cases, in which plasma
the gut. is essentially devoid of factor VIII, the patients may
The clotting process is modulated by inhibitory bruise readily and bleed apparently spontaneously
proteins present in normal plasma. Plasmin, a into soft tissues and joints, with the latter resulting
proteolytic enzyme that can be generated from its in crippling joint disease. Trauma, surgical proce-
plasma precursor, plasminogen, can digest fibrin dures, and dental extractions may lead to lethal
clots as well as certain other plasma proteins. bleeding. The life expectancy of those with severe
Antithrombin III inhibits all of the plasma proteases classic hemophilia is foreshortened, death coming
of the clotting mechanism, an action enhanced by from exsanguination, bleeding into a vital area, or
heparin, a glycosaminoglycan found in various tis- infection. The prognosis of classic hemophilia has

been greatly improved by modern therapy in which Geography
episodes of bleeding are controlled by transfusion of Worldwide, Christmas disease is perhaps one-eighth
fractions of normal plasma containing the function- to one-fifth as prevalent as classic hemophilia. Most
ally missing proteins. This therapy is not without reported cases have been in individuals of European
hazard, for transfusion of concentrates of factor VIII origin, but in South Africa and in the United States,
derived from normal plasma has been complicated as reflected by Ohio data, Christmas disease is rela-
by transmission of the viruses of hepatitis and the tively as common in blacks as in whites. Christmas
acquired immunodeficiency syndrome (AIDS). disease of moderate severity is particularly preva-
In those families in which classic hemophilia is lent among inhabitants of the village of Tenna, in
milder, bleeding occurs only after injury, surgery, or Switzerland, and among Ohio Amish. This disorder
dental extraction. The severity of clinical symptoms is said to be rare in Japan.
is paralleled by the degree of the deficiency of
antihemophilic factor (factor VIII), as measured in Von Willebrand's Disease
tests of its coagulant function.
Clinical Manifestations
Geography Classic hemophilia is not the only hereditary defi-
Classic hemophilia appears to be distributed world- ciency of antihemophilic factor. Von Willebrand's dis-
wide but geographic differences in its incidence have ease is a bleeding disorder of both sexes which in its
been described. In the United States, Great Britain, usual form is present in successive generations; thus,
and Sweden, estimates of the prevalence of classic it is inherited as an autosomal dominant trait. The
hemophilia range from about 1 in 4,000 to 1 in plasma of affected individuals is deficient in both
10,000 males; a somewhat lower prevalence has parts of the antihemophilic factor complex - that is,
been estimated in Finland. Whether classic hemo- the coagulant portion (factor VIII) and von Wille-
philia is less prevalent in blacks than in other brand factor (vWf). The bleeding time - the duration
groups, as has been suggested, is uncertain since of bleeding from a deliberately incised wound - is
milder cases may not be brought to medical atten- abnormally long, distinguishing von Willebrand's dis-
tion for socioeconomic reasons. ease from classic hemophilia or Christmas disease.
The disorder is usually mild, although variants have
been observed in which severe bleeding episodes are
Christinas Disease frequent. Inheritance in these cases is probably reces-
Clinical Manifestations sive in nature.
Christmas disease (hemophilia B), the hereditary
functional deficiency of Christmas factor (factor IX), Geography
is clinically indistinguishable from classic hemo- The prevalence of von Willebrand's disease is uncer-
philia, and can be differentiated only by laboratory tain because mild cases are easily overlooked. Using
tests. It is inherited in the same way as an X Ohio as something of a proxy for the United States,
chromosome-linked disorder and is therefore virtu- von Willebrand's disease is about one-fourth as
ally limited to males. As is true of classic hemo- prevalent as classic hemophilia, meaning about 2 or
philia, the disorder varies in severity from family to 3 cases per 100,000 individuals. Estimates of 3 to 6
family in proportion to the degree of the clotting cases per 100,000 have been made in the United
factor deficiency. Christmas disease is heterogene- Kingdom and Switzerland, whereas the prevalence
ous in nature, for in some families the plasma is is somewhat higher in Sweden, about 12 per
deficient in Christmas factor, whereas in others the 100,000. A study conducted in northern Italy on a
plasma contains one or another of several nonfunc- population of school children revealed that 10 of
tional variants of this clotting factor. Therapy for 1,218 had laboratory evidence of the disease as well
hemorrhagic episodes in Christmas disease is cur- as a family history of hemorrhagic problems. By
rently best carried out by transfusion of normal contrast, the disorder is relatively uncommon in
plasma, which contains the factor deficient in the blacks. Similarly, although the severe, autosomal
patient's plasma. An alternative therapy, infusion of recessive form of von Willebrand's disease is un-
concentrates of Christmas factor separated from nor- usual in most individuals of European extraction
mal plasma, may be needed in some situations, but (perhaps 1 per 1 million), it is particularly prevalent
its use may be complicated by the transmission of among Israeli Arabs, in whom it can be detected in
viral diseases as well as by other problems. about 5 individuals per 100,000, and in Scandinavia.

VIII. 18. Bleeding Disorders 621
Unusual Disorders of Hemostasis raeli Jews of Sephardic origin, the patients coming
Functional deficiencies of Hageman factor (Hage- from Iran, Iraq, and Morocco.
man trait), plasma prekallikrein (Fletcher trait), In each of these disorders, the deficiency appears
and high molecular weight kininogen (Fitzgerald, in both sexes and is inherited as a recessive trait,
Flaujeac, or Willimas trait) are all asymptomatic, and in a number of instances the parents have been
although in each case a major defect in clotting is consanguineous. In general, the basic nature of
found in the laboratory. These disorders occur with these functional deficiencies is variable. In some in-
equal frequency in both sexes, and are recessive stances, the plasma of the affected individuals ap-
traits, meaning that they must be inherited from pears to be deficient in the factors, as shown in
both parents. Hageman trait and deficiencies of functional assays. In others, the plasma contains an
plasma prekallikrein and high molecular weight incompetent variant of the supposedly missing fac-
kininogen are all rare, and data concerning their tor. For example, patients functionally deficient in
prevalence are available only for Hageman trait, prothrombin may either be truly deficient in this
which, in Ohio, occurs in about 1 in 500,000 individu- protein, or their plasma may contain one or another
als. By contrast, a disproportionately high number variant, nonfunctional form of prothrombin (congeni-
of cases of Hageman trait have been reported from tal dysprothrombinemia). A similar variability in
the Netherlands. No racial predilection for Hageman the nature of functional deficiencies of factor VII and
trait or deficiency of high molecular weight kini- Stuart factor (factor X) has been detected. In one
nogen had been described, but deficiency of plasma variant of factor X deficiency, first observed in pa-
prekallikrein appears to be more frequent in blacks tients in the village of Friuli in northeast Italy, Stu-
and in individuals of Mediterranean extraction. art factor could not be detected in the usual func-
Hageman trait is a heterogeneous disorder; in tional assays, but behaved normally when the
most families, the plasma appears to be deficient in venom of Russell's viper was added to the patients'
Hageman factor, but plasma in a few contains a plasma.
nonfunctional variant of this clotting factor. A simi- The symptoms of deficiencies of factor VII, Stuart
lar heterogeneity had been observed in plasma factor, and proaccelerin (the last called parahemo-
prekallikrein deficiency, with the plasma of those philia) are variable, some individuals having hemor-
patients of Mediterranean origin containing a non- rhagic episodes comparable to those of severe hemo-
functional variant of plasma prekallikrein. philia, whereas others are spared except in the event
The hereditary deficiency of plasma thrombo- of severe trauma. In women, excessive menstrual
plastin antecedent (PTA or factor XI deficiency) is bleeding may be a serious problem.
also inherited in an autosomal recessive manner. Disorders of fibrin formation are of peculiar inter-
The hemorrhagic symptoms are usually mild; in est. Patients with congenital afibrinogenemia (who
women, excessive menstrual bleeding may be trou- have no detectable fibrinogen in plasma) may bleed
blesome. Nearly all reported cases have been those excessively from the umbilicus at birth, and thereaf-
of Ashkenazi (i.e., eastern European) Jews or Japa- ter from injuries or surgical procedures. In addition,
nese, although cases in individuals of American they may exsanguinate from relatively minor vascu-
black, Arabic, Italian, German, Yugoslav, Dutch, lar injuries, and menorrhagia may be disastrous; yet
Scandinavian, English, Korean, and Asiatic Indian they may have little in the way of spontaneous bleed-
heritage have also been recognized. In Israel, as ing. Fortunately, cogenital afibrinogenemia is a rare
many as 0.1 to 0.3 percent of Ashkenazi Jews may be recessive disorder, detected in both sexes, and only
affected, and 5.5 to 11 percent may be heterozygous about 150 cases have been recorded to date. Often
carriers. Similarly, in Ohio, at least 0.3 percent of the parents are consanguineous. A milder form, con-
Ashkenazi Jews have PTA deficiency, and at least genital hypofibrinogenemia (in which the plasma
3.4 percent are heterozygotes. contains small but measurable amounts of fibrin-
Hereditary deficiencies of factor VII, Stuart factor ogen), has also been described in about 30 families,
(factor X), proaccelerin (factor V), and prothrombin and some investigators believe that this is the
are rare, and no racial or geographic distribution is heterozygous state for congenital afibrinogenemia,
yet apparent. An estimate of one case of factor VII meaning that these individuals have inherited the
deficiency per 100,000 has been made. A still rarer abnormality from but one parent. In still other fami-
syndrome, the combination of factor VII deficiency lies, the concentration of fibrinogen in plasma is
and Dubin-Johnson syndrome (the latter a disorder normal or only moderately decreased, but the
of billirubin metabolism) has been described in Is- fibrinogen is qualitatively abnormal. This disorder,

congenital dysfibrinogenemia, occurs in both sexes In Massachusetts, the prevalence is said to be about
and in successive generations; that is, it is inherited 50 per 100,000. No geographic or racial predilection
as a dominant trait. The affected individuals may be has been reported.
asymptomatic, detected only by chance, or they may Most of the reported cases of deficiencies of these
suffer mild bleeding problems. Paradoxically, they several inhibitors have been in individuals of Euro-
may also sustain thrombosis. Over 100 families with pean origin. Additional instances of antithrombin
dysfibrinogenemia have been described, and the mo- III deficiency have been recognized in Japanese, Al-
lecular defect in each family is almost always gerians, and American blacks; protein C deficiency
unique. has been seen in Jordanian and Israeli Arabs, and in
Fibrin-stabilizing factor (factor XIII) deficiency is Japanese; and protein S deficiency has been reported
similarly rare; perhaps 100 cases have been de- in Japan.
scribed thus far. In some, plasma appears to be defi-
cient in fibrin-stabilizing factor, and in others, History
plasma contains a nonfunctional variant of this The earliest record of the existence of hereditary
agent. Patients with fibrin-stabilizing factor defi- hemorrhagic disease is in the Babylonian Talmud.
ciency have severe bleeding problems beginning Recurrent descriptions of what was probably hemo-
with the umbilicus at birth. The patients may die of philia were recorded thereafter, but it was only in
central nervous system hemorrhage, and in women 1803 that John Otto, a Philadelphia physician, recog-
spontaneous abortion is frequent. Some evidence sug- nized that this disorder was limited to males and
gests that affected males are sterile. transmitted by certain of their asymptomatic female
Little information is available concerning a racial relatives. During the nineteenth century, the mode
or geographic predilection for any of these disorders of inheritance of hemophilia was delineated, and in
of fibrin formation, but the prevalence of fibrin- their 1911 review of all the published cases of hemo-
stabilizing factor deficiency in the United Kingdom philia, W. Bulloch and P. Fildes were unable tofinda
is said to be 1 in 5 million. single authentic case of hemophilia in a female.
Another disorder of great interest is the heredi- The mechanism underlying the defect in classic
tary deficiency of alpha-2-antiplasmin. In this dis- hemophilia was elucidated by A. J. Patek, Jr., and
ease, which is inherited as a recessive trait, patients R. H. Stetson in 1936, who determined that the pa-
may have symptoms suggestive of severe classic tients were functionally deficient in what is now
hemophilia. Bleeding apparently results from the called antihemophilic factor (factor VIII). Only later
rapid dissolution of clots by plasmin, whose proteo- was it realized independently by P. N. Aggeler, I.
lytic activity is unchecked because of the deficiency Schulman, and R. Biggs that an essentially identical
of alpha-2-plasma inhibitor. Too few cases have been disorder, inherited in the same way, resulted from a
recognized to determine whether there is a geo- deficiency of Christmas factor (factor IX). In 1926, E.
graphic predilection for this disorder, but it has been A. von Willebrand recognized the disease that now
reported in Japan, the Netherlands, Norway, the bears his name among inhabitants of the Aland Is-
United States, and Argentina. lands in the Gulf of Rothnia. This hereditary hemor-
rhagic disorder affects both sexes and was detected
Hereditary Thrombotic Disorders in succeeding generations; these characteristics,
In contrast to the deficiency states described to this along with the presence of a prolonged bleeding
point, a hereditary deficiency of certain of the inhibi- time, distinguishes von Willebrand's disease from
tors of clotting results in an increased tendency to hemophilia. In 1953, several independent groups of
thrombosis. Thus, familial recurrent thrombosis has investigators found that the titer of antihemophilic
been observed in individuals of both sexes, with in- factor (factor VIII) was abnormally low in patients
herited partial deficiencies of antithrombin III, pro- with von Willebrand's disease, and some years later
tein C, protein S, or heparin cofactor II. The affected T. S. Zimmerman reported a deficiency also in the
individuals, most of whom are heterozygotes (i.e., concentration of what is now called von Willebrand
they have inherited an abnormal gene from but one factor.
parent), have about half the concentration of the With few exceptions, the existence of the various
inhibitory proteins of normal individuals. Only a clotting factors required for normal coagulation of
handful of cases of deficiencies of heparin cofactor II, blood was detected by the study of patients with
protein C, or protein S have been recorded, but a unusual hemorrhagic disorders. In each instance, a
deficiency of antithrombin III is relatively common. protein extracted from normal plasma corrected the

VIII. 19. Botulism 623
specific defect in the patient's plasma. Thus, current Table VIII.19.1. Types o/"Clostridium botulinum,
knowledge about the physiology of blood clotting has susceptible species, and sites of outbreaks
been derived from the interplay between the clinic
and the laboratory. Type Species Site of outbreaks
Oscar D.Ratnoff A Humans U.S., former
U.S.S.R.
Bibliography B Humans, horses Northern Europe,
Bulloch, W., and P. Fildes. 1911. Hemophilia. In Treasury U.S., former
of human inheritance, Parts V and VI, Sect. XTVa: U.S.S.R.
169-347. London. C Birds, turtles, cat- Worldwide
Colman, R. W., et al. 1987. Hemostasis and thrombosia, 2d tle, sheep, horses
edition. Philadelphia. D Cattle, sheep Australia, South Af-
Jandl, J. H. 1987. Blood: Textbook of hematology. Boston. rica
Mammen, E. F. 1983. Congenital coagulation disorders. E Humans, birds Canada, Northern
Seminars in Thrombosis and Hemostasis 9:1-72. Europe, Japan,
Ratnoff, O. D. 1980. Why do people bleed? In Blood, pure U.S., former
and eloquent, ed. M. M. Wintrobe, 601-57. New York. U.S.S.R.
Ratnoff, O. D., and C. D. Forbes. 1984. Disorders of F Humans Denmark, U.S.
hemostasis. Orlando, Fl. G No outbreaks recog-
Stamatoyannopoulos, G., et al. 1987. The molecular basis nized
of blood diseases. Philadelphia.
Source: L. Smith (1977), Botulism: The Organism, Its Tox-
ins, the Disease. By courtesy of Charles C. Thomas, Pub-
lisher, Springfield, 111.
VIII. 19
To date, seven immunologically distinct forms of
Botulism botulinum toxins, labeled A through G, have been
identified. Botulism in humans has generally been
associated with A, B, E, or F toxins, whereas the C
Botulism is an uncommon, potentially fatal para- and D toxins have been identified in botulism out-
lytic disease caused by a protein neurotoxin that is breaks among various animal species, as shown in
produced by the bacterium Clostridium botulinum. Table VIII.19.1.
The disease is most frequently seen as a foodborne
intoxication first clearly documented in the early Clinical Manifestation and Pathology
nineteenth century; however, two other forms of the The onset of disease usually occurs within 12 to 36
disease have been identified in the latter part of hours of ingestion of food contaminated with
the twentieth century: wound botulism and infant botulinum toxin. Botulism typically presents with
botulism. an array of distressing signs of motor nerve dysfunc-
tion, including double or blurred vision and diffi-
Etiology culty with speech and swallowing. The unabated
Botulism is caused by very powerful neurotoxins disease progresses to generalized paralysis and
that are elaborated during the growth and multipli- death from respiratory muscle involvement.
cation of the bacterium C. botulinum. The bacte- Diagnosis is confirmed by detecting botulinum
rium, which exists in nature as a spore, multiplies toxin in the blood, feces, or wound site of the patient.
and produces its toxin in oxygen-deprived or anaero- Depending on the dose of toxin, untreated botulism
bic conditions, such as may occur in canned or her- carries a high fatality rate. Early treatment with
metically sealed foods or unclean wounds. Spores of antitoxin accompanied by respiratory assistance and
C. botulinum are found naturally in soil and marine other supportive intensive care may be life-saving.
sediments, and thus may readily occur as normal The pathophysiology involves inhibition of release
contaminants of many vegetable and animal sources of the neurotransmitter substance acetylcholine at
of food. The spores and their toxins are inactivated the neuromuscular junction, thus preventing the ini-
by boiling canned foods according to food industry tiation of the electrical impulse needed for muscle
specifications. contraction. Electromyography shows a characteris-

tic decrease in amplitude of the evoked muscle ac- Table VIII.19.2. Reports of botulism from various
tion potential in response to an electrical stimulus. countries in recent years
Infant botulism, a condition confined to babies be-
tween 2 weeks and 9 months of age, typically presents Average Average Case
with listlessness and generalized weakness ("floppy cases deaths fatality
baby") and has been shown to cause some cases of Country (per year) (per year) rate (%)
sudden infant death syndrome (SIDS). It has been Poland 310 31 10
associated with ingestion of various processed infant (1959-69)
foods - honey in particular — that contain botulinum Germany 66 3 5
spores. First described in the United States in 1976, (1962-71)
where the majority of cases have been reported, in- U.S.S.R. 47 14 29
fant botulism has also been documented in Europe, (1958-64)
Australia, Asia, and South America. United States 21 7 31
(1950-73)
Japan 19 5 27
History
(1951-9)
Botulism derives its name from the Latin word, France 9 1 5
botulus (sausage), based upon observations in the (1956-70)
late 1700s and early 1800s by physicians in southern China (Sinkiang) 9 4 44
Germany who noted the occurrence of an unusual (1949-57)
but frequently fatal disease following ingestion of Canada 8 3 35
spoiled sausage. Justinius Kerner, a district health (1961-7)
officer in Wurttemberg, compiled these reports in Belgium 4 NA<" —
official documents, with the result that botulism has (1946-71)
at times been called "Kerner's disease." A similar Norway 4 NA° —
illness seen in nineteenth-century Russia in associa- (1957-71)
tion with eating smoked or pickled fish was labeled Denmark 1 NA° _
"ichthiosismus." (1958-72)
Hungary 1 1 9
In 1896, Emile von Ermengem, student of Robert (1950-65)
Koch and professor of bacteriology at the University
of Ghent, established that the disease was caused by Source: Smith (1977), Botulism: The Organism, Its Toxins,
a neurotoxin produced by an anaerobic bacterium. the Disease. By courtesy of Charles C. Thomas, Publisher,
This discovery emerged from his laboratory investi- Springfield, 111.
a
gation of the cause of a dramatic outbreak of the NA = not available.
disease that occurred at a gathering of musicians in
a small Belgian village.
Following initial recognition of the disease in the
United States in 1899, the repeated occurrence of Foods primarily responsible for botulism vary con-
botulism outbreaks associated with commercially siderably among countries, reflecting differing di-
canned foods led to extensive applied research in the etary and food preservation practices. In Poland,
1920s. Sponsored by the National Canners Associa- Germany, and France, canned meats have accounted
tion, these studies established the safe food process- for the vast majority of outbreaks, whereas in Japan
ing practices that are now in widespread use by the and Russia home-preserved and pickled fish have
industry. been most commonly incriminated. In the United
States, low-acid canned vegetables, particularly
Geographic Distribution beans, peppers, and mushrooms, have been the most
A low incidence and sporadically occurring disease, common sources of botulism, with relatively few out-
botulism has been well documented in many parts of breaks traced to meat or fish. Most instances in all
the world, as indicated in Table VIII. 19.2. Although parts of the world are associated with improper
completeness of official reporting varies among coun- home canning or pickling, though the far more seri-
tries, hence preventing reliable estimates of true ous public health problem of botulism associated
distribution and incidence, it is clear that botulism with faulty commercial canning does continue to
is a disease with significant case fatality rates wher- occur.
ever reported. William H. Barker

VIII.20. Brucellosis 625
Bibliography melitensis. It is transmitted to human beings by
Arnon, Stephen S., Damus Karla, and James Chin. 1981. consumption of milk from infected goats; occasional
Infant botulism: Epidemiology and relation to sud- cases due to contamination of skin with infective
den infant death syndrome. Epidemiologic Reviews 3: material have also been observed. The mode of trans-
45-66. mission became established only during the first
Barker, William H., et al. 1977. Type B botulism outbreak decade of the twentieth century. In Malta and else-
caused by a commercial food product. Journal of the
where around the Mediterranean littoral, the dis-
American Medical Association 237: 456-9.
Merson, Michael H., and V. R. Dowell. 1973. Epidemio-
ease was endemic rather than epidemic during the
logic, clinical and laboratory aspects of wound botu- nineteenth century, its highest incidence occurring
lism. New England Journal of Medicine 289:1005-10. during the summer months. Officers of the services,
Meyer, K. F. 1956. The status of botulism as a world health and their wives and children, appeared to be more
problem. Bulletin of the World Health Organization susceptible than the lower ranks; and likewise
15: 281-98. among civilians, the professional classes suffered
Smith, Louis. 1977. Botulism: The organism, its toxins, the more than the laborers. Records going back to the
disease. Springfield, 111. mid-nineteenth century show very high annual mor-
U.S. Public Health Service. Centers for Disease Control. bidity rates, but low case-fatality rates.
1979. Botulism and the United States, 1899-1977: Other areas traditionally affected by undulant fe-
Handbook for epidemiologists, clinicians and labora-
ver due to B. melitensis show variations in epi-
tory workers. Atlanta.
demiological patterns. For example, in southeast
France where sheep and goats also vastly outnum-
ber cattle, the disease was still widespread in the
1930s. There it had more the character of an occupa-
tional disease than of a consumers' disease. The ma-
VIII.20 jority of cases occurred in the farming communities
and resulted from direct contact with infected ani-
Brucellosis mals and manure, although consumption of goats'
milk and of fresh cheese prepared from goats' or
ewes' milk also played some part.
Brucellosis, or undulant fever, is a zoonotic infection Present in all countries around the Mediterra-
caused in humans by organisms of three main spe- nean, brucellosis, caused by B. melitensis, is also
cies of the genus Brucella: Brucella melitensis, known in India, China, South Africa, and South
whose natural host is the goat; Brucella abortus, America. In 1918 Alice Evans suggested that the
transmitted largely from cattle; and Brucella suis, agent of the cattle disease known as contagious abor-
transmitted from pigs. Clinically, all three types tion was very similar to B. melitensis and might be
cause similar infections in humans characterized by capable of causing a similar disease in human popu-
intermittent waves of fever that may persist for lations. This was soon confirmed, and cases of
weeks, often with subsequent relapses and pro- brucellosis caused by B. abortus transmitted to hu-
longed periods of ill health. The causal relationship man beings by consumption of raw cows' milk have
between organism and disease was first recorded by occurred worldwide, especially in areas of high inci-
David Bruce in Malta in 1887; the name Malta fever, dence of epizootic abortion in cattle.
which reflects its prevalence among civilians and
British troops in that island in the nineteenth cen- The third major type of undulant fever is due to B.
tury, has been in general use for most of the present suis. As the name suggests, its natural host is the
century. More recently, other Brucella species have pig, and the human variety of the disease attacks
been found to be implicated in the human disease, mainly slaughterers and packers infected by han-
which has been shown to be widespread around the dling contaminated carcasses. In most cases, B. suis
globe. The terms "Malta fever" and "Mediterranean invades the human host through skin lesions, al-
fever" have been gradually replaced by undulant though airborne infection is also thought to be possi-
fever, or brucellosis. ble. The disease in pigs, and in human beings, is far
less common than its counterparts in goats and in
cattle, and therefore, undulant fever in human be-
Etiology and Epidemiology ings due to B. suis has been observed mainly in hog-
The type of brucellosis originally studied in Malta raising areas of the American Midwest, Brazil, and
and described by Bruce in 1887 is caused by B. the Argentine. Sporadic cases of undulant fever in

Alaskan Eskimos have resulted from a type of B. B. abortus, in particular, can give rise to latent
suis infecting wild reindeer. infection, leading to latent immunity, which occurs
more frequently in persons exposed to milk infection
Distribution and Incidence over a period of time than in those suddenly exposed
The three main types of Brucella infection in human to heavy doses of infective material. This may help
populations are widespread around the globe in ar- to explain the low rate of clinical disease in veteri-
eas dependent in one way or another on those domes- narians, who as a group show immunologic evidence
tic animals that are the main hosts of the respective of exceptionally high levels of response to erstwhile
organisms. Undulant fever caused by B. melitensis infection.
follows the distribution of goats all along the Medi- Vaccination is possible against B. abortus in cattle
terranean littoral (Malta or Mediterranean fever) as and against B. melitensis in sheep and goats, but in
well as in parts of China, India, South Africa, and human beings it is still at an experimental stage.
South America, although pasteurization of milk has Some knowledge of the immunogenic constituents of
substantially reduced its incidence during the sec- the bacillus has become available since the 1960s,
ond half of the twentieth century. The same applies but the animal vaccines developed thus far are too
to B. abortus infections. Contagious abortion of cat- toxic for use in humans. In Britain a free calf vacci-
tle, and with it the disease in humans, has been nation service was introduced by the Ministry of
almost completely eradicated from several countries Agriculture in 1962.
in northern Europe where the incidence is now very
low. The true incidence of B. abortus is difficult to Clinical Manifestations and Pathology
assess because it has low pathogenicity and often Undulant fever due to B. melitensis is essentially a
causes latent infections. septicemia or blood poisoning characterized by an ir-
In the United States, brucellosis is still not uncom- regular temperature curve with intermittent waves
mon, the causative organism being, in order of impor- of fever, usually lasting for 10 to 30 days. Although
tance, B. abortus, B. suis, and lastly B. melitensis. case fatality rates are low, the protracted character of
Most cases occur sporadically, although occasional many cases makes it a serious and debilitating ill-
minor outbreaks have been reported. Also, the situa- ness. Its duration varies; it may be only a few days, or
tion is constantly changing as a result, in part, to it may last as long as a year. Subsequent relapses
various eradication programs. may occur over a period of several years, accompa-
Bruce's discovery of the causal agent had no imme- nied by general ill health alternating with periods of
diate impact on the incidence of Malta fever; only apparent recovery. Symptoms included weakness,
after identification of the mode of transmission was muscular pain, nocturnal sweats, anorexia, chills,
there a dramatic fall in number of cases, first in the and nervous irritability. Recorded postmortem ap-
British armed services in Malta where supplies of pearances include congestion and enlargement of the
goats' milk to the troops were curtailed by 1906. In an liver and hypertrophy of the spleen; cultures taken
island where goats are the almost exclusive source of from both these organs have been found to be positive
milk, control of the disease in the civilian population for B. melitensis in 100 percent of cases.
was a much greater problem. It was achieved, in B. abortus appears to be less capable than B.
Malta and elsewhere, only after World War II, when melitensis of producing clinical cases in humans, but
pasteurization became generally accepted. more likely to give rise to latent infection, especially
in veterinarians. Once established, however, the
Immunology clinical disease seems to develop in similar fashion.
The failure of the immune systems of both animals It lasts an average of 13 weeks and may become
and humans to deal quickly and decisively with B. chronic. B. abortus can also cause a short influenza-
melitensis and B. abortus accounts for the persis- like illness, and sometimes a persistent low intermit-
tence of infection and thus frequent cases of long tent fever. In rare cases, infection in pregnant
duration. Evans, who first drew attention to the women has been followed by abortion.
similarities between the two organisms, contracted Undulant fever caused by B. suis is clinically simi-
a laboratory infection with the disease in 1922 and lar to the above types.
suffered recurring episodes of debilitating undulant
fever, alternative with periods of apparent recovery, History and Geography
for more than 20 years (in spite of this she lived, Among the fevers plaguing the Mediterranean peo-
after final recovery, until the age of 94). ples since antiquity, a low type with regular remis-

VIII.20. Brucellosis 627
sions or intermissions has been recorded since the 1009. 1907.

time of the Hippocratic writings. Its geographic ori-
gins are indicated by many synonyms of which the
best known are Malta fever and Mediterranean fe-
ver, although other variants involve Naples, Con-
stantinople, Crete, and Gibraltar. A differential de-
scription of Malta fever as distinct from other fevers
was first given by J. A. Marston in 1863; he called it
"gastric remittent fever" and described several cases
including his own ("a mild case of gastric remittent
fever"). In 1887, Bruce, a surgeon attached to the
Malta garrison like Marston before him, recorded
his discovery of a small microorganism in the spleen
of fatal cases. He proceeded to establish its causal
role and called it Micrococcus melitensis, although in
the 1920s it was changed to Brucella melitensis in
his honor. Returning from duty in Malta, Bruce
taught at the Army Medical College at Netley;
among his students was Matthew Louis Hughes
who, posted to Malta in 1890, enthusiastically em- I>4:1 C A S K S . 7 CASKS.
braced Bruce's interest in the prevailing fever. He

wrote, both alone and in collaboration with Bruce, Figure VIII.20.1. Graphs illustrating the dramatic reduc-
tion in the incidence of brucellosis in the British garri-
several papers dealing with the disease during the son in Malta from 1905 to 1907, following the ban on
next decade, until he died under enemy fire while the use of goat's milk. (From D. Bruce 1908.)
tending casualties in South Africa at Ladysmith in
December 1899. It was Hughes (1897) who published
a definitive clinical description of Malta fever, which
is still quoted today as a model of its kind. before the goat was identified as the natural host of
Since the time of Bruce, and because of the pres- B. melitensis and the mechanism of transmission to
ence of British troops in the island, the disease and humans became clear. In the case of B. abortus infec-
its epidemiology have received particular attention tions, the historical sequence of events was rather
in Malta, culminating in the work of the British different. The disease in cattle had been described by
Mediterranean Fever Commission, which began re- several authors during the first half of the nine-
porting in 1905. During this work, Themistocles teenth century. In the context of the times some
Zammit was able to establish the presence of the considered it contagious, others not. Its transmissi-
disease in local goats and the role of goats' milk in bility was demonstrated in pregnant cattle in 1878;
transmitting the disease to the human population. and just before the turn of the century Bernhard
The results of his research caused the British army Bang in Copenhagen was able to isolate and identify
and navy to prevent troops from drinking goats' the causal agent. It was only in 1918, however, that
milk; within a year the disease had all but disap- Evans noted a close morphological and biochemical
peared from the British forces in Malta (see Figure similarity between B. melitensis and B. abortus;
VIII.20.1). As already mentioned, for social and eco- within a few years B. abortus had been shown to be
nomic reasons control of the disease in the civilian pathogenic for human beings and to give rise to
population proved far more difficult to achieve; only cases of undulant fever in many areas around the
the advent of pasteurization could eventually solve world where raw cows' milk rather than goats' milk
this problem, although it should be noted that the was consumed, and where epizootic abortion of cattle
disease in goats is still resisting control. was a common occurrence.
B. melitensis infections had been observed and Last of the major types of undulant fever to attract
described in the late 1800s, following Robert Koch's attention was that caused by B. suis. The first case
epoch-making demonstration of the methods for iso- to be diagnosed appears to have been in the United
lating and identifying specific disease agents. It was States in 1922, although even then the identity of
Bruce, however, who isolated the causal microorgan- the agent was not immediately recognized. Clini-
ism in 1887. Nearly two more decades were to elapse cally (and bacteriologically) the disease is similar to

the two other major types although it is less exten-
sively distributed in either pigs or humans. B. suis VIII.21
infection of swine first began to cause concern in the Bubonic Plague
large hog-raising areas of the midwestern United
States in the 1930s. The disease has since been re-
ported to be present in a number of other countries, Plague has often been used as a synonym for pesti-
but cases appear to be mostly sporadic, with only a lence, which refers nonspecifically to any acute epi-
few recognized outbreaks in the United States, and demic accompanied by high mortality. But the term
one in Denmark in 1929. also refers to the recurrent waves of bubonic plague
Lise Wilkinson punctuating European history from 1348 to 1720.
Bubonic plague epidemics occurred when Yersin-
Bibliography ia pestis, a rodent disease, was communicated to
Bruce, David. 1908. The extinction of Malta fever. London. humans through the bite of infected fleas. Humans
Dudley, S. F. 1931. Some lessons of the distribution of have exceedingly poor immune defenses to this or-
infectious diseases in the Royal Navy. Lecture III. The ganism, and within 6 days of infection most victims
history of undulant fever in the Royal Navy. Lancet i: develop a grossly swollen lymph node, a bubo, signi-
683-91. fying the body's attempt to contain and arrest multi-
Duguid, J. P., B. P. Marmion, and R. H. A. Swain. 1978. plication of Y. pestis. On the average, around 60
Mackie and McCartney's medical microbiology. Edin- percent of those infected died within a week after the
burgh. appearance of the bubo. Thus bubonic plague
Evans, Alice. 1918. Further studies on Bacterium abortus brought high and dramatic rates of mortality when
and related bacteria II. A comparison of Bacterium
it extended into human communities.
abortus with Bacterium bronchisepticus and with the
organism which causes Malta fever. Journal of Infec-
tious Diseases 22:580-93.
Hughes, G. W. G., and M. H. Hughes. 1969. Matthew Louis Distribution and Incidence
Hughes and undulant fever. Journal of the Royal With the historically ironic exception of western Eu-
Army Medical Corps 115: 198-203. rope, Y. pestis today occurs naturally throughout the
Hughes, M. L. 1897. Mediterranean, Malta or undulant world among the wide variety of rodents and
fever. London. lagomorphs (i.e., rabbits and related species). Some
Huntley, B. E., R. N. Philip, and J. E. Maynard. 1963. of the more than 300 rodent species affected are
Survey of brucellosis in Alaska. Journal of Infectious relatively resistant to disease from Y. pestis and can
Diseases 112: 100-6. survive and reproduce while technically infected by
Hutyra, Franz, J. Marek, and R. Manninger. 1938. Special the organism. Y. pestis infects new animals either
pathology and therapeutics of the diseases of domestic because fleas transmit it or because the microbe is
animals. London. shed and survives in the protective microclimate of
Marston, Jeffery Allen. 1863. Report on fever (Malta). warm rodent burrows. Some literature refers to this
Army Medical Department Statistical Report 3: 486-
521.
part of the plague cycle as "sylvatic" plague, or
Meyer, M. E. 1964. Species identity and epidemiology of "enzootic" plague.
Brucella strains isolated from Alaskan Eskimos. Jour- The "disease," then, is not always a disease, and it
nal of Infectious Diseases 114: 169-73. is ecologically very complex. Indeed, it is occasional
Roux, J. 1972. Les Vaccinations dans les brucelloses ecological change or disturbance that brings suscep-
humaines et animales. Bulletin de I'Institut Pasteur tible rodents into contact with Y. pestis. Historically
70: 145-202. the most important of these rodents is considered to
Thomsen, Axel. 1934. Brucella infection in swine: Studies be Rattus rattus, the common, commensal black or
from an epizootic in Denmark 1929-1932. Copenha- brown house rat, that literally "shares man's table."
gen. When infected by Y. pestis these susceptible animals
Wilson, Graham, and Geoffrey Smith. 1983-4. Brucella die quickly of an overwhelming infection, with blood
infections of man and animals. In Bacterial diseases, levels of the microbe so high that their rat fleas
Vol. 3 of Principles of bacteriology, virology and immu-
nity, ed. G. R. Smith, W. W. C. Topley, and G. S.
imbibe large numbers of organisms.
Wilson, 141-69. London. The oriental rat flea Xenopsylla cheopis and the
World Health Organization. 1964. Expert committee on human flea Pulex irritans are thought to be histori-
brucellosis. World Health Organization Technical Re- cally important arthropod vectors transmitting
port Series, No. 289. "epizootic" plague to humans. X. cheopis is an effi-

VIII.21. Bubonic Plague 629
cient vector because a bend in its feeding tube, or very mild plague strains. Y. pestis causes severe
proventriculus, creates a location for growth of Y. human disease when it contains an envelope protein
pestis, such that the flea becomes "blocked," unable facilitating its entry into cells and other antigens
to swallow a full blood meal. Attempting to dislodge that impede the body's white blood cells' attempt to
this bolus or wad, the flea infects new mammalian kill infected cells. Y. pestis can liberate both endo-
hosts. Other fleas clear Y. pestis more quickly, so toxins and exotoxins, leading to circulatory collapse.
that only the excreta of the flea, or the crushing of These combined activities stimulate, and can defeat,
its body, will infect. P. irritans had an important both cellular and humoral immunity to plague, and
historical role because it is a flea that feeds indiffer- explain why the disease can carry extremely high-
ently upon both humans and the common house rat. case fatality rates. With a typical virulent strain of
Human plague usually arises after an epizootic the bacterium, over 60 percent of all infected hu-
plague has produced high mortality among suscepti- mans untreated will die within 10 days of infection.
ble rodents, when infected fleas, deprived of rodent If the organism reaches the lungs, there is even less
hosts, begin to feed on humans. Although some histo- chance the person will survive. A victim whose
rians speak of "endemic plague," no such phenome- lungs become infected during the course of bubonic
non can exist. Humans do not normally carry the Y. plague can cough out highly virulent, encapsulated
pestis organism, and thus cannot infectfleasor other- organisms, which are rapidly absorbed on the mu-
wise pass the disease to new hosts. For human com- cous membranes of any nearby, susceptible person.
munities, plague is an acute infection ultimately This can lead to "primary" pneumonic plague in
derived from infected rodents. which the bubonic plague of disease is bypassed and
In areas of the world today where plague routinely spreads directly from human to human. When this
infects resistant rodents, ecologists and public has occurred, case fatality rates have been close to
health officials try to monitor the passage of the 100 percent.
disease to susceptible species. In these regions - the
American southwest, south central Eurasia, and Clinical Manifestations and Diagnosis
Southeast Asia - humans who are likely to encoun- Once a human is infected with Y. pestis, the organ-
ter infected animals or their fleas must be revacci- ism rapidly replicates a t the site of the flea bite. This
nated often, for human immunity to Y. pestis is area can subsequently become necrotic, where dead
short-lived. tissue blackens to produce a carbuncle or necrotic
pustule often called a "carbone" in many historical
Immunity accounts. But in many cases the progress of infection
Yersinia pestis was once called Pasturella pestis, a is too rapid for this to happen. The lymphatic system
name that has persisted because it was used in much attempts to drain the infection to the regional lymph
of the older, widely consulted, historical literature node, where organisms and infected cells can be
about European plagues. In 1971, the name was phagocytized (ingested by macrophages and white
changed in part to honor Alexandre Yersin, a French blood cells). That node becomes engorged with blood
microbiologist and student of Louis Pasteur, who, and cellular debris, creating the grossly swollen
working in Southeast Asia during the late nine- bubo. Because infected fleas usually bite an exposed
teenth century outbreak of plague, successfully cul- area of the body, often a limb or the face, the location
tured the microorganism. of the subsequent bubo is often visible. Frequent
Other members of the Pasturella family are rarely sites are the groin, the axilla, or the cervical lymph
pathogenic in humans and do not provide cross- nodes.
immunization with Y. pestis. Two organisms, how- But drainage can occur to an internal lymph node,
ever, have been added to the Yersinia group: Yersinia or the infection can proceed too rapidly for the lym-
pseudotuberculosis, which causes a mild respiratory phatic system to effect a defense. In the latter case,
infection, and Yersinia enterocolitica, which causes a "septicemic" or blood-borne plague has occurred,
gastroenteritis that can be life-threatening in very seeding the organism quickly in many organs. Vic-
young children. Infection with either of the other tims of septicemic plague become rapidly moribund
Yersinia species establishes some cross-immunity and often develop neither eschar nor bubos, al-
with Y. pestis, because they have shared antigens. though the more usual clinical course is the forma-
The antigens, or components of the organism, tion of a bubo, described in historical accounts as
which stimulate an immune response, can vary in reaching the size of an egg, orange, or even grape-
virulence, such that vaccines can be created that are fruit. The area is inflamed, boggy or doughy to the

touch, and exquisitely painful. Patients often de- however, and any bibliography assembled on impor-
manded that a physician or surgeon incise and drain tant European works dealing with this second cycle
the bubo, a process that could have liberated infec- would contain several hundred listings.
tive organisms. This is the case because the plague has been
The bubo often appears within 4 to 6 days after viewed as pivotal in so many areas of historical
infection, and because of the multiple ways in which inquiry. Surely it was to some significant extent
Y. pestis is virulent to humans, disease progresses responsible for the stagnant demographic perfor-
quickly after this point. In about 5 to 15 percent of mance in Europe prior to the mid-eighteenth cen-
the cases the lungs are infected, but more often a tury, and surely, too, the plague stimulated new and
high fever with headache and mental disorientation important public health efforts in the great urban
are characteristic symptoms. Occasionally circula- centers of Europe. In addition, the continued pres-
tory collapse and hemorrhagic sepsis occurs, blacken- ence of the disease in Europe presents a mystery
ing the surface of the body. Death typically occurs because a t no other time in history was the disease
within 4 to 6 days after the onset of symptoms. In the able to survive in northern Europe without constant
past, a diagnosis of plague might have been made on reintroduction from the Middle East. Finally, over
the basis of this rapid clinical progression from the course of a half millennium the plague was the
health to death alone, although clearly this could source of inspiration for numerous literary works,
have been caused by countless other conditions. But and more than a few on medicine.
the acute formation of a bubo, visible in 60 percent of Historians frequently credit public health mea-
bubonic plague victims, is pathognomonic of plague, sures devised during the fifteenth through the seven-
meaning that no other disease commonly causes this teenth centuries to combat the plague with some
reaction. mitigation of the disease and its ultimate disappear-
ance. However, in the light of modern medical knowl-
History and Geography edge of bubonic plague, it is clear that such
Most of the historical literature of plague identifies measures — quarantine of well individuals, isolation
three lengthy time periods when bubonic plague re- of the sick and their household contacts, large
peatedly assaulted human communities. The first pesthouses or lazarettoes, and even the elaboration
known cycle of widespread human plague occurred of a theory of contagion - would have little effect on
during late Greco-Roman antiquity. Byzantine histo- its course.
rian Procopius of Caesarea described the acute Certainly the most important questions about
lymphadenopathy well: "Those in whom the bubo these 500 years of plague in Europe have to do with
grew to the largest size and suppurated while ripen- its disappearance and demographic consequences.
ing usually survived, no doubt because the malig- In the latter case, it is important to realize that
nant property of the already weakened boil was anni- much of the mortality credited to the plague was
hilated" (quoted in Biraben and Le Goff 1975). Proco- due to its indirect impact, rather than infection.
pius described the devastating epidemic of 542 in When an epidemic struck, panic ensued and this
Constantinople, which was dubbed the "Plague of alone, by bringing an end to normal sanitary and
Justinian" because of his dramatic account. The social services while precipitating headlong flight,
wave of epidemic reached western Europe by 547, would have taken a significant number of lives, as
which was also powerfully described by Bishop Greg- would isolating both ill and well in hospitals and
ory of Tours. Virulent, epidemic plague recurred pesthouses. Chief among these victims would have
throughout the Mediterranean for the next 200 been the very young, the very old, and the economi-
years. cally disadvantaged.
The second cycle of plague, at least in its early Beginning in the early eighteenth century, Europe
stages, is often referred to as the Black Death and is was increasingly protected from plague invasions
treated in this work as a separate entry, for certainly from Ottoman lands by a staunch Austrian barrier.
it is the most heavily studied of the plague cycles. Manned by over 100,000 men and featuring numer-
Beginning about 1300, the cycle is generally consid- ous quarantine and checkpoint stations, this famous
ered to have ended at about 1800, although the end- sanitary cordon limited both trade and human traf-
ing date can be disputed. This manifestation of the fic, which may have helped to spare Europe from the
disease took a very heavy toll in the Middle East as third or most recent cycle of the plague that seems to
well as in Europe and appears to have also invaded have had its beginning in central Asia about the
Asia. It has held a special fascination for Europeans, middle of the eighteenth century (Benedict 1988).

VIII.22. Carrion's Disease 631
From there the plague spread to the Yunnan region Pollitzer, R. 1954. Plague. Geneva, WHO.
of China and simultaneously to northern India and, Rothenberg, Gunther E. 1973. The Austrian sanitary cor-
then, aided by rapid sea transportation, radiated don and the control of the bubonic plague: 1710-1871.
globally from Hong Kong, Bombay, and Calcutta. Journal of the History of Medicine and Allied Sciences
But if Europe was bypassed, the Americas were 28: 15-23.
Shadwell, Arthur, and Harriet L. Hennessy. 1910. Plague.
not. Rather, along with Australia and eastern Af-
In Encyclopedia Britannica, 11th edition.
rica, North and South America were infected for the Shrewsbury, J. F. D. 1970. A history of bubonic plague in
first time, and by the early years of the nineteenth the British Isles. Cambridge.
century some regions of the Western Hemisphere Slack, Paul. 1985. The impact of plague in Tudor and
were experiencing relatively minor, but nonetheless Stuart England. London.
panic-inspiring, epidemics. Those that struck San Winslow, Charles-Edward Amory. 1980. The conquest of
Francisco are among the best documented in this epidemic disease. Reprint of 1943 edition. Madison,
pandemic cycle, although the disease killed millions Wis.
in India and in African countries.
If the Americas and Australia did not suffer
greatly from this third cycle of the plague, one conse-
quence was that the disease did establish itself
among the rodents and lagomorphs of these New
Worlds. In North America the geographic extent of VIII.22
the plague has subsequently widened each year, and
sporadic cases of human plague claim 8 to 15 victims Carrion's Disease
annually despite the effectiveness of therapy with
antibiotics such as tetracycline and streptomycin. In
the Americas, as elsewhere, smoldering enzootic foci Carrion's disease is an infectious disease caused by a
of plague demand a constant global effort in surveil- microorganism of the genus Bartonella. Two species
lance and control. have been described, the bacilliformis type and the
Ann G. Carmichael verrugiformis type. These bacteria are parasites of
human red blood and histiocytic cells. The ba-
cilliformis type produces two stages of the disease, a
Bibliography febrile acute hemolytic anemia known as "Oroya
Appleby, Andrew B. 1980. The disappearance of plague: fever," followed by a granulomatous mucocutaneous
A continuing puzzle. Economic History Review 33: eruption known as "Verruga Peruana." The verrugi-
161-73. formis type produces only the verrucose stage.
Benedict, Carol. 1988. Bubonic plague in nineteenth-
century China. Modern China 14: 107-55.
Biraben, Jean-Noel. 1975—6. Les Hommes et la peste, 2
vols. Paris.
Biraben, Jean-Noel, and Jacques Le Goff. 1975. The B. bacilliformis are pleomorphic bacteria, well
plague in the early Middle Ages, trans. E. Forster and stained with the Romanovsky stain. In the red blood
P. M. Ranum. In Biology of man in history: Selections cells and in the histiocytic cells, the bartonella as-
from the Annales; Economies, Societes, Civilisations. sumes a rodlike (bacillus) or coccoid shape, 1 to 3
Baltimore. microns in size (Figure VIII.22.1). The electron mi-
Carmichael, Ann G. 1986. Plague and the poor in Renais- croscope shows the flagella of the bartonella. It
sance Florence. New York. grows well in liquid and in semisolid blood media.
Ell, Stephen R. 1980. Interhuman transmission of medi- The human bartonella is closely related to the ani-
eval plague. Bulletin of the History of Medicine 54: mal bacteria Hemobartonella, Eperythrozoon, and
497-510. Grahamella.
Hirst, L. Fabian. 1953. The conquest of plague: A study of
the evolution of epidemiology. Oxford.
In 1913 Charles Townsend identified the sandfly
Link, Vernon. 1953. A history of plague in the United Phlebotomus verrucarum as the insect vector of the
States of America. U.S.P.H.S. Public Health Mono- disease. The female is the only transmitter, and the
graph No. 26. Washington, D.C. transmission occurs during the night. Carrion's dis-
1977. The plague reconsidered: A new look at its origins ease is a rural disease, and, like yellow fever, it does
and effects in 16th and 17th century England. Local not need a human reservoir because the bartonella
Population Studies Supplement. Derbyshire. lives in the small animals in the area.

person to a healthy person does not effect transmis-
sion of the disease. Rather the inoculation of a live
germ appears to produce immunity. Third and last,
direct inoculation of the B. baciliformis into a
splenectomized patient produces the disease, with
bartonellas evident within the erythrocytes and
blood cultures testing positive.
There are two stages in Carrion's disease: the "ane-
mic stage," characterized by an acute febrile anemia
with bartonellas in the red blood cells; and the
"verrucose stage," characterized by a disseminated
verrucous eruption in the skin and mucous mem-
branes. The anemia is of the macrocytic and
hypochromic types, and, in severe infection, erythro-
cyte levels plummet to less than a million in a few
days. The parasitic index in these cells reaches 80 to
100 percent.
Figure VIII.22.1. Bartonella bacilliformis within red
blood cells stained by Giemsa and Romanovsky stains. The onset is abrupt, with fever, chills, and general-
(From O. Urteaga-Ball6n and J. Calder6n. 1972. ized osteal pain. Bone marrow hyperplasia, reticulo-
Dermatologia Clinica, by permission of the author.) cytosis, and jaundice are observed, with an increase
of bilirubin in the blood and urine. The blood culture
is positive, even in the earliest days of the anemia.
Immunology (Experimental Transmission) The verrucose stage is characterized by a diffuse
Between 1948 and 1950, the author and collabora- generalized granulomatous eruption on the mucocu-
tors conducted a series of experimental transmission taneous integument. Usually this phase is separated
on human volunteers. Thirty healthy men were in- from the anemic stage by an asymptomatic interval
oculated with parasitic blood through subcutaneous, of several months to a year or more. There are sev-
intramuscular, and intravenous routes. None of the eral types of eruption. The first, called the "miliary
volunteers developed the disease, and the blood cul- form," is a profuse, homogeneous, small intradermic
ture remained negative after more than 120 days. eruption, which resembles multiple disseminated he-
Another four volunteers who had been splenecto- mangioma. In the second, the "nodular form," nod-
mized for other reasons were infected with the same ules appear primarily on the arms and the legs; they
inoculum. All of them developed the disease, with can be deep in the dermis or prominent on the sur-
bartonellas evident in the erythrocytes and blood face of skin; some are ulcerated and bloody. The
cultures positive. Antibiotics halted the parasitism, third type, the "mular form," has pseudotumoral
and the volunteers recovered immediately. lesions V2 to 1 inch in diameter which are seated in
After our experiments, three of the former healthy the deep tissue. The eruption become painful only
volunteers were exposed to the bite of the insect in when a secondary infection develops or with in-
the verrucogenous zone. None of them developed the creased bleeding (Figure VIII.22.2A-C).
disease. They appeared to have developed immunity In the uerrugiformis type, the clinical picture is
as a result of the previous live inoculation. Later on, that of a diffuse granulomatous eruption similar to
10 workers out of a group of 100 were inoculated the bacilliformis type, but less intense. One special
with attenuated live bartonellas in order to test a feature of the verrugiformis type is that the eruption
vaccine against the disease. None of them developed can recur two or more times during a lifetime; some
any symptoms, and the blood cultures remained of these patients of endemic areas become latently
negative. Meanwhile 45 of their companions who infected.
were not vaccinated developed the disease.
Our conclusions were as follows: First, the natural Pathology
infection of the bartonellosis occurs only through the The main pathogenic feature is the intracellular re-
sandfly vector. Second, the inoculation from a sick production of the bartonella inside the cytoplasm of

VIII.22. Carrion's Disease 633
Figure VIII.22.3. Intracellular reproduction cycle of the

Bartonella bacilliformis (top) the cytoplasm of a
histiocytic bone marrow cell, and (bottom) the
endothelial cells of a lymph node. (From O. Urteaga-
Ballon and J. Calderon. 1972. Dermatologia Clinica, by
Figure VIII.22.2. Verrucose eruptions: (top) miliary
permission of the author.)
form, diffuse and generalized; (middle) nodular form,
two intradermic nodules; (bottom) mular form. In the
pseudotumoral eruption (bottom), the granulomatous which then start a new intracellular colonization in
lesions are seated in the deep tissue; sometimes the other endothelial cells. Also, the bartonellas act as
eruption becomes painful when a secondary infection de- parasites on the peripheral erythrocytes, inducing
velops or when bleeding increases. (From O. Urteaga- the anemia syndrome.
Ballon and J. Calderbn. 1972. Dermatologia Clinica, by
Histopathological study of the anemia of Carrion's
permission of the author.)
disease reveals massive hyperplasia of the phago-
cytic reticuloendothelial cells in the spleen, lymph
the endothelial cell. Microscopically these cells are nodes, liver, and bone marrow. Erythrophagocytosis
swollen with tremendous numbers of bacteria, is responsible for the anemia. The macrophages ini-
which push the nucleus of the cell eccentrically (Fig- tiate the destruction of the parasitized erythrocytes.
ure VIII.22.3A,B). The pressure resulting from the The extraordinary phagocytic hyperplasia character-
multiplication of the bartonellas causes the cell izes the cellular immunoresponse of this disease. The
membrane to rupture, releasing millions of bacteria, macrophages contain, in their cytoplasm, 2 to 10

patient dies after physical collapse. Another 40 per-
cent die from secondary complications. The nonspe-
cific immunoreaction decreases to the "anergic
stages," but some quiescent chronic infection in the
patient will exacerbate to an acute stage. The most
frequent complications are salmonellosis, tuberculo-
sis, malaria, and amebiasis in carrier cases.
From the clinical point of view, the patient has
recovered. He or she appears to be normal, but the
bartonellas still live in the adventitial cells sur-
rounding the subcutaneous capillaries. Blood and
bone marrow cultures are still positive. There is an
unstable balance between the intracellular bacteria
and the immune response. In time, when this equilib-
rium breaks down, the bartonellas start a new cycle
of reproduction in the histiocytes. The second stage
of the disease appears as a disseminated verrucose
eruption. This histiocytic proliferation, with the in
situ presence of the microorganism, is a clear exam-
ple of cellular immunity. Sometimes the histiocytic
proliferation is so great that the lesion appears like
a tumor, a histiocytic lymphoma.
The histopathology of the granulomatous phase
shows an angioblastic proliferation with large, pale
histiocytes and endothelial cells, some filled with
coccobacillus bartonellas. The rupture of these cells
results in the dissemination of the bartonellas
through the skin, with the appearance of new
verrucose eruptions. The eruptive phase tends to
heal spontaneously without scars.
Diagnosis and Treatment

Figure VIII.22.4. Erythrophagocytosis of parasitized The diagnosis is made upon a finding of bartonellas
erythrocytes in (top) peripheral blood; and (bottom) within the red blood cells in acutely anemic patients.
spleen. Bottom panel, showing extraordinary phagocytic Blood and bone marrow cultures are the most useful
hyperplasia, and macrophages containing more than 10 diagnostic test for carrier cases in the endemic
erythrocytes, illustrates the mechanism responsible for zones. The eruptive phase is easily identified with
the anemia. (From O. Urteaga-Ball6n and J. Calder6n. some clinical experience, but surgical biopsy is re-
1972. Dermatologia Clinica, by permission of the
author.)
quired to show the bartonella inside the histiocytes
in the Giemsa stain. The cultured tissue is positive.
Before the advent of antibiotics the mortality rate
erythrocytes with bartonellas (Figures VIII.22.4 from Carrion's disease was very high. In acute se-
A,B)- Severe cases show thrombosis and infarction in vere cases, 30 to 70 percent of patients died in the
the spleen, centrolobular necrosis of the liver, and anemic phase, either directly from the bartonella
lung congestion. infection or from secondary complications. Antibiot-
At the end of the anemia stage, an immunore- ics have a powerful antibactericidal effect; the ane-
sponse is mounted against the active basilar bar- mia is arrested, and blood regeneration starts imme-
tonellas, which then are converted to the resistant diately. Until now, chloromycetin has been the most
coccoid stage. This is the most dangerous period of effective antibiotic in the anemic stage, because it is
the disease. The "anoxemia" is extremely severe, also specific for salmonellosis, the most serious com-
with the red blood cell count falling to below 1 mil- plication. Streptomycin is the ideal antibiotic during
lion. In at least 30 percent of the cases, the untreated the eruptive phase. In 4 to 5 days, the eruption

VIII.23. Catarrh 635
shrinks and the verrucose nodes subside without Strong, R., et al. 1913. Report of the first expedition to
any scar. South America. Cambridge.
According to our experiments a specific vaccine Townsend, Charles. 1913. La titira es transmisora de la
must be prepared with attenuated live bartonellas. verruga. La Crdnica Midica Lima 30: 588-600.
However, it must be kept in mind that the live germ Urteaga-Ball6n, O., and J. Calder6n. 1965. Ciclo biol6gico
vaccine will produce the acute anemic phase in de reproduccidn de la "Bartonella baciliformis" en los
tejidos de los pacientes de verruga peruana o
splenectomized patients. enfermedad de Carri6n. Archivos Peruanos de Pato-
logia y Cllnica 19: 1-77.
History and Geography 1972. Verruga Peruana o enfermedad de Carri6n. In
Carri6n's disease was probably depicted thousands Dermatologla Cllnica, ed. Jos6 Luis Cort6s, Cap. 54,
of years ago in the pottery of the ancient Peruvian 2d edition. Tlacotalpan, Mexico.
civilization. The diseaseflourishedjointly with ma-
laria and cutaneous leishmaniasis in the inter-
Andean valleys of western South America. The focus
of the endemic transmission is in Peru, although
some cases exist in Colombia and Ecuador. The en-
demic areas of the disease are confined to rural areas VIII.23
in narrow valleys where the elevation is 2,100 to Catarrh
7,500 feet.
The disease in both its forms was probably noticed
and described during the Spanish Conquest. It at- Catarrh is now regarded as inflammation of the mu-
tracted worldwide attention only in 1870, when an cous membranes, especially of the air passages, to-
epidemic of the acute febrile form of the disease gether with the production of a mucoid exudate.
killed thousands of workers during the construction Simple though this definition is, it bears evident
of a railroad from Lima to Oroya. In 1885, Daniel traces of the history of the disease.
Carri6n, a Peruvian medical student, contracted the
disease by self-inoculation with verruga and died of
Oroya fever, thus establishing the connection be- History
tween the two conditions. In 1909 Alberto Barton, a The name derives from Hippocrates' use of katarr-
Peruvian physician, described the presence of live hoos, "aflowingdown" of humors from the head. In
organisms in the red blood corpuscles of victims of that use, the term was probably not yet technical,
Oroya fever, and a decade later these findings were and so akin to such a Latin word as defluxio. In
confirmed by R. P. Strong and his colleagues (1913). commenting on Hippocrates, however, Galen distin-
They, however, felt that despite the work of Carridn, guishes from a general "downflowing" a more pre-
Oroya fever and verruga peruana were caused by cise meaning of "catarrh" - that is, a defluxion from
two distinct agents. The controversy was resolved by the head to the lungs, producing a hoarseness of
H. Noguchi and T. Battistine (1926), who reported voice and coughing.
the pair to be different manifestations of the same The Greek word became catarrhus in Latin and a
disease. M. Hertig in 1942 definitively described technical term with, increasingly, Galen's meaning
both the disease and its vector. attached to it. Although it is tempting to identify
Oscar Urteaga-Balldn
catarrhus and catarrh, we have to remember that for
Galen and doctors down to the seventeenth century,
catarrhus could not be defined without reference to
Bibliography Galenic pathology. Catarrhus was a process in which
Aldana, L., and O. Urteaga-Ball6n. 1947. Bartonellosis the brain, preternaturally affected by cold, produced
post-esplenectomia. Archivos Peruanos de Patologia y
a qualitatively unbalanced humor in excessive quan-
Cllnica 1: 289-312.
tity that passed down through the pores in the pal-
Barton, A. 1909. Descripci6n de elementos endo globulares
hallados en los enfermos de fiebre verrucosa. La
ate and by way of the trachea to the lungs. This
Crdnica Midica Lima 26: 7-17. unspoken assumption behind the name is paralleled
Noguchi, H., and T. Battistine. 1926. The etiology of Oroya by that behind the modern definition: We make the
fever. I. Cultivation of "Bartonella baciliformis." Jour- assumption that the "inflammation" of the defini-
nal of Experimental Medicine 49: 851-64. tion is due to infection by an organism. It is the

identity of the organism that gives us the ontology of Le Boe, Franciscus de (F. Sylvius). 1693. Opera medica.
the disease. A similar situation existed in all histori- Geneva.
cal periods; that is to say, definitions of disease have Maulitz, R. 1987. Morbid appearances. Cambridge.
always carried with them some part of a theory of Sweiten, G. van. 1792. Indicis in swieteni commen-
causation. (Purely empirical accounts of disease are tariorum tomos undecim supplementum. Wurtzburg.
descriptions of symptoms.) To put it another way,
disease in Western medicine has traditionally been
seen as disordered function. But function is a pro-
cess, and knowledge of it depends on knowledge of
how the body works. VIII.24
In the eighteenth and nineteenth centuries, there
were a number of different so-called systems of Cestode Infections
physiological knowledge, in each of which what was
indicated by a single disease-name was seen differ-
ently. For example Franciscus de Le Boe (F. Cestodes or tapeworms are a class of flatworms in
Sylvius), as an iatrochemist, divided catarrhs into the phylum Platyhelminthes. The adult stages of
groups distinguished by the chemical qualities of four species and the larval stages of two are impor-
the humor produced. As a hydraulically inclined tant parasites of humankind. Several other species,
mechanist, Hermann Boerhaave thought of catarrh most of which normally parasitize other vertebrates,
in terms of obstruction of the small vessels, which can also cause human disease.
caused swelling. Indeed, his most frequent use of K. David Patterson
the term was as an adjective to describe angina.
"Angina" was any difficulty in breathing, and ca-
tarrhous angina was the result of swollen mem-
branes. Although membranes also played an impor-
tant part in the new tissue-pathology of early VIII.25
nineteenth-century Paris, the Parisian view of the
body, and therefore disease, was again different. Chagas' Disease
Marie Francois Bichat had stressed the sympathies
between membranes and their ability to secrete and
imbibe the fluids of the cavity they lined. To this Chagas' disease (American; trypanosomiasis, trypa-
were added the new techniques of physical diagno- nosomiasis cruzi) is an illness of the Americas which
sis by percussion and stethoscope. can take the form of either an acute, febrile, general-
Catarrh again became a disease of membranes, of ized infection or a chronic process. The cause is a
excessive secretion, and of fluids moving audibly in protozoan, Trypanosoma cruzi, which is harbored by
their cavities. Some Bichatian sympathy of mem- both domesticated and wild animals. When it is
branes seems to lie behind the early nineteenth- transmitted to humans by insects, this essentially
century notion of a catarrh of the urinary bladder. untreatable disease is associated with fever, edemas,
This opinion is recorded in R. Hooper's Lexicon and enlargement of the lymph nodes and can cause
Medicum, which also distinguishes sharply common dilation of parts of the digestive tract leading to
catarrh, which is a cold and particularly a cold in the megacolon and megaesophagus as well as cardiac
head, from epidemic catarrh, which is identified enlargement and failure. In fact, Chagas' disease is
with influenza. The modern meaning is derived from the leading cause of cardiac death of young adults in
the former. parts of South America.
Roger K. French
The disease, which probably had its origins in Bra-
Bibliography
Blakiston's Gould medical dictionary. 1972. 3d edition.
zil, is limited to the Western Hemisphere, with
New York. heavy concentrations in Brazil, Argentina, Chile,
Boerhaave, H. 1728. Aphorismi de cognoscendis et and Venezuela. Cases are also reported in Peru, Mex-
curandis morbis. Paris. ico, and most other Central and South American
Hooper, R. 1848. Lexicon medicum, or medical dictionary. countries along with the Caribbean islands and the
London. United States.

VIII.25. Chagas' Disease 637
Epidemiology and Etiology The subacute form of Chagas' disease is normally

T. cruzi, a member of the class Mastigophora, family seen in young adults who suffer a rapidly progres-
Trypanisomidae, has over 100 vertebrate hosts in- sive cardiac failure.
cluding dogs, cats, armadillos, opossums, monkeys, The chronic form of the illness is the leading cause
and humans. Unlike other trypanosomes it does not of death in endemic areas. The heart becomes tre-
multiply in the bloodstream, but rather lives within mendously enlarged, and in about 30 percent of the
various tissues of the host and multiplies by binary cases, parasites may be found within pseudocysts in
fission. It is transmitted by reduvid bugs that ingest musclefibers.Although survival may be as long as 5
the trypanosome during a blood meal from a verte- years, death usually intervenes within 6 to 12
brate host. The trypanosomes in turn develop in the months.
intestines of the bug, and, while they neither enter The digestive form of Chagas' disease presents as
its saliva nor are injected when the bug bites, they megacolon or megaesophagus in endemic areas. The
do pass out in its feces. afflicted suffer the degeneration and diminution of
Thus the infection is transmitted when the infected nerve cells in the muscular layers of these organs,
insect breaks the skin to draw blood and then defe- leading to their enlargement. The condition by itself
cates following its meal, thereby contaminating the is normally not fatal, but patients often experience
site of the bite. Infection can also occur when the feces difficulty in swallowing because of the enlarged
is rubbed into the eyes or reaches the mucosa of the esophagus, and constipation that normally accompa-
mouth, and possibly through contaminated foods as nies megacolon. These difficulties in turn can pro-
well. The trypanosomes can also be transmitted via mote other illnesses that are life-threatening.
the placenta, maternal milk, and blood transfusions. The congenital form of the disease has long been
The insect vector, which is the principal means of known. The fetus is infected transplacentally, and
transmission, flourishes in huts in poor rural areas the result can be premature fetal death or a newborn
where it lives in cracks in the walls and in thatching with Chagas' disease in its acute stage.
and mats used as roofing. Cases may be few in spite
of large numbers of infected bugs, if the bugs are not History and Geography
domesticated - that is, adapted to living in houses. Chagas' disease is unusual in that its etiological
agent, vector, and the major features of its epi-
Clinical Manifestations and Pathology demiology were described before the first human
There are a number of different forms of the disease, case was ever reported. All this was done by Carlos
which will be considered separately. In all cases, Chagas, a Brazilian physician, in a series of publica-
however, the prognosis is poor because there is no tions beginning in 1909, with the result that the
effective treatment. The acute form ends in death in disease appropriately bears his name.
10 percent of the cases, and although the chronic The illness, however, is not new. Studies under-
form may last from 10 to as long as 40 years, few taken of mummies from the Tarapaca Valley in
individuals remain asymptomatic for life. Chronic northern Chile have revealed megacardia, mega-
cardiac disease as well as megacolon and megaesoph- colon, and megaesophagus in a number of individu-
agus all can shorten life. als who lived more than 2,000 years ago, and al-
The acute form, occurring primarily in young chil- though the etiological agent was not discovered, the
dren, is most commonly a febrile illness; other symp- valley today is an endemic area of Chagas' disease
toms are normally those of generalized lymph node (see Figure VIII.25.1).
enlargement as well as enlargement of the liver and According to L. J. da Silva (1985), nineteenth-
spleen, and edema of the face. When death occurs, it century visitors to Brazil reported instances of
is generally due to acute inflammation of the muscu- megaesophagus and the presence of the cone-nosed
lar walls of the heart (myocarditis) or to a complicat- bug vectors of Chagas' disease. Most interesting is
ing bronchopneumonia. the case of Charles Darwin, who wrote that he was
The latent form of the disease is seen in patients bitten by a huge Triatoma carrier of the infection
who have recovered from the acute form, as well as while in South America. Frank Burnet (1962) re-
others who have harbored the parasite but have not ported that Darwin's mysterious chronic illness, from
displayed symptoms of the illness. Multiple examina- which he always suffered, dated from this time, and
tions, however, often reveal changes in esophageal cited a distinguished protozoologist who believed
and peristaltic motility as well as electrocardio- that Darwin was infected with Chagas' disease.
graphic changes. The disease, although similar to the African form

Chagas en la provincia de Mendoza, Mission de
estudios de patologia regional Argentina. Buenos
Aires.
Rothamer, F., et al. 1985. Chagas' disease in pre-
Columbian South America. American Journal of
Physical Anthropology 68: 495-507.
Silva, L. J. da. 1985. A doenca de Chagas no Brasil.
Indicios de sua ocurrencia e distribuicao ate 1909.
Revista do Instituto de Medicina Tropical de Sao
Paulo 27: 219-34.
Figure VIII.25.1. Megaesophagus from a case of possible

Chagas' disease from the Tarapaca Valley in northern
Chile (c third century A.D.). (From author's original
slide.)
VIII.26
of trypanosome disease (sleeping sickness), most Chlorosis
likely had an independent evolutionary journey. Its
cradle is believed to be the Bahia-Minas-Gerais
area of Brazil, although as noted previously it has In current nosology, diseases are categorized as degen-
subsequently spread throughout the Americas and erative, malignant, genetic, endocrine, and so on. For
has a notable presence in Argentina. In fact, it was purposes of the history of diseases we must add a cate-
in that country that a systematic study carried out gory that we might term ephemeral. This requires a
by S. Mazza and colleagues (1941) established that bit of literary license, because many conditions that
the disease was much more widespread than previ- fall in the class of ephemeral diseases had a longer ex-
ously believed and stimulated other such studies, all istence than that word usually implies. Ephemeral
of which led to the recognition that Chagas' disease diseases comprise a large number of entities that car-
was a serious health threat to South America. It ried working diagnostic names for earlier physicians
would seem to be a growing threat as well. Since the (see, e.g., typhomalarial fever), but that are no longer
1950s, the illness has become increasingly common recognized, at least by their previous names (Straus
in the Arequipa area of southern Peru, although the 1970; Hudson 1977a; Jarcho 1980).
vector (called "chirimacha") is known throughout all
of Peru. Clinical Manifestations
Marvin J. Allison A historical example of a disease that died only to
leave behind a host of sprightly ghosts is the "green
Bibliography sickness" or chlorosis. Although noted in two Hippo-
Burnet, Frank MacFarlane. 1962. Natural history of infec- cratic treatises, Prorrhetic and The Diseases of
tious disease. 3d edition. Cambridge. Girls, the condition received its now classic descrip-
Chagas, C. 1909. Nova tripanozomaize humana. Estudos tion by Johann Lange in 1554 (Hippocrates 1853,
sobre a morfolojia e o ciclo evolutivo do Schizo- 1861). He called the condition morbus virgineus.
trypanum cruzi n. gen., n. sp., ajente etiolojico de nova His description contains many of the elements
entidade morbida do homen. Memorias do Instituto found in the Hippocratic texts, as does the account
Oswaldo Cruz 1: 159-218. by Ambroise Pare in 1561. Also reflecting the Hip-
Crowell, B. C. 1923. The acute form of American
pocratic corpus is the work of Jean Varandal who is
trypanosomiasis: Notes on its pathology with autopsy
reports and observations on trypanosomiasis cruzi in credited with first using the word "chlorosis" in
animals. American Journal of Tropical Medicine 3: 1615 (Starobinski 1981). For Varandal, chlorosis
425-54. was a class of syndromes.
Goldsmith, R. S., et al. 1985. Clinical and epidemiological Reflecting a different approach, Thomas Syden-
studies of Chagas' disease in rural communities in ham's description in 1683 embodied many of the
Oaxaca State, Mexico, and a seven-year follow-up: I. clinical features relied upon at least two centuries
Cerro del Aire. Pan American Health Organization later:
Bulletin 19: 120-38.
Mazza, S., et al. 1941. Primer quinquenio de la in- The face and body lose colour, the face also swells; so do the
vestigation por la MJZPMJL de la enfermedad de eyelids and ankles. The body feels heavy; there is tension

VIII.26. Chlorosis 639
and lassitude in the legs and feet, dyspnoea, palpitation of came a standard treatment, there was general agree-
the heart, headache, febrile pulse, somnolence, pica, and ment that the disease recurred when treatment was
suppression of the menses. (Sydenham 1850) stopped, but responded when iron was reinstituted
and continued.
The actual clinical entity was only defined later, by Ralph Stockman wrote the most comprehensive
Friedrich Hoffmann in 1731. and effective accounts of the nature and treatment of
After centuries of nosologic confusion, chlorosis chlorosis (Stockman 1893, 1895a, 1895b). In his se-
was associated almost entirely with Caucasian girls ries of 63 cases, 27 were suffering their first attack,
encountering puberty. Still, from clinical observa- 11 their second, and 22 several attacks. Of the last
tions alone, the etiology remained obscure. Inconsis- group, some were chronically anemic. If patients
tencies abounded. Not all young women developed remained on the prescribed iron long enough, the
the disease at the age of menarche. It struck the rich chronic cases responded as well as the newly diag-
as well as the poor. Some, but not all, suffered a nosed (Stockman 1895c). From what we now know of
morbid appetite termed pica (the consumption of iron deficiency anemia, those receiving proper doses
stones, clay, chalk, and other substances of no nutri- of iron should have done well, whereas the improp-
tional value). Even into the nineteenth century, con- erly or untreated cases would have ended badly,
fusion permeated medical thinking about chlorosis. even fatally.
The ailment has been likened to a lion in elephant Some observers might look on the use of iron in
grass; all physicians heard its roar, but none could treating chlorosis before an iron deficiency had been
delineate it with absolute certainty. S. Ashwell demonstrated as sheer luck, and one more example
opened his lengthy analysis in 1836 by saying. "Dis- in the history of medicine where physicians did the
ease of menstruation, especially chlorosis and right thing for the wrong reason. Yet although there
amenorrhea, are, in this country, of very frequent are many examples of right thing—wrong reason in
occurrence. . . . They are too greatly neglected in medicine's past, iron for chlorosis probably is not
their early stages, when they are most curable; and one of them. For when physicians employed proper
lastly, there is by no means an agreement of profes- iron compounds in correct doses, the clinical results
sional opinion as to their exact nature." were dramatic and altogether convincing. The fail-
By the time of William Osier later in the century, ures, when iron was used, might more properly be
medical opinion was far more confident. The clinical thought of as doing the right thing with the wrong
features of chlorosis had been distilled to the point regimen.
that in many instances the condition could be "recog- Even if it was correct that the central feature of
nized at a glance" (Osier 1893). chlorosis was an iron deficiency anemia, a good deal
of confusion remained. Still to be elucidated were a
Etiology and Treatment host of diseases marked by pallor, wasting, and lassi-
Developments in laboratory medicine brought physi- tude, some of which had anemia as a secondary mani-
cians to something approaching consensus regard- festation. These included nephritis, hypothyroidism,
ing the pathophysiology of chlorosis. By the mid- subacute bacterial endocarditis, mitral stenosis, and
nineteenth century, reasonably accurate methods tuberculosis. What did subside was the focus on
were available to determine the number of red blood many factors once thought of as central, but which
cells and their hemoglobin content. With this it be- were now relegated to a contributory role at most.
came apparent that the sine qua non of chlorosis was These included lack of fresh air and exercise, corsets,
an iron deficiency anemia. In the minds of many love sickness with its related sexual frustration, Ru-
physicians, chlorosis could now be separated from dolph Virchow's notion of hypoplasia of the arterial
earlier mimics such as love-sickness, hypochondria- system, and a variety of uterine disorders.
sis, and neurasthenia. Chlorosis reminds us of the complex interaction
The natural history of chlorosis, whether treated between physiology and social elements in the gene-
with iron or not, remained a matter of dispute. In sis of human disease. This interplay is better under-
part, this undoubtedly related to frequent misdiag- stood in light of our current notions of iron metabo-
noses. Using iron, some physicians reported that a lism. To protect the body against the destructive
single cure was lasting (Thomson 1886; Faber and effects of excessive iron, intestinal absorption is
Gram 1924). For others the disease progressed to fixed at a rate that barely replaces the small amount
phthisis, many cases of which probably were tubercu- lost normally. This balance is so exquisite that the
losis as such, rather than chlorosis. After iron be- prolonged loss of 2 teaspoons of blood daily will ex-

ceed the body's ability to absorb iron from a normal of the green skin of chlorosis, the available historical
diet, and anemia follows. Iron deficiency anemia can evidence permits us to go no further than a suspen-
result from a decrease in dietary iron, an increase in sion of judgment" (Hudson 1977b). At the very least,
bodily demand for iron, or a loss of blood. it is now reasonable to remove green skin as the
In chlorosis the decrease in iron intake came outstanding characteristic that the designation chlo-
about either from poverty that precluded the intake rosis implied.
of iron-rich foods or from cultural influences that led
young women to avoid meat, eggs, and even milk Distribution and Incidence
because of the belief that animal foods increased the The incidence of chlorosis in earlier times is impossi-
sexual drive, a very undesirable state of affairs in ble to determine. From the attention it received in
Victorian times. The increase in bodily demands for medical and other literature as well as in art, one
iron, for our purposes, resulted simply from the may infer that the condition was not rare. By the
rapid growth associated with adolescence. For the end of the nineteenth century, it was viewed as ex-
historian of disease seeking physiological explana- tremely common. Clifford Allbutt (1909) observed,
tions for chlorosis, these factors would combine to for example, that "the chlorotic girl is well-known in
produce an iron deficiency anemia. every consulting room, public or private." This con-
clusion is all the more striking in light of the rapid
Historical Interpretations exit of chlorosis from center stage. By 1915 medical
observers were commenting on the disappearance of
Clinical Manifestations and Diagnosis the green disease (Osier and McCrae 1915; Camp-
The green skin color of chlorosis, from which it may bell 1923). Between 1924 and 1930 only seven cases
have derived its name, remains, like the origin of of chlorosis were diagnosed in Guy's Hospital (Witts
syphilis, one of the more fascinating problems in the 1930). By 1936 W. M. Fowler was asking "What
history of disease. The conundrum appeared when disease . . . can compare with chlorosis in having
chlorosis was equated with iron deficiency; yet green- occupied such a prominent place in medical practice
ish skin in Caucasians was rarely observed in the only to disappear spontaneously while we are specu-
many cases of hypochromic anemia then being diag- lating as to its etiology?"
nosed. Some of these cases undoubtedly related to He was premature, in his use of the words "disap-
the conditions just mentioned in which a hypo- pear" and "spontaneously," but he was not alone.
chromic anemia appeared secondarily. Another possi- Others concluded that chlorosis had never been any-
bility is that chlorosis was a misnomer, that the thing but a simple iron deficiency anemia brought
word "green" was used metaphorically. In this sense on by an inadequate diet and a loss of menstrual
the word can be traced back to the Oxford English blood (Patek and Heath 1936). With this understand-
Dictionary to mean "of tender age, youthful. . . im- ing another physician wrote that "this disease about
mature, raw, inexperienced." which so much has been written and disputed has
Significantly, the green skin was included only finally ended its stormy career" (Bloomfield 1960).
sporadically in clinical descriptions of chlorosis over Again the optimism was premature. Physicians con-
the years. Lange made no mention of it in his origi- tinued to find chlorosis very much alive. In 1969 it
nal description. In one study, of 27 authors who was listed as one of the five major categories of
listed the usual signs of chlorosis, only 16 mentioned hypochromic anemia that were considered diseases
greenish skin as characteristic of the disease (Hud- sui generis (Witts 1969). In 1980 Irvine Loudon con-
son 1977b). In another analysis, of 19 descriptions cluded that chlorosis was a functional disease inti-
only 3 were considered definitely green, 3 possibly mately related to anorexia nervosa; that although
so, and 2 yellowish green (Loudon 1980). In 1915 chlorosis, like the Cheshire cat, "faded from sight, it
Richard Cabot, author of a popular textbook of physi- is, in this story, still there under another name."
cal diagnosis, concluded that "it takes the eye of Current medical dictionaries still carry the term and
faith to see any justification for the title of the dis- define it as an iron deficiency anemia of young
ease." On the other hand, the 1975 edition of a promi- women.
nent textbook of dermatology averred that "the skin
may have a green or brown tint in the iron defi- Owing perhaps to its ephemeral nature, chlorosis
ciency syndrome" (Siddall 1982). Yet recent work on has been particularly alluring to revisionist histori-
the nature of chlorosis has done nothing to alter this ans. Recent work has emphasized the importance of
author's conclusion of a decade ago: "In the question the general perception of women and their role in

VIII.26. Chlorosis 641
what physicians thought and did about disease, al- the proper paradigm for health professionals dealing
though there is surprisingly little about chlorosis as with disease in our time has always operated histori-
such in this literature (Hartman and Banner 1974). cally. Ockham's razor may be useful in logic, but it
Marxist and social historians have also become may slice too narrowly in history. Plethora rather
interested in chlorosis. These revisionist approaches, than parsimony more often illuminates the complexi-
to varying degrees, tend generally to diminish the ties of humanity's interaction with society at any
importance of pathological physiology in explaining given time and place. Chlorosis is a case in point.
the rise and decline of chlorosis. The more committed There remains ample reason to recall L. J. Witt's
the revisionists are to their historical biases, the remark (1969) that "however one looks at it, one
more difficulty they have squaring their interpreta- is left with the uneasy feeling that the mystery
tions with those of others as well as with more purely of chlorosis, like that of Edwin Drood, remains
medical explanations. The Marxist, for example, unsolved."
must construct social and political conditions that Robert P. Hudson
produced chlorosis in young women of the capitalist
class as well as the oppressed poor, because the evi- Bibliography
dence is incontrovertible that the condition affected Allbutt, Clifford. 1909. System of medicine by many medi-
both, as one of them readily acknowledges (Figlio cal writers, Vol. 5. London.
1978). Ashwell, S. 1836. Observations on chlorosis and its compli-
The feminists who would argue that nineteenth- cations. Guy's Hospital Reports 1: 529—79.
century physicians mistreated women consciously Bloomfield, Arthur L. 1960. Chlorosis. In A bibliography
on the basis of gender must account for the fact that of internal medicine: Selected diseases. Chicago.
many of the treatments accorded women by male Brumberg, J. J. 1982. Chlorotic girls, 1870-1920: A histori-
cal perspective on female adolescence. Child Develop-
physicians at the time derived from an inadequate
ment 53: 1468-77.
understanding of reproductive physiology, and that Cabot, Richard. 1915. Chlorosis. In Modern medicine: Its
masculine sexual conditions were also mistreated. theory and practice, ed. William Osier and Thomas
The historian who argues that chlorosis was nothing McCrae. Philadelphia.
more than a cultural construction of Victorian fam- Campbell, J. M. H. 1923. Chlorosis: A study of the Guy's
ily life, that physicians diagnosed the condition sim- Hospital cases during the last thirty years with some
ply because they expected to encounter it, and that remarks on its etiology and causes of its diminished
young women simply learned to manifest the clini- frequency. Guy's Hospital Reports 73: 247-97.
cal picture of chlorosis (Brumberg 1982) must ex- Evans, J. T. 1845. Cases of chlorosis in the male, with
plain the well-documented existence of the disease clinical remarks by Dr. Evans. Dublin Hospital Ga-
in young men as well (Fox 1839; Evans 1845; Witts zette 1: 79-81, 98-101.
1930). Faber, Knud, and H. C. Gram. 1924. Relations between
gastric achylia and simple and pernicious anemia.
Enthusiasm for new historical approaches to dis- Archives of Internal Medicine 34: 658-68.
ease should not obscure the importance of the final Figlio, Karl. 1978. Chlorosis and chronic disease in
common pathway of social, political, and cultural nineteenth-century Britain: The social constitution of
forces. And that common denominator for chlorosis somatic illness in a capitalistic society. Social History
in the nineteenth and early twentieth centuries was 3: 167-97.
an iron deficiency anemia. Social and cultural fac- Fowler, W. M. 1936. Chlorosis - an obituary. Annals of
tors certainly predisposed individuals to chlorosis, Medical History, new ser., 8: 168-77.
but persons became patients ultimately because they Fox, Samuel. 1839. Observations on the disorder of the
had red blood cells that were too small and lacked general health of females called chlorosis. London.
the normal amount of hemoglobin. Poor nutrition - Hartman, Mary J., and Lois Banner, eds. 1974. Clio's con-
whether due to poverty or cultural preferences- sciousness raised: New perspectives on the history of
certainly contributed. Physicians, with their heavy women. New York.
Hippocrates. 1853,1861. Oeuvres completes, Vols. 8 and 9,
reliance on blood-letting, even prophylactically in
trans. Emile Littre. Paris.
pregnant women, undoubtedly played a part as well Hudson, Robert P. 1977a. How diseases birth and die.
(Siddall 1980). Chlorotic women gave birth to iron- Transactions and Studies of the College of Physicians
deficient children - "larval chlorotics" they were of Philadelphia 45: 18-27.
called. Chlorosis, at bottom, was a deficiency disease. 1977b. The biography of disease: Lessons from chlorosis.
Explaining it historically demands an eclectic histo- Bulletin of the History of Medicine 51: 448-63.
riography. The biopsychosocial model emerging as Jarcho, Saul. 1980. Some lost, obsolete, or discontinued

diseases: Serpus apoplexy, incubus, and retrocedent
ailments. Transactions and Studies of the College of VIII.27
Physicians of Philadelphia 4: 241-66. Cholera
Loudon, I. S. L. 1980. Chlorosis, anaemia, and anorexia
nervosa. British Medical Journal 281: 1669-75.
Osier, William, 1893. The principles and practice of medi- Cholera is an acute diarrheal disease usually accom-
cine. New York. panied by vomiting and resulting in severe dehydra-
Osier, William, and Thomas McCrae. 1915. Modern medi-
cine. Philadelphia.
tion or water loss and its consequences. The disease,
Patek, Arthur, and Clark Heath. 1936. Chlorosis. Journal in the strict sense of the term cholera, is caused by a
of the American Medical Association 106: 1463-6. specific, comma-shaped bacterium, Vibrio cholerae,
Siddall, A. Clair. 1980. Bloodletting in American obstetric first isolated in Egypt and Calcutta by Robert Koch
practice, 1800-1945. Bulletin of the History of Medi- and colleagues in 1883. Mortality rates have reached
cine 54: 101-10. up to 50 percent and even 70 percent of those with the
1982. Chlorosis - etiology reconsidered. Bulletin of the disease during epidemics. It has apparently been long
History of Medicine 56: 254-60. endemic in the Ganges Delta of India and Bangladesh
Starobinski, Jean. 1981. Chlorosis - the "green sickness." from which it has spread in periodic epidemics to
Psychological Medicine 11: 459—68. other parts of India, the East, and eventually to much
Stockman, Ralph. 1893. The treatment of chlorosis by iron of the rest of the world. Most of this spread has oc-
and some other drugs. British Medical Journal 1: curred since 1817, when trie modern history of the
881-5, 942-4. disease outside India begins; it is now generally
1895a. Observations on the causes and treatment of
agreed that some seven pandemics have occurred
chlorosis. British Medical Journal 2: 1473-6.
1895b. On the amount of iron in ordinary dietaries and
since its initial spread. The most recent began in 1961
in some articles of food. Journal of Physiology (Lon- and is only now receding. The bacterium is dissemi-
don) 18: 484-9. nated by the so-called fecal-oral route as a conse-
1895c. A summary of sixty-three cases of chlorosis. Edin- quence of sewage and fecal contamination of water
burgh Medical Journal 41: 413-17. supplies and foodstuffs. This indirect transmission
Straus, Bernard. 1970. Defunct and dying diseases. Bulle- long made its spread difficult to understand.
tin of the New York Academy of Medicine 46: 686-705. In the course of history, the term "cholera" has
Sydenham, Thomas. 1850 The works of Thomas Syden- been variously applied. In order to understand the
ham, Vol. 2, trans. W. Greenhill. London. literature of cholera in the past, the reader must also
Thomson, William H. 1886. Chlorosis. In A reference hand- understand these varying usages. The word "chol-
book of the medical sciences, Vol. 2, ed. Albert H.
Buck. New York.
era" appears first in the Hippocratic corpus and
Witts, L. J. 1930. Chlorosis in males. Guy's Hospital Re- there refers to sporadic diarrheal disease. It has
ports 10: 417-20. been suggested that it derives from the Greek word
1969. Hypochromic anemia. Philadelphia. for "bile" and for "flow" (difficult to accept since
cholera excreta are singularly free of bile), or from a
Greek work for "spout" or "gutter." Later classical
writers including Celsus, Aretaeus, and Caelius
Aurelianus described a condition under the same
name. By late 1669, Thomas Sydenham employed
the term in describing an epidemic in London. The
term was also widely used to describe endemic or
sporadic diarrhea throughout the nineteenth cen-
tury and earlier in western Europe and the Ameri-
cas. This is sometimes specifically designated as chol-
era nostras.
The term cholera morbus has also been widely
used in a manner that can cause confusion because it
has been applied to indicate both epidemic and spo-
radic or endemic forms of illness marked by diar-
rhea. Today the term is applied as defined above and
thus is limited to the disease caused by V. cholerae.
Synonyms have included Asiatic cholera or cholera

VIII.27. Cholera 643
asiatica, epidemic cholera or cholera epidemica, ma-Control and Distribution

lignant cholera, cholera asphyxia, and cholera spas-The infection is spread solely by infected humans,
modica. It is now generally accepted that all cholera whose excreta may contaminate drinking water and
in the West prior to the nineteenth-century epidem- food. This is not the direct contact that contagionists
ics was endemic or sporadic - and not caused by V. in earlier generations expected from experience with
cholerae. It is also generally accepted that the chol- readily transmittable infections such as smallpox.
era of India prior to 1817 was an earlier expression Thus communicability was a highly controversial
of the epidemic cholera, with the first reference ap- matter until its bacterial etiology was established.
pearing in Western literature in the Lendas da In- With this in mind one can state that the appearance
dia, published in 1543 by the Portuguese explorer and spread of cholera in a community or country
Gaspar Correia. He describes an outbreak occurring depend first on the appearance of a person, either ill
in 1503 in the army of the Sovereign of Calicut. or well, who is discharging the cholera vibrio from
Cholera was also described in 1563 by Garcia da his or her intestinal tract, and second on the state of
Orta in one of the earliest books printed in Goa. Its hygiene, water supply, and sewage disposal in pro-
Portuguese name was mordexim, from which the moting or impeding the transmission of the bacte-
French mort de chien is derived. Other Eastern rium to a potential victim. In endemic areas such as
terms were hyza (Arabic and Hindustani), tokhmu the Ganges Delta, a water table hardly below the
(Persian), bisoochtau (Sanskrit), and fural (Mah- surface of the ground has posed almost insurmount-
ratta). That the differentiation is not universally able problems. In the past, unsatisfactory sanitary
accepted can be seen in the 1961 writings of the facilities have been necessary conditions for cholera
Indian bacteriologist S. N. De, who includes all types outbreaks in Europe and the Americas. Indeed, the
of conditions under one disease entry and therefore history of the control of cholera is the history of
objects to the implications of the term "Asiatic" chol- improved sanitation.
era. Nonetheless, this survey will be limited to the Current distribution of epidemic cholera is largely
epidemic of Asiatic cholera, unless specifically indi- limited to areas in the Indian continent and the
cated to the contrary. tropical Far East, where it persists and occasionally
breaks out in low-lying wet areas of contaminated
Etiology water supply and sewage disposal. Since the Second
As noted already the etiologic agent of Asiatic or World War, it has made sporadic forays into the
epidemic cholera is a comma-shaped bacterium, V. Middle East and Far East, often associated with
cholerae. It is gram-negative, made motile by means social disruption. In the early 1970s, cholera ap-
of a single terminal or polar flagellum - or motility peared briefly in Europe, with outbreaks in Mediter-
organ. This bacterium was seen in the excreta and ranean ports especially Naples (over 30 deaths), Bar-
intestinal contents of cholera victims by Filippo celona, and the Atlantic port of Lisbon with over
Pacini and described by him so accurately in a report 2,000 cases. Some cases were carried by rapid trans-
he published in Florence in 1854 that it still carries portation to the north, but resulted in no further
the name he gave it, although the finding made extension of the disease. One small area of persis-
little impact at the time. tent infection appears to be the lower bayou country
The bacterium can be grown in the laboratory in outside of New Orleans, the origin of these recurring
simple media and in an alkalinity greater than that cases.
tolerated by most other bacteria. This latter charac-
teristic is of significance for its growth in the human Immunology
small intestine, as will be duly noted. On the other A natural immunity or resistance to cholera seems
hand, it is more sensitive to acidity. This bacterium to exist because not all persons ingesting infected
survives and multiplies in the environment outside material contract the infection. C. Macnamara
the human body, notably in any relatively uncon- (1870) noted that of 19 persons accidentally drinking
taminated alkaline environment. It does not regu- infected water on shipboard in 1861, only 5 con-
larly infect animals; its host range is limited to hu- tracted the infection. This resistance might well be
mans. And it can be carried and spread by humans, nonspecific; the natural acidity of the stomach could
especially convalescents, in the absence of overt dis- act as a barrier to infection (a possibility well appre-
ease. The bacteria produce and secrete a toxin, ciated by Macnamara). On the other hand, one infec-
which is the actual cause of the symptoms that con- tion does not produce the solid immunity against
stitute the disease. repeated infections in survivors as in other infec-

tions such as smallpox and measles. When post- Treatment
infection immunity does arise, it is of relatively Norman Howard-Jones (1972) described the earlier
short duration. Extensive experimental and clinical treatment of cholera as follows: "In the whole of the
trials with immunization against cholera have not history of therapeutics before the twentieth century
been convincing. Such measures have been man- there is no more grotesque chapter than that on the
dated at times for travelers, nevertheless. The weak- treatment of cholera, which is largely a form of be-
ness of postinfection immunity is consistent with the nevolent homicide."
weakness of the case for immunization. Modern therapy consists simply of replacing the
lost water and salts. This may be done by intravenous
Clinical Manifestations and Pathology therapy, or by oral administration in milder cases or
The bacterial infection is limited to the intestinal as an adjunct to the intravenous therapy in more
tract; no microbes are found to invade the body tis- serious cases. This has greatly facilitated the treat-
sues. The low bacterial population normally in the ment of diarrhea patients, especially in resource-poor
small intestine as well as its high alkalinity contrib- countries. Thus cholera is essentially curable. Antibi-
ute to the cholera vibrio's ability to survive and grow otics play only a minor role, in that they may shorten
there, usually in massive numbers. They adhere to the duration of disease and reduce the massive
the intestinal wall and secrete a toxin that inhibits amounts of necessary fluid replacement.
the absorption of water and electrolytes (salts) from
the intestine into the circulation. Since the blood
delivers large amounts of water and salts into the History and Geography
intestinal tract, which are then normally reabsorbed Consideration of the historical literature under the
back into the bloodstream, failure of this reabsorp- rubric "cholera" requires appreciation of what dis-
tion results in the loss and excretion of many liters ease is being treated. Literature on cholera in west-
of fluid in the course of a single day. This loss pre- ern Europe and the Americas that was written prior
sents as a massive, debilitating diarrhea, which is to about 1830 and that described an endemic or
the major clinical feature of cholera. All other symp- sporadic disease called "cholera" is excluded from
toms of the disease are attributable to this water and the following account. There is a relatively sparse
salt depletion. These symptoms and clinical findings literature on the disease in India, which serves as a
include weakening and finally loss of palpable pulse, prelude to the modern history of true cholera. The
thickening of the circulating blood, suppression of modern literature on cholera starts slowly in 1817
urination, loss of tissue fluids giving the face a and accelerates with its appearance in Russia in
sunken appearance, cyanosis, muscular spasms, and 1829, eastern Europe in 1831, and western Europe
a disastrous fall in blood pressure leading to pro- and North America in 1832.
found shock, which represents the fatal conclusion of
the disease. The mind is ordinarily clear throughout
the course of the disease. Recovery, when it occurs, is Antiquity
marked by the return of the capacity to reabsorb and There have been conflicting opinions concerning the
retain fluids and salts, and a reversal of the signs possible references to cholera in the early Hindu
and symptoms discussed above. literature. James Annesley (1825) stated: "I have
Pathological changes observed in the past on ex- not been able to obtain any information from those
amination of the body at autopsy can now be attrib- acquainted with the writings of the Hindoos, favour-
uted to postmortem changes. Early reports describe ing the inference that cholera has prevailed in
an erosion of the intestinal wall leading to the fluid former ages as a wide-spreading epidemic." Robert
loss mentioned, with the intestinal lining being Pollitzer (1959) makes only a brief and doubtful ref-
found shed into the excreta. But in 1960, Eugene J. erence to the matter. Jan Semmelink (1885), for-
Gangarosa of the Walter Reed Hospital was able to merly principal physician of the army of the Nether-
observe the intestinal walls of cholera patients di- lands East Indies, in the French translation and
rectly and found no evidence of any structural dam- condensation of his much more heavily documented
age to cells in this area. Thus was research directed Dutch edition of the same year, reviewed available
toward damage at an enzymatic or molecular level, English, French, and German translations very criti-
pathologically caused by the cholera toxin already cally and rejected all references to possible early
discovered by De in 1959. epidemic cholera in the Far East.

Vm.27. Cholera 645
Sixteenth Through Eighteenth Century tal on March 22 alone of no less than 500 men of a
Reference has already been made to the explorer division of 5,000. It is curious to note that the report
Correia, who stated that in the spring of the year cited calls the disease a "pestilential disorder" and
1503, 20,000 men died in the army of the Sovereign does not name it cholera, although later writers (in-
of Calicut, some of a "disease, sudden-like, which cluding Macnamara) assumed that it was.
struck with pain in the belly, so that a man did not This outbreak is reported to have reached Cal-
last out eight hours time." Correia also met cholera cutta. In April of 1783, "cholera burst out at
in an epidemic form in Goa in the spring of 1543, Hurdwar, and in less than eight days is supposed to
called by the natives moryx, where the mortality have cut off 20,000 pilgrims." Fragmentary observa-
was so great that it was very difficult to bury all of tions continued to appear, some from travelers, de-
the dead. The disease was marked "by vomiting, scribing the following:
with drought of water accompanying it, as if the
stomach were parched up, and cramps that fixed the [D]isease broke out with terrible ferocity, and destroyed an
sinews of the joints" (Macnamara 1870). Garcia da enormous number of people. During the month of October,
1787, epidemic cholera committed terrible ravages at
Orta's report from Goa in 1563 called the disease Arcot and Vellore. With regard to this outbreak, Mr. Da-
hachaiza or haiza as the Arabs did, and also colerica vis, a member of the Madras Hospital Board, remarks: "I
passio and morxi. found in what was called the Epidemic Hospital, three
The Netherlander Jan Huygen van Linscoten de- different diseases, viz., patients labouring under cholera
scribed what he called mordexijn in Goa in 1584, as morbus; an inflammatory fever with universal cramps;
did the Frenchman Vincent Le Blanc also in Goa in and a spasmodic affection of the nervous system, distinct
1585. Reports followed through the rest of the 1500s from cholera morbus. I understood, from the Regimental
and 1600s, including that of the well-known Jacobus Surgeon, that the last disease had proved fatal to all who
Bontius in the earlier 1600s, who extended his obser- had been attacked with it, and that he had already lost
vations to Batavia, now Indonesia. Notices of the twenty-seven men of the regiment in a few days. Five
patients were then shown to me with scarce any circula-
disease continued to appear into the eighteenth cen-
tion whatever to be discovered; with their eyes sunk
tury when they were joined by those of Englishmen. within the orbits; jaws set, bodies cold, and extremities
Thomas Percival in 1788 reported that a ship sur- livid."
geon from Chester was treating cholera morbus with
radix Columbo in the East Indies during the 1750s,
and provided a fair description of the disease. The Nineteenth Century: The Pandemics
Scotsman James Lind described cholera throughout Cholera, or cholera-like disease, continued to be ob-
the East Indies and in India in the 1760s as a "conserved during the rest of the eighteenth and into the
stant vomiting of a tough white pellucid phlegm, nineteenth century. Then, in the year 1814, out-
accompanied by a constant diarrhea, [which] was breaks of cholera occurred in a number of Indian
deemed the most mortal symptom." He used the provinces, including the crowded barracks of Fort
term mordechin. William at Calcutta among recruits just arrived
from England.
Macnamara (1870) recorded that the "earliest ac-
Macnamara, who evaluated all these many re-
count of the occurrence of cholera in India, from the
ports of the appearance of the disease, concluded
pen of an English physician (Dr. Paisley), is dated
that "we a r e , . . . I think justified in arriving at the
Madras, February 1774, and is to be found in Cur-
conclusion that it was nothing new for cholera to
tis's Works on Diseases of India, published in Edin-
spread over India in an epidemic form prior to 1817
burgh in 1807." Although nothing further seems to
and 1819." At this point, something drastically
be known of this Paisley, his letter forms a corner-
"new" did occur, as cholera escaped the bounds of
stone in the history of the disease in British India.
India and initiated the waves of pandemics that
Annesley (1825), in an early English classic on chol-
were to engulf the world. This change in cholera's
era, quotes the following passage: "Thus," Paisley
pattern of activity has led a few to conclude that a
wrote from Madras, in 1774, "there can be no doubt
new disease arose in Bengal in 1817, a contention
that their (the troops') situation contributed to the
Pollitzer (1959) regards as untenable, observing the
frequency and violence of this dangerous disease,
following:
which is, as you have observed, a true cholera
morbus." In 1781, it ravaged the troops in the dis- Incomplete or even fragmentary though the evidence
trict of Ganjam, requiring the admission to the hospi- brought forward . . . often is, it leaves no room for doubt

that cholera, present in India since ancient times, not only through 1819 and 1820, extending into Ceylon and
continued to exist but was apt to manifest itself periodi- Burma, Siam, Malacca and Singapore, and the Phil-
cally in wide spread conflagrations. ippines. By 1821, it had invaded Java, Batavia, and
Dissenting views do, however, exist, including China to the east and Persia to the west, reaching
those of Annesley (1825) who, writing within a de- Baghdad with a besieging Persian army, and extend-
cade of the 1817 outbreak, states "[t]hat we have no ing from there to Aleppo. By 1823, it was in Egypt,
proof of the prevalence of cholera in India, as a wide- Astrakhan, and the Caspian shores and throughout
spreading epidemic in former times." Again the skep- Syria along the shores of the Mediterranean. But it
tical Semmelink devotes a whole work to the obser- receded for a number of years, thereby terminating
vations of cholera in the East before 1817, providing the First Pandemic.
detailed criticism of what must be essentially every
report in the European literature. And again he is The Second Pandemic. By 1824, cholera had re-
vehement in his judgment that the accounts refer to treated to its endemic area in Bengal, where it re-
other than the epidemic cholera of 1817 and after, mained active in the Ganges Delta through 1826.
although his nosology is sometimes archaic and diffi- But in 1827, it spread out again in the so-called
cult to follow. It has also been suggested in this age Second Pandemic into the Punjab, and by 1829 ex-
of genetic engineering that a genetic modification in tended through Persia to the shores of the Caspian
the microbe was responsible for this supposed Sea. In Orenburg in 1829 (August 26), it soon ex-
change in cholera's nature. panded north and west into Russia. By September of
1830, cholera was in Kharkov and Moscow, and be-
gan spreading west into Bulgaria. During the winter
The First Pandemic. In any event, in March 1817, of 1830-1, it persisted in the Russian army in Po-
a death from cholera took place in Fort William, but land, and then in the spring it invaded Warsaw and
because it was a solitary case no notice was taken of soon after, Riga. Meanwhile, cholera was also raging
it. By July, however, outbreaks occurred in several through Mecca and Turkey, reaching Constantino-
districts in the Province of Bengal. The first notice of ple and Alexandria by July and August. On August
this in the Proceedings of the Bengal Medical Board 3, it entered Berlin and Vienna, and reached Ham-
was a letter from Robert Tytler, civil surgeon of burg by the beginning of October. Around the end of
Jessore, dated August 23, 1817. He wrote: October, if not before, it appeared in England at
An epidemic has broken out in the bazaar, the disorder Sunderland, supposedly imported from Hamburg or
commencing with pain or uneasiness in different parts of Riga. Late fall and early winter brought a brief
the body, presently succeeded by giddiness of the head, respite, during which teams of observers were sent
sickness, vomiting, griping in the belly, and frequent to infected areas from as yet unaffected areas, while
stools. The countenance exhibits much anxiety, the body commissions at home were trying to prepare for the
becomes emaciated, the pulse rapidly sinks, and the pa- coming onslaught and arguments about such mat-
tient, if not speedily relieved with large doses of calomel, ters of quarantine, sanitation, contagiousness, and
followed by one of opium, ... [is carried off] within four treatment.
and twenty hours.
The opening of the year 1832 was soon followed by
In July and the following months, Calcutta was af- a reawakening of cholera. In February, it appeared
fected; 25,000 of its inhabitants were under medical in Newcastle, Edinburgh, and London, as well as
treatment for the disease of whom 4,000 died. Thus places in between. Next it reached France, bursting
begins the modern history of Asiatic or epidemic on Paris on March 24, and soon engulfing all dis-
cholera, although none of the documents immedi- tricts of the city. Within 18 days no fewer than 7,000
ately surrounding the event make reference to the persons were dead. Next, cholera hurdled the Atlan-
name "cholera," until a letter dated September 16 tic Ocean to appear on June 8 in Quebec and on June
specifically refers to "cholera morbus." 19 in Montreal. Presumably, it arrived with emi-
Within 3 months the disease had spread through- grants on the brig "Carricks," which left infected
out the Province of Bengal, and in November it Dublin in April and lost 42 of its 173 passengers
reached the camp of the Marquis of Hastings in before reaching Quebec on June 3. On June 23, chol-
Bundelcund. During 1818, it moved over the era invaded the United States, appearing in New
greater part of India including Delhi and Bombay, York on that date and in Philadelphia on July 5.
with estimated attack rates of up to 7.5 percent of From these ports of entry, it marched westward
the exposed population. It continued to rage across both North American countries.

VIII.27. Cholera 647
Entry into Spain, Portugal, and the Caribbean true that cholera was present in eastern Europe in
and Latin America was delayed until 1833, and into 1852, either because of persistent infection in these
Italy until 1835. Havana lost 8,253 persons in a areas (i.e., continuation of the earlier pandemic) or
population of 65,000 between February 26 and April because of a fresh wave of infection starting in India
20, 1833, and by August no less than 15,000 had in 1849 (Pollitzer 1959). But in either case, it seems
perished in Mexico. fairly unlikely that what for all appearances seems
Yet by 1834, the disease was beginning to recede, to have been a pandemic would break at mid-point.
and while it persisted in a number of Mediterranean The year 1854 found cholera widely spread in Eu-
and Central American areas for a few more years, it rope, England, Greece, Turkey, and North and South
retreated once again in 1837 to its Indian homeland. America. It was one of the worst cholera years on
This pandemic has been described in detail, as it was record. It was during this pandemic that John Snow
the first modern experience with the disease for made his observations in London that in 1855 led to
much of the world and because subsequent epidem- the publication of his critical, if not immediately
ics or pandemics were to follow much the same appreciated, study on cholera transmission by con-
route. In addition, a great deal of popular and govern- taminated water. In 1855 and after, the disease died
mental response to subsequent appearances was down in much of the West, but it continued in a few
based on experience gained during this pandemic. spots there as well as in much of the East.
The Third Pandemic. During the following decade, The Fourth Pandemic Pollitzer dates the Fourth
cholera continued to plague India, and it entered Pandemic from 1863; it was to last about 10 to 12
Afghanistan with British troops in 1839, and China years. In 1865, Macnamara estimated that a third of
in 1840 - again with troops from India - where it 90,000 pilgrims at Mecca succumbed. As before, it
remained into 1841 and 1842. In 1844-5, it extended reached Constantinople and spread around the Medi-
into Persia and Central Asia, reaching the Arabian terranean, reaching northern Europe in 1866 and
coast as well as the Caspian and Black seas in 1846- 1867, and the United States and the Latin Americas
7. Constantinople was attacked on October 24, 1847. in 1866. It raged over its old grounds until 1874.
In the spring of 1848, it broke out with renewed
vigor, advancing as far as a line drawn through The Fifth Pandemic. According to Pollitzer, the
Arabia, Poland, and Sweden, reaching Berlin in July Fifth Pandemic began in 1881, and lasted until
and Hamburg and Holland by September, and then 1896. It was during this epidemic that the studies of
London and Edinburgh in short order. After a short Koch in Alexandria and Calcutta in 1883-4 led to
period of comparative rest, it renewed its activity in the isolation and identification of the causative mi-
the spring, reaching Paris in March and by now was crobe. In addition to Egypt, the epidemic was at first
covering much the same ground of the earlier epi- largely limited to the Mediterranean shores of Af-
demic. Meanwhile, in December 1848 cholera had rica and Europe, although it later became wide-
crossed the Atlantic to invade New York and New spread in Russia, and in Germany where it was
Orleans, and spread rapidly across the continent marked by the explosive outbreak in Hamburg in
from these centers. In 1850, it reached California 1892. Importation into New York in 1887 was ar-
with the wagon trains as well as by ships from Pan- rested, but outbreaks did occur in Latin America.
ama. In that year it was reported in North Africa, The disease was also widely prevalent in the Far
Europe, and both North and South Americas. In East - in China and Japan.
many of these regions, it continued through 1851
and 1852. The Sixth Pandemic. The Sixth Pandemic ran from
1899 through 1923. It followed much the pattern of
There is some debate over the dates of the second the fifth - largely affecting India, the Near and Far
and third pandemics. Most accept the worldwide East, Egypt, western Russia, and the Balkan Penin-
spread of cholera during the decades of the 1840s sula. Sporadic outbreaks occurred in southern Eu-
and 1850s as constituting the Third Pandemic. How- rope and Hungary in the West and China, Japan,
ever, Pollitzer (1959) and a few others date the Third Korea, and the Philippines in the East. But this time
Pandemic at 1852 or 1853, and place the Second cholera did not reach the Western Hemisphere.
Pandemic within the mid-1840s to 1851, in spite of
the obvious lull from the mid-1830s to the mid- The Seventh Pandemic. The Seventh Pandemic
18408, at least outside the Indian subcontinent. It is datesfromabout 1961 to the mid-1970s and followed

much the pattern of the previous epidemic. It is and technical elegance of Koch in 1883 to isolate and
particularly important in providing an opportunity identify the microbe and to introduce the modern
for the significant advances in studies of cholera phase of the understanding of the disease. It was not,
pathogenicity and therapy extensively described by however, until 1959 that the toxin produced by the
W. E. Van Heyningen and John Seal (1983), studies microbe was discovered along with its role in disease
carried out in Egypt, India, Bangladesh, and the causation.
Philippines by several U.S. teams. The question of the "contagiousness" of cholera
was a matter of heated debate throughout most of
This brief sketch can provide only the barest outline the nineteenth century. It can be generally observed
of the nineteenth-century history of this significant that the contagionists were viewed by contemporar-
disease. Pollitzer's numbering of the pandemics is ies as archaic, conservative, and even antisocial,
utilized here for the later ones, although, as has been whereas the anticontagionists were seen as modern,
mentioned, historians of the disease have not always bourgeois, mercantile, and socially responsible.
agreed on this numbering. In fact, it is sometimes not Most of the debate focused on the question of quaran-
entirely clear why or when one pandemic is said to tine which, of course, was anathema to mercantile
have terminated and another to have begun. interests, and the anticontagionists gained ground
as the nineteenth century progressed. The demon-
Historical Considerations of Etiology, Control stration of Snow of the waterborne nature of cholera
and Prevention, and Treatment was slow to gain acceptance, but this development,
In addition to the history of the pandemics them- coupled with the discovery by Koch of the infective
selves, the history of several other aspects of the nature of the disease, finally proved the "contagion"
disease seems significant to the overall history of of the disease, providing, of course, that one allows
medicine. Among these are the discovery of the etiol- for the intermediary role of infected excreta and
ogy of the disease, concepts of contagion, develop- water or food, and that some individuals can act as
ments in sanitation and public health institutions, carriers but do not develop the disease.
and developments in therapy. Sanitation has always played a major role in the
Earlier thoughts on the causes of cholera were thinking and in the efforts of those aiming to under-
embedded in notions of disease causation going back stand and control the propagation of cholera. As a
to Hippocrates: weather, seasons, geographic envi- consequence, a large body of literature has been
ronment, bad air and miasmas, and dietary indiscre- generated on the role and influences of cholera epi-
tions. If an infecting agent was referred to at all, it demics on the development of public health policies,
was likely to indicate an "infection" by a poison or public health organizations, and the development of
miasma. sanitation procedures and techniques.
By the middle of the nineteenth century, however, The earlier history of the treatment of cholera has
ideas of a microbial etiology were gaining ground been thoroughly treated by Norman Howard-Jones
with the writings of such individuals as F. G. Jakob (1972) and Michael Durey (1979). Most of the thera-
Henle. In 1849, William Budd and two associates peutics employed were representative of the practice
described microscopic bodies in cholera excreta and of medicine generally in and before the nineteenth
published their findings with illustrations. The century. Emetics, purgatives, and bleeding seem in
French botanist Charles Robin reproduced these il- retrospect to have been worse than ineffective.
lustrations in 1853, denying their "vegetal nature." Calomel and opium were the standard drugs admin-
These were seen by the German botanist Ernst Hal- istered, beginning with British physicians in India.
lier, who rejected Robin's rejection and set out to Castor and croton oils, antimony, mustard, bismuth,
grow microbes from cholera excreta using bacterio- arsenic, camphor, and quinine were among other
logical techniques that could not have produced suc- drugs administered. A red-hot iron to the heel was
cess. He published his findings in Die Cholera- widely employed in India, to the spine in Paris. Wa-
Contagium in 1867. ter hot or cold orally, per rectum, or as baths was
T. R. Lewis tried to confirm Hallier's work in Cal- sometimes recommended.
cutta in 1870, and in failing, became somewhat of an The definitive treatment - intravenous fluid and
anticontagionist. In the meantime, as already de- salt replacement - was a long time in developing. As
scribed, Pacini made his correct but at the time early as 1830, the German chemist R. Hermann dem-
largely ignored observations of the actual V. cholerae onstrated in Moscow that the change in the blood's
in 1854. Thus it was left to the genius, persistence, fluid balance was reflected in the contents of the

VIII.28. Cirrhosis 649
cholera excreta. A German colleague on one occasion McGrew, Roderick E. 1965. Russia and the cholera, 1823-
injected 6 ounces of water into the terminally ill pa- 1832. Madison and Milwaukee.
tients, a treatment that produced a quick, temporary Morris, R. J. 1976. Cholera, 1832: The social response to an
return of the pulse, although death nonetheless oc- epidemic. London.
curred 2 hours later. In October 1831, the Berlin Pollitzer, Robert, 1959. Cholera. Geneva.
surgeon J. F. Dieffenback took the premature step of Rosenberg, Charles E. 1962. The cholera years: The United
States in 1832,1849, and 1866. Chicago.
injecting several ounces of whole blood into three
Semmelink, Jan. 1985. Histoire du cholera aux Indies Ori-
patients. They died 6 minutes, 2 hours, and 6 hours entales avant 1817. Utrecht.
later, respectively, the first during violent convul- Sticker, Georg. 1912. Abhandlungen aus der Seuchenge-
sions. In Great Britain in late 1831 and early 1832, W. schichte und Seuchenlehre. II. Band: Die Cholera.
B. O'Shaughnessy published papers suggesting the Giessen.
intravenous replacement of salt and water. These Van Heyningen, W. E., and John R. Seal. 1983. Cholera:
suggestions led Thomas Latta of Leith, Scotland, and The American scientific experience. Boulder.
two associates to try the treatment on patients. They Wendt, Edmund Charles. 1885. A treatise on Asiatic chol-
reported that 5 of 15 patients survived. Other spo- era. New York.
radic attempts followed, with some but not convinc-
ing success during the 1830s. Sporadic trials contin-
ued through the century in Britain and France, and
in Calcutta in the 1890s, but the treatment was not
successful until Leonard Rogers perfected it in Cal-
cutta in the early 1900s. There were a number of VIII.28
technical problems to be solved first, not the least Cirrhosis
being sterility. But with these difficulties resolved,
the definitive treatment of cholera was established.
Reinhard S. Speck Cirrhosis is a chronic hepatic disorder, anatomically
characterized by diffuse liver fibrosis and nodule
formation. These pathological changes produce the
Bibliography clinical features of portal hypertension and hepato-
Ackerknecht, Erwin H. 1948. Anticontagionism between cellular failure. Cirrhosis is the end product of pro-
1821 and 1867. Bulletin of the History of Medicine 22: gressive liver injury resulting from many diverse
562-93. causes including toxins, drugs, viruses, and para-
Annesley, James. 1825. Sketches of the most prevalent dis- sites. The clinical manifestations of cirrhosis vary
eases of India. London. according to the severity and duration of the underly-
Chambers, J. S. 1938. The conquest of cholera: America's ing disease. In the West, cirrhosis is a major cause of
greatest scourge. New York. disability and death among middle-aged alcoholic
Chevalier, Louis, 1958. he Cholera: La Premiere epidemie males. In the East and Africa, cirrhosis is predomi-
du XIX siecle. La Roche-sur-Yon. nantly an intermediate lesion in the evolution from
De, Sambhunath N. 1961. Cholera: Its pathology and chronic hepatitis B infection to primary hepatocel-
pathogenesis. Edinburgh and London.
lular carcinoma.
Delaporte, Francois. 1987. Diseases and civilization: The
cholera in Paris. Cambridge.
Dieffenbach, Johann Friedrich. 1832. Physiologisch-chirir- Classification
gische Beobachtungen bei Cholera-Kranken. Cholera- Cirrhosis is classified on the basis of morphology and
Archiv 1: 86-105. etiology. The morphological classification recognizes
Durey, Michael. 1979. The return of the plague: British
three types based on the size of the nodules:
society and the cholera, 1831—2. Dublin.
Evans, Richard J. 1987. Death in Hamburg: Society and
1. Macronodular cirrhosis. The liver is firm, large or
politics in the cholera years, 1830-1910. Oxford.
small in size, with bulging irregular nodules
Howard-Jones, Norman. 1972. Cholera therapy in the nine-
teenth century. Journal of the History of Medicine and
greater than 3 millimeters in diameter.
Allied Sciences 27: 373-95. 2. Micronodular cirrhosis. The liver is usually en-
Longmate, Norman. 1966. King cholera: The biography of larged, and very firm or hard in consistency. The
a disease. London. nodules on cut sections appear small and uniform,
Macnamara, C. 1870. A treatise on Asiatic cholera. London. less than 3 millimeters wide.
1876. A history of Asiatic cholera. London. 3. Mixed microlmacronodular cirrhosis. The liver

shows groups of small nodules interspersed with lar cirrhosis, and other causes in this category in-
fields of large nodules. clude primary biliary cirrhosis, primary hemo-
chromatosis, and chronic right heart failure. The
The terms "micronodular" and "macronodular" cir- macronodular deformation is seen in the cirrhosis
rhosis replace the older terminology, Laennec's and due to viral, drug, and cryptogenic origins, and in
postnecrotic cirrhosis. the end-stage cirrhosis of any etiology.
Neither the gross nor the microscopic appearance
of the liver can alone differentiate among the many Distribution and Incidence
causes (see Table VIII.28.1). In individual cases, the Cirrhosis is distributed worldwide, affecting all
etiology is often unknown. Alcohol injury is most races, nationalities, ages, and both sexes. Well over
frequently associated with the pattern of micronodu- 300,000 persons die of the disease annually. This
figure, based on World Health Organization statis-
tics of the 1960s, is an underestimate because coun-
Table VIII.28.1. Etiology and incidence of cirrhosis
tries such as mainland China and the former Soviet
Etiology Incidence
Union are not included. In the United States in
1983, cirrhosis ranked as the ninth leading cause of
Toxins and drugs 5—15% of chronic alcoholics mortality, accounting for 27,000 deaths.
Alcohol The worldwide incidence of cirrhosis is deter-
Methotrexate, methyldopa, mined chiefly by the per capita consumption of alco-
and isoniazid
hol and the prevalence of the hepatitis viruses. The
Infections 1-2% of acute infection rise in the number of cases of cirrhosis is attribut-
Hepatitis (non-A, non-B 5-15% of chronic disease able to an increase in one or both of these factors.
virus) Based on mortality statistics (WHO data, 1983 or
Hepatitis (delta virus) 20—60% of chronic disease 1984), the incidence of cirrhosis in various countries
Schistosomiasis japoni- can be grouped as follows:
cum
Disturbed immunity 1. Low incidence (less than 10 cirrhotic deaths per
Chronic active hepatitis 30-50% of chronic type B 100,000 population): Canada, Venezuela, En-
viral hepatitis gland, Scotland, Sweden, Netherlands, Australia,
Primary biliary cirrhosis 6-15 per 1 million popula- Hong Kong, and the United Arab Republic.
tion (incidence) 2. Intermediate incidence (11-23 per 100,000): Mex-
4-14 per 100,000 (preva- ico, United States, Denmark, and Japan.
lence) 3. High incidence (greater than 24 per 100,000):
Chronic cholestasis Chile, Austria, Italy, France, West Germany, and
Gallstone, biliary tumor, 1 per 8,000-15,000 live Portugal.
stricture, biliary atresia births Occurrence rates for the different types of cirrhosis
Mucoviscidosis 2-20% of patients (1 per are presented in Table VIII.28.1.
2,000 live births)
Metabolic disorders Epidemiology
Primary hemochromatosis 2-3 per 1,000 (prevalence) The statistics on cirrhosis suffer from the uncer-
Wilson's disease 30 per 1 million population tainty of diagnosis, which can be confirmed only on
(prevalence) autopsy or by liver biopsy. Nevertheless, the figures
Alpha-1-antitrypsin defi- 1 per 15,000 Scandinavian generated from many sources are sufficiently consis-
ciency adults
tent to establish that geography, race, age, sex, eco-
Vascular diseases nomic and social class and occupation; the amount,
Veno-occlusive disease duration, and pattern of alcohol consumption; and
Budd-Chiari syndrome prevalence of hepatitis viruses all modify the occur-
Chronic right heart failure rence of cirrhosis. The prevalence rate of cirrhosis in
Others autopsies averages 3 to 4 percent for most countries
Indian childhood cirrhosis in Europe, 5 to 8 percent for North and South Ameri-
Intestinal bypass cas, and 1 to 2 percent for Japan. Among selected
Cryptogenic causes
populations of patients, the prevalence rate of cirrho-
sis ranges from 0.7 percent in Copenhagen, to 1.3

percent in Wurzburg (Germany), 1.5 percent in Ath- whenever the sale of alcohol has been prohibited or
ens, and 3.8 percent in Abidjan (Ivory Coast). restricted during the twentieth century. A doubling
The older epidemiological studies, discussed by of alcohol intake in a country is followed by a 4-fold
John Galambos (1979), disclosed a rising incidence increase in alcohol-induced disease. The association
of cirrhosis, especially among women. Recent investi- between alcohol and cirrhosis has been further
gations have confirmed this trend. In the United strengthened by the confirmation of a dose-response
States, deaths from cirrhosis rose 71.7 percent from relation. The relative risk (RR) for cirrhosis among
1950 to 1974, while those due to cardiovascular dis- the French has been defined as follows:
ease fell 2 percent. The age-adjusted death rates
from cirrhosis in the United States in the period
1960-74 by race and sex showed that the increase 20-39 g alcohol/day 40-59 60-79 80-99
was marked for nonwhite males, moderate for non- Men 3.6 (RR) 4.56 13.47 21.60
white females, and only slight for white males and Women 4.13 21.60 32.17 _
females. For blacks in the United States, mortality
rates for cirrhosis were similar to or slightly lower
than those of the white population before 1955. The The risk of cirrhosis increases with the daily intake
pattern changed rapidly after that, with American of alcohol much faster in females than in males.
blacks experiencing an epidemic of cirrhosis com- Similar trends in cirrhotic risks also occur in Cana-
pared to the increase in whites. The rise in cirrhosis dian men and women for comparable levels of alco-
deaths followed a geographic pattern. Rates among hol consumption. Although progression to severe
the blacks quadrupled in urbanized coastal and liver injury is accelerated in women, the male/
northern regions and remained low in the southern female ratio remains at least 2:1 for most groups.
rural areas of the United States. Among whites the There are some notable exceptions, such as Ameri-
pattern was reversed, with the death rates increas- can Indian women - who account for 50 percent of
ing more in the southern than in the northern indus- the cirrhosis deaths of this ethnic group.
trial areas. For urban America, both male and fe- In the West, alcoholic cirrhosis comprises the major
male mortality rates for cirrhosis in the nonwhite share of all cirrhosis. An estimated 75 percent of
population are at least double those of the white cirrhosis in the United States is alcoholic in origin; 15
population. The overall cirrhosis mortality in the percent is viral, and 10 percent is cryptogenic. A
United States dropped in the late 1970s and, with different distribution pertains in Great Britain,
the exception of 1979, declined further in the early where 50 percent is alcoholic, 25 percent is crypto-
1980s. genic, and 25 percent is viral. In Asia and Africa,
Elsewhere, in Birmingham, England, the annual where the prevalence of hepatitis B virus is high and
incidence of cirrhosis rose from 5.6 per 100,000 the per capita consumption of alcohol is low, the pro-
population in 1959 to reach a peak of 15.3 in 1974, portion of virus-related cirrhosis to the alcoholic type
and then fell slightly. The annual death rate for is the reverse of that seen in the West. Past literature
cirrhosis in Denmark climbed from 7.5 per 100,000 written on the disease from data gathered from east
population in 1963 to 9.7 in 1978. When analyzed European countries suggests no association between
according to sex and age, the increase in mortality cirrhosis and viral hepatitis. The studies were done,
rate was 3-fold among young and middle-aged men, however, before the introduction of serologic markers
but fell by 50 percent among older women. In west- for hepatitis, and thus, the type of viral heptatitis was
ern Australia cirrhosis mortality for males over age not identified. The occurrence rate of hepatitis B vi-
30 increased from 14.1 per 100,000 in 1971 to 21.0 rus cirrhosis is uncertain (see Table VIII.28.1).
in 1982. Deaths from alcoholic cirrhosis increased Epidemiological studies strongly support the associa-
in Finland and Denmark 10-and 5-fold, respec- tion between chronic hepatitis B infection and the
tively, from 1961 to 1974. During the same period, development of primary hepatocellular carcinoma.
males in Sweden and Norway had, respectively, a Infection at birth results in chronic hepatitis, cirrho-
3-fold and 2-fold increase in mortality due to alco- sis, and carcinoma 2 to 3 decades later. How the virus
holic cirrhosis. causes the carcinoma is not understood, but the pro-
The steady rise in cirrhosis death rates in industri- cess involves cirrhosis, especially among males. Cir-
alized nations is linked to the increased per capita rhosis, like its sequela, hepatocellular carcinoma,
consumption of alcohol. Mortality figures from the is common in countries where hepatitis B virus is
United States, England, and France have dropped endemic.

Clinical Manifestations and Diagnosis discipline in the seventeenth century, sporadic re-
Clinically cirrhosis may be latent (5 to 10 percent of ports of the cirrhotic liver appeared. Among the earli-
cases), well compensated, or active and decompen- est illustrations of cirrhosis was that by Frederik
sated. The clinical features depend on the underly- Ruysch in his atlas of normal and abnormal anatomy
ing etiology and the appearance of the two cardinal (1701-16). In his massive tome on pathology, Gio-
manifestations, portal hypertension and hepatocel- vanni B. Morgagni (1716) introduced the term "tuber-
lular failure. As cirrhosis usually evolves over a cle" to denote any nodule of the liver. This covered a
period of several years, the course may be intermit- variety of lesions, and sowed the confusion between
tent with therapeutic intervention such as with carcinoma and cirrhosis of the liver for decades after-
corticosteroids or with temporary cessation of injury. ward. Among the English, William Harvey in 1616
During the early phase of disease, patients often reported on two cases of cirrhosis. He antedated John
present with nonspecific symptoms and signs includ- Browne, whose description in 1685 has been regarded
ing malaise, lethargy, anorexia, loss of libido, and by historians as the first in English. Matthew
weight gain. Incidental laboratory findings of abnor- Baillie's accurate description in 1793 established cir-
mal liver function tests, positive hepatitis B serology rhosis as a nosological entity in pathology. He also
and hypergammaglobulinemia, and incidental physi- noted the strong association between the disease and
cal findings such as icterus, hepatomegaly, gyneco- alcohol intake. During the eighteenth century, a sur-
mastia, and spider nevi may point to the presence of plus of corn led Parliament to promote distilling and
cirrhosis. With the progression of disease, portal hy- consumption of spirits as a way of stabilizing the
pertension and hepatocellular failure invariably su- price. The excessive consumption of cheap spirits
pervene. These two complications are interrelated in gave rise to an epidemic of cirrhosis, which became
their pathogenesis, and often represent the initial popularly known as "gin liver" in England and
presentation of many cirrhotics. Esophageal varices, "brandy liver" in other countries.
ascites, splenomegaly, and gastrointestinal hemor- Twenty-five years after Baillie, Rene Laennec,
rhage indicate elevated pressure in the portal ve- who invented the stethoscope, introduced the name
nous system. Jaundice and abnormal liver function cirrhosis in a brief footnote appended to a case discus-
tests may occur in early and mild hepatocellular sion. Subsequently, clinicians on the Continent be-
failure, which in its severe state is manifested as gan to speculate on the morphogenesis of the lesion.
hepatic encephalopathy and hepatorenal syndrome. In 1829, Gabriel Andral formulated the idea that
Prognosis need not be poor, as cirrhosis can be hypertrophy of the yellow substance of the liver that
checked, for example, in the alcoholic who abstains normally secretes bile accounted for the nodules,
from alcohol abuse. Treatment can reverse the he- whereas atrophy of the red substance containing the
patic fibrosis and improve the outlook of patients vessels represented the depressed areas of cirrhosis.
with chronic active hepatitis, primary hemochro- This concept, relating cirrhogenesis to the dual sub-
matosis, or Wilson's disease. On the other hand, stance of the liver, influenced thinking on this sub-
after ascites has developed, the 5-year survival rate ject for the next two decades. In 1838, Robert Cars-
falls to below 50 percent. well in England conjectured that cirrhosis depended
on the growth of interlobular connective tissue. The
History and Geography speculations acquired a more solid foundation when
The ancient Greeks recognized the clinical features microscopes with good resolving power became avail-
of cirrhosis. In about 300 B.C., Erasistratus associ- able. Also in the early nineteenth century, Gottlieb
ated ascites with liver disease. Galen, in the third Gluge and Dominique Lereboullet saw hepatic fat
century A.D., commented on the physical diagnosis, and argued that this was the basic lesion of cirrho-
and noted that heavy wine consumption "will in- sis, whereas Karl von Rokitansky attributed the
crease the damage to the liver when inflammation "granulations" of cirrhosis to the result of chronic
and scirrhus already existed." His contemporary, inflammation.
Aretaeus the Cappadocian, suggested that cirrhosis During the mid-nineteenth century, interest in
may evolve from hepatitis, and carcinoma, from cir- vascular studies gathered momentum after improve-
rhosis. The clinical descriptions left by the Greeks ments were made in cast corrosion techniques. The
remained unexcelled until recent times. vascular alterations in cirrhosis also came under
In the sixteenth century, Vesalius described rup- scrutiny during the latter half of that century and
ture of the portal vein in a lawyer with an indurated the first decades of this century, as researchers from
nodular liver. When pathological anatomy became a Lionel S. Beale writing in 1857-9, through the work

of A. H. Mclndoe in 1928, revealed the vascular as a routine method of diagnosis. The accumulated
damage that occurs with cirrhosis. Some, such as histologic studies clarified the relationship of hepati-
Karl von Liebermeister in 1864 and J. M. Legg in tis to cirrhosis, and cirrhosis to hepatocellular carci-
1872, continued to focus on the interlobular connec- noma. They also helped to consolidate the various
tive tissue as the seat of the cirrhotic process. Others classifications of cirrhosis proposed in the past. The
emphasized the regenerative aspects of cirrhosis recent standardization of nomenclature (see Table
which represented the end product of many injurious VIII.28.1) was proposed by the Fogarty Interna-
episodes. In 1911, Frank B. Mallory summarized the tional Center in 1976 and the World Health Organi-
clinicopathological features in an important paper zation in 1977.
that introduced the entity of alcoholic hepatitis. He Thomas S. N. Chen and Peter S. Y. Chen
regarded it as a precursor lesion of cirrhosis. Mal-
lory's concept was recently revived after a dormancy Bibliography
of 50 years. Chen, Thomas, S., and Peter S. Chen. 1984. Understand-
While pathologists debated the issue of morpho- ing the liver: A history. Westport, Conn.
genesis, speculations on etiology also abounded. Ear- Conn, Harold O., and Colin E. Attenbury. 1987. Cirrhosis.
lier it had been suggested that alcoholic fatty liver In Diseases of the liver, 6th edition, ed. Leon Schiff and
was the precursor of cirrhosis. By the second half of Eugene R. Schiff. Philadelphia.
the nineteenth century, most physicians accepted Galambos, John T. Cirrhosis. 1979. Philadelphia.
Garagliano, Cederic R, Abraham M. Lilienfeld, and Albert
this thesis, believing that alcohol intake increased I. Mendeldoff. 1979. Incidence rates of liver cirrhosis
hepatic fat, which in turn was converted into cirrho- and related diseases in Baltimore and selected areas
sis. However, experiments by P. Ruge in 1870 and G. of the United States. Journal of Chronic Disease 32:
de Rechter in 1892, among others, failed to demon- 543-54.
strate the cirrhogenic effect of alcohol in animals. Herd, Denise. 1985. Migration, cultural transformation
This result led to the notion that it was not alcohol and the rise of black liver cirrhosis mortality. British
but some contaminant in the alcohol, such as copper, Journal of Addiction 80: 397-410.
which damaged the liver, whereas another set of Jorke, D., and M. Reinhardt. 1982. Contributions to the
theories stressed that gastric malfunction was the epidemiology of liver cirrhosis and chronic hepatitis.
underlying cause in that disturbed gastric function Deutsche Zeitschrift fiir Verdauungs-und Stoffwechsel-
produced or allowed the absorption of hepatotoxins. krankheiten 42: 129-37.
The hypothesis of nutritional deficiency came to the Millward-Sadler, G. H., E. G. Hahn, and Ralph Wright.
foreground when experimenters such as J. M. Her- 1985. Cirrhosis: An appraisal. In Liver and biliary
disease, 2d edition, ed. Ralph Wright et al. Philadel-
shey and Samuel Soskin in 1931 and D. L. McLean phia.
and Charles H. Best in 1934 showed that the fatty Tuyns, A. J., and G. Pequignot. 1984. Greater risk of
liver condition caused by insulin deficiency could be ascitic cirrhosis in females in relation to alcohol con-
prevented by choline and other lipotropic agents. sumption. Internationsl Journal of Epidemiology 13:
Other dietary models of cirrhosis soon followed, in- 53-7.
cluding lipotroph deficiency, a low-fat diet, and vita-
min E deficiency. It remained for Harold P. Hims-
worth and L. E. Glynn in 1944 to correlate the two
pathways of cirrhogenesis: (1) a diffuse fatty liver
developing into a finely nodular cirrhosis seen in the
animal model with lipotroph deficiency; and (2) mas-
sive hepatic necrosis proceeding to the coarsely nodu-
lar liver created experimentally by cystine defi-
ciency. The nutritional theory declined in popularity
when careful experiments by Charles S. Lieber and
colleagues, among others, showed in 1968 that alco-
hol was directly hepatotoxic in humans, and
cirrhogenic in baboons.
Another technical innovation has advanced our
understanding of cirrhosis. Introduced by Paul Ehr-
lich in 1884, and popularized by P. Iversen and K.
Roholm in 1939, the liver biopsy achieved wide use

VIII.29
Clonorchiasis
The Chinese liver fluke is a small worm that The term croup is used in an inclusive way to iden-
parasitizes the bile ducts and livers of humans, dogs, tify several different respiratory illnesses of children
cats, pigs, and several wild animals in China, Japan, manifested by varying degrees of inspiratory stridor,
Korea, and Indochina. It was discovered in 1875, and cough, and hoarseness due to upper-airway obstruc-
recently, it was estimated that 20 million individuals tion. Classically croup was a manifestation of diph-
in China alone are infected. Eggs are laid in the bile theria. In the twentieth century, many other infec-
ducts, pass in the feces, and if they reach the proper tious causes of croup syndromes are recognized, and
freshwater snail, undergo a series of stages in this in addition, similar illnesses can be caused by non-
intermediate host. Eventually, free-swimming lar- infectious processes.
vae are formed, which penetrate and encyst the skin A classification of crouplike illnesses is presented
or muscles offish, expecially those of the carp family. in Table VIII.30.1. Although long-term obstruction
Human beings and other definitive hosts become in- in the glottic and subglottic regions can lead to
fected by eating the cysts (metacercaria) in raw or chronic illnesses, croup syndromes are described
poorly cooked fish. Rawfishare a delicacy in many here as acute self-limited or fatal illnesses. Most
Asian countries, and fish are sometimes raised in cases of croup today are either laryngotracheitis or
ponds fertilized with human feces. Encysted metacer- spasmodic croup.
caria larvae are resistant to smoking, pickling, salt-
ing, and drying. Imported fish have caused human Etiology
cases in Hawaii, and the popularity of Asian cuisine Acute epiglottitis (inflammation of the epiglottis) is
poses a potential danger to gourmets far beyond Asia. virtually always caused by Haemophilus influenzae
Light infections are often asymptomatic. Heavy type B; rare cases have been due to Streptococcus
infections may produce diarrhea, fever, jaundice, pneumoniae and Staphylococcus aureus. Laryngitis
and abdominal pain. Bile duct blockage and liver is usually due to the common respiratory viral
abscesses occur in chronic cases, and Clonorchis agents, the most important of which are adeno-
sinensis has been tentatively linked to liver cancer. viruses and influenza viruses.
Diagnosis is made by microscopic examination of the Laryngotracheitis and spasmodic croup are com-
feces to discover the characteristic eggs. Drug ther- mon illnesses in children and are due to viruses or
apy is sometimes successful. Preventive measures Mycoplasma pneumoniae. The most important agent
include rural sanitation, regulation of fish-farming is parainfluenza virus type 1. This virus, as well as
methods, and cooking fish thoroughly. It is unlikely, parainfluenza type 2 and influenza A and B viruses,
however, that long-established culinary practices results in outbreaks of disease. In areas of the world
can be changed.
K. David Patterson
Table VIII.30.1. Classification of
Bibliography crouplike illnesses
Hou, P. C. 1965. The relationship between primary carci-
noma of the liver and infestation with Clonorchis Infectious
sinensis. Journal of Pathological Bacteriology 72: Epiglottitis
239-46. Laryngitis
Kean, B. H., Kenneth E. Mott, and Adair J. Russell, eds. Laryngotracheitis and spasmodic croup
1978. Tropical medicine and parasitology: Classic in- Laryngotracheobronchitis
vestigations, Vol. II, 546—60. Ithaca and London. Laryngotracheobronchiopneumonitis
Kim, D. C , and R. E. Kuntz. 1964. Epidemiology of hel-
minth diseases: Clonorchis sinensis (Cobbold, 1875; Mechanical
Looss, 1907 on Taiwan, Formosa). Chinese Medical Foreign body
Journal 11: 29-47. Postintubation trauma
Komiya, Y. 1966. Clonorchis and clonorchiasis. In Ad- Allergic
vances in parasitology, ed. B. Dawes, 53—106. New Acute angioneurotic edema
York.

VIII.30. Croup 655
where diphtheria toxoid immunization is not carried will become worse and exhibit great anxiety if forced
out, laryngotracheitis is also caused by Coryne- to lie down.
bacterium diphtheria. Patients with epiglottitis will have leukocytosis
Laryngotracheobronchitis and laryngotracheo- with neutrophilia and positive blood cultures for H.
bronchiopneumonitis are frequently caused by the influenzae type B. The epiglottis is swollen and
same viruses that cause laryngotracheitis. These two cherry red. Therapy depends upon rapid diagnosis,
illnesses are caused also by S. aureus, Streptococcus the establishment of an airway, and the administra-
pyogenes, S. pneumoniae, and H. influenzae. tion of antibiotics appropriate for the treatment of
H. influenzae type B.
Epidemiology Acute Laryngotracheitis
Croup syndromes occur worldwide. Most illnesses
In this section, only viral causes of croup are dis-
are due to the common croup viruses: parainfluenza
cussed. Initial symptoms in laryngotracheitis are
types 1 and 2 and influenza viruses. Outbreaks occur
usually not alarming and include nasal dryness, irri-
every year during the cold-weather months; in the
tation, and coryza (profuse nasal discharge). Cough,
tropics croup is more common during the rainy sea-
sore throat, and fever occur. After 12 to 48 hours,
son. The highest attack rate occurs in children 7 to
signs and symptoms of upper-airway obstruction de-
36 months of age; few cases occur in children after
velop. The cough becomes "croupy" (sounding like a
the sixth birthday. During the second year of life,
sea lion), and there is increasing respiratory stridor
about 5 percent of children experience an episode of
(difficulty associated with inspiration). The degree
croup. Croup is more common in boys than in girls
of airway obstruction is variable. Most severe dis-
and also tends to be more severe in boys.
ease is manifested by marked respiratory distress
The viruses that cause croup are present in the with supra- and infraclavicular and sternal retrac-
nasal secretions of adults and children with colds tions, cyanosis, and apprehension. Hypoxia can oc-
and other upper and lower respiratory tract ill- cur, and if there is no intervention, asphyxial death
nesses. Virus is transmitted from infected persons will occur in some children.
by sneezing, nose blowing, and the general contami-
In laryngotracheitis the walls of the trachea just
nation of external surfaces (including the hands)
below the vocal cords are red and swollen. As the
with nasal secretions. A susceptible child can be-
disease progresses, the tracheal lumen will contain
come infected either by inhaling virus in droplet
fibrinous exudate, and its surface will be covered by
nuclei (small particles) or by a direct nasal hit of
pseudomembranes made up of exudative material.
virus-containing large droplets from a sneeze or nose
blowing. Infection can also occur indirectly as a re- Because the subglottic trachea is surrounded by a
firm cartilaginous ring, the inflammatory swelling
sult of contamination of the fingers of the recipient.
It is important to emphasize that parainfluenza vi- results in encroachment on the size of the airway; it is
rus infections in adults are manifested by colds; often reduced to a slit 1 to 2 millimeters in diameter.
older persons with relatively trivial illnesses may be The treatment of laryngotracheitis includes the
the source of severe croup in young children. following: oxygen for hypoxia,fluids(locally via aero-
sol and systemically) to liquefy secretions, racemic
epinephrine by aerosol to decrease inflammatory
Clinical Manifestations edema, and rarely the establishment of the mechani-
cal airway. Corticosteroids are also frequently ad-
Acute Epiglottitis ministered to decrease inflammation, but their use
Acute epiglottitis is a disease of relatively abrupt is controversial.
onset and rapid progression which, if untreated, re-
sults in death due to airway obstruction. Illness is Spasmodic Croup
characterized by fever, severe sore throat, dys- This croup is a distinct clinical syndrome, which in
phasia, and drooling. Airway obstruction is rapidly some instances is difficult to distinguish from mild
progressive and is associated with inspiratory dis- laryngotracheitis. In contrast to laryngotracheitis in
tress, a choking sensation, irritability, restlessness, which the obstruction is due to inflammatory exu-
and anxiety. In contrast to viral croup, the patient is date and cellular damage, the obstruction in spas-
not hoarse and does not have the typical "croupy modic croup is due to noninflammatory edema. Ill-
cough," but the speech is muffled or thick-sounding. ness always has its onset at night, and it occurs in
The child with epiglottitis insists on sitting up and children thought to be well or to have a mild cold

with coryza. The child awakens from sleep with sudan epidemic in Alkuaer, Holland. Then in 1576, Guil-
den dyspnea, croupy cough, and inspiratory stridor. laume de Baillou described an epidemic in Paris and
There is no fever. specifically commented on false membrane. In 1771
Spasmodic croup tends to run in families, and af- Samuel Bard published the first U.S. report on the
fected children often have repeated attacks. Treat- nature, causes, and treatment of suffocative angina.
ment relies upon the administration of moist air and Pierre Bretonneau named diphtheria in 1826 and rec-
reassurance by the parents. ognized its infectious nature. T. A. Edwin Klebs in
1883 noted the diphtheria bacillus in smears from
Acute Laryngotracheobronchitis and pseudomembranes, and a year later Friedrich Loffler
Laryngotracheobronchiopneumonitis established the organism as the etiologic agent.
These illnesses are less common than laryngo- From 1920 to 1940 the incidence of diphtheria in
tracheitis and spasmodic croup but are more serious. the United States fell from approximately 200 cases
Initial symptoms and signs are similar to those of to 20 cases per 100,000 population as a result of the
laryngotracheitis. Usually the signs of lower respira- use, first, of toxin-antitoxin and then of toxoid. In
tory involvement develop 2 to 7 days into the illness; association with this decline in diphtheria, and also
occasionally both upper- and lower-airway obstruc- predating it, there was a general realization of other
tions occur simultaneously. In addition to the usual cases of croup in this century. Prior to 1900, only
findings in croup, patients with laryngotracheo- occasional notations of illnesses suggesting nondiph-
bronchiopneumonitis will have rales, air trapping, theritic croup appeared. For example, E. Bouchut in
wheezing, and an increased respiratory rate. 1852 described false croup, Stridalous laryngitis,
The illness is due to a more generalized infection which seems to have been spasmodic croup. In his
with parainfluenza or influenza viruses or to secon- treatise (1887), Sanne referred to an epidemic of
dary bacterial infection of the trachea, bronchi, and simple croup in Germany, and Home (1765) noted
lungs. Exudate, pseudomembrane, and respiratory two forms of croup. Bretonneau differentiated diph-
epithelial damage occur. Care involves appropriate theria from spasmodic croup in 1826.
antibiotics in addition to conventional treatment for In the United States during the first half of the
laryngotracheitis. twentieth century, severe croup was called laryngo-
tracheal-bronchitis. It was recognized that it was
History caused by C. diphtheria bacteria and by other bacte-
The word croup is derived from the Anglo-Saxon word ria as well. In 1948, Edward Rabe described three
kropan, meaning "to cry aloud." Croup was first used types of croup infections: diphtheritic croup, H. influ-
in medical writing in 1765 by Francis Home, a Scot- enzae type B croup (epiglottitis), and "virus" croup.
tish physician. Until this century virtually all croup- Shortly thereafter, with the widespread use of tissue
like illnesses were confused with diphtheria. culture techniques, the viral etiology of croup was
Daniel Slade in 1864 traced the clinical history of confirmed. During a period of approximately 30 years
diphtheria to the time of Homer, and A. Sanne in (1950-79), croup due to bacteria other than C. diph-
1887 believed that the writings of Hippocrates dem- theria was overlooked in medical papers and text-
onstrate knowledge of diphtheria. Aretaeus of Cap- books. In 1976, nondiphtheria/bacterial croup was
padocia, in the second century A.D., noted extension rediscovered, and since then it has received consider-
of the disease to the lower respiratory tract, which able attention in the literature.
resulted in death by suffocation. Galen noted the The history of spasmodic croup is not clear because
expectoration of the pseudomembrane. At this time, the clinical and pathological aspects of the entity are
the disease was common in Syria and Egypt and was poorly defined. In the 1940s spasmodic croup was
called ulcus Syriacum or Egyptiacum by Aretaeus. separated from other more severe forms of croup by
Aetius of Amidu, in the fifth century, added his expe- Francis Davison; however, since then the patho-
riences to the previous descriptions of Aretaeus. Al- genesis of this entity has received little attention.
though both Aretaeus and Aetius were describing James D. Cherry
diphtheritic croup, it is clear that there was confu-
sion with other illnesses such as Ludwig's angina
Bibliography
and streptococcal tonsillitis. Bouchut, E. 1859. Bouchut on croup. In Memoirs on diph-
The historical trail of diphtheria disappeared in theria, ed. Robert Hunter Semple, 271-97. London.
the fifth century and did not reappear until the six- Cherry, James D. 1981. Acute epiglottitis, laryngitis, and
teenth century: First, in 1557, Peter Forest described croup. In Current clinical topics in infectious diseases,

VIII.31. Cystic Fibrosis 657
ed. J. S. Remington and M. N. Swartz, 1-29. New
York. vm.31
1987. Croup (laryngitis, laryngotracheitis, spasmodic
croup, and laryngotracheobronchitis). In Textbook of Cystic Fibrosis
pediatric infectious diseases, Vol. II, ed. R. D. Feigin
and J. D. Cherry, 237-50. Philadelphia.
Cramblett, Henry G. 1960. Croup - present day concept. Cystic fibrosis, also called fibrocystic disease of the
Pediatrics 25:1071-6. pancreas, and mucoviscidosis, is a genetically deter-
Davison, Francis W. 1950. Acute obstructive laryngitis in mined disease of infants, children, and young adults.
children. Pennsylvania Medical Journal 53: 250-4. Most of its many manifestations result from the ab-
Gittins, T. R. 1932. Laryngitis and tracheobronchitis in normally viscous mucus, which interferes with pul-
children: Special reference to non-diphtheritic infec- monary function, and the insufficient production of
tions. Annals of Otology, Rhinology and Larynology pancreatic digestive enzymes, which causes nutri-
41: 422-38. tional deficiencies and developmental retardation.
Guersant. 1959. Guersant on croup. In Memoirs on diph-
theria, ed. Robert Hunter Semple, 207-32. London.
Home, Francis. 1765. An inquiry into the nature, cause Etiology
and cure of the croup. Edinburgh. Among Caucasians, cystic fibrosis (CF) is the most
Jacobi, A. 1880. A treatise on diphtheria. New York.
common fatal disease having an autosomal recessive
Mortimer, Edward A. 1988. Diphtheria toxoid. In Vac-
cines, ed. S. A. Plotkin and E. A. Mortimer, 31-44.
inheritance. Despite the primary involvement of sev-
Philadelphia. eral organs, the disease is caused by a single defec-
Nelson, Waldo E. 1950. Acute spasmodic laryngitis. In tive gene that is located on chromosome 7 and is
Textbook of pediatrics, ed. Waldo E. Nelson, 951. carried by about 4 percent of the Caucasian popula-
Philadelphia. tion. Its expression is similar in both sexes.
1959. Acute laryngotracheobronchitis. In Textbook of
pediatrics, ed. Waldo E. Nelson, 778-80. Philadelphia.
1984. Bacterial croup: A historical perspective. Journal Clinical Manifestations
of Pediatrics 105: 52-5. CF manifests itself at birth in about 8 percent of
Rabe, Edward F. 1948a. Infectious croup: I. Etiology. Pedi- cases through mechanical obstruction of the small
atrics 2: 255-65. intestine by the secretion of abnormally viscous mu-
1948b. Infectious croup: II. "Virus" croup. Pediatrics 2: cus (meconium ileus). Symptoms of insufficient secre-
415-27.
tion of exocrine (noninsulin) digestive enzymes by
Sann6, A. 1887. A treatise on diphtheria. St. Louis.
the pancreas appear during the first year of life in 90
Slade, Daniel D. 1864. Diphtheria: Its nature and treat-
ment. Philadelphia.
percent of cases. The development of such symptoms
Top, Franklin H. 1964. Diphtheria. In Communicable and indicates that pancreatic function is less than 10
infectious diseases, ed. F. H. Top, 217—35. Saint Louis. percent of normal; and the more severe the defi-
ciency of pancreatic enzymes, the more severe the
fecal excretion of undigested fat, usually as diar-
rhea. As much as 80 percent of dietary fat may be
lost, thus partially explaining malnutrition. Loss of
undigested nutrients can be corrected only partially
by treatment with pancreatic enzyme tablets. Pulmo-
nary disease is responsible for most of the debility
and mortality. Onset occurs in the first 2 years of life
in at least 75 percent of cases, and by the age of 6
years in most of the remaining cases. The initial
pulmonary abnormality is obstruction of the small
bronchi by abnormally thick mucus. Structural dete-
rioration of the lungs results in part from this and is
exacerbated by an increased susceptibility to infec-
tions. A small number of patients retain sufficient
pancreatic function to maintain nearly normal diges-
tion; such patients also tend to have fewer respira-
tory difficulties. The variability in severity is ex-

plained by the occurrence of several different muta- Bibliography
tions on the pathogenetic gene. Andersen, D. H. 1938. Cystic fibrosis of the pancreas and
The sweat of a child with CF contains a concentra- its relation to celiac disease: A clinical and pathologi-
tion of sodium and chloride that is about five times cal study. American Journal of Diseases of Childhood
greater than normal, although salt is not lost exces- 56: 344-99.
sively by other routes. Determining the salt content Boat, T. E, M. J. Welsh, and A. L. Beaudet. 1989. Cystic
fibrosis. In The metabolic basis of inherited disease,
of perspiration has become a basic diagnostic test.
6th edition, ed. C. R. Scriver, et al., 2649-80. New
The propensity to become salt-depleted makes per- York.
sons with CF particularly intolerant to heat. As a Dean, M., et al. 1990. Multiple mutations in highly con-
result of pulmonary and metabolic therapy, many served residues are found in mildly affected cystic
CF patients are now living into reproductive age, fibrosis patients. Cell 61: 863-70.
and thus it has been found that CF men, but not CF Denning, C. R., S. C. Sommers, and H. R. Quigley. 1968.
women, are sterile. In spite of all efforts, few pa- Infertility in male patients with cystic fibrosis. Pediat-
tients survive to age 40. rics 41: 7-17.
Fanconi, G., E. Uehlinger, and C. Knauer. 1936. The
History and Geography coeliac syndrome in congenital cystic fibrosis of the
According to a medieval German saying, "The infant pancreas and bronchiectasis. Wiener Medizinische
who when kissed leaves a taste of salt will not reach Wochenschrift 86: 753-6.
Gaskin, K., et al. 1982. Improved respiratory prognosis in
the first year of life." Hence, ,CF was probably recog-
patients with cystic fibrosis with normal fat absorp-
nized many centuries ago. However, it was first iden- tion. Journal of Pediatrics 100: 857-62.
tified in 1936 by the Swiss pediatrician Guido Kerem, B., et al. 1989. Identification of the cystic fibrosis
Fanconi and associates, and further delineated by gene: Genetic analysis. Science 45: 1073-80.
Dorothy H. Andersen of New York in 1938. The Klinger, K. W. 1983. Cystic fibrosis in the Ohio Amish:
diagnostic perspirational salt loss was quantified by Gene frequency and founder effect. Human Genetics
Paul di Sant'Agnese and associates (New York) in 68: 94-8.
1953. Kulczycki, L., and V. Schauf. 1974. Cystic fibrosis in
CF is most prevalent among people of central Euro- blacks in Washington, D.C.: Incidence and characteris-
pean ancestry (1 in 2,000 to 3,000 births) and is tics. American Journal of Diseases of Childhood 127:
somewhat less common in Scandinavia. Inbreeding 64-7.
explains incidences of greater than 1 per 1,000 in Sant'Agnese, P. A. di, R. C. Darling, and G. A. Perea. 1953.
Abnormal electrolyte composition of sweat in cystic
small areas. For example, the prevalence of CF
fibrosis of the pancreas. Pediatrics 12: 549-63.
among nearly 11,000 Amish in one Ohio county was Sant'Agnese, P. A. di, and P. B. Davis. 1979. Cystic fibrosis
more than 1 per 600, with all cases within six fami- in adults. American Journal of Medicine 66: 121-32.
lies, whereas there were no cases in another Amish Selander, P. 1965. The frequency of cystic fibrosis of the
community in a nearby county. Similar results of pancreas in Sweden. Ada Paediatrica Scandinavica
inbreeding have been reported from Brittany and 51: 65-7.
from Afrikaners in Namibia. CF has been reported Wright, S. W., and N. E. Morton. 1968. Genetic studies on
in about 1 in 17,000 black Americans, and in 1 in cystic fibrosis in Hawaii. American Journal of Human
90,000 Orientals (mainly Japanese) in Hawaii. The Genetics 10: 157-68.
prevalence of CF has not been investigated ade-
quately in Asia or Africa1. It is possible that its true
prevalence is masked by high infant mortality in
large portions of these continents.
The CF gene was identified in 1989. With the
rapid advances in gene.transfer therapy, it may soon
become possible to correct the defect from which the
multiple pathological processes of this disease re-
sult. Then, instead of merely prolonging life by treat-
ing the symptoms, physicians may give CF infants a
normal future.
Thomas G. Benedek

VIII.32. Cytomegalovirus Infection 659
transfusion of blood or its products, the infectious
vm.32 mononucleosis syndrome usually appears as a post-
transfusion episode at 2 to 4 weeks. Immunocom-
Cytomegalovirus Infection promised patients are at special risk of exogenous
infection by transplanted organs or by transfusions,
Cytomegalic inclusion disease (CID) usually occurs or of activation of the latent state. Death may occur
as a subclinical infection followed by periodic reacti- from interstitial pneumonia, often complicated by
vation revealed by shedding of the virus. It may be superinfection with gram-negative organisms, fungi,
serious in the neonate when infection is transmitted or other unusual invaders.
to the fetus in utero.
Serologic studies show that cytomegalic inclusion
Clinical Manifestations and Pathology disease has a worldwide distribution. It remains
Cytomegalic infection is characterized histologically asymptomatic despite prolonged shedding of the vi-
by the presence of large cells containing inclusion rus at periodic reactivation but is not highly commu-
bodies in the midst of an infiltration of mononuclear nicable. Presumably the virus is spread mainly by
cells that may be present in any of the body organs. contact with oral secretions because it is shed from
the salivary glands, and cultures from pharyngeal
In prenatal infections most infants are born without lymphoid structures commonly are positive. The vi-
clinical evidence of disease, although some 10 to 15 rus has been isolated from urine, breast milk, se-
percent may show microcephaly, retardation of men, and cervix uteri, and consequently the infec-
growth or mental development, hepatosplenomegaly, tion may be a sexually transmitted disease.
jaundice, and calcifications in the brain. There may The most serious aspect of CID is its role as a
be abnormalities in liver function tests and in prenatal disease. Even though the mother is asymp-
hematopoiesis. Some 10 to 30 percent of infants with tomatic and immune, transmission of the virus to
symptomatic disease die in early life. Evidence of the fetus does occur. Recurrence of infection is the
involvement of the central nervous system can de- most probable explanation for prenatal infection al-
velop in the early years of life, even though the child though, of course, primary infection may occur dur-
may appear normal. The evidence is manifested as ing pregnancy, and there is evidence suggesting that
impaired intellect, neuromuscular abnormalities, infection in the offspring is more serious under such
chorioretinitis, optic atrophy, or hearing loss. circumstances than when infection takes place be-
Neonatal infection acquired at birth from an in- cause of recurrence in a mother protected by anti-
fected cervix or later from the mother's milk usually bodies. A recent study has shown that children in-
goes unnoticed but can be identified by the develop- fected in a day-care center may be the source of
ment of antibodies. In addition, respiratory symp- infection for pregnant mothers.
toms including pneumonia, as well as petechial rash With a disease spread mainly by oral secretions, a
and enlargement of the liver and the spleen, may higher incidence is to be anticipated in those living
occur. In these cases, however, acute involvement of in crowded and unhygienic surroundings. For exam-
the central nervous system is rare. ple, 100 percent of the women in Tanzania have
Infection in children is generally asymptomatic antibodies by the time they reach childbearing age.
and is evidenced only by the development of anti- Other studies show seropositivity in 50 to 80 percent
bodies and the shedding of virus. Occasionally of children in boarding schools and orphanages in
hepatosplenomegaly and abnormal liver function England as compared to 10 percent to 20 percent in
are found. There is no proof that pharyngitis occurs children of the same age attending day schools. In
at the presumed portal of entry. Puerto Rico, between 70 and 80 percent of adults
When infection occurs in adults the clinical pic- have the antibodies, whereas in London the figure is
ture is similar to infectious mononucleosis, with only 50 to 60 percent. J. A. Hanshaw has pointed out
pharyngitis; lymphadenopathy; systemic symptoms that studies in the United States and the United
of fever, chills, and headaches, and occasionally a Kingdom show that from 0.2 to 7.5 percent of new-
maculopapular rash being the primary symptoms. boras are virus positive, making this disease the
Atypical lymphocytosis is usual, and there may be most common fetal infection. In the United States,
abnormal liver function. the complement-fixing antibody is present in 5 to 25
In instances where the disease is transmitted by percent of infants 8 to 24 months of age. In a study of

the prevalence of cytomegalovirus excretion in 244 Jordan, M. Colin. 1983. Cytomegalovirus infections. In
children aged from less than 1 year to 4 years in five Infectious diseases, ed. Paul D. Hoeprich, Chap. 75, 3d
day-care centers of a southern city of the United edition. Philadelphia.
States, each child was tested for viral isolation by Lang, David J. 1924. Cytomegalovirus infections. In Sexu-
mouth swab and urine sample. It was found that 49 ally transmitted diseases, ed. King K. Holmes et al.,
percent, 40 percent, 32 percent, 13 percent, or 9 Chap. 44. New York.
percent of children, depending on the center, were Pass, R. R, et al. 1987. Young children as probable source
of maternal and congenital cytomegalovirus infection.
excreting virus. Of the workers at the centers, 50 to
New England Journal of Medicine 316: 1366-70.
100 percent had antibodies to the virus, as did 56 to Weller, Thomas H. 1971. The cytomegaloviruses: Ubiqui-
88 percent of the parents. tous agents with protean clinical manifestation. New
England Journal of Medicine 185: 203-14.
Immunology 1981. Clinical spectrum of cytomegalovirus infection. In
Antibodies develop upon infection to last for life. The human herpesviruses: An interdisciplinary per-
Nevertheless, as in other diseases caused by the her- spective, ed. Andrew J. Nahmias et al. New York.
pesviridae, the presence of circulating antibodies
even in high titer does not forestall recrudescences
of infection.

Early in this century, pathologists noted the en-
larged cells with inclusion bodies in organs of chil-
dren dying of presumed congenital syphilis. The in-
clusions were thought to be amebae. In 1921 E. W.
Goodpasture and F. B. Talbot noted their similarity Dengue is an acute febrile disease caused by infec-
to changes found in varicella and guessed they repre- tion with a group B arbovirus of four serotypes,
sented viral infection and described the cellular en- transmitted by the bite of infected Aedes aegypti and
largement as "cytomegaly." The virus was isolated Aedes albopictus mosquitoes. Endemic throughout
in 1956 by investigators working independently in the tropics and subtropics, uncomplicated dengue is
St. Louis, Boston, and Bethesda. Epidemiological rarely fatal, although return to normal health after
studies became feasible with the recognition of anti- an attack may take several weeks. It does not al-
bodies to the virus in 1968. A rapid expansion of ways have a benign course, however, and can be
knowledge concerning epidemiology, incidence, and complicated by hemorrhagic manifestations (hemor-
clinical manifestations continues from the late rhagic dengue) and circulatory collapse (dengue
1960s. shock syndrome) with a potentially fatal outcome
R. H. Kampmeier unless facilities are available for the urgent medical
treatment of those affected.
Bibliography Typical uncomplicated dengue has an incubation
Anon. 1985. Epidemiologic Note. Prevalence of cytomega- period of 3 to 15 days and is characterized by abrupt
lovirus excretion from children in five day care onset of chills, headache, lumbar backache, and se-
centers - Alabama. Morbidity and Mortality Weekly vere prostration. Body temperature rises rapidly, per-
Report. Centers for Disease Control. U.S. Public haps reaching as high as 40°C; bradycardia (slow
Health Service 34: 49-51. heart rate) and hypotension (low blood pressure) ac-
Diosi, P. L., et al. 1967. Cytomegalovirus infection associ- company the high fever. Conjunctival injection,
ated with pregnancy. Lancet 2: 1063—6. lymph node enlargement, and a pale, pink rash,
Goodpasture, E. W., and F. B. Talbot. 1921. Concerning the especially noticeable on the face, are usually present
nature of "protozoan-like cells" in certain lesions of during this first phase of the disease. In classical
infancy. American Journal Diseases of Children 21: dengue, the fever lasts for 48 to 96 hours initially,
415-25.
subsides for 24 hours or so, and then returns (saddle-
Hanshaw, J. A. 1971. Congenital cytomegalovirus infec-
tion: A fifteen year perspective. Journal of Infectious back fever), although the peak of temperature is usu-
Disease 123: 555-61. ally lower in the second phase than in the first. A
Harris, J. R. 1975. Cytomegalovirus infection. In Recent characteristic red rash appears in the second phase,
advances in sexually transmitted diseases, ed. R. S. usually covering the trunk and extremities, but spar-
Morton and J. R. W. Harris, Chap. 42. London. ing the face. The fever, rash, and headache, together

VIII.33. Dengue 661
with the other pains, are known as the dengue triad. transovarially (from female mosquitoes to their off-
The acute illness ends in 8 to 10 days, and one attack spring through infection of the eggs) and from per-
confers immunity to the particular dengue subtype. son to person. Populations of A. albopictus found in
Hemorrhagic dengue usually strikes children un- the United States are capable of overwinter survival
der the age of 10 and has its highest mortality rate in northern latitudes because they are capable of
in infants under the age of 1 year. It is more likely to diapause, and thus the spread of this particular mos-
occur when type 2 dengue virus infection follows an quito represents a major public health concern. Al-
earlier type 1 infection in the same individual or though recent outbreaks of dengue in Brazil have
when subgroup-specific antibodies have been ac- been attributed to A. aegypti, the presence of A.
quired transplacentally from an immune mother, a albopictus gives rise to serious concern that it may
phenomenon known as enhancement. Signs of this become an important vector for the introduction of
ominous complication usually occur between the sec- flaviviruses into areas previously free of them.
ond and the sixth day of the illness and include A. albopictus is primarily a sylvan species that
sudden collapse with a rapid pulse of low volume; has become adapted to the urban environment, al-
cyanosis (blue discoloration) of lips, ears, and nail though it is not as strongly dependent on humans as
beds; and cold, clammy extremities while the trunk is A. aegypti. It breeds in tree holes, bamboo stumps,
remains warm. Nosebleeds, the appearance of spon- coconut husks, and other naturally occurring con-
taneous bruising, prolonged bleeding from injection tainers in Asia, as well as in tires and discarded
sites, and bleeding from both the upper and lower water containers. It has apparently been established
gastrointestinal tract signal the gross disturbances in Hawaii for many years, although Hawaii seems to
of blood coagulation mechanisms that occur in this be free from dengue.
form of the disease. Dengue outbreaks are particularly likely in en-
The world dengue comes from the Spanish, a hom- demic areas when there has been a heavy rain-
onym for the Swahili Ki denga pepo (a sudden fall. Monthly rainfall exceeding 300 mm is asso-
cramplike seizure caused by an evil spirit); it was ciated with a 120 percent increase in the number of
introduced into English medical usage during the cases of dengue, and the lag time between the onset
Spanish West Indies epidemic of 1827 and 1828. The of heavy rain and the outbreak of dengue is between
synonym breakbone fever dates from Philadelphia in 2 and 3 months. Any condition that increases the
1780, and the term knokkel-koorts comes from Bata- number of mosquito breeding sites, or the number of
via about the same year. All of these terms refer to susceptible persons, in dengue endemic areas auto-
some characteristic of the disease, either its sudden matically facilitates the transmission of dengue.
onset or the severity of its musculoskeletal pain, or
both. Immunology
Infection with one dengue serotype confers long-
Etiology and Epidemiology lasting type-specific protection, a benefit that may be
Dengue viruses belong to the family of flaviviridae, more apparent than real because the type-specific
the prefix of the family name being derived from protection also brings a greatly increased susceptibil-
flavus (Latin: "yellow") and referring to the yellow ity to severe dengue disease in the event of infection
fever virus. The family consists of the genus with dengue virus of another serotype. Epidemiolo-
Flavivirus, %hich has 65 related species and two gical studies clearly link the severe forms of dengue
possible members - cell fusing agent (CFA) virus disease to previous dengue infection and to trans-
and simian hemorrhagic fever virus. placental acquisition of maternal dengue antibody.
Mostflavivirusesare arboviruses, and all are sero- Dengue virus infects mononuclear phagocytes,
logically interrelated. They infect a wide range of and there is both in vitro and in vivo evidence that
vertebrate hosts, causing asymptomatic infections the interaction is facilitated and severe infection
and diseases such as yellow fever, dengue, and nu- more likely when antibody to another dengue sero-
merous encephalitides. A. aegypti and A. albopictus type is present. This phenomenon alone has impor-
are responsible for dengue transmission in Asia. A. tant implications for the development of dengue vac-
albopictus has recently been discovered in the cines. Administration of monovalent or polyvalent
United States and in Brazil, but it has not yet been vaccines, even if they were now available for human
implicated in the transmission of disease. It is an use, carries with it serious risk of predisposing par-
aggressive, human-biting mosquito with both urban tially immune populations to further and more seri-
and rural habitats and transmits dengue viruses ous dengue virus disease.

Secondary dengue infections that carry no risk of membranes) in 13 patients, gastrointestinal bleed-
dengue hemorrhagic fever or dengue shock syn- ing in 4 patients, and gum bleeding in 1 patient.
drome can occur when sequential dengue infections Common laboratory findings in 29 patients admit-
occur at intervals of 5 or more years, when sequen- ted to hospitals were low white blood cell count,
tial infections do not end with dengue type 2, and relative lymphocytosis (71 percent), and a reduced
when two or more dengue viruses, including type 2, platelet count. All four dengue serotypes were iso-
are endemic in the same area. Malnourished chil- lated (12 cases of dengue 1, 4 cases of dengue 2, 5 of
dren and alpha-thalassemia patients have a greatly dengue 3, and 1 of dengue 4). All patients survived
reduced risk of dengue hemorrhagic fever and their illness and returned to normal health. This
dengue shock syndrome. outbreak of mixed classical benign dengue fever and
dengue hemorrhagic fever of multiple serotype is
Clinical Manifestations and Pathology typical of current dengue epidemics.
Dengue is characterized by sudden onset of high fe- Severe dengue disease - dengue hemorrhagic fe-
ver, headache, prostration, joint and muscle pain, ver and dengue shock syndrome - proceeds through
lymphadenopathy, and a rash that appears simulta- two stages. The first is similar to that of benign
neously with a second temperature rise following an dengue; however, patients deteriorate during or
afebrile period (saddle-back fever). However, classi- shortly after the fall in temperature. If hypovolemic
cal saddle-back fever occurs in only 50 percent of shock supervenes (because of a greatly reduced vol-
cases; lymphadenopathy is not an invariable finding; ume of plasma), untreated patients may expire
and the rash may either never develop at all or else within 6 hours. The clinical evidence of disturbances
not develop until the fourth or fifth day, or during the of blood coagulation is accompanied by abnormal
second phase if the fever is saddle-backed. laboratory tests. Hemoconcentration and reduced
An outbreak of dengue fever occurred at Clark Air platelet count are invariable findings. Reduced lev-
Force Base, a large U.S. military installation located els of serum albumin, elevations of serum trans-
about 70 kilometers north of Manila on Luzon Island, aminases and blood urea nitrogen, prolonged pro-
Republic of the Philippines, between June and Sep- thrombin time, and reduced serum levels of factors
tember 1984. Of 119 persons suspected of having II, V, VI, IX, and XII are common. Hypofibrino-
dengue, 42 cases were confirmed by hemaggluti- genemia is a frequent finding, and the condition is
nation-inhibition (HI) antibody seroconversion or by best described as an acute vascular permeability
virus isolation. Seroconversion implies that HI anti- syndrome accompanied by activation of the blood
body was lacking in the serum of patients at an early clotting and complement systems.
stage of their illness, but could be detected subse- The World Health Organization has developed di-
quently, usually during convalescence, providing in- agnostic criteria for dengue hemorrhagic fever and
direct evidence of the cause of the illness. Virus isola- dengue shock syndrome:
tion from the blood of dengue-infected persons is the
most accurate diagnostic test for dengue, but it is Clinical
impracticable for widespread use because the vast a. Fever - acute onset, high, continuous, and lasting
majority of cases of dengue infection occur in parts of for 2 to 7 days
the world where sophisticated medical facilities are b. Hemorrhagic manifestations including at least a
simply not available. A further nine cases were con- positive tourniquet test and any of:
sidered to be probable dengue, as HI antibody was petechiae, purpura, ecchymosis (skin eruptions)
detectable in serum obtained from patients during nose or gum bleeding
the acute phase of their illness. hematemesis and/or melena (passing of black
The most frequent clinical findings were fever (97 stools)
percent), headache (80 percent), and muscle and c. Enlargement of liver
joint pain (80 percent). Other signs and symptoms d. Shock - manifested by rapid and weak pulse with
frequently reported were malaise, chills, anorexia, narrowing of the range of pulse pressure (20
nausea, vomiting, diarrhea, and maculopapular skin mmHg/2.7 kPa or less) or hypotension, with cold,
eruption (blotchy, raised, red rash). Dizziness, un- clammy skin, and restlessness
usual taste sensation, and itching/scaling of the Laboratory
palms were less frequently reported. Hemorrhagic a. Thrombocytopenia (0.10 x 1012/L or less)
signs occurred in 18 patients and consisted of petech- b. Hemoconcentration - hematocrit increased by 20
iae (pinpoint hemorrhages into skin and mucous percent or more

VIII.33. Dengue 663
Distribution and Incidence with shock and death were reported during the
Dengue literally girdles the globe, with a distribution 1984-5 Mozambique epidemic. Review of data from
approximately equal to that of its principal vector, A. the 1897 epidemic of dengue in north Queensland
aegypti. Areas of dengue endemicity include tropical suggests that the deaths of 30 children were the
and subtropical regions of the Americas, Africa, Asia, result of dengue shock syndrome.
and Australia. There are areas of A. aegypti infesta- A. aegypti is primarily a domestic mosquito, breed-
tion in Europe and in the southern United States, ing around areas of human habitation in discarded
where dengue has caused epidemics in the fairly dis- tires, cans, and other containers that can act as
tant past, but which have no current dengue activity receptacles for the water necessary for the mosqui-
although they remain susceptible to its reintroduc- toes' breeding places. Worldwide increase in dengue
tion. The example of the 1927-8 outbreak of dengue activity appears to be directly related to a failure to
in Athens and adjacent areas of Greece illustrates control mosquito populations effectively, to overpopu-
such a situation, for, although type 1 dengue virus lation, to progressive urbanization, and to the social
caused an epidemic with a high incidence of hemor- and political disruptions caused by wars. Although a
rhagic manifestations and a high death rate in the jungle cycle involving forest mosquitoes and wild
region, that region today is not considered to be one of monkeys, in a fashion similar to that of yellow fever,
significant dengue prevalence. has been demonstrated, zoonotic acquisition of
Types 1, 2, 3, and 4 dengue viruses are endemic in dengue does not appear to be a factor in the general
Asia. Types 1, 2, and 3 are prevalent in Africa, pattern of increasing dengue prevalence.
where type 3 is the most recent arrival, first identi- The current pattern of dengue epidemiology in the
fied in Mozambique during the 1984-5 epidemic. Americas resembles that of Southeast Asia in the
Types 1, 2, 3, and 4 are now present in the Americas, 1950s, before it changed from a benign flulike illness
where type 1 made its first appearance in 1977; in to the leading cause of morbidity and mortality in
the Caribbean, type 4 appeared in the same region children.
in 1981. Type 1 dengue virus was found to be respon-
sible for the 1981—2 Australia epidemic in northern History and Geography
Queensland. Dengue has been known as a distinct disease entity
Dengue fever epidemics typically involve large for at least several centuries. Benjamin Rush is tradi-
numbers of people and have a high attack rate. As tionally given credit for historical priority with his
many as 75 percent of the susceptible persons exposed account of breakbone fever, the epidemic that af-
to dengue virus will acquire the disease. Mosquitoes flicted Philadelphia in 1780. Although his 1789 Ac-
take between 8 and 11 days to become infectious after count of the Bilious, Remitting Fever is generally
ingesting infected blood, and remain infectious for accepted as the first modern medical account of
life; therefore, a single mosquito can infect a number dengue, claims have also been made on behalf of
of members of a household. The 1977 Puerto Rican David Bylon, a Dutch physician who described an
dengue epidemic resulted in the infection of an esti- epidemic of knokkel-koorts (knuckle-fever), which
mated 355,000 persons with types 1, 2, and 3 virus; appeared in the Dutch East Indies in 1779.
the 1986 Rio de Janeiro type 1 epidemic affected The disease discussed by Bylon (1780) superfi-
100,00 persons between March and May alone. cially resembles dengue (sudden onset of high fever,
Recurrent outbreaks of dengue in the same geo- severe musculoskeletal pain, facial rash, and swell-
graphic region indicate either that new dengue vi- ing, benign outcome), but appears atypical in that
rus types have been introduced or that endemic the severe joint pain suggested by the name is more
types are now affecting groups of the population characteristic of Chikungunya (CHIK) fever, a
lacking immunity - generally those born since the group A arbovirus infection with a mosquito vector.
last epidemic. Bylon, state surgeon to the city of Batavia, treated
Dengue hemorrhagic fever is especially frequent 89 patients for knokkel-koorts and then caught it
in Southeast Asia, where it is among the leading himself. His illness began with pain in the joints of
causes of hospital admissions in children and the his right hand and arm, and rapidly progressed to
commonest cause of death from communicable dis- include a high fever within a few hours. He con-
ease at any age. Dengue hemorrhagic fever's first cluded his account of the epidemic by remarking
reported appearance in epidemic form in the West- that the disease was well known in Batavia, but had
ern Hemisphere came during the 1981 Cuban epi- never before reached epidemic proportions. That
demic. Several cases of dengue hemorrhagic fever alone would serve to distinguish knokkel-koorts

from dengue, given what we know of the epidemi- published an account of their experimental studies
ology of the latter disease. on dengue in the Philippines.
Patrick Macdowall was a Scot who participated in The general pattern of dengue activity since World
the Darien Scheme, which was an attempt to found a War II has been one of increasing prevalence and
Scottish colony in 1699 on the Isthmus of Panama, severity within the context of unrestrained prolifera-
then known as Darien. The plan was the brainchild tion of its vectors. Today those vectors that spread
of William Paterson, the founder of the Bank of yellow fever as well as dengue pose a very real
England, and was intended to gain for Scotland a threat to humanity.
share of the riches of the New World from Darien's James McSherry
advantageous position astride the Atlantic and Pa-
cific trade routes. The colonists were ravaged by
disease, and Macdowall, who kept a journal still
Bibliography
Anderson, C. R., W. G. Downs, and A. E. Hill. 1956. Isola-
preserved in the National Library of Scotland, gave tion of dengue virus from a human being in Trinidad.
an excellent description of his own illness, which Science 124: 224-5.
could well have been dengue. Macdowall survived Bancroft, T. L. 1906. On the etiology of dengue fever.
an acute febrile illness lasting 4 or 5 days that was Australian Medical Gazette 25: 17-18.
characterized by nausea, vomiting, prostration, se- Bylon D. 1780. Korte Aantekening Wegens Eene Alge-
vere retro-orbital headache, disordered sensation of meene Ziekte, Doorgaans Genaamd Knokkel-Koorts.
taste, bone and joint pain, generalized rash, and Verfiandelungen van het Bataviaasch Genootschop der
faintness. His convalescence was prolonged and Konsten en Wetenschappen. Batavia 2: 17—30.
marked by general weakness and a continual ten- Carey, D. E. 1971. Chikungunya and dengue: A case of
dency to faintness. mistaken identity. History of Medicine and Allied Sci-
ences 26: 243-62.
Was Macdowall's illness dengue? Classical sad- Carey, D. E., R. N. Myers, and P. M. Rodriguez. 1965. Two
dle-back fever occurs in only 50 percent of cases of episodes of dengue fever caused by type 4 and type 1
dengue, and even lymphadenopathy is not an in- viruses in an individual previously immunized
variable finding. Macdowall's personal case history against yellow fever. American Journal of Tropical
may well be the earliest recorded description of Medicine and Hygiene 14: 448—50.
dengue. Carey, D. E., et al. 1971. Dengue viruses from febrile
The importance of the mosquito in the transmis- patients in Nigeria, 1964-1968. Lancet 1: 105-6.
sion of dengue was recognized early this century Darien Papers. MS. DP 49/353-60. The National Library
when T. L. Bancroft, using human volunteers, of Scotland. [Cited in J. Preble. 1970. The Darien
proved that dengue could be transmitted via the bite disaster. Harmondsworth.]
of infected Stegomyia fasciata (A. aegypti) mosqui- Halstead, S. B. 1984. Selective primary health care: Strate-
gies for control of disease in the developing world. XI.
toes and that the infecting agent was neither an
Dengue. Review of Infectious Diseases 6 (2): 251-64.
intracorpuscular parasite nor a bacterium, but an Pepper O. H. P. 1941. A note on David Bylon and dengue.
ultramicroscopic organism. His observations also in- Annals of Medical History, 3d ser. 3: 363-8.
criminated A. aegypti, of all the possible culprits, as Robin, Y., et al. 1971. Les Arbovirus au Senegal: Etude
the actual disease vector. However, he erroneously dans la population humaine du village de Bandia.
concluded that the dengue organism lives only for a African Medicine 10: 739-46.
few days in infected mosquitoes, because his at- Simmons, James Steven, et al. 1931. Experimental studies
tempts to transmit the disease were unsuccessful of dengue. Philippine Journal of Science 44: 1—251.
when he used mosquitoes that had been infected 15 U.S. Public Health Service. Centers for Disease Control.
or more days previously. The most likely reason for 1986. Dengue in the Americas, 1985. Mortality and
this error is the inadvertent inclusion of immune Morbidity Weekly Reports 35: 141-42.
subjects in the study population. This, however, 1986. Dengue Fever in U.S. military personnel -
should not detract from the credit due him as the Republic of the Philippines. Mortality and Morbidity
person who recognized the viral etiology and mos- Weekly Reports 34: 495-501.
1986. Aedes albopictus infestation United States, Brazil.
quito transmission of dengue long before Albert Sa-
Mortality and Morbidity Weekly Reports 35: 493-5.
bin was able to cultivate the virus in the laboratory
Westaway, E. G., et al. 1985. Flaviviridae. Intervirology
in the late 1940s. 24: 183-92.
Proof that A. albopictus is a vector of dengue came World Health Organization. 1986. Dengue haemorrhagic
in 1931 when James S. Simmons and co-workers fever: Diagnosis, treatment and control. Geneva.

VIII.34. Diabetes 665
History of the Classification

vm.34 As early as the sixth century, Hindu physicians rec-
Diabetes ognized the clinical symptoms of diabetes and attrib-
uted them to dietary indiscretion. Early descriptions
were based on the classic symptoms of diabetes, in-
Diabetes mellitus (DM) is an endocrine disorder cluding its most salient sign of excessive urination.
characterized by the lack or insufficient production The term diabetes, meaning "to run through," was
of insulin by the pancreas. DM has been recognized first used in the second century by Aretaeus.
as a disease for at least two millennia, but only since In 1679 Tli imas Willis noted the sweet taste of
the mid-1970s has there been a consensus on its urine from diabetics, and in 1776 Matthew Dobson
classification and diagnosis. of Manchester was able to demonstrate that one
The primary diagnostic criterion for DM is eleva- could assay the amount of sugar in the urine by
tion of blood glucose levels during fasting or at 2 evaporating it and weighing the dried residue. Dob-
hours following a meal. Normal plasma glucose val- son stated that this residue looked and tasted like
ues for adults in the fasting state are 80 to 120 "ground sugar." It was by the absence of this sweet
milligrams per deciliter (mg/dL) or 4.4 to 6.7 taste that DM was distinguished from diabetes in-
millimoles per liter (mmol/L). Definition of unequivo- sipidus. The thirst and excessive urination of the
cal DM requires a 2-hour postingestion plasma glu- latter uncommon unrelated disease is caused either
cose level equal to or greater than 200 mg/dL (11.1 by a lack of the antidiuretic hormone from the poste-
mmol/L) for the appearance of classical symptoms of rior pituitary gland or by the unresponsiveness of
diabetes. These symptoms, which include excessive the renal tubules to this hormone. Therefore, glyco-
urination, urine containing sugar, hunger, thirst, suria (sugar in the urine) became diagnostically im-
fatigue, and weight loss, are common to all types of portant and later was used to measure the effective-
DM. ness of treatment of DM. In 1815 M. D. Eugene
Chevreul published his discovery that glucose is
present also in the blood of diabetics.
From the mid-1700s until the 1970s, many types
Classification of diabetes were described. Observations by Apolli-
Today the designation type I DM, or insulin- naire Bouchardat, culminating in his 1875 book on
dependent diabetes, has replaced terms such as glycosuria, clearly distinguished two types of diabe-
ketosis-prone, juvenile-onset, brittle, and so forth, tes: In type I, the patients were relatively young; the
whereas type II DM, or non-insulin-dependent dia- onset was acute, weight loss was striking, and death
betes, has replaced the terms ketosis-resistant, ensued rapidly from ketoacidosis - the buildup of poi-
maturity-onset, and mild diabetes. Many terms sonous ketones from excessive fat metabolism. In
were also used for impaired glucose tolerance, a type II, the patients were older and tended to be
condition that may be a precursor to overt diabetes. overweight, and the onset was slower. Some of these
Some of these earlier terms include latent, sub- individuals could control their glycosuria with a low
clinical, and chemical diabetes, or prediabetes. carbohydrate diet.
Other variants of DM include maturity-onset diabe- Much of the early work focused on elucidating the
tes of youth (MODY), tropical or J-type diabetes, causes of polyuria. John Rollo, in the late 1790s, did
which shows characteristics of both insulin depen- an extended metabolic study of an obese diabetic
dence and non-insulin dependence, and gestational patient at the Greenwich Naval Hospital. He noted
diabetes, which occurs during the latter part of that the amount of urine excreted depended upon
pregnancy. the type of food that was eaten. Urinary production
Approximately 90 to 95 percent of all individuals increased after ingestion of vegetables and de-
with DM may be classified as non-insulin-depen- creased when the diet was high in animal fat and
dent, and about 5 percent as classically insulin- protein. These findings shifted the focus from the
dependent. Diabetes may also be secondary to certain kidneys to the gastrointestinal tract and provided a
conditions or syndromes that result in the permanent scientific basis for therapeutic diets high in fat and
or temporary destruction of the insulin-producing protein and low in carbohydrates.
pancreatic islet cells. Some 2 percent of diabetes have The gross autopsies that were performed in the
DM secondary to disease, genetic syndromes, drugs, 1850s and 1860s revealed no abnormalities of the
chemicals, or traumatic injury. pancreas of diabetics. In 1855 the French physiolo-

gist Claude Bernard discovered that the liver se- Etiology and Epidemiology
cretes glucose from the "animal starch" stored in it.
Bernard and Moritz Schiff, furthermore, found that Insulin-Dependent Diabetes Mellitus (Type I)
the apparent destruction of the pancreas in experi- Insulin-dependent DM is characterized by clinically
mental animals did not result in the onset of diabe- acute onset, usually at an early age, lymphoid infil-
tes. These findings led some to believe that a liver tration of the islets of Langerhans, reduction in the
disease was the source of diabetes. Attention was functioning and production of their betacells, reduc-
redirected to the pancreas in 1889 when Josef von tion in the production and excretion of insulin, in-
Mering and Oscar Minkowski demonstrated that creases in islet cell antibodies, weight loss, thirst,
complete removal of the pancreas did cause diabetes frequent urination, and high levels of blood sugar.
in dogs. After the acute onset of type I diabetes, a clinical
remission may occur in 25 to 100 percent of the
Specialized "heaps of cells" had been identified in
the pancreas by Paul Langerhans in 1869. Contin- reported cases for periods ranging from 1.8 to 15
ued research by Minkowski and others in the 1890s months. After this initial period, all patients require
demonstrated that these "islets of Langerhans" were insulin therapy to prevent severe symptoms and pro-
the source of an "internal secretion" that regulated found biochemical aberrations that can lead to
glycosuria. This work suggested convincingly that ketosis, coma, and death.
DM is caused by a disorder of the endocrine portion Typical type I diabetes is uncommon. The preva-
of the pancreas. In 1921 Charles Best and Frederick lence of insulin-dependent diabetes mellitus is less
Banting (Toronto) were able to isolate the internal than 0.5 percent of the world's population. The re-
secretion and named it insulin. They realized that ported prevalence of type I diabetes ranges from 0.1
insulin is responsible for the control of blood glucose to nearly 4.0 per 1,000 children under 20 years of
levels and the appearance of clinical symptoms asso- age. There are 18 registries evaluating geographic
ciated with diabetes. During the 1920s, other hor- patterns of type I diabetes, many in northern Europe
monal secretions of the pituitary and adrenals were and North America, and as much as a 35-fold differ-
discovered, which indicated that glucose control is ence in prevalence has been reported among popula-
more complex. However, insulin alone constituted tions around the world.
the antidiabetes hormone used in therapy.
Although insulin was first used in 1922, it was not Genetic Markers. The etiology of type I diabetes is
until the 1950s that appropriate bioassays of human multifactorial. There is strong evidence for a genetic
insulin were developed. These definitive measure- susceptibility associated with the antigens of the
ments clearly showed that individuals with juvenile- major histocompatibility complex, the human leuko-
onset, or type I, diabetes produced no insulin at all, cyte antigens (HLA). Among individuals in whom
whereas individuals with maturity-onset, or type II, DM occurs before the age of 16 years, 90 to 96 per-
diabetes had varying amounts of insulin produced by cent carry either HLA DR3 or HLA DR4. These are
the pancreas. This discovery provided a clear ratio- present in about 22 percent and 25 percent of the
nale for insulin therapy in those individuals with white population, respectively. The presence of one
type I DM, and for diet, exercise, and, after 1955, oral of these antigens increases the risk of the occurrence
hypoglycemic agents in those with type II diabetes. of DM 3- to 4-fold. Since only 30 to 50 percent of even
The first major epidemiological study of DM, by these individuals develop DM, environmental fac-
Haven Emerson and Louise D. Larimore (1924), at- tors also appear to have an etiologic role.
tempted to explain the increases in diabetes mortal-
ity in New York City from 1866 to 1923. A number of Infectious Diseases and Immune Responses. The
factors were considered influential, including race, role of infectious diseases, particularly viruses, cou-
affluence, lack of physical activity, and changes in pled with the appropriate HLA type, has been inves-
dietary habits, which emphasized the increasing tigated in a number of populations. Although there
abundance of all foods. These authors also noted an is ample experimental and clinical evidence to impli-
increasing prevalence of DM among females over cate the role of Coxsackie B4, mumps, rubella, and
the age of 45. It is, however, the famous American other viruses in the destruction of the betacells of
diabetologist Elliott P. Joslin whose studies in the the pancreas, the epidemiological data are not defini-
1930s concerning the "epidemic" of diabetes (Joslin, tive. There were early reports of mumps-induced
Dublin, and Marks 1933; Joslin 1935) demonstrated pancreatitis. In 1927 E. Gunderson observed that
the utility of the epidemiological approach. mortality rates from diabetes increased 2 to 4 years

after epidemics of mumps. More recently, other vi- onset of type I diabetes peaks at the beginning of
ruses have been under investigation. For example, puberty and during the adolescent growth spurt for
investigators in Poland discovered increases in anti- both girls and boys.
bodies against enteroviral meningitis and Coxsackie
A and B viruses in newly diagnosed diabetics. The Nutritional Factors. Some nutritional factors have
meningitis epidemics regularly preceded periods of been suspected of being involved in the etiology of
increased incidence of diabetes by 4 to 6 months. type I diabetes, although again there is no consistent
Many studies have attempted to link infectious epidemiological picture. Excess caloric intake does
diseases to seasonal patterns in the onset of diabe- not seem to be the important etiologic factor it is in
tes. The results have not demonstrated a consistent type II diabetes. A Danish study has reported a nega-
picture. Furthermore, seasonal variation may be tive correlation between breast-feeding and type I
linked to factors other than infectious diseases. DM, and finally T. Helgason and M. R. Jonasson
Worldwide, there is apparently no "peak season" for (1981) suspect that AT-nitroso compounds from
the appearance of type I diabetes. smoked mutton may be responsible for the seasonal
Recent work indicates that there is an auto- incidence of type I diabetes found in Iceland, where
immune factor in the destruction of the beta cells of this meat is traditionally consumed at Christmas
the pancreas. Circulating immune complexes have time. The range of nutritional factors implicated in
been found in 30 to 90 percent of all newly diagnosed type II diabetes is much greater and is discussed
type I diabetics. Antibodies against islet cells are the below.
most common, but antibodies against gastric pari-
etal cells, thyroid, and adrenal tissue have also been
detected in some diabetics. A strong association ex- Other Factors. A further risk factor in type I DM is
ists between the presence of autoimmune antibodies urbanization with accompanying changes in life-
and HLA DR3. style and a greater risk of infection due to increased
population density. Thus there is generally a higher
prevalence of type I diabetes among urban as op-
Other Population Genetic Factors. Genetic factors posed to rural populations within a given country.
at the population level may play a role in the etiol-
ogy of type I diabetes. The relative risk of HLA DR3
is lowest for African blacks and is approximately the Non-Insulin-Dependent Diabetes (Type II)
same for Caucasians, African-Americans, and Japa- Between 90 and 95 percent of all individuals with
nese (relative risk: 3.3-3.5). On the other hand HLA diabetes have type II diabetes and are over the age of
DR4 shows a 3-fold higher risk (9.6) for American 35 years. In contrast to type I diabetes cases, there
blacks than for the other three groups. are many cases (up to 50 percent) that remain undi-
Low rates of type I DM are found among New agnosed. Type II diabetics produce insulin but may
World Asian-derived native populations (Eskimos, require more of it in order to manage their glucose
Aleuts, and Amerindians), as well as Old World levels. The majority of all patients are treated with
Asian populations, including the Japanese and Chi- dietary modifications, often with caloric reductions
nese. Prevalence rates vary considerably on the In- for weight loss, and with oral hypoglycemic tablets.
dian subcontinent. Rates are lower in the southern Type II diabetics are ketosis resistant but may suffer
part of India (i.e., Bombay) than in northern India from the macrovascular and microvascular complica-
(i.e., New Delhi). K. M. West (1978) cites a number of tions of ketosis (see Table VIII.34.1).
studies indicating an increased prevalence of type I Many factors have been implicated in the etiol-
diabetes among populations that previously showed ogy and pathogenesis of type II diabetes. Not only
low rates. Increases are particularly marked among are they numerous but also their interactions are
Japanese, black Africans, and black Americans. In complex.
general, these increases are associated with a "West-
ernization" in life-style since World War II. Genetic Factors. The numerous problems in discov-
ering a genetic mechanism responsible for diabetes
Biological Factors. Sex and age also play roles in have been outlined in works by W. Creutzfeldt, J.
the onset of type I diabetes. In most populations, the Kobberling, and J. V. Neel (e.g., 1976), and K. M.
number of boys and girls afflicted with the disease is West (1978). Unlike type I DM, type H DM (the more
nearly equal. However, in children under 5 years of common non-insulin-dependent DM) has no associ-
age, the incidence is slightly higher for boys. Age of ated genetic markers. However, genetic mechanisms

Table VIII.34.1. Causes and suspected causes of, ported a simple mode of inheritance. A 40-fold risk of
and risk factors for, diabetes DM occurs for children of fathers who had an age of
onset of diabetes under 20 years. Risks are some-
Generally accepted what less for children of type I mothers, and are
Obesity increased only one to three times for offspring of
Caloric excess, indolence parents who had an age of diagnosis of diabetes over
Heredity the age of 40.
Destruction or damage of beta cells
Cancer
Pancreatectomy
Pancreatitis from many causes Biological Factors. Both age and sex are risk fac-
Viral infections tors for type II diabetes. In most affluent societies,
Coxsackie viruses, measles the rate of diagnosed type II diabetes increases
Beta cytotoxic drugs steadily from 30 to 60 years of age. The decline in
Diabetogenic hormones (exogenous or endogenous) the rate in old age may be the result of the smaller
Growth hormone number of individuals at risk. The extent to which
Epinephrine physiological aging is a risk factor is unknown. How-
ACTH or glucocorticoids ever, H. Silwer (1978) showed that for Swedish popu-
Hemochromatosis lations the proportion of cases that were "severe"
Disorders of insulin receptors declined sharply in old age, from 28 percent in the
Factors of immunity and autoimmunity sixth decade to 4 percent in the ninth decade.
Human leukocyte antigens (HLA)
Many observations have been made on sex differ-
Widely suspected of causing or precipitating diabetes ences in the frequency of type II diabetes. Before
Pregnancy 1900, diabetes was observed to be more frequent in
Excessive serum iron men in both Europe and the United States. Indeed R.
Cassava (manioc or tapioca) consumption Lepine cited seven different studies from Europe in
Some drugs which women constituted 17 to 43 percent of the
Cirrhosis
Potassium deficiency
cases, whereas Emerson and Larimore found that in
Certain brain lesions England and Wales the male/female ratios were typi-
Affluence in some circumstances and poverty in others cally 2:1 before 1910. Since 1930, however, clinicians
Myotonic dystrophy in both America and Europe have repeatedly ob-
served a greater frequency in female diabetics.
Suspected by some scientists but doubted by others
Nonetheless, many developing nations show a
Dietary fat
Dietary sugars male predominance. Populations with a high male/
Refined carbohydrates female ratio include rural Africans, Hong Kong Chi-
Insufficient dietary fiber nese, and populations in Iraq, Jordan, Japan, Korea,
Contraceptive steroids India, and Pakistan. Populations with a predomi-
Deficiency states nance of females include the United States, the Ca-
Chromium, iron, zinc, pyroxidine ribbean countries, Sweden, Belgium, the former So-
Severe protein malnutrition viet Union, Thailand, and South Pacific countries.
Psychological stress Parity has also been considered a risk factor. In
Stress of prolonged or severe illness 1924, Emerson and Larimore reported that married
Temperate climate women in New York City had a rate of mortality
Hypertriglyceridemia from diabetes about four times higher than that of
Specific racial susceptibility
single women. Joslin and his associates, however,
(e.g., Jews, Indians, American Indians, Polynesians)
found that married diabetic women weighed on the
Source: Adapted from K. M. West (1978: 34). average about 20 pounds more than single diabetic
women, and in well-controlled studies no relation-
ship was found between parity and diabetes in Pima
interacting in complex ways with environmental fac- Indians. On the other hand, it is true that pregnancy
tors are involved in the risk for type II diabetes. can have a physiological effect that is diabetogenic,
Type II DM occurs more frequently in families in and women who suffer from gestational diabetes are
which one or more members have DM than in the at greater risk for type II diabetes in their nonpreg-
general population. Yet family studies have not sup- nant state. In summary, it appears that parity is not

a major risk factor for diabetes, and that the associa- Dietary Factors. Calories are units of energy de-
tion is confounded by both obesity and age. rived from food, and high caloric intake and low
caloric expenditure are both related to obesity. Diabe-
tes rates appear to have increased markedly in a
Exercise. Exercise would seem to be a potent protec-
number of countries wher caloric consumption per
tive factor in diabetes. It enhances both carbohy-
capita has also increased. These countries include
drate metabolism and the efficient use of insulin. As
Japan, Taiwan, Haiti (among the wealthy), New
early as 1893, B.C. Sen noted that active men in
Guinea, and many parts of Africa. A number of au-
India had a lower rate of diabetes than their more
thors have noted that during World War I and II in
sedentary counterparts. Overall, a decrease in en-
Europe and during World War II in Japan, when
ergy expenditure has been related to changes in life-
caloric intake was markedly decreased, the rate of
style, a relationship that has been particularly well-
obesity and diabetes both declined. On the other
documented in the South Pacific. Unfortunately,
hand, recent work in 1975 by J. H. Medalie and his
quantitative data on exercise are limited, and the
colleagues indicate no significant differences in calo-
short- and long-term effects of exercise on carbohy-
ric intake among diabetic and nondiabetic Israeli
drate metabolism are incompletely understood.
men.
Many dietary components have been investigated
Obesity. There is abundant worldwide evidence as- as potential risk factors for type II diabetes. Most
sociating obesity with type II diabetes, and the 1980 researchers agree that there is no convincing evi-
World Health Organization Expert Committee on dence that a single dietary component increases the
Diabetes has concluded that it is the most powerful risk of diabetes. For example, West reported 21 stud-
risk factor for non-insulin-dependent DM. Many ies indicating that table sugar or sucrose consump-
studies have shown that between two-thirds and tion was a risk factor for diabetes and another 22
nine-tenths of individuals may be classified as obese studies suggesting that it was not. Furthermore, the
at the time of diagnosis of DM. distinction between simple and complex carbohy-
This association between obesity and diabetes is drates has been called into question in recent years.
an old one, first noted by Indian physicians. Modern A number of researchers focusing on previously des-
concern with obesity began with Joslin's landmark ignated complex carbohydrates (starches such as po-
paper in 1921, in which he assembled overwhelming tato and wheat bread) have shown that these
data showing obesity as the major risk factor for starches can lead to the production of high levels of
type II diabetes. Diabetes rates were 6 to 12 times insulin and glucose in nondiabetics and type II dia-
greater in obese than in lean individuals. More re- betics. In fact, the glucose response to white potatoes
cently, West (1978) documented high frequencies of and dextrose sugar was approximately the same.
both obesity and diabetes among a number of Amer- H. C. Trowell, D. P. Burkitt, and colleagues sug-
indian tribes in Oklahoma. Later works on native gest that dietary fiber favorably alters absorption
American groups have corroborated these findings. patterns to decrease the risk for diabetes, and cur-
The positive relationship of diabetes with obesity is rently many different forms of dietary fiber are be-
also found in Latin American populations. Yet it ing investigated in this connection. In most of the
does not hold true for all peoples; in some popula- epidemiological work, however, it is difficult to disen-
tions with high levels of both conditions - for exam- tangle the effects of decreased fiber consumption
ple, the Pima Indians and Mexican-Americans - for from increased sugar and refined carbohydrate in-
specific age and sex groups diabetics are not more take, increased total calories, total fat, decreased
obese than nondiabetics. caloric expenditure, and stresses associated with
The distribution of body fat presents an additional rapid dietary change and modernization. Thus,
risk factor. A centripetal distribution of fat around there remain many unanswered questions concern-
the chest, waist, and abdomen presents a greater ing the role of refined and unprocessed carbohy-
risk than an increase in fat in the lower portion of drates and dietary fiber in the risk and treatment of
the torso, hips, and thighs. This central or android DM.
distribution of fat has been correlated with risk for Dietary fats have also been viewed as dietary risk
diabetes in a number of ethnic and racial groups. factors, although studies investigating fat intake
The duration of the diabetes and other hormonal are often confounded because of the higher caloric
factors may be additional risks related to the density of fat compared to carbohydrates and pro-
amount of fat tissue or degree of obesity. teins (ratio = 9:4:4). Furthermore, high fat intake is

generally associated with low fiber intake. Histori- tion of rural sugar-cane farming populations in the
cally, one of the more important works on the matter West Indies; (7) ketosis resistance; and (8) intermit-
is that of Harold P. Himsworth (1935-6), in which he tent need for insulin therapy.
presented evidence positively linking fat and nega- Information is relatively sparse on the genetics of
tively linking carbohydrate consumption to diabe- diabetes in tropical countries. Recent studies on the
tes. Yet other epidemiological observations have not human leukocyte antigens (HLA) and properdin (fac-
supported the relationship between high fat con- tor B, BF) system have shown that there is great
sumption and high diabetes rates when diet is con- population variability in the association of particular
trolled for caloric intake. Furthermore, evidence HLA haplotypes and increased susceptibility to diabe-
that challenges any such relationship is found tes. Genetic studies of Indian populations suggest a
among Eskimos living a traditional life-style with stronger familial or genetic factor among Indian dia-
diets high in fat and protein yet suffering little from betics compared to diabetics in other populations.
DM. Alternatively, protein deficiency in the tropics Environmental risk factors for tropical diabetes
has been implicated in certain types of diabetes, involve unique dietary items. In 1979, D. E. Mc-
particularly those secondary to pancreatic disease. Millan and P. J. Geevarghese suggested that the
Finally, deficiencies in micronutrients - in particu- cyanide-containing glycosides of some types of cas-
lar, chromium — have been postulated as potential sava (manioc) may be toxic to the beta cells of the
factors for diabetes. However, there are few epidemi- pancreas and thus produce pancreatic damage. Ab-
ological data and the clinical data are conflicting. normal changes in pancreatic tissue give support to
the cassava-cyanide hypothesis in the pathogenesis
Other Factors. Other life-style factors such as ur- of diabetes. However, many tropical areas show high
banization and psychosocial stress have been impli- rates of diabetes in populations that do not consume
cated in the etiology of type II diabetes. As popula- cassava, and conversely, some populations have high
tions become more "developed," there is an increase cassava consumption and low rates of diabetes. In
in diabetes. The populations of the South Pacific, for Kenyan (K type) diabetes, a local alcohol called
example, provide a natural laboratory in which the changaa is implicated in causing the disease. Fi-
degree of modernization has been correlated with nally, in most tropical areas carbohydrates consti-
increases in chronic diseases including diabetes. tute 70 to 80 percent of the total calories of the diet,
Many other factors associated with diabetes are which is considerably higher than the percentage of
listed in Table VIII.34.1. carbohydrates in diets of many developing countries.
Indeed, such a diet is implicated in classic "malnutri-
Tropical Diabetes. A third type of diabetes found tion diabetes" because of the relatively low nutrient
primarily in developing countries in tropical areas density and high fiber content.
has clinical characteristics of both type I and type II
diabetes. Tropical diabetes has been described in Gestational Diabetes. In 1882, J. M. Duncan noted
many areas of the world including the South Pacific, a type of diabetes present only during pregnancy.
the West Indies, Africa, Southeast Asia, and India. However, it was not until the 1940s that the term
Thus, the disease has been referred to variously as "gestational diabetes" appeared in the English lan-
phasic insulin-dependent diabetes, J-type diabetes guage medical literature. D. R. Haddon found that
for Jamaica, K-type diabetes for Kenya, malnutri- from 1975 to 1984, 165 studies on gestational diabe-
tion diabetes, and tropical pancreatic diabetes. The tes were published, representing investigations in
clinical profile involves the following: (Da different 25 countries. The majority (69 percent) were from
genetic pattern of diabetes than in temperate re- the United States and Europe, although 16 were
gions; (2) a low prevalence rate of type I DM; (3) a reported from Australia. One important difficulty in
younger age on onset of type II; (4) a sex ratio with evaluating the incidence of gestational diabetes is
male predominance in India and Africa, but female that the frequency of type II diabetes among women
predominance in the West Indies; (5) an association of childbearing age is unknown for many countries.
of low calorie and protein intake during childhood Therefore, a woman could have diabetes prior to
and adulthood with the presentation of lean or under- pregnancy, but not have it diagnosed until preg-
weight diabetic individuals in Old World tropical nancy. Babies born to diabetic mothers usually are
areas, but overweight diabetic individuals in the large (over 9 pounds), but may have organ systems
Western Hemisphere; (6) the predominance of diabe- that are not mature, in which case they may not
tes in urban areas in most countries, with the excep- survive.

The prevalence of gestational diabetes varied from Table VIII.34.2. Prevalence of diagnosed diabetes in
0.15 percent in Newcastle, United Kingdom, to 12.2 representative populations, 1960—85
percent in Los Angeles, California. In general, cities
in the United States report a higher prevalence of Population descrip-
gestational diabetes then do European cities. The Country tion Rate (%)
one African report from Nairobi, Kenya, indicates a United States American Indians 10.0
prevalence of 1.8 percent. The highest reported rate (multitribal adults)
of gestational diabetes occurs among the Pima Indi- United States >20 6.2
ans of Arizona, who also have the highest prevalence Canada all ages 2.0
of type II diabetes of any known population.
Argentina adults 2.9
Distribution and Incidence Costa Rica >30 years 5.4
Many methods have been used to ascertain the El Salvador >30 years 3.2
Guatemala >30 years 4.2
prevalence of DM. Methods have ranged from tele-
Jamaica <25 years 8.0
phone and household surveys, reviews of hospital
Panama >30 years 2.5
records, to screenings using urine and blood determi- Trinidad >20 years 4.5
nations of glucose concentrations. Because of its Uruguay >30 years 6.9
acute onset and obvious symptoms, type I diabetes is Venezuela >30 years 7.0
readily identified and, therefore, permits a more ac-
curate picture of worldwide prevalence. Data from England all ages 0.6
the 1960s through the 1980s indicated that popula- Germany all ages 1.3
tions with prevalence rates of insulin-dependent DM Italy all ages 2.5
of at least 1.0 per 1,000 include Finland, Sweden, the Scotland all ages 0.6
United States, England, France, and Australia. In- Spain all ages 1.3
termediate prevalence rates of 0.5 to 0.9 per 1,000 Sweden all ages 2.0
are found in Scotland, Switzerland, East Germany, Yugoslavia s l 5 years 1.1
and Denmark. Rates below 0.5 per 1,000 occur in
Australia adults 0.9
Italy, Japan, India, Taiwan, Vietnam, Libya, China,
India rural a 15 years 1.3
the South Pacific, Ethiopia, and the West Indies. India urbanal5 years 3.0
Type II DM is a chronic disease with generalized Japan all ages 0.4
symptoms; therefore, many cases are not diagnosed. Malaysia >30 years 4.2
The American Diabetes Association estimates that Singapore s i 5 years 6.1
40 to 50 percent of Americans with type II DM have
not been diagnosed. On the whole, however, rates of South Africa whitest 15 years 3.6
type II do appear to be increasing in developing South Africa Bantu&15 years 4.1
nations. Table VIII.34.2 lists the prevalence rates of Zambia urban all ages 0.3
diabetes in 1960-85 for 28 countries.
Fiji >20 years 11.8
Most surveys on the annual incidence of insulin-
Samoa urban>20 years 10.1
dependent DM include individuals in the age range 9.9
Tonga urbans20 years
0 to 14 or 0 to 16 years. High rates of 15 to 30 per
100,000 are reported for Finland, Sweden, Scotland, Sources: Hamman (1983), Bennett (1983), Taylor and
Norway, and Yugoslavia; intermediate rates of 10 to Zimmet (1983), West (1978: 132-4).
14.9 per 100,000 for Denmark, the United States,
the Netherlands, and New Zealand; and low rates of
0 to 9.9 per 100,000 for Israel, Japan, Great Britain, rise because of increased longevity of individuals
France, Canada, India, Italy, Ghana, and Nigeria. with type I diabetes.
The incidence data from Sweden also indicate an The incidence rates for type II diabetes vary exten-
increase in the number of cases of type I diabetes sively by age and sex for different populations. In
from 19.6 per 100,000 (1970-5) to 24.9 per 100,000 general, the incidence increases with age for both
(1980-2) for children age 0 to 14 years. Generally, males and females until the sixth or seventh decade
investigators have been cautious in interpreting the of life. The incidence of diabetes in the United
rates as an actual increase in the incidence of States, or the number of newly diagnosed cases per
insulin-dependent DM. Prevalence rates continue to 10,000 population per year, has risen 7-fold since the

first large-scale survey in 1935-6, when the rate Table VTII.34.3. Diabetes mortality trends by country
was 3.8 per 10,000. The highest incidence was re- and geographic area, 1970-2 and 1976-83 (rates per
ported in 1973 (29.7 per 10,000) and the information 100,000 population)
from 1979 to 1981 reveals a rate of 22.7 per 10,000.
Approximately 95 percent of these cases are type II Area and country 1970-2 1976-83 Increase/Decrease
diabetes. Africa
Incidence rates of greater than 200 per 100,000 Egypt 6.0 7.1 t
population of adults or total population are found in Mauritius 12.9 17.1 T
the United States, Israel, Finland, England, Den- Americas
mark, Saudi Arabia, the South Pacific islands, and Canada 8.9 13.0 T
Australia. Intermediate rates between 100 and 200 United States 18.8 14.8 1
per 100,000 population per year have been found in Mexico 19.8 18.8 1
Scotland, Germany, Spain, Yugoslavia, Czechoslova- Venezuela 8.9 11.4
kia, and Romania, and lower rates have been found r
Asia
in Canada, India, Southeast Asia, and some African Singapore 9.6 15.1
countries. T
Hong Kong 7.2 5.1 1
Japan 7.4 7.1 1
Europe
There are five stages in the natural history of DM: England and Wales 10.8 9.3 i
First stage: susceptibility based on a combination of Malta 76.3 21.7 i
Sweden 11.9 19.4 T
(1) genetic risk factors; (2) physiological states
such as obesity for type II diabetes; (3) and environ-
mental factors including diet, climate, activity, Source: World Health Organization (1972, 1984).
and other life-style patterns.
Second stage: glucose intolerance, which is recog- Asia rates range from 5.1 per 100,000 for Hong Kong
nized as a phase preceding both insulin-dependent to 15.1 per 100,000 for Singapore. In Europe, the
and non-insulin-dependent diabetes. Not all indi- rate ranges from a high of 21.7 per 100,000 for Malta
viduals having impaired glucose tolerance prog- to a low of 9.4 per 100,000 for England and Wales.
ress to symptomatic diabetes. The best early data on mortality are reported by
Third stage: chronic hyperglycemia without compli- Joslin and his associates in the 11 editions of Joslin's
cations. book, Treatment of Diabetes Mellitus, the first of
Fourth stage: frank diabetes with complications but which was published in 1916. These volumes docu-
without disability. ment a trend toward a decrease in early mortality
from diabetes, due to increasing sophistication in
Fifth stage: disability due to functional impairment
therapeutic approaches, particularly with the ad-
from the complications of diabetes, which involve
vent and wide-scale use of insulin. Table VIII.34.3
primarily the vascular system. Common complica-
reports comparative statistics for changes in diabe-
tions include renal disease, blindness due to
tes mortality rates by geographic region for both
retinopathy, neuropathy, cerebral vascular dis-
ease, cardiac disease, and peripheral vascular dis- developed and developing nations.
ease often leading to lower limb amputation.
Mortality One of the best accounts on the geography of DM,
Diabetes represents an underlying and contributing published in the British Medical Journal in 1907,
cause of death that places it among the top 10 causes was a symposium on diabetes in the tropics, which
of death in developed countries. In Western coun- was chaired by Richard Havelock-Charles. The au-
tries, DM ranks seventh as a cause of death. In the thors reviewed within- and between-country differ-
United States from 1976 to 1983, diabetes was listed ences in the prevalence of diabetes. It was noted, for
as the cause of death in 14.8 per 100,000 population. example, that diabetes was more common in Bengal
This rate was considerably higher in Mexico and in than in upper India, and was less common in Sudan
the Caribbean, with rates as high as 45 deaths per and the Cameroons than in Europe. Papers also indi-
100,000 for Trinidad and Tobago. In Africa the mor- cated the rarity of diabetes in Japan and China. In
tality rates are generally below 10 per 100,000. In 1908 Robert Saundby reviewed differences in the

prevalence of diabetes in Europe. Richard T. William- tion of blood glucose, either fasting or after an oral
son in 1909 reported high rates of DM in Malta, glucose challenge.
which were substantiated in later works. He also Many migrant populations have been especially
noted that there were low rates in Cyprus, Hong prone to high rates of diabetes. For example, Jews
Kong, Malaya, Aden, Sierra Leone, British Hondu- have shown an increased susceptibility to diabetes
ras, Cuba, Labrador (Eskimos), Fiji, and certain in native European enclaves as well as in various
populations of Asian Indians and Chinese. In addi- migrant groups. It was noted that Jews in New York
tion, he summarized available evidence on rates by City had rates 10 times higher than other U.S. eth-
time and place in many European populations. In nic groups. A number of studies from the early 1900s
1922 Fredrick L. Hoffman published data on mortal- show high rates of diabetes among Jews in Buda-
ity rates due to DM for 15 countries or regions for pest, Bengal, Boston, and Cairo. More recently, stud-
persons over the age of 20. These rates ranged from ies have shown that Sephardic Jews in Zimbabwe
67.8 per 100,000 in Malta to 8.6 in Italy. The exten- and Turkey have high rates of diabetes. Migration of
sive data on the epidemiology of diabetes of Emerson Jewish people to and from Israel has produced many
and Larimore published in 1924 included mortality different ethnic subgroups. Newly immigrant Ye-
statistics by geographic region. Comparative mortal- menites and Kurds to Israel show lower rates than
ity data were also published in the many editions of long-time residents of the same ethnic groups. A. M.
Joslin's Treatment of Diabetes Mellitus. In the 1930s, Cohen and colleagues, publishing in 1979, found
there were many reports showing very low rates of that in a 20-year period there was an increase from
diabetes among Eskimos and American Indians. 0.06 percent to 11.8 percent in the prevalence of
Other pioneering studies on the prevalence in other diabetes found among Israeli Yemenites. Medalie
European populations between 1916 and 1952 have and co-workers, studying various ethnic groups in
been summarized by Silwer (1958). 1975 in Israel, found that European-born Jews had a
Modern observations of geographic differences be- lower incidence of diabetes than those born in Af-
gan with the publication of S. M. Cohen's (1954) rica, Asia, or Israel. They found that obesity was a
paper showing marked differences in diabetes rates significant predictor of the prevalence of diabetes
among Amerindian tribes. This was followed shortly among these Israeli ethnic groups.
by J. G. Cosnett's (1957) work describing very high Early reports for Chinese populations indicate a
rates of diabetes in Asian Indian immigrants to very low prevalence of diabetes, and in fact,
South Africa. These rates were 30 to 40 times higher Saundby in 1908 observed that none of his col-
than among black South Africans. Diabetes Mellitus leagues had ever seen a case of diabetes in a Chinese
in the Tropics (1962), by J. A. Tulloch, summarized patient. In modern China, the rates remain very low,
much of the evidence on the prevalence of diabetes ranging from 0.2 percent to 1.2 percent. Most au-
in developing and developed countries. thors conclude that the Chinese have a reduced sus-
Attempts to standardize definitions and criteria ceptibility to diabetes, although rates are somewhat
began when the International Diabetes Federation higher in immigrant Chinese populations in Hawaii
held its first conference in 1952. The National Diabe- (1.8 percent), Singapore (1.6 percent), and Malaya
tes Data Group published the presently used classifi- (7.4 percent). The Japanese, like the Chinese, also
cation of diabetes in 1979, and in 1980 the World show a very low prevalence of diabetes in their na-
Health Organization Expert Committee on Diabetes tive countries. However, with migration, the Japa-
Mellitus published a second report standardizing nese in Hawaii and California have also showed
definitions and criteria for DM and imparied glucose increased rates of DM.
tolerance. One good example of these international Amerindians, in particular, have very high rates
efforts is the work edited by J. I. Mann, K. Pyorala, of diabetes. The highest rates occur among the south-
and A. Teuschner in 1983 covering epidemiology, western Indian groups, with the Pima Indians exhib-
etiology, clinical practice, and health services iting the highest rate (35 percent) of DM. Yet the
throughout the world. In 1985, the National Diabe- high rates among Amerindians appear to be recent.
tes Data Group published Diabetes in America. Early reports (using different testing methods, of
Data in Tables VIII.34.2 and VIII.34.3 show con- course) indicated very low prevalence of diabetes
temporary prevalence figures for different countries among North American Indian groups at the turn of
and, in some cases, distinguish between urban and this century. Moreover, rates among South Ameri-
rural populations. Virtually all of these figures were can Indian groups still tend to be low.
derived from actual determination of the concentra- Other aboriginal groups also seem to be particu-

larly prone to diabetes, among them Polynesians dicate that we may anticipate an increase in the
and Micronesians. Rates are somewhat lower among worldwide prevalence of DM. The focus has been
Melanesians. Hawaiians have a diabetes rate seven and remains on treatment of hyperglycemia and
times higher than Caucasians in Hawaii. Among the vascular complications of long-term diabetes.
New World black populations in the West Indies and Using the epidemiological data and historical
in the United States, there is a high prevalence of perspectives, we are now beginning to develop
type II diabetes, particularly among women. Mi- better programs aimed at early intervention and
chael Stern and other researchers have documented prevention.
high rates of diabetes among Mexican Americans. Leslie Sue Lieberman
One explanation of the high frequency of type II
DM among certain of these populations is that they
developed a highly efficient carbohydrate metabo- Bibliography
lism under traditional life-styles of a feast and fam- Ahuja, M. M. S., et al. 1976. National collaborative study
ine cycle. The thrifty mechanisms of carbohydrate on epidemiology of diabetes in India. Excerpta Medica
metabolism, however, became detrimental with rap- 400:183.
idly changing life-styles associated with a decrease Allen, C, M. Palta, and D. J. D'Alessio. 1986. Incidence
in physical activity, an increase in energy in the and differences in urban—rural seasonal variation of
diet, a reduction of dietary fiber, an increase of re- type I (insulin-dependent) diabetes in Wisconsin.
fined carbohydrates, and an increase in psychosocial Diabetologia 29: 629-33.
stress. Bennett, P. H., et al. 1976. Epidemiologic studies in diabe-
Among Asian Indians, diabetes rates are low. The tes in the Pima Indians. Recent Progress in Hormone
overall prevalence of diabetes in India is approxi- Research 32: 333-76.
Bennett, P. H. 1983. Diabetes in developing countries and
mately 2 percent. Diabetes is more prevalent among unusual populations. In Diabetes in epidemiological
urban populations, the rich, and the professional perspective, ed. J. J. Mann, K. Pyoralas, and A.
classes. In Indian men there also is a north-to-south Teuscher, 43-57. Edinburgh.
gradient of diabetes prevalence, with thrice the Berger, M., W. A. Muller, and A. E. Renold. 1978. Relation-
prevalence in the south. ship of obesity to diabetes: Some facts, many ques-
Yet like other migrant groups, Asian Indian mi- tions. In Advances in modern nutrition, Vol. 2: Diabe-
grants to other countries show high prevalence rates tes, obesity, and vascular disease, ed. H. Katzen and R.
compared to those of indigenous populations. For Mahler, 211-22. New York.
example, in South Africa only 1 to 4 percent of Bernard, Claude. 1855. Sur le mecanisme de la formation
blacks had DM compared to 17 to 32 percent of Asian du sucre dans le foie. Centre de la Recherche de
Indians. High rates have also been reported from I'Academie de Science 41: 46-9.
Blom, L., and G. Dahlquist. 1985. Epidemiological aspects
East Indian populations in Fiji, Trinidad, and Singa-
of the natural history of childhood diabetes. Acta
pore. The Indians in South Africa, in particular, Paediatrica Scandinavica [Supplement] 320: 20—5.
were brought over as indentured servants and had a Bonham, G. S., and D. W. Brock. 1985. The relationship of
life-style not dissimilar to those of New World black diabetes with race, sex and obesity. American Journal
populations. A diabetes-thrifty genotype may have of Clinical Nutrition 41: 776-83.
been selected for in these populations as well. Bornstein, J., and R. D. Lawrence. 1951. Plasma insulin in
Among black Africans DM is still comparatively human diabetes mellitus. British Medical Journal 2:
rare. Nevertheless, increased prevalence has been 1541.
noted by Tulloch for urban Africans in a number of Bouchard, C, and F. E. Jonston, eds. 1987. Fat distribution
nations. Apparently, for susceptible genotypes, the during growth and later health outcomes: Current top-
life-style changes associated with rural-to-urban mi- ics in nutrition and disease, Vol. 17. New York.
gration result in higher relative risks for type II Bouchardat, A. 1875. De la Glycosurie ou diab&te sucri.
Paris.
diabetes.
Chevreul, M. D. Eugene 1815. Note sur la sucre de diabe-
It is important to note that there is a great deal of tes. Annuaires de la Chimie 95: 319—20.
genetic heterogeneity among socially designated ra- Cohen, A. M., et al. 1979. Diabetes, blood lipids, lipo-
cial and ethnic groups. This heterogeneity should proteins and change of environment: Restudy of "New
not be ignored when looking at the environmental or immigrant Yemenites in Israel." Metabolism 28:
geographic factors that lead to increases in the rela- 716-28.
tive risks for type II diabetes. Cohen, S. M. 1954. Diabetes mellitus among Indians of the
The foregoing historical and geographic data in- American Southwest: Its prevalence and clinical char-

VTII.34. Diabetes 675
acteristics in a hospitalized population. Annals of In- the variations in diabetes incidence. American Jour-
ternal Medicine 40: 588-99. nal of Medical Sciences 189: 163-92.
Cosnett, J. G. 1957. Illness among Natal Indians. South Keen, H., and H. Rifkin. 1987. Complications of diabetes:
African Medical Journal 31: 1109. A soluble problem. International Diabetes Federation
Creutzfeldt, W., J. Kobberling, and J. V. Neel. 1976. The Bulletin 32: 121-2.
genetics of diabetes mellitus. New York. Klein, R. 1987. Management of diabetic eye disease. Inter-
Diabetes 1951- . (Journal) national Diabetes Federation Bulletin 32: 123-8.
Diabetes Care 1977- . (Journal) Knowler, W. C , et al. 1981. Diabetes incidence in Pima
Diaz, O. D., and O. F. Cepero. 1987. The diabetic foot and Indians: Contributions of obesity and parental dia-
peripheral vascular complications. International Dia- betes. American Journal of Epidemiology 113: 144-
betes Federation Bulletin 32: 134-7. 56.
Duncan, J. N. M. 1882. On puerperal diabetes. Trans- Kobberling, J., and R. B. Tattersall, eds. 1982. The genet-
actions of the Obstetrical Society of London 24: 256— ics of diabetes mellitus. London.
85. Lepine, R. 1909. Le Diabete sucre, ed. F. Alcan. Paris.
Ekoe, J. M. 1987. Diabetic complications in Africa. Interna- Levine, R. 1986. Historical view of the classification of
tional Diabetes Foundation Bulletin 32: 138-41. diabetes. Clinical Chemistry 32: 84-6.
Emerson, H., and L. D. Larimore. 1924. Diabetes mellitus: Liebermann, L. S. 1988. Diabetes and obesity in elderly
A contribution to its epidemiology based chiefly on black Americans. In Research on aging black popula-
mortality statistics. Archives of Internal Medicine 34: tions, ed. J. Jackson, 150-89. New York.
585-630. Mann, J. I., K. Pyorala, and A. Teuschner, eds. 1983.
Everhart, J., W. C. Knowler, and P. H. Bennett. 1985. Diabetes in epidemiological perspective. Edinburgh.
Incidence and risk factors in non-insulin-dependent Medalie, J. H., et al. 1974. Diabetes mellitus among
diabetes. In Diabetes in America, ed. National Diabe- 10,000 adult men: 1. Five year incidence and associ-
tes Data Group, 1-35. Washington, D.C. ated variables. Israeli Journal of Medical Science 10:
Flack, J. F., and D. K. Yue. 1987. Diabetes neuropathy: 681-97.
Recent developments and future trends. International 1975. Major factors in the development of diabetes
Diabetes Foundation Bulletin 32: 132-4. mellitus in 10,000 men. Archives of Internal Medicine
Freiherr, Greg. 1982. Pattern of body fat may predict occur- 135: 811-18.
rence of diabetes. Research Resources Reporter 6:1-4. Miki, E. 1987. Renal disease in diabetes mellitus. Interna-
Gundersen E. 1927. Is diabetes of infectious origins? Jour- tional Diabetes Federation Bulletin 32: 127-9.
nal of Infectious Disease 41: 197. Mohan, V., A. Ramachandran, and M. Viswanathan. 1985.
Hamman, Richard S. 1983. Diabetes in affluent societies. Tropical diabetes. In The diabetes annual, ed. K. G. M.
In Diabetes in epidemiological perspective, ed. J. I. M. Alberti and L. P. Krall, 82-92. New York.
Mann, K. Pyorala, and A. Teuscher, 7-42. Edinburgh. Morse, J. L. 1913. Diabetes in infancy and childhood. Bos-
Havelock-Charles, R. 1907. Discussion on diabetes in the ton Medical and Surgical Journal 168: 530-5.
tropics. British Medical Journal 2: 1051-64. National Diabetes Advisory Board, eds. 1983. The preven-
Helgason, T., and M. R. Jonasson. 1981. Evidence for a tion and treatment of five complications of diabetes.
food additive as a course of ketosis-prone diabetes. Washington, D.C.
Lancet ii: 716-20. National Diabetes Data Group. 1985. Diabetes in America.
Himsworth, H. P. 1935—6. Diet and the incidence of diabe- Washington, D.C.
tes mellitus. Clinical Science and Molecular Medicine Neel, J. V. 1962. Diabetes mellitus: a "thrifty" genotype
2: 117-48. rendered detrimental by "progress." American Jour-
Hirsch, A. 1885. Diabetes. Handbook of Geographical and nal of Human Genetics 14: 353-62.
Historical Pathology 112: 642-7. Omar, M., et al. 1985. The prevalence of diabetes mellitus
Hoffman, F. L. 1922. The mortality from diabetes. Boston in a large group of South African Indians. South Afri-
Medical and Surgical Journal 187: 135-7. can Medical Journal 67: 924-6.
Jackson, W. P. U. 1967. Diabetes and pregnancy. Acta Panzram, G. 1987. Mortality and survival in type 2 (non-
Diabetologica Latina 4: 1-528. insulin-dependent) diabetes mellitus. Diabetologia
Joslin, E. P. 1916. Treatment of diabetes mellitus. Philadel- 30: 123-31.
phia. Rollo, J. 1798. The history, nature and treatment of diabe-
1921. The prevention of diabetes mellitus. Journal of the tes mellitus. In Causes of the diabetes mellitus, ed. T.
American Medical Association 76: 79-84. Gillet and C. Dilley. London.
Joslin, E. P., L. I. Dublin, and H. H. Marks. 1933. Studies Rosenbloom, A. L. 1977. Nature and nurture in the expres-
on diabetes mellitus: 1. Characteristics and trends of sion of diabetes mellitus and its vascular manifesta-
diabetes mortality throughout the world. American tions. American Journal of Diseases of Children 131:
Journal of Medical Sciences 186: 753-73. 1154-8.
1935. Studies in diabetes mellitus: 3. Interpretation of Rosenbloom, A. L., et al. 1985. Screening for diabetes

mellitus. Journal of the Florida Medical Association Wilcox, H. B. 1908. Diabetes in infants and young chil-
72: 1033-7. dren. Archives ofPediatrics 25: 655-68.
Samanta, A., et al. 1985. Prevalence of known diabetes in Williamson, R. T. 1909. Geographic distribution of diabe-
Asians and Europeans. British Medical Journal 291: tes mellitus. Medical Chronicle 1: 234-52.
1571-2. Willis, Thomas. 1697. Of the diabetes or pissing evil. In
Saundby, R. 1908. Diabetes mellitus. In A system of medi- Pharmaceutics rationalis, Chap. 3. London.
cine by many writers, ed. C. Allbutt and H. D. World Health Organization. 1964. Statistical yearbook:
Rolleston, 167-212. London. epidemiology and vital statistics report 17: 40, 51,
Schiff, Moritz. 1857. Mitteilungen von Herrn Professor 307-30. Geneva.
Schiff in Bern. Archiv fur Physiolgische Heilkunde 1: 1972. World health statistics annual, 1970-1972. Ge-
263-6. neva.
Sen, B. C. 1893. Diabetes mellitus. Indian Medical Ga- 1980. Expert committee on diabetes mellitus, 2d Report.
zette, July, 241-8. Technical Report Series No. 646. Geneva.
Silwer, H. 1958. Incidence of diabetes mellitus in the Swed- 1984. World health statistics annual, 1978-1983. Ge-
ish county of Kristianstad. Incidence and coincidence neva.
of diabetes mellitus and pulmonary tuberculosis in a 1985. Multinational study of vascular diseases in diabe-
Swedish county. Acta Medica Scandinavian [Supple- tes: Prevalence of small vessel and large vessel dis-
ment] 335: 5-22. ease in diabetic patients from 4 countries. Diabeto-
Simpson, N. E. 1968. Diabetes in the families of diabetics. logia 28: 616-40.
Canadian Medical Association Journal 98: 427-32.
Sinha, Denesh. 1984. Obesity and related diseases in the
Caribbean. Cajanus 17: 79-106.
Stern, Michael. 1983. Epidemiology of diabetes and coro-
nary heart disease among Mexican-Americans. Asso-
ciation of Life Insurance Medical Directors of America VIII.35
67: 79-90.
Striker, Cecil. 1961. Famous faces in diabetes. Boston.
Diarrheal Diseases (Acute)
Tauscher, T., et al. 1987. Absence of diabetes in a rural
West African population with a high carbohydrate/
cassava diet. Lancet i: 765—8. Acute diarrheal illness can be defined as the sudden
Taylor, R., and P. Zimmet. 1983. Migrant studies and diabe- onset of the passage of a greater number of stools
tes epidemiology. In Diabetes in epidemiological per- than usual that show a decrease in form. It is gener-
spective, ed. J. I. Mann, K. Pyorala, and A. Teuscher, ally accompanied by other clinical symptoms such as
58-77. Edinburgh. fecal urgency, tenesmus, abdominal cramps, pain,
Tiwari, J. L., and P. I. Terasaki. 1985. PI: HLA and disease nausea, and vomiting. In most cases the symptom
associations. New York. complex is a result of intestinal infection by a viral,
Trowell, H., D. P. Burkitt, and K. Heaton. 1985. Dietary bacterial, or parasitic enteropathogen; occasionally
fiber,fiber-depletedfoods and disease. London. it is secondary to ingestion of a microbial exotoxin.
Tulloch, J. A. 1962. Diabetes mellitus in the tropics. Edin-
burgh.
1966. Diabetes in Africa. In Diabetes mellitus, ed. L. J. Distribution and Incidence
Duncan, 115-24. Edinburgh. Acute diarrhea is often hyperendemic in certain
Viveros, M. G. 1980. Research on diabetes mellitus. In populations: infants and young children in develop-
Biomedical research in Latin America: Background ing tropical countries of Latin America, Africa, and
studies, ed. U.S. Department of Health, Education and southern Asia; persons traveling from industrial-
Welfare, 165-78. Washington, D.C. ized to developing regions; military populations sta-
Von Mering, J., and O. Minkowski, 1889. Diabetes tioned in or deployed to tropical areas; and toddlers
mellitus nach Pankrease stirpation. Zentrablatt fur who are not toilet trained and are attending day-
klinische Medizin 10: 393-4. care centers. Diarrhea rates in children less than 5
Walker, A. R. P. 1966. Prevalence of diabetes mellitus.
years of age in developing countries range from
Lancet i: 1163.
Waugh, N. R. 1986. Insulin-dependent diabetes in a Scot-
between three and seven episodes per child each
tish region: Incidence and urban/rural differences. year. The rate of diarrhea for non-toilet-trained in-
Journal of Epidemiology and Community Health 40: fants in day-care centers in urban areas of the
240-3. United States is comparable to the rate of illness
West, K. M. 1978. Epidemiology of diabetes and its vascu- seen in Third World countries. Travelers' diarrhea
lar lesions. New York. occurs in 20 to 40 percent of persons visiting high-

VIII.35. Diarrheal Diseases (Acute) 677
risk areas from regions showing low disease en- efficient interchange of organisms during outbreaks,
demicity. The rate of diarrhea occurrence in infants several pathogenic organisms are often identified dur-
and young children under 5 years of age in the ing the same time period.
United States is approximately 0.8 to 1.0 episode By employing optimal enteric microbiological tech-
per child each year. In all populations, acute diar- niques, an etiologic agent can be detected in approxi-
rhea occurs less commonly in older children and mately 50 percent of cases of acute diarrhea. The
adults than in infants. specific agent responsible for acute diarrhea will
generally depend upon the age of the host, the geo-
Etiology and Epidemiology graphic location, and the season. Table VIII.35.1
The ultimate source of most of the enteric pathogens summarizes the most important etiologic agents in
is infected humans, although for selected pathogenic diarrhea, and Table VIII.35.2 indicates the microor-
organisms (i.e., Salmonella, Giardia), animals may ganisms most frequently associated with diarrhea in
serve as a reservoir. Environmental factors play an certain settings.
important role in disease endemicity. Both water
quality and water quantity are important. Although
the degree of microbial contamination of water may Immunology
be responsible for exposure to diarrhea-producing When an enteric infectious microorganism is highly
organisms, the availability of adequate amounts of endemic and there is a high degree of antigenic homo-
water for personal and environmental cleansing, geneity among the implicated strains, immunity
even if it is contaminated, may be beneficial. Sewage tends to develop with age. The infectious enteric or-
removal is a prerequisite for clean water and a ganisms that fit this description and to which immu-
healthful environment. nity is known to increase with age in endemic areas
Personal and food hygiene standards in a popula- are the following: Vibrio cholerae, Salmonella typhi,
tion are important to enteric infectious disease occur- enterotoxigenic Escherichia coli, Shigella, Norwalk
rence. Effective handwashing as a routine practice is virus, and Rotavirus. There is great hope that effec-
practically unheard of in many areas of the develop- tive immunizing agents against these organisms will
ing world. Food all too often is improperly handled. be developed for use in high-risk populations.
Vegetables and fruits rarely are washed properly
when reaching the house prior to preparation, despite
the fact that they may have been exposed to human Clinical Manifestations
excreta used as fertilizer. Foods may be contaminated For most of the enteric infections, a characteristic
by unclean kitchen surfaces or hands. One of the most clinical illness is not produced by a given etiologic
important errors in food hygiene is the storage of agent. When patients acquire enteric infection, a
foods containing moisture at ambient temperatures variety of symptoms other than diarrhea may result,
between meals, which encourages microbial replica- including abdominal cramps and pain, nausea, vom-
tion. This problem is especially severe during the iting, and fecal urgency and incontinence or the urge
warmer months. Medical care is often inadequate so but inability to defecate. When patients experience
that intestinal carriage of microbial pathogens and fever as a predominant finding, invasive bacterial
continued dissemination of the agents continue. Fi- pathogens should be suspected {Salmonella, Shi-
nally, underlying medical conditions can contribute gella, and Campylobacter). Vomiting is the primary
both to the occurrence of diarrhea and to the severity complaint in viral gastroenteritis (often due to
of the resultant disease; measles and malnutrition rotavirus in an infant or Norwalk-like viruses in
are two important examples. older children or adults), staphylococcal food poison-
In most countries where acute diarrhea is a seri- ing, or foodborne illness due to Bacillus cereus.
ous medical problem, it tends to be most prevalent When dysentery (the passage of small-volume stools
during the warmer months. The reason is probably that contain gross blood and mucus) occurs, amebic
that bacteria grow rapidly in warm, moist condi- Shigella or Campylobacter enteritis should be sus-
tions. Flies also can play a role in the transmission pected. In salmonellosis, gatroenteritis stools are
of enteric infections. grossly bloody in just under 10 percent of cases.
In day-care centers, when a non-toilet-trained Other less common causes of dysentery are inflam-
child develops diarrhea, a variety of fecal organisms matory bowel disease, Aeromonas, Vibrio parahemo-
may spread to the hands of teachers and children, and lyticus, Yersinia enterocolitica, Clostridium difficile,
to the toys shared by the children. Because of the and Entamoeba histolytica.

Table VTII.35.1. Commonly identified etiologic Table VIII.35.2. Etiologic agents of diarrhea,
agents in diarrheal disease characteristically identified in special settings
Agent Comment Setting Commonly identified agents
Bacterial Day-care centers Rotavirus, Giardia, Shigella,
Escherichia coli Cryptosporidium
Enteropathogenic E. coli Causes infantile diarrhea; Person traveling Enterotoxigenic Escherichia coli,
(EPEC) may cause chronic diar- from industrial to Shigella, Salmonella,
rhea developing coun- Campylobacter, Plesiomonas,
Enterotoxigenic E. coli Major cause of infant and tries Giardia
(ETEC) childhood diarrhea in de-
veloping tropical coun- Male homosexuals Herpes simplex, Chlamydia tra-
tries, and travelers' diar- chomatis, Treponema pallidum,
rhea Neisseria gonorrhoeae, Shigella,
Enteroinvasive E. coli Occasionally causes Salmonella, Campylobacter,
(EIEC) foodborne febrile diar- Clostridium difficile, Giardia
rhea Acquired immune Cryptosporidium, Isospora belli,
Enterohemorrhagic coli- Causes colitis, low-grade fe- deficiency syn- Herpes simplex, cytomegalovirus,
tis (EHEC) ver associated with ham- drome Salmonella, Mycobacterium
burger consumption; may avium-intracellulare
result in hemolytic
uremic syndrome
Shigella, Salmonella, Common in all areas, espe-
Campylobacter jejuni cially during the summer- Pathology
time A basic prerequisite for infection by enteric patho-
Aeromonas Of uncertain importance gens is attachment to the intestinal lining by the
Plesiomonas shigelloides Causes diarrhea in travel- pathogenic microorganism. The mechanism of the
ers and those exposed to attachment varies from a highly specific receptor-
seafood ligand interaction, as seen for enterotoxigenic E.
Vibrio parahemolyticus, Causes diarrhea in those ex-
other nonagglutinable posed to seafood coli, to a nonspecific type of attachment, as is seen
vibrios for the protozoan Giardia, which possess sucking
Staphylococcus aureus, Ba- Associated with foodborne disks for intestinal adherence. Variable degrees of
cillus cereus outbreaks of vomiting (± intestinal damage can be seen in enteric infection.
diarrhea) No anatomic or structural alterations are found in
Viral infection by enterotoxigenic E. coli or V. cholerae,
Rota virus Found in infants <2 years where intestinal secretion and watery diarrhea oc-
age; shows wintertime cur secondary to cyclic nucleotide stimulation.
propensity in temperate
climates; occurs in all sea- In shigellosis and campylobacteriosis, extensive
sons in tropical areas inflammation with microabscess formation is seen.
Norwalk viruses Major cause of waterborne Small bowel pathogens (rotavirus, Norwalk viruses,
and shellfish-associated and Giardia) may lead to depletions of intestinal
gastroenteritis disaccharidases and lactose (milk) intolerance. Mal-
Caliciviruses and enteric Of uncertain importance nutrition, which is common in areas where diarrhea
adenoviruses is highly endemic, leads to a more prolonged disease
Parasitologic of greater severity, although malnutrition does not
Giardia lamblia Causes protracted diarrhea predispose to the occurrence of diarrhea.
commonly in those ex-
posed to mountainous ar- The synergy between the effects of malnutrition
eas or day-care centers and diarrhea is an important reason why death from
Entamoeba histolytica Commonly causes recur- diarrhea is so common in Third World countries.
rent diarrhea in persons Diarrheal illnesses have adverse effects on growth
living in tropical coun- and contribute to malnutrition. There is a 20 to 60
tries percent decrease in body caloric intake during a bout
Cryptosporidium Causes diarrhea in patients of diarrhea. Ways in which malnutrition contributes
with AIDS, those in day-
care centers, and in trav- to more severe or prolonged diarrhea may include
elers to Leningrad decreased gastric acidity, impaired intestinal immu-
nity, greater exposure to a contaminated environ-

VIII.35. Diarrheal Diseases (Acute) 679
ment, delayed recovery of intestinal mucosa, and Prevention and Treatment
persistent lactase deficiency. The agents producing The factors contributing to the problem of acute diar-
the greatest frequency of dehydration are V. chol- rhea are well known. However, their modification
erae, enterotoxigenic E. coli, and rotavirus. Rota- will not be easy because of cost and required changes
virus is the major cause of death in infants with in behavior. The important variables that will re-
diarrhea. quire attention include the following: availability of
plentiful potable water; adequate systems of sewage
History removal; improved personal and food hygiene; im-
Diarrheal diseases have been important to all soci- proved nutrition through food supplementation pro-
eties since the beginning of recorded history. Hippo- grams; discontinuance of the practice of using night
crates used the term "dysentery" to denote a condi- soil as fertilizer; promotion of breast feeding; effec-
tion wherein the affected person, experiencing tive measles vaccine programs; availability of ade-
straining and painful defecation, passed many stools quate health care to administer oral rehydration
containing blood and mucus. Through the First therapy and selected antimicrobial therapy; family
World War, outbreaks of diarrhea and dysentery planning; insect control; vaccine development and
were as important to deciding the outcome of many implementation for certain enteric infections such
military campaigns as were war-related injuries. as cholera, enterotoxigenic E. coli diarrhea, rota-
The modern era of diarrheal diseases began, as virus gastroenteritis, shigellosis, and typhoid fever.
was the case with other infectious disorders, with Because achieving all of these activities will ini-
the identification of the causative agents involved. tially be too costly in developing areas, research in
During the mid-1800s, Giardia lamblia and Enta- developed countries will be essential to devising
moeba histolytica were first identified. Then during cost-effective prevention and treatment methods.
the latter part of the nineteenth century, Shigella Currently there are three forms of therapy for
and Salmonella organisms were characterized, and acute diarrhea. The first and most fundamental
the two forms of dysentery - bacillary and amebic - form of treatment is fluid and electrolyte replace-
were distinguished. ment. Nearly all forms of acute diarrhea can be
During the 1960s, a series of landmark studies successfully managed by administering oral rehydra-
helped to elucidate the mechanisms of disease production solution. For dehydrating choleralike illnesses,
tion when cholera toxin was purified. As an extension the solution should have optimal electrolyte-
of research with V. cholerae during the 1970s, en- glucose concentrations to facilitate intestinal absorp-
terotoxigenic E. coli were identified as important tion. The major problems with this solution are that
causes of diarrhea. Soon thereafter, other entero- it does not provide the caloric requirements of in-
toxin- or cytotoxin-producing bacteria were discov- fants with diarrhea, and it may actually increase
ered: Salmonella, Aeromonas, Yersinia, Clostridium stool fluid losses. Newer "super solutions" are being
perfrigens, C. difficile, enterohemorrhagic E. coli, evaluated that are better absorbed and furnish more
noncholera vibrios, and Staphylococcus aureus. calories at no osmotic expense. For nondehydrating
Also during the early 1970s, viruses were clearly forms of diarrhea, solutions with lower sodium con-
implicated as causes of diarrhea in humans. Initially, centrations are useful. The second form of therapy
Norwalk virus was shown to produce gastroenteritis involves drugs that reduce the symptoms of diarrhea
in volunteers fed bacteria-free stool filtrates derived by inhibiting secretion or by binding to luminal wa-
from an elementary school outbreak in Norwalk, ter. The final form is antimicrobial therapy directed
Ohio, and the 27-millimeter viral particle was visual- against a bacterial or parasitic agent, which is of
ized by electron microscopy. Soon thereafter, larger value in the treatment of enterotoxigenic E. coli
viral particles were observed in the duodenal mucosa diarrhea, shigellosis, and travelers' diarrhea.
of infants with diarrhea, and within a few years Herbert L. DuPont
rota viruses were established as a major cause of infan-
tile gastroenteritis. Additional pathogens are being
identified in cases of diarrheal disease as the research Bibliography
laboratory discovers novel mechanisms of patho- Davison, W.C. 1922. A bacteriological and clinical consider-
ation of bacillary dysentery in adults and children.
genesis or as new microbiological techniques for isola- Medicine 1: 389-510.
tion and identification are developed. The future will DuPont, H. L., and L. K. Pickering. 1980. Infections of the
bring studies of organism-specific epidemiology, ther- gastrointestinal tract, microbiology, pathophysiology,
apy, and disease prevention. and clinical features. New York.

DuPont, H. L., et al. 1971. Pathogenesis of Escherichia coli organism rarely causes a systemic infection, how-
diarrhea. New England Journal of Medicine 285: 1—9. ever, although skin infections are common in tropi-
Gorbach, S. L. 1978. Infectious diarrhea. Boston. cal regions. Most damage to the infected individual
Mata, L. J., 1978. The children of Santa Maria Cauque: A is produced by the powerful toxin disseminated
prospective field study of health and growth. Cam- through the bloodstream.
bridge, Mass.
Nalin, D. R., et al. 1968. Oral maintenance therapy for
cholera in adults. Lancet ii: 370—3.
Distribution, Incidence, and Immunity
Corynebacteria are distributed throughout the world,
Puffer, R. R., and C. V. Serrano. 1973. Patterns of mortality
in childhood. Pan American Health Organization Sci- but C. diphtheriae occurs naturally only in humans.
entific Publication No. 262. Washington, D.C. Farm animals can be infected through human cases,
and many laboratory animals are susceptible to delib-
erate infection. Indeed, diphtheria's wide host range
accounts for part of the success in studying this organ-
ism during the early bacteriologic revolution.
In historical accounts, it is often described as a
VIII.36 malignant sore throat, and one of the most puzzling
Diphtheria features is the sudden appearance of an epidemic. In
the "throat distemper" epidemic of colonial New En-
gland, Boston was spared the high childhood mortal-
Diphtheria is a human disease caused by Corynebac- ity and morbidity experience elsewhere in Massachu-
terium diphtheriae, so named for its clubbed shape setts and New Hampshire, illustrating the patchy
(Greek: koryne, or "club") and for the hidelike geographic distribution of severe cases that one
pseudomembrane (Greek: diphtheria, for "shield" or could observe even during an epidemic. Peter En-
"membrane") that forms on the tonsils, palate, or glish (1985) describes how a phage virus is associ-
pharynx in severe cases of infection. Although this ated with the virulence of the diphtheria bacilli in
bacillus may cause no more than an innocent, sub- that the "tox" gene can either elaborate toxin (tox+)
clinical infection and can be transmitted via well or not (tox"). But in both cases the presence of this
carriers, during diphtheria epidemics more virulent gene incorporated into the bacterial DNA stimulates
strains are responsible for case fatality rates rang- immunity to virulent diphtheria. Because a low-iron
ing from 30 to 50 percent of affected young children. environment or medium tends to stimulate or facili-
In such circumstances the bacterium itself is in- tate the production of toxin, English further specu-
fected by a phage virus responsible for the elabora- lates that the nutritional poverty of many premod-
tion of a potent exotoxin. Even though the exotoxin ern populations helped to discourage the frequent
can cause rapid fatty degeneration of the heart mus- recurrence of epidemic diphtheria. Many other re-
cle and peripheral nervous system damage resulting searchers, including Ernest Caulfield (1939), point
in paralysis, young children often die because the to a mixture of organisms during epidemics of sore
airway is occluded. Both the suddenness of suffoca- throat, diphtheritic and pseudodiphtheritic. In the
tion in children and the capricious emergence of Boston epidemic of sore throat in 1735, for example,
virulent epidemics of diphtheria are important fea- a rash accompanied clinical cases, suggesting coin-
tures of historical interest in the disease. fection with streptococcal organisms. Suprainfection
Also called the Klebs-Loffler bacillus in early with streptococcus is common even for true diphthe-
twentieth-century medical literature, this gram- ria, but it is not known what influence, if any, the
positive organism is usually spread by respiratory presence of a copathogen has in the elaboration of
secretions and droplet infection. After a brief incuba- toxin.
tion period of 2 to 4 days, the bacillus multiplies in The phage carrying the tox+ genome does en-
the upper respiratory tract, creating a membranous hance iron binding, permitting the microorganism
exudate on pharyngeal tissues. The bacillus invades to acquire this essential metabolite for its reproduc-
the local tissues and kills cells, causing necrosis and, tion. Normally the human immune system is able
often, discoloration of the membrane. The foul to withhold iron and "starve" a pathogen (Weinberg
breath associated with necrosis and the greenish or 1978). Thus the production of toxin and the emer-
blackened membrane are hallmarks of the disease to gence of virulent strains should not depend upon an
most clinical observers differentiating diphtheria individual host's nutritional status. Epidemiolog-
from streptococcal sore throat and from croup. The ically the appearance of virulent diphtheria epidem-

VIII.36. Diphtheria 681
ics should reflect increased opportunities for trans- Clinical Manifestations and Pathology
mitting the bacillus to susceptible hosts, as through Even virulent diphtheria begins quietly, after a brief
crowding or urbanization. Historically diphtheria incubation period. Its victims rarely suffer the high
epidemics were recorded only after medical theories fever, vomiting, or myalgias common in acute viral
supported recognition of the clinical specificity of illnesses, and the sore throat is much less pro-
this disease. nounced than it is in streptococcal pharyngitis. As
the organism multiplies and invades pharyngeal tis-
Epidemiology sues, however, the area around the neck can swell
The ultimate sources of diphtheritic contagion are dramatically, and internally the passage of air be-
humans. In addition to respiratory transmission of comes difficult. The "bullneck" appearance of a diph-
the bacillus through cutaneous diphtheritic lesions, theria sufferer differs from the streptococcus victim
the disease can be spread by touch and by fomites - because there is little enlargement of the regional
such as schoolchildren's pencils. Thus, an infection lymphatic nodes. If the victim can open his or her
can be transmitted to a cow's udders from an in- mouth, an observer usually will see a membrane 1 to
fected milker's fingers. Milk, if unpasteurized, can 3 millimeters thick, its rough edge curling away
also transmit the infection. Even dust around the from the tonsils, palate, uvula, or pharynx. Depend-
bed of a diphtheria patient can remain infective for ing upon the amount of destruction of local blood
weeks (Christie 1974). vessels, this "shield" can range in color from a more
The experience with diphtheria in England and benign-appearing yellowish white, to green or even
Wales, from 1915 to 1942, is probably typical of black. An exudate that remains white, whether or
industrialized countries in the twentieth century. not it looks like a membrane, is usually not due to
Early in this period, over 50,000 cases were reported diphtheria.
each year, and it was the leading cause of death for The German pathologist Edwin Klebs first identi-
children aged 4 to 10 years. Over this time period, fied the C. diphtheriae in 1883 by peeling off this
however, case fatality rates declined by 40 percent membrane and culturing the bleeding surface under-
as a result of more rapid diagnosis and therapeutic neath. The following year Friedrich Loffler devel-
interventions in the form of antitoxin and trache- oped an enriched medium on which to grow the deli-
ostomy (surgically providing a way to breathe when cate bacillus, which could be rapidly overgrown by
the upper pharynx is occluded). other organisms cultured from the mouth and phar-
After World War II, mass immunization efforts ynx. Both noted the absence of other affected organs
effected a rapid decline in the overall number of at autopsy of diphtheria victims. The bacillus is not
cases, and the age of incidence rose. In virulent cases distributed through the body, but the toxin alone
of diphtheria, mortality remains today around 5 per- seems to have the lethal effects described above.
cent, a fact that leads A. B. Christie (1974) to assert Most perplexing is the peripheral nervous system
that we do not possess convincing proof that anti- involvement, contributing to a characteristic pro-
toxin alone reverses the clinical course of diphthe- gression of paralysis in diphtheria victims: first the
ria. The organism itself is sensitive to penicillin. palate, then the eyes, then the heart, pharynx, and
Unlike measles, the common early springtime vi- larynx (with respiratory muscles), and finally the
ral disease of childhood, diphtheria in temperate limbs. In virulent diphtheria, patients appear quite
climates usually peaks in incidence in autumn and toxic, and, although the fever is not usually high,
early winter. Most cases during the last 200 years the pulse is elevated.
have occurred among individuals under 15 years of
age. Crowded conditions to which the poor are sub- Diagnosis and Treatment
jected facilitate passage of the organism, and so ac- The "Schick test" can help to identify diphtheria
counts of diphtheria before the germ theory of dis- sufferers in that it depends upon a patient's failure
ease was widely accepted often described it as a filth to react to a small amount of purified toxin injected
disease naturally favoring the poor (Ziporyn 1988). subcutaneously, thus signaling the absence of anti-
In tropical regions cutaneous diphtheria is much toxin in the body, in turn indicating an absence of
more common, resulting in "punched," weeping ul- previous diphtheria infection. Because many factors
cers sometimes called "desert sores." Contact with can influence the accurate reading and interpreta-
these lesions, usually on the extremities, is probably tion of such a test, most laboratory diagnosis de-
an important means of spreading the disease in such pends upon culture of the organism itself on en-
regions. riched "blood agar" or the "Loffler slant" tellurite

medium developed over a century ago. Penicillin, phenomenon led Loffler in 1887 to a description of
antitoxin, and maintenance of an open airway are nonvirulent strains of diphtheria.
the usual means of clinical intervention. Filtering cultures of bacilli in Louis Pasteur's labo-
ratory, P. P. Emile Roux and Alexandre Yersin demon-
History strated the probability of Loffler's hypothesis that a
It is impossible to determine whether diphtheria toxin was involved in lethal cases of diphtheria. In
was at any point a "new" disease in recorded human 1888 they showed that bacteria-free filtrates repro-
history, though it is so described during the early duced all features of the disease in experimental ani-
modern period. Diseases resembling diphtheria are mals except the formation of a membrane, and they
also described in Greek medical literature of antiq- tried unsuccessfully to apply Pasteur's rabies method
uity (English 1985) and during the sixteenth in habituating animals to the toxin. Soon afterward,
through eighteenth century. Historical interest in in 1890, Emil Behring and Shibasaburo Kitasato,
this particular disease has nevertheless been con- working in Koch's laboratory, explored the use of
fined largely to the role diphtheria played in the serum from convalescing individuals to treat diphthe-
emergence and confirmation of the germ theory of ria patients (and experimental animals). Thus before
disease. As Terra Ziporyn (1988) points out, diphthe- the beginning of the twentieth century, diphtheria
ria was to a considerable extent "the darling of the had provided the best single model for proving the
bacteriological revolution." germ theory of disease, and suggested the concept of
A clinician of Tours trained during the French the healthy carrier, the possibility of filterable (non-
Revolution, Pierre Bretonneau was the first to de- bacterial) disease agents, and the general usefulness
scribe the specific clinical features of diphtheria and of serology in diagnosis and treatment of infectious
to give the disease its name. Witnessing relatively disease.
severe epidemics in the mid-1820s, Bretonneau care- After a legendary, dramatic, Christmas eve rescue
fully noted the appearance of a pseudomembrane as of a diphtheritic child with the Kitasato-Behring
a hallmark of the disease and used this particular serum, Behring personally escalated his study and
infection to elaborate his concepts of disease specific- production of "antitoxin," standardizing and popular-
ity, based on uniform clinical and postmortem find- izing his procedures for harvesting immune serum
ings. Nevertheless, diphtheria was usually viewed from horses inoculated with filtered toxin. Diphthe-
as a disease of poverty, rather than as an exception- ria rapidly became a largely curable disease, and
ally severe threat to human survival, as were epi- Behring was honored as the "children's savior" and
demics of cholera and yellow fever. Periodic peaks in elevated to the hereditary nobility ofGermany. Simul-
diphtheria mortality received no attention among taneously, however, diphtheria was depicted as a clas-
clinicians. sic, feared contagious disease and, unlike so many
Immediately after Robert Koch articulated a germ diseases in this category, as a widespread, merciless
theory of disease based on his 1882 work with tubercu- killer of innocent children. Indiana physician Thur-
losis, Klebs and Loffler clearly demonstrated the pre- man Rice, for example, vividly recalled that his fa-
cise causal connection between diphtheritic organ- ther "drove two miles out of his way to avoid passing
isms and membranous sore throat. Loffler especially in front of a house where there was a case of diphthe-
provided an elegant summary of the isolation and ria, and yet this house stood at least one hundred
culture of C. diphtheriae together with a description yards back from the road; he had children and was
of Koch's principles as "postulates" proving the germ taking no chances" (Rice 1927). Diphtheria also
theory (Lechevalier and Solotorovsky 1974). Loffler's frames the plot for one of the most famous physician
classic paper in 1884 also introduced some of the most stories in the English language, William Carlos Wil-
basic and innovative research problems for germ theo- liams's "The Use of Force" (1933).
rists. Speculating upon the reasons why diphtheria Finally, the study of diphtheria was involved in
bacilli, unlike Mycobacterium tuberculosis, failed to two further stages of twentieth-century research on
invade areas of the body other than the nasopharynx, the germ theory and its applications. First, the
Loffler ventured that an "extraordinarily deleteri- Schick test helped to identify individuals who had no
ous" poison was disseminated through the blood- immune response to small doses of toxin injected just
stream. Moreover, his careful work illustrated that under the skin. In the testing of immunity and the
the organism could not always be cultured from the anaphylactic responses of individuals with "serum
throats of clinically "typical" cases and that healthy sickness" in response to foreign sera (a considerable
individuals could carry diphtheria bacilli. The latter problem with Behring's method), clinicians used

VIII.37. Down Syndrome 683
Table VIII.36.1. Diphtheria mortality rate per Levy, F. M. 1975. The fiftieth anniversary of diphtheria
100,000 population and tetanus immunization. Preventive Medicine 4:
226-37.
New Pitts- Washing- Major, Ralph H. 1965. Classic descriptions of disease, 3d
York Chicago Boston burgh ton edition. Springfield, 111.
Rice, Thurman B. 1927. The conquest of disease. New
1890-4 134.4 117.3 112.2 86.4 77.9 York.
1895-9 85.8 69.7 83.9 32.9 50.9 Weinberg, Eugene D. 1978. Iron and infection. Microbio-
1900-4 58.0 33.9 53.7 36.9 23.5 logical Reviews 42: 45—66.
1905-9 40.0 27.0 26.2 20.4 11.2 Williams, William C. 1984. The use of force. In The doctor
1910-14 28.0 37.9 20.0 29.3 6.9 stories, ed. Robert Coles. New York.
1915-19 21.8 31.2 26.3 22.3 11.9 Ziporyn, Terra. 1988. Disease in the popular American
1920-4 14.0 17.5 20.2 20.1 10.5 press: The case of diphtheria, typhoid fever, and syphi-
1925-9 10.7 11.7 8.3 11.5 7.1 lis, 1870-1920. Westport, Conn.
1930-4 2.2 4.5 3.2 5.1 3.7
1935-9 0.6 2.2 0.7 1.3 2.8
1940-4 0.1 0.8 0.4 0.5 0.2
Source: Diphtheria mortality in large cities of the United

States in 1947 (1948).
VIII.37
diphtheria throughout the early part of the century
to delineate the research problems in human immu-
Down Syndrome
nity (Levy 1975). (See Table VIII.36.1 for trends in
large U.S. cities.) Second, in the early 1950s, identifi- Down syndrome, previously called "mongolism," is
cation and isolation of the phage virus that infected a relatively common condition resulting from the
diphtheria bacilli greatly aided early research estab- presence of an extra chromosome, number 21, in all
lishing phage-bacterial chromosome relationships the cells of the body. In each human cell, there are
and, in the process, the fields of bacterial genetics 23 chromosome pairs containing basic genetic mate-
and molecular biology (Berksdale 1971). rial that organizes the body's development and phys-
Ann G. Carmichael iological functioning. Each pair has a distinctive
size and conformation and can be readily identified
Bibliography on microscopic examination. Chromosome pair num-
Berksdale, Lane. 1971. The gene tox+ of Corynebacterium ber 21 is one of the smaller chromosomes. In Down
diphtheriae. In Of microbes and life, ed. Jacques syndrome there are usually three (trisomy) rather
Monod and Ernest Borek. New York.
than two number 21 chromosomes (trisomy 21:
Biggs, H. M. 1899. The serum-treatment and its results.
found in 95 to 98 percent of all cases). In a small
Medical News 75: 97.
Billings, J. S. 1905. Ten years' experience with diphtheria number of children with Down syndrome, the extra
antitoxin. New York Medical Journal 82: 1310. number 21 chromosome is attached to a chromo-
Caulfield, Ernest. 1939. The throat distemper of 1735- some of a larger pair (numbers 13 to 15; transloca-
1740. New Haven. tion Down syndrome — about 2 percent of all cases).
Christie, A. B. 1974. Infectious diseases: Epidemiology and In some children with the features of Down syn-
clinical practice, 2d edition. London. drome, the extra chromosome is present in less
Diphtheria mortality in large cities of the United States in than 90 percent of the cells (mosaic Down syn-
1947. 1948. Journal of the American Medical Associa- drome - about 2 to 4 percent of all cases). Down
tion 137: 1525. syndrome is the most frequently occurring chromo-
Dolman, Claude. 1973. Landmarks and pioneers in the some abnormality in live-born humans, and is also
control of diphtheria. Canadian Journal of Public among the most frequently identified chromosomal
Health 64: 317-36.
abnormalities, representing about 4 percent of all
English, Peter C. 1985. Diphtheria and theories of infec-
tious disease: Centennial appreciation of the critical
aborted fetuses (Lilienfeld 1969). Down syndrome is
role of diphtheria in the history of medicine. Pediat- usually recognizable at birth as a cluster of physi-
rics 76: 1-9. cal and neurological abnormalities (see Clinical
Lechevalier, H. A., andM. Solotorovsky. 1974. Three centu- Manifestations), which develop in a characteristic
ries of microbiology. New York. fashion during the life cycle.

Distribution and Incidence longer and have an increased rate of nondis-
Recent estimates of overall worldwide incidence of junction.
Down syndrome are around 0.8 per 1,000 live births 4. Long-term exposure to environmental agents has
(Janerich and Bracken 1986). In the United States, resulted in damage to the spindle mechanism that
the 1983 Birth Defects Monitoring Program indi- in turn produces meiotic nondisjunction.
cated an incidence of 0.82 per 1,000 live births.
These figures evidence a decline from those reported Because the additional chromosome can be traced to
20 years ago in Western countries, where incidence the father in 20 percent of the cases of Down syn-
was about 1.7 per 1,000. This change is thought to be drome, studies have also evaluated a paternal age
the result of the use of prenatal diagnosis. effect on incidence. However, such an effect cannot be
Down syndrome occurs in all races and ethnic conclusively demonstrated (Janerich and Bracken
groups, though good documentation of specific inci- 1986).
dence in many groups and geographic areas is lack- About 30 to 60 percent of all Down syndrome
ing (Lilienfeld 1969). There is some evidence for births, however, are not age dependent, meaning
spatial aggregation, such as in northern Finland that they occur in mothers of ages under 30 years.
and British Columbia (Janerich and Bracken 1986), Indeed, a high incidence of infants with Down syn-
but these instances appear to be sporadic, and are drome has recently been reported in women less
probably related to environmental sources. than 15 years of age. In both younger and older sibs
of index patients, the risk of having offspring with
Down syndrome is increased 2- to 10-fold. Younger
Epidemiology and Etiology mothers are more likely to have a second offspring
The presence of the additional number 21 chromo- with Down syndrome than are older mothers. The
some in all cells of the individual with Down syn- recurrence risk is 1 in 3 for mothers who are
drome is usually the result of an error in cell divi- translocation carriers.
sion called nondisjunction. In normal cell division,
the two members of each of the 23 chromosome pairs A number of environmental and metabolic mecha-
separate and move into one of the two resulting nisms for Down syndrome have been evaluated,
cells, whereas in nondisjunction, both members of among them maternal drug, tobacco, alcohol, and
the chromosome pair end up in a single cell. In Down caffeine use; use of hormonal and nonhormonal con-
syndrome, the nondisjunction has usually occurred traceptives; fluoridated water; and radiation expo-
during meiosis (sex cell division) usually of the fe- sure. However, findings from these studies have
male sex cell (the ovum). Thus, when an ovum with been inconsistent. Some investigators have sug-
two number 21 chromosomes is fertilized, three num- gested that a possible recessive gene producing
ber 21 chromosomes (two from the mother and one nondisjunction might explain up to 10 percent of the
from the father) will be passed on to all the cells in cases. However, studies in consanguineous mar-
the developing fetus. The occurrence of Down syn- riages do not support this suggestion. Dwight
drome is most consistently associated with advanced Janerich and Michael Bracken (1986) indicate that
maternal age, with incidence rising from 0.45 per the association with elevated maternal age is un-
1,000 live births in women 20 to 24 years of age (8 doubtedly a surrogate variable for other underlying
studies) to 9.4 per 1,000 live births for women 40 to associated factors, the most important of which are
44 years (7 studies). The largest risk increase occurs probably endocrine changes associated with aging.
between the age groups 30 to 34 and 34 to 39 years
(Lilienfeld 1969). Clinical Manifestations
Four potential reasons for the maternal age asso- The most easily recognizable features of Down syn-
ciation have been suggested: drome derive from abnormalities in growth of the
cranium and face. These include a short, relatively
1. Whereas the prenatal incidence of Down syn- broad head (brachycephaly), hypoplastic maxilla,
drome is constant across all ages, the older uterus upslanting palpebral fissures, epicanthal folds, in-
is less selective in rejecting the Down syndrome creased neck skin, small ears, and flattened nasal
conceptus. bridge. Common postcranial anomalies include a
2. Longer delays between intercourse result in a wide space between the first and second toe, abnor-
relatively "aged ovum," more likely to experience mal finger and palm dermatoglyphs (in particular,
nondisjunction. the occurrence of single palmar creases), and short-
3. In older women, the ova themselves have aged ened distal long bones. About 80 percent of children

VIII.37. Down Syndrome 685
with Down syndrome are hypotonic and 90 percent red ectropic conjunctiva, coming to supply the cur-
are hyperflexible. There are also variably associated tailed skin at the margin of the lids" (quoted in
major organ anomalies, the most important being Brousseau and Brainerd 1928). The first formal de-
congenital heart disease (CHD), which occurs in 30 scription was given in a report by J. Langdon Down
to 50 percent of all children with Down syndrome. In in 1866. He described a type of congenital defect
addition, metabolic and hormonal systems are vari- bearing resemblance to the Tartar race which he
ably affected and include, among others, carbohy- called Kalmuc or Mongolian. Down, who had been
drate metabolism, deficient absorption of vitamin A, influenced by the racial hypothesis and the writings
elevated serum uric acid, and abnormal serotonin of Charles Darwin, suggested that the entity repre-
metabolism. sented a reversion to an earlier phylogenetic type.
In an extensive recent survey of 1,341 children This hypothesis never gained wide acceptance, and
with Down syndrome born between 1952 and 1981 in fact, Down's own son, also a doctor, disagreed with
in British Columbia, Patricia Baird and Adel it, suggesting that the features of the syndrome were
Sadovnick (1987) reported survival rates up to 30 accidental and superficial (Brain 1967).
years of age in 50 percent for those with CHD, but The next important reports were presented by
nearly 80 percent for those without CHD. The sur- John Fraser and Arthur Mitchell in 1875 at the
vival rate for the latter group, however, was less Royal College of Physicians in Edinburgh. Mitchell
than that for a comparison group of mentally re- pointed out the similarities between the syndrome
tarded individuals without Down syndrome. and "cretinism" (congenital hypothyroidism). Re-
Children with Down syndrome experience abnor- ports by W. W. Ireland and G. E. Shuttleworth fol-
mal physical and cognitive development. Birth lowed during the 1870s and 1880s. Shuttleworth
weight and length are near normal, but the growth suggested that children with the condition were actu-
rate in the first 3 years of life is significantly slower ally "unfinished," representing the persistence of
than normal, and most children are less than the anatomy characteristic of a particular phase in fetal
fifth percentile in height by the time they are 3 development. He specifically cited the already recog-
years of age. Growth rate during childhood is near nized association between the syndrome and ad-
normal, but the adolescent growth spurt is often vanced maternal age, pointing out the large number
absent (Cronk et al. 1988). Deficient growth differen- of children with Down syndrome who were the last-
tially affects distal segments of the long bones. born in large families. During the end of the nine-
Whereas some early developmental milestones are teenth and beginning of the twentieth centuries,
normal, more marked delays in walking, talking, many reports appeared, expanding the description of
and other motor and cognitive skills usually become the syndrome's phenotypic manifestations. Impor-
apparent by the end of the first year of life. Mild to tant among these were the extensive neuropathologi-
moderate mental retardation (IQ: 30 to 67) is com- cal descriptions by A. W. Wilmarth presented in
monly present by childhood. Recent innovations in reports from 1885 to 1890.
early intervention and new special education pro- From the initial description in the mid-nineteenth
graming allow individuals with Down syndrome to century to 1959, a large number of etiologic hypothe-
hold jobs as adults in sheltered work situations. ses were advanced for the syndrome, including ma-
ternal syphilis, familial tuberculosis, familial inci-
History and Geography dence of epilepsy, insanity, instability, and mental
Probably the earliest record of Down syndrome was retardation. Once the increased incidence of congeni-
a Saxon skull excavated in the seventh century show- tal heart disease in the syndrome was recognized by
ing osteological changes consistent with the condi- John Thomson and A. E. Garrod in 1898, a cause in
tion. There are also accounts of sixteenth-century early fetal existence was sought. Among theories
paintings of children having the features of the syn- advanced were maternal alcoholism, fetal hyperthy-
drome. The first accounts of Down syndrome, how- roidism, maternal dysthyroidism, hypoplasia of the
ever, did not appear until the nineteenth century. In adrenals, dysfunction of the pituitary, abnormality
1846 E. Sequin wrote of a specific type of mental of the thymus, chemical contraceptives, curettage,
retardation case, which he described as a "furfura- faulty implantation, degeneration of the ovum, and
ceous cretin with its white, rosy, and peeling skin, emotional shock in early pregnancy.
with its shortcomings of all the integuments, which As early as 1932, a chromosomal anomaly was
give an unfinished aspect to the truncated fingers suggested as a possible cause of the disorder (Bleyer
and nose; with its cracked lips and tongue; with its 1934). In 1959, shortly after the correct diploid

number of chromosomes in the human cell was es- gametic mutation of degressive type. American Jour-
tablished, a small sample of children with Down nal of Diseases of Children 17: 342-8.
syndrome were demonstrated to have an extra acro- Book, M. A., M. Fraccaro, and J. Lindsten. 1959. Cytogen-
centric chromosome and a total chromosome num- etical observations in mongolism. Acta Paediatrica 48:
ber of 47 in cultures of fibroblasts. Thisfindingwas 453-68.
verified by subsequent studies. Later in the same Brain, L. 1967. Historical introduction. In Mongolism,
year, J. A. Book and co-workers (Book, Fraccaro, CIBA Foundation Study Group No. 25, 1-5. London.
Brousseau, K., and H. G. Brainerd. 1928. Mongolism: A
and Lindsten 1959) concluded that the extra chro-
study of the physical and mental characteristics of
mosome was most similar to number 21 in the Den- mongolian imbeciles. Baltimore.
ver classification. In 1960, other investigators Collman, R. D., and A. Stoller. 1962. Epidemiology of
reported the case of a girl with Down syndrome congenital anomalies of the central nervous system
having only 46 chromosomes, and postulated a re- with special reference to patterns in the State of Victo-
ciprocal translocation occurring between two chro- ria, Australia. Journal of Mental Deficiency Research
mosome groups (Polani et al. 1960). 7: 60-8.
Initially, Down syndrome was thought to occur Cronk, C. E., et al. 1988. Growth charts for children with
only in the Caucasian race. Subsequently, however, Down syndrome, one month to 18 years. Pediatrics 81:
reports have shown that it occurs in every racial 102-110.
group and country although thorough, well-designed Down, J. Langdon. 1867. Observations on ethnic classifica-
tion of idiots. Journal of Mental Science 13: 121-3.
studies have not allowed an accurate picture of its
Janerich, D. T., and M. B. Bracken. 1986. Epidemiology of
true distribution across racial and ethnic groups. trisomy 21: A review and theoretical analysis. Jour-
Early reports indicated a low incidence in African nal of Chronic Disease 39: 1079-93.
and black American groups. However, recent investi- Lilienfeld, A. M. 1969. Epidemiology of mongolism. Balti-
gations in Ibadan, Nigeria, and in Memphis, Tennes- more.
see, found black incidence rates much the same as Penrose, L. S. 1954. Observations on the aetiology of mon-
those of white populations (Janerich and Bracken golism. Lancet 2: 505-9.
1986). Similarly, although detection in Oriental Polani, P. E., et al. 1960. A mongol girl with 46 chromo-
populations is thought to be' inhibited by sameness somes. Lancet 1: 721-4.
of features, recent studies in Japan reveal rates Pueschel, S. M. 1984. The young child with Down syn-
much like those in the United States. An extensive drome. New York.
study from the World Health Organization in 1966 Pueschel, S. M., and L. S. Steinberg. 1980. Down syn-
indicated that a low incidence of Down syndrome is drome: A comprehensive bibliography. New York.
reported in India, Malaysia, and Egypt (Lilienfeld Sheehan, P. M., and I. B. Hillary. 1983. An unusual cluster
1969), whereas by contrast a high incidence was of babies with Down's syndrome born to former pupils
of an Irish boarding school. British Journal of Medi-
reported in Yugoslavia, Czechoslovakia, and at least cine (Clinical Research) 287: 1428-9.
one location in Melbourne, Australia.
A. M. Lilienfeld (1969) summarized 11 studies
that attempted to indicate the spatial and temporal
clustering of the syndrome. However, even the most
sophisticated of these, carried out in Melbourne, Aus-
tralia (Collman and Stoller 1962), failed to give satis-
factory statistical proof for clustering. A 1983 report
by P. M. Sheehan and I. B. Hillary describes a cluster
of children with Down syndrome born to women who
attended the same boarding school in their youth.
This suggests that in some instances, an environ-
mental agent may influence the incidence of Down
syndrome.
Christine E. Cronk
Bibliography
Baird, P. A., and A. D. Sadovnick. 1987. Life expectancy in
Down syndrome. Journal of Pediatrics 110: 849-54.
Bleyer, A. 1934. Indications that mongoloid imbecility is a

VIII.38. Dracunculiasis 687
another 20 million at risk in India and Pakistan,

VHI.38 based on the assumption that everyone is at risk
Dracunculiasis who is living in a rural district where a minimum of
one case of dracunculiasis has occurred.
The number of persons affected annually by this
This disease is a pathological condition resulting infection is not known. Although diseases are often
from infection with the parasite Dracunculus medi- underreported in the countries affected, the report-
nensis. In most instances, the adult worms, which ing of dracunculiasis is especially poor because the
are about 1 meter long, are quite evident as they infection generally is found only in impoverished
emerge slowly through the skin of their victims. rural communities where medical facilities are rare,
and where many victims cannot walk and have little
Distribution and Incidence incentive to seek treatment because there is no drug
In the 1980s and 1990s, Dracunculiasis is found that can cure the infection. The best estimate is that
mainly in India, in Pakistan, and in a band of 19 probably between 5 and 15 million persons contract
African countries between the Sahara Desert and dracunculiasis each year.
the equator, from Senegal in the west to Ethiopia in
the east (see Map VIII.38.1). Formerly this disease Epidemiology and Etiology
was much more widespread in the Middle East and Dracunculiasis is a seasonal infection, usually occur-
Africa, and it occurred for some years in the Ameri- ring at the precise time of year when rural villagers
cas after it was introduced there by infected Africans must plant or harvest their crops. People are in-
during the slave trade. fected when they drink water containing a tiny crus-
In general, the incidence of dracunculiasis is sig- tacean of the genus Cyclops, called a copepod, which
nificantly higher in endemic rural Africa communi- harbors the infective larvae of the parasite. About a
ties than in endemic Asian villages. In West Africa year later, the adult worms emerge through the skin
especially, for example, rates of infection in affected to discharge larvae into freshwater, to be ingested by
areas often reach 20 to 40 percent, and sometimes an appropriate copepod, thus continuing the cycle.
exceed 50 percent, whereas in Asia, the rates usu- In drier ecological areas, such as the Sahelian zone
ally are below 20 percent. In rural areas, the disease in Africa, the infection appears during the brief
occurs sporadically, with adjacent villages some- rainy season (summer), when surface water is avail-
times differing greatly in the percentage of those able. In areas that receive more rainfall, such as the
infected. Susan Watts (1987), a medical geographer, coastal regions along the Bight of Benin, the infec-
has estimated that the number of persons at risk of tion appears, and is transmitted, during the dry sea-
this infection in Africa is about 120 million, with son (winter), when stagnant surface water sources
are scarcest and most polluted.
The most commonly affected age groups are gener-
ally persons 15 to 45 years of age - that is, working
adults. Younger children are affected, but not in-
fants under 1 year, and generally not many children
under 5 years. Often farmers are particularly liable
to infection, apparently because they drink large
volumes of contaminated water while laboring on
their farms. School children also suffer high rates of
infection in some areas. Male or female victims may
predominate in any given area, depending on their
relative exposures.
There is no drug suitable for effective mass treat-
ment of dracunculiasis, and from time immemorial,
the disease has been treated by slowly winding the
emerging worm around a stick. The disease can,
however, be prevented by teaching villagers to boil
their drinking water or filter it through a cloth, by
Map VIII.38.1. Areas in which dracunculiasis is reported treating contaminated sources of water with a chemi-
or probably exists. cal (temephos), or by providing protected sources of

drinking water, such as tube wells or draw wells bian physicians described dracunculiasis. Of these,
(rather than ponds or open "step wells"). Avicenna gave the first detailed clinical description
of what he called "medina sickness," because the
Clinical Manifestations and Pathology infection was then so common in Medina. Shortly
Usually the first clinical sign of infection is a blister, before, Rhazes showed that the swelling caused by
which the adult worm produces, accompanied by se- the infection was due to a parasite.
vere burning of the skin, at the site where the worm Sixteenth-century European travelers mentioned
is about to start emerging. This begins about 1 year having encountered cases of the disease in Persia
after the contaminated water has been drunk. The and the Congo. It is said to have been called "Guinea
blister ruptures when the affected part of the body is worm" for the first time by another European who
immersed in water, leaving a small ulcer, at the saw persons suffering from the infection on the
center of which is the worm. Most worms emerge on Guinea Coast (West Africa) early in the seventeenth
the foot, ankle, or lower leg, but they can emerge century. The disease is also mentioned in the tradi-
through the skin on any part of the body. Sometimes tional legend by which the Dahomeyans explained
the worm first appears as a curvy line beneath the the founding of their ancestral cult. Although G. H.
skin, or at the center of a painful abscess or nodule. Velschius described the parasite clearly in his mono-
Worms that do not emerge from the body die and graph, published in 1674, it was left for Linnaeus
are then absorbed, or calcify, in which case they (Carl von Linne) to give the worm its modern scien-
appear as characteristic curled lines on X-ray. The tific name of Dracunculus medinensis in 1758.
worms may invade a major joint, the brain or spinal British army medical officers reported seeing
cord, or other vital area, producing more serious cases of dracunculiasis among British military per-
manifestations, although this is rare. Much more sonnel serving in India in the nineteenth century,
common are secondary infections of the local wound and a large punitive English expedition sent to in-
that give rise to abscesses, local arthritis, and some- vade Ethiopia in 1868 also suffered greatly from the
times tetanus. In most patients, only one worm same disease. The role of the copepod intermediate
emerges at a time, though as many as two dozen or host in the life cycle of the parasite was discovered
more may present themselves simultaneously in one only in the 1870s, by a Russian, Aleksei Fedchenko.
person. The geographic extent of dracunculiasis shrank
Affected persons may be crippled for several considerably during the first half of the twentieth
weeks or even months, by the pain associated with century, largely, it appears, because of gradually im-
the worm's slow emergence and secondary infec- proving standards of living, and especially stan-
tions. Because the infection appears at such a criti- dards that have produced better water supplies. The
cal time of year for food production and cripples disease was eliminated from the southern area of the
large numbers of persons simultaneously, it has an Soviet Union in the 1930s by means of a deliberate
enormous economic impact. Moreover, people who campaign, and from Iran in the 1970s. With the
are infected develop no immunity, so they may be advent of the United Nations-sponsored Interna-
and often are infected year after year. tional Drinking Water Supply and Sanitation De-
cade in the 1980s, India and several other endemic
History and Geography countries began national campaigns to eradicate
This is a very old infection, which many believe to dracunculiasis. In 1986, the World Health Assembly
have been the "fiery serpent" said by Moses to have adopted a resolution calling for the elimination of
attacked the Israelites when they were on the shores this disease country by country. It appears likely
of the Red Sea. At least one calcified Dracunculus that this ancient disease will not plague humankind
worm has been discovered in the mummy of a 13- much longer.
year-old Egyptian girl who died around 1000 B.C., Donald R. Hopkins
and a treatment for this condition may be described
in the Ebers Papyrus.
Bibliography
Some Greek and Roman writers described the in- Foster, William C. 1965. A history ofparasitology. London.
fection, and it was Galen who named it "dracontia- Hopkins, Donald R. 1983. Dracunculiasis: An eradicable
sis." The ancient medical practice of treating infec- scourge. Epidemiologic Reviews 5: 208-19.
tions by winding the worm slowly around a stick is 1987. Dracunculiasis eradication: A mid-decade status
thought by some historians to have been the origin report. American Journal of Tropical Medicine and
of the Staff of Aesculapius. Several medieval Ara- Hygiene 37: 115-18.

VHI.39. Dropsy 689
Muller, Ralph. 1971. Dracunculus and dracunculiasis. Ad-sues, much as salt draws water to the cut surface of a
vances in Parasitology 9: 73-151. raw potato. Thus, fluid accumulates in tissues when
Watts, Susan J. 1987. Dracunculiasis in Africa: Its geo-either intracapillary pressure increases or the blood's
graphical extent, incidence, and at risk population. ability to remove water from tissues decreases. In
American Journal of Tropical Medicine and Hygiene both cases,fluidthat has moved out of the capillaries
33:121-7. is poorly reabsorbed. Most hydrostatic defects are pri-
World Health Organization. 1989. Dracunculiasis: Global
mary heart diseases, whereas most oncotic defects
surveillance summary - 1988. Weekly Epidemiolog-
ical Record 64: 297-300.
result from renal and hepatic disease.
Congestive heart failure produces dropsy, or edema,
when the heart becomes too weak to maintain the
normal pressure head behind bloodflowin the capil-
laries, so that even the normal resistance to flow
through them facilitates the leakage of water from
capillary blood into surrounding tissues. The adjec-
tive "congestive" refers to the accumulation and
stagnation - congestion — of blood in organs, espe-
cially the lungs, when they are not adequately emp-
The historical diagnosis of dropsy - which is now tied because of backward pressure from obstructions
obsolete - indicated simply an abnormal accumula- distal to them.
tion of fluid; the word derives from the Greek hy- The other major causes of dropsy, which appear
drops (water). Alternative or supplementary terms chiefly as edema of the foot (pedal edema) and ankle,
included hydrothorax (fluid in the chest cavity), ascites, and occasionally anasarca, are listed below
ascites (which still indicates excess free fluid in the for the sake of completeness, but will be discussed
abdominal cavity), anasarca (still used to describe further only in relation to heart failure:
generalized edema throughout the body), hydro-
cephalus (used until the nineteenth century to indi- 1. Liver failure capable of producing ascites most
cate excess fluid within the skull), and ovarian often occurs in advanced cirrhosis because the
dropsy (large ovarian cystsfilledwith fluid). Edema diseased liver cannot manufacture sufficient pro-
was often a synonym for dropsy, but it now has tein (albumin) to maintain the oncotic pressure of
additional connotations, and pulmonary edema has the blood. Right ventricular failure (see below)
been differentiated from hydrothorax. Since the can also produce hepatic congestion and failure.
mid-nineteenth century, dropsy has been recognized 2. Renal failure causes dropsy when the glomerular
as a sign of underlying disease of the heart, liver, or filtering units become so diseased (e.g., in
kidneys, or of malnutrition. Untreated dropsy was, glomerulonephritis, first known as Bright's dis-
eventually, always fatal. ease) that albumin and other large molecules are
lost from the blood into the urine, resulting in
decreased oncotic pressure.
3. Malnutrition results in ascites when protein in-
The major underlying causes of dropsy are conges- take is so low that the liver is unable to manufac-
tive heart failure, liver failure, kidney failure, and ture adequate amounts of albumin. Beriberi, the
malnutrition. Because they were not clearly differen- result of insufficient dietary thiamine, can also
tiated before the nineteenth century, a historical weaken the heart.
diagnosis of dropsy cannot be taken to indicate any
one of these alone in the absence of unequivocal The epidemiology of dropsy is that of its underly-
supporting evidence, as from an autopsy. However, ing causes. For instance, elevated serum cholesterol
heart failure was probably the most frequent of the levels and smoking both predispose to hypertension
four. and myocardial infarction ("heart attack"), which
The etiologies of dropsy can be explained most con- are major causes of heart failure. Beriberi heart
veniently in terms of fluid balance. One principal disease is associated with diets consisting chiefly of
force in the maintenance of normal fluid balance is highly polished rice, and with alcoholism. Similarly,
the hydrostatic (or hydraulic) pressure within capil- the epidemiology of streptococcal infections governs
laries. The other major force is oncotic pressure, the the appearance of the inflammatory reactions that
normal tendency for sodium or large particles (e.g., can eventuate in glomerulonephritis or in cardiac
proteins) in capillary blood to draw water out of tis- valve distortions.

However, the epidemiology of some forms of Framingham (Mass.) Heart Study in 1971. In 1985,3
dropsy has changed in recent years. The introduc- of every 1,000 Americans were reported to develop
tion of penicillin for the treatment of streptococcal heart failure annually, producing an overall inci-
infections after World War II, for example, has re- dence of about 1 percent of the population, regardless
duced the occurrence of their cardiac and renal se- of age; 34 to 58 percent of heart failure patients die
quelae. On the other hand, the increasing life expec- each year.
tancy of Americans in the twentieth century for
many years meant an increased incidence of heart Clinical Manifestations and Pathology
disease. Now, however, recent data suggest that the This discussion focuses only on congestive heart fail-
incidence of coronary artery disease and myocardial ure because it was probably the major underlying
infarction has been falling, perhaps as a result of cause of dropsy. The heart is able to compensate, up
factors such as changes in diet and exercise level. to a point, for diminished strength of contraction, for
Heart failure occurs more often in men than increased resistance to arterial outflow (resulting in
women, inasmuch as men are at greater risk for "pressure overload"), and for accumulations of blood
most forms of cardiovascular disease. The risk is that cannot be completely removed from the ventri-
greater for older than younger patients: Three quar- cles at each contraction (resulting in "volume over-
ters of heart failure patients are over 50 years of age. load"). The usual responses to these stresses include
Risk factors for hepatic cirrhosis include chronic alco- the following: (1) reflexly increased heart rate
holism and hepatitis, just as renal causes of dropsy (tachycardia), to speed blood flow (actually, oxygen
may be associated with rheumatic fever or the delivery) into the arteries; (2) hypertrophy (in-
nephrotic syndrome. creased mass) of ventricular muscle, in response to
pressure overloads; and (3) dilation and thinning of
Distribution and Incidence ventricular walls, in response to volume overloads,
The distribution of dropsy within or among popula- although hypertrophy can be expected to follow as a
tions parallels the distributions of its underlying further adjustment.
causes, such as hypertension, myocardial and coro- Symptoms of heart failure begin to occur when no
nary artery insufficiency, hypercholesterolemia, val- further compensations can be made. "Forward fail-
vular disease, streptococcal infection, cirrhosis, and ure" symptoms occur when the heart can no longer
renal glomerular disease. Risk factors for these con- empty the left ventricle completely because of rea-
ditions are still being identified and their clinical sons such as myocardial weakness or obstruction to
implications evaluated. Only for malnutrition are aortic outflow. Normally the ventricles eject 60 to 66
geographic distinctions clear-cut (e.g., in drought- percent of the blood in them at each beat. But when
stricken areas of Africa, or countries where diet cen- only 40 percent of the blood in the left ventricle can
ters too closely on polished rice). be expelled, symptoms begin to appear, and they
Historically, a diagnosis of dropsy was based sim- become severe when only 20 percent can be expelled.
ply on abnormal accumulations of fluid in the legs, Symptoms of "backward failure" occur when the
abdomen, or chest. The diagnosis was so easy that heart chambers become incapable of complete fill-
artists such as Thomas Rowlandson (in his 1810 print ing, due to incomplete relaxation of the heart be-
"Dropsy Courting Consumption") could portray it in tween beats, or to obstructions to venous inflow into
popular prints with the expectation that their custom- the right atrium.
ers would recognize it immediately. Consequently, it Heart failure can be produced by several underly-
is not surprising that the reported incidence of dropsy ing pathological causes, although seldom does any
has not changed substantially over the 400 years for one of them occur alone:
which comparable records are available. That is,
dropsy has been diagnosed in about 3 to 5 percent of 1. Myocardial insufficiency, in which the heart is too
deaths, hospital admissions, or adult patients in Lon- weak to maintain normal blood flow, occurs
don in 1583—1849, and in American villages and cit- acutely when a substantial portion of the muscle
ies in 1735—1839. Typical modern incidences of con- is incapacitated by infarction, or in association
gestive heart failure include 7 percent of patients with gradual left ventricular failure. Both dila-
discharged from a Baltimore hospital medical service tion and hypertrophy are likely adaptations.
in 1969-70, 2.31 percent of outpatients who had pre- 2. Left ventricular failure may occur suddenly, after
scriptions filled in a San Francisco hospital in 1971, a myocardial infarction, or slowly, owing to pres-
and 3.05 percent of persons over 30 years of age in the sure overload, most often imposed by increasing

VIII.39. Dropsy 691
resistance (hypertension) to blood expelled into tem attempts to compensate for the lack of oxygen.
the aorta. Other causes include stenosis (narrow- Both dyspnea and tachypnea increase as fluid from
ing) of the aortic valve, which increases the pres- the pulmonary capillaries begins to flood the lungs.
sure against which the heart must pump, and When the lungs become sufficiently congested (pul-
aortic insufficiency, also called regurgitation, monary edema), the patient coughs up copious spu-
which occurs when an incompetent valve that can- tum, which is characteristically rust-colored (with
not close permits a volume overload to build up as small amounts of blood) if mitral stenosis is pres-
bloodflowsback into the left ventricle instead of ent. Stertor (noisy inspirations) often accompanies
forward into the aorta. the dyspnea. A more serious form of dyspnea is
3. Right ventricular failure usually follows when the orthopnea. This term is applied to shortness of
pressure head built up as a result of left ventricu- breath that prevents the patient from sleeping hori-
lar failure is transmitted backward through the zontally because venous blood, which remains in
pulmonary vessels to the right ventricle. Other the lower part of the body as a result of gravity
causes of right heart failure include stenosis of during waking hours, further congests the lungs,
the mitral valve, cor pulmonale (see below), and causing dyspnea. An exaggerated form of orthopnea
insufficiency of the tricuspid valve. called paroxysmal nocturnal dyspnea may waken
4. Failure of both ventricles simultaneously usually the patient suddenly at night; it is sometimes called
accompanies a strain common to both sides of the "cardiac asthma" because it produces wheezing and
heart, as in constrictive pericarditis, beriberi, hy- labored breathing.
pothyroidism, or anemia so severe that the heart Physical examination and X-rays reveal cardiac
rate increases markedly to compensate for the enlargement and fluid in the lungs and chest; other
reduced number of red blood cells delivering oxy- tests can confirm that cardiac output is low. Fur-
gen to the tissue. ther symptoms of left heart failure as it worsens
5. Chronic cor pulmonale (pulmonary heart disease) include pale dusky skin, sweating, cold hands and
occurs when chronic obstructive pulmonary dis- feet, and tachycardia, all reflex responses to dimin-
ease (e.g., emphysema) increases resistance to out- ished cardiac output, and decreased urine output
flow from the right ventricle, resulting in right (oliguria) secondary to diminished bloodflowthrough
ventricular failure. the kidneys.
6. Acute cor pulmonale is caused by sudden massive Although right heart failure is far more likely to
obstruction of the pulmonary circulation, almost occur as a sequela of left heart failure than by itself, it
always by a clot that has formed as a result of does produce distinctive symptoms in addition to the
thrombophlebitis in a leg vein, and has dislodged usual dyspnea and tachypnea, both of which may be
(embolized) so that it follows the venous pathway more pronounced in right than left heart failure.
to the right heart and thence into the lungs, Pedal edema occurs, accompanied by hydrothorax.
where it becomes wedged so as to obstruct blood Ascites is a late sign of right heart failure, and may be
flow distal to it. The results include infarction of followed by anasarca and oliguria. The skin becomes
the affected lung, impaired venous return, and bluish (cyanosis), because the sluggishly moving red
dilation of the right ventricle. cells are not adequately oxygenated in the lungs. The
7. Less frequent causes of congestive heart failure jugular veins in the neck distend because the in-
include, among others, diminished arterial blood creased pressure in the right heart prevents them
flow to both kidneys, resulting in decreased so- from emptying completely into the superior vena
dium excretion. cava. Other evidence of increased venous pressure
includes congestive enlargement of the liver (hepato-
Whatever the underlying cause, the major mani- megaly) and sometimes the spleen (splenomegaly).
festation of heart failure is reduced cardiac output,
measured as the liters of blood ejected from the left History and Geography
ventricle per unit time. The associated symptoms Dropsy is not much different from one geographic
and signs are usually clearly recognizable. area to the next, except when it accompanies local-
For instance, the first symptoms of left heart fail- ized famines or beriberi induced by local dietary hab-
ure are those of being quick to tire and having its, and the symptoms of dropsy have not changed
shortness of breath {dyspnea), due to insufficient over the centuries. Its history is the story of evolving
delivery of oxygen to the body's tissues, followed by interpretations of its clinical features over 2,000
rapid breathing (tachypnea) as the respiratory sys- years as the relationships of dyspnea, "suffocative

catarrh," pulmonary edema, hydrothorax, ascites, because its drying action was analogous to that of
syncope, and "fever" to heart failure were elucidated. the sun in dispelling rain.
Like his contemporaries, Girolamo Capivaccio of
Italy agreed with Galen that dropsy was due to liver
Antiquity Through the Fifteenth Century
disease and impaired blood formation, so that fluid
The first known mention of dropsy is in an Egyptian
was released into the abdominal cavity to form
medical text of about 1550 B.C., the Ebers Papyrus.
ascites, which he detected by percussion, as Celsus
It associates dropsy with increased abdominal girth,
had. Capivaccio also attributed dropsy to disease in
and hints that it is accompanied by a weak pulse.
other organs, such as obstruction of the pathways to
The Hippocratic Aphorism VII, 47, correctly prognos-
the kidneys, but he did not mention the heart or
ticates that "[t]here is no hope when a patient suffer-
even hydrothorax; he surmised that dyspnea was
ing from dropsy develops a cough." And Jesus defied
caused by upward pressure from a pathologically
the lawyers and Pharisees by healing a man with
enlarged liver on the diaphragm.
dropsy on the Sabbath (Luke 14), although no symp-
toms are recounted. Soon after, Aulus Cornelius The sixteenth-century physician Ludovicus Merca-
Celsus described two forms of dropsy: (1) generalized tus of Valladolid defined dyspnea as rapid, difficult
edema (aqua inter cutem), which could be drained breathing, sometimes accompanied by stertor, caused
through small skin incisions above the ankle; and by constricted airways or by excess heat in the heart
(2) ascites, in which the excess fluid detectable by and lungs; he thought the chief function of respira-
observing fluid waves in the abdominal wall could tion was to cool the heart. He followed Galen's classi-
be removed by paracentesis, or tapping (i.e., drain- fication of dyspnea into three stages of increasing
age through a metal tube inserted through an inci- severity: tachypnea, asthma (by which he meant con-
sion in the abdominal wall). vulsive gasping for breath), and orthopnea. Mercatus
thought that hydrothorax fluid descended from the
Galen of Pergamum listed several causes of dropsy brain to produce the "suffocative catarrh" described
in the first century A.D., including a hardened liver, by Galen as suffocation in the absence of inflamma-
as well as inadequate blood formation (which he tion, and that its associated dyspnea was caused by
thought occurred in the liver), hemorrhoids, and fluid in the lungs, or even by heart disease. He theo-
both amenorrhea and uterine hemorrhage. Virtu- rized that hydrothorax fluid was overflow from
ally all writers on dropsy until the mid-seventeenth ascites or from obstructed urinary passages.
century cited the teachings of Hippocrates, Celsus,
and Galen. Their ideas were also relayed in the Throughout the seventeenth century, it became
eleventh century by Avicenna of Baghdad, who increasingly clear that dropsy was associated with
thought that the tachycardia, palpitations, pulmo- altered fluid dynamics as postmortem dissections
nary edema, dyspnea, and syncope (fainting or and experimentation were exploited more fre-
shock, which he postulated was a sign of a weak quently. For instance, Carolus Piso (Charles le Pois)
heart) that accompanied dropsy were related to one of Lorraine detected hydrothorax as "bubbling"
another. when he applied his ear to the chest. Coupling clini-
cal observations with autopsy findings, he attrib-
uted paroxysmal nocturnal dyspnea to fluid in the
Sixteenth and Seventeenth Century chest cavity. Fabrizio Bartoletti of Italy disagreed
Five centuries later, the French surgeon Ambroise with Mercatus and Capivaccio in some of their inter-
Pare described dropsy in identical terms. His coun- pretations, but he used observations like Piso's to
tryman Jean Fernel relied on the same theories hypothesize that hydrothorax fluid came from the
when he associated heart disease, but not dropsy lungs. He noted that the first clue to its presence was
specifically, with palpitations, syncope, and the pal- dyspnea on exertion, followed by "fever" (which he
lor, cold sweat, and weak pulse often observed in probably detected as modest tachycardia), tachyp-
cardiogenic shock. Also in the sixteenth century, nea, orthopnea, dry cough, thirst, syncope, leg and
Paracelsus theorized that dropsy (wassersucht) oc- scrotal edema, and, finally, ascites. Bartoletti
curred when the body's tissues dissolved. He associ- thought that although hydrothorax was not rare, it
ated it with dyspnea, cough, and oliguria. Following was always fatal because it suffocated its victims.
his usual mystical chemical reasoning, he recom- In 1616 William Harvey found that edema accu-
mended that dropsy be treated with mercuric oxide mulated behind ligated veins. Later he postulated
to remove superfluous water, with other metallic that if the entire venous system were maximally
oxides to dry the patient's body, and with sulfur, distended, the heart would stop and suffocation

VIII.39. Dropsy 693
would follow. In De Motu Cordis (1628), he described the first clues that cardiac disease might not be
the heart and lungs as "storehouses" for the blood, incompatible with life. One of them, Raymond
the metaphor that Saul Jarcho, the leading student Vieussens of Montpellier, correlated the work of Har-
of dropsy, thinks led to the concepts of pulmonary vey, Lower, and Malpighi with his own postmortem
engorgement and passive congestion - concepts that dissections of dropsy patients. By 1705, he had con-
would prove to be critical to further understanding cluded that structural disease of the heart could
of dropsy in the chest. result in dropsy, after showing how mitral or pulmo-
In his Tractatus de Corde (1669), Richard Lower of nary stenosis, or aortic insufficiency, could produce
Oxford and London described how he had produced the clinical signs of what is now called backward
edema and ascites in dogs by ligating the jugular failure. At almost the same time, Giovanni Maria
veins and the superior vena cava. He also found that Lancisi was dissecting victims of sudden death in
excess fluid in the pericardial sac could restrict car- Rome. Although among the last to cite Fernel, his
diac expansion sufficiently to diminish venous re- own observations permitted him to recognize that
turn, resulting in bradycardia, syncope, and death. edema, hydrothorax, and ascites could be related to
Lower went on to postulate that the right and left failure of the heart's propulsive force (i.e., forward
sides of the heart should be of equal strength in failure), to aortic regurgitation, and to obstructions
order to maintain the circulation, while noting that in the right heart. Explicitly recognizing the impor-
the left side alone may be weakened, an early expres- tance of hydrostatic principles in cardiovascular
sion of the notion of forward failure. He also per- physiology, Lancisi went on to explain how stagna-
ceived that excessive amount, pressure, orflowrate tion of blood within the pulmonary vasculature
of blood might adversely affect health. Finally, he could result in dyspnea, and he learned how to diag-
recognized Galen's "suffocative catarrh" as pulmo- nose hydrothorax ante mortem. He cited Lower's
nary edema, although they were considered to be experiments to support his conclusion that right
separate clinical entities for many years afterward. heart failure could produce engorgement and pulsa-
In 1681 Marcello Malpighi of Bologna carried Har- tion of the jugular vein. Thus together Lancisi and
vey's quantitative approach to experimental physiol- Vieussens uncovered the cardiac basis of dropsies of
ogy an important step further when he noted the the lungs and thorax.
increased weight of dyspneic lungs (attributable to Their work was expanded a few years later by
the stagnant blood within them). Because he had another of Malpighi's pupils, Ippolito Francesco Al-
discovered capillaries 20 years earlier, he could hy- bertini, also of Bologna. He echoed his mentor's
pothesize that blood escaped from them into the conclusion that sluggish circulation through the
lungs. Malpighi thought that stagnant blood in the lungs leads to dyspnea. A frequent dissector, Al-
pulmonary vessels produced palpitations and irregu- bertini emphasized the time course of dyspnea
lar pulses because it precluded an orderly blood sup- when he pointed out that it comes on rapidly when
ply to the heart. He reasoned that an imbalance obstructions occur in the pulmonary vein of the left
between arterial outflow and venous resorption of heart, resulting in delayed removal of blood from
water from the blood caused dropsy, but he attrib- the lungs, erosion of the pulmonary vessels, hemop-
uted the imbalance to chemicals that constricted tysis, and hydrothorax.
blood vessels or irritated and thus stimulated the Another interpretation of dropsy arose from Har-
nerves that controlled the heart and the respiratory vey's demonstration that the blood circulates within
muscles. One of Malpighi's students, Giorgio Bag- a closed system. In this case, dropsy came to be seen
livi, described the symptoms of suffocative catarrh as a febrile disease, because it was usually accompa-
so that it finally became clearly recognizable as nied by a fast pulse, regarded as a cardinal clinical
acute pulmonary edema (not the result of fluid fall- sign of fever over the centuries before clinical ther-
ing from the head): dyspnea, cough, stertor, sensitiv- mometers became widely available in the 1870s.
ity to cold, chest pain, thirst, anxiety, and, one of his Thus Thomas Willis, Lower's mentor and colleague,
major original observations, foaming at the mouth. defined fever as an "intestine motion or commotion
of the blood" arising in chemical disturbances like
Eighteenth Century to Modern Times those described over a century earlier by Paracelsus.
Physicians were slow to understand that the heart Hermann Boerhaave of Leyden was a major propo-
could be diseased, probably because it was thought nent of the idea that dropsy was a fever, which
to be absolutely essential to life, but in the early should be treated accordingly. He based much of his
eighteenth century two students of dropsy provided teaching on the work of Friedrich Hoffmann of Prus-

sia, who saw the body as a machine, subject to the of small or large vessels, or any debilitating disease.
effects of mechanical forces. This led Boerhaave to Neither Monro nor later writers mentioned the blood
argue that in dropsy, fever is the result of increased viscosity hypothesis.
cardiac work and increased vascular resistance to In 1763 Samuel Clossey of Dublin and New York
blood flow - in short, of friction. Therefore, by his applied the principles governing the relationship be-
reasoning, dropsy was a fever because it was associ- tween pressure and flow velocity, outlined 35 years
ated with a fast pulse. At the same time, he postu- earlier by Daniel Bernoulli of Basel, to his own stud-
lated that dropsical fluid accumulated because defec- ies of the hydrostatic properties of the cardiovascu-
tive veins released more fluid into body tissues than lar system. Clossey realized that the development of
those weakened vessels could reabsorb. In Italy, hydrothorax is a long process, when he computed
Luca Tozzi, who adopted the newer ideas of that it would take about 2 years for 3 pints of
Paracelsus, Lower, Malpighi, and Hoffmann, was hydrothorax fluid to accumulate. He followed Lan-
among the first to differentiate hydrothorax, pulmo- cisi in associating dropsy with weakness of the
nary edema, and pneumonia at autopsy, which per- heart, but postulated that cardiac strength derived
mitted him (and, later, Albertini) to differentiate from that of the blood vessels.
pulmonary and thoracic dropsies ante mortem by Thus, regardless of how they were interpreted, the
palpating the chest and apical impulse of the heart. major clinical manifestations of dropsy had been
A new method for detecting hydrothorax appeared identified by the mid-eighteenth century. Some phy-
in 1761, when Leopold Auenbrugger of Vienna de- sicians followed Boerhaave's dictum that dropsy was
scribed how to strike the chest with the fingers to caused by weak blood vessel fibers, whereas others
estimate, by the resonance they produced, the attributed the omnipresent dyspnea to weakened
amount and nature of fluid in the pleural cavity and cardiac contraction, as did the medical encyclopedist
lungs. However, his discovery of percussion added no Robert James of London in his Medicinal Dictionary
new information about the pathology of dropsy, and of 1745. But by the turn of the century, unproven -
was neglected until it was reintroduced in France in and unprovable - theories of dropsy based on fever,
1808. chemical disturbances, blood viscosity, and fiber
The first book devoted to dropsy alone was pub- tone began to fade, and the role of the diseased heart
lished in 1706 by the Leopoldine Academy of Sci- came into sharper focus.
ences in Breslau; its principal author was probably In 1806, Jean-Nicholas Corvisart, who would soon
Christianus Helwich. The Academicians described popularize Auenbrugger's discovery of percussion in
the clinical features of dropsy much as previous au- French translation, showed how heart disease could
thors (especially Piso) had done, but they attributed produce dropsy, dyspnea, and orthopnea when ve-
the escape of fluid from the vessels to diminished nous return was slowed. Three years later Allan
blood viscosity and to defective vessel walls, as Burns of Glasgow demonstrated that ossification of
Boerhaave, too, was suggesting. the mitral and pulmonary valves leads to right heart
In 1733, Stephen Hales, a rural English clergy- dilation and dropsy, although it is not clear whether
man, concluded from his experiments in animals that he was aware of Vieussens's pioneering observations
dropsy could be caused by decreased numbers of red along the same lines. And in 1835 James Hope of
blood cells. However, he did not reason that the pau- Cheshire showed how myocardial failure results in
city of red cells would decrease blood viscosity, much dyspnea.
less oncotic pressure. Rather, he thought that the In 1813 John Blackall of London was among the
body would compensate for the lack of "red Globules" first to suggest that dropsy can result from non-
by heating the blood into a feverish state that re- cardiac conditions such as liver and kidney disease,
sulted in dropsy. He was perhaps the first to recognize when he demonstrated that the albumin content of
that inadequate venous return to the heart in dropsy urine can help differentiate among the underlying
could lead to compensatory (reflex) tachycardia. causes of dropsy. Blackall's thesis about renal causes
Donald Monro of Edinburgh published the second of dropsy was confirmed by Richard Bright, whose
book devoted to dropsy in 1755. He followed careful autopsies at Guy's Hospital in London led
Boerhaave in ascribing it to "a weakness and laxity him to report, in 1827, that albumin could be found
of the fibers . . . when the vessels do not act with in the urine of patients with glomerulonephritis who
sufficient force," and listed several factors that died of dropsy. A few years later, Bright showed that
would tend to weaken blood vessels: a watery diet, renal disease could also be associated with left ven-
"any great evacuation," kidney disease, obstruction tricular hypertrophy, presumably because hyperten-

VIII.39. Dropsy 695
sion is often associated with renal disease. In 1909 leaked into the tissues could be removed more
C. J. Rothberger and H. Winterberg in Austria, and readily. So did Clossey and Monro, who said that
Thomas Lewis in London, independently showed dropsy should be treated with tonic drugs, "which by
that a nonanatomic cardiac condition, atrial fibrilla- their stimulus force the sensible [i.e., excitable] or-
tion, could produce heart failure, and in 1935 Paul gans into contractions."
Dudley White and Sylvester McGinn of Boston de- In 1785, there appeared the single most influen-
scribed acute cor pulmonale. tial - and perhaps most widely read and immedi-
Although many details of the pathophysiology of ately accepted - book in the history of dropsy, An
congestive heart failure are still being ascertained, Account of the Foxglove, by William Withering of
all investigators continue to exploit the relation- Birmingham, England. His was the first prospec-
ships discovered by Ernest Henry Starling at Univer- tive study of the clinical efficacy and safety of any
sity College, London. He noted in 1897 that the drug, for the treatment of any disease. Using his-
strength of heart muscle fiber contraction is propor- torical controls as negative controls, Withering
tional to fiber length - up to a point. But it was not clearly demonstrated the therapeutic benefit of digi-
until 1920 that he adduced experimental evidence to talis in patients with dropsies that were not related
demonstrate the relevance of the rate of blood flow to primary disease in other organs, such as the
from the veins into the heart, and of the arteries' ovaries. Because increased urine production usually
resistance to outflow, to his basic "Law of the Heart." followed the administration of digitalis, he thought
In 1936 Tinsley R. Harrison of Vanderbilt Univer- it was a diuretic. Although he noted that the pulse
sity consolidated Starling's and other surviving con- rate fell in patients whose symptoms were amelio-
cepts of heart failure to explain the phenomenon rated by the new drug, he did not recognize the
more or less as we understand it today, although drug's tonic effect on the heart.
heart failure remains the subject of many increas- Because dropsy had been seen since the mid-
ingly detailed investigations. eighteenth century as a "weakness and laxity of the
fibers," some physicians who followed Withering con-
Historical Treatments cluded that digitalis stimulated the "system,"
The earliest measures for treating dropsy were whereas others concluded that it was a depressant
chiefly attempts to correct humoral imbalances. Cel- because it reduced fast heart rates. In 1813 Blackall
sus, for example, recommended drugs he regarded as (not John Ferriar, as some have supposed)firstsug-
diuretics, as well as a wide variety of other medicines gested that digitalis actually strengthens the heart.
with different physiological effects. (One of his diuret- This concept resurfaced in papers published in
ics, squill, was finally abandoned only after White 1905-11 by James Mackenzie of London and Karel
demonstrated its lack of dependability in 1920.) Dur- Frederik Wenckebach of Holland and Vienna, but it
ing the Renaissance, Capivaccio, Mercatus, and Piso was only verified in 1938-44, by H. J. Stewart and
were still recommending Galenic drugs to carry away John McMichael. Wenckebach also demonstrated
dropsicalfluid,especially cathartics, emetics, diapho- the efficacy of digitalis in atrial fibrillation.
retics, expectorants, and diuretics like squill. In addi- The two major clinical goals of treatment in con-
tion, Capivaccio pointed out that blistering with gestive heart failure today are improved oxygen-
cantharides ("Spanishflies")and paracentesis would ation of the tissues by increasing cardiac output, and
remove dropsicalfluid,but he recommended bleeding reduction of hydrostatic pressures in the veins. Digi-
only if the patient's blood had been diseased because talis glycosides (chiefly digoxin and digitoxin, both
of disturbed liver function. of which must still be extracted from the purple
The number of drugs recommended for dropsy di- foxglove, Digitalis purpurea, or the white species,
minished during the course of the seventeenth cen- Digitalis lanata) increase cardiac output by strength-
tury. The Leopoldine Academicians described some ening the force with which the heart contracts;
they thought would increase blood viscosity by re- diuresis occurs secondarily, because the resulting
moving excess fluid from the body, such as diuretics, increase in the amount of blood that can then be
cathartics, and diaphoretics. Baglivi and Lancisi fa- circulated to the kidneys permits increased removal
vored diuretics almost exclusively. Malpighi and his of water into the urine. True diuretics, which act on
student, Albertini, on the other hand, who based the kidneys alone, relieve pressure in the venous
their treatments on the teachings of Hoffmann, rec- system by removing excess fluid from the body via
ommended tonic drugs to strengthen the tone of the the urine.
weakened resorbing veins, so that fluid that had Other drugs now used in the treatment of heart

failure include dopamine, dobutamine, hydrala-
zine, nitroprusside, and enalapril; although all of VIII.40
these agents reduce hydrostatic pressures by dilat- Dysentery
ing blood vessels, they act on the vessels in different
ways. Enalapril is unusual in that it can also facili-
tate reversal of left ventricular hypertrophy. In addi- Dysentery is an inflammation of the large intestine
tion, amrinone and milrinone both dilate vessels and characterized by loose stools containing blood and
increase the force of cardiac contraction. Oxygen and mucus, and by tenesmus - painful and unproductive
rest, which may have to be induced with sedatives, attempts to defecate. Diarrhea, marked by the fre-
are important adjuncts to drug therapy. Paracentesis quent production of watery stools, may be confused
and thoracentesis may occasionally still be required, with dysentery in historical accounts, but references
but the subcutaneous leg drainage tubes described to "bloody flux" refer to true dysentery. The condi-
by R. Southey of London in 1871 were abandoned tion may be caused by an ameba, Entamoeba histo-
with the advent of true diuretics. Patients with lytica, or by several species of bacteria, especially in
acute pulmonary edema (as in acute cor pulmonale) the genus Shigella. See Amebic Dysentery, Bacillary
are often treated with morphine, which reduces not Dysentery, and Diarrheal Diseases (Acute), Chap-
only their anxiety and their tachycardia but also ters VIII.5, VIII.14, and VIII.35, this volume.
their hydrostatic pressures against bloodflow(via K. David Patterson
an effect in the central nervous system).
J. Worth Estes
Bibliography
Blackall, John. 1813. Observations on the nature and cure
of dropsies, 3d edition. London.
Estes, J. Worth. 1979. Hall Jackson and the purple fox-
VIII.41
glove: Medical practice and research in revolutionary Dyspepsia
America, 1760-1820. Hanover, N.H.
Fye, W. Bruce. 1983. Ernest Henry Starling, his law and
its growing significance in the practice of medicine. Derived from Greek roots meaning "difficult diges-
Circulation 68: 1145-8. tion," dyspepsia has long served as a synonym for
Jarcho, Saul. 1980. The concept of heart failure from indigestion, one of the most common - and etiologi-
Avicenna to Albertini. New York.
cally varied — of human miseries. It has thus been as
Jarcho, Saul, trans, and ed. 1971. Practical observations on
dropsy of the chest [Breslau, 1706]. Transactions of the regularly employed to label the symptoms of diverse
American Philosophical Society 61 (n.s.): 3-46. organic disorders as to identify a distinct disease,
McKee, P. A., et al. 1971. The natural history of congestive with the result that some gastroenterologists find
heart failure: The Framingham study. New England the word uselessly elastic: "This is really a meaning-
Journal of Medicine 285: 1441-6. less term because it has so many meanings." The
Monro, Donald. 1755. An essay on the dropsy. London. majority of practitioners, however, have reached a
Tendon, Owsei. 1952. The elusiveness of Paracelsus. Bulle- consensus to use dyspepsia to denote either the ail-
tin of the History of Medicine 26: 201-17. ment of functional indigestion or the symptoms of
White, Paul Dudley. 1951. Heart disease, 4th edition. New peptic ulcer.
York.
Withering, William. 1785. An account of the foxglove, and
some of its medical uses; with practical remarks on Distribution and Incidence
dropsy and other diseases. Birmingham. [See, espe-
cially, the edition annotated by J. K. Aronson (Lon-
Peptic ulcer dyspepsia is rare in people under the
don, 1985).] age of 20, but by age 30, 2 percent of the males and
0.5 percent of the females in a population have devel-
oped the condition. For men, the incidence increases
steadily with age, reaching a peak of around 20
percent in the sixth decade of life. The incidence for
women remains low, about 1 percent, until meno-
pause, after which it climbs as rapidly as in men. A
morbidity rate of nearly 14 percent has been re-

VTII.41. Dyspepsia 697
ported in women in the age group 70 to 79. Death History and Geography
from peptic ulcer occurs three times as often in men
Great suppers do the stomach much offend,
as women. Sup light if quiet you to sleep intend.
The prevalence of functional dyspepsia, by con-
trast, is uncertain. Having no distinct pathology, So advised the author of the medieval Regimen
being neither communicable nor reportable, and Sanitatis Salernitanum, and no doubt his words
only occasionally motivating its victims to seek medi- were already age-old wisdom. Yet if indigestion has
cal help, it does not generate statistics. The widely plagued the human race for as long as it has eaten,
shared clinical impression is that women are af- and no less hoary an expert than Hippocrates de-
fected more than men, and people under the age of scribed its tortures, it was not until the nineteenth
40 more than those over age 40. Functional dyspep- century that dyspepsia attained a prominent stand-
sia is also believed to be more prevalent in developed ing in pathology. Previously it was regarded as a too
countries. common but predictable and temporary discomfort
brought on by immoderacy in diet. Alexander Pope's
scolding couplets characterized pre-Victorian views
Epidemiology and Etiology (Davis 1966):
Although the most common, peptic ulcer is hardly the
only organic source of dyspepsia. Esophagitis; hiatus [T]he stomach cramm'd from every dish,
hernia; gastritis; carcinoma of the stomach, colon, or A tomb of roast and boil'd, offleshand fish,
pancreas; Crohn's disease; disease of the biliary tract; Where bile and wind, and phlegm and acid jar.
chronic nephritis; or any of several other conditions, And all the man is one intestine war.
including pregnancy, can produce indigestion. In ap- The sources of intestinal turbulence came to ap-
proximately half of the cases of dyspepsia, however, pear more numerous during the early nineteenth cen-
no lesion can be found, and symptoms arise from tury. The distrust of sensuality that marked the Victo-
derangements of motor, secretory, or absorptive func- rian ethos more than once expressed itself in the
tions, especially delayed gastric motility, esophageal blaming of physical decline on moral perversion. And
reflux, and hyperacidity. This functional indigestion because dyspepsia was so often found in patients
has been related to physical stress (aerophagia, fa- guilty of some excess and just as often lacked any
tigue, dietary indiscretion) and, more commonly, to apparent organic basis, physicians found it easy to
nervous stress. Anxiety, anger, frustration, and other explain the condition on the basis of any aberrant
indications of emotional turmoil can significantly im- behavior that might plausibly have upset the pa-
pair digestive function in sensitive or tense individu- tient's system. Gluttony, of course, was still a sin, and
als (a similar psychic component - chronic tension doctors had no quarrel with Ambrose Bierce's (1911)
and repression of emotion - has been implicated in definition of a glutton as "a person who escapes the
peptic ulcer). Because the symptoms of functional evils of moderation by committing dyspepsia." They
dyspepsia are virtually identical to those of peptic generally added to gluttony the bolting of inade-
ulceration, the condition has also been termed X-ray quately chewed food, a practice that many charged
negative dyspepsia and nonulcerative dyspepsia; the was epidemic in the dining rooms of ever-in-a-hurry
term endoscopy-negative dyspepsia has been pro- America. Nevertheless, a nineteenth-century attack
posed as well in recent years. of dyspepsia was just as likely to be blamed on the
abuse of spirits or tobacco, to the reading of French
Clinical Manifestations novels, or to masturbation or "excessive venery."
That most eminent of Victorian dyspeptics, Thomas The nineteenth century's list of dyspepsia's causes
Carlyle, likened his torment to "a rat gnawing at the was also lengthened by examples of fast living of a
pit of the stomach." Dyspepsia's victims still com- second type, that of the mental and emotional excita-
plain of gastric pain, along with fullness or heavi- tion accompanying the bustling anxiety-filled life of
ness in the stomach, nausea and vomiting, belching, the industrial city. A. P. W. Philip's Treatise on Indi-
flatulence, and/or acid eructations. Finally, dyspep- gestion (1825), which recommended against exces-
tics may suffer heartburn, a caustic pain behind the sive venery, also warned, in the same breath, of the
sternum that sometimes climbs into the throat, re- dangers of "too long application to business [and]
sulting from esophageal reflux. Heartburn is the severe study." Such caveats would appear with in-
special affliction of those with sliding hiatus hernia creasing regularity in medical texts and home
when they bend or lie down. health guides alike until finally becoming manda-

tory with the ascension of neurasthenia, or nervous "dyspepsia," historically associated with nervous,
exhaustion, to the position of the disease of modern nonorganic illness, is becoming antiquated. In the
society during the last quarter of the century. last decades, medical writers have taken to encapsu-
George Beard, neurasthenia's prophet, declared lating the word in quotation marks to call attention
"delicacy of digestion" to be "one of the best known to its quaintness, and inserting it into the index only
and first observed effects of civilization upon the to be followed with "see indigestion."
nervous system," and his message that dyspepsia James Whorton
was on the rise as the special complaint of the mod-
ern brainworker and risk-taker met with universal Bibliography
acceptance. The 1873 proclamation of The House- Bierce, Ambrose. 1911. The devil's dictionary. Cleveland.
hold Physician by Ira Warren and A. E. Small was Coghill, N. F. 1969. Dyspepsia. In Diseases of the digestive
not hyperbole for the time: system, ed. Martin Ware, 1-7. London.
Davis, Herbert, ed. 1966. Pope. Poetical works. Oxford.
Dyspepsia is a disease of civilization. Savages know noth- Horrocks, J. W., and F. T. DeDombal. 1978. Clinical presen-
ing of it. It is the costly price we pay for luxuries. All tation of patients with "dyspepsia." Gut 19: 19—26.
civilized nations suffer from it, more or less, but none so Jones, F. Avery, J. W. P. Gummer, and J. E. Lennard-Jones.
much as the people of the United States. It is here, in the 1968. Clinical gastroenterology, 2d edition. Oxford.
new world, that the disease has become domesticated, and Mendeloff, Albert. 1983. Epidemiology of functional gas-
we, as a people, who have threatened to monopolize its trointestinal disorders. In Functional disorders of the
miseries. digestive tract, ed. William Chey, 13-19. New York.
The neurasthenia era, furthermore, defined "mod- Philip, A. P. W. 1825. A treatise on indigestion and its
consequences, 5th edition. Philadelphia.
ern dyspepsia" as a nervous complaint that gave as
Sleisinger, Marvin, and John Fordtran. 1973. Gastrointesti-
good as it got, one that having originated in anxiety, nal disease. Philadelphia.
then generated more anxiety, as well as irritability, Spiro, Howard. 1977. Clinical gastroenterology, 2d edition,
depression, and other neurotic suffering in addition New York.
to mundane heartburn. This virtual equation of dys- Susser, Mervyn, and Zeno Stein. 1962. Civilization and
pepsia with nervousness led to its being defined al- peptic ulcer. Lancet 1: 115—19.
most exclusively as a functional condition produced Warren, Ira, and A. E. Small. 1873. The household physi-
by stress. cian. Boston.
During the first half of the twentieth century, that Wightman, K. J. R., and K. N. Jeejeebhoy. 1973. Assess-
same stress of coping with civilization seems to have ment of symptoms. In Gastroenterology, ed. Abraham
brought about an abrupt increase in dyspepsia of Bogoch, 9-41. New York.
organic origin as well. Between the two world wars,
peptic (particularly duodenal) ulcer grew from a
rarely encountered condition to a significant cause
of disability, reaching a high point in the 1950s, then
declining sharply to the present. This pattern has
suggested that ulcer dyspepsia is less a disease of
civilization than a condition of adjustment to civiliza-
tion; the first generations to confront the pressures
of urban-industrial life are buffeted more heavily
than those born after the turbulent transition pe-
riod. Functional dyspepsia, of course, might be ex-
pected to decrease for the same reason, yet its do-
main has been diminished still more rapidly by the
X-ray and the endoscope, improved diagnostic tech-
niques having transferred many cases of "nervous
indigestion" to peptic ulcer's column. Advances in
understanding of the neurohumoral mechanisms
that regulate the digestive tract and the biochemical
basis of emotion, furthermore, promise to provide
organic interpretations for the dyspepsias now iden-
tified as functional. As a consequence, the very term

VIII.42. Ebola Virus Disease 699
other, and people are continually passing back and
vm.42 forth between these regions.
Ebola Virus Disease Epidemiology, Distribution, and Incidence
The epidemic of a highly fatal disease (later named
Textbooks on tropical diseases in Africa are well Ebola virus disease) began in June 1976, with an
out of date. With the recognition of new and deadly index case in Nzara, southern Sudan, among work-
viral infections - Lassa, Marburg, Ebola, Congo- ers in a cotton factory. This patient went to a large
Crimean Hemorrhagic Fever, Rift Valley Fever, and hospital in Maridi, where the disease spread rapidly
AIDS - the classical descriptions of major diseases among hospital patients and staff. The epidemic ran
such as malaria and yellow fever must be thor- its course by November 1976. There were 148 deaths
oughly revised, and to the roster of more minor ail- in 284 detected cases (52 percent mortality). In 1979
ments can be added dengue, Chikungunya, O'Nyong a further outbreak occurred in southern Sudan, with
Nyong, West Nile fever, and others. One must be fewer cases and a small number of deaths.
ready to challenge earlier descriptions of African The epidemic in Zaire was traced to an index case
fevers in general. Malaria in particular has been an seen on September 1, 1976. The individual in ques-
"umbrella" diagnosis, which obscured and still ob- tion had received an intravenous injection of
scures the diagnosis of other, sometimes dangerous chloroquine for presumptive malaria with fever at
concomitant illnesses in regions where malaria it- the outpatient clinic of Yambuku Mission Hospital,
self is endemic to hyperendemic. The absolute need Bumba District. He recovered, but within a week a
for laboratory confirmation to support the clinical large epidemic of fever began in hospital patients
impression is slowly being recognized. This must and staff. A total of 318 cases occurred, with 288
extend beyond the simple demonstration of pres- deaths (90.5 percent mortality). A number of inpa-
ence of malaria parasites in the blood. Malaria para- tients and members of the hospital staff, physicians,
sites in the blood certainly prove that the individ- and attendants also died. The epidemic had termi-
ual in question harbors the parasite. But it is not nated by November 5, 1976. The diagnosis of the
necessarily proof that the actual immediate in- first epidemiological team sent to the area was "a
fection from which the individual is suffering is fulminating epidemic of typhoid fever in a non-
related to the existing chronic malarial position. vaccinated population." Fatalities, however, oc-
Treatment of the malarial infection is indicated, curred in a hospital in Kinshasa in the cases of three
and is followed almost universally in tropical Af- nurses who had been transferred from the infected
rica, with or without confirmation of the presence of area, and it became clear, as investigations contin-
malaria parasites. The first diagnosis entertained ued, that passage of the virus from human to human
for all of the viral infections listed above is almost had occurred through the medium of contaminated
always "malaria." needles and syringes. Whereas formerly rigidly en-
It is when the patient does not respond to the forced isolation and barrier procedures had been
antimalarial therapy exhibited that other possible somewhat relaxed, strict syringe and needle disci-
diagnoses are considered. In addition to the viral pline and isolation of patients were reestablished
possibilities, the list should also include influenza, and maintained as a permanent part of hospital op-
typhoid fever, various rickettsioses, leptospiral infec- erations protocol.
tions, bacterial and viral enteropathogenic agents - The epidemics in the Sudan and Zaire terminated
indeed the range of infections capable of inducing a as abruptly as they had started. However, in 1979
febrile response. another hospital-centered outbreak occurred in Tan-
After the appearance of the Marburg virus in 1967 dala, Zaire, 300 kilometers distant from the original
and the Lassa virus in 1969 had given a jolt to Bumba outbreak. In total, 33 patients were diag-
complacency, the Ebola virus in 1976 provoked a nosed, of whom 22 died (66 percent mortality).
convulsive shudder. The Ebola story began with al- Through the 1980s no further outbreaks have been
most simultaneous outbreaks of a deadly infection in reported in Sudan or Zaire or elsewhere in Africa,
the Maridi region of southern Sudan and in the with the exception of a probable case from Kenya
Bumba Zone of the equator region of north central reported in 1983.
Zaire, neighboring on the Sudan, and in towns along Complacency was shattered in the United States
the course of the Ebola River. The Sudan and Zaire and internationally in early November 1989 when
foci are about 150 kilometers distant from each an epidemic, confirmed to be caused by Ebola virus,

erupted in a shipment of 100 Macaco, cynomolgus Unsophisticated patients unfortunately cherish
monkeys originating in the Philippines and shipped an intuitive feeling that drugs, from vitamin prepa-
to a laboratory in Virginia, in the United States, via rations up the scale to specific therapeutic agents,
Amsterdam and J. F. Kennedy airports. Sixty of the are much more effective when given intradermally,
100 monkeys died. A second shipment received 2 to 3 subcutaneously, intramuscularly, or intravenously.
weeks later in Virginia had two infected monkeys Indeed, patients often demand parenteral adminis-
therein. tration of drugs and think poorly of a physician who
Extensive epidemiological explorations interna- does not oblige them. This view unfortunately is not
tionally have focused on this frightening episode. No discouraged by some practitioners of the medical
human cases have been reported. At the time of arts, both licensed and unlicensed, and the practice
writing (February 14,1990), no satisfactory explana- also greatly increases the bill for Pharmaceuticals
tions have been advanced. All exposed individuals benefiting drug companies and pharmacists. The
are being monitored. poorer countries can ill afford the increased cost.
This demonstration of the danger of transmission Epidemiologists have been active in trying to
of virus by use and reuse of inadequately sterilized trace the origins of the Ebola virus and the distribu-
needles and syringes has important implications for tion of the infection throughout Africa, locate host
medical practice, not just in underdeveloped coun- vertebrates other than humans, as well as learn
tries but also in developed cultures because of AIDS. methods of transmission to humans and the ways
Excessive parenteral administration of many drugs, the virus is maintained and propagated in nature.
which could be equally efficacious given by mouth, Table VIII.42.1 summarizes these data. Although it
constitutes bad medical practice. Parenteral adminis- may appear that much has been done, actually ef-
tration of drugs in medical emergencies is under- forts have been limited to a handful of dedicated
standable and desirable. But such a practice for the investigators, and to a scattered, spotty sampling of
"typical" patients seen at the clinic for undiagnosed the vast expanse of Africa south of the Sahara.
fevers that are not immediately life-threatening is Primates have been sampled (see Table VIII.42.1)
indefensible. and have revealed no involvement, or at best mini-
Table VIII.42.1. Ebola serosurveys

Study area Date No. examined No. positive Percent positive Remarks
Humans
Northern Senegal 1977 273 5 1.8 semidesert region
Zaire, Bumba province 1979 251 43 17 region of 1967 outbreak
Cent. African Republic 1980 499 17 3.4 several regions
Zaire, Tandala 1980 ? 9 7 region of 1969 outbreak
Liberia 1982 400+ 24 6 several regions
Zaire, Tandala 1982 138 7 5.1
Cameroons 1982 1517 — 3.2-23.5 several regions
Kenya 1983 52 2 4
Kenya 1983 741 8 1.1
Kenya 1986 471 46 10 in fever cases
Northern Sudan 1986 % of2000 ? v. few pos desert region, north of out-
break
Southern Sudan 1986 % of2000 ? 15-30 in Maridi region; agricul-
tural
Nigeria 1988 1677 30 1.8 several regions
Primates
Kenya 1982 136 0 0 monkeys of 3 species
Kenya 1982 184 3 1.6 baboons
Zaire 1981 200+ 0 0 monkeys
Guinea pigs
Zaire, Tandala 1982 138 36 26.1 region of 1979 epidemic

VTII.42. Ebola Virus Disease 701
mal involvement. In connection with the 1979 ways present. Myalgia appeared early. Arthralgia of
Tandala, Zaire, outbreak is the unexpected finding the large joints was very common from the onset.
of guinea pig immunes. Guinea pigs are South Severe generalized disease followed in a matter of a
American rodents, inquilines in human habitations day or two. Patients were lethargic, their faces ex-
in the high Andes. The inhabitants raise them for pressionless with deep set eyes. Loss of appetite,
pets and for food. They were introduced to Africa sometimes accompanied by vomiting and rapid
decades ago and in some regions have established weight loss, was a nearly constant feature. In 2 to 3
themselves as inquilines in houses. In this respect, days, gastrointestinal symptoms developed, fre-
their behavior resembles that of the abundant quently accompanied by cramping.
multimammate rat (Mastomys natalensis), already In later stages, particularly in patients with hem-
known to be involved in Lassa virus maintenance orrhagic manifestations, red blood was seen in the
and spread to human beings. Guinea pig immune stools. Vomiting was common, being seen in nearly
rates as high as 26.1 percent were found in these half of the patients with hemorrhagic signs; vomitus
animals in some houses in Tandala. Study of the was often of red blood or changed blood (cf. the
background of those who were positive, however, vomitusniger of yellow fever). Other common mani-
failed to indicate guinea pig-to-guinea pig transmis- festations included sore throat and dysphagia, fis-
sion, guinea pig-to-human spread, or human-to- sures and open sores on the lips, conjunctivitis some-
guinea pig spread. times accompanied by subconjunctival bleeding, and
coughing. Jaundice occurred in some. Pancreatitis
Etiology (clinical diagnosis) was also seen frequently, and
The Ebola agent was demonstrated by electron mi- abortion occurred in 23 percent of 82 infected preg-
croscopy to consist of long filamentous rods, some- nant women. Hemorrhagic manifestations, seen in
times branched, often intertwined. The virion con- many patients and in over half of those who died,
tains one molecule of single-stranded RNA and is probably resulted from disseminated intravascular
not of itself infectious. coagulation. Death occurred as early as the fourth
The infectious virus particle is inactivated by ul- day, but more usually on the fifth or sixth day and in
traviolet (UV)-irradiation, gamma-ray irradiation, 1 occasional cases as late as the twentieth day.
percent formalin, beta-propiolactone, and lipid sol-
vents. The particles closely resemble those of the Pathology and Diagnosis
Marburg agent, but there are some distinguishing Very few specimens were obtained for histological
characteristics. The Ebola agent, for example, has study. In three adequately preserved liver specimens
more branching than the Marburg agent. Oligonucle- available, fatty changes and necrosis of hepatocytes
otide patterns are distinctive. Seven nucleoproteins and Kupffer cells were noted, necrosis being of the
have been described. Serologically no relationship focal type, distributed throughout the liver lobules.
has been demonstrated, either to Marburg or to Intact cells with hyalinized cytoplasm and ghostlike
Lassa or to any other of a long list of arbo and nuclei (Councilman bodies of yellow fever fame)
nonarbo viruses. Another distinguishing characteris- were seen, as were large amounts of karyorrhectic
tic of Ebola-Sudan and Ebola-Zaire is pathogenic- debris. Inflammatory changes were minimal in the
ity. Both cause excessive mortality, but mortality is liver and other organs.
lower for the Sudan strain than for the Zaire strain. Comparisons were made with Marburg disease,
Cercopithecus monkeys infected with and recovered for which there was a large amount of pathological
from Ebola-Sudan virus, and therefore resistant to material available, both from human beings and
superinfection by the homologous virus, nonetheless from experimental animals. Here, in addition to the
succumbed when inoculated with Ebola-Zaire virus. focal necrotic centers in the liver, was evidence of
A new family, Filoviridae, has been created for the hemorrhagic diathesis in many organs and of pan-
agents Marburg and Ebola. As of 1988, no further encephalitis in the brain, with glial nodule forma-
agents have been proposed. tion, perivascular lymphocyte cuffing, and intersti-
tial edema.
Clinical Manifestations Several pathologists deemed the differential diag-
Onset of illness was usually sudden, with progres- nosis of Ebola infection to be extremely difficult in
sively more severe frontal headache of a type fre- settings where there might be malaria, Lassa fever,
quently seen with P. falciparum malaria infection, Marburg disease, yellow fever, Congo-Crimean hem-
spreading occipitally. Fever and weakness were al- orrhagic fever, typhoid fever, infectious hepatitis,

leptospirosis, brucellosis, and other fevers. Some in different cell lines. In WHO-PLITM Colloquium,
other pathologists felt the lesions observed to be 157-67.
adequately specific to permit an Ebola diagnosis. Heymann, D. L., et al. 1980. Ebola hemorrahgic fever:
Clinical pathological data are extremely limited. Tandala, Zaire, 1977-1978. Journal of Infectious Dis-
A few white blood cell counts were normal to slightly eases 142: 372-6.
elevated. No differential counts were made. Pro- Isaacson, M. 1977. Containment and surveillance of a hos-
pital outbreak of African hemorrhagic fever due to
teinuria occurred frequently.
Ebola virus in Kinshasa, Zaire. In WHO-PLITM Col-
loquium, 117-30.
Treatment and Prevention Johnson, K. M., P. A. Webb, and D. L. Heymann. 1977.
Plasmapheresis with plasma from recovered pa- Evaluation of the plasmapheresis program in Zaire.
tients has been tried as treatment. Interpretation of In WHO-PLITM Colloquium, 157-60.
limited trials (at the tail end of the epidemics) indi- Kiley, M. P. et al. 1982. Filoviridae: A taxonomic home for
cates little hope of an effective therapy. No drugs Marburg and Ebola viruses. Intervirology 18: 24-32.
have been effective. A hospital staff member attend- Murphy, F. 1977a. Pathology of Ebola virus infection. In
ing an Ebola patient (from Africa) in a hospital in WHO-PLITM Colloquium, 38-9.
England became ill and soon was gravely ill. Inter- 1977b. Ebola and Marburg virus morphology and taxon-
feron and immune plasma were both given and the omy. In WHO-PLITM Colloquium, 40-60.
patient recovered. A possible vaccine remains a Pattyn, S. R. 1977. Virological diagnosis of Ebola virus
dream. infection. In WHO-PLITM Colloquium, 61-8.
Piot, P., and P. Sureau. 1977. Clinical aspects of Ebola
Interestingly, 11 of 11 blood donors for plasma- virus infection in Yambuku Area, Zaire. In WHO-
pheresis had microfilariae, although no protozoa, in PLITM Colloquium, 9-25.
their blood. It should be emphasized that most of the Regnery, R. L., K. M. Johnson, and M. Kiley. 1980. Virion
Ebola patients who came to a clinic or a hospital had nucleic acid of Ebola virus. Journal of Virology 36:
had several days of treatment with an antimalarial 465-9.
drug, often followed by typhoid treatment or antibiot- Robin, Y., et al. 1971. Les Arbovirus au Senegal: Etude
ics of whatever kind available. Malarial parasites dans la population humaine du village de Bandia.
could hardly be expected to be found under such Africain Medicale 10: 739-45.
circumstances. Sanchez, A., and M. P. Kiley. 1987. Identification and
Wilbur G. Downs analysis of Ebola virus messenger RNA. Virology 157:
414-20.
Sareau, P., and P. Piot. 1977. Containment and surveil-
Bibliography lance of an epidemic of Ebola virus infection in
Baskerville, A., et al. 1985. Ultrastructural pathology of Yambudu Area, Zaire. In WHO-PLITM Colloquium,
experimental Ebola hemorrhagic fever virus infec- 91-116.
tion. Journal of Pathology 147: 199-209. WHO Weekly Epidemiological Record. 1989. No. 49, De-
Bowen, E. T. W., et al. 1977. Virological studies in a case of cember 8, and No. 50, December 15. Geneva.
Ebola virus infection in man and in monkeys. In World Health Organization and Prince Leopold Institute
WHO-PLITM Colloquium, 78-85. of Tropical Medicine. 1977. International colloquium
Cox, N. J., et al. 1983. Evidence for two subtypes of Ebola on Ebola virus infection and other hemorrhagic fevers.
virus based on oligonucleotide sequences. Journal of Antwerp, Belgium.
Infectious Diseases 147: 272-5.
Downs, W. G. 1975. Malaria, the great umbrella. Bulletin
of the New York Academy of Medicine 51: 984-90.
El Mekki, A., and G. van der Groen. 1977. Attempts to
classify ungrouped arboviruses by electron micros-
copy. In WHO-PLITM Colloquium, 281-8.
El Tahir, B. M. 1977. The hemorrhagic fever outbreak:
Maridi-Western Equatoria, southern Sudan. In
WHO-PLITM Colloquium, 131-4.
Elliot, L. H., M. P. Kiley, and J. B. McCormick. 1985.
Descriptive analysis of Ebola virus proteins. Virology
147: 169-76.
Germain, M. 1977. Collections of mammals and arthro-
pods, Zaire. In WHO-PLITM Colloquium, 38-9.
Groen, G. van der, et al. 1977. Growth of Lassa and Ebola

VIII.43. Echinococcosis (Hydatidosis) 703
Turkana problem is linked to a very close associa-

VHI.43 tion between children and dogs.
Echinococcosis (Hydatidosis) Echinococcosis is often difficult to diagnose. Cysts
can be detected by X-rays or surgery; several
serologic tests are also used. Surgery was the only
The larval stages of three tapeworms of the genus effective therapy until the early 1980s, when the
Echinococcus can cause severe disease in humans. drug mebendazole was employed with at least some
All three normally become adults in the intestines of success.
dogs or other canids. Eggs are passed in the feces K. David Patterson
and, if ingested by a herbivore, develop in the liver
or other organs into a saclike container of larvae, the Bibliography
hydatid cyst. Carnivores become infected by eating Araujo, F. P., et al. 1975. Hydatid disease transmission in
cysts with the flesh of the herbivore. Echinococcus California: A study of the Basque connection. Ameri-
granulosus, which commonly has a sheep—dog cycle, can Journal of Epidemiology 102, 4: 291-302.
Beard, Trevor C. 1973. The elimination of echinococcosis
but which may also infect goats, cattle, swine, and
from Iceland. Bulletin of the World Health Organiza-
camels, is the most likely to infect human beings. tion 48: 653-60.
Human echinococcosis occurs primarily in sheep- Foster, W. D. 1965. A short history of parasitology. Edin-
rearing areas. Dogs ingest cysts in the offal of dead burgh and London.
sheep and pass eggs in their feces. Humans acquire Gemmel, M. A., J. R. Lawson, and M. G. Roberts. 1986.
the eggs from a dog's fur or from contaminated food Control of echinococcosis/hydatidosis: Present state of
or water. Cysts holding 2 or more liters of fluid and worldwide progress. Bulletin of the WorldHealth Orga-
larvae can grow for years in the liver, lungs, brain, nization 64: 333-9.
or other organs and exert enough mechanical pres- Kean, B. H., Kenneth E. Mott, and Adair J. Russell, eds.
sure to cause grave or fatal consequences. Rupture of 1978. Tropical medicine and parasitology: Classic in-
a cyst by trauma or surgery releases daughter cysts, vestigations. Vol. II, 636-52. Ithaca and London.
which may grow elsewhere in the victim; the Leuckart, Rudolph. 1886. Parasites of man and the dis-
hydatid fluid can cause fatal anaphylactic shock. eases which proceed from them. Edinburgh.
Nelson, G. S. 1986. Hydatid diseases: Research and control
Hydatid cysts in humans and animals have been in Turkana, Kenya 1. Epidemiological observations.
known since Roman times, but, as was true for the Transactions of the Royal Society of Tropical Medicine
other tapeworms, the relationship between the lar- and Hygiene 80: 177-82.
val cyst and the adult worm was not suspected until Nelson, George S., and Robert L. Rausch. 1963. Echino-
the eighteenth century. E. granulosus was described coccus infections in man and animals in Kenya. An-
as a separate species in 1850, and its life cycle was nals ofTropical Medicine and Parasitology 57: 136—49.
worked out with feeding experiments in 1863. O'Leary, Patricia. 1976. A five-year review of human
The parasite first became a serious danger to hu- hydatid cyst disease in Turkana district, Kenya. East
mans when animals were domesticated. The expan- African Medical Journal 53: 540-4.
sion of European settlement spread infection to the Schantz, Peter M., and Calvin Schwabe. 1969. World-wide
Americas and Australasia. Echinococcosis is also status of hydatid disease control. Journal of the Ameri-
can Veterinary Medical Association 155: 2104—21.
found in North Africa, Cyprus, the Middle East, Stallbaumer, M. R, et al. 1986. The epidemiology of
northern and central Asia, and most of sub-Saharan hydatid disease in England and Wales. Journal of
Africa. Iceland was a major focus in the mid- Hygiene (Cambridge) 96:121-7.
nineteenth century, but education, dog control, and
sanitary slaughtering have eliminated the disease.
Similar methods, including the mass treatment of
dogs, have greatly reduced its incidence in Australia
and New Zealand. The highest known prevalence of
echinococcosis is among the Turkana, a stock-
raising people in northwestern Kenya. Colonial
medical authorities in Kenya did not recognize the
disease until the 1950s, and an incidence rate of 96
per 100,000 was estimated in 1976, more than seven
times the previous record rate in Cyprus. The

conclusive studies indicating that race is a factor,
VIII.44 though it has been suggested that black women in
Eclampsia the United States are more likely to suffer from
eclampsia than their white counterparts because of
greater tendency to develop chronic hypertension on
Eclampsia is a puzzling hypertensive disorder affect- the one hand, and less opportunity for proper mater-
ing only women. Associated solely with pregnancy nal care on the other. The disorder occurs in 6 to 8
and childbirth, it is an epileptic form of convulsions percent of all pregnancies. Statistics show that it is
that develops during the second half of pregnancy more common in urban areas, though this associa-
and disappears after conception. The severity de- tion may reflect only the fact that urban women who
pends upon the degree and timing of the illness as experience eclampsia or preeclampsia receive more
well as the characteristics of the patient. Eclampsia medical assistance in giving birth than rural
is associated with hypertension, edema, and toxemia, women, and thus the condition is more frequently
and all three can cause the symptoms of the disease to noted and reported. Indeed, it is difficult to deter-
vary widely. Preeclampsia refers to hypertension, ab- mine the frequency of eclampsia in rural areas or
normal edema, or proteinuria during pregnancy, Third World nations because women there seldom
whereas eclampsia is the disease's most extreme seek, have access to, or can afford regular prenatal
form, manifested by severe convulsions, coma, and care and a hospital delivery. In the United States it
even death. Eclampsia is a leading cause of maternal has been estimated that the incidence of toxemia is
and fetal mortality and can cause stillbirths or prema- between 5 and 7 percent of all deliveries, and that of
ture labor. Medical experts remain confused about eclampsia between 0.12 and 0.26 percent of all deliv-
the cause of this disorder and have no effective way to eries. On the other hand, the incidence figures from
cure the disease other than to terminate pregnancy several Navajo studies soar to as high as 15.2 and
by delivering the baby. Through careful prenatal .41, respectively, yet hypertension does not seem to
care, however, physicians can usually control the be a predisposing factor (Slocomb and Kunitz 1977).
problem, and it is now relatively rare in the United Afro-Americans also have a much higher incidence
States and Europe. of toxemia and eclampsia than the general U.S. popu-
lation, but in this case hypertension does seem to
Not only is the disease difficult to define, but also predispose to the disease (Williams, ed. 1975).
accurate records of its existence are rare, especially
in Third World countries where prenatal care by a
medical attendant is uncommon. Although eclamp- Clinical Manifestations
sia is one of the diseases most troubling to obstetri- Symptoms of eclampsia and preeclampsia include
cians, research on the illness is difficult because it is excessive and sudden weight gain, edema, hyperten-
found only in human beings. Its etiology remains sion, and proteinuria. Patients may also suffer from
unknown but may be multifactorial. headache, dizziness, visual disturbances, anorexia,
nausea, vomiting, upper abdominal pain, and swell-
Distribution and Incidence ing of the face and extremities. In severe cases,
For reasons not understood, eclampsia seems to be women experience visual and neurological distur-
more common among the economically underprivi- bances, oliguria (a deficiency of urine excretion),
leged. The typical patient is a young woman in her and, of course, convulsions. In addition, cardiac out-
first pregnancy, who is of low socioeconomic status put increases and the kidneys (which seem to be the
and has had little or no prenatal care. It is more target organ for the disease) are affected. Eclampsia
common among women who (1) are diabetic; (2) have can lead to lethal complications affecting the liver,
high blood pressure or suffer from renal or vascular kidney, uterus, and brain, such as abruptio pla-
diseases; (3) suffer from poor nutrition or hydatiform centae, acute renal failure, cerebral hemorrhage, dis-
moles; (4) are on the age extremes of their childbear- seminated intravascular coagulation, and circula-
ing years; and (5) bear twins. It occurs more fre- tory collapse. Preeclampsia does not occur before the
quently in the spring and summer and in certain twentieth week of pregnancy, and eclampsia rarely
locations. It also evinces a familial tendency, suggest- before the thirty-second week. Doctors carefully
ing some kind of genetic disorder. monitor blood pressure and weight gain to prevent
Eclampsia is less likely to occur in women who its occurrence, although the disease's progress can
have experienced a previous case. There are few be rapid and sudden.

VIII.44. Eclampsia 705
History and Geography Therapy was generally "heroic." Solutions in-

It is difficult to determine how common or serious cluded warm baths, doses of opium, extensive bleed-
eclampsia was in ancient times. The writings of ing from the jugular vein or a temporal artery, deple-
Egyptian, Chinese, Indian, and Greek scholars do tion to rid the body of toxins, removal of meat or
not convincingly note cases, other than an occa- milk from the diet, mustard poultices, ice or cold
sional remark describing a pregnant woman's con- water on the head, snuff, clysters, emollients to di-
vulsion, fit, or headache. For centuries eclampsia late the cervix, and plasters to the lower body to
was commonly mistaken for epilepsy. If discussed at draw the uterus downward. Doctors disagreed on
all, writers generally attributed the disease to uter- whether it was wise to deliver the baby immediately.
ine suffocation, believing that the uterus had wan- Heroic cures, especially those emphasizing deple-
dered into the abdominal region. Therapy focused on tion, doubtlessly contributed to maternal deaths.
encouraging a retrograde motion of the uterus to In 1768 Thomas Denman wrote one of the earliest
relieve pressure on the upper body and brain. Medi- monographs on the disease in English. John Lever
eval writings only hint at the disease, but perhaps and James Young Simpson in 1843 simultaneously
the reason for this paucity of information was that discovered the consistent occurrence of proteinuria
midwives had a monopoly on assisting births and did in preeclamptic patients by finding albumin in their
not provide written descriptions of problems they urine. This was a major breakthrough, for the dis-
encountered. In the second century, Galen noted that ease could now be considered a toxemia rather than
epilepsy could be fatal to pregnant women, and one caused by mechanical pressure. Until the twenti-
Eucharius Rosslin in the sixteenth century stated eth century, eclampsia was associated with wealthy
that convulsions and unconsciousness were ominous women, probably because they used male doctors
signs in pregnant women. Jacques Guillimeau in who wrote about the disorder. Not until the 1930s
1612 concluded that convulsions occurred because were poor women viewed as susceptible. Unwed
the fetus was striving to come forth or that improper mothers were also seen as vulnerable, perhaps be-
positioning extended the womb, thus fostering con- cause their infants were more likely to be primo-
vulsions. Frangois Mauriceau in 1688 was the first gravids. Early in the twentieth century, eclampsia
physician systematically to describe eclampsia, was usually associated with hypertension and ele-
thereby indicating a new concern with the disorder vated blood pressure, though speculation as to its
as men began entering thefieldof obstetrics. He also origin was still common.
was the first to note that primogravids were at Today physicians depend upon careful monitoring
greater risk that multigravids. Mauriceau sug- of blood pressure and proteinuria during pregnancy,
gested several causes, including excessive hot blood while watching for edema and excessive weight
flowing from the uterus and malignant vapors from gain. Early detection is essential. If a woman should
a dead fetus. In 1694, he recommended that two or suffer preeclampsia, physicians recommend rest and
three phlebotomies be performed routinely during constant monitoring. If a patient suffers from convul-
pregnancy should a woman exhibit eclamptic tenden- sions, attendants take immediate measures to pre-
cies. All early medical experts agreed that it was a vent physical injury by suctioning her air passage,
dangerous disease. providing oxygen, and employing magnesium sul-
During the nineteenth century, speculation about fate to control the seizures. Should the convulsions
the disease was widespread, and physicians consid- persist, in rare cases sodium amorbarbital, a barbit-
ered it to be the most dreaded disorder associated uate, is administered. Seizures can cause fetal death
with pregnancy. Doctors speculated on numerous pos- because the convulsive woman is not breathing and
sible causes of eclampsia, including a woman's rap- thus the baby is cut off from its oxygen supply. If the
idly changing emotions, a sanguine or plethoric state, baby is near term, doctors make every effort to de-
excessive hemorrhaging, blood to the brain, nutri- liver it once the convulsions have subsided and the
tional deficiency, excessive protein in the system, patient is conscious. Eclampsia remains one of the
albuminuria, renal deficiency, retention of urinary greatest puzzles in the list of human diseases and
constituents, nerve irritation, high blood pressure, fosters much debate and concern. Doctors have devel-
seasonal changes, lethargy, melancholia, wealth, im- oped better means to manage the disease but still
proper positioning of the womb, corrupt menstrual lack an understanding of its etiology.
flow, a bad seed, an unstable personality, passions of Sally McMillen
the mind, and interrupted circulation.

Bibliography
Brewer, Thomas H. 1966. Metabolic toxemia of late preg- VIII.45
nancy: A disease of malnutrition. Springfield, 111.
Chesley, Leon C. 1981. Hypertensive disorders in preg-
Emphysema
nancy. New York.
Coudon, James. 1813. An inaugural essay on eclampsia or
puerperal convulsions. Baltimore. Pulmonary emphysema is defined in morphological
Davies, A. Michael. 1971. Geographical epidemiology of rather than clinical terms. The 1958 Ciba Sympo-
the toxemias ofpregnancy. Springfield, 111. sium defined emphysema as an "increase beyond the
Denman, Thomas. 1768. Essays on the puerperal fever and normal of air spaces, distal to the terminal
on puerperal convulsions. London. bronchiole, either from dilation or from destruction
Dieckmann, William Joseph. 1952. The toxemias of preg- of their walls." The subsequent American Thoracic
nancy, 2d edition. St. Louis. Society statement in 1962 made anatomic destruc-
International Society for the Study of Hypertension in tion a part of the definition: "Emphysema is an ana-
Pregnancy and Pregnancy Hypertension. 1980. Pro- tomic alteration of the lung characterized by an ab-
ceedings of the First Congress of the International Soci- normal enlargement of the air spaces distal to the
ety, ed. John Bonner, Ian Macgillivray, and Malcolm terminal, nonrespiratory bronchiole, accompanied
Symond. Baltimore. by destructive changes of the alveolar walls."
Kitzmiller, John. 1977. Immunologic approaches to the
study of preeclampsia. Clinical Obstetrics and Gynecol- The definition was refined in 1985 in a workshop
ogy 20, 3: 717-35. report of the National Heart, Lung, and Blood Insti-
MacGillivrary, Ian. 1983. Pre-eclampsia: The hypertensive tute: "Emphysema is defined as a condition of the
disease ofpregnancy. New York. lung characterized by abnormal, permanent enlarge-
Pritchard, J. A., ed. 1985. Hypertensive disorders in preg- ment of airspaces distal to the terminal bronchiole,
nancy. In Williams' obstetrics, 17th edition, 525—60. accompanied by the destruction of their walls, and
Norwalk, Conn. without obvious fibrosis."
Slocomb, John C, and Stephen J. Kunitz. 1977. Factors Emphysema can also be subclassified in anatomic
affecting maternal mortality and morbidity among terms. The acinus is the gas-exchanging unit of the
American Indians. Public Health Reports No. 92. lung served by a single terminal bronchiole. Within
Washington, D.C.
the acinus, the terminal bronchiole is succeeded by
Williams, Richard Allen, ed. 1975. Textbook of black-
related diseases. New York.
three orders of branching respiratory bronchioles
that are subsequently succeeded by alveolar ducts
and terminal alveolar sacs, all of which bear alveoli.
If emphysematous changes predominate in the re-
gion of respiratory bronchioles, the condition is
termed centriacinar or centrilobulaf emphysema.
More uniform involvement constitutes panacinar or
pan/o&ufaremphysema. Emphysema located predom-
inantly in the periphery of the acinus along lobular
septa isparaseptal emphysema. Occasionally, emphy-
sema may occur adjacent to a scar orfibroticprocess
and is called paracicatricial emphysema.

Because emphysema is, by definition, a morphologi-
cal diagnosis, its presence and prevalence depend on
the interpretation of an examination of the lungs
during an autopsy. Obvious emphysema is likely to
be found in at least 50 percent of an average autopsy
population, with a frequency of about 65 percent in
men and 15 percent in women. Incidence increases
with age, reaching 30 percent by the fourth decade
and 60 percent by the seventh decade of life. It has
been suggested that at least some emphysema may

VTII.45. Emphysema 707
be a universal finding in elderly adults if properly by mechanisms still under study. Although some
prepared lungs are carefully examined. forms of mild emphysema are quite common and can
occur in nonsmokers, there is nonetheless a strong
Epidemiology association between cigarette smoking and emphy-
Whereas most epidemiological studies are based on sema. Thus, although the precise mechanisms re-
information elicited by questionnaires or physiologi- main to be elucidated, cigarette smoking is the most
cal tests, emphysema is a morphological diagnosis important cause of the moderate to severe forms of
and epidemiological studies must be confined to au- emphysema, causing clinical symptoms, respiratory
topsy data. Furthermore, the lungs must be properly impairment, disability, and death.
fixed on inflation and examined using comparable
techniques and emphysema grading methods. Per-
haps because of a younger average age of the popula- Clinical Manifestations
tion examined and a lower prevalence of cigarette The patient with clinically significant emphysema is
smoking, studies from Africa reveal a lower fre- typically an older male smoker who gives a history
quency of emphysema than elsewhere. Yet even of breathing difficulties that increase in severity
when populations are of the same age, and the lungs over time. On physical examination, he is usually
are examined by the same investigators, there ap- thin, with a thoracic configuration (barrel chested)
pear to be some national and even regional differ- suggesting hyperinflation, and has markedly dimin-
ences. For example, the frequency of emphysema is ished breath sounds when listened to on ausculation.
greater in parts of the United Kingdom than in Airflow obstruction can be demonstrated by slowing
Sweden or some parts of North America, and lower of forced expiration. The chest radiograph confirms
in some North American cities than in others. The hyperinflation with a relatively small heart and de-
frequency differences may reflect different patterns creased peripheral lung markings. However, this
of cigarette smoking or levels of air pollution, or the "typical" clinical picture is more often the exception
selection of people autopsied. The various studies do than the rule. In several reported series of autopsies,
agree that the amount and severity of emphysema moderate to severe forms of emphysema were found
increase with advancing age, and cigarette smoking in a significant proportion of individuals who did not
is a primary cause of the disease. In the various exhibit clinical evidence of the disease. In addition,
studies, emphysema is found, and in more severe chest radiographs are not reliable in either diagnos-
form, at least twice as often in men as in women. The ing or ruling out emphysema. Most often, emphy-
greater incidence of emphysema in males may re- sema occurs in conjunction with chronic bronchitis
flect the greater prevalence of smoking in men; if and is accompanied by a chronic productive cough.
that is the case, then as more women take up ciga- The presumptive diagnosis of emphysema cannot
rette smoking, this sex preference may change. Al- be made without pulmonary function tests. Chronic
though emphysema is remarkably common, it is a airflow obstruction manifested by slowing of forced
cause of, or contributes to, death in only a small expiration is characteristic of moderate to severe
percentage of cases. emphysema, although even this finding may not be
universal. When emphysema increases in severity,
hyperinflation is reflected by an increase in total
Etiology lung capacity and residual volume, and the carbon
The disruption of alveolar architecture characteris- monoxide diffusing capacity is reduced. Loss of lung
tic of emphysema appears to be the result of tissue elastic recoil is commonly associated with emphy-
destruction caused by elastolytic proteases derived sema. Such physiological data provide more sensi-
from polymorphonuclear leukocytes and alveolar tive indicators of the presence of emphysema than do
macrophages. Uninhibited digestion of tissue is ob- clinical signs and symptoms or radiological findings.
served in patients with alpha-1-antitrypsin defi-
ciency. This genetically determined protease inhibi-
tor phenotype Z (PiZ) occurs in no more than 1 in History
1,000 individuals in a general population, however, In a postscript to his 1698 Treatise of the Asthma,
and thus can account for only a small proportion of John Floyer described bullous emphysema, together
emphysema cases. Evidence suggests that cigarette with hyperinflation and loss of lung elastic recoil,
smoke can enhance accumulation of leukocytes and from his dissection of a broken winded mare. In his
macrophages in the lung with release of elastolytic 1793 book on Morbid Anatomy, Matthew Baillie de-
enzymes, and can also inhibit antiprotease activity scribed the morphology of human emphysema with

tissue destruction leading to airspace enlargement.
There is good evidence that the lung used as an VIII.46
illustration in Baillie's book was that of Samuel
Johnson, whose lungs, at autopsy, were found to be
Encephalitis Lethargica
permanently distended and failed to collapse on
opening the chest. Rene Laennec's classic Treatise Foremost among recorded encephalitis epidemics
on the Diseases of the Chest first appeared in 1819 was the global pandemic of encephalitis lethargica
and was expanded in a subsequent edition in 1826, that emerged in and from Europe during the last
the year of his death. In it, Laennec provided the years of the Great War and occurred in successive
first description of pulmonary emphysema, the de- waves throughout the world during the following
structive nature of the disease, and its association decade. Although the diagnosis of encephalitis le-
with chronic bronchitis. James Jackson, Jr., accumu- thargica is sometimes applied to sporadically occur-
lated a series of cases of emphysema and noted that ring cases of inflammation of the brain having a
the disease exhibited a familial predisposition. strong lethargic or stuporous aspect, this discussion
Though he died in 1834, his work was published in a focuses upon the encephalitis pandemic that accom-
paper by his mentor Pierre Louis in 1837. It was not panied and followed the 1918 influenza pandemic.
until 1963 that the genetically determined alpha-1-
antitrypsin deficiency associated with emphysema
was described. The physiological changes associated Clinical Manifestations and Pathology
with emphysema have attracted the attention of Clinically, encephalitis lethargica was characterized
many investigators over the years. The loss of lung by diffuse involvement of the brain and spinal cord,
recoil associated with emphysema was inferred from producing practically the entire range of the signs
early observations. It was noted by Fritz Rohrer in and symptoms of neurological disease. Sometimes
1916 and studied by K. von Neergaard and K. Wirz occurring in close conjunction with respiratory-
in 1927 and Ronald Christie in 1934 among others. spread influenza, but more often after a long interval,
Recent advances in the pathological anatomy of em- encephalitis patients developed an illness usually
physema stem from the work of J. Gough in 1952 characterized by the triad signs of fever, lethargy, and
using techniques developed by him and by J. E. disturbances of eye movement, along with a broad
Wentworth. The precise mechanisms leading to the range of other signs and symptoms. These included
lung destruction characteristic of emphysema are headache, tremor, weakness, depression, delirium,
under current investigation. convulsions, the inability to articulate ideas, coordi-
Ronald J. Knudson nate movements, or recognize the importance of sen-
sory stimuli, as well as psychosis and stupor.
Oculogyric crisis (eyeballsfixedin one position for a
Bibliography period of time) and other disorders of eye movement,
American Thoracic Society. 1962. Definitions and classifi- the most frequent sign of localized damage to the
cations of chronic bronchitis, asthma, and pulmonary nervous system, were present in three-fourths of the
emphysema: A statement by the American Thoracic cases. Lethargy, another common symptom, in some
Society. American Review of Respiratory Diseases 85:
patients lasted only a few days, but in others it per-
762-8.
Ciba Symposium. 1959. Terminology, definitions, and clas- sisted for weeks and months or until death from coma-
sification of chronic pulmonary emphysema and re- tose respiratory failure. Not infrequently, spasmodic
lated conditions: A report of the conclusions of a Ciba twitching and severe psychic and behavior changes
guest symposium. Thorax 14: 289—99. persisted long after the acute illness. Approximately
Report of a National Heart, Lung, and Blood Institute, a third of encephalitis lethargica patients died of
Division of Lung Diseases Workshop. 1985. The defini- their acute illness, and a large proportion (80 per-
tion of emphysema. American Review of Respiratory cent) of survivors developed parkinsonism during en-
Diseases 132: 182-5. suing decades.
Snider, Gordon L., ed. 1983. Clinics in chest medicine, Vol.
4, No. 3. The main pathological findings during the acute
Thurlbeck, William M. 1976. Chronic airflow obstruction encephalitic illness were a diffuse inflammatory re-
in lung disease. Philadelphia. action in the meninges and around the blood vessels
1982. The anatomical pathology of chronic airflow ob- of the brain and the spinal cord; degenerative
struction. In Current pulmonology, ed. D. H. Sim- changes were found in the neurones, especially in
mons, 1—24. New York. the brainstem, basal ganglia, and cerebellum, but

VHI.46. Encephalitis Lethargica 709
ENCEPHALITIS LETHARGICA DEATHS
By Month of Onset of Illness
mini
in mini
•in mini ii
•HI iiiiiiiiiiiiim
INFLUENZA-PNEUMONIA DEATHS
By Month of Occurrence
OTHER PNEUMONIA/BRONCHITIS DEATHS

Bv Month of Occurrence
1920 1921
I IMl • 1926
Figure VIII.46.1. Encephalitis lethargica, influenza- Ravenholt and Foege. 1981. 1918 influenza, encephalitis
pneumonia, other pneumonia/bronchitis deaths in lethargica, parkinsonism. Lancet 2: 860-4, by permis-
Seattle-King County, Washington, 1918-26. (From sion of The Lancet.)
also including the cortex and the subcortical white class by itself with respect to virulence and sequelae.
matter. In the spinal cord, both the white and gray Along with its unique time distribution, 1917—26,
matter were involved in the inflammatory, degenera- the encephalitis lethargica epidemic, as Figure
tive disease process. VIII.46.1 indicates, also had a pronounced seasonal
predilection for the winter months. Encephalitis
Epidemiology cases often occurred in such close conjunction with
The dominant epidemiological feature of encephalitis individual and community attacks of influenza that
lethargica was its unique time distribution. Al- many professional and laypersons initially believed
though epidemics of encephalitic disease had oc- the disease to be caused by the devastatingly virulent
curred in conjunction with many previous influenza influenza. But the fact that many cases and epidem-
epidemics - 1580,1658,1673-5,1711-2,1729,1767, ics of encephalitis subsequently occurred at times
1780-2, 1830-3, 1847-8, and especially 1889-92 - when, and in places where, there was no discernible
the global pandemic of encephalitis accompanying influenza activity generated confusion and skepti-
and following the 1918 influenza pandemic was in a cism that influenza could be the principal cause. Long

latent intervals and slow viruses were not well recog- more than 1.5 million - of whom about 500,000 died
nized in 1918; hence encephalitis epidemics occur- of acute illness and more died from parkinsonism
ring a year and more after attacks of influenza were and other complications following the acute illness
perceived as evidence against rather than supportive stage.
of influenza as the cause. Likewise, the fact that
influenza was highly contagious and encephalitis Etiology
was not was misinterpreted as indicating that these Despite the assertions of F. G. Crookshank (1919),
were unrelated diseases rather than being different Rudolf von Jaksch (1923), and others that 1918 influ-
manifestations of the same viral agent. enza was the principal cause of encephalitis lethar-
Earliest reports of epidemic encephalitis in 1917 gica, leading researchers of the 1920s, such as E. O.
by Constantin Economo in Vienna and by French Jordan (1927) and A. J. Hall (1924), judged the rela-
observers differed little in substance; but Economo's tionship between influenza and encephalitis to be so
provocative title, encephalitis lethargica - giving inconsistent and confusing that they stated the etiol-
unique emphasis to one sign in the broad spectrum ogy of encephalitis lethargica to be "unknown." But
of clinical manifestations - gained him lasting now, 60 and more years after the pandemic, from
recognition while generating ongoing diagnostic research done in Seattle and Samoa by R. T. Ra-
confusion. venholt and W. H. Foege (1982), the etiology of en-
Although these reports of encephalitis preceded cephalitis lethargica seems clear. Death records in
the explosive general global dissemination of influ- Seattle show a characteristic modal lag of approxi-
enza in 1918, influenza was active in war-torn Eu- mately a year from influenza-pneumonia death
rope during the winter of 1916-17. In 1918, in close peaks to onset of encephalitis lethargica clusters
association with the initial massive waves of influ- terminating in death (Figure VIII.46.1), providing
enza, encephalitis was reported in Britain, Scandina- strong evidence that encephalitis cases previously
via, Germany, the United States, and many other thought to have occurred independently of influenza
countries; but the greatest epidemic peaks of en- were actually late sequelae.
cephalitis occurred in 1919—20 and during subse- The Samoan Islands were chosen as another site
quent winters - as shown for Seattle in Figure for study because the sharply contrasting experience
VIII.46.1. of Western and American Samoa with respect to the
Typically, encephalitis lethargica was generally 1918 influenza epidemic provided a unique basis for
distributed by age, sex, race, occupation, education, study of its pathological effects. As stated by Jordan:
economic status, and geographic location. Ages of
cases ranged from infancy to old age, with the high- In no part of the world did influenza exact a more crushing
est attack rates among young adults; and the sexes toll than in the islands of the South Sea. In Western
were equally represented. Rarely was there discern- Samoa the steamer Talune from Auckland introduced the
ible clustering of encephalitic cases within families disease on November 7,1918, into the islands of Upolu and
Savaii. As a result there were nearly 8,000 deaths, the
and neighborhoods; and where such was reported, it population during the two months ended December 31,
is retrospectively apparent that the clustering arose 1918, being reduced from 38,178 to 30,636.
as a result of diagnostic confusion with other causes
of central nervous system disease - for example, Meanwhile, American Samoa, just 70 kilometers
botulism. away, and inhabited by the same racial stock, man-
Attack rates for encephalitis lethargica during the aged to exclude the infection with strict quarantine
pandemic years 1918-26 approached 1 case per measures and good fortune.
1,000 general population in the United States and in During May 1982, American Samoa records stored
European countries where fairly complete records in the National Archives and Records, in San Bruno,
were maintained. Of those afflicted, roughly one California, along with death records for American
third died during their acute illness. Extensive but Samoa maintained by the Lyndon B. Johnson Tropi-
less precise reports from throughout the world indi- cal Medicine Center on Tutuila, and death records for
cate that attack rates for encephalitis lethargica Western Samoa available in the Registrar's Office at
may have been similar worldwide, except in those Apia were analyzed. Although the rudimentary na-
few small populations, most notably American ture of the death records in Western Samoa limited
Samoa, where neither influenza nor encephalitis oc- the comparative studies that could be made of mortal-
curred during the pandemic years. Hence, the world ity patterns in American and Western Samoa during
total of encephalitis lethargica cases was probably the 1920s, it was clear that whereas Western Samoa

VIII.46. Encephalitis Lethargica 711
suffered heavily from both influenza-pneumonia and Table VIII.46.1. Time interval from encephalitis to
encephalitis lethargica during the years 1918-22, parkinsonism to death in six patients
American Samoa was remarkably free of both these
diseases during those years. The evidence, then, is Years from
compelling that the pandemic of influenza beginning Year of encephalitic Years from
in 1918 and the pandemic of encephalitis lethargica encephalitic illness to encephalitic
generally beginning the following year had a com- Patient illness parkinsonism illness to death
mon etiology. Both pandemics were globally distrib- 1 1925 1 47
uted and were closely related in time, and only one 2 1927 13 45
etiologic agent (swine influenza virus) has been reli- 3 1924 2 48
ably identified. 4 1926 17 46
Local, regional, and national influenza-pneumonia 5 1921 12 51
epidemics ordinarily (perhaps invariably) preceded 6 1918 30 54
local, regional, and national epidemics of encephali- Source: Gamboa et al. (1974).
tis lethargica. A large proportion of individual en-
cephalitis lethargica cases during the early years of from brains of persons with idiopathic (not posten-
the pandemic had had clinical influenza. Later, as cephalitic) parkinsonism. The long intervals be-
influenza and encephalitis occurrence patterns tween the several manifestations of 1918 (swine)
shifted from massive epidemic to sporadic endemic, influenza virus - pneumonia, encephalitis lethar-
the relationship between these two diseases became gica, parkinsonism - must be kept in mind when
progressively obscured. seeking to understand the interrelated epidemiology
Seasonal and global occurrence patterns of en- of these diseases (see Table VIII.46.1).
cephalitis lethargica rule out the possibility that
this pandemic was caused by an arbovirus or any History
known nonrespiratorily spread infection. Moreover, From among all causes of encephalitis - structural,
although influenza-pneumonia was highly communi- chemical, and microbiological - it was a difficult task
cable from person to person, encephalitis lethargica sorting out the many infectious causes of encephalitis
was remarkably noncommunicable from person to by specific causative organism and route of transmis-
person by any known route. sion. But with the explosion of scientific knowledge in
Analogous pandemics of encephalitis have been the late nineteenth and twentieth centuries, many
recorded in close association with other influenza important agents and vectors of encephalitis were
epidemics, although none as severe as that in asso- identified, among them, the spirochete of syphilis,
ciation with the 1918 influenza pandemic. Guillain- and the trypanosome of African sleeping sickness,
Barre's disease following inoculation with swine in- transmitted by sexual contact and tsetse flies,
fluenza antigen suggests a neurotoxic effect of this repectively; the bacterial toxin of botulism, from
organism, even in the killed state. Likewise occur- ingested food; the viruses of yellow fever, Japa-
rence of parkinsonism during convalescence from nese B encephalitis, equine encephalitis, trans-
influenza and/or encephalitis and during many mitted by mosquitoes; the virus of rabies, trans-
years and decades thereafter demonstrates the extra- mitted by the bite of rabid animals; the viruses of
ordinary neuropathogenic qualities of the causative influenza, mumps, and measles, transmitted by
agent - now identified as the 1918 (swine) influenza the respiratory route; the enteroviruses, trans-
virus. mitted by the fecal-oral route; and, most recently,
the human immunodeficiency virus, transmitted
Immunology by sexual contact and blood.
The immunologic findings of E. T. Gamboa and col- Adding to the diagnostic confusion generated by
leagues in 1974 support the contention that the 1918 these numerous encephalitic microorganisms were
influenza (swine, type A) and encephalitis lethar- the many cases and deaths from stuporous encepha-
gica epidemics had a common etiology: They found litic reactions to various toxins and drugs, especially
deceased patients with well-documented postenceph- Reye's syndrome following the use of aspirin (intro-
alitic parkinsonism to have intranuclear fluorescent duced in 1899) to control the fever and discomfort of
antibody to neurotropic influenza A strain antigen influenza, varicella, and other childhood diseases.
in hypothalamic and midbrain sections, whereas no The role of aspirin in the production of Reye's syn-
such fluorescence was observed in similar sections drome has become known only in the last decade.

But the main causative agent of epidemic encepha- Hall, A. J. 1924. Epidemic encephalitis (encephalitis lethar-
litis during the pandemic years 1917—26 was the gica). New York.
respiratorily spread influenza virus. Successive Jaksch, Rudolf von. 1923. Influenza encephalitis. Acta
peaks of encephalitis occurred in European, Asian, Medica Scandinavica 58: 557-84.
African, and American countries from 1918 to about Jordan, E. O. 1927. Epidemic influenza: A survey. Chicago.
1926. In the United States, encephalitis lethargica Matheson Commission Reports I, II, III. 1929, 1932, 1939.
progressed across the country from the east to the Epidemic encephalitis: Etiology, epidemiology, and
treatment. New York.
west in 1919, just as influenza had the previous year,
Menninger, K. A. 1926. Influenza and schizophrenia: An
reaching peak occurrence in New York during Janu- analysis of post-influenzal "dementia praecox" as of
ary 1919, in Virginia during February, and in Illi- 1918, andfiveyears later: Further studies of the psy-
nois, Louisiana, and Texas during March; whereas chiatric aspects of influenza. American Journal ofPsy-
in California more cases were reported in April than chiatry 5: 469-529.
in any other month, and in Seattle the first encepha- Merritt, H. H. 1967. A textbook of neurology, 4th edition.
litis lethargica cases were reported in October 1919. Philadelphia.
Although Britain reported its peak number of cases Ministry of Health. 1924. Memorandum on encephalitis
in 1924, this was apparently a reporting artifact - as lethargica. HMSO, London.
judged from the mortality pattern during the 1920s. Ravenholt, R. T., and W. H. Foege. 1982. 1918 influenza,
For too long, medical science has tended to rele- encephalitis lethargica, parkinsonism. Lancet 2: 860-
4.
gate the 1918 influenza-encephalitis lethargica- Shope, R. E. 1931. Swine influenza I: Experimental trans-
parkinsonism puzzle to an intellectual ash heap, mission and pathology. Journal of Experimental Biol-
apparently on the assumption that these epidemics ogy 54: 373-85.
are past history and of little or at least dwindling Wimmer, A. 1924. Chronic epidemic encephalitis. London.
importance to current and future health. But fail- Winternitz, M. D., L. M. Wasson, and F. P. McNamara.
ure to identify influenza virus as the cause of en- 1920. The pathology of influenza. New Haven.
cephalitis lethargica and parkinsonism has crippled
progress toward the understanding of influenza pa-
thology and epidemiology needed to fuel and guide
prevention of these elusive but exceedingly impor-
tant diseases. VIII.47
According to William Osier, Karl Menninger, and
August Wimmer, almost every disease of the cen- Enterobiasis
tral nervous system (CNS) may follow influenza.
Thus we should look to the diminutions of CNS
structures caused by influenza attacks during ear- The pinworm Enterobius vermicularis (formerly
lier life when seeking the keys to prevention of Oxyuris) is a common parasite around the world and
much serious CNS disease, especially senile demen- is the most prevalent parasitic helminth in devel-
tia (Alzheimer's disease). oped countries today. Enterobiasis has afflicted and
R. T. Ravenholt
annoyed humans from ancient times; it was known
to ancient Chinese, classical, and Islamic writers
and was present in pre-Columbian America. Hu-
Bibliography mans are the only hosts. Mature worms, ranging
Collins, S. D., and J. Lehmann. 1953. Excess deaths from from 2 to 13 millimeters in length, inhabit the
important chronic diseases during epidemic periods, cecum and adjacent regions of the large and small
1918-51. Public Health Monographs. U.S.P.H.S. Pub- intestines. Gravid females migrate out the host's
lication No. 213. anus and deposit thousands of eggs on the skin of the
Crosby, A. W. 1976. Epidemic and peace: 1918. Westport, perianal region. The eggs mature quickly and are
Conn. infectious in several hours. Infection by ingestion of
Crookshank, F. G. 1919. Epidemic encephalomyelitis and eggs from the hands is common, as the worms induce
influenza. Lancet 1: 79-80. itching and scratching. Eggs are frequently eaten
Economo, C. 1931. Encephalitis lethargica: Its sequelae
and treatment, trans. K. O. Newman. London.
with contaminated food, and, because they are light,
Gamboa, E. T., et al. 1974. Influenza virus antigen in they are easily inhaled in household dust. Eggs
postencephalitic parkinsonism brain. Archives of Neu- hatch in the small intestine and develop into mature
rology 31: 228-32. adults in as short a time as 4 weeks. Retroinfection,

VIII.48. Epilepsy 713
when the eggs hatch on the perianal skin and the
larvae crawl back into the rectum, is possible but VIII.48
rare. Pinworms are especially prevalent among
small children and often become a family affair.
Epilepsy
Enterobiasis is rarely a serious disease. Intestinal
disturbances, if any, are minor, but pinworms can Epilepsy is characterized by the repeated occurrence
cause great discomfort, and scratching can lead to of seizures that result from recurrent, abnormal,
secondary infections. Migrating worms occasionally excessive, synchronous discharges of populations of
reach the vagina or appendix, but rarely cause seri- cerebral neurons (Epilepsy Foundation of America
ous harm. Rectal itching and consequently insom- 1981). It has a worldwide distribution and probably
nia, especially in children, are suggestive of pin- has been in existence since the dawn of human his-
worm infection. tory. The condition is chronic but rarely fatal, and
Diagnosis is made by microscopic examination of most types of epilepsy do not disturb the affected
perianal swabs to detect eggs. The condition nor- individual's desire or ability to lead a normal life.
mally is self-limiting in the absence of continuing Modern antiepileptic medications most often control
reinfection. Drug treatment is safe and effective, but seizures, and the limitations imposed by the disorder
often the whole family or institutional living group may be negligible. Unfortunately, epileptics are all
must be treated simultaneously, and bedding and too frequently stigmatized and excluded from many
clothing must be thoroughly cleaned. Even the most activities of daily life. Outdated beliefs and miscon-
fastidious housekeepers may find it very difficult to ceptions about epilepsy have only recently shown
rid a home of airborne eggs. Personal hygiene is the signs of lessening in the United States and other
best preventive measure. industrialized societies.
K. David Patterson It is misleading to think of epilepsy as one disease.
There are many causes of this symptom cluster, just
Bibliography as there are for the symptom cluster of nausea and
Kean, B. H., Kenneth E. Mott, and Adair J. Russell, eds. vomiting. A better term would be "the epilepsies."
1978. Tropical medicine and parasitology: Classic in- The epilepsies do, however, share certain physiologi-
vestigations, Vol. II, 363-4. Ithaca and London. cal characteristics. Clusters of neurons in some parts
Stoll, Norman R. 1947. This wormy world. Journal of of the brain begin to discharge impulses in a disorga-
Parasitology 33: 1-19.
nized fashion. The parts of the body controlled by the
affected neurons respond with disorganized activity
such as convulsions or tremors, or by loss of normal
function such as loss of consciousness, paralysis of a
limb, or localized numbness. The condition is also
chronic, marked by the recurrence of seizures. By
monitoring the brain with electrodes, an electroen-
cephalographer can often detect abnormal brain
waves, either localized in one part of the brain or
coming from all parts at once.
Etiology
Although epilepsy can begin at any age, the major-
ity of patients have their first seizure before the age
of 20. In fact, the age of onset is often related to the
cause. Perinatal injuries, severe hypoxia, develop-
mental brain defects, and genetic metabolic defects
are common causes of epilepsy among infants and
the newborn. Brain infections such as meningitis
and encephalitis often result in damage to some
brain cells with subsequent development of epilepsy.
Many children experience seizures during periods of
high fever caused by infection in parts of the body

other than the brain. Only a very small percentage vary among cultures, they are often very difficult to
of these febrile seizures persist after the age of 4, distinguish from epileptic seizures. Between 8 and
however. Head trauma is one of the most common 20 percent of epileptics are thought to experience
causes of seizures among adults, although brain tu- pseudoseizures in addition to their epileptic sei-
mor must also be suspected, as about 40 percent of zures, and it has been estimated that even experi-
all patients with brain tumors have seizures. Later enced neurologists can identify pseudoseizures only
in life, seizures may be caused by cerebrovascular 75 percent of the time (Lechtenberg 1984).
attacks.
Despite medicine's increased ability to determine Epidemiology
the various causes of epilepsy, no known cause can Because epilepsy is a nonreportable disease, it is
be found or reasonably presumed for a large propor- difficult to arrive at reasonable estimates of its inci-
tion of seizures. Until a very few years ago, genetic dence. Perhaps half the cases in the United States
predisposition was thought to be the cause of what are preventable in the sense that they are the se-
was called "idiopathic" epilepsy. Today, most experts quelae of trauma, infections, birth injury, and so
do not believe that heritability plays as large a role forth, with clear damage to the brain, the seizures
as the proportion of patients whose seizures have appearing as a secondary symptom of the underlying
been diagnosed as idiopathic might suggest. That brain damage. In cases of cerebral palsy or mental
genetic factors are involved, however, is indicated by deficiency, epileptic seizures are often the least dra-
the fact that people with a family history of epilepsy matic of the symptoms. These secondary cases are
have a higher incidence of seizures than the popula- more frequent when there is poor prenatal and
tion in general. In addition, the electroencephalo- perinatal care and in populations suffering from pov-
gram (EEG) tracings of asymptomatic relatives of erty with its attendant overcrowding, malnutrition,
patients with some forms of epilepsy show a higher neglect, and violence. From a world health point of
incidence of abnormal discharge than is found view, epilepsy is a very common and disabling condi-
among the rest of the population. tion, particularly in regions where there is a high
Epilepsy is characterized by recurrent seizures; incidence of low virulence central nervous system
therefore, an individual's first seizure does not, of infections causing secondary cases, and where trau-
itself, indicate its presence. Nervous system infec- mas, particularly the subdural hematomas of in-
tions, metabolic imbalance, and transient reactions fancy and early childhood, are neglected.
to head injury may all result in a seizure episode
without putting the individual at risk for further Distribution and Incidence
seizures. Among epileptics an almost infinite num- In the United States the incidence of epilepsy is
ber of stimuli may trigger seizure activity. Fatigue, about 0.3 to 0.4 percent per year, or roughly one
alcohol abuse, and infection, for example, com- tenth the incidence of mental deficiency and perhaps
monly precipitate attacks in people whose epilepsy one half the incidence of schizophrenia. The rate for
is otherwise well controlled. Despite the great vari- males is slightly higher than that for females for all
ability in thresholds and types of seizures and in types of seizures combined, and is highest for ages 0
the unpredictability of its course during the pa- to 4 years, reaches a low level after adolescence, and
tient's lifetime, some features appear with striking peaks again after 70 years as the result of late cere-
frequency, and some attacks are remarkably simi- bral disease (Kurland 1949).
lar for many people. Since the early 1970s, several good epidemiolog-
Epileptics as well as nonepileptics may experience ical surveys of epilepsy have been made in Iceland,
seizures that are not associated with abnormal brain England, and the United States, which report crude
wave activity and that have no known physiological prevalence rates between 3.6 and 5.5 per 1,000 popu-
cause. These pseudoseizures are often called hysteri- lation (Kurland, Kurtzke, and Goldberg 1973).
cal seizures or conversion reactions. Like epileptic Epidemiological studies of epilepsy, however, are
seizures, pseudoseizures have characteristics that ap- plagued by a variety of problems. Of prime impor-
pear repeatedly. Epileptics with pseudoseizures tend tance in this regard is the lack of agreement on the
to exhibit the same signs and symptoms in the same definition of epilepsy itself as well as what consti-
sequence with each episode. Nonepileptics' symp- tutes an active or an inactive case. In addition, there
toms may vary in site and nature if there are many are difficulties involved in estimating the size of the
episodes. Despite the fact that pseudoseizures are population universe and the number of cases not
responsive to the social environment and appear to identified by the case finding procedures. The most

rigorous survey conducted in a community in the tion of the diaphragm and chest muscles. The eyes
United States was done in Rochester, Minnesota may roll up or turn to one side, and the tongue may
(Hauser and Kurland 1975). The crude rate for all be bitten. After this, a period of jerky, clonic, spasms
types of epilepsy was 5.7 per 1,000 population. alternately flex and extend the muscles of the head,
Seventy-five percent of the patients' seizures were of face, and extremities. During this phase, the patient
undetermined cause, and approximately 70 percent may injure him- or herself as well as be incontinent.
had generalized seizures. A prevalence rate of 2.8 Cyanosis is generally marked. Breathing is deep,
per 1,000 population has been reported for Tokyo and there is sweating and salivation. Subsequent to
(Tsuboi 1988) and of 2.47 for rural Kashmir, India the seizure, the patient may wake in a confused
(Koul, Razdan, and Motta 1988). state (postictal twilight state) and even display some
Crude prevalence rates between 7.6 and 8.4 per bizarre behavior. Sometimes patients are hard to
1,000 population have been reported for four North arouse, sleep for hours, and awaken with headache
American Indian tribes (Levy, Neutra, and Parker or sore muscles. Although most tonic-clonic seizures
1987). Environmental factors account for the differ- last for only a few minutes, some patients develop a
ence between Indians and the non-Indians of Roch- series of seizures with no letup, or a continuous
ester. The former have significantly more epilepsy prolonged seizure. This is a serious condition known
attributed to trauma, postencephalopathy, and in- as status epilepticus, which may lead to death if
flammatory disease. Even higher rates are found in immediate care is not provided.
urban ghettos, where lead poisoning and drug addic- A variety of other generalized seizures have also
tion are among the leading causes of epilepsy been recognized. Sometimes patients exhibit only
(Hauser, personal communication). the tonic or clonic aspects of the seizure. Between
the ages of 4 and 12 years, absence seizures often
occur. These have been known as petit mal because
Classification, Clinical Manifestations, and
they are of such brief duration, no more than a few
Pathology seconds, that they often go unrecognized and un-
The growing emphasis on physiological mecha- treated. During the brief lapse of consciousness, the
nisms and electroclinical correlations has led to a child stares vacantly and neither speaks nor hears.
classification of the epilepsies by the localization of Subsequently, activity is resumed with no period of
the electrical abnormality in the brain. The major stupor. Equally brief are atonic seizures, during
division is between generalized (centrencephalic) sei- which the child simply falls to the ground; myoclonic
zures, where the brain activity is spread over the seizures, which are sudden, brief, and massive, in-
entire cerebral cortex; and partial (focal) seizures, volving either the entire body or confined to the
which occur when only one part of the brain is extremities, face, or trunk; and infantile spasms,
involved. Generalized seizures demonstrate bilat- during which the child is jerked into a fetal position
eral motor activity and involve a loss of conscious- with the knees drawn up. Many children with infan-
ness, which may or may not occur in partial sei- tile spasms are also mentally retarded.
zures depending upon the part of the brain initially
affected and the subsequent involvement of other
structures. There is an approximate correspondence Partial Seizures
between the sites of the brain where electrical ab- All partial seizures begin in one part of the brain,
normality occurs and the clinical manifestation of and, because different parts of the brain control dif-
the seizure. ferent parts of the body as well as mental and sen-
sory functions, their signs and symptoms are varied
and, often, quite complex. Many patients exhibit
Generalized Seizures behaviors easily mistaken as psychiatric problems
The term "epilepsy" was first used to denote the which can make accurate diagnosis difficult. It is
symptoms of major, or grand mal seizure, currently also among victims of partial seizures that one is
referred to as a tonic-clonic seizure. To this day, over most likely to observe displays of bizarre, learned,
60 percent of all individuals diagnosed as epileptic culturally conditioned behavior.
have tonic-clonic seizures. A sudden burst of dis- Simple partial seizures have been variously called
charges involving the whole brain occurs without focal, focal motor, or focal sensory seizures. Although
warning. The patient falls to the ground uncon- the symptoms may be motor, autonomic, psychic,
scious. Then, in the tonic phase, the patient goes sensory, or a combination, they are all linked to the
rigid and often gives a short cry, due to the contrac- affected area of the brain. The patient does not lose

consciousness as a general rule, and the attacks last tance. EEGs administered between seizures may or
no more than 30 seconds. One type of simple partial may not reveal patterns suggestive of epilepsy. Nev-
seizure has been called the Jacksonian. It character- ertheless, because they often do reveal abnormal
istically begins with the twitching of one foot or discharges, routine administration of EEGs is of sig-
hand, and the patient retains consciousness. Until nificant value in the evaluation of any patient with
very recently, seizures were classed as Jacksonian a history suggestive of epilepsy.
even if the activity subsequently spread to both sides By conservative estimates, some 50 percent of pa-
of the body and involved loss of consciousness. Today, tients can have their recurrent seizures controlled
however, such seizures are classed as partial but without side effects when optimal medical treatment
secondarily generalized. is available. Another 30 percent can achieve seizure
Complex partial seizures are characterized by com- control but experience some side effects of the medi-
plex symptoms and, unlike simple partial seizures, cation. For some patients whose seizures cannot be
by impairment of consciousness. Often the patient controlled by medication, surgery may be an option
appears to be conscious but later has no recollection if a distinct piece of brain tissue that is causing the
of the episode. These seizures are usually associated seizures can be identified, and if its removal will not
with the temporal or frontal lobe and often begin cause unacceptable neurological deficits such as
with an aura that warns of the impending attack. speech difficulty or memory loss.
Auras may include any of a large variety of sensa-
tions. Some of those most commonly reported are History
nausea; faintness; dizziness; numbness of the hands,
lips, and tongue; choking sensations; and chest pain. Antiquity
Less often, patients have reported visions, palpita- The antiquity of epilepsy is attested to by an ancient
tion, or disturbances of smell or hearing. Some pa- Akkadian text that speaks of a person whose neck
tients have sensations that may begin hours or even turns left, whose hands and feet are tense and eyes
days before the seizure. These symptoms are called wide open, from whose mouth froth flowed, and who
the prodrome and most often involve irritability or lost consciousness. The Greeks referred to it as "the
feelings of uneasiness. When psychomotor symp- sacred disease" as well as "epilepsy," which means
toms appear during a seizure, they are generally seizure and which may derive from the idea that all
semipurposeful and inappropriate actions such as diseases represented attacks by supernatural be-
clumsy attempts to disrobe. Patients often stagger ings. The term "sacred disease" is found first in the
about uttering guttural sounds. Such behavior is writings of Heraclitus and Herodotus, but its identifi-
often confused with psychiatric disorder and is often cation with epilepsy is made explicit in the book On
alarming to those present. the Sacred Disease, part of the Hippocratic collection
Secondarily generalized partial seizures occur of medical writings from about the year 400 B.C. and
when seizures with a focal onset spread throughout the first monograph on epilepsy we possess.
the brain and produce generalized tonic-clonic sei- Underlying the great variety of explanations of-
zures. Because the generalized phase is so dramatic, fered by the ancients lies the basic belief that epi-
patients and their families often overlook the focal lepsy is an affliction or possession by a higher power
onset. The presence of an aura indicates the pres- and that its cure must be supernatural. The Ro-
ence of the focal onset and the need to observe the mans called epilepsy morbus comitalis because the
initial phase more closely. attack spoiled the day of the comitia, the assembly
The diagnosis of epilepsy and the classification of of the people. There was also the idea that the
the type of seizure depend primarily on information disease was contagious: The epileptic was unclean
obtained from the medical history. The first task is and whoever touched him or her might become prey
to determine whether the patient has epilepsy or has to the demon. The idea that epilepsy was contagious
experienced another kind of brief, reversible alter- was one of the factors that made the epileptic's life
ation of consciousness or behavior. Subsequently, miserable and gave him or her a social stigma. To
specifying the type of epileptic seizure is important the ancients the epileptic was an object of horror
for confirming the diagnosis and as a major guide in and disgust and not a saint or prophet as has some-
choosing the initial antiepileptic medication. Be- times been contended. Wherever the physicians of
cause the physician is most often unable to observe antiquity wrote of the sacred disease, they meant
the patient or obtain an EEG reading during a sei- epilepsy and differentiated it from hysterical at-
zure, an accurate medical history is of crucial impor- tacks as well as from madness.

In the struggle between supernatural and scien- from solicitude for the epileptics who might suffer
tific explanations of disease, science has gradually from contact with the insane than from the belief
emerged victorious in the Western world. The fight, that epilepsy was an infectious disease that would
however, has been long and eventful, and in it epi- affect the insane even more than it did the healthy.
lepsy held one of the key positions. Showing both The confinement of epileptics in separate wards of
physical and psychic symptoms, epilepsy more than lunatic asylums became established procedure in Eu-
any other disease was open to interpretation both as rope around 1850 and was soon followed by requests
a physiological process and as the effect of supernatu- for special institutions for epileptics.
ral influences. The first record we have of the battle During the early part of the nineteenth century,
is in On the Sacred Disease, an attack on popular the most valuable contributions to the medical his-
superstition that called epilepsy the "sacred" dis- tory of epilepsy were made by physicians associated
ease. It maintained that epilepsy was hereditary, with hospitals and lunatic asylums, and it was then
that its cause lay in the brain, and its treatment was that new terminology, increased use of statistics,
to be by diet and drugs as long as it had not yet and interest in the psychiatric side of epilepsy devel-
become chronic. It is here we first find the fundamen- oped. The terms grand and petit mal, absence, status
tal statement that the seat of the disease is in the epilepticus, and aura, for example, were in common
brain and that the brain is the organ of all psychic usage and survive to this day. The growing use of
processes both normal and pathological. Moreover, statistics fostered investigations into the inheritabil-
according to the author of this work, not only epi- ity of epilepsy and determination of the various
lepsy but all mental diseases were to be explained by causes of the illness, prominent among which were
disturbances in the brain. fright, sorrow, and masturbation. Despite the in-
creased attention paid to epilepsy, however, modern
Middle Ages Through the Eighteenth Century medicine's understanding is usually said to have
During the Middle Ages, the literature on epilepsy begun around 1880, when the impact of John
propounded two contrasting views. On the one hand, Hughlings Jackson's work in England and that of
the "falling evil" was bound to demoniac beliefs and Jean Charcot in France began to be felt. Jackson
theological speculations; on the other, physicians outlined a neurological theory of epilepsy, while
clung to the idea of a definite natural disease. Little Charcot separated epilepsy from hysteria more em-
effort was made to force the issue, however; physi- phatically than any of his predecessors. Jackson's
cians rarely discussed the theological aspects and principles were publicly demonstrated in 1888, by
seem, moreover, to have been unable to rid them- William Macewan, who was "probably the first sur-
selves of traditional definitions and explanations. By geon to localize the cerebral focus by inference from
the end of the sixteenth century, this appears to have the motor or sensory signs of the epileptic seizure"
changed, the debate became open, involving the role (Temkin 1971).
of the devil, witchcraft, and various types of magical Jerrold E. Levy
treatment. Despite many efforts to define epilepsy
and classify types of seizures, little progress was Bibliography
made medically, although, gradually, the idea that Epilepsy Foundations of America. 1981. How to recognize
epilepsy was a natural disease did gain more cre- and classify seizures. Landover, Maryland: Epilepsy
dence, especially after the Age of Enlightenment. Foundation of America.
Ervin, Frank R. 1967. Brain disorders. IV: Associated
Nineteenth Century with convulsions (epilepsy). In Comprehensive text-
By the beginning of the nineteenth century, epilep- book of psychiatry, ed. Alfred M. Freedman and Har-
tics were hospitalized, but unlike the insane, were old I. Kaplan, 795-816. Baltimore.
allowed to go to mass on Sundays. Confined epilep- Hauser, W. Allen, and Leonard T. Kurland. 1975. The
tics, however, became the object of systematic medi- epidemiology of epilepsy in Rochester, Minnesota,
1935 through 1967. Epilepsia 16: 1-66.
cal attention only in the early nineteenth century.
Koul, Roshan, S. Razdan, and Anil Motta. 1988. Preva-
The care of epileptics, especially children, pro- lence and pattern of epilepsy (Lath/Mirgi/Laran) in
gressed slowly. Only in 1838 were epileptic children rural Kashmir, India. Epilepsia 29: 116-22.
in Paris transferred from the Hospital of the Incur- Kurland, Leonard T. 1949. The incidence and prevalence
ably 111 to the Bicetre, where some kind of education of convulsive disorders in a small urban community.
was provided for them. The separation of hospital- Epilepsia 1: 143.
ized epileptics from the insane was motivated less Kurland, Leonard T., John F. Kurtzke, and Irving D. Gold-

berg. 1973. Epidemiology of neurologic and sense or- Clinical Manifestations and Pathology
gan disorders. Cambridge. Convulsive or spasmodic ergotism affects the central
Lechtenberg, Richard. 1984. Epilepsy and the family. nervous system, causing areas of degeneration in
Cambridge. the spinal cord. Early German accounts mentioned
Levy, Jerrold E., Raymond Neutra, and Dennis Parker. tingling and mortification in the fingers and toes,
1987. Hand trembling, frenzy witchcraft, and moth with occasional extension to the rest of the body, and
madness: A study ofNavajo seizure disorders. Tucson.
Temkin, Owsei. 1971. The falling sickness: A history of
vomiting, diarrhea, intense hunger, anxiety, unrest,
epilepsy from the Greeks to the beginnings of modern headache, vertigo, noises in the ear, stupor, and in-
neurology, 2d edition. Baltimore. somnia as symptoms. Often the limbs became stiff,
Tsuboi, Takayuki 1988. Prevalence and incidence of epi- accompanied by convulsive contractions of the mus-
lepsy in Tokyo. Epilepsia 29: 103-10. cles which led to staggering and awkward move-
ments, often aggravated by being touched. Although
many victims recovered, symptoms sometimes re-
mained for long periods, resulting in permanent stiff-
ness of the joints, muscular weakness, optic disor-
ders, and occasional imbecility. In the 1930s, Ralph
VIII.49 Stockman demonstrated that convulsive ergotism
was "caused by poisons (phytates) normally present
Ergotism in rye and other grains" which, unless broken down
in the bowel, were absorbed, creating lesions in the
nervous system.
Ergotism is a disease condition acquired by eating
cereal grains infected with ergot fungus. Known Midwives and empirics discovered that spasmodic
since the time of Galen, it was prevalent in medieval ergotism caused abortion or miscarriage in pregnant
Europe, particularly among the poor who, during women, the drying up of milk in lactating mothers,
famine, consumed bread made from spoiled rye. Er- and amenhorrea in young girls. This abortifacient or
got (secale cornutum, spur of the corn, horned rye, oxytocic effect was later noted by orthodox medicine
womb grain), the dried sclerotium of Claviceps and led to the widespread use of ergot to accelerate
purpurea, develops on the ovary of common rye, or uterine action. Before long, doctors began distin-
on corn, where it was previously known as corn guishing ergot with such sobriquets as poudre obstet-
smut. The actual cause of ergot in grasses was hotly rical, forcing powders, or more commonly, forcing
debated by early naturalists, some of whom thought drops. Not surprisingly, it also played a major role
it occurred in rainy weather and was attributable to among quacks, charlatans, and "private specialists"
fog or impure atmosphere. Others believed it to be who promised a quick and painless cure for women
the work of worms or butterflies, whereas still oth- desiring to "regulate" their menstrual cycles. The
ers regarded it as the product of improper fecunda- term "regulation" was euphemistically used to mean
tion or perhaps the cooking of the sexual parts of the the termination of a pregnancy. For some, ergot sub-
plants. stituted for the more common borax, cinnamon, and
turpentine as an abortifacient.
Gangrenous ergotism often began with itching and
Classification formications in the feet, or sensations of extreme
Ergotism has two forms: (1) convulsive, or spas- coldness, followed by burning pain, or a crop of blis-
modic, also known as creeping, which affects the ters. A dark spot usually appeared on the nose or
central nervous system; and (2) gangrenous, which affected extremity, leading to loss of sensibility in the
affects the blood vessels and blood supply to the part. Early nineteenth-century accounts mentioned
extremities. Common names for the gangrenous headache, dizziness, nausea, vomiting, diarrhea, and
form are St. Anthony's fire (after the patron saint of spreading erysipelatous redness. The epidermis was
the disease), hidden fire, saint's fire, evil fire, devil's raised by serous exudation, and the surface assumed
fire, and holy fire. As a result of early imprecision in the appearance of gangrene with the extremities be-
disease specificity and diagnosis, physicians con- coming withered and blackened. Usually the gan-
fused ergotism with the plague and a variety of grene was dry, but the moist variety was not un-
other diseases including leprosy, anthrax, typhus, known. The patient suffered from a continual low
smallpox, and scurvy. fever and phthisical symptoms, and faced eventual

VIII.49. Ergotism 719
death from exhaustion or septicemia. Often, however, swept through the rural countryside prior to the
recovery followed loss of the affected limb. When gan- French Revolution, and even the seasonability of
grene attacked the viscera, however, death occurred mortality and conception patterns in Europe.
quickly. Matthias Grunewald's Isenheim Altarpiece,
commissioned between 1508 and 1516 at the An- Epidemiology and Etiology
tonite monastery, and currently displayed in the Research in the 1930s suggested that the distribu-
Musee d'Unterlinden in Colmar, testifies to the out- tion of convulsive and gangrenous ergotism was a
break of St. Anthony's fire in France and its grue- function of the presence or absence of vitamin A in
some impact on those afflicted. the diet. An analysis of the 1770 epidemic of gangre-
nous ergotism in Sologne and of convulsive ergotism
History and Geography in Hanover indicated that Sologne, on the left bank
First allusions to ergotism are concurrent with the of the Rhine, was a dairy district that provided a diet
French monastic hospices, which cared for the com- rich in vitamin A, whereas Hanover, on the right
mon people and which took special note of the dis- bank, was unable to sustain a dairy economy. The
ease. Along with these observations came the desig- striking difference in the effects of ergot on the two
nation of patron saints for ergotism, including St. communities in close proximity caused researchers
Benedict of Umbria, St. Martial of Limoges, St. Gene- to study their differing experiences in a laboratory
vieve of Paris, St. Martin of Tours, and St. Anthony by feeding ergot to dogs along with different levels of
of Egypt whose remains were carried to France in vitamin A. The results confirmed the efficacy of vita-
the eleventh century. From this last saint the name min A in mitigating the effects of ergotism.
St. Anthony's fire was derived. Similarly, while some researchers believed that
In his Handbook of Geographical and Historical England's relative freedom from ergotism was due to
Pathology (1883-6), August Hirsch recorded 132 epi- the abundant ingestion of meat and potatoes, others
demics of ergotism between 591 and 1789. Accounts demonstrated that the English diet, which was rich
of ergotism are also found in the Annals of the Con- in milk and butter products, had enabled its inhabit-
vent at Xanten, near the Rhine, detailing an out- ants to remain relatively free from the convulsive
break in 857, and are described by Frangois Eudes effects of ergotized grain. In areas rich in dairy prod-
de Mezeray in the seventeenth century as St. An- ucts, the phytase and the bowel bacteria broke down
thony's fire. Later French epidemics of the gangre- the poisonous phytates of the grain into the compara-
nous type reportedly killed 40,000 in 922 and 14,000 tively innocuous inorganic phosphates. Thus, the
in Paris alone during 1128-9. The spasmodic form convulsive ergotism which had been common to
occurred in Spain in 1581 and 1590 and in Germany nondairy areas was virtually absent in England and
in 1595; epidemics in the Sologne district of France, certain sections of France.
in Germany, and in Switzerland recurred through- John S. Holler, Jr.
out the seventeenth century. The French districts of
Sologne and Dauphin^, frequently subject to flood- Bibliography
ing, suffered continuously from outbreaks of er- Barger, George. 1931. Ergot and ergotism. London.
gotism, as did Artois, Lorraine, and the Limousin. Berde, B., and H. O. Schild, eds. 1978. Ergot alkaloids and
The disease also affected the Netherlands, Sweden, related compounds. Berlin.
Majorca, Italy, Poland, and central Russia, where Bove, Frank J. 1970. The story of ergot. Basel.
outbreaks were reported as late as 1926. Hirsch Caporael, L. R. 1976. Ergotism: The Satan loosed in Sa-
noted three epidemics in the British Isles, and dur- lem? Science 192: 21-6.
ing the American Revolutionary War soldiers sta- Haller, John S., Jr. 1981. Smut's dark poison: Ergot in
tioned in upper New York State reportedly sickened history and medicine. Transactions and Studies, Col-
on ergotted flour shipped from Ohio. A later Ameri- lege of Physicians of Philadelphia, Ser. 5, HI: 62-79.
can outbreak reportedly occurred at a New York Hirsch, August. 1883-6. Handbook of geographical and
prison in 1825. historical pathology, 3 vols. London.
Matossian, Mary. 1982a. Ergot and the Salem witchcraft
More recent research has suggested that ergotism affair. American Scientist 70: 355-7.
can explain the convulsions and hallucinations that 1982b. Religious revivals and ergotism in America. Clio
attended religious revivals, including the Salem Medica 16: 185-92.
witchcraft affair, as well as the time of "The Great Stockman, Ralph. 1934. The cause of convulsive ergotism.
Fear" (between July 20 and August 6, 1789), which Journal of Hygiene 34: 235-41.

tions made by Galen, and consequently included a
vni.5o wide variety of ailments including diseases of the
Erysipelas uterus and lungs among the varieties of erysipelas.
Nineteenth Century
The term erysipelas (erythros = red, pella = skin) During the nineteenth century, physicians began giv-
was used in Hippocratic times (often but not always) ing greater attention to the causes and prevalence of
to describe classic cellulitis. For the past century or erysipelas because, on the one hand, the disease
so, however, erysipelas has commonly referred to seemed connected to wound infection, and, on the
infection of the derma with a streptococcal organ- other hand, because epidemics of erysipelas were
ism, usually Streptococcus pyogenes. Infection with a occurring simultaneously with peak years of puer-
group A, beta-hemolytic streptococcus can produce a peral sepsis, or "childbed fever." Their investiga-
painful, red, edematous indurated skin lesion called tions eventually led to the discovery of streptococci
peau d'orange for its resemblance to the texture of and the distinctions that have provided us with our
an orange skin. Sharp borders of the infection ex- current definitions of erysipelas.
tend rapidly, dissecting the underlying dermis from In 1795 Alexander Gordon of Aberdeen became
the epidermis. Erysipelas usually appears on the the first clinician formally to associate erysipelas
face, producing a butterfly rash over the cheeks and with puerperal fever (Loudon 1987). Then around
nose. The same streptococci that cause erysipelas the middle of the nineteenth century, two seminal
can also cause scarlet fever, giving both diseases a studies appeared. In 1842, Oliver Wendell Holmes
fairly distinctive age pattern: Erysipelas is much published an essay on the contagiousness of puer-
more common among adults who generally escape peral fever, and in 1861 Philip Ignaz Semmelweis
scarlet fever, which normally attacks the young. The published his classic study of The Etiology, Concept,
prognosis for untreated erysipelas is especially seri- and Prophylaxis of Childbed Fever. Both men blamed
ous when this infection is secondary to some other physicians for carrying infective particles to the bed-
insult such as laryngeal infection, or puerperal sep- sides of parturient women. Holmes stated specifi-
sis. Indeed distinctions are still made among gangre- cally that puerperal sepsis could be caused "by an
nous erysipelas, erysipelas grave internum (a form infection originating in the matter or effluvia of
of puerperal fever), surgical erysipelas (which occurs erysipelas" (Carter ed. 1983). The great French clini-
after a surgical procedure), and traumatic erysipelas cian Armand Trousseau, writing during this same
(which begins in a wound). period, regarded even trivial skin injuries as precur-
sors to erysipelas.
History In 1882 following the discovery of streptococci, Frie-
drich Fehleisen published a study of the etiology of
Antiquity Through the Eighteenth Century erysipelas, which he associated with S. pyogenes. In
Early accounts of erysipelas are often confusing be- addition, he reported using his cultures on human
cause they lumped purulent and gangrenous afflic- subjects, justifying the production of iatrogenic infec-
tions under this rubric. Thus Hippocrates distin- tion as a means of combatting some forms of cancer -
guished between "traumatic" erysipelas, which a procedure in vogue in Germany at the time. In
accompanied wounds, and a myriad of other skin follow-up studies, another German surgeon, Frie-
lesions that had no known external cause. Galen in drich Julius Rosenbach, described the ability of the
turn distinguished between "phlegmon," including erysipelas-causing streptococci to spread through
suppurative ulcers and gangrene, and nonnecrotic host tissues without causing suppuration. This
cellulitis — but viewed both as forms of erysipelas. research was of paramount interest to surgeons con-
Celsus, in the first century A.D., considered septic cerned with controlling the omnipresent infections -
ulcers, "canker," erythematous wound infections, occasionally called "hospitalism" - that killed survi-
and Ignes Sacer to all be types of erysipelas. vors of otherwise "successful" operations.
Such confusion has continued into the modern pe-
riod, with some historians interpreting epidemics of Twentieth Century
Ignes Sacer (sacred fire) or Saint Anthony's fire as Although the use of aseptic and antiseptic techniques
ergotism, whereas others have viewed these scourges led to dramatic reductions in postsurgical mortality
as recurrent erysipelas. Before the modern period, rates, maternal mortality still remained high. Dur-
however, physicians tended to embrace the distinc- ing the 1920s and 1930s, the research of Leonard and

Vm.51. Fascioliasis 721
Dora Cook and others permitted the identification

and typing of strains of streptococci. This, in turn, led vni.5i
to irrefutable evidence that puerperal fever was an Fascioliasis
exogenous infection, usually transmitted from a phy-
sician, midwife, or nurse attending a parturient
woman (Loudon 1987). Yet even family and friends The liver fluke Fasciola hepatica is usually a para-
could communicate the streptococci that caused puer- site of sheep and cattle. "Liver rot" in sheep was
peral sepsis in women in labor, for these were the described in a French work in 1379, and the first
same streptococci that caused erysipelas. Conse- human case was described in 1760. The fluke's life
quently, maternal mortality from puerperal fever de- cycle was discovered in 1881. Fascioliasis is a signifi-
clined only some time after effective antibiotics be- cant veterinary problem, but human infection is also
came available. Indeed, Irvine Loudon (1987) has fairly common. The fluke's life cycle is much like
shown that despite well-known changes in the viru- that of Fasciolopsis buski (see Fasciolopsiasis), with
lence of streptococcal organisms historically, no sud- people or herbivores infected by eating raw water-
den and spontaneous decline in the virulence of the cress or other plants contaminated by the cysts of
organism can account for the abrupt decline in mortal- the fluke. Adult worms settle down in the bile ducts
ity from erysipelas, scarlet fever, and puerperal fever. after a period of wandering in the liver. Mild infesta-
Instead, credit for moderating these ancient scourges tions may cause little damage, but fever, jaundice,
belongs to the beginning of the antibiotic era and, in and right upper quadrant abdominal pain radiating
particular, to the use of sulfonamides. to the shoulder blade are common symptoms. Bile
AnnG. Carmichael ducts may become partially or totally obstructed,
and liver destruction can be severe.
Bibliography F. hepatica is cosmopolitan in distribution, with
Carter, Codell, ed. and trans. 1983. Translator's Introduc- important foci of human infection in southern
tion to Ignaz Semmelweis, The etiology, concept, and France, in Algeria, and in South America. Diagnosis
prophylaxis of childbed fever. Madison, Wis. is made by examining the feces of symptomatic pa-
Celsus. 1938. De medicina, Vols. 3 and 5, trans. W. G. tients with a microscope to find the eggs. Treatment
Spencer. London.
is generally effective. Prevention is by treating
Lenhartz, Hermann. 1902. Erysipelas and erysipeloid. In
Nothnagel's encyclopedia of practical medicine, ed.
sheep to keep them from perpetuating the cycle,
John W. Moore, trans. Alfred Stengel. Philadelphia. controlling snail intermediate hosts, and keeping
Loudon, Irvine. 1987. Puerperal fever, the streptococcus, domestic animals away from ponds where water-
and the sulphonamides, 1911-1945. British Medical cress is grown.
Journal 295: 485-90. K. David Patterson
Wilson, Leonard. 1987. The early recognition of strepto-
cocci as causes of disease. Medical History 31: 3-14. Bibliography
Deschiens, R., Y. LeCorroller, and R. Mandoul. 1961.
Enquete sur les foyers de distomatose hep6atique de
la Vall6e de Lot. Annales de I'Institut Pasteur 10: 5 -
12.
Foster, W. D. 1965. A short history of parasitology. Edin-
burgh.
Kean, B. H., Kenneth E. Mott, and Adair J. Russell, eds.
1978. Tropical medicine and parasitology: Classic in-
vestigations, Vol. II, 561-83. Ithaca and London.
[Nine important accounts, including two from the six-
teenth century.]
Reinhard, Edward G. 1957. The discovery of the life cycle
of the liver fluke. Experimental Parasitology 6: 208-
32.

VIII.52 VIII.53
Fasciolopsiasis Favism
Fasciolopsiasis is caused by the giant intestinal Favism is an acute hemolytic reaction triggered by
fluke, Fasciolopsis buski. Discovered in 1843, the exposure either to fava beans (Vicia faba) or to cer-
organism occurs in China, Korea, Southeast Asia, tain drugs (e.g., sulfa-based antibiotics and the
and parts of India and Indonesia. The adult worm, antimalarial primaquine) in people with an inher-
which has a life-span of only 6 months, attaches ited deficiency of the enzyme glucose-6-phosphate
itself to the wall of the small intestine of humans. dehydrogena.se (G6PD). In favism, the patient can
Pigs and dogs can also be infected, and sometimes suffer from destruction of red blood cells, severe ane-
are important reservoir hosts. Eggs produced by the mia, and possibly death. There are two necessary
hermaphroditic adults pass out in the feces and, if conditions for the disease: (1) genetic inheritance of
they reach fresh water, produce motile larvae that the "Mediterranean" variant of the abnormal gene
penetrate into the tissues of certain planorbid snails. trait for G6PD deficiency; and (2) ingestion of fava
After two generations of reproduction, another mo- beans, usually fresh, or exposure to some drugs. The
tile form leaves the snail, finds a plant like the bean is a dietary staple in areas where favism is
water chestnut, water caltrop, or water bamboo, and reported. Only an estimated 20 percent of those with
encysts on it. Humans become infected with cysts by the genetic trait for G6PD are likely to experience
peeling raw fruits of plants with their teeth or eat- episodes of favism. Under modern medical condi-
ing them uncooked. The disease can become very tions the hemolytic anemia caused by favism is only
prevalent in areas where these plants are cultivated rarely fatal. Strong evidence suggests that both the
with human feces as fertilizer. gene for G6PD deficiency and the cultural practice of
Mild infections are often asymptomatic, but flukes fava bean consumption are evolutionarily adaptive
can irritate and even ulcerate the intestinal mucosa. traits that protect against death from all types of
Abdominal pain, diarrhea, anemia, and fluid accu- malaria. Favism, then, could be described as a nega-
mulation in the abdomen are common symptoms. tive outcome of the interaction of the positive adap-
Extreme cases can be fatal. Diagnosis is made by tive qualities of both the gene and the bean.
discovery of the eggs in the feces. Drug therapy is
usually effective. Prevention includes better rural Distribution and Incidence
sanitation and control of swine reservoir hosts. Cook- Favism is found primarily in the Mediterranean and
ing vegetables would also be very beneficial, but Middle East regions where fava beans are a staple
drastic changes in long-established culinary habits food and the Mediterranean variant of G6PD defi-
are unlikely. ciency gene is relatively common. Mark Belsey
K. David Patterson (1973) reports that it is frequently encountered in
Greece, Sardinia, Italy, Cyprus, Egypt, Lebanon, Is-
Bibliography rael, Iran, Iraq, Algeria, and Bulgaria, and is par-
Kean, B. H., Kenneth E. Mott, and Adair J. Russell, eds. ticularly common among Sephardic Jews. Favism
1978. Tropical medicine and parasitology: Classic in- has also been sporadically reported in China, Ger-
vestigations, Vol. II, 584-99. Ithaca and London. many, France, Poland, Romania, Yugoslavia, Great
Sadun, E. H., and C. Maiphoom. 1953. Studies on the Britain, and the United States. The disease is consid-
epidemiology of the human intestinalfluke.Fasciolop- ered a serious public health problem in contempo-
sis buski (Lankester) in central Thailand. American rary Greece (Trakas 1981).
Journal of Tropical Medicine and Hygiene 2:1070-84. The incidence of favism has been estimated for few
areas. The most complete study in two Iranian prov-
inces on the Caspian coast found an annual inci-
dence that ranged between 0.65 and 6.39 cases per
10,000 population, with some areas reporting inci-
dences as high as 9.27 cases per 10,000 (Lapeys-
sonnie and Keyhan 1966). William Crosby (1956), on
the other hand, estimated 50 cases per 10,000 for
Sardinia. Mortality is generally rare, with rates

VIII.53. Favism 723
ranging between 1 and 4 percent of the reported of the gene have been identified. Both population
cases. genetic data and in vitro studies indicate that the
distribution of these genes is correlated with the
Epidemiology and Etiology historical distribution of malaria. Favism occurs in
Favism is generally a pediatric illness in which the only a small proportion of individuals with the Medi-
majority of victims are between 2 and 5 years of age, terranean variant of G6PD deficiency, and within
although cases as young as 6 months and as old as 65 that population it follows familial lines. It has been
years have been reliably reported. The disease has a recently recognized that there is substantial genetic
marked seasonal cycle corresponding to the harvest variation within the Mediterranean variant (Luz-
of fresh fava beans, a 4- to 5-week period between zatto and Battistuzzi 1985).
April and July, although in areas where the bean is
dried for later consumption, cases can occur all year. Clinical Manifestations
There is evidence that the toxic factor that induces Favism is characterized by five general symptoms:
the favism crisis has four characteristics: weakness, fatigue, pallor, jaundice, and hemoglobi-
nuria (blood in the urine). The anemia caused by
1. It is located in the skin of the bean. hemolysis is severe. In a clinical study in Greece, one-
2. It is heat stable. third of favism cases had hemocrit levels below 4
3. It is able to enter the breast milk of lactating grams of hemoglobin per 100 milliliters ofblood (Katt-
women. amis, Kyriazakov, and Chidas 1969). In populations
4. Its toxicity decreases when the beans are dried at risk, this set of symptoms is recognized as a distinct
and the skin changes color. illness, often referred to as "fava bean poisoning."
Active biochemical agents in the skin of the bean -
the pyrimidine oxidant compounds vicine, isoura- History and Geography
mil, divicine, and L-dopa - are probably responsible. The historical puzzle of favism is that peoples of
These same biochemical agents are believed to pro- Mediterranean and Middle Eastern societies would
vide some protection against malaria for people continue to eat a food that regularly causes illness
with normal genotypes when they eat fresh fava and even death. From an evolutionary perspective,
beans. Although it is widely believed that inhala- both fava bean consumption and G6PD deficiency
tion of pollen of the V. faba can trigger cases of appear to be retained in populations because they
favism, recent studies indicate that this is not true. provide some protection from malaria. The correla-
Boys are much more likely to suffer favism attacks tion between the geographic distribution of these
than girls, with male/female case ratios varying from traits and malaria is one line of evidence for this
2.1:1 to 2.7:1. The reason for the increased risk for relationship. Fava bean cultivation dates back to the
males is that G6PD deficiency is a sex-linked trait; Neolithic period in areas that have favism. Ancient
the gene is located on the X chromosome. Only carrier Indo-European culture, and particularly Greek cul-
males (hemizygotes) and homozygous females can ture, placed remarkable emphasis on the symbolic
suffer from favism. Heterozygote females appear to rather than nutritional qualities of the fava bean.
be at an evolutionary advantage because they have Alfred Andrews (1949) argues that "no plant or ani-
no risk of favism and also enjoy a degree of protection mal known to the Indo-Europeans has produced a
against the malaria protozoa Plasmodium. more luxuriant growth of benefits than fava beans."
The G6PD enzyme, found in all tissues, plays im- Fava beans have had three primary symbolic asso-
portant housekeeping functions in red blood cell me- ciations: the life principle, the souls of the dead, and
tabolism. The cells of enzyme-deficient individuals the generative powers of male sexuality, and they are
tend to become oxidant-sensitive, and any exoge- ritualistically eaten at certain times of the year, a
nous sources of increased oxidants (malaria para- practice that continues in European folk cultures. On
sites, antimalaria drugs, or fava beans) can result in the other hand, taboos against the consumption of
the lysis (explosion) of the cell (Katz and Schall fava beans for certain groups, particularly priests,
1979). In enzyme-deficient individuals, this process have been reported in ancient Greece, Egypt, India,
can result in either favism or protection from a se- and Africa. The most famous case of such a taboo was
vere malaria infection, depending on the context. among the Pythagoreans, who had the maxim, "It is
The geographic distribution of the many varieties an equal crime to eat beans and the heads of one's
of G6PD-deficient genes has been exceptionally well parents." Although many historical analyses for this
studied by population biologists. Over 200 varieties taboo have been suggested, a medically informed hy-

pothesis based on the risk of favism appears most
reasonable (Brumbaugh and Schwartz 1979). VIII.54
In the history of medicine, the early clinical de- Filariasis
scriptions by the Italian physician Antonio Gasbar-
rini were a landmark for the diagnosis and treat-
ment of favism attacks of varying severity. Within The term "filariasis" refers to several diseases of
the tradition of Galenic medicine, treatment, al- both humans and animals caused by infection with a
though not always for favism attacks, emphasized specific group of parasitic nematodes called filarial
the reinforcement of the blood with red wine among worms (named for the hairlike appearance of the
other things. Understanding the evolutionary his- adult form). Those worms that affect humans belong
tory of favism has been a recent development that to the Order Filarioidea, Family Dipetalonematidae.
paralleled the discovery of the malaria connection They include (1) Wuchereria bancrofti and Brugia
with other genetic polymorphisms like thalassemia malayi, which are common causes of elephantiasis
and sickle-cell anemia. The analytical connection (extreme swelling and skin thickening of the legs,
with G6PD deficiency was first suggested in 1956, scrotum, labia, or arms) and chyluria (lymph and
by Crosby, and the development of a genetic screen- emulsified fat globules in the urine); (2) Loa loa, the
ing technique for the trait created a wealth of popula- "eye worm"; and (3) Onchocerca volvulus, the cause
tion genetic data during the 1960s. Such data on of onchocerciasis. Depending upon their species,
genetic markers in populations - for example, the adult filarial worms of both sexes reside in the lym-
variants of G6PD deficiency - have a potential for phatic system, subcutaneous tissues, or peritoneal
historical reconstruction of population movements and pleural cavities. Sexual reproduction results in
and culture contact (Brown 1981). embryos (microfilariae) that enter blood or skin,
Peter J. Brown where they are ingested by a particular intermedi-
ate host (certain species of mosquitoes, horse fly,
Bibliography blackfly,or other arthropods). The microfilariae de-
Andrews, Alfred C. 1949. The bean and Indo-European velop into larvae in their intermediate hosts and
totemism. American Anthropologist 51: 274-92.
then reenter vertebrate hosts (humans or animals)
Belsey, Mark A. 1973. The epidemiology of favism. Bulle-
tin of the World Health Organization 48: 1-13. through bites in the skin made by the intermediate
Brown, Peter J. 1981. New considerations on the distribu- host arthropods. Loa Loa is endemic in West and
tion of thalassemia, glucose-6-phosphate dehydroge- central Africa, whereas onchocerciasis is found in
nase deficiency and malaria in Sardinia. Human Biol- Mexico, Central America, and West Africa. Discus-
ogy 53: 367-82. sion of human lymphatic filariasis in the remainder
Brumbaugh, Robert, and Jessica Schwartz. 1979. Pythago- of this entry will be limited to the most prevalent
ras and beans: A medical explanation. Classical World form (90 percent of infections), that caused by W.
73: 421-2. bancrofti (Sasa 1976; Beaver, Jung, and Cupp 1984;
Crosby, William H. 1956. Favism in Sardinia. Blood 11: Mak 1987; Manson-Bahr and Bell 1987).
91-2.
Kattamis, C. A., M. Kyriazakov, and S. Chidas. 1969.
Favism: Clinical and biochemical data. Journal of Distribution and Incidence
Medical Genetics 6: 34-41. Bancroftian filariasis is widely distributed through-
Katz, Solomon, and Jean Schall. 1979. Fava bean consump- out the tropics. Though it no longer exists in areas
tion and biocultural evolution. Medical Anthropology such as North America (most notably the Charleston,
3: 459-76. S.C. area), southern Europe, Australia, and some Ca-
Lapeyssonnie, L., and R. Keyhan. 1966. Favism in the ribbean islands, and is decreasing in prevalence in
Caspian littoral area. In Proceedings of the first semi- other Caribbean islands, Central America, and South
nar on favism in Iran. Teheran. America, W. bancrofti is becoming more prevalent in
Luzzatto, L. 1969. Glucose-6-phosphate dehydrogenase de- parts of Asia. At some time nearly every nonarid re-
ficient red cells: Resistance to infection by malarial gion of the tropics or subtropics as well as temperate
parasites. Science 164: 839—42. parts of China and Japan has experienced W. ban-
Luzzatto, L., and G. Battistuzzi. 1985. Glucoses-phos- crofti infection (Sasa 1976; Beaver et al. 1984; Mak
phate dehydrogenase. Advances in Human Genetics
14: 217-327.
1987; Manson-Bahr and Bell 1987).
Trakas, Deanna. 1981. Favism and G6PD deficiency in Although no precise count of the number of people
Rhodes, Greece. Ph.D. thesis, Michigan State Univer- infected with W. bancrofti exists, in 1984 the World
sity. Health Organization estimated that number at more

VIII.54. Filariasis 725
than 81 million. Prevalence is highest in Asia (espe- crofilariae in the peripheral blood), the density of
cially China, India, and Indonesia) and Africa. The the intermediate host mosquito population, and the
disease affects primarily the rural and urban poor of presence of a susceptible human population avail-
working age living in areas of poor sanitation where able for repeated bites by infected mosquitoes are
mosquitoes abound (Mak 1987; Partono 1987). key factors in the epidemiology of bancroftian
filariasis. The significance of filariasis in an area
Etiology and Epidemiology may be measured by either the microfilaria rate or
The threadlike, white, adult W. bancrofti (males: 40 the actual disease rate (percentage of the population
mm long x 0.1 mm in diameter; females: 65-100 displaying symptoms of filarial infection) (Beaver et
mm x 0.2-0.3 mm) lie coiled together in human al. 1984; Manson-Bahr and Bell 1987).
lymphatic vessels and lymph glands, where they can
live for 10 to 18 years. Within 6 months to 1 year of Clinical Manifestations and Pathology
infection, tiny larvae called microfilariae leave the In nature, only humans develop elephantiasis from
adult female and enter the host's peripheral blood filarial infection of the lymphatics, so scientists
and lymph channels. Microfilariae move freely could not easily study the pathogenesis of ban-
through the lymph or blood and, depending on the croftian filariasis until the recent development of a
strain, show nocturnal or diurnal periodicity in the cat model. As a result of this and other work, re-
blood. Nocturnal microfilariae (the most common in- searchers have described the pathogenesis and pa-
fective form) reside in the arterioles of the lungs thology of bancroftian filariasis more accurately.
during the day, whereas the diurnal (also called Filarial disease may not manifest itself for many
subperiodic) strain appears in the peripheral blood years despite the presence of microfilaremia. If
continuously, although in reduced numbers at night. reexposure to larvae does not occur, infection usu-
Geographically, nocturnally periodic microfilariae ally disappears within 8 years. Repeated exposure
are generally found west of 140° east longitude, and over many years generally results in clinical disease
diurnal microfilariae are present east of 180° east during adulthood. Newly exposed adults display a
longitude. Both types may be found between these different disease pattern and a stronger reaction
two meridians. The largest concentrations of diurnal than do persons who are exposed from childhood. In
microfilariae exist in the Polynesian and New Cale- both cases clinical symptoms occur throughout the
donian regions of the Pacific Ocean (Sasa 1976; Bea- body because of widespread disruption of the lym-
ver et al. 1984; Manson-Bahr and Bell 1987). phatics (Beaver et al. 1984).
Bancroftian filariasis is transmitted only by mos- Once the filarial larva settles in a human lymph
quito. There is no known animal reservoir of W. ban- channel and begins to mature, it provokes a localized
crofti. Microfilariae may be transmitted to another response consisting of lymph vessel dilation and a
human through blood transfusion, and from the ma- slowing of lymph flow through that worm-occupied
ternal to the fetal circulation, but in both situations channel. With time the host body responds immuno-
the microfilariae never develop into adults (Beaver et logically, sending eosinophils, plasma cells, and
al. 1984; Manson-Bahr and Bell 1987). macrophages to the sites of infection. Lymphangitis
Microfilariae have adapted their daily cycles to (inflammation of lymph channels) usually results in
either day- or night-feeding mosquitoes, depending swelling, redness, and pain, and, when the lymph
on the species and activity of these insects in a par- vessels become hypertrophied, in varices. Fibrosis of
ticular geographic area. The mosquito becomes an the vessel occurs, trapping and killing the adult
intermediate host of microfilariae after taking a worm, which is absorbed or calcified. Obliteration of
blood meal. Microfilariae develop into infective lar- the lymph vessel forces extravasation of lymph into
vae within the insect host in less than 2 weeks, and the tissue space, where it accumulates and causes the
escape from its proboscis onto the skin of the mos- typical lymphedema of filarial elephantiasis. The
quito's next human host during feeding. The larvae swelling can become quite large, consisting of lymph,
burrow into the human's skin through the tiny punc- fat, and fibrotic tissue under tightly stretched and
ture wound and find their way to lymph vessels thickened skin (Beaver et al. 1984; Manson-Bahr and
where they mature within a year and mate, produc- Bell 1987).
ing more microfilariae (Beaver et al. 1984; Manson- The clinical course of bancroftian filariasis can
Bahr and Bell 1987). follow one of two paths: In highly endemic areas,
In a given geographic area, the microfilaria rate people are exposed to repeated filarial infections
(percentage of a given population carrying mi- from a very young age. The microfilariae provoke

only a weak local tissue response, and the children in 1947. This drug also kills adult worms. When
show little effect of infection. When the larvae move DEC is used in conjunction with a comprehensive
to and then reside in lymph vessels, their hosts in mosquito control plan, the rate of W. bancrofti infec-
these highly endemic areas do not react with a tion in an area declines dramatically. Mosquito con-
strong immunologic response (or display severe trol alone is not highly effective because of the long
symptoms), thus allowing new microfilariae to be reproductive life of the adult worms in human lym-
discharged through the now dilated lymph channels phatics. Behavioral measures, such as wearing
into the blood. The living worms survive for years, clothes that leave little of the body exposed to mos-
producing microfilariae that circulate in their hosts' quitoes, avoiding outdoor gatherings at night, and
blood. These microfilariae soon become part of mos- avoiding outdoor work at peak mosquito biting
quitoes' meals and are passed on in their larval times, also help to reduce transmission of the dis-
stage to other human hosts. As the adult worms ease, but these measures are difficult to implement
eventually die in their tolerant human hosts' lym- (Beaver et al. 1984; Mak 1987; Manson-Bahr and
phatics, fibrosis and calcification of these channels Bell 1987).
disrupt the lymph system. In this chronic phase of Surgical treatment of elephantiasis does not perma-
filarial infection, as lymph channels become ob- nently cure the problem, though removal of thick-
structed, typical elephantoid manifestations de- ened skin and extra tissue from the affected area
velop, especially in the groin and lower extremity. generally relieves the patient's burden. Pressure ban-
People in highly endemic areas are repeatedly in- daging of affected lower limbs helps reduce swelling.
fected over the years and so will manifest various Once a person is infected with W. bancrofti, progno-
stages of filariasis simultaneously. sis depends on the extent and nature of the infection,
Uninfected adults newly arrived in an endemic reexposures to the parasite, and the body's reaction
region generally show an inflammatory response to to the infection. Chronic cases have a poor prognosis.
filarial infection. American troops in the Pacific dur-
ing World War II experienced this problem. Their History and Geography
immune systems reacted quite strongly to the pres-
ence of microfilariae in lymphatics, sending a variety Antiquity Through the Eighteenth Century
of cellular defenders to the affected areas. They sur- The preponderance of evidence indicates that ban-
rounded the worms, ultimately causing stenosis of croftian filariasis existed in the ancient tropical
the lymphatics. Many soldiers developed very painful world. One can find discussions of something called
swelling of the scrotum, spermatic cord, and arms or elephantiasis in the works of many ancient Greek
legs, as well as orchitis, lymphangitis, and filarial and Roman authors, including Celsus, Galen,
fever (acute fever with headache and symptoms re- Aretaeus, Caelius, Aurelianus, Pliny, and Plutarch.
sembling malaria, recurring sometimes for years). The disease many of them were describing, however,
Such a powerful response generally kills the worm, was probably leprosy, which came to be known as
making it impossible for microfilariae to develop and elephantiasis graecorum, to distinguish it from an-
circulate in the blood, but also causing disruption of other form of elephantiasis with a different appear-
the lymphatic system and the early development of ance, elephantiasis arabum, probably bancroftian
elephantiasis. Some researchers believe that ex- filariasis. Leprosy can cause affected parts of the
treme elephantiasis occurs as a result of secondary skin to resemble that of an elephant, but does not
infection with streptococcus or other bacteria. cause the scrotal or leg swelling so characteristic of
Chronic obstructive filariasis can result in lymph filarial infection.
gland enlargement, chyluria (due to obstructed Bancroftian filariasis was probably not endemic in
lymph flow to the thoracic duct above the lymphatic ancient Italy, Greece, or the Mediterranean region
branches of the kidney), lymph scrotum (scrotal in general, except for certain parts of the Nile Delta.
thickening with lymphatic varicosities), hydrocele, Traders and travelers brought knowledge of the con-
and elephantiasis of the legs, scrotum, labia, arms, dition to residents of the region, and an occasional
or (rarely) breasts (Beaver et al. 1984; Manson-Bahr newcomer undoubtedly carried the disease from his
and Bell 1987; Partono 1987). or her home country and suffered from its various
manifestations in the Mediterranean region. An-
Treatment and Control cient descriptions of a medical condition resembling
Several microfilaricidal drugs exist; the most effec- bancroftian filariasis exist not only from Greco-
tive is diethylcarbamazine citrate (DEC), first used Roman writers but also from people in the Nile

Delta, Polynesian islands such as Fiji and the Soci- acceptance of, the microscope in the latter half of the
ety Islands, and India. Late Roman and medieval nineteenth century. Between 1863 and 1900, re-
Arab writers also discussed elephantiasis, the searchers uncovered the basic etiology and epidemi-
former primarily describing leprosy, and the latter, ology of bancroftian filariasis (Manson-Bahr 1959;
including Rhazes, Avicenna, and Albucasis, filaria- Foster 1965; Sasa 1976; Chernin 1983).
sis (Adams 1844, 1846, 1847; Bhishagratna, ed. The first breakthrough in understanding the
1911; Castellani 1919; Hoeppli 1959; Foster 1965; cause of elephantiasis occurred in 1863 when a
Laurence 1967; Sasa 1976). French physician, Jean-Nicolas Demarquay, de-
The historian B. R. Laurence argues that ban- scribed microfilariae (Demarquay 1863). Demar-
croftian filariasis actually originated in Southeast quay withdrew a milky fluid from the swollen
Asia and spread with the migration of people from scrotal sac of an 18-year-old Cuban in 1862 and then
that region to the South Pacific islands (especially again a year later. This latter time, viewing the
Polynesia) and to Africa. To survive, the filarial substance under a microscope, he reported: "Atten-
worm adapted its life cycle to the mosquito vectors tion was drawn above all to a little elongated and
available in these new areas, thus explaining why cylindrical creature" that "had extremely rapid
W. bancrofti shows both diurnal (i.e., microfilariae movements of coiling and uncoiling" (Demarquay
present in peripheral blood during the daytime) and 1863). Demarquay and his colleagues found these
nocturnal periodic strains. The elephantiasis de- worms and their eggs infivesuccessive preparations
scribed by early Indian writers, Laurence argues, but found none once the scrotal fluid had cooled
was actually caused by B. malayi (another filarial down. He could not explain the worms' presence in
worm, much more limited in its distribution) rather the microscopic preparation, but hoped that there
than by W. bancrofti. The continued migration of would be some scientific value for others in publish-
tropical peoples and the opening of the tropical ing the case.
world to trade over the past 300 to 400 years, plus Exactly 4 years after Demarquay's discovery, Otto
the adaptability of W. bancrofti to a variety of mos- Eduard Heinrich Wucherer, a Portuguese-born physi-
quito vectors, resulted in the spread of the parasite cian of German parentage who practiced in Bahia,
throughout the tropics, including China and India Brazil, found "some threadlike worms" in a urinary
(Laurence 1968, 1977). Filariasis came to the New blood clot of a woman suffering from hematuria
World, most likely as a result of the African slave (Wucherer 1868). Theodor Bilharz had discovered a
trade. That trade, conducted by white Europeans, worm in Egypt in 1852 that caused hematuria (Schis-
brought concentrations of infected black Africans to tosoma haematobium); Wucherer was investigating
slave depots on West Indian islands like Barbados, the urine of Brazilian hematuria patients to learn
where they were sold and redistributed to other West whether the cause of the disease was the same in the
Indian islands, or to the North and South American New World. What he saw under the microscope dif-
mainlands. A legacy of this black African slave fered greatly from the schistosomes Bilharz had de-
trade in the United States was the establishment of scribed. Two years later, after seeing these worms in
a focus of bancroftian filariasis at Charleston, South two more hematuric patients and finding that he
Carolina, and the surrounding "Low Country," could not identify their species from the books on
which survived until the early twentieth century human parasites that he possessed, Wucherer pub-
(Savitt 1977; Chernin 1987; Reynolds and Sy 1989). lished his story "as an incentive for some of my
colleagues, better qualified and more fortunate than
Seventeenth Through Nineteenth Century I, to attempt to shed light on a disease, the etiology
Seventeenth-, eighteenth-, and nineteenth-century of which is still enigmatic today" (Wucherer 1868).
European observers in tropical lands described nu- In March of 1870, in a different part of the tropical
merous cases of leg and scrotal elephantiasis, and world, India, Timothy Richards Lewis found worms
some of endemic hydrocele and of lymph scrotum. A like those Wucherer had described. An 1867 medical
few even recognized and traced the development of graduate of the University of Aberdeen, Scotland,
elephantiasis from fever through lymphangitis and Lewis was treating a 25-year-old East Indian male
lymphadenitis, to gradual swelling of a limb or scro- suffering with chyluria. That patient left the hospital
tum. Though these writers located the seat of the before Lewis could study his condition further, but a
disease in the lymphatics, none could identify the second patient, a woman with hematuria and chylous
cause (Castellani 1919; Laurence 1970). That discov- urine, entered the hospital a few days later. Lewis
ery had to await refinements to, and physicians' now took a step beyond Demarquay and Wucherer

and removed blood from the patient'sfingerand stud- Andrews University in Scotland, moved to Queens-
ied it microscopically. He found what he called land in 1864 and found a number of patients with
filariae in this blood, just as he found them in the lymphatic conditions, though none with elephantia-
urine. Lewis's report of these and other patients, pub- sis. His first adult worm came from a patient with a
lished in 1872, documented for the first time both the lymphatic abscess of the arm. He obtained another
presence of microfilariae and the presence of any four from a hydrocele of the spermatic cord. He for-
microorganism in human peripheral blood. He also warded these specimens in 1877 to Cobbold in Lon-
described, but could not explain, the disappearance of don, the leading British helminthologist of the time.
microfilariae from the blood. Lewis (1872) named the The latter published Bancroft's cover letter with his
organism Filaria hominis sanguinis. own commentary in the Lancet (Cobbold 1877).
All three of these filarial researchers knew they Cobbold had previously encouraged Bancroft to look
had identified an immature form of the filarial for the adults after Bancroft sent him, through a
worm. Nor were they the only ones who saw the former teacher, immature filariae obtained from
microfilariae in chylous urine. Both T. Spencer these patients. It was Cobbold who suggested nam-
Cobbold of London and M. Robin of Reunion Island ing the filarial worm for Bancroft. A co-worker of
reported similar findings in the early 1870s. Wucherer wrote to the Lancet shortly after Cobbold's
The man who brought together the various bits of article appeared, suggesting that Wucherer de-
knowledge published about human filarial infection served credit for discovering the parasite. Both physi-
and produced a useful theory was Patrick Manson. cians were so honored, and the filaria is known as
Born in Aberdeenshire and an 1866 medical gradu- Wuchereria bancrofti (Foster 1965).
ate of Aberdeen University, Scotland, Manson spent How did the wormfindits way into humans? Man-
much of his early professional life, beginning in son continued his work in China and made a key
1866, as a medical officer in the Chinese Imperial suggestion in an 1877 essay (not published until
Maritime Customs Service. He treated many Chi- 1878), the same year Cobbold announced the discov-
nese elephantiasis patients, recognized and named ery of the adult worm in human lymphatics (Manson
the condition called "lymph scrotum," and devised 1877). The Filaria sanguinis hominis embryos, Man-
an operation to remove scrotal tumors. During a 1- son argued, could not develop, mature, and enter the
year leave in England in 1875, he read the available bloodstream without overwhelming their human
literature on the conditions he had been treating, host by their sheer number. Using his knowledge of
including descriptions of lymph scrotum in India, the known life cycles of animal parasites and of
the relation of lymph scrotum to elephantiasis, and certain human parasites, Manson suggested and
Lewis's papers on filarial worms in the blood and then demonstrated that the mosquito was the
lymph of patients with tropical chyluria (Foster "nurse" of the filarial embryo. The insect ingested
1965). In articles published in 1876 and 1877 in the filariae in its blood meal and the young worm devel-
China Imperial Maritime Customs Medical Reports, oped in the body of this second host. When the mos-
Manson presented case studies to show that lymph quito died, usually on stagnant water a few days
scrotum, elephantiasis, and tropical chyluria were after feeding, Manson continued, the filariae es-
etiologically related, all caused by the filarial worm caped into the water and were ingested by humans
described by Lewis, seated in lymphatics (Manson drinking the now contaminated liquid. The need for
1876-7). He apparently knew nothing of Demar- a certain mosquito host, in addition to the human
quay's or Wucherer's articles, published in journals host, Manson concluded, explained "the limitation of
as poorly circulated as the one in which he himself the distribution of elephantoid diseases to certain
published. districts and zones of the earth's surface . . . where
Manson tried in vain to obtain an adult filarial the mosquito flourishes" (Manson 1877).
worm from newly deceased patients. Thwarted by Another filarial mystery remained to be solved:
the Chinese people's reluctance to allow autopsies of the unpredictable disappearance and reappearance
humans, Manson suggested in print that physicians of worm embryos from the blood of patients known to
in India, where the prejudice against dissection was harbor the parasite. Manson employed two assis-
much less, seek out adult worms in patients who had tants to take blood around the clock from a filariasis
died with these conditions (Foster 1965). The first patient. He discovered that the number of micro-
person to demonstrate the presence of adult filariae filariae grew and shrunk in a regular diurnal pat-
in humans practiced, not in India, but in Australia. tern, the embryos reaching their peak presence in
Joseph Bancroft, an 1859 medical graduate of St. blood in the hours just before and after midnight. He

concluded, in his 1879 article (published in 1880), Chernin, Eli. 1983. Sir Patrick Manson's studies on the
that "[t]he nocturnal habits of the Filaria sanguinis - transmission and biology of filariasis. Reviews of Infec-
hominis are adapted to the nocturnal habits of the tious Diseases 5:148—66.
mosquito, its intermediary host, and is only another 1987. The disappearance of bancroftian filariasis from
of the many wonderful instances of adaptation so Charleston, South Carolina. American Journal of
Tropical Medicine and Hygiene 37: 111—14.
constantly met with in nature" (Manson 1879).
Cobbold, T. S. 1877. Discovery of the adult representative
What happened to the filariae during the rest of of microscopic filariae. Lancet 2: 70-1. [Includes letter
the day? Manson asked that question in his 1879 from Joseph Bancroft reporting discovery of adult
article but could not answer it for almost another 20 filarial worms in man.] [In Tropical medicine and
years. In February 1897, Manson, now in London, parasitology: Classic investigations, 2 vols. B. H.
had the opportunity to study the organs of a patient Kean, Kenneth E. Mott, and Adair J. Russell, eds.
with filariasis who had committed suicide at 8:30 in 1978. Vol. 2, 392-4. Ithaca and London.]
the morning, presumably just after the worms would Demarquay, Jean-Nicolas. 1863. Note on a tumor of the
have left the peripheral blood for the day. Postmor- scrotal sac containing a milky fluid (galactocele of
tem examination revealed huge numbers of the em- Vidal) and enclosing small wormlike beings that can
bryo parasites in the small blood vessels of the lungs be considered as hematoid helminthes in the embryo
and others in the large pulmonary blood vessels stage. Gazette Medicale de Paris 18: 665-7. [Trans,
(Manson 1899). from French in Kean etal., eds., 1978. Tropical medi-
cine and parasitology, Vol. 2, 374—7.]
Over the next few years, Manson helped revise the
Foster, W. D. 1965. A history of parasitology. Edinburgh
answer to a question he had asked in 1877: How did and London.
the filariae pass from mosquitoes to humans? Man- Grassi, B., and G. Noe. 1900. The propagation of the
son's earlier answer, that humans ingested them filariae of the blood exclusively by means of the punc-
with contaminated drinking water, was challenged ture of peculiar mosquitoes. British Medical Journal
shortly after it was suggested. The work of Thomas 2: 1306-7.
Bancroft, Joseph Bancroft's son in Australia, and of Hoeppli, R. 1959. Parasites and parasitic infections in early
Manson's protege, George C. Low, who used the mos- medicine and science. Singapore.
quito specimens Bancroft sent to Manson, published Laurence, B. R. 1967. Elephantiasis in Greece and Rome
in 1900, suggested that filarial embryos exited from and the Queen of Punt. Transactions of the Royal
the mosquito's proboscis and entered human skin Society of Tropical Medicine and Hygiene 61: 612—13.
when the insect was in the act of biting (Low 1900). 1968. Elephantiasis and Polynesian origins. Nature 219:
561-3.
That idea was confirmed by B. Grassi and G. Noe
1970. The curse of Saint Thomas. Medical History 14:
(1900) later that year. 352-63.
British physicians working in various tropical 1977. The evolution of filarial infection. In Medicine in a
colonies of the empire had made almost every break- tropical environment, ed. J. H. S. Gear, 644—56. Cape
through in uncovering the mystery of filarial infec- Town and Rotterdam.
tion during the previous 40 years. By 1900 the Lewis, Timothy Richards. 1872. On a hematozoon inhabit-
medical world had a basic understanding of a dis- ing human blood, its relation to chyluria and other
ease that had plagued and puzzled people since an- diseases. Appendix to the eighth annual report of the
cient times. sanitary commissioner with the government of India,
Todd L. Sauitt 1-50. [In Kean et al., eds., 1978. Tropical medicine
and parasitology, Vol. 2, 379-85.]
Low, George Carmichael. 1900. A recent observation on
filaria nocturna in Culex: Probable mode of infection
Bibliography of man. British Medical Journal 1: 1456—7. [In Kean
Adams, Francis. 1844, 1846, 1847. The seven books of et al., eds., 1978. Tropical medicine and parasitology,
Paulus Aegineta, 3 vols., II, 6-15. London. Vol. 2, 402-5.]
Beaver, Paul Chester, Rodney Clifton Jung, and Eddie Mak, J. W. 1987. Epidemiology of lymphatic filariasis. In
Wayne Cupp. 1984. Clinical parasitology, 9th edition. Filariasis (Ciba Foundation Symposium No. 127), 5 -
Philadelphia. 14. Chichester, U.K.
Bhishagratna, Kaviraj Kunjalal, trans, and ed. 1911. An Manson, Patrick. 1876—77. Filaria sanguinis hominis.
English translation of the Sushruta Samhita, 3 vols., Medical Reports, China Imperial Maritime Customs
II, 79-84. Calcutta. 13:30-8. [In Kean et al., eds., 1978. Tropical medicine
Castellani, Aldo. 1919. Manual of tropical disease, 3d edi- and parasitology, Vol. 2, 385-7.]
tion, 1595-1618. London. 1877. Further observations on Filaria sanguinis homi-

nis. Medical Reports, China Imperial Maritime Cus-
toms 14: 1-26. [In Kean et al., eds., 1978. Tropical VHI.55
medicine andparasitology, Vol. 2, 387-92.] Fungus Infections (Mycoses)
1879. Additional notes on Filaria sanguinis hominis and
filaria disease. Medical Repots, China Imperial Mari-
time Customs 18: 36-9. [In Kean et al., eds., 1978.
Tropical medicine and parasitology, Vol. 2, 394—5.] Although today, some 200 fungi are established as
1899. On filarial periodicity. British Medical Journal 2: pathogenic for humans, causing a wide range of di-
644—6. [In Kean et al., eds., 1978. Tropical medicine verse mycoses (with an incidence measured in mil-
and parasitology, Vol. 2, 400-2.] lions and a worldwide distribution), through the
Manson-Bahr, P. E. C. 1959. The story of Filaria bancrofti. mid-nineteenth century, only two human diseases
Journal of Tropical Medicine and Hygiene 62: 53-61, (or rather disease complexes) caused by fungi were
85-94, 106-17, 138-45, 160-73. [Note: Be sure to generally recognized. These were ringworm and
read Chernin 1983, for corrections to these Manson- thrush, known since Roman times. Two important
Bahr articles.] additions came at the end of the century: mycetoma
Manson-Bahr, P. E. C, and D. R. Bell. 1987. Manson's of the foot (Carter 1874) and aspergillosis (Lucet
tropical diseases, 19th edition. London.
1897; Renon 1897).
Partono, Felix. 1987. The spectrum of disease in lymphatic
filariasis. In Filariasis (Ciba Foundation Symposium Fungi were the first pathogenic microorganisms
No. 127), 15-31. Chichester, U.K. to be recognized. Toward the end of the eighteenth
Reynolds, Wade D., and Francisco S. Sy. 1989. Eradication century and the opening years of the nineteenth,
of filariasis in South Carolina: A historical perspec- they had been shown experimentally to cause dis-
tive. Journal of the South Carolina Medical Associa- ease in plants and insects, and during the 1840s both
tion 85: 331-5. ringworm and thrush were shown to be mycotic in
Sasa, Manabu. 1976. Human filariasis: A global survey of origin. For a short period, fungi were blamed for
epidemiology and control. Tokyo. causing many diseases. Cholera, for example, was
Savitt, Todd L. 1977. Filariasis in the United States. Jour- attributed to fungi. But with the recognition of the
nal of the History of Medicine and Allied Sciences 23: major role played by bacteria (and later, viruses) in
140-50. the etiology of human disease, fungi were neglected
Wucherer, Otto Eduard Heinrich. 1868. Preliminary re-
and medical mycology became very confused. It has
port on a species of worm, as yet undescribed, found in
the urine of patients with tropical hematuria in Bra-
been only since the 1930s, with the deployment of
zil. Gazeta Medica deBahia 3:97—9 (trans,fromPortu- trained mycologists to work in conjunction with clini-
guese). [In Kean et al., eds., 1978. Tropical medicine cians, that the identity of the pathogenic fungi has
and parasitology, Vol. 2, 377-9.] been clarified, and studies on their ecology have
done much to elucidate epidemiological problems. In
general, the geographic distribution of mycoses
(which at first tended to coincide with that of medi-
cal mycologists) has been established, and the rela-
tion of mycoses to other human diseases has been
brought into perspective.
Some of the fungi causing human disease show
clear adaptations for the pathogenic state, whereas
others do not, and it is probable that none is depen-
dent on a human or animal host for survival. Most
are also pathogenic for animals, both domesticated
and wild, which are also subject to mycoses caused
by related species able to induce human infections.
Many fungi pathogenic for humans are apparently
members of the normal fungus flora of the environ-
ment, and their pathogenicity is regarded as "oppor-
tunistic" or "iatrogenic" when infection is rendered
possible by the side effects of therapy.

VIII.55. Fungus Infections (Mycoses) 731
Classification could be accommodated in the three genera: Mi-

Mycoses (which exhibit a wide range of symptoms) crosporum, Trichophyton, and Epidermophyton. To-
have often been named according to the part of the day the number of ringworm fungi accepted is of the
body affected (e.g., bronchomycosis, dermatomy- order of 30. At first, only asexual spore states of
cosis, tinea capitis, ringworm of the scalp, athlete's these pathogens were known, but later sexual states
foot) or the name of the pathogen (e.g., aspergillosis, were obtained, and evidence provided that dermato-
cryptococcosis, dermatophytosis, rhinosporidiosis), phytes are closely related to a group of predomi-
and they have been categorized as cutaneous, subcu- nantly soil fungi.
taneous, systemic, opportunistic, and iatrogenic, al- Two historical landmarks in the treatment of ring-
though these divisions are not mutually exclusive. worm were the introduction of X-ray epilation for
In this study, for convenience, mycoses are consid- the therapy of head ringworm in the opening years
ered under ringworm, candidiasis (including thrush, of this century and the introduction of the antibiotic
which is oral candidiasis), systemic mycoses, and griseofulvin in 1958 as an orally administered
opportunistic and iatrogenic mycoses. antimycotic drug.
Ringworm (Tinea, Dermatophytosis) Distribution and Incidence

The geographic distribution of the ringworm fungi is
History interesting. In Sabouraud's time the distribution cor-
Favus (Latin for "honeycomb"), a distinctive type of responded to that of interested dermatologists. Now
ringworm because of the characteristic scutula, was the ringworm fungi of most countries have been
described by Celsus in the first century, A.D., in his surveyed, or at least sampled, so that a more accu-
De Medicina. He called it porrigo, a term also used rate knowledge of their geographic distribution is
by Pliny in his Historia Naturalis of the same cen- available. Some, such as Trichophyton mentagro-
tury and by dermatologists up to the nineteenth phytes (causing tinea pedis and so forth) and
century. It is now, however, obsolete, having been Epidermophyton floccosum (tinea cruris), occur
replaced by tinea (derived from Tineola, the generic worldwide.
name of the clothes moth). Celsus also described the Microsporum audouinii (tinea capitis; the classi-
inflammatory lesion of some forms of ringworm, cal cause of ringworm in children), which appears to
which has been known ever since as the "kerion of have originated in Europe, is now endemic in North
Celsus." America. Although frequently introduced by Euro-
Not until the mid-1840s was the mycotic nature of pean children to the tropics, it has never established
favus recognized by three independent workers: J. L. itself there in the indigenous population. Likewise
Schoenlein and Robert Remak in Berlin, and David Trichophyton concentricum (tinea imbricata) is en-
Gruby in Paris. The latter also differentiated mi- demic in Southwest Asia and the South Sea islands,
crosporosis and the ectothrix and endothrix tricho- where it was first recorded by William Dampier in
phytosis, which he showed to be caused by distinct 1686 when circumnavigating the globe. It has other
fungi. minor endemic centers in South America, and, al-
A period of mycologic confusion followed, compli- though frequently seen in Europe on returning trav-
cated by the difficulty of determining the life histo- elers, it has never become endemic there. By con-
ries of the pathogens (largely due to deficiencies in trast, Trichophyton rubrum, believed to have been
culture technique) and settling the question as to introduced into the United Kingdom by troops re-
whether there was one ringworm fungus or many. turning from the Boer War, is now widespread in
Gruby's findings had been forgotten and had to be north temperate regions.
rediscovered during the 1890s by Raymond Sabour- In similar fashion, Trichophyton ferrugineum es-
aud, a famous Parisian dermatologist, who consoli- tablished itself in western parts of the Soviet Union,
dated his researches in an impressive monograph after being introduced by soldiers returning from
published in 1910. Many ringworm fungi were de- the Far East. Classical favus in western Europe is
scribed and classified variously according to the de- caused by Trichophyton schoenleinii, but typically
gree of emphasis placed by different workers on by Trichophyton violaceum in North Africa and the
mycologic and clinical features. Some thousand dif- Mediterranean basin. Microsporum canis (tinea
ferent names had been proposed up to 1934 when C. canis [cat and dog ringworm], tinea capitis, and
W. Emmons, a mycologist by training, in the United tinea corporis), coextensive with cats and dogs as
States showed that, mycologically, the many species pets, has become endemic in New Zealand in feral

cats. Human infections are also contracted by con- favorable conditions. Numerous surveys have shown
tact with ringworm in cattle (Trichophyton verru- that many apparently normal individuals carry C.
cosum), horses, and other farm animals. Mi- albicans: 10 percent, in the mouth; about the same
crosporum gypseum (which could be considered as an proportion of women, in the vagina (with higher
opportunistic dermatophyte) has a worldwide distri- values in pregnant women); and 25 percent, in the
bution, the outbreaks in humans usually being spo- feces and gut. Although C. albicans has occasionally
radic, short-lived, and sometimes traceable to a been isolated from soil, from hospital bedding (the
group of people having access to the same soil in incidence of Candida in hospital patients is often
which the pathogen is an inhabitant. high), and from a wide range of animals (especially
domestic animals and birds), it is clear that most
Candidiasis (including "Thrush") human infections have an endogenous origin. Infec-
Reports and studies of the many and diverse manifes- tion (clinical candidiasis) seems always to be deter-
tations of candidiasis caused by Candida albicans mined by predisposing factors that may be environ-
and other species of Candida (e.g., Candida guillier- mental: For example, having the hands frequently
mondii, Candida krusei, Candida stellatoidea, Can- wet favors paronychia (candidiasis of the nail fold).
dida tropicalis) have made a major contribution to Age, debility, dentures, and drug therapy also can
the literature of medical mycology, as they still do. predispose one to infection.
As for ringworm, a stable taxonomic base was neces- The patenting of the orally administered antibi-
sary to underpin both clinical and microbiological otic nystatin in 1956 was a notable contribution to
observations and research on this mycotic complex the therapy of candidiasis, which has been the sub-
because C. albicans was described as new on a num- ject of several monographs.
ber of occasions and acquired some 90 specific names
distributed among a dozen genera. Much confusion Systemic Mycoses
resulted. One taxonomic error that the reader must The pathogens of the five systemic mycoses to be
still remember when consulting the earlier litera- considered all show specialization for parasitism.
ture is the assignment back in 1890 of the thrush All are dimorphic - that is, the saprobic state is
fungus to the genus Monilia because "moniliasis" mycelial (filamentous) and the pathogenic phase is
became the generally accepted, worldwide name for unicellular and yeastlike. It is possible to effect the
candidiasis. It was mainly a group of yeast special- mycelial-to-yeast conversion in vitro. For Blas-
ists working in the Netherlands who clarified the tomyces dermatitidis (blastomycosis), the transfor-
taxonomy; the genus Candida was proposed in 1923. mation is temperature dependent; for the others,
nutritional adjustments are also necessary. On first
Thrush (Oral Candidiasis) description there was a tendency to assign these
This disease (infection of the mucous membrane, pathogens to the Protozoa.
especially of the mouth) in infants was referred to in
the Hippocratic corpus (400 B.C.) and later by Galen Coccidioidomycosis
and other classical writers under the heading The first case of this disease was described from
"aphthae." Over the centuries, references to thrush Argentina by Alejandro Posadas in 1892. About the
in the young, as a feature of terminal illness and as a same time a case was also studied in California by E.
vaginal infection in women, continued, with the Rixford and T. C. Gilchrist, who attributed the cause
clinical descriptions being given increasing preci- to a protozoan, which, in 1896, they named
sion (see Higgs 1972). Candidiasis, like ringworm, Coccidioides immitis. In 1905, however, a fellow
was demonstrated to be mycotic by three indepen- American, W. Opuls, established its mycotic nature.
dent workers in the 1840s: B. Langenbeck in Berlin, It was known only as a rather rare, acute, or chronic
F. T. Berg in Stockholm, and Gruby in Paris. Berg, disseminating and often fatal disease. In 1938,
who had studied under Gruby, subsequently pub- Myrnie A. Grifford and E. Dickson, independently,
lished on thrush in infants and in 1844, J. H. Ben- and then in collaboration, established that "valley
nett described in Edinburgh what was probably C. fever," prevalent in the San Joaquin Valley of Cali-
albicans from the human lung. fornia, was a mild form of coccidioidomycosis. Fur-
A wide range of pathological conditions attributed ther investigations showed mild, often subclinical,
to Candida were subsequently recorded; virtually respiratory Coccidioides infection to be widespread
all parts of the body, with the notable exception of in arid parts of California and neighboring states
the hair, were susceptible to such infection under and to induce lifelong immunity to subsequent at-

tack. This immunity is demonstrable by a positive Blastomycosis was first described by Gilchrist in
skin test with an antigen (coccidioidin) prepared the United States in 1894, and paracoccidioidomyco-
from cultures of the pathogen. sis, by Adolfo Lutz in Brazil during 1908. Neither
C. immitis was isolated from soil, and when Em- has a mild form such as that characteristic of
mons showed desert rodents to be infected, they were coccidioidomycosis and histoplasmosis, and though
atfirstthought perhaps to constitute an animal reser- there have been a few records of both pathogens
voir of infection. But it soon became clear that these from soil, the natural habitats of both these fungi
rodents, like humans, were subject to infection by have not been established with certainty.
this soil-inhabiting fungus. It also became clear that Paracoccidioidomycosis is confined to Central and
the dry, airborne (or dustborne) spores of the patho- South America, where it has been the subject of
gen were extremely infectious (there have been many intensive study. Blastomycosis is endemic to the
accidental laboratory infections) and that coccidioido- western and southeastern states of the United
mycosis could be contracted, for example, by servic- States, where epidemics occur; there are also records
ing automobiles that had been driven through areas of the disease from a number of tropical African
where the mycosis was endemic. In addition, dust countries.
storms were found to increase the rate of conversion
from negative to positive skin tests with coccidioidin Sporotrichosis
in local inhabitants and their domestic animals. It This disease shows certain parallels with mycetoma
may be noted, that although light- and dark-skinned but is included here because the causal pathogen is
peoples appear to be equally susceptible to C. immitis dimorphic. It is a cutaneous and subcutaneous infec-
infection, the disease is more likely to be systemic intion characterized by the development of nodular le-
those with pigmented skin. Filipinos and blacks, sions, often in a series affecting successive lymph
along with the Portuguese, are those chiefly em- nodes. Infection is frequently initiated by a lesion,
ployed in agriculture in the districts where coccidioi-often of the hand. It is caused by Sporothrix schenckii
domycosis is endemic. and was first described in the United States by B. R.
Coccidioidomycosis is endemic and of high inci- Schenck in 1898. Subsequently many cases were re-
dence in warm dry regions (the Lower Sonoran Life ported from Europe, especially France, where the
Zone) of the United States and Mexico and also in disease was the subject of a massive monograph, Les
parts of Central and South America where the clima- Sporotrichoses, by C. L. de Beurmann and H.
tic conditions are similar. Records from other parts Gougerot in 1912. Sporotrichosis, which is sporadic in
of the world are of doubtful validity. north temperate regions, has also been recorded in
Central and South America. In Uruguay, J. E.
Histoplasmosis Mackinnon (1949) attempted to correlate incidence of
This disease (Histoplasma capsulatum) shows many the disease with the weather, and obtained evidence
parallels with coccidioidomycosis and may be viewed that infection occurred during periods of moist warm
as the humid region equivalent. At first considered a weather, which he suggested encouraged growth of
rare protozoan disease, it has been shown to be the pathogen on plant material from which humans
mycotic, and to have a mild form affecting millions are infected. S. schenckii is one of the rare fungus
of the inhabitants of the midwestern United States. pathogens ofhumans that has been shown experimen-
The pathogen shows a predilection for bird (chicken, tally to cause disease in plants (carnations). The larg-
starling) and bat droppings. est outbreak of sporotrichosis ever recorded was in
the Witwatersrand gold mines in South Africa during
Blastomycosis and Paracoccidioidomycosis 1941-3, when approximately 3,000 miners were in-
The former (North American blastomycosis), caused fected. The epidemic was brought under control by
by B. dermatitidis, and the latter (South American potassium iodide therapy for the men affected and
blastomycosis), caused by Paracoccidioides brasilien- fungicidal treatment of the mine timbers from which
sis, are both chronic granulomatous diseases of the the infection was contracted.
skin and internal organs, characterized by budding
cells of the pathogen in the infected tissues. The two Opportunistic and Iatrogenic Infections
were at first confused both with each other and with To categorize some fungal infections as opportunistic
cryptococcosis (called "European blastomycosis" or is convenient, if artificial. Most fungi pathogenic for
"torulosis" and caused by Cryptococcus neoformans), humans, even those causing such significant mycoses
but these three mycoses are now well differentiated. as coccidioidomycosis and histoplasmosis, seem to

have some natural habitat in the environment and for mycetoma caused by actinomycetes. Today the
infect humans only incidentally. Candida infections terms "Eumycetoma" (or "Eumycotic mycetoma")
are different in that they are endogenous, and some and "Actinomycetoma" (or "Actinomycotic myce-
types of ringworm are also to some extent opportunis- toma") are preferred. Classical actinomycosis caused
tic. The mycoses to be considered next include exam- by the anaerobic Actinomyces Israeli, which gives rise
ples of infection resulting from the exposure of a to yellow grains ("sulfur granules"), is excluded from
susceptible individual to the normal fungus flora of the complex.
the environment, and attention is drawn to the in- There have been many publications on the inci-
creased risk shown by compromised patients. dence and etiology of mycetoma, which occurs most
frequently in a band of the tropics north of the
Mycetoma equator extending from India, across Africa, to Cen-
This disease is a well-defined clinical entity charac- tral and South America. Incidence is particularly
terized by swelling that affects the subcutaneous high in India, the Sudan, and Senegal (where M.
tissues, with sinuses discharging grains or granules mycetomatis predominates) and Mexico (where
of the pathogen, which vary in color from white actinomycetoma predominates). All these regions
through yellow, red, and brown to black. The foot is are hot and arid. Pseudallescheria boydii seems to
most frequently involved ("Madura foot"), but the favor more humid conditions, with species of
hand or other part may be infected. Its geographic Nocardia responsible for mycetoma in temperate
distribution is mainly tropical. Europe and North America. Madurella grisea is lim-
The condition was first recorded in the Indian Vedic ited to South America, whereas Cephalosporium in-
Medical treatises (c. 2000-1000 B.C.) as padaaval- fections are cosmopolitan.
mika ("foot ant-hill") and first described in modern It was early thought probable that infection was
times from southern India by members of the Indian initiated by injury, and a correlation between
Medical Service during the mid-nineteenth century. mycetoma and injury from plant thorns has fre-
H. Vandyke Carter, who coined the designation quently been made. Sometimes the pathogen may
"mycetoma," wrote a monograph on the disease in have been growing as a saprobe on the thorns {.Lepto-
1874. Carter suspected the disease to be mycotic and sphaeria senegalensis and Pyrenochaeta romeroi
submitted material to the Rev. M. J. Berkeley, the have been isolated from such sites, and M. myce-
leading British mycologist of the time, who described tomatis will grow on dead wood in sterile water); or
a now unidentifiable fungus he obtained from the the thorn may provide the point of entry for an
material as a new species. From the turn of the cen- organism present in the environment (dry granules
tury onward, more than 25 diverse fungi (including from mycetoma have a long survival time), espe-
representatives of the genera Acremonium, Asper- cially in soil from which pathogenic species of
gillus, Curvularia, Leptosphaeria, Madurella, and Nocardia and P. boydii have been isolated. All this
Pseudallescheria) and actinomycetes (aerobic species evidence points to mycetoma being a typical opportu-
of Actinomadura, Nocardia, and Streptomyces), re- nistic infection.
sponsible for the condition, were identified by work-
ers in North Africa and elsewhere, with the color of Cryptococcosis
the grains often providing a clue to the identity of the This disease is a subacute or chronic infection of the
pathogen. lungs, skin, or other parts, especially the central
Carter distinguished "melanoid" and "ochroid" nervous system, caused by the yeast Cryptococcus
mycetoma, and, as his illustrations show, his black- neoformans, which is widely distributed in nature
grained form was caused by the fungus that E. and is sometimes the dominant organism in the drop-
Brumpt in 1905 taxonomized as Madurella myceto- pings and debris of pigeon roosts. Although the pi-
matis, which is the most important cause of myce- geon is not infected and the yeast survives passage
toma. In 1894, H. Vincent had described and named through the bird, human cases have frequently been
the actinomycete that he had isolated from yellow- associated with inhalation of the pathogen when
grained mycetoma from Algeria as Streptothrix clearing out old pigeon roosts. The most frequent
madurae (now designated Actinomadura madurae). infections are subclinical and self-limiting, with fa-
Later, when differentiating the two classes, research- tal and more generalized infection occurring mostly
ers A. J. Chalmers and R. G. Archibald at the Well- in debilitated patients or in those "compromised" by
come Laboratory for Tropical Medicine at Khartoum drug treatment.
in the Sudan introduced the term "madura mycosis" First recorded in Europe in 1894, human cryptococ-

cosis has a worldwide distribution. In 1946, L. B. losis were those of French pigeon squab feeders in
Cox and Jean C. Tolhurst published a monograph, the late 1890s, who chewed in their own mouths the
based on 13 Australian cases termed "torulosis" grain used for fattening the birds. Interest in
caused by Torula histolytica; later a very comprehen- aspergillosis in France was then at its height.
sive study of the disease was published by M. L. Several other species of Aspergillus are patho-
Littman and L. E. Zimmerman (1956). genic. Aspergillus niger is often associated with in-
fection of the ear, whereas aspergillomas or "fungus
Rhinosporidiosis balls" sporulating growths of the pathogen in lung
This disease, an infection of mucous tissue, espe- tissues or cavities are not uncommonly associated
cially of the nose, results in the development of large with pulmonary disease.
polyps and is exceptional among mycoses in that the Diverse mucoraceous fungi are regularly, if spo-
causal agent, Rhinosporidium seeberi, has not been radically, recorded in north temperate countries as
cultured and its taxonomic position is uncertain. responsible for human infections, especially of the
Outbreaks of the disease, which attacks both hu- rhino-facial-cerebral region when the outcome is fa-
mans and animals (especially bullocks set to the tal. Debility is a predisposing factor.
plough), have been associated with water and the
soil. Rhinosporidiosis was first reported from Argen-
tina in 1900, but it occurs sporadically throughout Dependent Mycoses
the tropics, the highest incidence being in southern The attribution of disease to the human "constitu-
India and Sri Lanka. A monograph was published by tion" has a long history. Even at the beginning of the
J. H. Ashworth (1923) in Edinburgh from a case nineteenth century, dermatologists, unable to accept
involving an Indian student at the university. the concept of pathogenicity, were attributing ring-
worm in children to constitutional factors, and nutri-
AspergiUosis and Mucormycosis tion does apparently affect symptom expression. Dur-
Species of Aspergillus and mucoraceous fungi are a ing World War II, for example, ringworm symptoms
disappeared in European prisoners held under star-
conspicuous and ubiquitous component of what has
been called "common mold." They are therefore not vation conditions by the Japanese, only to reappear
infrequently found as contaminants of cultures from on the restoration of a full diet. Also, tinea capitis
morbid material and may be mistaken for patho- (Af. audouinii) in children, although a persistent
gens. On the other hand, human infections by these infection, resolves spontaneously at puberty for rea-
and similar molds do occur sporadically and have sons not yet fully understood. Tinea pedis has been
claimed as an occupational disease of coal miners
been reported worldwide.
and soldiers who wear heavy boots. It is well estab-
The pathogenicity of Aspergillus fumigatus is well lished that Candida infection is affected by preg-
established. It is widespread in the environment; nancy, and that metabolic disorders such as diabetes
found on decaying vegetation, it has spores that are are also frequently associated with the disease.
readily airborne. Because its growth is favored by
high temperatures, and it is customary to incubate Recently, iatrogenic mycoses have been aggra-
bacterial cultures at 37° C (a temperature detrimen- vated by or have resulted from the use (or abuse) of
tal to many common molds); A. fumigatus frequently antibacterials, which can cause a change in oral
occurs as a contaminant of cultures from sputum conditions whereby bacterial competition is elimi-
and other pathological material. Thus, its signifi- nated and candidosis is thus induced. In addition,
cance, when it is detected, is often uncertain, and the introduction of heart surgery and organ trans-
clinical and other evidence must be considered in its plantation following the use of immunosuppressive
detection. drugs has resulted in Candida endocarditis and
A. fumigatus is able to cause fatal infections, par- mycotic septicemia so that antimycotic therapy is
ticularly in birds in which it was first recorded early now a routine supplementary practice.
in the nineteenth century, lining the airsacs with a Geoffrey C. Ainsworth
profuse sporulating growth. J. B. G. W. Fresenius in
1850 proposed the name Aspergillus fumigatus Bibliography
based on an isolate from a bustard (Otis tarda). Ru- Ainsworth, G. C. 1987. Introduction to the history of medi-
dolf Virchow in Germany in 1856 described human cal and veterinary mycology. Cambridge.
pulmonary aspergillosis caused by the same species. Ashworth, J. H. 1923. On Rhinosporidium seeberi
The classical cases of human pulmonary aspergil- (Wernicke, 1903) with special reference to sporulation

and affinities. Transactions of the Royal Society, Edin-
burgh 53: 301-38. VIII.56
Austwick, P. K. C. 1965. Pathogenicity. In The genus
Aspergillus, ed. K. B. Raper and D. I. Fennell, 82-
Fungus Poisoning
126. Baltimore.
Carter, H. V. 1874. On mycetoma or the fungus disease of
India. London.
Two categories of fungus poisoning may be distin-
Connant, N. E, et al. 1971. Manual of clinical mycology, 3d
edition. Philadelphia. guished: (1) mycetism, the result of eating poisonous
Emmons, C. W. 1934. Dermatophytes: Natural grouping fungi mistaken for the edible variety (which has a
based on the form of the spores and accessory organs. long history and a worldwide incidence), and (2)
Archives of Dermatology and Syphilology 30: 337-62. mycotoxicoses, the result of inadvertent ingestion of
Emmons, C. W., C. H. Binford, and J. P. Utz. 1971. Medical food containing toxins produced by fungi. The latter,
mycology. 3rd ed. Philadelphia. although also of worldwide incidence, has (with the
Fiese, M. J. 1958. Coccidioidomycosis. Springfield, 111. exception of ergotism) been generally recognized
Higgs, J. M. 1972. Muco-cutaneous candidiasis: Historical only during the twentieth century.
aspects. Transactions of the St. John's Hospital Derma-
tological Society 59: 175-94. Mycetism
Howard, D. H., ed. 1982. Fungi pathogenic for humans and Calamities tend to impress, and the first reference to
animals, 3 vols. New York and Basel.
fungi in the Greek classics is an epigram by Euripi-
Littman, M. L., and L. E. Zimmerman. 1956. Cryptococ-
cosis. New York. des writing about 450 B.C. He was commemorating
Lucet, A. 1897. De I'Aspergillus fumigatus chez animaux the death of a woman and her two children, in one
domestiques et dans les oeufs en incubation. Paris. day, after eating poisonous fungi. During Roman
Mackinnon, J. E. 1949. The dependence on the weather of times, edible fungi were a delicacy, and diverse ad-
the incidence of sporotrichosis. Mycopathologia 4: vice regarding them was offered by several authors
367-74. such as Horace, Celsus, Dioscorides, Galen, and
Mahgoub, El L., and I. C. Murray. 1973. Mycetoma. London. Pliny. The advice consisted of how to avoid poisonous
Odds, F. C. 1979. Candida and candidosis. Leicester Uni- species, how to render poisonous forms harmless,
versity Press. and how to treat fungus poisoning.
R6non, L. 1897. Etude sur I'aspergillose chez les animaux Much of this ancient folklore on precautions to
et chez I'homme. Paris. ensure edibility was compiled by the authors of the
Stevens, D. 1981. Coccidioidomycosis: A text. New York.
first printed herbals in the fourteenth and fifteenth
Warnock, D. W., and M. D. Richardson, eds. 1982. Fungal
infection of the compromised patient. Chichester, U.K. centuries, and some has even survived to the present
day. It is, however, invariably unreliable because the
distribution of poisonous and edible species seems to
be random. For example, the esteemed esculents
Amanita caesarea ("Caesar's mushroom," a Roman
favorite) and Amanita rubescens ("the blusher") are
congeneric with Amanita phalloides ("death cap")
and several related species (Amanita pantherina,
Amanita verna, Amanita virosa) that have been, and
still are, responsible for most fatalities from fungus
poisoning in north temperate regions. The only reli-
able guide is correct identification.
The most frequent effect of fungus poisoning is
gastroenteric disturbance of greater or lesser sever-
ity. Amanita phalloides toxins, symptoms of which
occur 4 to 6 hours or more after ingestion, also cause
severe damage to the liver and kidneys. Other Ama-
nita toxins have a hemolytic effect, whereas halluci-
nogenic species cause psychosomatic symptoms. Fe-
ver is unusual.
The chemistry of toxic fungi has been under investi-
gation since muscarine was isolated in Germany in

VIII.56. Fungus Poisoning 737
1869. That name came from the "fly agaric" {Amanita ing soil did not freeze deeply, and the spring was
muscaria) which has been equated by R. G. Wasson mild with frequent thawing and freezing, the grain
(1971) with the Indian soma. T. Wieland (1986), was molded by Fusarium species and other fungi
together with his father, brother, and other collabora- that produced toxins (mostly trichothecines).
tors, has made extensive studies of the Amanita tox- Known in Japan from the seventeenth century, a
ins (amatoxins, phallotoxins, virotoxins). form of cardiac beriberi (Shoshin-Kakke) was shown
As already indicated, mycetism is of worldwide in 1891 to be caused by eating moldy rice. In 1940
distribution, the species of fungi implicated depend- the toxin involved was identified as citreoviridin,
ing on the locality, but there are variations in its produced by Penicillium citreo-viride. After World
reported incidence. In western Europe, for example, War II, a severe outbreak of a similar but different
there are more published records of mycetism in mycotoxicosis due to eating rice that had deterio-
France, where edible forms of fungi are widely col- rated in storage ("yellowed rice") was recorded in
lected from the wild for sale, than in the United Japan.
Kingdom, where eating wild forms is still regarded Several major mycotoxicoses of farm animals have
with suspicion. Most poisonous fungi are larger been documented in Russia, and a few more have
basidiomycetes, but a few ascomycetes with large been reported elsewhere. Significant attention was
fruit bodies are poisonous (e.g., Gynmitra esculenta, focused on mycotoxicoses after the summer of 1960,
which is, however, edible if dried or if the cooking when more than 100,000 young turkeys and other
water is discarded). poultry died in the United Kingdom after being fed a
A recent development that has led to increased ration containing ground peanut (Arachis hypogea)
incidence of fungus poisoning originated from the meal imported from Brazil. Cattle and pigs were also
ethnomycological studies of Wasson (1971). These affected, and feeding experiments induced cancer of
studies drew attention to the hallucinogenic proper- the liver in the rat. The toxin, found to be produced
ties of some larger fungi, particularly species of by strains of Aspergillus flavus, was designated
Psilocybe containing the compound psilocin — which aflatoxin. At first, testing for aflatoxin was limited
is able to induce psychotropic effects similar to to animal tests using 1-day-old ducklings, which are
lysergic acid and mescalin. Collection of such forms particularity sensitive to the toxin, but a sensitive
in the wild for self-administration or illegal sale has chemical test was soon developed.
resulted in misidentifications or overdoses and the Aflatoxin was shown to be widespread in foods
need for medical attention. containing peanuts, and in parts of Africa and Asia
the incidence of human liver cancer has been corre-
Mycotoxicoses lated with the intake of aflatoxin. It has not been
Until the twentieth century, the only mycotoxicosis possible, however, to legislate for aflatoxin-free pea-
of human beings generally recognized in the West nut products because the methods of harvest and
was ergotism, although serious outbreaks of human storage of peanuts in the primary peanut-producing
mycotoxicoses had occurred in Russia and Japan. countries are such that the introduction of the neces-
Kaschin-Beck (or Urov) disease of children is charac- sary changes could be effected only in the long term.
terized by generalized osteoarthritis caused by eat- The U.S. Food and Drug Administration, therefore,
ing moldy grain. It was prevalent among the Cos- has set an aflatoxin tolerance of 20 parts per billion
sacks and endemic in both Asiatic and European (ppb) for finished peanuts products. Interest in
Russia and in northern Korea and China in the aflatoxicosis, because of its carcinogenic potential, is
1860s. A similar mycotoxicosis (the "drunken [or still intense. The literature on this subject is very
intoxicating] bread syndrome") was also prevalent extensive, and includes two major monographs (Gold-
in Russia. But the most extensively documented blatt 1969; Heathcote and Hibbert 1978) and numer-
mycotoxicosis in Russia is alimentary toxic aleukia ous reviews.
(or septic angina); it was known before World War I Geoffrey C. Ainsworth
and became epidemic during World War II in the
Russian grain belt, when some 10 percent of the Bibliography
population was affected and suffered high death Ainsworth, G. C. 1976. Introduction to the history of mycol-
rates (Mayer 1953). The problem was that in af- ogy. Cambridge.
fected districts it was the practice to allow the ripe 1987. Introduction to the history of medical and veteri-
cereal crop to go through the winter under the snow. nary mycology. Cambridge.
When the snow cover was so heavy that the underly- Ammirati, J. E, J. A. Traquair, and P. A. Horgen. 1985.

Poisonous mushrooms of the northern United States stones occur in 40 to 60 percent of patients with
and Canada. Minneapolis. sickle-cell disease. Brown pigmented stones are asso-
Bresinsky, A., and H. Bresl. 1985. Giftpilz mit einer ciated with infection. These were historically more
Einfiihrung in die Pilzbestimmung. Stuttgart. common in China and Japan, perhaps related to bile
Goldblatt, L. A., ed. 1969. Aflatoxin: Scientific background, stasis and infection caused by Ascaris lumbricoides
control and implications. New York and London. (roundworm) and Clonorchis sinensis.
Heathcote, J. G., and J. R. Hibbert. 1978. Aflatoxins:
Chemical and biological aspects. Amsterdam.
Lincoff, G., and D. H. Mitchell. 1977. Toxic and hallucino- Etiology and Epidemiology
genic mushroom poisoning: A handbook for physi- Though incompletely understood, the three major
cians and mushroom hunters. New York. factors in gallstone formation are abnormality in
Mayer, C. F. 1953. Endemic panmyelotoxicosis in the Rus- bile composition, biliary stasis, and gallbladder infec-
sian grain belt. Military Surgeon 113: 173-89, 295- tion. These factors are interrelated, but current
315. thinking ascribes the primary role to abnormal bile
Rumack, B. H., and E. Salzman. 1978. Mushroom poison- composition, related to cholesterol and bile acid me-
ing: Diagnosis and treatment. West Palm Beach, Fla. tabolism. This in turn is affected by dietary, genetic,
Wasson, R. G. 1971. Soma: Divine mushroom of immortal- and hormonal factors.
ity. Octavo, New York (first issued as a folio, limited A common medical maxim describes a typical pa-
edition, 1968). tient with gallstones as "fat, fair, female, and forty."
Wieland, T. 1986. Peptides of poisonous Amanita mush-
rooms. New York.
Obesity is associated with increased cholesterol se-
Wyllie, T. D., and L. G. Morehouse, eds. 1977-8. Mycotoxic cretion, producing a supersaturated or lithogenic
fungi, mycotoxins, mycotoxicoses: An encyclopedic bile. Overconsumption of calories, particularly
handbook, 2 vols. New York and Basel. through refined sugar and flour, appears to be the
major factor accounting for the high incidence in
Western countries (Heaton 1973). It also explains
the increasing prevalence of cholesterol and mixed
gallstones among Japanese, Eskimo, and certain Af-
VIII.57 rican populations adopting a more Western diet. A
diet high in cholesterol-rich foods may have a secon-
Gallstones (Cholelithiasis) dary role.
Gallstones are two to four times more common in
females than in males. Estrogen causes increased
Classification secretion of cholesterol as well as decreased produc-
Gallstones are quite common in modern populations, tion of bile salts required to form soluble micelles
occurring in nearly 20 percent of autopsies. Though with cholesterol. In addition, childbearing results in
often asymptomatic, they can produce significant further elevation of estrogen in the third trimester
morbidity, leading to cholecystitis, cholangitis, bi- and also promotes biliary stasis; thus multiparity is
liary cirrhosis, and pancreatitis. a risk factor.
The chief constituents of gallstones are choles- There is a steady increase in gallstone prevalence
terol, bilirubin, and calcium. Other components may with advancing age. Clinically, the symptoms of gall-
include fatty acids, triglycerides, protein, and poly- bladder disease related to gallstones most commonly
saccharides. Descriptively, there are four major present between the ages of 40 and 60 years.
types of gallstones: (1) pure cholesterol stones; (2)
mixed stones composed of cholesterol, bilirubin, and Distribution and Incidence
calcium; (3) combined stones having a cholesterol Conclusions regarding the geographic distribution
center and laminated exterior of cholesterol, bili- of gallstones are based on a variety of autopsy, hospi-
rubin, and calcium; and (4) black or brown pig- tal admission, and population survey data. The large
mented stones composed of calcium bilirubinate. Framingham, Massachusetts, study showed a preva-
The first three types comprise the vast majority of lence of documented gallbladder disease among
gallstones and may be grouped together as choles- adult males (30 to 62 years old) of 1.3 percent and
terol-based stones, pathogenetically related to abnor- among adult females of 5.9 percent (Friedman,
mal cholesterol and bile salt metabolism. Black pig- Kannel, and Dawber 1966). Many studies have
mented stones are commonly associated with chronic shown a higher prevalence among American Indian
hemolysis, particularly sickle-cell disease. Gall- groups, particularly in the Southwest (Brown and

VIII.57. Gallstones (Cholelithiasis) 739
Christensen 1967; Comess, Bennett, and Burch groups, including Pima, Navajo, and Chippewa as
1967; Heaton 1973). For example, a study of the well as in groups with significant Indian admixture
Pima Indians using identical criteria and age groups from Mexico, Bolivia, Chile, and Peru (Weiss et al.
as the Framingham study showed a prevalence of 1984). It has been postulated that a genetic defect in
5.9 percent among adult males and 36 percent conversion of cholesterol to bile acid results in
among females (Comess et al. 1967). lithogenic bile (Grundy, Metzger, and Adler 1972).
Gallstones are usually asymptomatic. This fea- The geographic epidemiology of gallstones indi-
ture, in combination with the increased prevalence cates a susceptibility in New World populations that
with age, explains the much higher incidence of gall- is not shared, however, by their Asian ancestral rela-
stones at autopsy. A large autopsy series from Phila- tives. The Americas were settled by crossing via the
delphia spanning the years 1920 to 1949 demon- Bering land bridge formed during glacial epochs.
strated gallstones in 7.8 percent of males and 16.8 Survival under the harsh climatic conditions de-
percent of females. The incidence among blacks was pended on hunting and gathering strategies with
less than half that for whites (Lieber 1952). An au- unpredictable periods of near starvation. Individu-
topsy series of adult whites in New York City found als who could rapidly store excess calories as fat
gallstones in 16.0 percent of males and 32.5 percent would have had a pronounced survival advantage
of females (Newman and Northup 1959). over individuals lacking this trait. This is the
A similar prevalence of gallstones has been dem- "thrifty gene" theory postulated to explain the preva-
onstrated in autopsy series from Europe, including lence of diabetes among American Indians (Neel
England, France, and Germany, as well as Western- 1962, 1982) and possibly accounting for the associa-
style societies such as Israel, South Africa, and Aus- tion of obesity, parity, and puberty, with the forma-
tralia (Brett and Barker 1976). Sweden appears to tion of gallstones in American Indian females and to
be second only to certain American Indian groups in a lesser degree in males now exposed to a perpetual
the frequency of gallstones. An autopsy survey from "feast" of calories and sedentary living (Weiss et al.
Malmo found stones in 32 percent of men and 57 1984). Indeed, the worldwide distribution of other
percent of women over 20 years old. The prevalence populations with high risk of gallstones corresponds
rose to peaks of 70 percent in women by age 70, and closely to the area covered by the last glacial epoch
50 percent in men by age 90. (Lowenfels 1988).
Gallstones are relatively uncommon in oriental
countries; prevalence rates as low as 1.8 percent History and Paleopathology
among adult men and 3.9 percent of adult women Hippocrates and Aristotle were familiar with the
are found in Thailand. Prevalence remains low in clinical findings of jaundice and biliary disease, but
Japan; however, there has been a shift from the their writings do not specifically mention gallstones.
infection-related pigmented stones to the Western Hippocrates differentiated four types of jaundice due
diet-related cholesterol stones. to disease of the liver, but he did not describe any
Most African populations demonstrate an ex- cause related to obstruction. Diocles of Carystus re-
tremely low prevalence of gallstones. Only 1.3 per- ferred to possible mechanical obstruction of the flow
cent of autopsied adults in Uganda had gallstones. of bile. Accounts of Alexander the Great's illness
Many of these were black pigmented stones related prior to his death in 323 B.C. are quite suggestive of
to chronic hemolysis (Owor 1964). No gallstones gallstones and cholecystitis (Gordon-Taylor 1937).
were found in a series of 4,395 autopsies in Ghana. Galen described various types of jaundice, includ-
The disease is virtually unknown among the Masai ing obstructive jaundice. He stated that small for-
of East Africa. eign bodies such as grain or fig and pomegranate
There is a general impression that gallstones are seeds could obstruct the common bile duct. Given the
increasing in frequency in industrialized countries close similarity of small gallstones to certain seeds,
as well as in countries undergoing rapid develop- Galen may in fact be referring to gallstones. Gall-
ment. A recent review of pre- and post-1940 autopsy stones in lower animals had been recognized for cen-
series shows increasing prevalence of gallstones in turies, and crushed gallstones were an important
Europe, North America, Japan, Chile, and Australia ingredient in yellow pigment. The codified Talmudic
(Brett and Barker 1976). law of the fourth century A.D. considered animals
A genetic tendency to develop gallstones under with sharp-edged gallstones unfit to eat (terefah),
certain dietary conditions may account for the high but kosher to eat if the gallstones were smooth like a
rates of gallstones noted in various American Indian date pit.

Alexander of Tralles of the sixth century was a B.C., revealed an intact gallbladder filled with
Byzantine physician with wide clinical experience stones. A radiograph of an intact mummy from the
but scanty knowledge of anatomy and physiology. late Dynastic period (525 to 343 B.C.) shows a clus-
He described both gallstones and renal calculi. Haly ter of gallstones in the gallbladder. Subsequent
Abbas, a tenth-century Persian physician often analysis showed these to be the mixed variety (Gray
quoted in early Renaissance medicine, recorded the 1967).
presence of calculi in the gallbladder and liver An extremely well preserved body of a 50-year-old
(Wilkie 1934). female from the Hunan province of central China
Mundinus was professor of anatomy and surgery demonstrated multiple gallstones, including one ob-
at the University of Bologna from 1295 to 1326. His structing the common bile duct. This example dates
manuscript on anatomy was based on the writings of to the Han Dynasty (206 B.C. to A.D. 220) (Wei
Hippocrates, Galen, and Arabic authors and was 1973).
widely used for nearly 250 years. He also mentions In Europe, gallstones were recovered along with
stones formed within the gallbladder and kidneys. skeletal remains in a wooden coffin dating to Merovin-
Gentile da Foligno was a graduate of Bologna and gian times or about A.D. 750. The coffin was found in
professor at Padua, who died of the plague in 1348. Mainfranken, Germany. In Herault, France, the re-
In 1341 he carried out one of the earliest autopsies mains of an older adult buried in the ninth century
on record, and an account of that autopsy states that also yielded gallstones. A single gallstone was recov-
a gallstone was found embedded in the cystic duct of ered from 234 graves in a London cemetery dating
the gallbladder. from A.D. 1000 to 1200 (Steinbock in press).
Antonio Benivieni wrote the first book devoted to In the New World, 16 individuals from the Libben
pathological anatomy, which was published posthu- site in Ohio exhibited gallstones (Lovejoy 1979).
mously by his brother in 1507. This work, De This Late Woodland site dates from A.D. 1000 to
Adbitis, contains 111 observations based on 20 autop- 1200. In northern Chile, at a site dating from A.D.
sies, including two descriptions of gallstones found 100 to 300, 2 of 75 mummies had gallstones
within the gallbladder and liver. Numerous other (Munizaga, Allison, and Paredes 1978). Both indi-
Renaissance physicians were familiar with gall- viduals had pure cholesterol stones.
stones encountered in clinical practice or more often The frequency of cholesterol-based gallstones is
at autopsy (Steinbock 1990). affected by age, sex, parity, diet, genetics, and other
Giovanni Battista Morgagni profoundly altered factors. Infection and hemolysis are important in the
medicine in 1761 with the publication of On the Sites formation of pigmented stones. A variable frequency
and Causes of Disease. He provided a vast array of in ancient human populations is to be expected, and
pathological findings related to the clinical picture because of dietary factors they may have been quite
for a large number of diseases, including gallstones. rare in many instances.
Morgagni noted the increased frequency of gall- R. Ted Steinbock
stones with age, the greater preponderance of
women suffering from them, the variation by locale, Bibliography
and an association with a very sedentary life. Bile Angel, L. 1973. Human skeletons from grave circles at
stasis again figured as a prominent factor in gall- Mycenae. Appendix in The grave circle B of Mycenae,
stone formation. He also considered irritation or in- G. E. Mylonas, 379-97. Archaeological Society of
flammation of the glands within the gallbladder Athens.
wall as a cause of stones. Bennion, L. J., and S. M. Grundy. 1978. Risk factors for the
Gallstones have been recovered in burial excava- development of cholelithiasis in man. New England
tions, and this evidence greatly extends the known Journal of Medicine 299: 1161-7.
antiquity of the disease. Given their frequency, more Brett, M., and D. J. P. Barker. 1976. The world distribution
of gallstones. International Journal ofEpidemiology 5:
such examples should be expected. The earliest case
335-41.
comes from Mycenae, Greece, dating 1600 to 1500
Brown, J. E., and C. Christensen. 1967. Biliary tract dis-
B.C. Several gallstones were found between the ease among the Navajos. Journal of the American
right lower costal margin and right iliac crest of the Medical Association 202: 1050-2.
skeleton of a 45- to 55-year-old man (Angel 1973). Comess, L. J., P. H. Bennett, and T. A. Burch. 1967. Clini-
The stones are reddish brown in color with green cal gallbladder disease in Pinna Indians. New England
patches and have several facets. Journal of Medicine 277: 894-8.
The mummy of a priestess of Amen, who died 945 Friedman, G. D., W. B. Kannel, and T. R. Dawber. 1966.

VIII.58. Gangrene 741
The epidemiology of gallbladder disease: Observa-
tions in the Framingham study. Journal of Chronic VHI.58
Disease 19: 273-92.
Gordon-Taylor, G. 1937. Gallstones and their sufferers.
Gangrene
British Journal of Surgery 25: 241-51.
Gray, P. H. K. 1967. Radiography of ancient Egyptian
mummies. Medical Radiography and Photography 43: Gangrene is the term used by the clinician to de-
34-44. scribe local death of tissue (necrosis) occurring in the
Grundy, S. M., A. L. Metzger, and R. Adler. 1972. Patho- living body. Gangrene implies a fairly rapid process
genesis of lithogenic bile in American Indian women (developing in days) extending over a large visible
with cholesterol gallstones. Journal of Clinical Investi- area (a few to many centimeters) with an obvious
gation 51: 3026-31. inability of the tissues to repair or replace the gan-
Heaton, K. W. 1973. The epidemiology of gallstones and grenous part. Although gangrene can occur in inter-
suggested etiology. Clinical Gastroenterology 2:67-83. nal organs (e.g., large intestine), it generally refers
Lieber, M. M. 1952. The incidence of gallstones and their to a process occurring on the surface of the body. It
correlation with other diseases. Archives of Surgery may involve only the skin, or it may extend into
135: 394-405.
deeper tissues such as muscle or nerves.
Lovejoy, C. O. 1979. Referred to in December Paleopathol-
ogy Association Newsletter 28: 7.
Gangrene may be either dry or moist. Dry gan-
Lowenfels, A. B. 1988. Gallstones and glaciers: The stone grene describes necrosis of the tissues of the extremi-
that came in from the cold. Lancet 1: 1385-6. ties resulting from vascular occlusion, such as occurs
Munizaga, A., M. J. Allison, and C. Paredes. 1978. in severe arteriosclerosis of the legs. Wet or moist
Cholelithiasis and cholecystitis in pre-Columbian gangrene occurs when bacteria invades dead tissue,
Chileans. American Journal of Physical Anthropology producing putrefaction. When the gas-forming group
48: 209-12. of bacteria is involved, gas gangrene occurs. A gan-
Neel, J. V. 1962. Diabetes mellitus: A "thrifty" genotype grene may be dry at first, and be converted to the
rendered detrimental by "progress"? American Jour- moist type by invading bacteria.
nal of Human Genetics 14: 353-62.
1982. The thrifty genotype revisited. In The genetics of Clinical Manifestations
diabetes mellitus, ed. J. Kobberling and R. Tattersall,
In dry gangrene, the arterial supply is gradually cut
283-93. New York.
off and a drying or mummification of the tissues
Newman, H. E, and J. D. Northup. 1959. Collective re-
view: The autopsy incidence of gallstones. Interna- results. There is frequently an absence of inflamma-
tional Abstracts of Surgery 109: 1-12. tion, but pain of varying degree may precede the
Owor, R. 1964. Gallstones in the autopsy population at color changes. The soft tissue slowly and progres-
Mulago Hospital, Kampala. East African Medical sively shrinks and the color gradually deepens until
Journal 41: 251-3. the whole area is coal black. Constitutional symp-
Steinbock, R. T. 1990. Studies in ancient calcined soft toms may occur but are less severe than in moist
tissues and organic concretions. III. Gallstones (chole- gangrene.
lithiasis). Journal of Paleopathology. Moist gangrene may be preceded by inflammation
Wei, O. 1973. Internal organs of a 2100 year old female or trauma. The part is initially swollen and painful.
corpse. Lancet 2: 1198. The color is at first red then blue and finally turns to
Weiss, K. M., et al. 1984. Genetics and epidemiology of
a green black. There is boggy swelling and putrid
gallbladder disease in New World native peoples.
odor. If the moist gangrene is extensive, constitu-
American Journal of Human Genetics 36: 1259-78.
Wilkie, D. P. D. 1934. Gallstones. In A short history of some
tional symptoms, such as fever, may be present.
common diseases, ed. W. R. Brett, 146-53. London. A vivid description of hospital gangrene illus-
trates well the clinical aspect of moist gangrene:
A wound attacked by gangrene in its most concentrated
and active form presents a horrible aspect after the first
forty-eight hours. The whole surface has become of a dark-
red color, of a ragged appearance, with blood partly coagu-
lated, and apparently half putrid, adhering at every point.
The edges are everted, the cuticle separating from half to
three-fourths of an inch around, with a concentric circle of
inflammation extending an inch or two beyond it; the limb
is usually swollen for some distance, of a white, shining

color, not peculiarly sensible except in spots, the whole of Table VIII.58.1. Causes of gangrene
it being oedematous and pasty. The pain is burning and
unbearable in the part itself, while the extension of the Vascular disease
disease, generally in a circular direction, may be marked Vascular spasm
from hour to hour; so that in from another twenty-four to Ergotism (St. Anthony's fire)
forty-eight hours nearly the whole of a calf of a leg, or the Raynaud's syndrome
muscle of a buttock, or even the wall of the abdomen may Embolism
disappear, leaving a deep great hollow or hiatus of the Arteriosclerosis
most destructive character, exhaling a peculiar stench Organisms
which can never be mistaken, and spreading with a rapid- Fat and gases
ity quite awful to contemplate. The great nerves and arter- Dysproteinemias
ies appear to resist its influence longer than the muscular Abnormalities of coagulation
structures, but these at last yield; the largest nerves are Primary vascular disease (peripheral vascular disease)
destroyed, and the arteries give way, frequently closing Arteriosclerosis
the scene, after repeated hemorrhages, by one which Thromboangiitis obliterans (Buerger's disease)
proves the last solace of the unfortunate sufferer. . . . The Diabetes
joints offer little resistance; the capsular and synovial Vasculitis of the so-called collagen diseases
membranes are soon invaded, and the ends of the bones Rheumatoid arthritis
laid bare. The extension of this disease is in the first Systemic lupus erythematosus
instance through the cellular structures. The skin is under- Hypersensitivity to certain drugs
mined and falls in, or a painful red and soon black patch is
perceived at some distance from the original mischief, Physical agents
preparatory to the whole becoming one mass of putridity, Burns
while the sufferings of the patient are extreme. (Buck Cold
1902) Trauma
Pressure
Ionizing radiation
Etiology Electrical burns
Gangrene can have many causes; Table VIII.58.1
indicates the major ones. Some are now quite rare Chemical agents
Caustics
but at one time were common. Using this table as a
Venoms
guide, we shall discuss the various causes, highlight- Certain drugs
ing those that have been of major consequence Coumadin
throughout recorded history. Heparin
Chemotherapeutic agents
Vascular Causes
Microbiological agents
Historically, ergotism resulted from ingesting rye
Bacterial infections
bread contaminated by the fungus Claviceps purpu- Anthrax
rea. It led to a permanent decrease in the caliber of Streptococci (necrotizing fasciitis, Fournier's gangrene)
arterioles and, eventually, to dry gangrene of the Mixed (postoperative synergistic gangrene)
fingers and toes and, less commonly, of the ears and Leprosy
nose. Ergotism was responsible for many epidemics Pseudomonas aeruginosa
of gangrene during the Middle Ages in Europe. Mycobacterial organisms (tuberculosis, Buruli ulcer)
Along with erysipelas it was known as St. Anthony's Viral infections
fire. Although rare, ergotism may still occur today, Herpes (simplex and zoster)
as ergot preparations are often used in the treat- Smallpox
ment of migraine headaches. Chickenpox
Treponemal infections
Raynaud's Syndrome. This syndrome is character- Syphilis
Yaws
ized by marked episodic vascular spasms of the ex-
Bejel
tremities. During a typical attack, one or more digits Rickettsial infections
initially turn white. After a few minutes, the color Rocky Mountain spotted fever
changes to a bluish red. Slowly, the normal color Typhus
returns. These episodes are often triggered by cold or Protozoal infections
emotional stress. In severe cases, gangrene may en- Amebiasis cutis
sue, which is characteristically symmetrical and con- Schistosomiasis cutis

VIII.58. Gangrene 743
Table VIII.58.1 (cont.) of the legs, so that blood supply to the feet can be
restored.
Fungal infections
Histoplasmosis Physical Agents
Mucormycosis (phycomycosis) Various types of injuries such as frostbite, compound
Actinomycosis/nocardiosis bony fractures of the legs, contusions, gunshot
Cryptococcosis
wounds, and burns, if serious enough, may be the
Blastomycosis (North and South American)
initial factor that triggers production of gangrene.
However, this complication was more prevalent be-
fore effective medical care became widely available.
fined to the fingers and toes. It was once known as
relapsing gangrene. Raynaud's syndrome may occur Chemical Agents
alone {Raynaud's disease) or in association with an- Tissue can also be destroyed by chemicals either of
other condition usually of the collagen group of dis- exogenous or endogenous origin. Caustics such as
eases (scleroderma, systemic lupus erythematosus, carbolic acid (previously used as an antiseptic solu-
rheumatoid arthritis). It has also been seen as an tion) have been known to cause gangrene. Venoms of
occupational hazard in people who manipulate vibra- certain snakes (i.e., water moccasin), spiders (i.e.,
tory instruments such as jackhammers or chainsaws. brown recluse spider), and jellyfish (i.e., Portuguese
man-of-war) can cause local necrosis at the site of
Embolism. Embolism is the sudden occlusion of an the sting or bite. Many chemotherapeutic agents
artery by blood-borne particles. These may be (such as those used to treat malignancies) may also
atheromatous material dislodged from a vascular lead to local tissue destruction when they inadver-
plaque upstream; vegetations from an infected heart tently seep into the surrounding area during intrave-
valve; or other unusual particles such as fat (after nous administration. Some systemically adminis-
extensive bony fractures), gas (decompression sick- tered drugs may rarely cause gangrene (i.e., some
ness), abnormal blood proteins (dysproteinemias), or anticoagulants such as coumadin).
blood clots. The acute vascular compromise can lead
to gangrene of the extremities, usually of the dry Microbiological Agents
type. Many organisms produce a toxin that will directly
cause cell death. Other toxins have vascular effects
Arteriosclerosis. Arteriosclerosis may be an under- such as spasm or vasculitis. Some organisms pro-
lying cause of embolism, and can also lead to grad- duce enzymes that can break down tissue locally.
ual local vascular occlusion (thrombosis) of large and Other organisms - in particular, viruses - can di-
medium-sized arteries. It is common in the elderly rectly destroy cells by invasion. Only a few of the
and therefore has been called senile gangrene. A dry most important infections will be discussed here.
gangrene, it occurs mainly in the foot and was there- Many can be found elsewhere in this work.
fore previously called Pott's disease of the toe. It is Various streptococci, including Streptococcus pyo-
generally preceded by severe pain and discomfort in genes (group A beta hemolytic strep.), have been
the lower leg and foot. A special form of arterioscle- found to be the cause of certain varieties of gangrene.
rosis is thromboangiitis obliterans or Buerger's dis- Of historical importance is hospital gangrene, also
ease. It commonly occurs in young and middle-aged known as necrotizing fasciitis and pourriture des
men who are heavy smokers. Finally, diabetes can hopitaux. This form of gangrene was the scourge of
predispose to arteriosclerosis of smaller vessels with hospitals in the preantiseptic era. Today it is almost
eventual gangrene of the feet and toes. Diabetic gan- never seen. Trauma is usually the initiating factor,
grene is usually of the moist type. There are multi- whereas predisposing factors are diabetes, alcohol-
ple other factors that may predispose to arterioscle- ism, and a generally debilitated state. Within 48 to 96
rosis. They include hereditary factors and general hours, gangrene would set into a wound and charac-
life-style habits such as overeating of animal fats, teristically was rapidly progressive and deeply de-
lack of exercise, and smoking. With recent changes structive. The patient would become febrile and even-
in these habits and better control of diabetes, arterio- tually succumb. Although some authorities feel that
sclerosis and its resultant gangrene are now becom- this type of gangrene was due solely to S. pyogenes,
ing less common. Surgical techniques are also avail- there is now more evidence to suggest that other
able for replacing or recanalizing occluded arteries organisms (alone or in combination) may give a simi-

lar clinical picture. Another streptococcal gangrene, of wounds, is known as Listerism, in honor of Lord
called Fournier's gangrene, is an acute gangrene local-
Joseph Lister, who was the first to recognize the
ized to the scrotum. Finally, anaerobic streptococci in
value and clinical application of Pasteur's discovery.
combination with other bacteria such as Staphylococ- Finally, the introduction of penicillin in the early
cus aureus are the cause of postoperative synergistic 1940s totally eradicated hospital gangrene.
gangrene. After a few days or weeks, gangrene devel- Arteriosclerosis is probably as old as humankind.
ops around an abdominal or thoracic surgical wound Leonardo da Vinci, in the fifteenth century, illus-
site. The process is rapidly progressive and may, if left
trated the arteries of a subject with senile arterio-
untreated, lead to the death of the patient. sclerosis in one of his anatomic sketches. Along
with prolonged life expectancy has come a greater
History and Geography susceptibility to degenerative diseases such as arte-
Ergotism has long been an important cause of cer- riosclerosis and other vascular disorders. In the
tain epidemics of gangrene in humankind. Gan- early nineteenth century, it gradually became clear
grene of the limbs has been recognized since ancient that organic occlusion of the arteries could cause
times, and a description of gangrene following dry gangrene. Maurice Raynaud, in his now famous
trauma appears in Hippocrates. It is probable that 1862 thesis, On Local Asphyxia and Symmetrical
gangrene in ancient Greece and Rome was due Gangrene of the Extremities, attempted to prove
mainly to infections initiated by trauma of either that there was a disease of the arterial system that
accidental or military origin. might produce gangrene, but in which arterial oblit-
In temperate and Arctic zones of the world, cold eration was not present. Only recently have the
injuries causing frostbite that led to gangrene have roles of life-style, diabetes, and hypertension been
always occurred. Explorers of cold regions were of- recognized as contributing factors in the production
ten affected, and gangrene produced by cold injury of arteriosclerosis. Fortunately, widespread public
has also been a tremendous problem in troops en- education is now contributing to the decline of se-
gaged in wartime activities. Gangrene, for example, vere peripheral vascular disease and its associated
was quite prevalent among soldiers during Napoleon gangrene.
Bonaparte's invasion of Russia. Yet frostbite was In advanced countries of the world today, gangrene
only one of the causes of gangrene associated with is much less common. Infectious gangrenes are easily
military activity. Trauma from penetrating wounds, treated or avoided by the appropriate antiinfective
contusion of soft tissues, and compound bony frac- agents. However, there are now a growing number of
tures were often the initial insult. The introduction individuals who are immunosuppressed from chemo-
of gunpowder in Europe in the sixteenth century therapeutic agents and corticosteroids, which are
produced a tremendous loss of life and limbs from used to prevent rejection in transplant patients, and
gangrene that developed in these traumatic wounds. to treat various cancers and autoimmune diseases
Poor hygienic conditions and overcrowding in hospi- such as rheumatoid arthritis. In such an immunocom-
tals led to epidemic wound infections. Because hospi- promised state, these patients are at increased risk
tal gangrene was rapidly progressive and lethal, of developing unusual infectious gangrenes whose
many lives were lost, particularly during the Napole- etiologic agents may not be easily recognized or be
onic Wars, the Crimean War, and the American Civil readily treatable.
War. In many cases, there were almost as many Diane Quintal and Robert Jackson
soldiers killed from wounds and gangrene as were
killed in action. Bibliography
By the time of World War I, hospital gangrene was Brooks, Stewart. 1966. Civil war medicine. Springfield, 111.
much less prevalent. The art of amputation and set- Buck, Albert, ed. 1902. A reference handbook of the medi-
ting of fractures was advanced by the important cal sciences, Vol. IV, 300-8. New York.
contributions of such surgeons as Ambroise Pare in Buerger, Leo. 1924. The circulatory disturbances of the
extremities. Philadelphia.
the sixteenth century, Pierre-Joseph Desault in the
1983. Thrombo-angiitis: A study of the vascular lesions
eighteenth, and John Bell at the turn of the nine- leading to presenile spontaneous gangrene. American
teenth, among others. Their work significantly con- Journal of Medical Sciences 266: 278-91. [Reprint of
tributed to decreased mortality from gangrene. The Buerger's 1908 article in same journal.]
concept of antisepsis and asepsis was introduced in Enjalbert, Lise. 1978. De la pourriture d'hopital a l'infec-
the late nineteenth century with the work of Louis tion nosocomiale. Memoires de lAcadimie des Sci-
Pasteur. This concept, when applied to management ences (Toulouse) 140: 67-73.

VIII.59. Giardiasis 745
Moschella, Samuel L. 1969. The clinical significance of There has been considerable dispute in the past
about the clinical importance of Giardia infection.
necrosis of the skin. Medical Clinic of North America
53: 259-74. Although many cases are in fact asymptomatic, it is
Tanner, J. R. 1987. St. Anthony's fire, then and now: Anow clear that the flagellates damage the intestinal
case report and historical review. Canadian Journal of
wall and that heavy infestations can cause nutrition-
Surgery 30: 291-3. ally significant malabsorption of food. Symptoms in-
U.S. Army. 1884. Index catalogue of the Library of the clude diarrhea, flatulence, abdominal discomfort,
Surgeon-General's Office. 1263-80.
and light-colored, fatty stools. The classic method for
detecting Giardia infections is to find the tropho-
zoites in the feces with a microscope, but surveys
that depend on this technique will generally underes-
timate prevalence because trophozoites do not ap-
VIII.59 pear consistently in the stools. Repeated examina-
Giardiasis tions and use of serologic techniques developed in
the 1980s give more accurate results for either an
individual patient or an entire population. Most in-
Infection with the small flagellate Giardia lamblia fections are self-limiting and treatment is effective,
is found around the world. This protozoan inhabits but reinfestation must be avoided. There is some
the small intestine of humans and is especially com- evidence that mothers' milk helps protect infants
mon in children. Other mammals, including beavers against infection.
and muskrats, also harbor Giardia and are impor- K. David Patterson
tant reservoir hosts. The parasite was first seen by
Anton van Leeuwenhoek in 1681 and described sci- Bibliography
entifically in 1859. Dykes, A. C , et al. 1980. Municipal waterborne giardiasis:
Adult parasites, the trophozoites, attach to the An epidemiological investigation. Beavers implicated
intestinal wall with sucking disks. As trophozoites as a possible reservoir. Annals of Internal Medicine
detach and pass down the intestinal tract, they trans- 92:165-70.
form themselves into cysts that are able to resist Gilman, R. H., et al. 1985. Epidemiology and serology of
many environmental pressures, including water fil- Giardia lamblia in a developing country: Bangladesh.
Transactions of the Royal Society of Tropical Medicine
tration and chlorination. Humans almost always ac-
and Hygiene 79: 469-73.
quire infection by swallowing fecally contaminated Goodman, A., et al. 1983. Gastrointestinal illness among
food or water. In developed countries, many cases of scuba divers-New York City. Morbidity and Mortality
giardiasis have been traced to campers who have Weekly Report 32: 576-7.
drunk from what appeared to be pure wilderness Kean, B. H., Kenneth E. Mott, and Adair J. Russell, eds.
streams, but that had been contaminated by ani- 1978. Tropical medicine and parasitology: Classic in-
mals. Because the cysts are surprisingly resistant to vestigations, Vol. 1,169-70. Ithaca and London.
normal water purification methods, public water sup- Markell, E. K., et al. 1984. Intestinal protozoa in homosex-
plies can become infected by faulty sewer lines, as ual men of the San Francisco Bay area: Prevalence
happened in two fashionable Colorado ski resorts in and correlates of infection. American Journal of Tropi-
1964 and 1978. Giardiasis is a frequent cause of cal Medicine and Hygiene 33: 239—45.
"traveler's diarrhea," and tourist groups in Lenin- World Health Organization. Parasitic Diseases Pro-
gramme. 1986. Major parasitic infections: A global
grad have suffered well-publicized outbreaks. In
review. World Health Statistics Quarterly 39: 145-60.
1983, 22 of New York City's 55 police and fire depart-
ment scuba divers had Giardia, presumably from
the heavily polluted waters of the harbor. Four per-
cent of 1 million stool samples submitted to state
laboratories in the United States from 1977 to 1981
were positive for Giardia. Prevalence rates in devel-
oping countries range from 8 to 20 percent and
higher. In poor countries like Bangladesh, where
water and sanitation standards are often very favor-
able for transmission, a majority of the children and
many adults repeatedly acquire infection.

VIII.60
Glomerulonephritis
(Bright's Disease)
Glomerulonephritis, an immunologic disease of the

kidneys, affects the glomerulus. This structure, a
cluster of capillaries, is the filter in the functioning
unit of the kidney, the nephron. Inflammation, initi-
ated by immune complexes (defined below), injures
the glomerulus. Often the disease is acute, but it
may be silent and completely undetected until signs
and symptoms of chronic kidney failure prompt a Figure VIII.60.2. Normal glomerulus. It consists largely
biopsy, leading to diagnosis. Alternatively, this si- of a tangle of tiny blood vessels (capillaries), many of
lent disease may prove fatal, and the diagnosis is which have been cut in a cross-sectional plane. They ap-
made at autopsy. pear as spherical or oval empty spaces surrounded by a
The urine-secreting structure (nephron) (Figure thin membrane. Many contain a nucleus (dark-stained
VIII.60.1) consists of the glomerulus and its tubular spots) of the capillary lining (endothelial) cells.
system. Each glomerulus consists of a tangle of inter-
connecting capillaries branching between two tiny
arteries (arterioles). A glomerular cross section ing on their size and charge. Normally red blood
shows these capillary loops (Figure VIII.60.2). The cells and albumin are not permitted to pass through
glomerulus is a blood filter that controls passage of the membrane. The tubules reabsorb, secrete, syn-
molecules through the basement membrane, depend- thesize, and excrete solutes and metabolites, thereby
maintaining physiological equilibrium.
This article will deal only with poststreptococcal
PROXIMAL CONVOLUTED
TUBULE
glomerulonephritis. This disease, described by Rich-
DISTAL CONVOLUTED
ard Bright in the early part of the nineteenth century,
GLOMERULUS TUBULE still bears his name. Other forms of glomerulo-
nephritis, which he also described, and the glomeru-
lar diseases termed glomerulopathies, seen in diabe-
tes or amyloidosis, are not discussed.
AFFERENT /
ARTERIOLE
Glomerulonephritis occurs worldwide. The disease
was seen frequently in Europe during the eigh-
teenth and nineteenth centuries as a complication of
scarlet fever during epidemics. Today glomerulone-
phritis occurs sporadically. Several epidemics have
occurred since the 1950s in the United States, Trini-
dad, and Venezuela. The disease would seem to be
more prevalent in the Western world, probably only
because modern diagnostic aids are available. Chil-
dren contract it more commonly than adults, but it
occurs in all age groups. Because the disease is often
silent, the exact incidence of glomerulonephritis re-
mains unknown.
Figure VIII.60.1. Urine-secreting structure (nephron).
(Modified from Arthur C. Allen. 1962. The Kidney: Medi- Epidemiology, Etiology, and Immunology
cal and Surgical Diseases, 2d edition, 27, plate 13A. For more than 200 years, physicians have known that
New York.) swelling of the face and extremities (dropsy) occurred

VIII.60. Glomerulonephritis (Bright's Disease) 747
in some individuals 10 to 14 days after bouts of scarlet

fever (scarlatina). Early physicians believed that tox-
ins, released during the fever, caused the dropsy, and
long after Bright discovered the association of post-
scarlatina dropsy with changes in the kidney, the role
played by scarlet fever still remained a mystery.
These earlier beliefs were afforded credibility with
the discovery, in the latter part of the nineteenth cen-
tury, that the scarlatina rash resulted from strepto-
coccal toxins.
It was only in the latter half of the twentieth
century that F. G. Germuth (1953) and F. J. Dixon
and others (1961) found that rabbits developed
glomerulonephritis when given injections of a for-
eign protein (bovine albumin). About 2 weeks after Figure VIII.60.3. Acute glomerulonephritis. As com-
these injections, the glomerulus sustained injury pared with Figure VIII.60.2, the glomerulus is larger
from immune complexes. An immune complex con- and the nuclei (dark-stained spots) are both more numer-
sists of an antigen (the protein), an antibody (pro- ous and swollen to the point of obliterating the capillary
duced by the rabbit), and a complement (humoral lumens, rendering them indistinguishable.
component). Immune complexes localize in the
glomerulus and damage the basement membrane.
The damaged membrane leaks protein and red blood Hal crescents, surround the glomeruli, and strangle
cells into the urine; swollen cells lining the capillary bloodflowto the capillaries, causing kidney failure
block the glomerular capillaries. and death to the patient unless hemodialysis is
undertaken.
In humans, events mimicking this model follow
certain streptococcal infections caused by "nephrito-
genic" strains. Before the advent of antibiotics,
glomerulonephritis usually followed an attack of Early Accounts Through the Eighteenth
scarlet fever. Today, in the Western world it more Century
often follows streptococcal infections of the throat Dropsy, a clinical finding, occurs not only in
and skin, since scarlet fever is quite uncommon. glomerulonephritis, but also in a number of other
Some part (still not identified) of the streptococcus conditions and diseases including heart failure and
serves as the stimulus for antibody formation. end-stage liver disease. There are early accounts of
dropsy, and some of these certainly refer to
Clinical Manifestations and Pathology glomerulonephritis. Glomerulonephritis also causes
Signs of kidney disease usually follow infection, but bloody urine, but other common causes of this symp-
not all patients have such a history. Many have no tom include urinary tract stones, tumors, and para-
known or recognized antecedent illness. Generalized sitic diseases.
edema is often an early symptom. Red-brown or In the writings of Rufus of Ephesus, of about A.D.
frankly bloody urine, reduced urine volume, hyper- 100, we read of "hardening of the kidneys." This was
tension, and headache from fluid accumulation are noted in patients who had only small amounts of
other common symptoms. urine, were free of pain, and who sometimes devel-
In children, poststreptococcal glomerulonephritis oped dropsy. This description could certainly be
is usually a mild disease, and most children recover chronic glomerulonephritis. Ancient Hindu writings
without permanent kidney damage. In adults, in refer to dropsy attributed to heart disease. Avicenna,
contrast, permanent kidney damage occurs more of- an Arabian physician and author of the Canon, per-
ten. The reasons for this difference are unknown. haps the most famous medical text ever written,
The main pathological changes in glomerulonephri- referred to patients with "chronic nephritis" around
tis are an increase in glomerular cellularity (Figure A.D.1000.
Vm.60.3) and red blood cells in the tubules. With The treatise on surgery written by Gulielmus de
special studies, one can detect immune complexes in Saliceto of Bologna about the middle of the thir-
the glomeruli on the basement membranes. In an teenth century but not published until 1476, has a
occasional individual, masses of cells, called epithe- reference to dropsy, scanty urine, and hardened kid-

neys. This is chronic kidney disease, and was very looked for serum in the urine of 130 persons who
likely glomerulonephritis. had dropsy and found it present in 78 of the sam-
In another surgical text, Peter Lowe, a Scottish ples. He also noted that "urine in dropsy, when it
physician, wrote that "hydropsie" is a "Tumor contains serum, is often more abundant than in
against nature, engendered of great quantitie of Wa- health." (The increased urine volumes probably
ter, Winde, or Flegme, which sometimes is dispersed compensate for the loss of urine concentration in
through the whole bodie, and is called Universall," patients with failing kidneys.) He observed altered
and "The cause interne of hydropsie . . . cometh . . . kidneys in one dropsical patient at autopsy who had
through the vice of the . . . kidneyes." serum in his urine, but with this limited observa-
Scientific urinalysis, representing a major step for- tion did not feel justified in associating the findings
ward from the "looking and tasting" era of the Pisse with the kidney abnormalities, and wrote that "the
Prophets, commenced with Frederick Dekkers, who morbid appearances in the kidneys might be alto-
discovered in 1695 that some urine samples, like gether unconnected with morbid secretion. . . ."
serum, would coagulate with the application of heat In 1818 John Blackall also observed dropsy, albu-
or the addition of acetic acid. Today we know such a minuria, and bloody urine in patients after scarla-
coagulum as albumin. tina. Sometimes these patients at autopsy had "kid-
In the next century, Domenico Cotugno, an anat- neys firmer than the ordinary, in one of them very
omy professor at Naples University, was attending a strikingly so, approaching the scirrhus; but whether
young soldier with a febrile illness, who "on the fifth this is merely accidental, or the effect of such a
day had a wonderful eruption of intercutaneous wa- course and what relation it bears to the discharge of
ter." This fluid and the urine each "contained a co- serum must be left for future observations."
agulable matter . . . over the fire." There is no indica- Those observations were soon to be made by Bright,
tion that he knew of Dekkers' observation, and a giant of medicine, who was conducting his land-
Cotugno may be the first to have noted albumin in mark studies as a staff physician at Guy's Hospital in
the urine, associated with dropsy. London, on patients with post-scarlatina dropsy and
About this same time, Nils Rosen von Rosenstein, albuminuria. In 1827, he first reported his findings
a Swedish physician, wrote an account of observa- and wrote, "The observations which I have made re-
tions made during the scarlatina epidemic in Upsala specting the condition of the urine in dropsy, are in a
in 1741: great degree in accordance with what had been laid
down by Dr. Blackall in his most valuable treatise."
But others . . . between the eighteenth and twenty second Bright's meticulously recorded accounts of the clini-
days, when the disease was to supposed to be quite cal features of the disease, and his colored illustra-
cured . .. complained of weakness . . . and then the body
began to swell, as in a dropsy [anasarca]; and upon this tions of the pathological changes in the kidneys, re-
came on a fever, anxiety, uneasiness, oppression and main a model for us today. Hefirmlyestablished that
asthma. Very little was discharged, and it is said to have dropsy was accompanied by pathological changes in
been bloody in some patients, or appeared as water in the kidneys. His studies, however, did not address the
which fresh meat has been washed. question of how albumin enters the urine. This ques-
tion could not be answered until nephron structure
This is an early, accurate account of post- was further defined.
streptococcal glomerulonephritis. Marcello Malpighi had tried to answer the ques-
tion in 1666 at Bologna. He knew of the glomeruli,
Nineteenth-Century Writings and that they could befilledby injected dye into the
The relationship between scarlet fever and dropsy blood vessels, but his frustration in being unable to
was well recognized over the next 50 years. Thomas establish their function is indicated in his writing:
Bateman described eight patients with post-scarla-
tina dropsy seen between 1804 and 1816 in the I worked a long time in order that I might subject to the
eye this evident connection [between "glands" and tu-
public dispensary in London. At St. Thomas Hospi-
bules] which reason sufficiently attests. For I have never
tal, William Charles Wells observed in 1811 that been able to observe liquids perfused through the arteries
the urine in patients with dropsy after scarlet fever penetrating the urinary vessels, even though theyfillthe
"contains almost always the serous, and sometimes glands, and the same is true when the veins are filled. .. .
the red matter of blood." Unaware of Cotugno's writ- So that, in spite of many attempts (but in vain) I could not
ings, he credits another with first noting, in 1798, demonstrate the connection of the glands and the urinary
"serum" in the urine of patients with dropsy. He vessels. (Italics mine)

VIII.60. Glomerulonephritis (Bright's Disease) 749
In the early nineteenth century, the Berlin school, duced it into their classification. That classification
led by Johannes Peter Mueller, dominated anatomy remained in use with little modification for nearly a
and physiology in Europe. Mueller knew of Malpi- half century.
ghi's descriptions of the glomeruli, but he considered The active use of biopsy to evaluate the nature of
them to be simply receptacles of blood. He believed the kidney disorder in the patient was also an impor-
that urine was secreted by the epithelium of the tant clinical contribution. As biopsy experiences ac-
proximal tubules. cumulated in the 1950s, 1960s, and 1970s, clinical
But William Bowman in 1842 (then just 26 years and pathological classifications of Bright's disease
old) wondered, as Malpighi had, why the glomerulus appeared in large numbers. Basic science investiga-
would end blindly in a space opening into the tors gave us an understanding of the important role
tubules. He wrote: of the immune system in glomerulonephritis, and
It would indeed be difficult to conceive a disposition of
they established the glomerular basement mem-
parts more calculated to favour the escape of water from brane as the site of leakage in albuminuric states.
the blood than that of the Malpighian body. . . . Why is so The tubule is not the source of the urine protein, but
wonderful an apparatus placed at the extremity of each altered tubular reabsorption possibly plays a lesser
uriniferous tube, if not to furnish water, to aid in the role in albuminuria. The major contributions of pa-
separation and solution of the urinous products from the thology in the twentieth century are the use of thin
epithelium of the tube? This abundance of water is appar- sections, immunofluorescent techniques, and elec-
ently intended to serve chiefly as a menstruum for the tron microscopy in biopsy interpretation.
proximate principles and salts which this secretion con- Thus, today Bright's disease consists of many dif-
tains, and which, in speaking generally, are far less sol- ferent disorders, all of which can be considered
uble than those of any other animal product.
glomerulonephritis. The diagnosis and management
Bowman suggested that protein and red cells might of these disorders will continue to challenge clini-
pass through the glomerulus under abnormal cians, pathologists, and basic science investigators
circumstances! into the twenty-first century.
A German physiologist, Carl Ludwig, followed up Donald M. Larson
on Bowman's anatomic observations just a few years
later, with the view that the glomerulus was a semi- Bibliography
permeable filter. Hydrostatic pressure pushed fluids Bright, Richard. 1827. Reports of medical cases, selected
through the capillaries that held back the proteins. with a view of illustrating the symptoms of cure of
In 1861 Thomas Graham showed that membranes diseases by a reference to morbid anatomy. London.
could hold back colloids but permit the passage of 1836. Cases and observations illustrative of renal dis-
crystalloids. The glomerulus was established as the ease accompanied with the secretion of albuminous
source of urine, but albuminuria was still thought to urine. Guy's Hospital Reports I: 338-400.
Castiglioni, Arturo. 1975. A history of medicine, trans. E.
come from tubular epithelium. For many years the
B. Krumbhaar. New York.
term nephrosis was used to express this belief and Dixon, F. J., J. D. Feldman, and J. J. Vazquez. 1961. Experi-
define proteinuric states. mental glomerulonephritis: The pathogenesis of a
Through the rest of the nineteenth century, pa- laboratory model resembling the spectrum of human
thologists adhered to this view, even as microscopic glomerulonephritis. Journal of Experimental Medi-
studies advanced. The source of urinary albumin in cine 113: 899-920.
dropsy was not determined for more than a century. Germuth, F. G., Jr. 1953. A comparative histologic and
Bright's descriptions of the kidney contained no immunologic study in rabbits of induced hypersensi-
records of microscopic examination. Rudolph Vir- tivity of the serum sickness type. Journal of Experi-
chow established the cellular basis for pathology in mental Medicine 97: 257-82.
1858, and classified Bright's disease into three Heptinstall, Robert H. 1983. Pathology of the kidney, 2
categories - involving the tubules, the connective tis- vols. Boston and Toronto.
Major, Ralph H. 1932. Classic descriptions of disease.
sue, and the blood vessels. In some of his later writ-
Springfield, 111.
ings, he referred to glomerular changes, but he contin- 1954. A history of medicine, Vols. I and II. Springfield,
ued to believe the main changes were in the tubules.
The first pathologist to use the word "glomerulone- m.
phritis" was Edwin Klebs in 1879. The term became Talbott, John H. 1970. A biographical history of medicine.
New York.
synonymous with Bright's disease after F. Volhard
and T. Fahr (1914, in Heptinstall 1983, Vol. 1) intro-

Classification and Diagnosis
VHI.61 Although shown on an occasional autopsy or dissec-
Goiter tion, the connection between goiter and the thyroid
gland was not clear as a concept. Other diseases of
Quis tumidum guttur miratur in Alpibus? the neck confounded the connection in a living pa-
Juvenal, Satire 13, c. A.D. 127 tient. The main confounder was scrofula, which in
Goiter is an ancient disease that has always been medieval Latin meant "swelling of the glands" and
more common in some places than in others. Chi- today is still used to connote tuberculous lymph
nese writings show that goiter was known at least glands (or nodes) in the neck.
by the third century B.C. (Lee 1941) and possibly Because obvious and severe goiter affecting large
earlier (Needham et al. 1970). When Juvenal (Deci- portions of a population occurred only in certain
mus Junius Juvenalis), the Roman satirist, wrote, regions, the disease in these areas was called en-
about A.D. 127, "Who is amazed at a swollen neck demic. In these instances the connection to the thy-
in the Alps?" he knew that goiter was so much roid gland was fairly clear. But where only a few
more common there than elsewhere that it should individuals in a population had a mass in the neck,
be no surprise. it might be called sporadic goiter — because not
endemic - or something else. If the mass was not too
large, it might move with swallowing and so was
Terminology called an enlarged thyroid. But if the mass were
The word "goiter" (or goitre in Europe) derives from nodular, firm, and immovable, then it was consid-
the Latin gutter, but the meaning has shifted from ered to be probably characterized by tuberculous
"throat" or "neck" to mean specifically an enlarged nodes. This diagnostic confusion persisted until the
thyroid gland. An ancient Greek synonym was mid-nineteenth century. Jean Louis Alibert, for ex-
bronchocele, a term actually used to describe any ample, classified endemic goiter as a type of scrofula
enlargement in the neck, although it meant literally ("endemic scrofula") found in rural areas (Alibert
a swelling or an outpouching of the trachea. Over 1835). Today endemic goiter is arbitrarily defined; it
time this term also came to mean an enlarged thy- is present, according to some, if more than 10 per-
roid (e.g., the English "bronchocele" of the eigh- cent of a population is goitrous.
teenth and nineteenth centuries). Modern synonyms Besides the occasional large and disfiguring goi-
are the Spanish bocio (from Latin, botium), the Ital- ters that were cosmetically distressing and some-
ian gozzo, and the German Kropf. The ancient Latin times blocked breathing, endemic goiter areas also
word struma was probably originally used to de- produced a much smaller number of people who were
scribe inflamed lymph nodes in the neck, most likely retarded from birth, both mentally and physically,
tuberculous, but was later used to denote the normal whose faces were disfigured, and who were some-
thyroid gland, and is still so used although it is times deaf and mute. Most but not all had goiter,
almost obsolete. which was also common in their mothers. They were
Confusion over names is understandable, as the called cretins, and their disease, endemic cretinism.
thyroid gland itself was unknown until the six- The word "cretin" probably derives from the French
teenth century. Leonardo da Vinci may have drawn cretien, and thence from the Latin christianus (or
the thyroid about the year 1500, but the drawing Christian); the term was probably used to make
was not published until much later. Andreas Vesa- clear that these persons were truly human.
lius did note "laryngeal glands" in 1543, but not in Cretinism is probably as ancient a disease as
humans. Nevertheless, by the end of the sixteenth goiter, but descriptions are not as old. Travelers'
century, Vesalius's contemporaries and successors observations, again in the Alps, go back to the early
had clearly identified the human thyroid gland as a thirteenth century, but clinical allusions begin with
discrete structure: Bartolomeo Eustachi in 1552, Paracelsus (Theophrastus Bombastus von Hohen-
Realdo Colombo in 1558, and Giulio Casserio in heim), lecturing about 1527, who connected cre-
1600. In 1619, Hieronymus Fabricius ab Aquapen- tinism (or at least "fools") with goiter. Good descrip-
dente realized that goiter arises from an enlarge- tions begin with Felix Platter, who probably ob-
ment of this gland, and in 1656 Thomas Wharfton served it in 1562 and who also made the association
named the gland by virtue of its proximity to the of cretinism with goiter (Cranefield 1962).
thyroid ("shield-shaped") cartilage. Thus, by the seventeenth century, the concept of

VIII.61. Goiter 751
goiter as an abnormally enlarged thyroid gland was was to remove it, or at least part of it, surgically. The
reasonably well established as was its association problem was that surgery commonly killed the pa-
with cretinism and with the mountainous alpine ar- tient, and some surgeons said that such an operation
eas of Europe. Yet, cretinism in particular was rare should simply not be done. Others persisted, and by
outside densely goitrous sites in the Alps, and thus the 1880s were able to remove all or most of a
most European physicians never saw it. Just as goiter goitrous thyroid with death rates under 1 percent.
could be confounded with other neck diseases, so E. Theodor Kocher in Berne and the cousins
could cretinism with any sort of mental retardation. Jacques-Louis and Auguste Reverdin in Geneva
Thus a certain amount of diagnostic "fuzziness" per- were pioneers in this surgery. In 1882-3, however,
sisted into the nineteenth and twentieth centuries. these Swiss surgeons realized that removing the en-
Today goiter means only an enlarged thyroid, and tire thyroid caused symptoms resembling cretinism,
any large thyroid is a goiter. The goiter may be but that this did not happen when only part of the
uniformly and diffusely enlarged ("simple" or diffuse thyroid was taken out. Simultaneously in London,
goiter), have several lumps in it (multinodular goi- Felix Semon proposed that cretins, patients after
ter), or be only a single nodule, although on closer total thyroid removal, and adults with a mysterious
study many of the latter prove to be multinodular. disorder called myxedema (described by William
The standard screening method of the World Health Withey Gull in 1873) all suffered because they
Organization in endemic areas is to assign grada- lacked thyroid glands. He was ridiculed, but 5 years
tions to the disorder. Grade O is no goiter, grade 1 is later a committee appointed to investigate this
a goiter that is palpable but not visible, grade 2 is an theory found Semon to be correct (Ord 1888). Thy-
easily visible goiter, and grade 3 is a very large roid deficiency or myxedema, now called hypothy-
goiter visible 30 meters away (Stanbury and Hetzel, roidism, is a synonym for decreased thyroid function
eds. 1980). or a lack of thyroid hormone secretion.
Some goiters are malignant (e.g., thyroid cancer
or lymphoma), but the vast majority are benign.
Some are associated with specific thyroid diseases
Etiology
such as hyperthyroidism (an overactive thyroid); its
opposite, hypothyroidism (an underactive thyroid;
Early Theories
Many theories were generated over the centuries to
such as in goitrous cretinism); and thyroiditis (an
explain goiter. An ancient idea was that goiter is due
inflammation of the thyroid that can be acute or
to an excess of phlegm descending from the head to
chronic). The taxonomies (geographic, clinical, and
the throat. An excessiveflexingof the head was seen
etiologic) persist today, derived from different types
as the cause by many, including Michelangelo (Mi-
of data with different historical origins. They over-
chelagniolo Buonarroti), who suggested it in 1509.
lap considerably and continue to give rise to confu-
Geographic peculiarities were frequently blamed as
sion in diagnosis and treatment.
well, such as high altitude or narrow valleys, as
Cretinism is called endemic if it is found in an were climatic features such as high humidity, too
area of endemic goiter, but is called sporadic if not much sun, and polluted air, proposed by physicians
found in an endemic area; the latter is almost al- such as Horatio-Benedict de Saussure in 1779 and F.
ways nongoitrous. Again, entirely different causes E. Fodere in 1789. Differences in drinking water
underlie the two types. Both goiter and cretinism, were also viewed with suspicion, especially cold wa-
whether endemic or sporadic, can be associated with ter, water made from snow, and water from streams
hypothyroidism, although the notion that cretinism or springs believed to be tainted. Finally, hereditary
is synonymous with childhood hypothyroidism is or constitutional factors were thought important;
false. Hypothyroidism is common but not universal that idea is attributed to Jacques de Vitry about
in cretinism, and it occurs only occasionally with A.D.1220.
goiter.
Early Treatment Nineteenth-Century Theories

Goiter of itself is not particularly harmful unless it During the nineteenth century, the major theories of
grows to compress the trachea or causes emotional the etiology of goiter focused at least in part on some
upset. But when therapy for a large goiter was re- peculiarity of the drinking water, a lack of iodine, an
quired, the only solution until the twentieth century infection of some sort, or some combination of these.

Climatic factors had been dismissed when it turned cist and botanist, using a somewhat better assay for
out that goiter can occur in almost any climate, dry iodine, found the element in freshwater plants and
or wet, from the Arctic to the equator (Hirsch 1885). suggested these plants be used to prevent goiter
High altitude had been rejected as well, for the dis- (Chatin 1850a). He went on to measure iodine in
ease was not limited to mountainous regions; flat- water samples from all over France, and in some
lands had endemic goiter as well. foods as well, and concluded that a lack of iodine in
The long process of linking endemic goiter and drinking water in certain areas appeared to be the
cretinism to iodine deficiency began in 1811, when principal cause of goiter (Chatin 1850b). The follow-
Bernard Courtois discovered the element while making year, the French Academy of Sciences appointed
ing saltpeter for gunpowder during the Napoleonic a committee to study Chatin's results; its report
Wars. He noticed it as a violet vapor released from (Th6nard et al. 1852) congratulated Chatin for his
the residue of burnt seaweed by sulfuric acid. It was work, but viewed the association between a lack of
subsequently named iodine by Joseph Louis Gay- iodine and goiter as unproven.
Lussac from the Greek word for "violet." The key There were successful trials of iodine prophylaxis
was the seaweed. For hundreds of years, dating at of endemic goiter in the nineteenth century, notably
least from the twelfth and thirteenth centuries in in South America in 1835 (Dumas et al. 1851) and in
Europe, and from the third century A.D. in China, Savoy in the 1840s. Yet success did not encourage
seaweed and marine sponge had been placed among further trials, and the question of iodine as a goiter
the many animal and vegetable remedies for goiter, preventive was not pursued.
sometimes burned before use. Within a few years The rise of the "new pathology" with Rudolph
after Courtois' discovery, iodine was detected in vari- Virchow as its leader in the mid-nineteenth century
ous seaweeds by Humphry Davy, Gay-Lussac, and also interfered with the idea of iodine deficiency as
Andrew Fyfe. the cause of endemic goiter. During the 1860s
In 1818, Jean-Frangois Coindet, a Geneva physi- Virchow himself felt that excessive growth of a tis-
cian, suggested that because some seaweeds were sue, in this case goiter, must be due to some irrita-
effective in treating goiter, iodine might be the action that stemmed from a "positive substance" and
tive principle. He asked Jean-Baptiste Dumas (then not a deficiency (Follis 1960). In France the view
aged 18 and later to become one of France's most persisted that goiter and cretinism were serious prob-
famous chemists) to look for iodine in marine lems but that the cause was not iodine deficiency.
sponge; Dumas did and found it (Thorpe 1902). Rather, an agent toxique special was thought to be
Coindet then gave iodine, mostly as potassium responsible (Baillarger 1873).
iodide, to goitrous patients, with good results that The reluctance to accept iodine deficiency as a
were almost immediately confirmed by other Swiss cause of goiter is understandable: There was then no
physicians. good example of a disease known to be caused by a
An effective therapy, however, does not necessar- deficiency. Further, the theory did not explain why
ily mean that a disease is due to a deficiency of the only some people in low-iodine areas got goiter while
therapeutic agent. (Few would suggest, for example, others did not. This problem remains unresolved
that pneumococcal pneumonia results from penicil- today.
lin deficiency.) Thus although the chemist Jean Bap- Later in the nineteenth century, after the discov-
tiste Boussingault suggested as early as 1825 that ery of the bacterial cause of many diseases, it was
iodine deficiency might be the cause of goiter and postulated that goiter was caused by either a bacte-
recommended the addition of iodine to table salt to rium or a bacterial toxin, perhaps in the water. Ed-
prevent it, little came of this suggestion. win Klebs, a pioneer microbiologist, believed he had
A generation later, Jean-Louis Prevost, another found such an agent in 1877, and August Hirsch
Geneva physician, made the same suggestion as (1885) stated flatly that "endemic goitre and cre-
Boussingault. But iodine had fallen into disfavor as tinism have to be reckoned among the infective dis-
therapy for goiter because of toxic side effects when eases." Indeed, the notion that goiter has an infec-
given in excess, including (in retrospect) iodine- tious cause had its twentieth-century adherents at
induced hyperthyroidism. Coindet himself had seen least until mid-century, although the evidence put
this (he used a dose of 1 to 2 grains of iodine per day) forth has never been convincing. But while the infec-
and had cautioned against too high a dose, but to no tious hypothesis has faded, the parallel notion of a
avail. toxin in the water, possibly of bacterial origin, is still
In the 1850s, Adolphe Chatin, a French pharma- alive (Gaitan et al. 1983) and warrants serious con-

VHI.61. Goiter 753
sideration, particularly in areas where there is goiter - through William Halsted, his teacher at
much goiter despite adequate iodine intake. Johns Hopkins Medical School. By 1910, he showed
Iodine as a therapy in medicine, in contrast to its that iodine prevented goiter in brook trout (Marine
use solely to treat goiter, caught on rapidly in the 1910), and therefore gave it to patients at Cleve-
decade after its discovery. Beginning in the late land's Lakeside Hospital and to children of friends to
1820s, for example, Jean-G. A. Lugol, another Ge- prevent goiter. In fact, he tried to give it to all school-
neva physician whose name is memorialized in the children in Cleveland, but the school board, led by a
still-used Lugol's solution of iodide-iodine, em- goiter surgeon, said it would poison the children. (At
ployed it against any scrofulous disease (Lugol the time there was also a controversy over compul-
1829). Its use spread rapidly to include treatment of sory smallpox vaccination.) Not until several years
other conditions, among them rheumatic diseases, later was Marine able to carry out a large-scale
almost any pulmonary condition, any disease that study of iodine prophylaxis for goiter. The results
involved swelling of a part of the body, and syphilis. were clear-cut: Sixty-five percent of goiters became
Late-nineteenth-century texts on medicine and phar- smaller, whereas this happened in only 14 percent of
macology indicate its continued wide use while recog- the control group, and new goiter was largely pre-
nizing the hazards of overdosage (Wood 1881; Pepper vented (0.2 percent got new goiter among those
1894; Osier 1892). Iodine as therapy for goiter did treated versus 21 percent for those untreated) (Ma-
persist (Inglis 1838; Wood 1881) but only as one of rine and Kimball 1920). This study provided the
several possible treatments (Pepper 1894; Osier impetus, in the United States, for the use of iodized
1896) and was employed without much enthusiasm. salt, which now contains 0.01 percent potassium
In sum, up to the 1890s there was no resolution of iodide.
the problem of the cause of endemic goiter or cre- Even though Marine showed iodine to be both a
tinism. No clear choice could be made among the treatment and a preventive for endemic goiter, he
drinking water, iodine deficiency, or toxic-infective had not proven that these patients were iodine defi-
hypotheses. Prophylaxis of goiter with iodine on a cient. It remained for J. F. McClendon, a nutrition
mass scale was not popular and hence not done. Fear officer in the U.S. Army during World War I, to mea-
of inducing serious side effects if everyone took iodine sure accurately iodine in water and food. He showed
in salt or food was widespread since, after all, iodine not only that there was a correlation between lower
was a known poison. Social and political issues fre- iodine in food or water and the presence of human
quently arose, similar to those that surround ques- goiter, but also that rats on a low-iodine diet got
tions of the chlorination or fluoridation of water. goiter (McClendon and Williams 1923). He later put
It was in the 1890s, however, that substantial together worldwide data to support his thesis that
advances began to be made in goiter research. low iodine in the water causes goiter (McClendon
George R. Murray (1891) discovered that a glycerin 1939); although the data in general did support the
extract of sheep thyroid cured myxedema (hypothy- idea, close reading shows many exceptions.
roidism). After this, investigators began to look for By 1924, Michigan, a state with endemic goiter,
iodine in the thyroid gland itself. Eugen Baumann offered iodized salt to the public after an intense
(1895), for example, in looking for the active com- public education campaign; within 12 years goiter
pound in the thyroid, made a fairly potent extract. prevalence fell from 37 percent to 8 percent and, by
When analyzing that extract, he routinely looked for 1951, to 2 percent. Ohio, Marine's own state, never
iodine, not expecting to find it; to his surprise it was acted. Still, Marine's statement that "endemic goiter
there. is the easiest known disease to prevent," though a
bit hyperbolic, was finally shown to be reasonably
Twentieth-Century Theories correct.
From this point research diverged: One path led to Over the years since Marine's study, the average
the isolation of a specific thyroid hormone, thyrox- daily iodine intake in the United States has in-
ine, by Edward C. Kendall in 1914 (Kendall 1915) at creased several times not only because of iodized salt
the Mayo Clinic; and another led to studies relating (the label now says that iodine is "a necessary nutri-
goiter to the iodine content of the thyroid rather ent"), but because of the widespread use of pur-
than to that of the environment. chased foods that contain iodine, such as bread and
David Marine came to Cleveland, Ohio, an area of milk. Thus, in the United States, few can today
endemic goiter, in 1905. He was aware of the impor- develop iodine deficiency, and, as in countries with
tance of hyperplasia - the process that leads to similar food sources, goiter is mostly sporadic and

occurs either spontaneously or as a result of factors Conclusions
other than iodine deficiency, such as exposure to Overall, changes in how goiter was defined pro-
therapeutic X-rays (DeGroot et al. 1983) or radiation gressed erratically. As theories and techniques em-
from atomic fallout (Hamilton et al. 1987; Morimoto ployed in anatomy and pathology were developed,
et al. 1987). Sporadic goiter is also called nontoxic the concept of "goiter" shifted from the simplistic
goiter, meaning that the patient is not hyperthyroid. idea of a swollen neck, to an enlarged thyroid of
Sporadic goiter can be any of the clinical types (i.e., several types, to a range of different thyroid dis-
diffuse or nodular). Yet, some areas of endemic goi- eases. However, early taxonomies did not disappear
ter persist in the United States, especially in parts of but persisted along with the new.
Appalachia, and may be caused by a goitrogen (a Along with these changes in taxonomy came paral-
substance that causes goiter). Goitrogens certainly lel changes in purported causes and the possibilities
exist, but how much they contribute to human goiter of prevention. Focusing for the moment only on io-
is unclear (Delange and Ermans 1976). dine, one can demonstrate a continuous link from
the Chinese use of seaweed through the European
Prevention and Treatment Middle Ages and folk medicine, to the discovery and
In many other parts of the world, both rich (Scriba et use of the element in the nineteenth and twentieth
al. 1985) and poor (Prevention 1986), goiter remains centuries. In actuality, however, although empirical
endemic (World Health Organization 1960; Stan- "folk" medicines containing iodine were effective
bury and Hetzel 1980) with its attendant disfigure- against goiter, they were used along with many oth-
ment, cretinism, and hypothyroidism. It is worth ers that seem to have had no benefit. Nineteenth-
noting that persons in an endemic area could have century French physicians may have been "right" in
any of the diseases that cause sporadic goiter, which proposing iodine as a treatment for endemic goiter,
is one reason why goiter prevalence never falls to but they did not convince their colleagues. That io-
zero even with iodine repletion. For some areas this dine deficiency might cause goiter was confounded
endemia is a major public health problem, and mil- by iodine's use in goiter treatment and prophylaxis;
lions of people remain at risk. The disease, when furthermore, the technical inability to measure con-
endemic, is almost always associated with low iodine sistently and accurately small amounts of iodine led
intake and iodine deficiency, and while there re- to persistent and valid controversy. Improvements in
mains no good explanation as to why some do not the iodine assay in the late nineteenth and early
develop goiter in areas of low dietary iodine, iodine twentieth centuries provided a solid basis for resur-
does prevent the disease. The issue then becomes a recting earlier beliefs in its effectiveness; moreover,
social and political one of providing iodine to those because it was thought that iodine ought to prevent
in deficient areas and then getting them to take it. endemic goiter, the studies were done that proved it.
As Marine wrote, "Endemic goiter will be prevented But the pendulum then swung to the other extreme,
only when society decides to do it." with many researchers believing that iodine was the
If a large goiter already exists, however, iodine answer to all endemic goiter. It was not, however,
will likely not be of help and surgery may be needed. and we now face the scientific challenge of teasing
On the other hand, thyroid therapy alone can shrink out several probable factors in addition to iodine
some goiters, as was shown as early as 1894 (Bruns deficiency that can produce endemic goiter, as well
1894; Reinhold 1894), and prevent recurrence of oth- as the political challenge involved in iodine prophy-
ers after surgery even if the goiter is cancerous laxis on a worldwide basis.
(Mazzaferri and Young 1981). Thus thyroid hormone In conclusion, sporadic goiter is usually not due to
can be the initial treatment for goiter and should be iodine deficiency but is mainly the result of an intrin-
used after any goiter surgery. sic thyroid disease, often related to genetic, immuno-
Therapies for endemic and sporadic goiter and cre- logic, or enzymatic factors; it is apparently influ-
tinism are fairly straightforward, although some dis- enced by gender, as it is more common in women.
agree on details of testing or timing. In developed Sporadic cretinism (or neonatal hypothyroidism) is
countries they are easy to apply in principle; the almost never caused by iodine deficiency, but is usu-
major problems are societal and relate to detection ally the result of failure of the thyroid gland to
and prevention. In less developed countries the pub- develop; thus there is no goiter. For this condition, a
lic health aspects are paramount, especially where public health approach, with testing of all newborns,
budgets are limited; prevention of endemic goiter is mandatory to prevent irreversible brain damage.
and cretinism is an effective use of funds. On the other hand, endemic goiter and cretinism

VIII.61. Goiter 755
are usually related to a low dietary iodine, although pathology, Vol. II. Chronic infective, toxic, parasitic,
goitrogens, genetic, and immunologic factors may be septic and constitutional diseases, trans. C. Creighton,
operative in some locales. Taking iodine cures some from the 2nd German edition. London.
and prevents almost all; again a public health ap- Inglis, J. 1838. TreatiseonEnglishbronchocelewithafewre-
proach is essential. marks on the use of iodine and its compounds. London.
Kendall, E. C. 1915. The isolation in crystalline form of
Clark T. Sawin
the compound which occurs in the thyroid: Its chemi-
cal nature and physiologic activity. Journal of the
Bibliography American Medical Association 64: 2042—3.
Alibert, J.-L. 1835. Monographic des dermatoses ou precis Lee, T. 1941. A brief history of the endocrine disorders in
theorique et pratique des maladies de la peau, 2d edi- China. Chinese Medical Journal 59: 379-86.
tion. Paris. Lugol, J.-G.-A. 1829. Memoire sur I'emploi de l'iode dans
Baillarger, J. G. F. 1873. Enquete sur le goitre et le cre- les maladies scrophuleuses. Paris.
tinisme. Reviewed in: Gazette Hebdomadaire de Medi- Marine, D., and C. H. Lenhart. 1910. On the occurrence of
cine et de Chirurgie, 2d ser., 10: 807. goitre (active thyroid hyperplasia) in fish. Bulletin of
Baumann, E. 1895. Ueber das normale Vorkommen von Johns Hopkins Hospital 21: 95—8.
Jod im Thierkorper. Hoppe-Seyler's Zeitschrift fiirPhy- Marine, D., and O. P. Kimball. 1920. Prevention of simple
siologische Chemie 21: 319-30. goiter in man. Archives of Internal Medicine 25: 661—
Bruns, P. 1894. Ueber die Kropfbehandlung mit Schild- 72.
rusenfiitterung. Deutsche Medizinische Wochenschrift Matovinovic, J. 1983. Endemic goiter and cretinism at the
41: 785-6. dawn of the third millennium. Annual Review of Nu-
Chatin, A. 1850a. Existence de l'iode dans les plantes trition 3: 341-412.
d'eau douce: Consequences de ce fait pour la geog- Mazzaferri, E. L., and R. L. Young. 1981. Papillary thyroid
nosie, la physiologie v6getale, la therapeutique et carcinoma: A 10-year follow-up report of the impact of
peut-etre pour l'industrie. Comtes Rendus Hebdoma- therapy in 576 patients. American Journal of Medi-
daires de I'Acadimie des Sciences 30: 352—4. cine 70: 511-18.
1850b. Recherches sur l'iode des eaux douce (suite): De McClendon, J. F. 1939. Iodine and the incidence of goiter.
la presence de ce corps dans les plantes et les animaux Minneapolis.
terrestres. Comtes Rendus Hebdomadaires de I'Acad- McClendon, J. F, and A. Williams. 1923. Experimental
emie des Sciences 31: 280-3. goitre and iodine in natural waters in relation to
Cranefield, P. F. 1962. The discovery of cretinism. Bulletin distribution of goitre. Proceedings of the Society for
of the History of Medicine 36: 489-511. Experimental Biology and Medicine 20: 286—7.
DeGroot, L. J., et al. 1983. Retrospective and prospective Merke, F. 1984. History and iconography of endemic goitre
study of radiation-induced thyroid disease. American and cretinism. Berne-Hingham. [An excellent guide
Journal of Medicine 74: 852-62. to older works.]
Delange, F. M., and A. M. Ermans. 1976. Endemic goiter Morimoto, T., et al. 1987. Serum TSH, thyroglobulin, and
and cretinism: Naturally occurring goitrogens. Phar- thyroidal disorders in atomic bomb survivors exposed
macology and therapy [C] 1: 57-93. in youth: 30-year follow-up study. Journal of Nuclear
Dumas, (J.-B.), et al. 1851. Rapport sur les recherches de Medicine 28:1115-22.
M. le Dr. Grange, relatives aux causes du crelinisme Murray, G. R. 1891. Note on the treatment of myxoedema
et du goitre, et aux moyens d'en preserver les popula- by hypodermic injections of an extract of the thyroid
tions. Comtes Rendus Hebdomadaires de I'Acadimie gland of a sheep. British Medical Journal 2: 796-7.
des Sciences 32: 611-18. Needham, J., et al. 1970. Proto-endocrinology in medieval
Follis, R. H., Jr. 1960. Cellular pathology and the develop- China. In Clerks and craftsmen in China and the West.
ment of the deficiency disease concept. Bulletin of the Cambridge.
History of Medicine 34: 291-317. Ord, W. M. (chairman). 1888. Report of a committee of the
Gaitan, E., et al. 1983. In vitro measurement of antithy- Clinical Society of London nominated December 14,
roid compounds and environmental goitrogens. Jour- 1883, to investigate the subject of myxoedema. Trans-
nal of Clinical Endocrinology and Metabolism 56: actions of the Clinical Society of London 21 (Supple-
767-73. ment): 1-215.
Hamilton, T. E., et al. 1987. Thyroid neoplasia in Marshall Osier, W. 1892. The principles and practice of medicine, 1st
Islanders exposed to nuclear fallout. Journal of the edition. New York.
American Medical Association 258: 629-366. 1896. The principles and practice of medicine, 2d edition.
Harington, C. R. 1933. The thyroid gland: Its chemistry New York.
and physiology. London. [A historical chapter on goi- Pepper, W., ed. 1894. A textbook of the theory and practice
ter and cretinism.] of medicine by American teachers, Vol. 2, 1021-2.
Hirsch, A. 1885. Handbook of geographical and historical Philadelphia.

Prevention and control of iodine deficiency disorders. death, but, if untreated, it produces serious sequelae
1986. Lancet 2: 433-4. in both men and women.
Reinhold, G. 1894. Ueber Schilddrusen Therapie bei kropf- The gonococcus, Neisseria gonorrhoeae, shares an
leidenden Geisteskranken. Milnchener medizinische ecological niche with other sexually transmitted
Wochenschrift 41: 613-14. pathogens such as Chlamydia trachomatis, Urea-
Rolleston, H. D. 1936. The endocrine organs in health and plasma ureslyticum, and T-mycoplasmas. It depends
disease with an historical review. London. [See espe-
cially pp. 192-207.]
for its survival on variable virulence, sufficient num-
Scriba, P. C, et al. 1985. Goitre and iodine deficiency in bers of asymptomatic infectees, an ability to produce
Europe. Lancet 1: 1289-93. a rapid genomic response to antibiotic pressure, a
Stanbury, J. B., and B. S. Hetzel, eds., 1980. Endemic symbiotic relationship with new pieces of genetic
goiter and endemic cretinism: Iodine nutrition in material (called plasmids), and propitious set of so-
health and disease. New York. [A modern detailed cial and sexual mores among its hosts. As history
text.] demonstrates, this seemingly delicate balance has
Thenard, L. J., et al. 1852. Rapport sur les travaux de M. been universally available.
Chatin, relatifs a la recherche de l'iode, et sur differ-
entes notes ou memoires presentes sur le meme sujet,
par MM. Marchand, Niepce, Meyrac. Comtes Rendus
Etiology and Diagnosis
Hebdomadaires de I'Academie des Sciences 35: 505- The causative agent of gonorrhea is the gonococcus
17. (N. gonorrhoeae) - a small, diplococcus whose flat-
Thorpe, T. E. 1902. Essays on historical chemistry. London. tened apposing surfaces, tinctorial properties (when
Wood, H. C, Jr. 1881. A treatise on therapeutics, 3d edition. stained by Gram's method), and association with
Philadelphia. polymorphonuclear leukocytes provide a typical mi-
World Health Organization (WHO). 1960. Endemic goitre. croscopic picture. In certain sites (e.g., urethra, joint,
Geneva. [Strong on epidemiology with good maps and cerebrospinal fluid, ocular conjunctiva), demonstra-
a short historical chapter.] tion of the typical morphology is virtually diagnos-
tic. From other sites (rectum, pharynx), however, the
possible presence of other gonorrhea types renders
the Gram-stained smear less sensitive. For all sites,
culture of the organism on artificial media is re-
quired for diagnostic assurance. Confirmation re-
VIII.62 quires typical morphology, demonstration of indo-
Gonorrhea phenol oxidase production, and the ability of the
organism to metabolize glucose, but not fructose,
maltose, sucrose, or mannitol.
The name gonorrhea, which means "flow of seed,"
and its vernacular counterparts ("clap," "dose," Clinical Manifestations
"strain"), reflect a hazy comprehension of the dis-
ease. The only accurate term in common use is Genital Site Infections in Men and Women
"drip," which acknowledges the white-to-yellowish Pus issuing from the penile opening, often accompa-
milky discharge from the male penis. But even this nied by discomfort, pain, or burning on urination, is
more honest description includes only the male ure- the most frequently recognized clinical manifesta-
thral portion of a broader syndrome. tion of gonorrhea. The gonococcus adheres to cells
Gonorrhea is an infection of mucosal surfaces that line the distal urethra, establishing - in the
caused by a small gram-negative bacterium - the symptomatic individual - an inflammatory reaction
gonococcus — whose only reservior in nature is hu- and the subsequent outpouring of polymorphonu-
man. Its presence in the lower male or female geni- clear leukocytes. (This primary pathological process
tal tract defines the condition gonorrhea; otherwise, is basically the same at all mucosal sites of infec-
the adjective "gonococcal" is used to precede a ge- tion.) Though the majority of men will become symp-
neric infective syndrome (as in "gonococcal endocar- tomatic 3 to 5 days after adequate exposure, the
ditis"). Though gonorrhea is transmitted primarily clinical spectrum varies. In perhaps one-quarter of
to genital mucosa through sexual contact, it may patients, pain or discharge will be attenuated or
cause localized abscesses or generalized dissemina- subsymptomatic (i.e., insufficient to cause the pa-
tion, with infection of the skin, heart valves, joints, tient to seek medical care). In addition, a substantial
and central nervous system. It is rarely the cause of proportion of men with gonorrhea will be asympto-

VIII.62. Gonorrhea 757
matic. Before the advent of antibiotics, the major association with characteristic skin lesions and ar-
sequelae of male urethral infection were postinflam- thritis. The skin lesions are small, hemorrhagic ar-
matory fibrosis and stricture of the urethra. Such eas with necrotic centers, and generally number
complications are now rare. fewer than 20. The infected joint(s) usually exhib-
Though women have long been known to harbor its) the four classic features of arthritis: swelling,
the organism, only recently have distinct clinical redness, pain, and heat. The knee is most frequently
syndromes been identified. Part of the delay is due to involved, followed by elbows, ankles, wrists, and
the fact that asymptomatic infection probably occurs small joints of the hand. Patients with DGI usually
more frequently in women, and little clinical atten- respond well to routine treatment and rarely suffer
tion is paid to the "normal" vaginal discharge. Infec- long-term musculoskeletal complications.
tion of the female urethra occurs in 70 to 90 percent
of women with gonorrhea, but rarely in the absence Other Clinical Manifestations
of concomitant infection of the endocervix. The more A variety of other rare infections with the gonococ-
important lower tract manifestation of gonorrhea in cus have been documented. Adults occasionally de-
women is infection of the uterine cervix. A syndrome velop gonococcal conjunctivitis, with a potential for
of purulent or mucopurulent endocervical discharge more serious ocular involvement, through direct
characterizes the infection. Though the clinical diag- (i.e., hand-to-eye) contact with infected secretions.
nosis may be complicated by the coexistence of infec- Gonococcal endocarditis, myocarditis, hepatitis, and
tion with other pathogenic organisms, cervical meningitis may occur as part of the disseminated
mucopus is clearly not "normal" and requires system- syndrome. Perihepatitis (termed the Fitz-Hugh-
atic bacteriologic investigation. Curtis syndrome) has traditionally been attributed
Both sexes contract anal and throat infection from to gonococcal infection in the upper right quadrant,
direct exposure to infected penile secretions. Both usually in association with classic PID. Recent evi-
are associated with symptoms in a minority of cases. dence, however, indicates that the syndrome is more
Asymptomatic rectal infection probably plays a ma- often associated with chlamydial, rather than gono-
jor role in transmission. Throat infection is of minor coccal, infection.
importance, except as a site for dissemination of the
gonococcus into the bloodstream. Gonococcal Infection in Children
The other major mode of transmission of the gonococ-
Pelvic Inflammatory Disease (PID) cus is from mother to child. A newborn may become
Perhaps the major modern concern about gonorrhea infected during passage through an infected birth ca-
is its potential for destruction of female reproductive nal, and the most common clinical manifestation is
organs. The gonococcus may spread upward from the gonococcal ophthalmia. The typical syndrome in-
cervix to inflame the uterine lining of the fallopian cludes the development of purulent discharge from
tubes (salpingitis) and ultimately cause peritonitis. one or both eyes with relatively rapid progression, in
Once established, PID becomes chronic, of long dura- the untreated child, to more generalized ocular
tion, and with serious consequences. Approximately involvement, scarring, and blindness. The use of rou-
20 percent of women will have a recurrence after tine eye prophylaxis with silver nitrate (see discus-
treatment for a primary episode of gonococcal PID. sion under History, below) was a landmark in preven-
The syndrome of chronic pain, lower abdominal dis- tive medicine and greatly reduced the occurrence of
comfort, and dyspareunia reflects insidious scarring this syndrome. Children may develop gonorrhea in
and closure of the fallopian tubes, which may cause sexual sites as well. It has become apparent, in recent
ectopic pregnancy and lead ultimately to involun- years, that the majority of infected children have suf-
tary infertility. Studies in Sweden indicate that the fered sexual abuse. In boys, symptomatic or asympto-
risk of sterility is 12 to 16 percent after a single matic anogenital infection may occur. In girls, the
episode of salpingitis and rises to 60 percent after primary manifestation is a vulvitis, because the
three episodes. prepubertal cervix is not an adequate milieu for sur-
vival of the gonococcus.
Disseminated Gonococcal Infection (DGI)
An uncommon but distinctive picture appears when Classification, Immunology, and Pathology
the gonococcus is spread via the bloodstream. The The importance of gonorrhea is measured not only by
classic picture includes (often) asymptomatic infec- its considerable burden of acute disease and long-
tion of the pharynx, penis, vagina, or rectum in term consequences, but also by some of its extraordi-

nary biological characteristics. The virulence of the the wide variation in clinical and diagnostic facili-
gonococcus rests in its ability to adhere to muscosal ties, the extent of disease reporting, and the degree
surfaces, to resist immunological defenses, to cause of care given to case finding. The disease is wide-
asymptomatic infection, and to resist antibiotic kill- spread in both the industrialized and the developing
ing. These qualities have been important in the devel- world, but it is likely that the burden on developing
opment of four major classification schemes based nations is greater. It is estimated that the incidence
upon the following: in some large African cities may be as high as 3,000
to 10,000 per 100,000 population. Because gonor-
1. The presence or absence of pili (long, filamentous rhea is, in principle, a disease of high incidence and
projections on the surface of the gonococcus), low prevalence, it is noteworthy that surveys of
which determine adherence to mucosal cells. Their women attending prenatal and family planning clin-
presence is, in turn, reflected in the size, shape, ics in Africa disclose a prevalence as high as 17
and opacity of gonococcal bacterial colonies, and percent. Among prostitutes in Latin America, Asia,
forms the basis for the earliest classification and Africa, the prevalence of gonorrhea may be 30 to
scheme used. 50 percent. These are, of course, occasional surveys
2. The nutritional requirements of the gonococci. of selected populations, but, in the absence of system-
Typing of organisms based on their need for cer- atic information, they provide some sense of the mag-
tain amino acids (auxotyping) has determined the nitude of the problem.
presence of special strains that are more or less
A number of industrialized nations, on the other
sensitive to antiobiotics, and that have a greater
hand, do have systematic reporting of gonorrhea. Rou-
propensity to cause disseminated infection.
tinely collected statistics have permitted documenta-
3. The antigenic structure of the gonococcal cell en-
tion of the major epidemiological event in the history
velope, which provides a mechanism for classifica- of gonorrhea: a worldwide pandemic that began in
tion (serovars). Serovars have been used, in con-
the late 1950s and peaked in the mid-1970s.
junction with auxotyping, to show patterns of dis-
A comparison of disease rates in the United
tribution and to link cases epidemiologically.
States, the United Kingdom, Sweden, and Canada
4. Susceptibility to antibiotics. Four transferable (Figure VIII.62.1), all of which have advanced
pieces of genetic material (plasmids) have been
identified, which have helped in geographic local-
ization of cases. 500
These systems for classification reflect the consider-

able pathogenetic repertoire available to the gonococ-
cus. In contrast, the immunologic armamentarium of I "00
the host seems inadequate. Genital secretions may 5
have some inhibitory effect on gonococci in vitro, but
are not protective. Local immunoglobulin production o 300
has been demonstrated but may be counteracted by 8
protease produced by the gonococcus. Serum anti-
body is usually demonstrable in previously infected
i 2OO-
persons, but resistance to serum killing is a typical
feature of freshly isolated gonococci. Indeed the net
result of studies to date simply reflects the time- I
I 100
honored observation that people may contract gonor-
rhea again and again. There is no apparent protective
human immunity. The existence of asymptomatic in-
fection, and the apparent immunologic tolerance of 1950 1960 1970 1980
1940
the host, may account in part for the ecological suc- Years
cess of the gonococcus.
Figure VIII.62.1. Gonorrhea incidence in selected coun-
tries, 1940-83. (From R. C. Barnes and K. K. Holmes.
Distribution and Incidence 1984. Epidemiology of gonorrhea: Current perspectives.
Gonorrhea is found worldwide, but documentation of Epidemiological Reviews 6: 1-30; 3, fig. 1, by courtesy of
its true extent is lacking. Direct comparisons of inci- Epidemiological Reviews and the American Journal of
dence among nations are difficult to make because of Epidemiology.)

health care systems, indicates a rise in gonorrhea
occurrences after World War II, with a subsequent
fall to a nadir in the mid-1950s. Though varying in
size and timing, an increase in gonorrhea through-
out the 1960s, with termination of the accelerated
rise by the mid-1970s, was experienced by each na-
tion. The graph is representative of the situation for
most industrialized countries during the interval,
and conveys the disparity with which nations were 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45*
apparently affected. At the peak, in the mid-1970s, TEAR
rates among industrialized nations differed by as
much as 10-fold. (By contrast, rates among develop- Figure VIII.62.3. Gonorrhea: age-specific rates for men
and women, United States, 1985.
ing nations during the interval differed even more
wildly, but here the variation in reporting clearly
plays an important role.)
The impact and specific features of the pandemic 80 percent of the world's population in the coming
may be demonstrated by examining the history of years.
the disease in the United States during this period.
Between 1956 and 1985, rates of gonorrhea in- History
creased in all age groups for both men and women Gonorrhea is the oldest, as well as the most common,
(Figure VIII.62.2). Rates for females are higher at of the venereal diseases. An Egyptian papyrus from
younger ages, and peak at ages 15 to 19 years. Rates approximately 3500 B.C. prescribes plant extracts to
for males peak at ages 20 to 24, producing a cross- soothe painful urination. The Hebrew Bible makes
over pattern (Figure VIII.62.3). The origin of this reference to treatment of genital exudates, which
increase, and of the pandemic in general, is not fully may well refer to gonorrhea. Hippocrates recognized
understood. It is often attributed to changes in sex- the venereal nature of transmission at about the
ual mores during the 1960s and 1970s, with major beginning of the fourth century B.C., and Galen, in
increases reported in the frequency of premarital the second century A.D., is believed to have coined
sexual experiences by both men and women, a the name. In the fourteenth century, a description of
greater availability of contraceptive technology, and the ailment that stressed a major symptom, chaude
an increase in the number of individuals entering pisse, or "hot piss," led to the disease's receiving this
the age of sexual activity (the so-called baby boom appellation from the French.
generation). By 1500 or so, interest centered on the distinction
It is likely that the pandemic has not yet had its between syphilis and gonorrhea. The majority opin-
full impact on the developing world, though the peak ion appeared to favor the notion that they were dif-
in industrialized nations seems to have passed. If so, ferent manifestations of the same disease, particu-
the burden of morbidity, long-term sequelae, and larly because syphilis was so clearly protean in its
mortality will continue to have a major influence on manifestations. However, in the middle of the six-
teenth century, a French physician, Jean Fernel,
wrote of gonorrhea as a separate disease from syphi-
lis in his Medicina. The British physician Francis
Balfour, writing two centuries later, has also been
credited with the belief that syphilis and gonorrhea
were distinct.
Confusion set in, however, following John Hunter's
argument that the cause of both diseases was the
same and that gonorrhea was a manifestation of the
disease on a secreting surface (mucosa) whereas
syphilis was its manifestation on a nonsecreting sur-
1956 1959 1962 I96S 1968 1971 1974 1977 1980 1983 face (skin). To prove this, he infected himself with
YEAR
pustular discharge from a patient he thought had
Figure VIII.62.2. Gonorrhea rates in men and women, gonorrhea, and developed syphilis instead. The pa-
aged 20-4, United States, 1956-85. tient may have been dually infected, but at any rate,

this was an unfortunate instance of a brilliant and ments in the understanding of gonorrhea until the
heroic use of the scientific method gone wrong, and it sulfonamides (e.g., sulfamidochrysoidine, Prontosil)
postponed scientific understanding of the two dis- were introduced in 1937. This success was short-
eases for decades. lived, and true antibiosis for gonorrhea appeared
It was during this same period (1760-90) that the only in the 1950s with the general availability of
most lucid literary account of gonorrhea appeared. penicillin. The next critical breakthroughs were the
James Boswell, the biographer of Samuel Johnson, description of the different colonial morphologies by
kept a meticulous diary of his own repeated encoun- Douglas S. Kellogg et al. in 1963 and the develop-
ters with gonorrhea. The diary details the clinical ment of a selective medium for culturing the
manifestations and psychological effects of 19 epi- gonococcus by James D. Thayer and John E. Martin
sodes. There is little question of the impact of gonor- in 1964. Subsequent events, including the world-
rhea on his life, and, by extension, on the life of wide pandemic of the 1960s and 1970s, and the ma-
countless others in the era. He is believed to have jor advances in immunology and molecular biology,
died of gonorrheal complications. were alluded to earlier. Clearly, it is only in recent
In the 1790s, Benjamin Bell of Edinburgh, who times that gonorrhea's effect on us, and in turn, our
was in disagreement with Hunter, published several ability to alter its course, have dramatically
tracts that explored the clinical and epidemiological changed.
evidence for gonorrhea and syphilis as separate dis-
ease entities. He posed a number of simple ques-
tions: Why is gonorrhea more common when the Geography
skin of the penis is at greater risk of exposure than Through gonorrhea is found worldwide, the lack of
the urethra? Why are there geographic differences systematic data precludes meaningful global map-
in the distribution of the two diseases? Why have ping. But even if national rates were universally
their manifestations appeared in the same popula- available, a local approach might be more informa-
tions at different points in time? tive. In its transmission, its endemicity, and its con-
tinued propagation, gonorrhea is a neighborhood dis-
It remained, however, for Philippe Ricord, in a ease. An understanding of the local geography is
series of clinical observations and direct experi- predicated on a coherent theory for transmission.
ments in the mid-1800s, to provide a definitive dis-
tinction between the two diseases. It is of interest
that Ricord commented that there is no justification Epidemiology
for experimentation with grave diseases in human The clinical epidemiology of the classic gonorrhea
beings, although he inoculated 17 prisoners with syndromes forms the basis for the population epidemi-
gonorrheal pus, producing occasional ulcers with ology of the disease. Gonorrhea is transmitted by
prompt healing, but no evidence of syphilis. sexual contact. The probability of transmission from
In 1879, Albert Neisser, an assistant in dermatol- male to female after a single contact is approximately
ogy at the University of Breslau, Germany, pub- 50 percent; from female to male, 22 percent. The
lished his preliminary findings which confirmed the incubation period is 3 to 5 days in men and slightly
conclusions of Ricord by describing the organism longer in women. A significant proportion of both
that now bears his name. This was probably the sexes never becomes symptomatic. The incidence of
second description of a major human pathogen (after disease in a given community, then, is a function of
Koch's identification of the anthrax bacillus 3 years two major parameters: (1) the degree of sexual inter-
earlier). In 1882, the organism was first grown in action, which includes the frequency of new partners,
vitro by Ernst von Bumm. The first major preven- as well as the duration, intensity, frequency, and logis-
tive action was taken in the following year when tics of sexual contact; and (2) the duration of infec-
Karl Siegmund Crede, at the Lying-in Hospital in tiousness, which takes into account the proportion of
Leipsig, recognized the benefit of instillation of 2 asymptomatic infection, the proportion of a popula-
percent silver nitrate solution (later reduced to 1 tion that will seek health care, the adequacy of ther-
percent) in the eyes of newborns. The occurrence of apy, and the extent to which sex partners are apprised
gonococcal ophthalmia diminished rapidly with the of their risk. Clearly, the final epidemiological pic-
widespread adoption of this procedure. ture will be a complex interaction of biological, social,
Unfortunately, advances did not follow in rapid and individual events. In general, however, gonor-
succession. In fact, after the initial diagnostic proce- rhea is a disease of high incidence but short duration
dures were established, there were no major improve- and, hence, of low prevalence.

Transmission Dynamics tain the endemicity of gonorrhea - were drawn
Beginning in the early 1970s, mathematicians Her- from so-called core groups. These groups were de-
bert Hethcote and James Yorke constructed a theo- fined as persons with stable sociodemographic and
retical framework for the transmission dynamics of geographic characteristics who constituted a small
gonorrhea. Using some of the concepts of population minority of cases (under 5 percent), but who
ecology, they noted that the reproduction rate for accounted - either directly or indirectly - for most
gonorrhea (i.e., the ability of an infected person to gonorrhea transmission. It is within such groups
replace him- or herself) must be determined when that the epidemiological features of gonorrhea (no
the disease is at endemic equilibrium. In the steady immunity, immediate infectiousness, year-round
state, therefore, each infected person must have two transmission) were fully operative. The limit to gon-
"adequate" contacts for transmission on average orrhea spread within a core group was termed the
("adequate" means that the gonococcus is transmit- saturation effect: that is, sexual contact between
ted). There must be a "source" contact and a infected persons.
"spread" contact for disease propagation. Because In a series of elegant mathematical discussions,
not all sexual contacts are "adequate," it follows that Hethcote and Yorke developed a model for the dy-
the average number of total contacts must be namics of transmission based on population compart-
greater than 2. ments that included core and noncore groups. They
In constructing a model of transmission dynamics, were able to demonstrate the plausibility of an equi-
several key epidemiological observations must be librium state in which most cases were attributable
considered: to small groups of active transmitters. Parallel with
this theoretical development, some empirical evi-
1. Gonococcal infection does not confer protective
dence for the physical existence of core geographic
immunity; thus an individual is "immune" only
areas and definable core groups emerged.
when infected.
It was shown in 1979, based on the routine report-
2. Individuals become infectious soon after expo- ing of gonorrhea morbidity data, that the city of
sure; there is, then, no "exposed, incubating"
Denver contained four different areas with high con-
group to be considered in a model. centrations of infectees (see Figure VIII.62.4). Each
3. Seasonal variation of gonorrhea is well denned, geographic area housed a distinct population sub-
with a peak in late summer in temperate cli- group: black heterosexuals, Hispanic heterosexuals,
mates, but the variation is small (about 10 per- white homosexual men, and military recruits.
cent) in comparison with other diseases. This im-
Through analysis of over 120,000 geocoded cases
plies that the parameters used in the model can
be constant.
4. Data derived from interviewing gonorrhea pa-
tients about their sex partners suggest that the
average number of "adequate" contacts is well
below 2. In 1985, there were only 0.3 infected
contacts found for each person with gonorrhea
interviewed. Even with allowances for slippage in
the system of interviewing cases, finding con-
tacts, and bringing them to medical examination,
E53 Group 1 -69%8tock
this is far below the two infected contacts per case U S Group H - «8% Chicono
needed to maintain a reproduction rate of 1 and to I3U Group m -94% White
EDGroupEZ -95% While (Military)
preserve endemic equilibrium. roupJZ -Single Suburbon loci
It was reasoned, then, that the observed number

of infected contacts per case is a weight average of
two groups: (1) those for whom one or no contacts
were identified (nontransmitters); (2) those with two Figure VIII.62.4. Distribution of gonorrhea in Denver,
or more contacts identified (transmitters). Those in Colorado, 1974-6. [From R. B. Rothenberg. 1979. Analy-
the first group - the vast majority of gonorrhea sis of routine data describing morbidity from gonorrhea.
infectees - were unlikely to pass the infection to Sexually Transmitted Diseases 6(1): 5-9; 6, fig. 1, by
another person. Hethcote and Yorke hypothesized courtesy of Lippincott/Harper & Row, Philadelphia,
that the transmitters - those who actually main- Penna.]

of gonorrhea in upstate New York from 1975 to 1980, views of 97 percent of the cases that occurred during
a general geographic pattern emerged. Within all 12 a 6-month interval. Again, clustering of over 50 per-
Standard Metropolitan Statistical Areas (SMSAs, cent of the cases was demonstrated in about 5 per-
the urban centers), there was intense concentration cent of census tracts. Social aggregation of cases was
of gonorrhea in a small number of contiguous census demonstrated by the consistent use of six drinking
tracts (core areas) within the inner cities. In a con- establishments by a major proportion of infectees,
centric circle surrounding the core were a group of and by the aggregation of patients and their sexual
census tracts with somewhat lessened gonorrhea partners in the same census tracts. Contrary to com-
rates (adjacent areas). The rest of the SMSA consti- monly held belief, the majority of sexual partners
tutes the peripheral area, with a markedly dimin- had known each other socially prior to sexual con-
ished gonorrhea burden. The concentration of gonor- tact. The interconnection of individuals in networks
rhea in the core area was 20-fold higher than that could be demonstrated through linkage provided by
for New York State in general, and several of the the interview process. Further analysis demon-
census tracts in the core had rates that were 40-fold strated that the core groups in Colorado Springs
higher. Not only was this pattern repeated in all generated a high force of infectivity (i.e., days of
SMSAs, but all the core areas were similarly charac- potential transmission in infected exposed partners),
terized by high population density and low socioeco-
nomic status. The geographic configuration for Buf-
falo, New York, is typical (Figure VIII.62.5).
This pattern was also documented in Colorado
Springs, Colorado, using data collected from inter-
PPNG % TOTALS
Esa >3o% PPNG = 1670 Cases
E ^ l 21-30% pen sensitive = 4084 Cases
CHID 11-20% Total = 5754
f—n 1-10% PPNG % Total = 29%
I 1 0%
Figure VIII.62.6. Penicillinase-producing Neisseria gonor-

rhea (PPNG) as percentage of total gonorrhea, by zip
code analysis in Miami, Florida, March 1985 to February
Figure VHI.62.5. Occurrence of gonorrhea in Buffalo, 1986. (From J. M. Zenilman et al. 1988. Penicillinase-
New York, 1975—80; distribution of core and adjacent producing Neisseria gonorrhoeae in Dade County, Flor-
tracts. (From R. B. Rothenberg. 1983. The geography of ida: Evidence of core-group transmitters and the impact
gonorrhea: Empirical demonstration of core group trans- of illicit antibiotics. Sexually Transmitted Diseases 15:
mission. American Journal of Epidemiology 117(6): 688- 45-50; 47, fig. 2, by courtesy of Lippincott/Harper &
94; 691, fig. 1.) Row, Philadelphia, Penna.)

Vni.63. Gout 763
and had a heightened degree of sexual interaction Kampmeier, R. H. 1977. John Hunter — a man of convic-
both inside and outside their core groups. tion. Sexually Transmitted Diseases 4(3): 114-5.
Similar geographic clustering was documented in 1978. Identification of the gonococcus by Albert Neisser.
Seville, Spain, where it was noted that all the STD Sexually Transmitted Diseases 5(2): 71-2.
syndromes appeared to exhibit a similar geographic 1979. The early identification of several venereal infec-
pattern. The presence of penicillin-resistant N. gon- tions. Sexually Transmitted Diseases 6(2): 79-81.
Kellogg, D. S., et al. 1963. Neisseria gonorrhoeae: I. Viru-
orrhoeae has provided a convenient marker for the lence genetically linked to clonal variations. Journal
demonstration of core-group aggregation as well. In of Bacteriology 85:1274-9.
an initial outbreak reported from Liverpool in 1976, Ober, W. B. 1969. BoswelPs gonorrhea. Bulletin of the New
clustering of cases occurred within two small inner- York Academy of Medicine 45(6): 587-636.
city districts. In Miami, a major endemic area for re- Potterat, B. A., et al. 1985. Gonorrhea as a social disease.
sistant gonorrhea in the United States, the clustering Sexually Transmitted Diseases 12(1): 25-32.
of resistant cases within presumed core-group areas Rice, R. J., et al. 1987. Gonorrhea in the United States
paralleled that for all of gonorrhea (Figure VIII.62.6). 1975—1984: Is the giant only sleeping? Sexually Trans-
It cannot be assumed that the geographic charac- mitted Diseases 14(2): 83-7.
teristics displayed in these examples are universal. Rothenberg, R. B. 1979. Analysis of routine data describ-
In particular, differences in human ecology and sexu- ing morbidity from gonorrhea. Sexually Transmitted
Diseases 6(1): 5-9.
ality in developing countries may dictate a different
1983. The geography of gonorrhea: Empirical demon-
pattern, and data are not yet available. It might stration of core group transmission. American Jour-
tentatively be concluded, however, that a concentric nal of Epidemiology 117(6): 688-94.
pattern of gonorrhea risk, which diminishes out- Thayer, J. D., and J. E. Martin. 1964. A selective medium
ward from the central inner city, exists in many for the cultivation of Neisseria gonorrhoeae and Neis-
major urban areas. The potential for use of geo- seria meningitidis. Public Health Report 79: 49—57.
graphic patterns in the development of disease con- Zenilman, J. M., et al. 1988. Penicillinase-producing
trol strategies, and in the understanding of other Neisseria gonorrhoeae in Dade County, Florida: Evi-
sexually transmitted syndromes, is an area for fur- dence of core-group transmitters and the impact of
ther development. illicit antibiotics. Sexually Transmitted Diseases 15:
Richard B. Rothenberg 45-50.
This chapter was written in the author's private capacity. No

official support or endorsement by the Centers for Disease Con-
trol is intended or should be inferred. VIII.63
Bibliography
Gout
Alvarez-Dardet, C , S. Marquez, and D. J. Peres. 1985.
Urban clusters of sexually transmitted disease in the
city of Seville, Spain. Sexually Transmitted Diseases Gout is a chronic, intermittently symptomatic dis-
12(3): 166-8. ease. It is manifested primarily by small numbers of
Barnes, R. C , and K. K. Holmes. 1984. Epidemiology of acutely painful swollen joints that result from an
gonorrhea: Current perspectives. Epidemiologic Re- inflammatory reaction to the precipitation of crys-
views 6: 1-30. tals of monosodium urate.
Britigan, B. E., M. S. Cohen, and P. F. Sparling. 1985.
Gonococcal infection: A model of molecular patho- Etiology
genesis. New England Journal of Medicine 312(26): The predisposing metabolic factor for primary gout
1683-94. is an abnormally high or rapidly changing concentra-
Hethcote, H. W., and J. A. Yorke. 1984. Gonorrhea trans- tion of uric acid in the blood. Hyperuricemia may
mission dynamics and control. Lecture Notes in Bio- result from an accelerated synthesis of uric acid, or
mathematics. New York.
decreased excretory capacity for uric acid in other-
Holmes, K. K. (Chairman). 1986. WHO Expert Committee
on Venereal Diseases and Treponematoses. Technical
wise normal kidneys as a result of unidentified but
Report Series No. 736. Geneva. probably heritable causes. Hyperuricemia leading to
Holmes, K. K., et al. 1984. Sexually transmitted diseases. secondary gout occurs particularly (1) in diseases of
New York. the blood-forming tissues that increase the availabil-
Hook, E. Q., and K. K. Holmes. 1985. Gonococcal infec- ity of precursors of uric acid; (2) in kidney failure,
tions. Annals of Internal Medicine 102: 229-43. which limits the excretion of uric acid; or (3) as a

result of medications that either accelerate the relationship between gout and urate nephrolithiasis
breakdown of purine-rich cells (e.g., antineoplastic may be is uncertain. Although 22 percent of the
drugs) or interfere with the renal excretory mecha- 1,258 New York gout patients studied by T.-F. Yu
nism (e.g., some diuretics). Dissolved in the serum, and A. B. Gutman (1967) had renal calculi at some
uric acid is harmless. However, because of unidenti- time, this condition antedated the first attack of
fied local circumstances it may leak from capillaries gout in 40 percent, and in 14 percent the delay was
and crystallize. The crystals of monosodium urate from 11 to 39 years. The probability of nephroli-
elicit the inflammatory reaction, which is the gouty thiasis is correlated with the serum urate content.
attack, and the microscopic identification of the crys- Thus, 15 percent of their total cases of gout had
tals in synovial fluid confirms the diagnosis. Why serum urate of less than 8 milligrams per 100 grams
this inflammation occurs predominantly in joints, of blood (mg%) without treatment, and nephrolith-
and why much more commonly in some joints (such iasis developed in 15 percent of these; in 32 percent
as those of the feet or in the knee) than in others of the gout patients the urate concentration ex-
(such as the hip or those of the vertebral column) are ceeded 10 mg%, and 43 percent of these had
unexplained characteristics. Unexplained as well is nephrolithiasis. In other large series of cases of gout,
the question why tophi, which are urate deposits nephrolithiasis has ranged from 28 percent (German
that form beneath the skin, are usually painless and spa) to 4 percent (San Francisco private practice)
the antiuricemic effect of estrogens. (Table VIII.63.1).
Allopurinol therapy, which reduces the uric acid
Clinical Manifestations pool, decreases the incidence of uratic kidney stones
Fully 90 to 95 percent of patients are male, and gout and has the same effect in nongouty urate hyper-
rarely develops in women before menopause. The excretors who have a history of calcium stone forma-
first attack most often occurs in the fifth decade in tion.
men and in the sixth decade in women. The rate of
production of uric acid and, related thereto, the on- History
set of primary gout, thereafter diminishes. For many centuries the term gout and podagra were
The normal uric acid content, the "miscible pool," as nonspecific as arthritis is in modern usage. The
in men is about 1.2 grams, and in women, 0.6 grams clinical differentiation of the disease was begun in
(Seegmiller, Laster, and Howell 1963). Because of an the late seventeenth-century works of Thomas
imbalance between synthesis and excretion, uric Sydenham, although his contemporary, Anton van
acid accumulates in part as the subcutaneous depos- Leeuwenhoek, using his simple microscope, de-
its called tophi. About 50 percent of untreated pa- scribed the appearance of crystals from a tophus.
tients have tophi 10 years after their first attack of Nearly a century later, in 1776, Karl W. Scheele, a
gout. Thus 53 percent of the cases seen in the Mount Swedish pharmacist, discovered an organic acid in
Sinai Hospital (New York) Gout Clinic during 1948- urinary concretions which for that reason he called
53 had tophi, whereas tophi were found in only 14 lithic acid. In 1797, at Cambridge, William H.
percent of the cases of gout first seen at the Mayo Wollaston analyzed tophi and found that they con-
Clinic in 1949. The difference presumably was the tained "lithic acid." In 1798, this substance was re-
result of referral bias. However, the incidence of named acide ourique by the French chemist Antoine
tophaceous gout has decreased steadily in both insti- F. de Fourcroy because he also found it to be present
tutions: In New York during 1969-73, it was 17 in normal urine.
percent of all gout patients, and at the Mayo Clinic Another half century passed before uric acid was
in 1972 it was only 3 percent (Yu 1984). Statistics of shown to be even more intimately related to gout. In
cases gathered in London during 1958—67 revealed 1847 and in 1854, London physician Alfred B.
that 21 percent had tophi, whereas 28 percent of Garrod devised two tests whereby uric acid could be
cases seen at a German health resort during 1955- detected in blood in hyperuricemic states such as
64 had tophaceous gout. gout and uremia. He also demonstrated urate in
Next to tophi the most common uratic manifesta- subcutaneous tissues and articular cartilage in cases
tion of gout is kidney stones {nephrolithiasis). This of gout. Garrod hypothesized that gout might result
association has been noted since at least the six- either from a loss of renal excretory capacity or from
teenth century. Uric acid stones constitute no more increased formation of uric acid. A century after the
than 5 percent of all kidney stones, but about 80 publication of his 1859 monograph on gout, both
percent of calculi in cases of gout. How close the concepts were proved to be correct. In 1876 Garrod

VIII.63. Gout 765
Table VIII.63.1. Occurrence of nephrolithiasis with gout

Cases of gout % Nephrolithiasis
Author Year Location Male Female Total Male Female Total
Bartels 1954 Boston 450 3
Kuzell 1955 San Francisco 373 131 504 5.4 0.7 3.9
Nishioka 1980 Tokyo 2,455 5.5
Grahame 1970 London 311 43 354 9.0
Ruiz-Moreno 1959 Buenos Aires 593 44 637 10.0 2.3 9.4
Hench 1928 Rochester, Minn. 100 12.0
Kittredge 1952 New Orleans 324 13.9
Br0chner- 1941 Copenhagen 100 15.0
Mortensen
Hall 1967 Framingham, Mass. 271 34 306 15.4 11.8 15.0
Talbott 1960 Buffalo 184 7 191° 15.8 28.5 16.2
Yu 1967 New York 1,207 51 1,258 22.4 19.6 22.2
Gamp 1965 Bad Kreuznach 200 28.0
Serane 1954 Paris 136 136 33.1 33.1
"Autopsied cases.
also postulated that acute gout results from the pre- The Devonshire Royal Hospital in England repre-
cipitation of sodium urate in a joint or adjacent tis- sented the other extreme. During 1896-1900, gout
sue. This was proven in 1962 by the elicitation of was diagnosed in 2.42 percent of 14,224 admissions
gouty inflammation following the injection of suspen- (324 male, 20 female); during the next 5-year period,
sions of sodium urate crystals into human and ca- with changes in the physician staff, the frequency of
nine knee joints (Rodnan 1965). the diagnosis more than doubled to 5.26 percent of
Beginning in 1871 numerous gravimetric assays 15,836 admissions (743 male, 91 female) (Hill 1938).
of urinary uric acid were devised, but none was sensi- Clearly, such data do not prove the traditional im-
tive enough to be applicable to the much smaller pression that gout was peculiarly prevalent in En-
concentration in the blood. The wide variations of gland but, rather, suggest that the diagnosis was
uric acid excretion and the lack of understanding of being made or missed very subjectively.
uric acid metabolism cast doubt on the causative The first practical colorimetric technique sensi-
relationship of uric acid to gout. Two paradoxical tive enough to detect normal concentrations of uric
effects on clinical practice resulted. One was that the acid in blood was devised by Otto Folin at Harvard
old belief in "retrocedent" or "anomalous" gout - the University in 1912. Its sensitivity was gradually
idea that a wide variety of symptoms or diseases are improved so that in 1938 the uric acid content of the
caused by a "gouty poison" - gained new adherents. blood was shown to be greater in men than in
The other was that clinicians virtually ceased mak- women, thereby correlating with the rarity of gout
ing the diagnosis of gout. For example, at the Johns in women. However, physicians continued to be
Hopkins Hospital (Baltimore), only 42 cases were poorly aware of true gout. Philip Hench (1936) com-
admitted with this diagnosis during 1889-1903. At mented on this as follows:
the Massachusetts General Hospital, only 9 cases of
gout were found among 1,033 medical admissions for If more than 50-70% of his patients have tophi he is too
rheumatic diseases during 1893-1903 (Benedek exclusive and is probably omitting cases of bona fide (even
1987). Likewise, at a hospital in Cologne the diagno- if pretophaceous) gout. If less than 35-40% have tophi or if
sis of gout was made only 14 times among 23,870 more than 2-5% are females he is too inclusive, diagnos-
medical admissions (0.06 percent) during 1895- ing gout where it does not exist.
1900. However, in that hospital the diagnosis was
made in 10 cases or 0.35 percent of the admissions Methodological specificity in uric acid determina-
during the first year that Oscar Minkowski, who tion was achieved in 1953 with a technique that
was interested in this disease, was in charge of a employs the enzyme uricase. Nevertheless, most
medical service. laboratories continue to use less specific methods

that lend themselves to automation and give some- particularly to blood cell formation in elderly per-
what higher than "true" values (Benedek 1987). sons, and it has therefore fallen into disfavor.
Another pair of important pharmaceutical discov-
Treatment eries was introduced in 1963. Indomethacin effec-
Therapy of gout has two components: (1) treatment tively counteracts the acute gouty attack, and, al-
of the acute attack and (2) prophylaxis, which seeks though it does not alter the excretion of uric acid, it
to decrease the uric acid pool of the body. The former also does not depress blood formation; therefore, it
has always been predominantly medicinal, whereas gradually superseded phenylbutazone. Since then
the latter has been both dietetic and medicinal. many other "nonsteroidal antiinflammatory drugs"
Colchicum in the form of various alcoholic or aque- have been found to be similarly effective. Allopuri-
ous extracts from the bulb, stem, or seeds of the nol lowers the uric acid pool like probenecid, but by a
meadow saffron came into use in the second decade different mechanism. It diminishes the synthesis of
of the nineteenth century in France and England. It uric acid by inhibiting the activity of an enzyme
was included in the Dispensatory of the United States (xanthine oxidase). Like probenecid, allopurinol is of
of America in 1836, although its use was advocated no value in an acute gouty attack, but it has the
somewhat earlier. Hesitation about using colchicum advantages of effectiveness in the presence of renal
was due to recognition of its toxicity, as manifested failure, and the convenience of once per day dosage
by severe diarrhea, which also was believed to be the (Benedek 1987).
mechanism of its therapeutic effect. The active com- Dietetic attempts to treat or prevent gout are an-
ponent, colchicine, was isolated in 1820. Colchicine cient. They were based on beliefs in the virtue of
was available in pill form by 1900, but crude tinc- moderation in all things and, more specifically, in the
tures were still in use in the 1950s (Rodnan and belief that gout is caused in large measure by
Benedek 1970). excesses in the consumption of food and alcoholic
Until about 1910, when cinchophen was intro- beverages. Aside from the demonstration in 1924
duced, colchicine was the only remedy for acute that starvation results in an increased blood uric acid
gout. Cinchophen not only was effective in the acute concentration, scientific investigations of gout have
gouty attack but, in contrast to colchicine, also was been done only since the 1960s. The most important
an analgesic. Because of its chemical resemblance to finding has been that circumstances that result in the
salicylate, cinchophen was presumed to be tolerated formation of certain organic acids, particularly lac-
better than colchicine, which it virtually replaced in tate and beta-hydroxybutyrate, block the excretion of
the treatment of acute gout. However, by the 1930s uric acid and thereby increase the possibility that a
it became evident that cinchophen may cause severe gouty attack may occur. Starvation, substantial alco-
and even fatal liver damage. Hence, its use faded out hol ingestion, especially without eating, and uncon-
over a decade, and colchicine again became the stan- trolled diabetes mellitus are such conditions.
dard treatment. Uric acid found in the body is not absorbed as
The fact that both cinchophen and salicylates in- such, but is synthesized from breakdown products of
creased the renal excretion of uric acid and thereby various foodstuffs, particularly those that are rich
reduced the uric acid content of the blood was discov- in nucleoproteins (Seegmiller, Laster, and Howell
ered in 1913 and 1915, respectively, but was not 1963). A low-fat, largely vegetarian (60 g/day pro-
adapted to therapy. Two pharmaceutical break- tein) diet reduces the serum uric acid concentration
throughs occurred in 1951. Probenecid, a drug that by 1 to 2 milligrams below that found in a more
had been developed to retard the excretion of penicil- typical American diet (Gutman and Yu 1955). The
lin, was found to accelerate the excretion of uric effect such diets have on reducing gouty attacks is
acid. Although it has no analgesic or antiinflamma- equivocal. Since the advent of urate-depleting drugs
tory effect, it was well tolerated and convenient to such as probenecid and allopurinol, however, di-
take. As it reduced the serum uric acid concentra- etetic therapy has become irrelevant except for the
tion, the frequency of gouty attacks diminished and general advantages of weight reduction for the obese
tophi shrank. The other discovery was phenylbuta- gout patient.
zone, which proved to have therapeutic effects simi- Gout rarely is a direct cause of death, although
lar to cinchophen. Like probenecid, it increased the premature death due to diseases with which gout is
excretion of uric acid, but also like colchicine, it associated (principally hypertensive or arterioscle-
counteracted the acute attack, and it was a nonspe- rotic cardiovascular disease) is fairly common. For
cific analgesic as well. However, it proved to be toxic, reasons that are unclear, untreated hypertension

VHI.63. Gout 767
with grossly normal renal function is frequently as- duce another obstacle to any comparison of data
sociated with hyperuricemia. Because treatment of from various surveys.
hypertension usually includes drugs that interfere The prevalence of gout that is reported depends on
with the excretion of uric acid, hyperuricemia is the diagnostic criteria used; on the population from
greater and more prevalent in treated than in un- which the cohort is drawn; and on whether the di-
treated hypertensive patients. Thus, according to a agnosis is based on questionnaires or on single or
survey in London, 31 percent of untreated hyperten- repetitive examinations. For example, a predomi-
sive men and 23 percent of untreated hypertensive nantly younger population can be expected to have a
women had hyperuricemia, 12 percent having had lower prevalence of gout than one with a higher
attacks of gout, whereas 59 percent and 57 percent, mean age; a workforce may have a lower prevalence
respectively, of hypertensive men and women under than a random sample that may include persons who
treatment were hyperuricemic (Breckenridge 1966). are disabled by gout and associated diseases. Secon-
Conversely, in a series of 354 gout patients in Lon- dary gout, in which the disease results from (1) accel-
don, 52 percent had a diastolic blood pressure in erated purine metabolism inherent in another dis-
excess of 90 millimeters (Grahame and Scott 1970), ease, usually of the blood, (2) diminished excretion of
and of the cases studied by Yu (1984) in New York, uric acid resulting from renal failure, or (3) effects of
30 percent were considered hypertensive. Hyper- toxins such as lead, is not an epidemiological con-
lipidemia appears not to be correlated directly with founder because these circumstances are readily
hyperuricemia. Rather, both are associated with hy- identified and uncommon. At present, secondary
pertension and obesity. According to the Framing- gout arises most frequently as an incidental effect of
ham study, angina pectoris is twice as frequent certain antihypertensive medications.
among gouty as among nongouty men (Abbott et al.
1988), and Yu found that the causes of death among United States and Europe
427 gout patients were cardiovascular in 66 percent Only a few of the larger American and European
of the cases (Yu 1984). surveys of serum uric acid values will be cited. In a
survey in Tecumseh, Michigan, 9.2 percent of men
Epidemiology over 20 years of age had uric acid values greater
When considering the epidemiology of primary gout, than 7.0 mg%, and 8.7 percent of the women had
one must focus separately on hyperuricemia and the values greater than 6.0 mg% (Mikkelsen, Dodge,
factors that influence it. Although a rough correla- and Valkenburg 1965). In Framingham, Massachu-
tion does exist between the level of hyperuricemia setts, 4.8 percent of men and 3.3 percent of women
and the likelihood of an attack of gouty arthritis, the met this criterion (Hall et al. 1967). Racial compari-
predictive value is poor and appears to be worse in sons in rural Georgia (31 percent black men, 35
certain groups than in others. Of the measurable percent black women) revealed no racial differences
factors that affect the serum uric acid concentration, in mean uric acid values. However, the prevalence of
the most important are the protein content of the hyperuricemia was high, ranging from 13.6 percent
diet and overweight. Weight and the rate of uric acid for white men to 21.1 percent for black women. This
metabolism are to some extent genetically predeter- was attributed largely to the association between
mined. However, the immediate cause of a gouty hypertension and hyperuricemia and the use of
attack remains unknown. antihypertensive medications (Klein et al. 1973). A
Worldwide the severity and prevalence of gout comparison of uric acid values between white U.S.
have changed paradoxically since the 1940s. In the and Brazilian male military recruits showed Ameri-
highly developed countries, as a result of the advent cans to have higher uric acid concentrations: mean
of effective prophylactic drug therapy, the disease is 4.87 mg% versus 4.05 mg%, with 3.26 percent versus
now rarely disabling. Elsewhere, however, it has 0.35 percent having a value above 7.0 mg%. The
become more prevalent, predominantly as a result of difference correlated best with the 17 percent
"improved" diets. Unfortunately, there were no epi- greater mean weight of the Americans (Florey and
demiological surveys of serum uric acid or gout in Acheson 1968).
primitive societies before the 1960s, so that hypothe- Several American surveys have compared the se-
ses about whether ethnic differences are genetic or rum uric acid levels of executives and either lower-
the result of recent environmental changes are weak- level employees or age-matched general population
ened by a lack of baseline data. The different samples. The executives have consistently been
biochemical techniques that have been used intro- found to have higher mean urate concentrations and

a larger proportion of cases of hyperuricemia (Mon- alcohol consumption of 68 percent (Thiele and
toye et al. 1967). This finding, which has been incon- Schroeder 1982).
sistently confirmed in Europe, has not been ex- A study based on the records of general practitio-
plained by differences in physiognomy, blood pres- ners in Great Britain showed the prevalence of gout
sure, or medications. over the age of 15 years to be 7.3 per 1,000 males in
In a survey of nearly 24,000 men in Paris, 17.5 England, but only 2.8 per 1,000 in Scotland. Among
percent were found to have a uric acid value of 7.0 females the prevalence was 1.3 and 0.7 per 1,000 in
mg%, and 9.9 percent with a value of 7.5 mg% England and Scotland, respectively (Currie 1979). A
(Zalokar et al. 1972). Two English studies gave re- survey among men between the ages of 45 and 74 in
sults more consistent with U.S. findings, with 7.2 three English towns demonstrates that not only sex
percent and 10.8 percent of men having concentra- and age distribution but also how data are obtained
tions of 7.0 mg%. In Finland, 5.2 percent of men and influence the results. A simple questionnaire was
3.5 percent of women had uric acid values of 7.0 mg% mailed to over 15,000 men, of whom two-thirds com-
and 6.0 mg%, respectively (see Table VIII.63.2). The pleted it. In the three communities, 3.9 percent, 4.5
relation of uric acid values to nutrition was demon- percent, and 4.8 percent (average 4.4 percent)
strated epidemiologically by an investigation con- claimed to have gout, which was more than three
ducted in East Germany from 1969 until 1980 with times the prevalence for age-matched English men
samples of 726 to 1,199 adults. During these 12 years obtained from physicians' records (Gardner et al.
the mean serum urate content increased by about 50 1982).
percent (4.2 mg% to 6.3 mg% in men; 3.4 mg% to 5.2 In the Framingham investigation, gout was diag-
mg% in women), and the percentage with hyperuri- nosed in 2.8 percent of the men and 0.4 percent of the
cemia increased from 2.4 to 29.0 in men and from 1.8 women (Hall et al. 1967). The biennial incidence has
to 19.7 in women. These changes correlated well with been 3.2 per 1,000 men and 0.5 per 1,000 women
increases in the meat consumption of 37 percent and (Mikkelsen, Dodge, and Valkenburg 1965). A survey
Table VIII.63.2. Prevalence of hyperuricemia

Males Females
Location Year Cases Percent >7 mg% Cases Percent >6 mg%
England 1962 436 2.3 475 2.3
Japan (Osaka) 1966 378 4.0 434 2.5
U.S. (Mass.) 1967 2,283 4.8 2,844 3.3
Bulgaria 1966 188 4.8 232 7.0
Finland 1969 737 5.2 1,048 3.5
England 1977 512 7.2 254 0.4
Scotland (Glasgow) 1977 337 8.0
U.S. (Mich.) 1965 2,987 9.2 3,013 8.7
England (Liverpool) 1966 331 10.8
U.S. (New York) 1971 984 12.3
France (Paris) 1972 23,923 17.5
New Zealand (white) 1966 202 23.3 228 16.7
Palau Islands 1972 219 36 291 24
Samoa (urban) 1981 319 36 415 23
Samoa (rural) 1981 356 43 384 29
Rarotonga 1966 243 44 227 43
Mariana Islands 1966 160 45 175 28
Mariana Islands 1972 395 49 504 30
Tokelau Islands 1966 191 48 188 49
New Zealand (Maori) 1966 388 49 378 42
Nauru 1978 217 64 238 60

Vm.63. Gout 769
Table VIII.63.3. Prevalence of gout in relation to the disease. Similarly, a military surgeon in New
serum uric acid content in men Zealand in the 1850s found that although "rheumatic
affections" were much more frequent among New
Framingham, Zealanders than among the English, gout was un-
Mass." Paris, France 6 known. Hench, a leading expert, wrote in the 1948
Uric acid
(mg%) Subjects %Gout Subjects %Gout edition of Cecil's Textbook of Medicine that gout "is
common in England and France, less common but
<6.0 1,615 1.1 2,099 1.3 increasing in North America. Hebrews are affected,
6.0-7.9 432 8.6 1,852 3.2
prosperous American Negroes occasionally." Eugene
>8.0 22 36.3 306 17.6
Traut, in his textbook on rheumatic diseases, stated
Total 2,069 3.0 4,257 3.3 similarly in 1952 that gout "is unknown in China,
Japan, and the tropics. . . . It is rare in Negroes."
"Hall et al. (1967). 6Zalokar et al. (1972). The extent to which such statements reflected ei-
ther ignorance or changing circumstances cannot be
of more than 4,000 employed men in Paris found ascertained. They clearly are incorrect now. The
that 3.5 percent reported a history of gout and 3.0 most ubiquitous factor to account for an increased
percent had been treated for this disease (Zalokar et prevalence of gout is the increased proportion of
al. 1972) (Table VIII.63.3). However, most investiga- proteins in many diets, which increases the amount
tions of adult male Caucasian populations have iden- of uric acid that is synthesized. Comparisons of
tified gout in less than 1 percent. A large survey of mean serum uric acid values of most adequately
industrial workers in New York, for example, re- nourished populations worldwide give similar val-
vealed no cases among women or among men under ues. The exceptions remind us that there are uniden-
the age of 40, and a prevalence of only 0.12 percent tified, presumably genetic factors that result in dif-
above that age (Brown and Lingg 1961). No inferences among groups that would be assumed not to
stances of gout were detected among nearly 3,400 differ empirically. A comparative study between
persons above age 15 in Holland in 1954, or among Blackfeet Indians in Arizona and Pima Indians in
4,300 persons in Sofia, Bulgaria. In a small Finnish Montana provides an example (Table VIII.63.4). The
town, one case was found among 787 men and none mean urate concentration and the prevalence of
in 1,048 women. hyperuricemia of the Blackfeet of both sexes were
significantly higher than among the Pima. Further-
Non-Caucasian Populations more, although a high degree of correlation between
Reports of gout in non-Caucasian populations are obesity and hyperuricemia generally is found, more
relatively recent. The first case report pertained to a of the Pima, especially the women, were obese.
31-year-old African servant who died of an infection It was noted coincidentally in Honolulu and Seat-
in Edinburgh in 1807, where he had often been subtle in 1957-8 that an unusually high proportion of
ject to severe pains that occurred about midnight in Filipino men who visited outpatient clinics had gout
one or the other of his great toes. A medical mission- or hyperuricemia. In Honolulu, remarkably, in a
ary in Hawaii in the early 1830s reported that rheu- study of 100 men over 40 years of age, fully half were
matism frequently occurred there, and, although found to be hyperuricemic, and 32 had clinical gout.
gout might also be expected to be common because of Among admissions to the county hospital in Seattle
indulgent eating habits, the mild quality of the food during 64 months, new cases of gout were diagnosed
suggested otherwise and was unlikely to promote in 2.5 percent of Filipinos and in 0.13 percent of all
Table VIII.63.4. Serum uric acid in two American Indian tribes

Mean urate Percent Percent Percent
Tribe Subjects Total (mg%) >7 mg% >6mg% gout
Blackfeet M 587 5.21 ± 1.12 5.4 0
F 435 4.47 ± 1.16 9.2 0
Pima M 473 4.56 ± 1.20 2.5 0.4
F 475 . 3.85 ± 1.05 1.0 0
Source: O'Brien et al. (1966)

other patients. The high prevalence of gout among to Filipinos, nor is alcohol consumption necessarily
Filipinos living in Hawaii was confirmed by other a contributory factor. The highest prevalence of
data, such as the fact that, in a 16-month period, 20 hyperuricemia has been found on the Micronesian
of 24 health insurance claims for treatment of gout island of Nauru (64 percent of men, 60 percent of
were submitted by Filipinos. The mean serum uric women). The diet here, as among the Rarotongans
acid of Filipino men in Seattle, as in Honolulu, was and Samoans, had largely become Westernized by
significantly higher than that of other ethnic the time these surveys were conducted. However,
groups. This contrasted with a diagnosis of gout in disparate groups such as aborigines in northern Aus-
0.004 percent of admissions to the general hospital tralia and natives of New Guinea and of the Tokelau
of Manila and a normal mean serum uric acid among Islands (north of Samoa) were hyperuricemic on
Filipino men sampled at four sites in the Philippine their traditional diets. The complexity of the
Islands. This difference could not be attributed en- uricemia-gout relationship is illustrated by the un-
tirely to the larger mean body mass of the Filipinos explained observation that, although the New Zea-
who lived in Hawaii or Washington State (Healey et land Maoris, Tokelauans, and Rarotongans have the
al. 1967). same high prevalence of hyperuricemia, a fourfold
Although the ability of gouty individuals to excrete difference exists in the prevalence of gout: 10.4 per-
uric acid generally is normal, when this function is cent, 5.3 percent, and 2.5 percent, respectively (Prior
challenged by administering a purine (urate precur- 1981).
sor) load, individual differences in the maximum ex- Nevertheless, a prospective study of gout in
cretory capacity can be identified. In such a study, 4 of Maoris has shown a high correlation between the
13 nongouty Filipino men were unable to increase occurrence of acute gout and the level of uricemia
their excretion of uric acid. The other 9 Filipino and (Brauer and Prior 1978). In 11 years, gout developed
all 10 Caucasian men exhibited the normal response in 31 percent of men and 36 percent of women with a
of approximately doubling the quantity excreted serum uric acid greater than 8 mg%, versus 2.8
(Healey and Bayani-Sioson 1971). This observation percent and 0.6 percent, respectively, of subjects hav-
led to the hypothesis that some ethnic groups, such as ing uric acid concentrations below 6 mg% (Yu 1984).
Filipinos, include an unusually large proportion of These data closely resemble thefindingsin Framing-
persons who have a relatively low genetically deter- ham, Massachusetts. In the larger sample of that
mined limit to their renal excretory capacity for community, clinical gout had developed in 36 per-
urate. As long as such individuals consume a low- cent of men with serum uric acid levels greater than
protein diet, such as many of the Asian rice-based 8 mg% and in 25 percent of women with a value
diets, or diets based on yams, their excretory mecha- greater than 7 mg% (Hall et al. 1967). The difference
nism is not saturated, serum urate remains in the between these two cohorts lies in the 2 mg% greater
normal range of Caucasians, and gout rarely occurs. mean serum uric acid content of the Maoris, and
When the protein consumption of persons with this probably not in any other predisposing factor for the
latent defect increases — that is, as their diet be- occurrence of gout.
comes "Westernized" — the excretory capacity is over- Surveys in the early 1960s in the Osaka district of
whelmed, urate accumulates, and gout becomes more Japan showed a very low prevalence of hyperuri-
frequent. cemia. Gout was diagnosed in 0.3 percent of men and
There is a marked difference in the prevalence of in no women. With the continued Westernization of
hyperuricemia between Caucasian and various Pa- the diet, however, an anticipated increase in the
cific island populations. When 7.0 mg% and 6.0 mg% prevalence of gout is occurring. Studies in Tokyo in
are used as the upper limits of normal for men and the 1970s have shown mean uric acid levels to be the
women, respectively, less than 10 percent of most same as in Caucasian populations (males: 5.64 ±
unselected Caucasian populations, but more than 40 1.45 mg%; females: 4.40 ± 1.09 mg%). The preva-
percent of many Pacific populations, exceed these lence of gout in men has increased to 1.2 percent, but
values (Table VIII.63.2). Many surveys have been the proportion of gouty women was still much lower
conducted since the 1960s: among Maoris in New (0.9 percent of all cases) than in Caucasians. The
Zealand, Polynesians on Rarotonga (south of Samoa) clinical characteristics of gout are the same and oc-
and in the Cook Islands, Micronesians in the Mari- cur in similar frequencies as in Caucasian popula-
anas and Nauru, Melanesians in Samoa, among oth- tions (Nishioka and Mikanagi 1980).
ers. The hyperuricemia cannot be attributed en- A Chinese author claimed that the first case of
tirely to dietary changes, as discussed in regard gout to be described in China occurred in 1948, and

VIII.63. Gout 771
that by 1959 he could collect only 12 cases, 10 with Table VIII.63.5. Serum uric acid in South African
tophi. This almost certainly reflects socioeconomic black and white populations
rather than biological circumstances. The general
prevalence of gout may indeed have been low be- Mean uric acid
cause of the widespread, inadequately low protein Population Age range Subjects (mg%)
diet, but this would have pertained particularly to African males
the large segment of the population that lacked medi- Tribal 18-75+ 80 4.7 ± 1.03
cal care. In regard to the well-nourished upper Rural 14-84 128 5.0 ± 1.11
classes, a lack of diagnostic acumen may have been Urban 15-90 144 6.1 ± 1.45
at least partially responsible. White urban 16-95 213 6.2 ± 1.27
In the Taiwanese literature, only 19 cases of gout
were reported between 1903 and 1964, according to African females
one author. However, in 1963 another author re- Tribal 15-75+ 399 3.9 ± 0.85
ported 61 cases - 5 percent of the clientele of a Rural 14-96 242 4.6 ± 1.44
Urban 15-90 280 5.2 ± 1.34
rheumatology clinic. Of these, 35 were immigrants
from the Chinese mainland. White urban 16-88 298 5.0 ± 1.20
A study of serum uric acid of 100 Chinese men
who lived in British Columbia showed a higher Source: Beighton et al. (1977).
mean value (5.44 ± 1.08 mg%) than that of 200
Caucasian men (4.55 ± 1.02 mg%) (Ford and de Mos
The effect on uricemia of the urbanization of primi-
1964). The difficulty of interpreting such data is
tive people has been well illustrated by studies in
shown by a comparison of serum uric acid of Chinese
South Africa that showed the lowest mean serum
living on Taiwan and in Malaya, using the same
values in a tribal population, higher values in a
analytic technique. The mean concentration on Tai-
village, and the highest levels, equal to those of
wan was 4.99 ± 0.91 mg% for men and 3.87 ± 0.78
urban whites, in urban (Soweto) blacks (Table
mg% for women, whereas in Malaya these values
VIII.63.5). The combined three black populations
were, respectively, 6.11 ± 1.29 mg% and 4.52 ± 0.9 8
(621 men, 1,364 women) contained no cases of gout,
mg% - significantly higher (Duff et al. 1968). At a
whereas 3 of 240 white men and 1 of 332 white
hospital in New York, 13 cases of gout were seen
women had this disease (Beighton et al. 1977). A
among Chinese patients in 11 years, an incidence
survey in Ethiopia in 1961-3 similarly showed the
similar to that of other races. Only 1.9 percent of the
lowest values among rural Ethiopians, intermediate
2,145 primary gout patients of the Mount Sinai Hos-
values among urban Ethiopians, and the normal,
pital of New York were Chinese. Yu (1984) inter-
highest value among Caucasian and Indian urban
preted this as evidence of the infrequency of gout
professionals.
among this racial group.
Data from Israel are analogous. Desert Bedouins
Aside from South Africa, there is little relevant
were found to have lower serum uric acid values
information from the African continent, and most is
than villagers of the same Arabic stock, and the
derived from hospital admissions. Seven cases of
latter results were the same as were obtained from a
gout (five "upper class") were seen at the principal
nearby Jewish population in Haifa. These variations
Ugandan hospital in 6 years (1962-7). During 30
are presumed to be related to changes in nutrition
months (1960-2) 3 cases were diagnosed at a hospi-
associated with changes in life-style (Dreyfuss,
tal in Nairobi, Kenya, which represented 11 per
Yaron, and Balogh 1964).
100,000 admissions, whereas during the 5 years
1977-81,19 cases were seen at the University Hospi- Thomas G. Benedek
tal in Durban, South Africa, which represented 4.7
per 100,000. Fifteen of these patients were male, and Bibliography
most were poor city dwellers (Mody and Naidoo Abbott, R. D., et al. 1988. Gout and coronary heart disease:
The Framingham study. Journal of Clinical Epidemi-
1984). A survey in a Nigerian village showed uric ology 41: 237-42.
acid levels above 6 mg% in 34 percent of men and 13 Beighton, P., et al. 1977. Rheumatic disorders in the South
percent of women. A more extensive investigation in African Negro. Part IV. Gout and hyperuricemia.
rural south Africa revealed a normal Caucasian dis- South African Medical Journal 51: 969-72.
tribution of uric acid values, but no cases of gout Benedek, T. G. 1987. A century of American rheumatol-
among more than 1,000 adults. ogy. Annals of Internal Medicine 106: 304-12.

Brauer, G. W., and I. A. Prior. 1978. A prospective study of Mody, G. M., and P. D. Naidoo. 1984. Gout in South African
gout in New Zealand Maoris. Annals of the Rheumatic blacks. Annals of Rheumatic Diseases 43: 394—7.
Diseases 37: 466-72. Montoye, H. J., et al. 1967. Serum uric acid concentration
Breckenridge, A. 1966. Hypertension and hyperuricemia. among business executives. Annals of Internal Medi-
Lancet 1: 15-18. cine 66: 838-49.
Brown, R., and C. Lingg. 1961. Musculoskeletal com- Nishioka, K., and K. Mikanagi. 1980. Hereditary and envi-
plaints in an industry. Arthritis and Rheumatism 4: ronmental factors influencing on the serum uric acid
283-302. throughout ten years' population study in Japan. Ad-
Currie, W. J. 1979. Prevalence and incidence of the diagno- vances in Experimental Medicine and Biology 122A:
sis of gout in Great Britain. Annals of the Rheumatic 155-9.
Diseases 38: 101-6. O'Brien, J. B., T. A. Burch, and J. J. Bunim. 1966. Genetics
Dreyfuss, E, E. Yaron, and M. Balogh. 1964. Blood uric of hyperuricaemia in Blackfeet and Pima Indians.
acid levels in various ethnic groups in Israel. Ameri- Annals of the Rheumatic Diseases 25: 117.
can Journal of the Medical Sciences 247: 438—44. Prior, 1.1981. Epidemiology of rheumatic disorders in the
Duff, I. F., et al. 1968. Comparison of uric acid levels in Pacific with particular emphasis on hyperuricemia
some Oriental and Caucasian groups unselected as to and gout. Seminars in Arthritis and Rheumatism 13:
gout or hyperuricemia. Arthritis and Rheumatism 11: 145-65.
184-90. Rodnan, G. P. 1965. Early theories concerning etiology and
Florey, C. D., and R. M. Acheson. 1968. Serum uric acid in pathogenesis of gout. Arthritis and Rheumatism 8:
United States and Brazilian military recruits, with a 599-609.
note on ABO blood groups. American Journal of Rodnan, G. P., and T. Benedek. 1970. The early history of
Epidemiology 88: 178-88. antirheumatic drugs. Arthritis and Rheumatism 13:
Ford, D. K., and A. M. de Mos. 1964. Serum uric acid levels 145-65.
of healthy Caucasian, Chinese and Haida Indian Seegmiller, J. E., L. Laster, and R. R. Howell. 1963. Bio-
males in British Columbia. Canadian Medical Asso- chemistry of uric acid and its relation to gout. New
ciation Journal 90: 1295-7. England Journal of Medicine 268: 712-6, 764-73,
Gardner, M. J., et al. 1982. The prevalence of gout in three 821-7.
English towns. International Journal of Epidemiology Thiele, P., and H.-E. Schroeder. 1982. Epidemiologie der
11: 71-5. Hyperurikamie und Gicht. Zeitschrift fur die Gesamte
Grahame, R., and J. T. Scott. 1970. Clinical survey of 354 Innere Medizin und ihre Grenzgebiete 37: 406—10.
patients with gout. Annals of the Rheumatic Diseases Yu, T.-F. 1984. Diversity of clinical features in gouty arthri-
29: 461-8. tis. Seminars in Arthritis and Rheumatism 13: 360-8.
Gutman, A. B., and T.-F. Yu. 1955. Prevention and treat- Yu, T.-F., and A. B. Gutman. 1967. Uric acid nephrolithi-
ment of chronic gouty arthritis. Journal of the Ameri- asis in gout: Predisposing factors. Annals of Internal
can Medical Association 157: 1096-102. Medicine 67: 1133-48.
Hall, A. P., et al. 1967. Epidemiology of gout and Zalokar, J., et al. 1972. Serum uric acid in 23,923 men and
hyperuricemia. A long-term population study. Ameri- gout in a subsample of 4257 men in France. Journal of
can Journal of Medicine 42: 27—37. Chronic Disease 25: 305-12.
Healey, L. A., and P. S. Bayani-Sioson. 1971. A defect in
the renal excretion of uric acid in Filipinos. Arthritis
and Rheumatism 14: 721—6.
Healey, L. A., et al. 1967. Hyperuricemia in Filipinos:
Interaction of heredity and environment. American
Journal of Human Genetics 19: 81-5.
Hench, P. S., et al. 1936. The problem of rheumatism and
arthritis (third rheumatism review). Annals of Inter-
nal Medicine 10: 754-909.
Hill, L. C. 1938. Gout. Lancet 1: 826-31.
Klein, R., et al. 1973. Serum uric acid: Its relationship to
coronary heart disease risk factors and cardiovascular
disease, Evans County, Georgia. Archives of Internal
Medicine 132: 401-10.
Mikkelsen, W. M., H. J. Dodge, and H. Valkenburg. 1965.
The distribution of serum uric acid values in a popula-
tion unselected as to gout or hyperuricemia. American
Journal of Medicine 39: 242-51.

VIII.64. Herpes Simplex 773
women in a study of a lower socioeconomic sample,

VHI.64 the antepartum infection rate was 1.02 percent. The
Herpes Simplex infant was safe from infection if the mother's infec-
tion had cleared 3 to 4 weeks before delivery. On the
other hand, the experience of 283 women with genital
Herpes simplex is caused by Herpes virus hominis, of herpes suggests that those women who suffer from
which there are two distinct serologic types desig- genital herpes during pregnancy are three times
nated as HSV-1 and HSV-2. The first mainly causes more likely to abort than other women during the
disease above the waist, such as cold sores; the sec- first 20 weeks of pregnancy. In this same study, the
ond most commonly causes disease below the waist, risk of neonatal infection was 10 percent if infection
especially genital herpes. Exceptions to this general- occurred after 32 weeks of pregnancy, and increased
ization occur especially among the newborn. The to 40 percent if infection was present at confinement.
initial active phase is followed by prolonged latency. Neonatal infection from infected mothers is almost
But the virus can be reactivated by another infec- certainly of the HSV-2 type, acquired by passage
tion, stress, exposure to sunshine, or any number of through an infected birth canal. In addition HSV-2
other bodily changes. may be transmitted from infant to infant in the hospi-
tal nursery by its personnel.
Etiology and Epidemiology The epidemiology of recurrent herpes is compli-
The herpes viruses are visible in infected cells by cated by unknown factors that cause reactivation of
electron microscopy and may be grown in the chick the virus. Because the epidemiology of recurrence
embryo, in tissue cultures, and in laboratory ani- depends on recollection, the most acceptable studies
mals that react differently to types HSV-1 and of reccurent herpes labialis come from students in
HSV-2. health care professions. These show inexplicable dif-
HSV-1 is shed from cells in the lacrimal and sali- ferences in recurrence: 45 percent in Wales and the
vary glands, and both types are shed from the pri- United Kingdom, 40 percent in North America, 30
mary and recurrent lesions of the mucous mem- percent in Europe and Africa, 17 percent in Asia,
branes and skin. Samples of infected adults show and 16 percent in South America.
that 2 to 4 percent are excreting the virus at a given The possible relationship of HSV-2 to carcinoma of
time. the cervix has been explored in recent years in light
Infection with the herpes simplex virus results of its ability to transform cells in vitro, the incidence
from person-to-person contact. HSV-1 infections com- of antibodies to HSV-2 in cancer patients, and the
monly are transmitted by oral secretions through demonstration of viral RNA in cancer cells from the
kissing or the sharing of eating utensils, and thus cervix. No conclusive studies have been published to
herpetic infection can easily be spread within a fam- date.
ily. Normally HSV-1 infections are painful and both-
ersome but have no serious consequences. An excep- Distribution and Incidence
tion can be when the virus invades the cornea of the Infection by herpes virus is reported worldwide, as
eye. Conjunctival or corneal herpes may produce determined by antibody studies, and is related to the
scars that impair vision. It may occur among wres- socioeconomic state. The prevalence of positive anti-
tlers from skin-to-skin contact. Another form of body tests to HSV-1 approaches universality (100
HSV-1 infection, called herpetic paronychia, may oc- percent) in the lower strata, falling to 30 to 50 per-
cur in dentists and in hospital personnel. cent among those of higher socioeconomic levels.
HSV-2 infections are generally the result of sex- Obviously, transmission is more likely among those
ual transmission at a time the virus is being shed. living in a crowded and unhygienic environment.
Lesions appear on the penis, vulva, buttocks, and The prevalence of positive antibody response begins
adjacent areas, and the mucosa of the vagina and in early childhood and rises to its peak in adult life.
cervix. Transplacental antibodies are present in infants up
The prevalence of HSV-2 infection during preg- to 6 months of age. Then a sharp rise in antibodies
nancy and its incidence in neonates are related to the occurs for those aged 1 to 4 years, mainly to HSV-1.
socioeconomic level, age, and sexual activity of a popu- This is followed by a slight rise from 5 to 14 years,
lation. In one urban population study, 35.7 percent of and after 14 there is a marked rise in antibodies
women attending an obstetrical clinic had serologic through late adulthood, which is in part due to HSV-
evidence of past HSV-2 infections. Moreover, of these 2 infection (see Figure VIII.64.1).

100- • United States, with 300,000 to 500,000 new cases
90. .
developing annually. Undoubtedly, contributing fac-
tors include increased sexual activity as well as a
80- . Type 2 antibodies preference for the use of oral contraceptives over the
BB3 Intermediate antibodies condom, although a wider use of diagnostic tests
70-. I—I Type 1 antibodies
may account for some of the apparent increased
60 prevalence. Certainly, publicity concerning herpes
% With HSV genitalis has alerted the medical profession to the
antibodies 50
disease and has made the public aware that "chafing
of a menstrual pad" and lesions on the male genitals
may entail more than temporary annoyance.
In any event, beginning with its 1983 Annual Sum-
mary, Morbidity and Mortality Reports, the U.S. Pub-
lic Health Service has included herpes genitalis. The
report for 1984, based on physician consultations, of-
fice visits, and the first office visits for the disease,
Age 0-6 7-11'/ 2 1-4 5-9 10-14 15-19 20-24 25-34 35-44 >44
"reflects a 16 fold increase from 28,000 to 423,000 in
mo mo yr yr yr yr yr yr yr yr the number of consultations for genital herpes in the
No. 24 15 20 19 15 29 27 40 24 26 period 1966-1983" (see Figure VIII.64.2).
Figure VIII.64.1. Percentage distribution of antibodies to
HSV-1, HSV-2, and intermediate form (types 1 and 2) in Immunology
239 patients of various age groups. (From A. J. Nahmius Antibodies to the herpes viruses last throughout the
and D. E. Campbell. 1983. Infections caused by herpes patient's lifetime. An antigen common to both HSV-
simplex viruses. In Infectious Diseases, 3d edition, ed. 1 and HSV-2 produces crossreacting antibodies to
Paul D. Hoeprich, 859, by permission of Harper & Row, both strains that can be differentiated immunologi-
publishers.) cally by immunofluorescence and microneutrali-
zation tests. Antibody to one type, however, pre-
Because HSV-2 infection is a sexually transmitted cludes neither an infection with the other nor the
disease, it has been studied more intensively in re- development of specific antibodies to the second in-
cent years than the more common HSV-1 infection. fection. Yet previous infection with HSV-1 does miti-
On the other hand, most observers agree that her- gate the clinical manifestations of the first episode of
pes genitalis has been on the increase in recent genital herpes caused by HSV-2. The antibodies that
years, and in 1983 the National Institutes of Health respond to an initial herpes simplex virus infection
estimated that there were 20 million cases in the are complement-fixing, neutralizing, cytotoxic, pre-
600-1
550
500-
450
Figure VIII.64.2. Number of con- |

sultations, all five office visits,
and first of five visits for genital
herpes, United States, 1966-83.
All consultations (solid line) in-
clude any type of patients
physician interaction, such as tele-
phone calls, house calls, and office
visits. [From U.S. Public Health
Service. Centers for Disease Con-
trol. 1984. Morbidity and Mortal-
ity Weekly Reports, Annual Sum- 1970 1972 1974 197E 1978 1980 1982
mary (March) 33: 90.]

cipitating, and nonprecipitating antibodies, and ap- cal pneumonia than other types of pneumonia or
pear early in the infection. Lawrence Corey (1984) febrile disease.
has stated that although complement-fixing and neu- Conjunctivitis with or without keratitis may be the
tralizing "antibodies usually are maintained and in primary lesion of herpes virus infection. Then the
high titer, and inactivate extracellular virus, contin- preauricular lymph node commonly is enlarged.
ued replication of virus by cell to cell transfer en- Keratitis is characterized by dendritic ulceration.
sues. These data help explain frequent reactivation Cutaneous herpes (HSV-1) may involve the skin of
of the disease in the presence of high levels of anti- the body, anywhere above the waist and including
body titer." The relation of humoral antibodies to the feet. (HSV-2 has been isolated from fingers from
reactivation of disease is unclear. Whereas the hu- autoinoculation or genital-to-finger contact in sex-
moral immune response remains at high levels, the ual play.) It may be accompanied by edema, fever,
in vitro cellular immune response to HSV antigens lymphangitis, and lymphadenopathy.
appears to fluctuate. Herpes genitalis also has the incubation period of
several days following exposure to infection. It may
Pathology and Clinical Manifestations be subclinical, especially in women having lesions
The virus multiplies in the epithelium at the portal only in the vagina or the cervix rather than on the
of entry. The epithelial cells increase in size and vulva. Herpetic infection is more obvious in men
contain an enlarged nucleus with intranuclear inclu- with localized pain, erythema, and the development
sions. The developing blisterlike vesicle is intra- of one or a group of vesicles on the glans, prepuce, or
dermal and is surrounded by inflammatory cells, elsewhere on the penis. The inguinal lymph nodes
edema, and congestion. Viremia may develop in may be swollen and tender. Urethral involvement in
malnourished infants as an accompaniment to mea- both sexes is manifested by dysuria (painful or diffi-
sles, and in patients with extensive burns or in those cult urination), and a discharge may be noted in
on immunodepressant drugs. Systematic disease ac- male patients. Pelvic pain accompanying the dys-
companies viremia. uria is common in women. (The virus can be isolated
The initial lesion at the site of inoculation or at from the urethra of both sexes. Primary infection
the site of recurrence, whether in the skin or mucous with HSV-2 virus often is accompanied by systemic
membrane, is a small reddened area that develops symptoms during the first several days (see Figure
into a small, thin-walled, blisterlike vesicle filled VIII.64.3). Complications of primary infection reveal
with clear fluid. Equally as common is the appear- a generalized infection, especially as aseptic menin-
ance of a group of small vesicles on the erythema- gitis and other indications of viral invasion of the
tous base. central nervous system.
Gingivostomatitis is the usual type of primary or In a study of 148 newborns with herpes, A. J.
initial HSV-1 lesion in infants and young children Nahmias and colleagues (1970) reported an incuba-
and is seen occasionally in adults. There may be tion period of up to 21 days; almost all were infected
several days of prodromal symptoms such as mal- with HSV-2 and had evidence of dissemination. The
aise, fever, and usually cervical lymphadenopathy. overall fatality rate was 71 percent, and 95 percent
Commonly, by the time a physician is consulted, the among those with disseminated infection. Of those
gums are inflamed and ulcerated. Pain is distressing recovering, 15 percent had sequelae, especially de-
and may interfere with eating; the course is nor- fects in the central nervous system.
mally a week to 10 days. Some studies show recurrences within the first
Labial herpes only occasionally represents the ini- year in 80 percent of infections with HSV-2. Recur-
tial HSV-1 lesion, but the "cold sore" or "fever blis- rent lesions commonly present with milder symp-
ter" of the lip is the most common lesion of recurrent toms initially, are generally of shorter duration, and
disease. Here a cluster of vesicles appears after a are rarely accompanied by overt systemic symptoms.
couple of days of hyperesthesia and erythema, to last These lesions commonly appear on the genitalia, but
from several to 10 days. Most commonly these ap- may appear on the buttocks and elsewhere adjacent
pear at the vermilion line of the skin of the lower lip to the genital area. Latent infection presumably is
or on the skin of the upper lip, at times extending to established in the sacral-nerve-root ganglia. From a
or into the nostril. The term "fever blister" stems study of 375 patients, Stanley Bierman (1983) found
from the frequency with which herpetic recurrence that recurrences ceased in half of them after some 7
accompanies febrile illnesses. Before the age of anti- years following the onset of disease. In others, how-
biotics, it was more likely to accompany pneumococ- ever, the recurrences may span many years.

DURATION VIRAL SHEDDING
VESICULE WET ULCER HEALING

PUSTULE ULCER-CRUST
Systemic \ Local
symptoms/
Figure VIII.64.3. Schematic graph

of the clinical course of primary
genital herpes. (From L. Corey.
1984. Genital herpes. In Sexually
Transmitted Diseases, ed. King K. -6 -4 -2 0 2 4 6 8 10 12 14 16 18 20 Days
Holmes et al., 453, by permission • • 4 • f
Lesions
Sexual Lesions Physician New Lesions Symptoms
of the McGraw Hill Book contact noted contacted lesion start gone unless healed
formation to lesions
Company.) common heal irritated
It is unclear what triggers recurrent genital her- London in 1754. His description of vesicles in both
pes. Emotional stress, fever, heat, trauma, coitus, male and female patients unmistakably indicates
and the menses have all been suggested. But they those of herpes genitalis. Toward the end of the eigh-
lack the certainty that a febrile illness seems to play teenth century, the English physician Robert Willan
as a provoking factor in HSV-1 recurrences. developed a classification, published in 1808, of the
bewildering varieties of skin diseases, among which
History and Geography was a category of vesiculae.
The word herpes is derived from the Greek verb "to In his Synopsis of Cutaneous Diseases (1818),
creep," and the identification of disease in ancient Thomas Bateman described herpes labialis, which
writings depends upon one's interpretation of the "occasionally appears as an idiopathic affection . . .
description of physical signs. Thus, one may decide frequently in the course of disease of the viscera of
either that a described lesion was of the herpetic which it is symptomatic." His accurate description of
type or accept the translation of the term "herpes" herpes praeputialis emphasized the hazard of inter-
itself. No doubt aphthae and herpetic lesions were preting a cluster of vesicles as a syphilitic chancre.
not differentiated. He described the prodromes, development of the
The oldest record of disease of the genitalia ap- erythema and vesicles, and their course to healing,
pears in the Ebers Papyrus (c. 1550 B.C.). The trans- ending with, "I have not been able to ascertain the
lator commented on the inflammation of the vulva causes of this eruption on the prepuce. . ..
and thighs of a woman in nonspecific terms, but in Whencesoever it may originate, it is liable to recur
the same papyrus describes treatment for "herpes of in the same individual at intervals of six or eight
the face." Hippocrates spoke of "herpetic sores" and, weeks."
again in his Epidemics, that "many have aphthae Jean Louis Alibert (1832) not only described her-
and ulcerations of the mouth, frequentfluxationsof pes praeputialis but stated that the lesion may occur
the genital organs and ulcers." Herodotus described at the introitus of the vagina. F. L. Legendre (1853)
herpetic eruptions "which appear about the mouth described three instances of herpes of the vulva,
at the crisis of simple fevers." H. Haeser (1875), in with the observation that herpes may recur 2 or 3
reviewing the medical writings of the Byzantine Em- days before menstruation.
pire, quotes from three physicians (the fourth to The most descriptive paper on herpes progenitalis
seventh centuries) concerning "superficial aphthae" was presented by Boston physician F. B. Greenough
and "vesicular eruptions" of the vulva. J. Preuss (1881), at the meeting of the American Dermatologi-
(1911), a Biblical scholar, in referring to the Tal- cal Association. He documented its frequency among
mud's permission to delay the rite of circumcision, private patients and its rarity among patients in the
said, "Mila betzaraath is probably harmless herpes Venereal Disease Clinic of the Boston Dispensary.
of the foreskin." His explanation for this discrepancy was that pa-
The first definitive description of herpes appears tients in a charitable institution were less apt to
in Jean Astruc's 1736 publication of De Morbis complain of a trivial abnormality unless they be-
Venereis, translated into English and published in lieved it to be a manifestation of a more serious

disease. He made the important observation that herpes zoster, triggered by genital irritations: Just
one of the "three" venereal diseases had existed be- as there are "men who are habitually attacked by
fore the appearance of herpes genitalis. His sum- herpes after each act of coition, so, too, there are
mary included the statement: prostitutes who have an eruption of herpes every
time they menstruate."
[S]ome of its most interesting and important characteris-
R. Bergh of Copenhagen (1890) confirmed a high
tics are, its tendency to relapse, the very great frequency
with which it will be found to have been preceded by the
incidence of herpes genitalis among prostitutes, re-
act of coitus, the fact that it rarely, if ever, is found in porting that the episodes were related to the menses
patients who have been perfectly free from all venereal in 73.4 percent of 877 women admitted to the hospi-
trouble, and that it is confined to the period of youth and tal for the disease. Aware of the relationship of her-
early manhood. pes labialis to bacterial infection, he was puzzled by
the lack of such a relationship in herpes genitalis in
In addition, Greenough made the surprising obser- spite of the not infrequent coincidence of herpes la-
vation that he had never seen an instance of genital bialis and genitalis. He did not accept any relation-
herpes in a woman. Among the numerous dis- ship between herpes genitalis and venereal disease
cussants of Greenough's paper was Louis A. Duhring because he had seen it in a recently married woman
(1881), president of the association, who commented and in youths who masturbated frequently. There-
in his discussion that though others had seen the fore, he concluded the lesions were of a nervous
disease in women, he, too, had never seen such an origin, being due to congestion of the parts, as after
instance. This phase of the discussion prompted a masturbation or coitus in men and with menses in
paper 2 years later by Paul Unna of Hamburg prostitutes. E. Levin (1906) reported observations on
(1883), published in an American journal. He, too, 1,584 women admitted to the venereal disease shel-
had never seen herpes genitalis in his private female ter in Berlin in 1898-9. There were 112 with herpes
patients, but cited observations made in Germany of whom 83 had genital herpes. Twenty-nine women
and France where medical examination of prosti- had recurrent episodes, and thus 154 episodes were
tutes was under police surveillance. In addition, he analyzed: 118 genital and 26 at other sites. Coinci-
pointed out that among women admitted to the dence with menstruation occurred in 70 percent of
syphilis department of the Hamburg General Hospi- the episodes.
tal, from 1878 to 1881, with admission of 1,357 to A few years later, Prague physician O. Baum
1,459 patients annually, the incidence of herpes geni- (1920) reported herpetic keratitis, following inocula-
talis was 64, 126, 121, and 112 cases during the 4 tion of rabbit corneas with vesicular fluid from two
years. For the same years, males admitted to the cases of herpes labialis, two of herpes genitalis (one
syphilis department, with admissions of 634 to 795 in a recurrence), one of herpes faciei, and one each of
annually, had an incidence of herpes genitalis of 4, 9, herpes after the injection of bismuth and salvarsan.
4, and 0, respectively. Results of such experiments with material from
Unna (1883) summarized: three cases of herpes zoster and several other vesicu-
lar skin diseases were negative. Four years later,
It is now evident that the conclusions arrived at by mem-
bers of the American Dermatological Society are correct,
investigators at the University of Turin, while carry-
in so far as the general rarity of herpes vulvae is con- ing out successful experiments of inoculating blood
cerned; but, on the contrary, the conclusion that women as and cerebrospinal fluid from patients having her-
such are therefore less susceptible of being thus affected is petic disease (or during a period between recur-
erroneous. Indeed, herpes progenitalis is found more fre- rences) into corneas, found instances of positive reac-
quently in women who are only distinguished by their tion among control subjects. This led to experiments
vocation than in men. We may therefore say only this with blood and cerebrospinal fluid from subjects who
much: that women are just as susceptible to herpes as men had not had herpetic eruptions for a long time; of 21
are; there is no immunity from herpes for the female sex. patients, only 3 gave negative results with both
On the contrary, the exciting cause that induces virile blood and spinal fluid. In 4, the spinal fluids were
herpes is usually absent in women; but when this is pres- abnormal, and in 4 the Wassermann reaction was
ent (as in puellae publicae) herpes is frequently found; for
positive.
women herpes is so to say a vocational disease. (Italics
added) In 1921, B. Lipschiitz successfully inoculated mate-
rial from vesicles on the genitalia into the skin of
Unna dismissed the usual theories to account for human subjects. Four years later, S. Flexner and
the disease and suggested that it was a variant of H. L. Amos (1925) demonstrated the herpes virus,

and in 1934 Albert Sabin and colleagues isolated it. Morton, R. S. 1975. Herpes genitalis. In Recent advances
K. E. Schneweiss (1962) identified two strains of her- in sexually transmitted diseases, ed. R. S. Morton and
pes virus by neutralization tests, a finding confirmed J. R. W. Harris. London.
by W. R. Dowdle and Nahmias in 1967. The literature Nahmias, A. J., C. A. Alford, and B. K. Sheldon. 1970.
in subsequent years has contributed to knowledge Infection of the newborn with Herpes virus hominis.
concerning epidemiology and immunology. Advances in Pediatrics 17: 185-226.
Nahmias, A. J., and Donald E. Campbell. 1983. Infections
R. H. Kampmeier caused by herpes simplex viruses. In Infectious dis-
eases, ed. Paul D. Hoeprich, 3d ed. Philadelphia.
Bibliography Nahmias, A. J., H. L. Keyserling, and G. M. Kerrick. 1983.
Alibert, J. L. 1832. Monographic des dermatoses. Paris. Herpes simplex virus. In Infectious diseases of the
Bateman, Thomas. 1818. A practical synopsis of cutaneous fetus and newborn infants, ed. J. Remington and J. O.
diseases. Longman. Klein, 2d ed. Philadelphia.
Baum, O. 1920. Ueber die Uebertragbarkeit des Herpes Nahmias, A. J., et al. 1969. Genital infection with type 2
Simplex auf die Kaninchenhornhaut. Dermatolo- herpes virus hominis: A commonly occurring venereal
gische Wochenschrift 70: 105-6. disease. British Journal of Venereal Diseases 45: 294—
Bergh, R. 1890. Ueber Herpes Menstralis. Monatshefte fur 8.
Praktische Dermatologie 10: 1—16. 1981. Clinical aspects of infection with herpes simplex
Beswick, T.S.L. 1962. The origin and the use of the word viruses 1 and 2. In The human herpesviruses, ed. An-
herpes. Medical History 6: 214-32. dre J. Nahmias, Walter R. Dowdle, and Raymond F.
Bierman, Stanley M. 1983. A retrospective study of 375 Schinazi. New York.
patients with genital herpes simplex infections seen Preuss, J. 1978. Biblical and Talmudic medicine (1911).
between 1973 and 1980. Cutis 31: 548-65. New York.
Bolognese, R. J. 1976. Herpesvirus hominis type II infec- Rapp, Fred, ed. 1984. Herpesviruses: Proceedings of a Bur-
tions in asymptomatic pregnant women. Obstetrics roughs Wellcome—UCLA Symposium, April 8—13,
and Gynecology 48: 507-10. 1984.
Corey, Lawrence. 1984. Genital herpes. In Sexually trans- Rawls, W. E., et al. 1971. Genital herpes in two social
mitted diseases, ed. King K. Holmes et al. New York. groups. American Journal of Obstetrics and Gynecol-
Dowdle, W. R., and A. J. Nahmias. 1967. Association of ogy 110: 682-9.
antigenic type of herpes virus hominis with site of Sabin, Albert B., A. Bond, and A. M. Wright. 1934. Acute
viral recovery. Journal of Immunology 99: 974—80. ascending myelitis following a monkey bite, with iso-
Duhring, Louis A. 1881. Discussion of Greenough paper. lation of a virus capable of reproducing the disease.
Archives of Dermatology 7: 29. Journal of Experimental Medicine 59: 115—36.
Flexner, S., and H. L. Amos. 1925. Contributions to the Schneweiss, K. E. 1962. Serologische Untersuchungen zur
pathology of experimental encephalitis: II. Herpetic Typendifferenzierung des Herpesvirus Hominis. Zeit-
strains of encephalitogenic virus. Journal of Experi- schrift fur Immunitdtsforschung und Experimentelle
mental Medicine 41: 223-43. Therapie 124: 24-48.
Greenough, F. B. 1881. Herpes progenitalis. Archives of Unna, P. G. 1883. On herpes progenitalis, especially in
Dermatology 7: 1-29. women. Journal of Cutaneous and Venereal Diseases
Haeser, H. 1875. Lehrbuchgeschichte der Medizin und der 1: 321-34.
epidemischen Krankheiten, 3 vols. Jena. U.S. Public Health Service. 1984. Morbidity and Mortality
Hoeprich, P. D., ed. 1983. Infectious diseases, 3d edition. Weekly Report. Annual Summary, March 33: 90.
New York. Willan, Robert. 1808. On Cutaneous Diseases, Vol. 1. Lon-
Holmes, King K., et al., eds. 1984. Sexually transmitted don.
diseases. New York.
Kampmeier, R. H. 1984. Herpes genitalis: A clinical puzzle
for two centuries. Sexually Transmitted Diseases 11:
41-5.
Legendre, F. L. 1853. M6moire sur l'herpes de la vulve.
Archives Ginirales de Medecine 2: 171-204.
Levin, E. 1906. Ueber Herpes bein Frauen und seine
Beziehungen zur Menstruation. Deutsche Medizi-
nische Wochenschrift 26: 277-9; 293-6.
Lipschiitz, B. 1921. Untersuchungen uber die Aetiologie
der Krankheiten den Herpesgruppe (Herpes zoster,
Herpes genitalis, Herpes febrilis). Archiv fur Derma-
tologie und Syphilis 136: 428-82.

Vni.65. Herpesviruses 779
new cases each year. The number of serious infec-
vm.65 tions requiring diagnosis and treatment is very
Herpesviruses small, perhaps 1 or 2 percent of the total.
In contrast to the highly endemic central United
States, only a handful of individual cases have been
The family of herpesviruses (Herpetoviridae) in- documented in Europe. Skin test surveys show about
cludes herpes simplex 1 and 2 viruses, varicella 0.5 percent of the population positive to histo-
zoster virus, Epstein—Barr virus, and the cytomega- plasmin. In Italy, positive skin tests are slightly
lovirus. All are double-stranded DNA viruses of more common (about 2 percent) (Mantovani 1972).
icosahedral form, enclosed in a lipid-containing enve-
lope, and ranging in size from 120 to 180 Etiology and Epidemiology
nanometers. H. capsulatum is a thermal dimorphic fungus. At
R. H. Kampmeier 25°C, it grows on Sabouraud agar as a fluffy-white
mycelium, which bears microconidia and also charac-
teristic tuberculate macroconidia. The organism is
free-living in nature in this form. At 37°C, it grows
as a small (2- to 4-/im diameter) yeast. The organism
is found in this form in infected tissue.
VIII.66 A minor disturbance of fungus-laden soil may scat-
Histoplasmosis ter spores into the air. The microconidia are inhaled,
causing infection. Within the lung the organism con-
verts to the yeast phase, which is not infectious.
Histoplasmosis is an infection caused by Histoplasma Person-to-person transmission does not occur. So-
capsulatum, a soil fungus. Exposure occurs by inhala- called epidemics of histoplasmosis are more accu-
tion, and the primary infection is in the lung. The rately point-source outbreaks.
disease is usually benign and self-limited, despite a Within a highly endemic area, the organism is
strong tendency for invasion of the bloodstream dur- widely but not uniformly distributed. Microfoci
ing the primary infection. This fungemia seeds with high concentrations of organisms are found by
reticuloendothelial organs throughout the body. Un- chicken coops and starling roosts, and in caves in-
der favorable conditions, the organism can cause pro- habited by bats. The nitrogen-rich excrement of
gressive disease in one or in multiple sites, resulting birds and bats provides a favorable growth environ-
in a wide variety of clinical manifestations. ment for the fungus. Exposure of small groups of
people to high concentrations of organisms at such
Distribution and Incidence sites may result in outbreaks of symptomatic infec-
H. capsulatum has been isolated from soil of more tion. These are fairly easy to identify because a se-
than 50 countries. It is most common in temperate vere respiratory illness occurs simultaneously in a
climates along river valleys and has been found in group of people who were together for a particular
North, Central, and South America; India; South- activity 14 days earlier. Extremely large outbreaks
east Asia; and rarely Europe. of longer duration have occurred during excavation
By far the most heavily endemic area in the world for road or building construction. A good example is
is the east central United States, particularly the the community-wide outbreak of histoplasmosis
Mississippi and Ohio River valleys. It is most preva- that occurred during the building of a swimming
lent in the states of Ohio, Kentucky, Indiana, Illi- pool and tennis court complex in Indianapolis, Indi-
nois, Kentucky, Tennessee, and Arkansas. Surround- ana, infecting perhaps over 100,000 people (Wheat
ing states also have many infections. et al. 1981).
Infection is almost universal in the most heavily Most cases of histoplasmosis, however, are spo-
endemic areas. Skin test surveys reveal that over 90 radic and result from casual exposure to environmen-
percent of persons living in some counties in the tal spores. Patients with sporadic illness probably
central United States have had histoplasmosis be- inhale fewer spores and are more likely to be
fore age 20 (Edwards et al. 1969). Based on skin test asymptomatic or minimally symptomatic. The vast
surveys, there are probably 40 to 50 million people majority of these infections are never recognized and
in the central United States who have had histo- are known to exist only as a result of skin test
plasmosis, and there are severalThundred thousand surveys.

Immunology followed by healing may result in concentric rings of
Cell-mediated immunity is crucial in host defense. calcium as the lesion slowly enlarges. Lymph node
Inhalation of spores causes patchy areas of pneumo- calcification, either in association with a paren-
nitis. The spores are transformed into the yeast chymal nodule or as a solitary finding, is common.
form, which is engulfed by macrophages. The yeasts Finally, small "buckshot" calcifications may be scat-
multiply intracellularly with a generation time of 11 tered over both lung fields, a pattern characteristic
hours (Howard 1965). The regional lymph nodes are of uneventful recovery after exposure to a heavy
quickly involved, and hematogenous spread occurs. inoculum of organisms.
The fungus is cleared from the blood by reticuloendo- Primary histoplasmosis has several uncommon lo-
thelial cells throughout the body. Specific cell- cal complications within the chest. Involvement of
mediated immunity develops and rapidly checks the the pericardium can cause a nonspecific acute pericar-
infection in the lung and at distant sites. Granuloma ditis (Wheat et al. 1983). The inflammation probably
formation and necrosis occur at sites of infection. represents a response to adjacent infection in the
Humoral antibody also develops. Although circu- lung, as the cultures of pericardial fluid are usually
lating antibodies are the basis of many diagnostic sterile. Many cases are probably misdiagnosed as
tests, they have little importance in limiting the benign viral pericarditis. Rarely, the process pro-
infection. Hyperimmune serum is of no benefit in gresses to chronic constrictive pericarditis. More
experimental infections, and hypogammaglobulin- delayed and more serious, an extensivefibrosingpro-
emic patients are not prone to progressive infections. cess in the mediastinum can cause vascular compres-
sion and result in the superior vena caval syndrome
with edema of the head and upper extremities and
Clinical Manifestations and Pathology development of superficial venous collaterals across
the chest wall. Inflammation adjacent to the esopha-
Primary Pulmonary Histoplasmosis gus may cause a traction diverticulum. A lymph node
This disease is asymptomatic at least half of the impinging on a bronchus may cause a chronic cough.
time. Symptomatic patients become ill about 2 If a calcified lymph node erodes through a bronchus,
weeks after exposure. They have an influenza-like it becomes a broncholith. Hemoptysis is a common
illness with fever, chills, myalgias, headache, and a clinical manifestation.
nonproductive cough. Rare manifestations include
arthralgias, arthritis, and erythema nodosum. With
Chronic Cavitary Histoplasmosis
or without symptoms, the chest roentgenogram may
Although it may occur anywhere in the lung, chronic
show patchy areas of pneumonitis and prominent
cavitary histoplasmosis usually involves both upper
hilar adenopathy.
lobes and closely resembles reinfection tuberculosis
A primary fungemia probably occurs in most
in its roentgenographic appearance. The mechanism
cases. The calcified granulomas commonly found in
of infection, however, is not endogenous reactivation.
spleens and livers of patients from endemic areas
Rather the infection is the result of a primary infec-
result from this primary, self-limited fungemia, not
tion in abnormal lungs, typically the lungs of middle-
from progressive dissemination.
aged or older male smokers who have centrilobular
Following exposure to an unusually heavy inoc- emphysema (Goodwin et al. 1976). Acute pulmonary
ulum, a more diffuse pulmonary involvement may histoplasmosis in this setting usually resolves un-
occur, with an extensive nodular infiltrate on the eventfully although very slowly. In about a third of
chest roentgenogram. Dyspnea may be added to the cases, infected air spaces persist. A progressive
other symptoms, and symptoms are more severe and fibrosing and cavitary process gradually destroys ad-
last longer. Most patients recover without treat- jacent areas of the lung. Chronic cough is the most
ment, but extreme cases may progress to respiratory common symptom. Constitutional symptoms, includ-
failure. ing low-grade fever, night sweats, and weight loss,
The chest roentgenogram often returns to normal increase as the illness progresses.
after a primary pulmonary infection, but a variety of
residual abnormalities may be seen. Initial soft infil-
trates may harden and contract, leaving one or sev- Disseminated Histoplasmosis
eral nodules. Central necrosis may result in a dense This condition refers to any progressive extrapul-
core of calcium (a "target" lesion), but this is not monary infection. There is a range of infection with
universal. Infrequently, alternate periods of activity different tissue responses. At one extreme there are

VIIL66. Histoplasmosis 781
massive numbers of organisms in all reticuloendo- Diagnosis
thelial organs with little tendency to granuloma for- The histoplasmin skin test is a valuable epidemiologi-
mation. Clinical features include high fever, hepato- cal tool that has permitted mapping of the endemic
splenomegaly, lymphadenopathy, and pancytopenia area. However, it is worthless in individual case
due to bone marrow involvement. This type of dis- diagnosis. A positive skin test means only that the
seminated histoplasmosis has been called the "infan- person is one of many millions who have had
tile" form and may lead to death within days or histoplasmosis, probably remotely and without se-
weeks. Other patients, often older adults, have a quelae. It does not mean that a current illness under
more indolent illness, many months in duration, investigation is being caused by the fungus.
characterized by low or moderate fever, weight loss, Primary histoplasmosis is usually not diagnosed
and skin and mucous membrane lesions. Biopsies of at all. Sputum cultures are positive in less than 10
involved tissues show well-formed granulomas simi- percent of cases. Most recognized cases are diag-
lar to sarcoidosis. Organisms are scanty and often nosed by serology. Serologic tests include immunodif-
are demonstrated only with special stains. fusion (M and H bands) and complement fixation
Disseminated histoplasmosis also occurs as an op- (yeast and mycelial antigens) tests. An M band by
portunistic infection. The degree of granulomatous immunodiffusion is fairly specific. The H band is
tissue response may vary from none to a consider- never found alone. When present with the M band
able amount and has prognostic value. If the bone (10 to 20 percent of the time), it adds further to
marrow biopsy shows epitheloid granulomas or even specificity. Unfortunately, the immunodiffusion test
recognizable aggregates of macrophages, the re- is insensitive and appears slowly after primary infec-
sponse to treatment is quite good. If the biopsy tion. Less than 25 percent of symptomatic patients
shows no granulomas, tissue necrosis, and a large have a positive test 2 weeks after the onset of clini-
number of organisms, the prognosis is very poor cal illness (Davies 1986). The complement fixation
(Davies, McKenna, and Sarosi 1979). test is more sensitive but less specific. The titer
Disseminated histoplasmosis often presents as a against the mycelial antigen is not important be-
nonspecific systemic febrile illness rather than as a cause it is almost always lower than the titer
pulmonary infection. There is usually no cough. against the yeast antigen. A titer of 1 to 32 or higher
The chest roentgenogram may be normal. If abnor- against the yeast antigen is diagnostic if the clinical
mal, it often shows a diffuse infiltrate, suggesting picture suggests histoplasmosis. Unfortunately, only
hematogenous spread to the lung, rather than a 60 percent of patients have a positive test 2 weeks
focal infiltrate. after the onset of clinical illness, and many have 1:8
Immunosuppressed patients probably get dissemi- or 1:16 titers (Davies 1986). What this means is the
nated histoplasmosis in two ways. If they inhale the serologic tests are most useful for diagnosing pa-
organisms while immunosuppressed, the primary in- tients who have already recovered. Patients with
fection will progress, as documented in the India- rapidly progressive pneumonias not responding to
napolis outbreak (Wheat et al. 1982). On the other antibacterial antibiotics need urgent diagnosis, espe-
hand, if they become profoundly immunosuppressed cially if respiratory failure is impending or actually
long after their primary infection, the disease may develops. Some patients are diagnosed by serology.
reactivate (Davies, Kahn, and Sarosi 1978). This is Others require lung biopsy for histopathological di-
suggested by the systemic, nonpulmonary nature of agnosis, because a negative serology cannot exclude
the illness and is supported by the recent experience the diagnosis, and empirical treatment for all possi-
with the acquired immune deficiency syndrome ble causes of progressive pulmonary infection is not
(AIDS). Patients with past exposure to endemic ar- possible.
eas are developing disseminated histoplasmosis Chronic cavitary histoplasmosis is easier to diag-
while living in nonendemic areas such as New York nose. The pace is slower. Tuberculosis is suspected
City (Huang et al. 1988), San Francisco, and Los first, but the tuberculin skin test is negative and the
Angeles. sputum is negative for tuberculosis by smear and
Disseminated histoplasmosis may also present as culture. Sputum cultures for H. capsulatum are usu-
a more localized infection. Examples include central ally positive, as are serologic tests (immunodiffu-
nervous system histoplasmosis, meningeal histoplas- sion: 75 percent; complement fixation: 90 percent).
mosis, and isolated gastrointestinal histoplasmosis, Disseminated histoplasmosis is difficult to diag-
which often involves the terminal ileum. All are nose because the illness is so nonspecific. Serologic
extremely rare. tests are positive in over half of cases and may pro-

vide an important clue. Serodiagnostic tests are cases, and concluded that histoplasmosis was a rare
least helpful in the immunosuppressed because they systemic infection that was nearly always fatal.
are less sensitive and because the pace of the illness However, in the same year, A. Christie and J. C.
may be so fast that there is no time to wait for the Peterson (1945) and also C. E. Palmer (1945), using
results. Histopathological examination of tissue biop- antigen derived from the first isolate, demonstrated
sies is the method of diagnosis in most cases. Bone that great numbers of asymptomatic persons in the
marrow biopsy is particularly valuable in febrile central United States had been infected with the
illnesses without localizing features. Special stains, fungus. Furthermore, they showed that almost all
such as one of the many modifications of the silver tuberculin-negative persons with calcifications on
stain, are necessary to ensure visualization of the chest roentgenogram had positive histoplasmin skin
organisms. Cultures of blood, bone marrow, and tests. Quickly the endemic area was mapped and
other tissues and of body fluids may also give the fungus was isolated from soil in areas with high
diagnosis in some cases. skin-test positivity. The new conclusion was that
histoplasmosis is very common and almost invari-
History and Geography ably benign and self-limited. The fatal cases were
Infection with H. capsulatum was first described in rare and exceptional.
April 1906 by Samuel Darling (1906). From an au- Most of the skin-test reactors in the early surveys
topsy of a laborer who died while working on the had had asymptomatic or minimally symptomatic
Panama Canal, he described a disseminated infec- nonspecific infections. The retrospective discovery of
tion of the reticuloendothelial system caused by an a highly symptomatic but also self-limited form of
organism that he believed was protozoan. Macro- primary histoplasmosis soon followed. Small groups
phages were filled with small organisms. Within a of patients exposed to high concentrations of organ-
few years he reported two other similar cases. In isms, often in closed spaces, had been verified as
1913, H. da Rocha-Lima discussed the published pho- victims of epidemics of an unknown but relatively
tomicrographs of Darling's cases and speculated that severe acute pulmonary illness. An epidemiological
the organism might be a fungus rather than a proto- investigation of one such outbreak, which occurred
zoan (Rocha-Lima 1913). in 1944 and was reported 3 years later (Cain et al.
Another autopsy case was reported in Minnesota 1947), demonstrated convincingly that H. capsu-
in 1926 by W. A. Riley and C. J. Watson (1926), who latum had been the offending agent.
credited Darling with being the first to describe the Upper-lobe cavitary histoplasmosis resembling tu-
infection in 1906. Later, however, there was some berculosis was first described in Missouri in 1956 by
confusion as to whether a case report of R. P. Strong M. L. Furculow and C. A. Brasher among sanitorium
(1906) from the Philippines in January 1906 had patients being treated for tuberculosis. The mecha-
described histoplasmosis first. But in a personal let- nism of infection was most likely progressive pri-
ter many years later, Strong stated his belief that mary infection in an abnormal lung, and not reacti-
the case he had described was not histoplasmosis, vation (Goodwin et al. 1976).
but rather a rare human infection with Cryptococcus In 1955, the isolation of amphotericin B was de-
farciminosus, the cause of farcy in horses (Parsons scribed by W. Gold and colleagues, and within a few
and Zarafonetis 1945). Thus credit for the first case years the drug was available for treatment of a wide
description remains with Darling, who recognized variety of fungal infections. This drug, despite some
that the disease was previously undescribed and toxicity, proved highly effective for histoplasmosis
who named the organism and the illness. and remains the agent to which newer alternatives
After Riley and Watson's paper, scattered autopsy must be compared. Ketoconazole, a nontoxic oral
reports of similar cases followed, mostly from the imidazole, arrived in the 1980s. It is not as effective
central United States. Then in 1934, thefirstpre- as amphotericin B but is reasonable therapy for mild
mortem diagnosis of such a patient was made by to moderately ill patients with chronic cavitary dis-
finding the characteristic intracellular organisms on ease and indolent forms of disseminated disease.
a peripheral blood smear (Dodd and Tompkins 1934). With the increase in the use of glucocorticoids and
W. A. DeMonbreun (1934) isolated the infectious cytotoxic drugs for malignant and nonmalignant dis-
agent, proved that it was a fungus, and demon- eases, disseminated histoplasmosis assumed increas-
strated its thermal dimorphism. ing importance (Davies, Khan, and Sarosi 1978;
In January 1945, R. J. Parsons and C. J. Zara- Kaufman et al. 1978). Endogenous reactivation was
fonetis (1945) reported 7 cases, reviewed 71 previous suspected as a mechanism in some cases because the

VIII.66. Histoplasmosis 783
illness presented as a nonspecific febrile illness. Howard, D. H. 1965. Intracellular growth in histoplasma
Treatment with amphotericin B was very effective if capsulatum. Journal of Bacteriology 89: 518—23.
the diagnosis was made quickly and if the patient Huang, C. T., et al. 1988. Disseminated histoplasmosis in
had some degree of cell-mediated immune response. the acquired immunodeficiency syndrome: Report of 5
Finally, as previously noted, AIDS brought a new cases from a non-endemic area. Archives of Internal
level of suppression of the cell-mediated immune sys- Medicine 2147: 1181-4.
Johnson, P. C , et al. 1986. Progressive disseminated histo-
tem. The concept of endogenous reactivation received plasmosis in patients with the acquired immunode-
further support, for, unlike other immunosuppressed ficiency syndrome. Seminars in Respiratory Infections
patients, even those AIDS patients who respond to 1: 1-8.
treatment are not cured but require long-term sup- Kaufman, C. A., et al. 1978. Histoplasmosis in immunosup-
pressive therapy to prevent relapse of infection (John- pressed patients. American Journal of Medicine 64:
son et al. 1986). 923-32.
Scott F.Davies Mantovani, A. 1972. Histoplasmosis in Europe. Annales
de la Soci6t6 Beige de Medecine Tropicale 52: 421—34.
Bibliography Palmer, C. E. 1945. Non-tuberculosis pulmonary calcifica-
Cain, J. C , et al. 1947. An unusual pulmonary disease. tion and sensitivity to histoplasmin. Public Health
Archives of Internal Medicine 79: 626-41. Reports 60: 513-20.
Christie A., and J. C. Peterson. 1945. Pulmonary calcifica- Parsons, R. J., and C. Zarafonetis. 1945. Histoplasmosis in
tion in negative reactors to histoplasmin. American man: A report of 7 cases and a review of 71 cases.
Journal of Public Health 35: 1131-47. Archives of Internal Medicine 75: 1—23.
Darling, S. T. 1906. A protozoan general infection produc- Riley, W. A., and C. J. Watson. 1926. Histoplasmosis of
ing pseudo tuberculosis in the lungs and focal necrosis Darling with report of a case originating in Minnesota.
of the liver, spleen and lymph nodes. Journal of the American Journal of Tropical Medicine 6: 271-82.
American Medical Association 46: 1283-6. Rocha-Lima, H. da. 1913. Beitrag zur Kenntnis der Blasto-
Davies, S. F. 1986. Serodiagnosis of histoplasmosis. Semi- mykosen: lymphangitis epizootica und histoplasmo-
nars in Respiratory Infections 1: 9-15. sis. Zentralblatt filr Bakteriologie, Parasitenkunde,
Davies, S. E, M. Khan, and G. A. Sarosi. 1978. Dissemi- Infektionskrankheiten; and Hygiene Seminars in Res-
nated histoplasmosis in immunologically suppressed piratory Infections 1: 9-15.
patients: Occurrence in non-endemic area. American Strong, R. P. 1906. A study of some tropical ulcerations of
Journal of Medicine 64: 94-100. the skin with particular reference to their etiology.
Davies, S. E, R. W. McKenna, and G. A. Sarosi. 1979. Philippine Journal of Science 1: 91—115.
Trephine biopsy of the bone marrow in disseminated Wheat, L. J., et al. 1981. A large urban outbreak of
histoplasmosis. American Journal of Medicine 67: histoplasmosis: Clinical features. Annals of Internal
617-77. Medicine 94: 331-7.
DeMonbreun, W. A. 1934. The cultivation and cultural 1982. Risk factors for disseminated or fatal histoplas-
characteristics of Darling's histoplasma capsulatum. mosis. Annals of Internal Medicine 95: 159—63.
American Journal of Tropical Medicine 14: 93-125. 1983. Pericarditis as a manifestation of histoplasmosis
Dodd, K., and E. H. Tompkins. 1934. Case of histoplasmo- during two large urban outbreaks. Medicine 62: 110-
sis of Darling in an infant. American Journal of Tropi- 18.
cal Medicine 14: 127-37.
Edwards, L. D., et al. 1969. An atlas of sensitivity to
tuberculin, PPDB, and histoplasmin in the United
States. American Review of Respiratory Disease 90
(Supplement) 1: 132.
Furcolow, M. L., and C. A. Brasher. 1956. Chronic progres-
sive (cavitary) histoplasmosis as a problem in tubercu-
losis sanitariums. American Review of Tuberculosis
and Pulmonary Disease 73: 609-19.
Gold, W., et al. 1955. Amphotericins A and B, antifungal
antibiotics produced by a streptomycete. Antibiotics
Annual 579-86.
Goodwin, R. A., et al. 1976. Chronic pulmonary histoplas-
mosis. Medicine 55: 413-52.
Grayston, J. T., and M. L. Furcolow. 1953. Occurrence of
histoplasmosis in epidemics: Epidemiological studies.
American Journal of Public Health 43: 665-76.

VIII.67 Although A. duodenale can be ingested in contami-
Hookworm Disease nated food, water, or possibly breast milk, the more
common route of infection, and the only one for N.
americanus, is through penetration of the skin. Lar-
vae in the soil typically enter through the skin of the
Ancylostomiasis, or hookworm disease, is caused by feet, frequently causing dermatitis, once called
hookworm infection and is characterized by progres- "ground itch" or "dew poison" in the southern United
sive anemia. In 1989, it was estimated that perhaps States, and "water itch" or "coolie itch" in India. Then
as many as one billion people, most of them living in the parasites travel through the bloodstream to the
tropical and subtropical regions, are afflicted to alveoli of the lungs, climb the respiratory tree, and
some extent with hookworm infection, although it is make their way into the esophagus. During their
not known how many thus infected can be said to be migration through the airways into the esophagus,
victims of hookworm disease. It is difficult to define the host sometimes develops a cough, wheeziness, or
the difference between hookworm infection and hook- temporary hoarseness. The hookworms are then swal-
worm disease because a host whose diet contains lowed and pass into the gut, where some will success-
adequate amounts of iron may sustain a worm bur- fully attach themselves to the small intestinal
den without debilitating consequences that would mucosa and begin nourishing themselves on their
render a malnourished person anemic. A person ex- host's blood. In the small intestine, hookworms will
hibiting signs of the anemia associated with hook- grow to a length of about 1 centimeter and mature in
worm infestation, therefore, may be said to have 6 to 8 weeks after initial infection. Depending on the
hookworm disease regardless of the number of para- species, hookworms generally live from 1 to 5 years,
sites present. Hookworm disease does not appear on although a few apparently live longer. The adult fe-
the short list of major causes of death in developing male may produce thousands of ova per day, which
countries, but it should be regarded as an important pass out of the body with the host's feces. Egg produc-
contributing factor in millions of deaths annually tion varies with the species, the age of the worm, the
and as a source in its own right of widespread hu- number of worms in the gut, and the degree of the
man suffering. host's resistance. If deposited on warm, moist soil, the
Two species of intestinal nematode, Ancylostoma eggs will produce larvae that will molt twice over 2
duodenale and Ne.cator americanus, are the parasites weeks before becoming infective and can survive in a
that cause ancylostomiasis. Although they appar- free-living state for over a month before finding a
ently cause the same disease, there are important host.
differences between the two species. A. duodenale is Hookworms thrive on human ignorance and pov-
slightly larger, sickle-shaped, with hooks or teeth; N. erty. If the billions of people living in areas of hook-
americanus is smaller, "S" shaped, with shell-like worm infestation were able to eat moderately well,
semilunar cutting plates instead of teeth. Despite wear good shoes, and defecate in latrines, hookworm
being named the "American killer," N. americanus is disease would soon no longer pose a serious threat to
less pathogenic than A. duodenale, as measured by human health. Understood as an index of socioeco-
comparative blood loss. A. duodenale has a higher nomic status, hookworm infection will likely remain
reproductive rate and a shorter life-span. It is also a daunting public health problem as long as there
able to infect the host in more ways than can N. are poor people, inadequately educated, living in
americanus. Hookworm disease has been called by warm climates. The historical record is not reassur-
nearly 150 different names, taxonomic as well as ing: Documentary and physical evidence suggest
colloquial. Many, such as geophagia and langue that hookworms have infected humans in different
blanche, describe physical symptoms, clinical fea- parts of the world for millennia. In the early de-
tures, or unusual behavior associated with the afflic- cades of the twentieth century, massive campaigns
tion. The name Ancylostoma duodenale itself was a launched to eradicate hookworm disease ended in
subject of disagreement among parasitologists, until disillusionment and failure. Modern public health
resolved in 1915 by the International Commission on officials now pursue the more modest goal of contain-
Zoological Nomenclature. Commonly used variations ment, with reductions in the incidence of acute infec-
at one time or another have included Agchylostoma, tion. If anything resembling the optimism of the
Anchylostomum, Ankylostoma, and Uncinaria. Ancy- early days of antihookworm work still survives, it is
lostomiasis was also known as uncinariasis. in the possibility that a vaccine may yet be pro-

VTII.67. Hookworm Disease 785
duced, thus permitting overmatched agencies to fi- be regarded as a stubborn condition of rural poverty
nesse the intractable political problems of malnutri- in developing nations. The campaigns of the 1910s
tion and poverty. and 1920s seemed to demonstrate the futility of
treating the condition in a systematic way without
Distribution and Incidence major improvements in the general standard of liv-
The earliest global survey of hookworm distribution ing. Other diseases such as smallpox and malaria
was conducted in 1910, in preparation for a cam- were both deadlier and less obviously the conse-
paign against hookworm disease carried out by the quences of social and economic circumstances be-
Rockefeller Foundation. Responses from 54 coun- yond the control of public health workers.
tries led to a preliminary description of a "hookworm Other parasitic diseases for which there are no
belt" girdling the Earth between 30° south latitude effective anthelmintics were given research priority
and 36° north. Another survey conducted at the and funding, thus distracting workers in developed
same time estimated that 40 percent of the inhabit- countries and signaling public health officials in de-
ants of the southern United States suffered in vary- veloping countries that hookworms and other soil-
ing degrees from hookworm infection. The larvae transmitted parasites were no longer as important
prefer shade, and light sand or loam soils. They as they once had seemed. Geopolitical factors — the
thrive in the southeastern coastal plains of the economic depression of the 1930s, the Second World
United States, but not in the Piedmont clays. Al- War, the dismantling of the European and American
though infection has not been eliminated in the colonial empires, the Cold War, and political instabil-
United States, the public health menace of hook- ity in many of the countries where hookworm infec-
worm disease has disappeared, only in part because tion is endemic - have also contributed to the reduc-
of the earlier treatment and control programs, but tion of support for elaborate countermeasures.
largely as an incidental consequence of the concen-
tration of the population in cities and towns with Clinical Manifestations and Pathology
sewer systems, and the general improvement in sani- Theoretically, the presence of a single parasite is
tary conditions and the standard of living for those detrimental in some way to the host. In reality, how-
remaining on the farms. Likewise in Europe and the ever, adequately nourished persons with light infec-
United Kingdom, where the disease was sometimes tions are not likely to suffer discernible ill effects or
found in mines, hookworm infection is no longer a to exhibit the clinical features associated with hook-
problem. In Japan as well, rising living standards worm anemia. Children and pregnant women will
and antihookworm campaigns have eradicated the begin to manifest symptoms of hookworm disease at
disease. lower levels of infection, as greater demands on their
It is still, however, a chronic fact of life in most of normal iron stores already exist. Efforts to establish
the rest of the regions within the old "hookworm a threshold of infection above which the host might
belt." In the Caribbean, Central and South America, be expected to begin to show signs of hookworm
Africa, China, India, Southeast Asia, and Oceania, anemia have been frustrated by the inability to con-
endemic hookworm infection remains widespread trol other significant variables such as nutrition and
and largely untreated. After a flurry of activity in general health in a population large enough to be
thefirstthree decades of the twentieth century, hook- statistically valid. An otherwise healthy person with
worm prevention and treatment programs have a normal daily intake of iron can apparently tolerate
been sporadic and uncoordinated. This recent his- several hundred hookworms without patently ad-
tory of neglect has made it difficult even to estimate verse effects. The likelihood of hookworm disease in
the incidence of hookworm disease in areas of the an individual varies in direct proportion to the worm
world where hookworm infection is known to be burden and in inverse proportion to iron intake.
prevalent. A combination of factors helps to explain Hookworm disease shares many of the same clini-
why hookworm lost the attention it once received cal symptoms accompanying other kinds of anemia.
from philanthropic organizations and public health Persons suffering from severe hookworm infection
agencies. The failure of earlier intensive efforts to often have a pale and wan appearance, a tell-tale
make quick, dramatic reductions in the incidence of yellow-green pallor to the skin that helps to explain
hookworm infection and hookworm disease led pub- why the disease was sometimes called "Egyptian
lic health officials with limited budgets to conclude chlorosis" or "tropical chlorosis" in the years before
that a concentration of resources elsewhere would the parasite was discovered and described in the
produce better results. Hookworm infection came to medical literature. In children, growth may be sig-

786 VEIL Major Human Diseases Past and Present
nificantly retarded. A distended abdomen and pro- For example, an extensive treatment and control
nounced, sharply pointed shoulder blades ("pot campaign in China in the early 1920s foundered on
belly" and "angel wings" in the American South) the age-old practice of fertilizing mulberry trees
were once thought to identify children with hook- with human feces, often infested with hookworm
worm disease, although the same features often ac- ova, acquired in massive quantities from brokers
company malnutrition as well. In pregnant women, who collected it for that purpose in nearby villages.
hookworm infection increases the likelihood of fetal For centuries, then, the Chinese silk industry had
morbidity. Victims of hookworm anemia, regardless sustained a disease afflicting its workers whose con-
of age or sex, may be chronically sluggish, listless, taminated feces nourished the crop on which their
and easily tired, symptoms that prompted a face- livelihoods depended.
tious American newspaper reporter early in the
twentieth century to dub hookworm the "germ of History and Geography
laziness." Dropsy, dizziness or giddiness, indigestion,
shortness of breath, tachycardia, and in very ex- From Ancient Times Through the Nineteenth
treme cases congestive heart failure have also all Century
been associated with advanced hookworm disease. Hieroglyphic entries on the Ebers Papyrus (c. 1550
Hookworm sufferers will sometimes eat dirt, chalk, B.C.) describe a mysterious affliction, a-a-a disease,
or clay as well. thought by some to be hookworm anemia, but by
A diagnosis of hookworm infection can be made others, schistosomiasis. In the fifth century B.C.,
easily if ova are detected during a microscopic exami- Hippocrates described a pathological condition
nation of a fecal smear. Quantitative methods have marked by dirt eating, intestinal distress, and a
made it possible to estimate both the total number of yellowish complexion. A handful of other sketchy
eggs based on a quick count in the area under the descriptions from the Mediterranean basin in the
cover slip and the quantity of hookworms lodged in ancient and early medieval periods now appear to be
the intestine. Since the nineteenth century, dozens reports of hookworm disease. From the Western
of anthelmintic drugs have been tried, including Hemisphere in the centuries after European coloni-
thymol, oil of chenopodium, carbon tetrachloride, zation came scattered accounts from English,
and tetrachloroethylene. More recently developed French, Spanish, and Portuguese settlers of epidem-
hookworm vermifuges include bephenium, mebenda- ics among their slaves, called by a rich variety of
zole, pyrantel, and thiabendazole. A regimen combin- colloquial names and now thought to be descriptions
ing chemotherapy with the simultaneous adminis- of widespread hookworm infestation.
tration of iron tablets now seems to be the most The Italian physician Angelo Dubini was the first
effective way to eliminate the parasites and at the to report the discovery of hookworms in a human. He
same time to restore the hemoglobin to a normal detected them first during an autopsy in 1838 and
level quickly. again in 1842. His interest aroused, Dubini exam-
The probability of reinfection is high, however, if a ined 100 cadavers for hookworms and found them in
person thus treated continues to walk barefooted on more than 20. His 1843 article provided a detailed
ground contaminated with hookworm larvae. This description of the parasite, which he named "Agchy-
discouraging realization has bedeviled public health lostoma" (a faulty transliteration of the Greek words
workers since the days of the massive early control for "hook" and "mouth") duodenale. Dubini did not
programs. Numerous designs for sanitary latrines believe that hookworms had caused the deaths of
have come and gone over the years; their construc- any of the people he had examined, although he did
tion costs placed them beyond the means of impover- detect a slight inflammation of the intestinal
ished agricultural workers. Cheaper and less sani- mucosa at the point of attachment. By 1846,
tary latrines were often worse than no latrines at Dubini's parasites had been found in Egypt and, by
all, as they tended to concentrate the locus of infec- 1865, in Brazil. In 1878, a trio of Italian scientists -
tion in a small area where people habitually went to Giovanni Battista Grassi, Corrado Parona, and Er-
defecate. Reinfection would occur rapidly in such nesto Parona - announced that they had detected
instances, although it would take somewhat longer hookworm ova in the feces of anemic patients, thus
to reach pretreatment worm burdens. making it possible for anyone with access to a micro-
The problems posed by unsanitary latrines were scope to diagnose hookworm infection.
universal. Other difficulties were specific to certain In 1880, an outbreak of anemia among the miners
regions or cultures, though no less imposing for that. digging the St. Gotthard tunnel in the Alps gener-

VIII.67. Hookworm Disease 787
ated a wave of public concern in Italy. Within weeks, slaves. Within 2 years, N. americanus had been
hundreds of miners were examined and found to be found extensively not only in Africa but also in India
infected with hookworms. Edoardo Perroncito, a pa- and Australia. Whether A. duodenale might also
thologist at the University of Turin who had found have been introduced into the Americas at about the
over 1,500 hookworms in a postmortem examination same time by the first Spanish explorers and the
of a miner, argued that the presence of hookworms conquistadors has been the subject of some disagree-
in large numbers and the epidemic of anemia were ment. The theory that A. duodenale existed in pre-
causally related. In 1881, Camillo Bozzolo reported Columbian America seems to have been bolstered by
that he had had success using thymol to treat the the discovery in 1974 of what appears to be an A.
infection. For the next 35 years, thymol remained duodenale in the intestine of a Peruvian mummy
the most widely used drug in the treatment of hook- dating from about A.D. 900. Both species are wide-
worm disease. spread in both hemispheres, although their origins
remain murky.
Twentieth-Century Writings In 1909, John D. Rockefeller created an organiza-
In 1898, Arthur Looss in Cairo first suggested that tion to eradicate hookworm disease in the southern
hookworm larvae could penetrate the skin. He had United States. Stiles, who maintained that eradica-
accidentally infected himself by spilling water con- tion was an unrealistic goal, had nevertheless per-
taminated with hookworm larvae on his hand. suaded Rockefeller's principal philanthropic advisor,
Shortly afterward, the spot on his hand where the Frederick T. Gates, that hookworm infection was a
water had spilled began to burn and turned red. He serious problem. With $1 million at its disposal, the
surmised that the hookworm larvae were responsi- Rockefeller Sanitary Commission established opera-
ble. Two to three months later, he found hookworm tions in 11 American states. Over its 5-year exis-
ova in his feces. Although Looss's announcement tence, the Rockefeller Sanitary Commission awak-
was initially greeted with considerable skepticism, ened the public to the nature and extent of the
further experimentation by himself and others had threat, stimulated widespread concern for improved
by 1901 confirmed beyond doubt the percutaneous sanitation, treated almost 700,000 people suffering
route of infection. Looss was later to describe the from hookworm infection, and invigorated long-
migratory path of the hookworm within the host. moribund state boards of health. It failed, however,
While Looss was developing his theory of skin to eradicate hookworm infection anywhere.
penetration in Egypt, a U.S. Army physician sta- At the invitation of the British Colonial Office, the
tioned in Puerto Rico, Bailey K. Ashford, discovered Rockefeller Foundation in 1914 undertook a world-
in 1899 that hookworm infection was rampant wide campaign modeled on the experience of the
among the agricultural workers in the sugar cane Rockefeller Sanitary Commission. They opened op-
fields (Ashford 1900). In 1903, Ashford persuaded erations in the British possessions in the West Indies
the governor to budget funds for the creation of the before extending the work into British Guiana,
Anemia Commission of Puerto Rico, the first large Egypt, Ceylon, and Malaya. By the end of the First
antihookworm program of its kind in the world. World War, Rockefeller programs were underway or
Ashford had believed that the hookworms he ready to begin in Central America, Brazil, and
found in Puerto Rico were A. duodenale. At the time China. Shortly thereafter, Rockefeller-sponsored
of his discovery, no other species was known to infect campaigns were in place in most of the countries in
humans. Charles W. Stiles, a zoologist trained in the tropics. Their earlier experience in the southern
Germany working for the U.S. Department of Agri- United States had led administrators of the Rockefel-
culture, examined a sample of Ashford's hookworms ler Foundation programs to employ a combination of
and others sent to him from different parts of the two approaches to the problem of hookworm infec-
United States. He compared them with samples of A. tion. The dispensary method attracted people from
duodenale and concluded in 1902 that these hook- the surrounding area to a day-long demonstration
worms were indigenous to the Western Hemisphere conducted by a Rockefeller physician assisted by mi-
and were a different species, which he named croscopists during which examinations were carried
Necator americanus. In 1905, Looss found N. ameri- out and treatments dispensed, while the crowd
canus in six Central African pygmies brought to heard lectures on prevention and improved sanita-
Cairo for a music hall exhibition. He speculated that tion. The intensive method was based on a different
N. americanus originated in the Eastern Hemi- approach to the problem of hookworm infection. A
sphere and was brought to the Americas by African clearly delimited area was selected for a saturation

campaign of aggressive hookworm treatment and Link, William. 1988. Privies, progressivism, and public
latrine construction. schools: Health reform and education in the rural
Beginning in the early 1920s, the Rockefeller Foun- south, 1909-1920. Journal of Southern History 54:
dation had begun to rethink its basic approach to 623-42.
hookworm work. The early days of extensive, pro- Rockefeller Foundation. 1913/14-1929. Annual Report.
tracted campaigns had produced negligible results. New York.
1922. Bibliography of hookworm disease. New York.
The incidence of hookworm infection in Puerto Rico,
Rockefeller Sanitary Commission. 1910-1915. Publica-
for example, was as high in 1920 as it had been in tion Nos. 1-9. Washington D.C.
1903, just before Ashford's Anemia Commission be- Savitt, Todd L., and James Harvey Young. 1988. Disease
gan to go to work. Not yet prepared to abandon hook- and distinctiveness in the American South. Knoxville,
worm work altogether, the Rockefeller Foundation Tenn.
gradually withdrew from massive treatment cam- Schad, G. A., and J. G. Banwell, 1989. Hookworms. In
paigns and began to redirect its efforts toward labora- Tropical and geographical medicine, ed. K. S. Warren
tory research, withfieldwork restricted to the gather- and A. A. F. Mahmoud, 379-92. New York.
ing of data and the testing of hypotheses and drugs. Schad, G. A., T. A. Nawalinski, and V. Kochar. 1983. Hu-
By the mid-1920s, disillusionment had set in and the man ecology and the distribution and abundance of
days of the antihookworm crusades were over. Since hookworm populations. In Human ecology and infec-
then, although laboratory work has revealed much tious diseases, ed. N. Croll and J. Cross, 187-223. New
more about the relationship between humans and York.
hookworms, little has been done in a practical way to Schad, G. A., and K. S. Warren. 1990. Hookworm disease:
Current status and new directions. London.
rid the former of the latter, except where there have Stiles, C. W. 1939. Early history, in part esoteric, of the
been improvements in living conditions. hookworm (uncinariasis) campaign in our southern
John Ettling states. Journal of Parasitology 25: 283-308.
Warren, K. S. 1989. Hookworm control. Lancet 1 (8616):
Bibliography 897-900.
Ashford, Bailey K. 1900. Ankylostomiasis in Puerto Rico. Williams, Greer. 1969. The plague killers. New York.
New York Medical Journal 71: 552-6.
1934. A soldier of science. New York.
Boccaccio, Mary. 1972. Ground itch and dew poison: The
Rockefeller Sanitary Commission, 1909—14. Journal
of the History of Medicine and Allied Sciences 27: 30— VIII.68
53.
Brown, E. Richard. 1979. Rockefeller medicine men: Medi- Huntington's Disease
cine and capitalism in America. Berkeley.
Cassedy, James H. 1971. The "germ of laziness" in the
(Chorea)
South, 1909-1915: Charles Wardell Stiles and the para-
dox. Bulletin of the History of Medicine 45: 159-69.
Chandler, A. C. 1929. Hookworm disease: Its distribution, Huntington's disease (HD) is a rare progressive neu-
biology, epidemiology, pathology, diagnosis, treatment, rological disorder, in which normal central nervous
and control. London. system development is succeeded in early adulthood
Dock, G., and C. Bass. 1910. Hookworm disease. St. Louis. by premature and selective neuronal death. First-
Ettling, John. 1981. The germ of laziness: Rockefeller phi- rank symptoms consist of rapid, involuntary jerking
lanthropy and public health in the New South. Cam- movements, or chorea, due to lesions in the putamen
bridge, Mass. and the caudate nucleus, and a progressive dementia
Fosdick, Raymond B. 1952. The story of the Rockefeller due to loss of cells in the cerebral cortex (Hayden
Foundation. New York. 1981). Onset of symptoms is typically in the third or
Gates, Frederick T. 1977. Chapters in my life. New York. fourth decade, and the clinical course is progressive
Hoeppli, R. 1959. Parasites and parasitic infections in early and relentless over a period of 10 to 30 years. At
medicine and science. Singapore. autopsy, gross examination of HD brains reveals se-
Kean, B. H., K. E. Mott, and A. J. Russell. 1978. Tropical
medicine and parasitology: Classical investigations.
vere, symmetrical atrophy of the frontal and tempo-
Ithaca, N.Y. ral lobes as well as, to a lesser degree, the parietal
Keymer, Anne, and Don Bundy. 1989. Seventy-five years and occipital lobes. The caudate nucleus is pro-
of solicitude. Nature 337: 114. foundly involved, and diffuse neuronal loss extends
Lane, Clayton. 1932. Hookworm infection. London. into the cerebral cortex, basal ganglia, thalamus,

VIII.69. Hypertension 789
and spinal motor neurons. Various neurotransmitter disease-linked G8 (D4S10) locus in Wolf- Hirschhorn
systems have also been shown to be progressively syndrome. Nature 318: 75-78.
affected (Rosenberg 1986). Hayden, M. R. 1981. Huntington's chorea. New York.
References to the disorder have been found as Rosenberg, R. N. 1986. Neurogenetics: Principles and prac-
early as 1841, but the first full description of the tices. New York.
Vessie, P. R. 1932. On the transmission of Huntington's
disease was made by George S. Huntington in 1872
chorea for 300 years: The Bures family group. Journal
(Gates 1946). Referring to a large family on Long of Nervous and Mental Diseases 76: 553—73.
Island, Huntington distinguished this condition
from other known choreiform movement disorders
such as Sydenham chorea, or St. Vitus dance. The
remarkable history of HD in the New World was
recounted in a paper by P. R. Vessie (1932). The
carriers of the mutant gene responsible for nearly all VIII.69
known cases of the disease sailed for Massachusetts
from Suffolk in 1630. Upon arrival, these individu-
Hypertension
als founded family lines that included not only the
Long Island cases but also the celebrated "Groton Arterial hypertension is a condition characterized
witch," whose violent and uncontrollable move- by abnormally high systolic and/or diastolic blood
ments were recorded in 1671 as evidence of posses- pressure levels. Systolic and diastolic blood pressure
sion (Vessie 1932). Compilations of the pedigrees levels are usually estimated indirectly by use of an
encompassing the various branches of the families inflatable rubber bladder to compress the artery in
founded in seventeenth-century Massachusetts dem- the upper arm. The pressure exerted on the artery
onstrated a clear pattern of autosomal dominant by the bladder is registered by a device called a
transmission, meaning that the disease will appear manometer. The level of the blood pressure is a mea-
in one-half the offspring of an affected parent. sure of the force exerted against the walls of the
During the century that has passed since the first artery during each heart beat or pulse. The peak of
description of HD, numerous biochemical and the pressure wave occurs when the heart beats or
histological studies have been carried out. However, contracts (systole) and is called the systolic pressure.
the primary defect in HD remains unknown. A ma- The valley of the pressure wave occurs when the
jor breakthrough occurred in 1983 when J. F. heart relaxes (diastole) and is termed the diastolic
Gusella and colleagues announced the discovery of pressure. Blood pressure is recorded as systolic over
an anonymous DNA sequence closely linked to the diastolic.
putative HD gene (Gusella et al. 1983, 1985). This Although longitudinal research studies such as
molecular probe, which has been refined by sub- the one in Framingham, Massachusetts, and the
cloning, is now a tool for presymptomatic diagnosis life insurance industry have noted that even slight
of HD (Folstein et al. 1985). An effort is underway to elevations of blood pressure are associated with in-
clone and sequence the HD gene itself in order to creased risk of premature death, the World Health
determine the precise nature of the pathological Organization has recommended that the following
changes leading to clinical HD (Gilliam et al. 1987). blood pressure levels be used to classify adults
Eric J. Devor (blood pressure levels defining juvenile hyperten-
sion are under review):
Bibliography Hypertensive: Greater than or equal to 160 millime-
Folstein, S. E., et al. 1985. Huntington's disease: Two ters of mercury (mmHg) systolic and/or greater
families with differing clinical features show linkage
than or equal to 95 mmHg diastolic.
to the G8 probe. Science 229: 776-9.
Gates, R. R. 1946. Human genetics. New York.
Normotensive: Less than or equal to 140 mmHg sys-
Gilliam, T. C , et al. 1987. Localization of the Huntington's tolic and less than or equal to 90 mmHg diastolic.
disease gene to a small segment of chromosome 4 Borderline Hypertensive: Between hypertensive and
flanked by D4S10 and the telomere. Cell 50: 565-5711. normotensive.
Gusella, J. E, et al. 1983. A polymorphic DNA marker
genetically linked to Huntington's disease. Nature The condition is also divided etiologically into two
306: 75-8. types: secondary and primary or essential hyperten-
Gusella, J. F.( et al. 1985. Deletion of Huntington's sion. Secondary hypertension, resulting from some

known cause (including diseases of the kidney or the Table VIII.69.1. Prevalence of hypertension in 20- to
adrenal glands), represents less than 10 percent of 59-year-olds, by region, in ascending order by
all the cases of the disease. Essential hypertension, prevalence: 52 populations, INTERSALT Study,
occurring in over 90 percent of the cases, is denned 1988
as high blood pressure without evident cause. Most
of the discussion that follows deals with this latter, Rank Prevalence
more prevalent type of the disease. of hypertension Site, country
52 (%) (race) n
Distribution and Incidence Africa
In most societies the average blood pressure levels 4 05.0 Kenya 176
and the diseases associated with higher blood pres- 42 24.0 Zimbabwe 195
sure increase as people get older. However, blood Asia
pressure does not increase with age in all popula- 2 00.8 Papua New Guinea 162
tions. Indeed, the disease appears to be totally ab- 6 08.1 South Korea 198
sent from societies described as "stone age." In such 7 08.5 Beijing, P.R. China 200
societies, blood pressure does not rise with age, and 8 10.0 Ladakh, India 200
hypertension is extremely rare. However, a 1988 9 10.0 Toyama, Japan 200
World Health Organization literature survey on 10 10.9 Tochigi, Japan 194
high blood pressure in less developed countries re- 11 11.7 Osaka, Japan 197
vealed that the prevalence of hypertension there is 17 13.5 Nanning, P.R. 200
increasing. China
18 13.6 New Delhi, India 199
A recent international survey, the INTERSALT 20 15.0 Tianjin, P.R. China 200
study, highlights the wide geographic variability of 28 17.6 Taiwan 181
hypertension throughout the world. INTERSALT, a
52-center, 32-country study, found that the preva- Europe
lence of hypertension (hypertensives were denned as 12 12.5 Iceland 200
anyone having greater than 140 mmHg systolic or 14 13.0 Naples, Italy 200
15 13.1 Heidelberg, F.R. 196
greater than 90 mmHg diastolic or of persons on
Germany
antihypertensive medication) between the ages of 20 200
19 15.0 Birmingham, U.K.
and 59 ranged from zero percent in the Yanomamo 21 15.5 Soviet Union 194
Indians of northern Brazil to over 33 percent in an 22 15.5 Torrejon, Spain 200
African-American population in Jackson, Missis- 23 16.0 Manresa, Spain 200
sippi. There was a significant within-continent vari- 24 16.2 Gubbio, Italy 199
ability as well (see Table VIII.69.1). It is likely that 25 16.6 Bernried, F.R. 197
this wide variability in the prevalence of hyperten- Germany
sion is due to differences in both environmental and 26 17.0 Ghent, Belgium 200
genetic factors. 30 18.6 Belfast, U.K. 199
31 19.0 Krakow, Poland 200
Etiology and Epidemiology 33 19.7 Charleroi, Belgium 157
34 20.5 Mirano, Italy 200
Many have hypothesized that environmental factors 198
36 20.7 German Democratic
are primarily responsible for the development of Republic
high blood pressure. Principal evidence for this view 37 21.0 South Wales, U.K. 199
consists of reports that unacculturated or "primi- 39 23.0 Joensuu, Finland 200
tive" populations are virtually free of hypertension, 40 23.0 Malta 200
but when members of these populations migrate to 43 24.2 The Netherlands 199
urban areas their blood pressures rise. There are 45 24.6 Bassiano, Italy 199
conflicting interpretations of this phenomenon: 46 25.0 Warsaw, Poland 200
Some postulate that the change in diet (especially 47 26.0 Turku, Finland 200
salt intake) and/or the weight gain that often accom- 49 26.6 Denmark 199
pany the move to a modern area are the primary 50 31.0 Hungary 200
reasons for the development of high blood pressure 51 32.0 Portugal 198
in populations that were previously free from it.
Others suggest that an increase in the level of psy-

Table VHI.69.1 (cont.) nesium, calcium, fat, and even licorice. Most interest
has centered around salt - more specifically, the so-
Rank Prevalence dium portion of the molecule. The most compelling
of hypertension Site, country evidence for the influence of salt on blood pressure is
52 (%) (race) n the fact that every low-salt-intake population ever
North America studied has manifested very low blood pressure that
13 12.6 Chicago, U.S. 196 does not rise with age. Significantly, INTERSALT
32 19.2 Goodman, U.S. 198 reported a positive and statistically significant rela-
(white) tionship between salt intake and blood pressure in
35 20.6 Jackson, U.S. 199 their 52-center study.
(white) Psychosocial stress is also believed to be associated
38 22.6 Labrador, Canada 161 with hypertension. In some population surveys, inves-
41 23.2 Hawaii, U.S. 187
tigators have reported that societies under high
44 24.5 St. Johns, Canada 200
48 26.1 Goodman, U.S. 186
stress also have higher mean blood pressure levels
(black) than those under low stress. Unfortunately, stress
52 33.5 Jackson, U.S. 184 has been a difficult phenomenon to measure, and the
(black) association between stress and blood pressure has
been difficult to demonstrate in human populations.
South America One of the most compelling animal models for stress-
1 00.0 Yanomamo, Brazil 195
3 01.0 Xingu, Brazil 198
induced hypertension has been that developed by J. P.
5 05.9 Mexico 172 Henry and associates (1975). This model makes it
16 13.5 Argentina 200 necessary for mice to compete for food and territory;
27 17.1 Colombia 191 most animals in the system develop very high blood
29 18.0 Trinidad and 176 pressure and die from kidney failure. Notable excep-
Tobago tions are dominant males whose blood pressure is less
elevated. Some believe that this is a valid model appli-
Note: At each site the investigators randomly chose about cable to human societies as well.
200 individuals from population-based registries from 4 Heredity is known to be an important contributor
equally sized age groups between the ages of 20 and 59 to blood pressure regulation, and hence to abnor-
years. Subjects were defined as hypertensive if systolic mally elevated blood pressure or hypertension. Like
blood pressure was a 140 mmHg, or if diastolic BP was a many quantitative genetic traits such as height, lev-
90 mmHG, or if the subject was on antihypertensive medi-
cation. Total N = 10,079.
els of blood pressure tend to run in families; some
have higher blood pressure, some have lower blood
Source: INTERSALT (1988). pressure. Other evidence of genetic influence is re-
vealed by the concordance of hypertension in sib-
chosocial stress is the culprit. Still others surmise lings, especially identical, or monozygotic (MZ),
that those who experienced the greatest rise in blood twins: If one member of a set of MZ twins has hyper-
pressure may have inherited a genetic predisposi- tension, there is a strong likelihood that the other
tion to the disease that is sparked by some environ- will have the disease as well. Genetic influences on
mental phenomena such as dietary salt or psychoso- arterial pressure have also been demonstrated in
cial stress. Interestingly, salt and stress have been inbred strains of rats, mice, and other animals. The
assumed to be related to the disease for eons. A hereditary mediators of these genetic influences on
Chinese physician stated over 4,000 years ago that blood pressure are not known but probably reside in
"if too much salt is used in food, the pulse hardens genetic influences on the major blood pressure con-
[and] when rebellious emotions rise to Heaven, the trol systems.
pulse expires and leaves the body." Many investigators believe that neither genetic
A gain in body weight as a result of a generalized nor environmental factors act alone, that in fact
increase in food intake is most definitely associated there is an interactive relationship between genes
with high blood pressure, and a sustained reduction and environment. A compelling example of this is
in body weight is one of the most effective methods of the simple breeding experiments in rats carried out
lowering blood pressure. by L. K. Dahl and colleagues in the early 1960s. By
Specific dietary factors that may affect blood pres- selective breeding they were able, in a very few
sure include salt (sodium chloride), potassium, mag- generations, to develop two strains of rats: One, ex-

tremely sensitive to the blood pressure-raising ef- and death. In about 2500 B.C., for example, a Chi-
fects of salt in the diet, was called "salt sensitive"; nese physician remarked: "[W]hen the pulse is abun-
the other, resistant to the blood pressure-raising ef- dant but tense and hard like a cord, there are dropsi-
fects of salt, was termed "salt resistant." Humans cal swellings."
manifest similar differences, in that some are "salt More than 4,000 years later, in 1827, the British
sensitive" and others are not, and the Dahl model physician Richard Bright suggested that the dropsi-
may be applicable to understanding the evolution of cal swellings he encountered in a patient were due to
"salt sensitivity" in human populations as well. obstruction in the kidney's circulatory system.
In former times, as isolated populations diverged Bright's argument was so persuasive that through-
and migrated into different ecological systems, they out the remainder of the nineteenth century most
may also have experienced different "selection pres- physicians considered a strong or tense pulse a symp-
sures" related to salt metabolism. These included tom of kidney disease.
different temperatures, salt intake, and mortality By the late nineteenth century, the earlier discover-
from salt-depletive diseases such as diarrhea and fe- ies on the measurement of systolic blood pressure by
ver. These "selection pressures" may have resulted in Stephen Hales, Samuel von Basch, and others led to
a new genotype that enhanced survival in the new the invention of the sphygmomanometer (blood pres-
ecology environment by protecting against prema- sure cuff). Coupled with the 1905 description of
ture mortality from salt-depletive conditions. If this diastolic blood pressure by N. Korotkoff, this device
protective genotype included an enhanced ability to effectively replaced diagnosis by "pulse," and its wide-
conserve sodium, then it is likely that these adapta- spread use led observers to the realization that most
tions predispose to salt-sensitive hypertension today. patients with elevated arterial pressure did not have
It is argued that this may have occurred when many a kidney disorder. This newly discovered condition
sub-Saharan Africans were forced to migrate to the was given various names including angiosclerosis,
Western Hemisphere. Mortality rates were very high presclerosis, hyperpiesis, primary hypertensive car-
from salt-depletive diseases, and it is surmised that diovascular disease, and essential hypertension. The
those with the superior salt-retaining abilities sur- condition was soon recognized as one of the most
vived and passed their genes on to present-day Afri- common types of cardiovascular disorders. Insurance
can Americans. This enhanced genetically based abil- companies led the way in quantifying the association
ity to conserve salt may, therefore, be found in greater between this new disease and premature death.
frequency in Western Hemisphere blacks than in In the 1910s, the medical director of the North-
West African blacks, and may be part of the reason western Mutual Life Insurance Company, J. W.
the former group today has a higher prevalence of Fisher, reported the results of several years of study
hypertension than does the latter. of the relationship between blood pressure levels
and premature death. Table VIII.69.2 provides a
Clinical Manifestations brief summary of trie findings.
Although in the past a "hard pulse" or "dropsical It was obvious to Fisher that the higher the sys-
swellings" (edema) may have signaled hypertension, tolic blood pressure, the greater the risk of death.
today the only acceptable way to detect the condition Those with systolic blood pressure levels above 160
is through the use of the blood pressure cuff (sphyg- mmHg had a probability of premature death about
momanometer). Because the disease is usually 2.5 times greater than those with a systolic blood
asymptomatic, essential hypertension has been ap- pressure of about 140 mmHg. In recommending that
propriately termed the "silent killer." Undetected any insurance application with a persistent blood
and uncontrolled, it can damage the arteries, the pressure of "15 mm Hg above the average for his or
kidneys, and the heart, and, as several important her age" should be investigated further, Fisher was
long-term studies revealed, hypertension is a precur- probably the first to offer a quantifiable definition of
sor to premature death from coronary heart disease, "high blood pressure" (see Table VIII.69.3).
stroke, congestive heart failure, kidney (renal) fail- The scientific world was interested in what caused
ure, and atherosclerosis. this newly discovered, deadly, and extremely preva-
lent disease. During the 1930s and 1940s, research-
History ers conducted detailed examinations on the influence
For centuries, the only way to assess "blood pres- of the sympathetic nervous system, the endocrine
sure" was to feel the pulse, and interpreting its force system, and the renal system on arterial pressure,
and rhythm proved to be a useful predictor of disease and were successful in cataloging several types of

Table VIII.69.2. Relationship between blood pressure and mortality: Northwestern Mutual Life Insurance
Company, 1907-14
Systolic Observed Expected Proportion
Age Insurance status BP deaths deaths obs/expected
40-60 insured 142.43 85 91.17 0.93
"All ages" insured 152.58 33 23.62 1.40
"All ages" not insured 161.44 83 34.95 2.37
Note: Expected deaths = expected deaths in company (80% of M.A. table in source); systolic BP = systolic blood pressure;
observed deaths = observed deaths of those with noted systolic blood pressure.
Source: Adapted from Fisher (1914).
secondary hypertension. Pheochromocytoma was teams, one in the United States and one in Argen-
first reported in 1929, Cushing's syndrome in 1932, tina, simultaneously discovered that the blood from
pyelonephritis in 1937, renal artery stenosis in 1938, a "Goldblatt kidney" contained a substance that
and Conn's syndrome (primary aldosteronism) in caused vasoconstriction (squeezing of the arteries).
1955. In very few cases these "secondary" causes of The American group called their substance "angio-
high blood pressure were cured through surgery, but tonin," while the Argentine group christened the
in the great majority of cases - those with essential compound "hypertensin." These two teams met and,
hypertension - the ultimate determinant of elevated deciding they were working on the same substance,
arterial pressure remained a mystery. One very im- combined their two names for the compound; the
portant breakthrough in understanding the patho- substance became angiotensin. These discoveries led
physiology of essential hypertension occurred among to extensive biochemical research into the neural,
investigators working in animal physiology. cellular, and hemodynamic systems that control
In the 1920s, Harry Goldblatt progressively con- blood pressure, and eventually to the development of
stricted blood flow to the kidney in a dog, which the most widely prescribed antihypertensive medica-
produced a rapidly developing high blood pressure tions today. The discovery and elucidation of the
that resulted in death due to heart failure. The ex- biochemical mechanisms controlling blood pressure
periment, said by T. A. Stamey to have "stimulated were extremely important in understanding and con-
more medical research than any single experiment trolling high blood pressure, but researchers were
in medical history," sparked a worldwide search for a still a long way from finding the ultimate cause of
kidney (renal)-based pressor substance that pro- the disease.
duced hypertension. By the end of the 1930s, two In the 1950s and 1960s, an important debate oc-
curred between two British physicians over the influ-
ence of heredity on high blood pressure in humans.
Table VIII.69.3. "Normal" and "unacceptable" Robert Platt argued that essential hypertension was
systolic blood pressures by age: Northwestern a "qualitative" disease, controlled by a single gene,
Mutual Life Insurance Company, 1914 with a bimodal population distribution. George Pick-
ering, on the other hand, reasoned that what was
"Unacceptable"
termed "hypertension" was only the upper end of a
"Normal" systolic systolic
Age group blood pressure blood pressure
continuous unimodal distribution of blood pressure
levels. He thought that hypertension was a "quanti-
15-20 119.85 >134.85 tative" disease and was controlled by multiple genes
21-25 122.76 >137.76 in combination with environmental influences. The
26-30 123.65 >138.65 debate was never resolved by the two participants.
31-35 123.74 >138.74
Epidemiological research since then has tended to
36-40 126.96 >141.96
favor Pickering's quantitative definition; however,
41-45 128.56 >143.56
46-50 130.57 >145.57
in 1983 the analysis of a biostatistician showed the
51-55 132.13 >147.13 bimodal distribution of blood pressure values in a
56-60 134.78 > 149.78 very large sample from Norway.
Today, both environmental and genetic factors are
Source: Adapted from Fisher (1914). under intense study as possible etiologic factors at

the individual level and the population level. How- Page, I. H. 1988. Hypertension research: A memoir, 1920-
ever, it is still the case that the cause of abnormally 1960. New York.
elevated blood pressure in over 90 percent of the Ruskin, A. 1956. Classics in arterial hypertension. Spring-
cases remains unknown. Fortunately, however, suc- field, 111.
cessful efforts are being made to lower blood pres- Stamey, T. A. 1963. Renovascular hypertension. Baltimore.
sure through diet, stress reduction, exercise, weight Swales, J. D., ed. 1985. Platt versus Pickering: An episode
in recent medical history. London.
control, medication, and other means, in the hope
Wakerlin, G. E. 1962. From Bright to light: The story of
that the frequency of premature deaths from hyper-
hypertension research. Circulation Research 11: 131-
tension will be reduced throughout the world. 6.
Thomas W. Wilson and Clarence E. Grim Waldron, I., et al. 1982. Cross-cultural variation in blood
pressure: A quantitative analysis of the relationships
Bibliography of blood pressure to cultural characteristics, salt con-
Allanby, K. D. 1958. The evolution of the treatment of sumption, and body weight. Social Science Medicine
essential hypertension. Guy's Hospital Review 107: 16:419-30.
515-30. White, P. D. 1946. The heart in hypertension since the
Dahl, L. K., M. Heine, and L. Tassinari. 1962. Role of days of Richard Bright. Canadian Medical Journal 54:
genetic factors in susceptibility to experimental hyper- 129-36.
tension due to chronic excess salt ingestion. Nature Wilson, T. W., and C. E. Grim. 1992. Unnatural selection:
194: 480-2. The history of the trans-Atlantic slave trade and
Fasciolo, J. C. 1977. Historical background on the renin- blood pressures today. In The Atlantic slave trade:
angiotensin system. In Hypertension: Physiopathol- Effects on economics, societies, and peoples in Africa,
ogy and treatment, ed. E. Koiw Genest and O. Kuchel, the Americas, and Europe, ed. J. E. Inikori and S.
134-9. New York. Engerman, 339-59. Durham, N.C.
Fisher, J. W. 1914. The diagnostic value of the sphygmoma- World Health Organization. 1988. Arterial hypertension.
nometer in examinations for life insurance. Journal of Technical Report Series N. 628.
the American Medical Association 63: 1752-4.
Flexner, M. 1959. The historical background of medical
therapy in essential hypertension. Journal of the Ken-
tucky Medical Association 57: 1210—13.
Henry, J. P., P. M. Stephens, and G. A. Santisteban. 1975.
A model of psychosocial hypertension showing revers- VIII.70
ibility and progression of cardiovascular complica- Infectious Hepatitis
tions. Circulation Research 36: 156—64.
INTERSALT Cooperative Research Group. 1988. INTER-
SALT: An international study of electrolyte excretion Hepatitis literally refers to any inflammation of the
and blood pressure. Results from 24 hour urinary so-
liver. Even when restricted by the term "infectious,"
dium and potassium excretion. British Medical Jour-
nal 297: 319-28. it has many causes, including malaria and many vi-
Janeway, T. C. 1915. Important contributions to clinical ruses including that of yellow fever. By convention,
medicine during the past thirty years from the study however, infectious hepatitis usually refers to a small
of human blood pressure. Bulletin of the Johns Hop- group of diseases caused by several unrelated vi-
kins Hospital 26: 341-50. ruses, whose most obvious and most consistent symp-
Kannel, W. B., M. J. Schwartz, and P. M. McNamara. 1969. toms are due to liver damage. Because these diseases
Blood pressure and risk of coronary heart disease: The are unrelated, except in liver involvement, they will
Framingham study. Diseases of the Chest 56: 43—52. be treated individually. Only their early undifferenti-
Kaplan, N. M. 1986. Clinical hypertension. Baltimore. ated history can be reviewed in general terms.
Laragh, J. H., and B. M. Brenner, eds. 1990. Hypertension: Even the distinction between infectious and non-
Pathophysiology, diagnosis, and management, 2 vols. infectious hepatitis is a problem. Autoimmune
New York.
chronic active hepatitis will not be considered here,
Lew, E. A. 1973. High blood pressure, other risk factors
although there is evidence of viral involvement in
and longevity: The insurance viewpoint. American
Journal of Medicine 55: 284. triggering the autoimmune reaction. Liver cancer
Major, R. 1930. The history of taking blood pressure. An- will be included as a late consequence of infection
nals of Medical History 2: 47-55. with hepatitis B virus, because that seems to be the
Nissinen, A., et al. 1988. Hypertension in developing coun- main cause. Other clinically similar diseases that
tries. World Health Statistics Quarterly 41: 141-54. are not covered here are cirrhosis due to toxins such

VIII.70. Infectious Hepatitis 795
as alcohol, and jaundice due to physical obstruction through fecal contamination of food and water. The
of the bile duct. virus is very fastidious in its host range. It is known
to infect only humans, apes, and marmosets, and it
History replicates in vitro only in a few primate cell lines.
Until the mid-1900s, hepatitis was frequently
equated with jaundice, although jaundice is only a Geography and Epidemiology
sign of a failure to clear normal breakdown products The virus of hepatitis A is essentially worldwide in
from the blood. Under this terminology, hepatitis its distribution, but it is very much commoner where
and other liver diseases played a very important role drinking water is unsafe and sanitation inadequate.
in early medical writings, but it is difficult to deter- Like poliomyelitis, however, the prevalence of dis-
mine which references relate to hepatitis as we now ease is often inversely related to the prevalence of
know it, and which refer to the various other causes virus. In the less developed countries most people
of jaundice. It is even more difficult to distinguish become immune through infection in childhood, of-
one type of hepatitis from another in the early refer- ten with no apparent illness. In semideveloped coun-
ences. Hippocrates identified at least four kinds of tries, porcelain water filters may be used to remove
jaundice, one of which he considered epidemic and the causes of acute bacterial and protozoal diseases,
thus, by implication, infectious. Another was "au- but not the cause of hepatitis virus. Persons from
tumnal hepatitis"; this condition, which appeared developed countries, especially when traveling in
after an interval appropriate to the incubation pe- lesser developed areas, are likely to become infected
riod following the dry Mediterranean summer when as adults with serious consequences.
water supplies would have shrunk, could have been
hepatitis A. An emphasis on the liver has persisted Clinical Manifestations
into modern times in French popular medicine, Hepatitis A is manifested by general malaise, loss of
where the liver is commonly blamed for ill-defined appetite, and often, jaundice. Definitive diagnosis of
ailments. hepatitis requires the demonstration of elevated
Postclassical writers continued to have difficulty in blood levels of bilirubin and of certain enzymes. Spe-
distinguishing infectious forms from noninfectious cific diagnosis can be confirmed only by electron
forms of jaundice because of the long and variable microscopic examination of the feces or, more practi-
incubation periods of the infectious diseases. Clear cally, by demonstration of specific antibodies. The
recognition of the infectivity of hepatitis is usually disease is seldom fatal when uncomplicated by other
ascribed to Pope Zacarias (St. Zachary), who in the conditions, and rarely leaves sequelae. Recovery nor-
eighth century advocated a quarantine of cases. This mally occurs in 4 to 8 weeks.
had little effect on general thinking, however, be-
cause of the variety of circumstances that were associ- History
ated with different outbreaks. Many cases seemed to As noted above, although the existence of a hepatitis
be sporadic, but epidemics of what must have been transmitted by conventional infectious routes could
hepatitis A, or enterically transmitted non-A, non-B, be inferred from the early literature, specific identifi-
were known from the early seventeenth century to be cation of hepatitis A was not accomplished until the
common in troops under campaign conditions. An epi- late 1960s and 1970s. Then, the development of
demic of hepatitis B, associated with one lot of small- methods for recognizing hepatitis B, and Saul
pox vaccine of human origin, was well described by A. Krugman's (1967) demonstration of two distinct
Lurman in 1885. In spite of this, as late as 1908, the agents in his studies of children in a home for the
dominant medical opinion held that all hepatitis was retarded, made its existence apparent. The agent of
due to obstruction of the bile duct. The picture did not this disease remained enigmatic because it could not
really begin to clear until the middle of the twentieth be propagated, except in humans. S. M. Feinstone,
century. A. Z. Kapikian, and R. A. Purcell identified the virus
in feces in 1973. F. W. Deinhardt and others showed
Hepatitis A in 1972 that the marmoset was susceptible. Finally,
in 1979, P. J. Provost and M. R. Hilleman found a
Etiology tissue culture line that could be used to grow the
Hepatitis A is caused by an RNA virus 27 nano- virus. An attenuated vaccine has been produced and
meters in diameter. It is very similar to poliovirus in successfully tested, but not marketed because of con-
general structure and also in its ability to spread tinuing production problems.

Hepatitis B low infection in early life, and liver cancer is a com-
mon sequela to persistent infection. In these parts of
Etiology the world, cancer of the liver is the most common of
The cause of hepatitis B is a very unusual virus. all cancers and a major cause of death in middle age.
Most important, it is unusually stable and can with- The situation is self-perpetuating, in that persons
stand boiling temperatures and drying without inac- infected in infancy are most likely to become carri-
tivation. Although the virus is of moderate size, 45 ers and, hence, most likely to transmit to the next
nm in diameter, it has the smallest DNA genome generation.
known. It accomplishes all its necessary functions
by using overlapping stretches of the same genetic Clinical Manifestations and Prevention
information to produce different proteins. The pro- Infection with hepatitis B can have a variety of out-
tein that is used for the external surface of the vi- comes. It may be inapparent, or it may cause a dis-
rus is produced in such great excess that the host ease indistinguishable from that caused by hepatitis
immune system cannot cope, and becomes para- A. It may also, however, cause chronic active hepati-
lyzed. To reproduce itself, the virus first makes a tis with or without cirrhosis. Any of these forms may
copy of its genome in RNA, then recopies that back lead to a chronic carrier state in which large quanti-
into DNA. The virus DNA can be integrated into ties of surface antigen, and sometimes infectious
the human genetic material, to provide a secure whole virus, circulate in the blood. This may damage
resting place for the virus and, perhaps, to interfere the kidneys or, as described above, lead to cancer.
with the host's growth control mechanism and Thus, although uncomplicated hepatitis B is not of-
cause cancer. ten fatal in the acute phase, the total mortality that
it causes can be great.
Geography and Epidemiology A good vaccine is available. It was proven effective
The stability of hepatitis B virus means that it can in an extraordinary trial, published by Wolf Szmu-
persist on any article that is contaminated with ness and others in 1980, which was carried out with
blood, most significantly, used needles and surgical the help of the New York male homosexual commu-
instruments. In developed countries it has usually nity. Thousands participated, either as vaccine re-
been transmitted in this way. Disposable needles, and cipients or as part of a placebo group. Because of the
tests to make certain that blood for transfusion is free high homosexual transmission rate, the incidence of
of the virus, have reduced the incidence of this dis- disease in the unvaccinated group was high enough
ease in most of the population, but it continues to be a to provide a good level of significance in the results.
serious problem among intravenous drug abusers. The first vaccine was produced by purifying hepati-
Hepatitis B can also be sexually transmitted. It is tis B antigen from the blood of carriers. This method
excreted in the semen and transmitted from male to was efficient, and never proved unsafe, but it left
female and from male to male in this way. Because open the possibility that some other disease might
the heterosexual transmission does not form a combe transmitted with the vaccine. Bacterial clones
plete cycle, this has been less of a problem among have now been developed that carry the gene for the
heterosexuals than in the male homosexual commu- virus antigen, and the product of these clones has
nities of Europe and North America. now replaced blood as a source of antigen in the
The ability of the virus to remain infectious when United States. This technology has been expensive,
dried means that it can persist on sharp stones and however, and blood-derived vaccine is still used else-
thorns along paths and, perhaps, also on the probos- where. The Chinese of Taiwan have used this type of
cises of mosquitos. This provides a particularly im- vaccine to immunize children of infected mothers,
portant mode of spread in primitive societies, where and, it is hoped, to break the cycle leading to liver
shoes are not worn and scant clothing is used. There, cancer.
hepatitis B attains very high prevalence levels It must be remembered that the vaccine only pre-
through gradual exposure over a lifetime. vents infection. There is as yet no way to cure the
The most serious pattern of hepatitis B infection is disease or abort the carrier state. A person who
seen in South Asia and sub-Saharan Africa, where becomes a carrier is likely to remain so for many
transmission from mother to child is common. Infec- years. This means that many people already infected
tion may occur during birth or via the mother's milk. are still doomed to liver cancer, and it emphasizes
The significance of this pattern of transmission is the need for vaccination of health workers who may
that persistent infection is particularly likely to fol- be exposed frequently.

VHI.70. Infectious Hepatitis 797
History in untransfused persons. Transmission by intrave-
Although it had been clear for many years that blood nous drug use is more frequent, and sexual transmis-
products could transmit hepatitis, the full import of sion seems also to occur.
this fact did not register on the medical profession.
Normal human serum continued to be used to pre- Clinical Manifestations
vent measles in children and to stabilize vaccines. In Hepatitis C is a serious disease in that a high propor-
1942, a new yellow fever vaccine, mixed with human tion of cases develop permanent liver damage. In
serum, was administered to U.S. troops headed over- spite of the paucity of our knowledge about this
seas: Of those vaccinated, 28,000 developed hepati- disease, it is almost unique among viral infections in
tis, and many died. being treatable. Alpha interferon results in dra-
The discovery of hepatitis B virus followed an un- matic improvement of hepatitis C liver disease. Un-
usual course. In the early 1960s, Baruch Blumberg fortunately, the disease often recurs when treatment
was studying blood groups in diverse populations stops, and the treatment is both expensive and ac-
and found a new antigen in the blood of Australian companied by unpleasant side effects.
aborigines. Later, he found that one of his staff, who
worked with the blood samples, had acquired the Hepatitis Associated with Delta Agent
"Australia antigen," and he recognized that it was
infectious. Ultimately, it turned out that this anti- Etiology
gen was the surface protein of the hepatitis B virus. A fourth hepatitis virus, the delta agent, is unable to
grow independently; it grows only in cells that are
Hepatitis C also infected with hepatitis B. Its defect is an inabil-
ity to make coat protein, and it must, therefore,
Etiology wrap itself in the surface protein of another virus to
The virus of hepatitis C has neither been seen nor become infectious. As has been noted, hepatitis B
cultured to the time of writing. However, in 1989, a produces large quantities of coat protein; in this way,
3,000-kiloDalton strand of RNA from the blood of an delta can attain very high titers in the blood. Envel-
experimentally infected chimpanzee was transcribed opment in the other's coat also gives delta the advan-
into DNA by Qui-Lim Choo and his associates. Propa- tage of hepatitis B virus's freedom from immune
gated into a bacterial clone, this DNA codes for an attack, and the fact that hepatitis B is commonly
antigen that crossreacts with the agent of an impor- persistent in infected persons gives delta a reason-
tant transfusion-transmitted hepatitis virus. The dis- ably large field in which to forage. Like hepatitis A,
coverers suggested that this "hepatitis C Virus" but not B, delta virus has an RNA genome. It does
might be structurally similar to the virus of yellow produce one distinctive protein that permits sero-
fever or equine encephalitis. This implies that the logic identification of the infection. Wrapped in the
virus genetic material was the original RNA strand, hepatitis B coat, it is intermediate in size between A
not DNA. Hepatitis C is inactivated by chloroform, and B, at 36 nanometers.
showing that, unlike the viruses of hepatitis A or B, it
has a lipid-containing envelope. The agent of some Geography and Epidemiology
other transfusion-transmitted non-A, non-B hepati- Delta virus has been found in most countries of Eu-
tis is resistant to chloroform, indicating the existence rope and North America as well as in much of the
of at least one more unidentified agent of this disease. rest of the world. Its distribution, however, seems to
be more spotty than that of the A or B virus. Al-
Geography and Epidemiology though there is no evidence that delta shares the
Wherever hepatitis A and B have been distin- unusual stability of hepatitis B virus, they are often
guished, a residuum of non-A, non-B cases have re- transmitted together by parenteral injection.
mained. Some of these cases are associated with
blood transfusions, whereas others, as described be- Clinical Manifestations
low, are not. Hepatitis C is the most common Infection with delta virus, which is always superim-
transfusion-transmitted non-A, non-B in the United posed on an underlying hepatitis B infection, has the
States, but its role in the rest of the world is un- highest acute fatality rate of all the hepatitides.
known. Although it is important as a cause of Outbreaks of unusually severe hepatitis have often
posttransfusion hepatitis, this is not its main mode proven to have been caused by it. Otherwise, the
of transmission, and it is encountered sporadically symptoms caused by delta are not distinctive.

History cause of the epidemic remained undetermined until
The antigen of delta virus was first recognized in recently, when Daniel Bradley and his associates
Italy in 1977. Since that time, there has been a developed a test based on reactions (observed in the
number of studies of its distribution and its molecu- electron microscope) of immune sera and virus from
lar characteristics. No vaccine is available as yet. feces of patients in a more recent Burmese epidemic.
Francis L. Black
Enterically Transmitted Non-A, Non-B
Hepatitis (ET-NANBH)
Etiology Bibliography
ET-NANBH is a virus structurally similar to but Alter, Marion J., and R. F. Sampliner. 1989. Hepatitis C:
immunologically distinct from hepatitis A. It has And miles to go before we sleep. New England Journal
recently been associated with a number of previ- of Medicine 321: 1538-9.
Beasley, R. Palmer, et al. 1981. Hepatocellular carcinoma
ously inexplicable hepatitis epidemics. As yet the
and hepatitis B virus, a prospective study of 27,707
virus has not been grown in culture, but it can be men in Taiwan. Lancet 2: 1129-33.
serially passed through monkeys and has been iden- Blumberg, Baruch S., et al. 1967. A serum antigen (Aus-
tified by electron microscopy. Biochemical character- tralia antigen) in Down's syndrome, leukemia and
ization remains to be done. hepatitis. Annals of Internal Medicine 66: 924—31.
Bonino, Ferrucio, et al. 1984. Delta hepatitis agent: Struc-
Geography and Epidemiology tural and antigenic properties of the delta-associated
Most epidemics attributed to ET-NANBH have oc- particle. Infection and Immunity 43: 1000-5.
curred in less developed countries at times when even Bradley, Daniel W., and James E. Maynard. 1986. Etiology
the normally limited sanitation procedures have bro- and natural history of post-transfusion and enter-
ken down. Most of these have been in South Asia, but ically transmitted non-A, non-B hepatitis. Seminars
in Liver Disease 6: 56—66.
there have also been epidemics in the southern Deinhardt, F. W., et al. 1972. Viral hepatitis in nonhuman
former Soviet Union, in refugee camps in Somaliland, primates. Canadian Medical Association Journal 106
and in Mexican villages, where water supplies be- (Supplement): 468-72.
came grossly contaminated. All ages are commonly Feinstone, S. M., A. Z. Kapikian, and R. A. Purcell. 1973.
affected, but there may actually be a preponderance Hepatitis A: Detection by immune electron micros-
of adult cases. These circumstances suggest that ET- copy of a viruslike antigen associated with acute ill-
NANBH virus is less infectious than hepatitis A and ness. Science 182: 1026-8.
that, even in conditions of generally poor sanitation, Hadler, S. C , and H. S. Margolis. 1989. Viral hepatitis. In
most people remain only minimally susceptible. Viral infections of humans, ed. Alfred S. Evans. New
York.
Hilleman, Maurice, R. 1984. Immunologic prevention of
human hepatitis. Perspectives in Biology and Medi-
ET-NANBH usually causes a hepatitis that is indis- cine 27: 54357.
tinguishable from that caused by hepatitis A or B. Krugman, Saul. 1967. Infectious hepatitis: Evidence for
However, infected pregnant women have an unusu- two distinctive clinical, epidemiological and immuno-
ally high mortality rate, which may reach 20 percent. logical types of infection. Journal of the American
Medical Association 200: 365-73.
History Krugman, Saul, and Joan P. Giles. 1970. Viral hepatitis.
A major epidemic of ET-NANBH occurred in New Journal of the American Medical Association 212:
Delhi in 1955. The New Delhi sewage emptied into 1019-29.
the Ganges River a little below the point of a water Lurman, A. 1885. Eine Icterusepidemie. Berliner klinische
supply intake. In that year there was a drought, the Wochenschrift 22: 20-3.
Murray, K. 1987. A molecular biologist's view of viral
river became low, and the sewage began to flow
hepatitis. Proceedings of the Royal Society of Medi-
upstream. Alert water technicians recognized the cine, Biology 230: 107-46.
problem and raised chlorination levels, so that there Provost, P. J., and M. R. Hilleman. 1979. Propagation of
was no unusual outbreak of bacterial disease. How- human hepatitis A virus in cell culture in vitro. Pro-
ever, a month or so later, 68 percent of the exposed ceedings of the Society for Experimental Biology and
population developed jaundice, and more than 10 Medicine. 160: 213-21.
percent of the affected pregnant women died. Care- Szmuness, Wolf, et al. 1980. Hepatitis B vaccine demon-
ful investigations were made at the time, but the stration of efficacy in a controlled clinical trial in a

VIII.71. Infectious Mononucleosis 799
high risk population. New England Journal of Medi- Pathology and Clinical Manifestations
cine 303: 833-41. Although the pathological findings may be multivis-
Vyas, Girish H., and Jay H. Hoofhagle, eds. 1984. Viral ceral, the predominant finding is follicular hyper-
hepatitis and liver disease. Orlando. plasia of the lymph nodes. The lymphoid tissues show
Zuckerman, Arie J. 1975. Human viral hepatitis. Amster- diffuse proliferation of the atypical lymphocyte that
dam.
is present in the spleen and the walls of blood vessels,
is periportal in the liver, and appears in the periph-
eral bloodstream. These monocytoid lymphocytes
(Downey cells) may make up 10 percent or more of the
VHI.71 white cells and are of diagnostic significance.
In childhood the disease is subclinical or masquer-
Infectious Mononucleosis ades as one of many episodes of upper respiratory
infection. In the typical youthful adult, after an incu-
bation period of about 5 or 6 weeks, clinical disease
Infectious mononucleosis is an acute infectious dis- shows itself with prodromes of malaise, fatigue,
ease of children, adolescents, and young adults. It is headache, and chilliness followed by high fever, sore
caused by the Epstein—Barr virus (EB virus) and is throat, and tender swollen cervical lymph nodes.
followed by lifelong immunity. Examination shows, in addition to the lymphadenop-
Distribution and Incidence athy, paryngitis often with scattered petechiae and
On the basis of the populations investigated, it swelling of the pharyngeal lymphoid structures,
would seem that infectious mononucleosis occurs hepatosplenomegaly, and, not infrequently, a tran-
worldwide but attacks only those persons who have sient maculopapular rash. Palpebral and periorbital
had no EBV antibodies. The virus replicates in the edema may develop. Mild jaundice appears in some
salivary glands, is present in the oropharyngeal se- 10 percent of patients. Rarely are symptoms related
cretions of patients ill with the disease, and contin- to the central nervous system. Following an initial
ues to be shed for months following convalescence. leukopenia, a leucocytosis of 15,000 to 20,000 or
As a lifelong inhabitant of the lymphoid tissues, it is higher appears with an absolute lymphocytosis and
excreted intermittently into the oropharynx. with atypical lymphocytes prominent as noted
In the underdeveloped countries it is a disease of above.
childhood, and, since it spreads by contact with oral In most patients the disease is mild, and recovery
secretions, crowding and unhygienic surroundings fa- occurs within several weeks. College students are
vor its ready transmission. In more developed coun- generally up and about within a week or so. Compli-
tries, it strikes especially those of the 15- to 25-year cations in the nervous system may occasionally oc-
age group and is recognized clinically as infectious cur in adults, but death from the disease is ex-
mononucleosis. In the United States, on college cam- tremely rare, splenic rupture being the most serious
puses, the disease is commonly known as the "kissing complication.
disease."
Children of low socioeconomic state almost univer-
sally show antibodies to the virus. (In Ghana, 84 History and Geography
percent of infants have acquired antibodies by age This disease was described first by a Russian pedia-
21 months.) In a worldwide prospective study of trician, Nil F. Filatov, in 1885, as idiopathic adenitis.
5,000 children and young adults without EB virus Four years later, a German physician, Emil Pfeiffer,
antibodies, 29 percent developed antibodies within a also described a disease that was epidemic in chil-
period of 4 to 8 years. Among susceptible college dren and characterized by glandular enlargement.
students the annual incidence of the disease is about He gave it the name Drusenfieber (glandular fever).
15 percent. In 1896, J. P. West wrote of a similar epidemic in the
United States, but it was only in 1920 that Thomas
Immunology Sprunt, of Baltimore, gave it the name infectious
Specific antibodies to EB virus are demonstrable mononucleosis. H. Downey and C. A. McKinly de-
early after the onset of the disease. Although the scribed the characteristic mononuclear leucocytes in
higher titers may decrease in subsequent months, 1923. The Epstein - Barr virus was identified by W.
they remain at detectable levels throughout life, Henle and associates in 1968.
along with immunity to the disease. R. H. Kampmeier

Bibliography
Epstein, M.A., and B. G. Achong. 1977. Pathogenesis of VIII.72
infectious mononucleosis. Lancet 2: 1270—2.
Davidsohn, I., and P. H. Walker. 1935. Nature of hetero-
Inflammatory Bowel Disease
phile antibodies in infectious mononucleosis. Ameri-
can Journal of Clinical Pathology 5: 455—65.
Downey, H., and C. A. McKinly. 1923. Acute lymphade- The inflammatory bowel diseases (IBD) - ulcerative
nosis compared with acute lymphatic leukemia. Ar- colitis and Crohn's disease - constitute a group of
chives of Internal Medicine 2: 82—112. disorders of the small and large intestine whose
Henle, W., and G. Henle. 1979. The virus as the etiologic causes and interrelationships remain obscure (Kirs-
agent of infectious mononucleosis. In Epstein—Barr ner and Shorter 1988). Their course is acute and
virus, ed. B. G. Epstein and B. G. Achong, New York. chronic, with unpredictable remissions and exacerba-
1981. Clinical spectrum of Epstein-Barr virus infections, and numerous local and systemic complica-
tion. In The human herpesviruses: An interdisciplin- tions. Treatment is symptomatic and supportive.
ary perspective, ed. Andre J. Nahmias, Walter R. The economic drain imposed by these diseases in
Dowdle, and Raymond F. Schinazi. New York. terms of direct medical, surgical, and hospitalization
Niederman, James C. 1982. Infectious mononucleosis. In expenses, loss of work, and interrupted career devel-
Cecil's textbook of medicine, ed. James B. Wyngaarden opment is enormous. The emotional impact upon the
and Lloys H. Smith, Jr. Philadelphia.
Paul, John R., and Walls W. Bunnell. 1932. Presence of
patient and upon the family is equally substantial.
heterophile antibodies in infectious mononucleosis. In these contexts, the inflammatory bowel diseases
American Journal of Medical Science 183: 90—104. today are one of the major worldwide challenges in
Pfeifer, Emil. 1889. Driisenfieber. Jahrbuch Kinderheil- medicine.
kunde 29:257-64.
Sprunt, Thomas, and Frank A. Evans. 1920. Mononucleo- Ulcerative Colitis
sis leucocytosis in reaction to acute infections ("infec-
tious mononucleosis"). Bulletin ofJohns Hopkins Hos- Clinical Manifestations, Pathology, and
pital 31: 410-17. Diagnosis
Strauss, Stephen E. 1987. Editorial - EB or not EB - that The principal symptoms of ulcerative colitis are
is the question. Journal of American Medical Associa- rectal bleeding, constipation early (in ulcerative
tion 257: 2335-6. proctitis), diarrhea usually, abdominal cramping
pain, rectal urgency, fever, anorexia, fatigue, and
weight loss. The physical findings depend upon the
severity of the colitis, ranging from normal in mild
disease, to fever, pallor from loss of blood, dehydra-
tion and malnutrition, and the signs of associated
complications. X-ray and endoscopic examinations
demonstrate diffuse inflammation and ulceration of
the rectum and colon in 50 percent of patients, and
the adjoining terminal ileum. Ulcerative colitis be-
gins in the mucosa and submucosa of the colon (the
inner bowel surface); in severe colitis the entire
bowel wall may be involved. The principal histo-
logical features are the following: vascular conges-
tion, diffuse cellular infiltration with polymorpho-
nuclear cells, lymphocytes, plasma cells, mast cells,
eosinophils, and macrophages; multiple crypt ab-
scesses; and shallow ulcerations. Chronic ulcerative
proctitis is the same disease as ulcerative colitis,
except for its restriction to the rectum and its milder
course.
The laboratory findings reflect the severity of the
colitis. The white blood cell count usually is normal
except in the presence of complications. The hemoglo-
bin, red cell, and hematocrit are decreased in propor-

VIII.72. Inflammatory Bowel Disease 801
tion to the loss of blood. The sedimentation rate may Salmonella paratyphi, Proteus organisms, viruses
be elevated but frequently is normal. Blood proteins (e.g., lymphopathia venereum), parasites, and fungi
including serum albumin often are diminished. The {Histoplasma, Monilia). Immunologic mechanisms
stools contain blood. Cultures are negative for have been implicated on the basis of clinical, morpho-
known pathogenic bacteria. logical, and experimental observations. The immuno-
Complications are numerous. In the colon, they logic disorder may be one of defective immunoregula-
include pericolitis, toxic dilatation, perforation, peri- tion, as in an altered response to a microbial infection
tonitis, hemorrhage, obstruction, polyps, carcinoma, or to usual bowel organisms. Nutritional deficiencies
and lymphoma. The many systemic complications are common but are secondary developments.
include iron-deficiency anemia, hemolytic anemia, Various circumstances such as acute respiratory
protein loss, malnutrition, retardation of growth in illness, enteric infections, and antibiotics may act as
children, arthritis, iritis, sacroileitis, metabolic bone a "trigger mechanism," precipitating the disease in
disease, skin problems (erythema nodosum, pyo- genetically "vulnerable" persons. Genetic influences
derma gangrenosum), pyelonephritis, nephrolith- may be expressed through the immune response
iasis, liver disease (fat infiltration, hepatitis, peri- genes and the mucosal immune system of the bowel.
cholangitis, sclerosing cholangitis), and vascular Emotional disturbances are common in patients
thromboses. with ulcerative colitis, but they probably do not ini-
The differential diagnosis includes specific bacte- tiate the disease. The important interactions among
rial infections, ischemic colitis, diverticulitis, and the central nervous system, the gut, and the endo-
Crohn's disease of the colon. crine and immune systems now under investigation
may clarify these issues.
Treatment
The therapeutic emphasis in ulcerative colitis in- Crohn's Disease
volves a general program of nutritional restoration, Crohn's disease, also called regional enteritis, jeju-
emotional support, sulfasalazine, 5-aminosalicylic noileitis, ileocolitis, and Crohn's colitis, is an acute
acid, antispasmodics, antibacterial drugs, adrenocor- and chronic inflammatory disease of the small intes-
ticotropin (ACTH), and adrenal corticosteroids. Proc- tine, especially the terminal ileum, but actually in-
tocolectomy and ileostomy is a highly successful op- volving the entire gastrointestinal tract, from the
eration for ulcerative colitis. The Kock continent mouth to the anus. The disease occurs frequently
pouch, and total colectomy together with ileoanal among children, adolescents, and young adults, but
anastomoses, with and without ileal pouch, offer use- is increasing in people over the age of 60. There is a
ful surgical alternatives in selected patients. The slight female:male predominance.
prognosis of ulcerative colitis has improved consider-
ably, and the mortality has diminished to less than 1 Clinical Manifestations
percent as a result of the many medical and surgical The clinical manifestations include fever, diarrhea,
therapeutic advances. cramping abdominal pain, anemia, and weight loss.
Initial symptoms may include arthralgias suggest-
Etiology ing an arthritis, gynecological difficulties, urinary
Ulcerative colitis is common among young people, es- symptoms (frequency, dysuria), or a combination of
pecially below the age of 40 years, but no age range severe loss of appetite, weight loss, and depression,
is exempt and the number of older patients is in- suggesting anorexia nervosa. Slowing or retardation
creasing. There is no sex predominance. The circum- of growth may be the first clinical indication of ill-
stances of onset of ulcerative colitis in most instances ness in children. Occasionally, the initial presenta-
are not known. Patients usually appear to be in good tion is indistinguishable from an acute appendicitis.
health; occasionally, symptoms appear after visits to The physicalfindingsinclude fever, "toxemia," ten-
countries such as Mexico and Saudi Arabia, implicat- derness in the mid abdomen and right lower abdomi-
ing an enteric infection. Initial thoughts as to etiol- nal quadrant, and often a tender loop of bowel or an
ogy emphasized a microbial infection, and this possi- inflammatory mass composed of adherent inflamed
bility continues today. Many organisms have been bowel, thickened mesentery, and enlarged abdomi-
implicated and discarded, including diplostreptococ- nal lymph nodes, palpated in the right lower abdomi-
cus, Streptococcus, Escherichia coli, Pseudomonas nal quadrant. The laboratory findings include a nor-
aeruginosa, Clostridium difficile, Sphaerophorus nec- mal or elevated white blood cell count, increased
rophorus, Morgan's bacillus, Shigella organisms, sedimentation rate, anemia, decreased total proteins

and serum albumin, and evidence of undernutrition. of foreign material (e.g., talc), producing an obstruc-
By X-ray, the intestinal lumen is found to be ulcer- tive lymphangitis; sarcoidosis; altered intestinal neu-
ated and narrowed. Fistulas to adjacent structures rohumoral mechanisms; and nutritional deficiencies.
are not uncommon. The histological features include
transmural disease, knifelike ulcerations overlying Ulcerative Colitis and Crohn's Disease:
the epithelium of lymphoid aggregates in Peyer's General Aspects
patches, profuse cellular accumulations, lymphatic
dilatation, prominent lymphoid follicles, and granu- Epidemiology, Distribution, and Incidence
loma formation. Ulcerative colitis and Crohn's disease share similar
The complications of regional enteritis include epidemiological and demographic features. The inci-
most of the problems enumerated for ulcerative coli- dence of ulcerative colitis, still considerable, appar-
tis and, in addition, perianal abscess, perineal fistu-ently has stabilized or possibly diminished in many
las, abdominal abscess and fistual formation, intesti- areas of the world, with several exceptions (Norway,
nal narrowing and obstruction, carcinoma of the Japan, Faroe Islands, northeast Scotland). Ulcera-
small and large intestine, and obstructive hydrone- tive colitis appears to be more prevalent in the
phrosis. In patients with multiple bowel resections United Kingdom, New Zealand, Australia, the
and significant loss of intestinal digestive capacity, United States, and northern Europe. It is less fre-
the complications include altered bile salt metabo- quent in central and southern Europe, infrequent in
lism, steatorrhea, increased absorption of dietary the Middle East, uncommon in South America and
oxalate and hyperoxaluria, increased frequency of Africa, but increasing in Japan.
kidney stones, zinc and magnesium deficiencies, Similarly Crohn's disease is most common in the
other nutritional deficits including vitamins B12 and United Kingdom, the United States, and Scandina-
D, bone demineralization, and osteopenia. via, on the rise in Japan, but less frequent in central
and northern Europe and uncommon in Africa and
Treatment South America. The incidence of Crohn's disease has
As in ulcerative colitis, medical treatment is symp- been increasing throughout much of the world (Great
tomatic, supportive, and individualized, with em- Britain, the United States, Norway, Finland, Switzer-
phasis upon restoration of nutrition, antispasmodic land, Israel, and South Africa) but appears to have
medication, and antibacterial and antiinflamma- stabilized in such diverse cities as Aberdeen (Scot-
tory medication. Corticotropin and adrenal steroids land), Baltimore (United States), Cardiff (Wales), and
reduce the inflammatory reaction, but do not neces- Stockholm (Sweden). B. M. Mendeloff and A. I.
sarily cure the disease. Immunosuppressive drugs Calkins (1988) estimate that in the United States the
(6-mercaptopurine, azathioprine) may be helpful annual incidence "for the sum of both disorders" is 5
adjuncts but require continuing administration. to 15 new cases per 100,000 population. The world-
Surgical treatment is necessary for complications, wide prevalence of Crohn's disease, especially in in-
especially abscess and fistula formation, unrelent- dustrialized areas, and the worldwide similarity of its
ing intestinal obstruction, and uncontrollable hem- clinical, radiological, and pathological features, re-
orrhage. The recurrence rate is high. gardless of geographic, ethnic, dietary, and sociocul-
tural differences, are noteworthy.
Etiology The inflammatory bowel diseases are more fre-
As in ulcerative colitis, etiologic hypotheses vary quent among white than black populations; but
widely, from the excessive eating of cornflakes, re- Crohn's disease in particular is increasing among
fined sugars, or margarine, to bottle-feeding rather the black populations of the United States and Great
than breastfeeding, environmental pollutants, the in- Britain. Ulcerative colitis and especially Crohn's dis-
discriminate administration of antibiotics, and the ease are much more common among the Jewish popu-
use of oral contraceptives among young women. A lation of the United States, the United Kingdom,
wide variety of bacteria and viruses have been impli- and Sweden than among other members of the popu-
cated, and although none has achieved etiologic sta- lation. In Israel, Crohn's disease is more common
tus, the "new" microbial pathogens now being identi- among Ashkenazi than among Sephardic Jews. Over-
fied have renewed interest in microbial possibilities all, ulcerative colitis and Crohn's disease occur
including mycobacteria. Other suggested but un- among all ethnic groups, including the Maoris of
proven etiologies have included blunt trauma to the New Zealand, Arabs (e.g., Kuwait, Saudi Arabia),
abdominal wall (e.g., seat belt injury); the ingestion and probably the Chinese, albeit infrequently. An

VIII.72. Inflammatory Bowel Disease 803
intriguing and unexplained epidemiological observa- families with multiple instances of IBD show an inter-
tion has to do with the scarcity of cigarette smokers mingling of ulcerative colitis and Crohn's disease.
in patients with ulcerative colitis and the appar- Both diseases share the same epidemiological and
ently increased vulnerability of former smokers to demographic features. They also share many symp-
ulcerative colitis, whereas by contrast there is an toms (abdominal pain, diarrhea, weight loss, rectal
excess of smokers in Crohn's disease populations. It bleeding), local complications (hemorrhage, perfora-
should be noted that the "smoking connection" does tion, toxic dilatation of the colon), and systemic com-
not obtain among children with IBD. plications (erythema nodosum, pyoderma gangre-
nosum, arthritis, liver disease, kidney stones).
Genetic (Familial) Aspects
Ulcerative colitis and Crohn's disease are not The Differences. Ulcerative colitis is a continuous
"classic" genetic disorders. There are no inheritable mucosal disease, at least initially, with diffuse in-
protein or metabolic abnormalities, no antecedent volvement of the colon. Crohn's disease is a trans-
chromosomal defects, no genetic markers, no con- mural process, focal in distribution, penetrating
sanguinity, and no Mendelian ratios. However, through the bowel wall, and producing microab-
genetic influences are important in the develop- scesses and fistulas. Histologically, granulomas and
ment of ulcerative colitis and even more so in prominent lymphoid aggregates are much more com-
Crohn's disease, as reflected in their familial clus- mon in Crohn's disease than in ulcerative colitis.
tering (20 percent for ulcerative colitis and up to 40 Ulcerative colitis is limited to the colon and occa-
percent for Crohn's disease). In addition to the sionally a short segment of terminal ileum; Crohn's
initial patient, one more member of the family is disease focally may involve any segment of the ali-
usually affected, but up to 8 patients in a single mentary tract, mouth to anus. Ulcerative colitis is a
family have been observed. IBD occurs with a high continuous inflammatory reaction; Crohn's disease,
degree of concordance among monozygotic twins. wherever located, is a discontinuous, focal process.
The nature of the genetic influence in IBD is not Perianal suppuration and fistula formation (entero-
known. Thus far, no universally distinctive histo- cutaneous, enteroenteric, enterocolonic, enteroves-
compatibility haplotype linkage has been demon- ical, enterouterine) characterize Crohn's disease,
strated. The occasional occurrence of Crohn's dis- but not ulcerative colitis. Immune-modulating drugs
ease or ulcerative colitis in adopted children or are more helpful in Crohn's disease than in ulcera-
later in the initially healthy mate of a patient with tive colitis. Proctocolectomy and ileostomy are cura-
IBD supports an environmental (possibly viral) tive in ulcerative colitis, but the same operation in
rather than a genetic mechanism. Current etiologic Crohn's disease carries a recurrence rate of approxi-
studies focus upon a genetically mediated abnormal- mately 15 to 20 percent.
ity in the immune response genes (defective immu-
noregulation in the bowel's mucosal immune sys- The answer to the question whether the two ailments
tem), possible linkage with a known genetic locus, are related would seem to be that ulcerative colitis
or with specific T-cell antigen receptor genes. and Crohn's disease are probably separate disorders,
with limited morphological and clinical expressions
Comparisons and Contrasts accounting for overlapping manifestations.
Is there a pathogenetic relationship between ulcera-
tive colitis and regional ileitis/colitis? In the absence History of IBD
of differentiating biological markers, a definitive
answer to this important question is not possible at Ulcerative Colitis
present. The simultaneous presence or sequential Early Literature to 1920
evolution of both active ulcerative colitis and active
regional ileitis/colitis, and the sequential develop- In all probability, we shall never know for certain who
ment of ulcerative colitis followed by Crohn's dis- first described ulcerative colitis (UC)... for although the
ease in a single patient, though they may occur, disease was initially referred [to] by name in the latter
probably have never been documented to everyone's half of the century, it seems likely that its existence was
recognized for over two millennia before that time.
satisfaction. (Goligher et al. 1968)
The Similarities. Both disorders have significant Hippocrates was aware that diarrhea was not a
familial associations. Approximately 25 percent of single disease entity, whereas Aretaeus of Cappado-

cia in the second century described many types of In 1895 Hale-White reported the association of
diarrhea, including one characterized by "foul evacua- liver disease and ulcerative colitis, and in 1920 R. F.
tions," occurring chiefly in older children and adults. Weir performed the operation of appendicostomy to
Instances of an "ulcerative colitis" apparently were facilitate "colonic drainage" in ulcerative colitis. J.
described by Roman physicians, including Ephesus P. Lockhart-Mummery (1907) described seven in-
in the eleventh century. "Noncontagious diarrhea" stances of colon carcinoma among 36 patients with
flourished for centuries under a variety of labels, ulcerative colitis, and emphasized the diagnostic
such as the "bloody flux" of Thomas Sydenham in value of sigmoidoscopy at the Royal Society of Medi-
1666. In 1865, medical officers of the Union Army cine. By 1909, approximately 317 cases of patients
during the American Civil War described the clinical with "ulcerative colitis" had been collected (between
and pathological features of an "ulcerative colitis- 1888 and 1907) from London hospitals, and in 1909
like" process in patients with chronic diarrhea. Sev- Allchin recorded perhaps the first instance of "famil-
eral of these cases actually suggested Crohn's disease ial" ulcerative colitis. Additional instances of ulcera-
more than ulcerative colitis but in the absence of tive colitis were noted at the Paris Congress of Medi-
modern microbiological studies, the question is moot cine in 1913. J. Y. Brown (1913) of the United States
(Kirsner and Shorter 1988). may have been the first to suggest the procedure of
S. Wilks and W. Moxon (1875) wrote: "We have ileostomy in the surgical management of ulcerative
seen a case affected by discharge of mucus and blood, colitis.
where, after death, the whole internal surface of the
colon presented a highly vascular soft, red surface American and European Literature, 1920—45. Dur-
covered with a tenacious mucus and adherent ing the 1920s, the number of reports increased
lymph. . . . In other examples there has been exten- steadily and included those by H. Rolleston, C. E.
sive ulceration." Because the concept of microbial Smith, J. M. Lynch and J. Felsen of New York, A. F
illnesses had not yet emerged, the possibility of a Hurst, and E. Spriggs. During the same decade, Her-
specific infection, in at least some instances, cannot mann Strauss of Berlin may have been the first to
be excluded. W H. Allchin (1885), W. Hale-White recommend blood transfusions in the treatment of
(1888), and H. Folet, writing in 1885, are among ulcerative colitis. In 1924 J. A. Bargen of the Mayo
those cited by G. Placitelli and colleagues (1958), Clinic published his experimental studies implicat-
who provided accurate clinical accounts. G. N. Pitt ing the diplostreptococcus in the etiology of ulcera-
and A. E. Durham in 1885 described a woman of 29 tive colitis - a notion later discarded. More impor-
years with a 5-year history of diarrhea: tant was his (1946) comprehensive clinical study of
the course, complications, and management of
[M]ore than half of the area of the whole colon was covered "thrombo-ulcerative colitis." C. D. Murray first drew
with small friable villous polypi. . . the intervening de- public attention to the psychogenic aspects of ulcera-
pressed white areas in the muscular coat, the mucous coat tive colitis in 1930, which were confirmed by A. J.
having entirely ulcerated away. . . . the circumference of
the bowel is only 1V3 — 2 inches, being narrower than the
Sullivan and C. A. Chandler (1932). This initiated
small intestine. (Kirsner 1988) the period (1930-60s) of intense psychiatric interest
in ulcerative colitis.
During the 1880s and 1890s, instances of an ul- Worldwide attention was directed to "oolites ul-
cerative colitis were reported by numerous physi- cereuses graves non-ambienne" at the 1935 Interna-
cians from England, France, Germany, Italy, and tional Congress of Gastroenterology in Brussels; the
other European countries (Kirsner 1988). In 1888 amount of literature on the disease increased rap-
Hale-White, a contemporary of Wilks at Guy's Hospi- idly after this, with clinical contributions initiated
tal, described 29 cases of ulcerative colitis and re- by many physicians from many countries.
marked that "[t]he origin of this ulceration is ex- By the 1940s, ulcerative colitis, if not increasing in
tremely obscure . . . it is not dysentery." He cited prevalence, at least was recognized more often than
similar observations by W. Leube (Ziemssen's Cyclo- regional ileitis and was the dominant IBD disease.
pedia), K. Rokitansky ("Pathological Anatomy"), H. However, by the end of World War II, Crohn's disease
Nothnagel (Beitrage zur Physiologie und Pathologie (regional enteritis, Crohn's colitis) had become more
des Darmes, 1884), and A. Bertrand and V. Fontana frequent. Concurrently with an apparent stabiliza-
("De l'enterocolite chronique endemique des Pays tion of the frequency of ulcerative colitis in the
Chauds"), but again complete confirmation is not United States, Crohn's disease has been the more
possible. prominent of the two prototypes of nonspecific IBD.

VTII.72. Inflammatory Bowel Disease 805
Crohn's Disease ported a "chronic infectious granuloma" involving

the ileocecal region in a 44-year-old male presenting
Literature before 1900. The initial description of with rectal bleeding.
Crohn's disease may date back to Giovanni Battista Soon after Crohn's (1932) paper, A. D. Bissell
Morgagni who, in 1761, described ileal ulceration (1934) of the University of Chicago reported on two
and enlarged mesenteric lymph nodes in a young patients. The first patient was a 39-year-old male
man who died of an ileal perforation; or, perhaps with symptoms of 4 years' duration, including ab-
even earlier, to the "iliac passion" - claims that can dominal cramps, diarrhea, and weight loss who re-
never be substantiated. More suggestive early in- quired resection of an ileocecal mass. The second
stances of Crohn's disease include an 1806 report by patient, a 28-year-old male, also required resection
H. Saunders and that by C. Combe and Saunders of the terminal ileum and cecum. These early case
(1813). Nineteenth-century descriptions of ileocecal reports depicted Crohn's disease ("regional ileitis")
disease consistent with today's concept of Crohn's as a mass-producing, bowel-narrowing process, virtu-
disease, regional ileitis, or ileocolitis were authored ally always requiring surgical intervention.
by J. deGroote, J. Abercrombie, J. S. Bristowe, N.
The principal clinical differentiation in the early
Moore, and Wilks. Wilks's (1859) description of the
part of the twentieth century included intestinal
postmortem examination on the celebrated Isabella
tuberculosis and granuloma formation simulating
Bankes is of interest:
tumor in the bowel. E. Moschowitz and A. D.
The intestines lay in a coil adherent by a thin layer of Wilensky (1923), from New York's Mount Sinai Hos-
lymph indicative of recent inflammation; the ileum was pital, reflecting that center's interest in granulo-
inflamed for three feet from the ileo-caecal valve though matous inflammations of the bowel, described four
otherwise the small intestine looked normal. The large patients with nonspecific granulomatous disease of
intestine was ulcerated from end to end with ulcers of the intestine. Ginzburg and Oppenheimer, in the
various sizes mostly isolated [t]hough some had run to- Pathology Department of the same hospital, identi-
gether. . .. Inflammation was most marked at the proxi-
fied a dozen instances of a localized hypertrophic,
mal colon and the caecum appeared to be sloughing caus-
ing the peritonitis.
ulcerative stenosis of the distal 2 or 3 feet of the
terminal ileum. Specific causes such as amebiasis,
Thirty years later, Samuel Fenwick (1889) de- actinomycosis, intestinal tuberculosis, and syphilis
scribed the necropsy findings suggestive of Crohn's were ruled out. In 1930, Crohn had two patients
disease, in a 27-year-old female: with a similar process. Crohn's first case was a 16-
year-old boy with diarrhea, fever, a mass in the right
Many of the coils of intestine were adherent and a commu-
nication existed between the caecum and a portion of the
lower abdominal quadrant, and pain, requiring ileo-
small intestine adherent to it, whilst the sigmoid flexure cecal resection. Interestingly, the patient's sister
was adherent to the rectum, and a communication also also required an operation for regional ileitis several
existed between them. The lower end of the ileum was years later - the first recorded instance of "familial
much dilated and hypertrophied, and the ileocecal valve regional ileitis." Bargen, anticipating the more ex-
was contracted to the size of a swan's quill. tensive involvement of the small intestine, sug-
gested the term regional enteritis instead of "termi-
Literature after 1900. Early in this century, T. Ken- nal ileitis."
nedy Dalziel (1913) of Glasgow described a group of In 1925 T. H. Coffen of Portland, Oregon, referring
13 patients dating back to 1901 withfindingsclosely to earlier reports of intestinal granulomas, described
resembling those recorded by B. B. Crohn, L. Ginz- a 20-year-old man with abdominal symptoms since
burg, and G. D. Oppenheimer (1932): "The affected 1915, diagnosed as phlegmonous enteritis. In 1916,8
bowel gives the consistence and smoothness of an eel inches of thickened bowel were removed because of
in a state of rigor mortis, and the glands, though obstruction. A second obstruction 5 months later
enlarged, are evidently not caseous." Many reports necessitated the removal of 24 inches of ileum. Eight
of single instances of a chronic stenosing inflamma- months later a third resection was performed for the
tion of the last portion of the small bowel ("terminal same condition. The pathological description of the
ileitis") appeared subsequently. In addition, F. J. resected bowel today would be consistent with a diag-
Nuboer (1932) of Holland described two patients nosis of Crohn's disease.
with "chronic phlegmonous ileitis," manifesting the In other notable articles, H. Mock in 1931 and R.
same gross and histological findings that Crohn and Colp in 1933 chronicled involvement of the colon. C.
associates described. Similarly, M. Golob (1932) re- Gotlieb and S. Alpert (1937) described regional

jejunitis, and J. R. Ross (1949) identified "regional nal tract. It is to the credit of Crohn, Ginzburg, and
gastritis." W. A. Jackman and J. L. Kantor in 1934 Oppenheimer that their clinical description stimu-
and R. Marshak in 1951 described the roentgeno- lated worldwide interest in this disease. Certainly
graphic appearance of Crohn's disease of the small much credit belongs to Crohn for his long clinical
bowel and the colon, and in 1936 Harold Edwards interest in the illness, his many publications and
described a resected terminal ileum, with "the consis- lectures on the subject, and his encouragement of
tency of a hosepipe" from a 23-year-old woman with others in the further investigation of the problem.
a history of persistent diarrhea, abdominal pain, and On the matter of eponyms, the comment of
weight loss. R. Shapiro (1939) comprehensively re- Thomas Lewis (1944) seems appropriate: "Diagnosis
viewed the literature through the 1930s and identi- is a system of more or less accurate guessing, in
fied numerous case reports mainly in the earlier which the end point achieved is a name. These
German surgical literature of "inflammatory tu- names applied to disease come to assume the impor-
mors" of the gastrointestinal tract, especially the tance of specific entities . . . whereas they are, for
colon; some of these probably were instances of the most part, no more than insecure and therefore
Crohn's disease. temporary conceptions."
Authoritative descriptions of the pathological fea- Joseph B. Kirsner
tures of Crohn's disease have been provided by S.
Warren and S. C. Sommers (1948), G. Hadfield
(1939), and H. Rappaport and colleagues (1951). In Bibliography
1952, Charles Wells of Liverpool distinguished be- Allchin, W. H. 1885. A case of extensive ulceration of the
tween ulcerative colitis and what he termed "seg- colon. Transactions of the Pathological Society of Lon-
mental colitis," and suggested that this latter form don 36: 199.
Bargen, J. A. 1946. Chronic ulcerative colitis. In The cyclo-
of colonic lesion was a variant of Crohn's disease. In
pedia of medicine, surgery, and specialties, ed. G. M.
1955 Bryan Brooke and W. Trevor Cooke of England Piersol, Vol. 4: 382, 398. Philadelphia.
were among the first to recognize "right-sided coli- Bissell, A. D. 1934. Localized chronic ulcerative ileitis.
tis" as Crohn's disease of the colon rather than as Annals of Surgery 99: 957-66.
ulcerative colitis, but it was not until reports in 1959 Brown, J. Y. 1913. The value of complete physiological rest
and 1960 by Lockhart-Mummery and B. C. Morson of the large bowel in the treatment of certain ulcera-
(1960) that Crohn's disease of the colon was gener- tive and obstructive lesions of this organ. Surgery,
ally accepted as a valid entity. Gynecology and Obstetrics 16: 610.
Combe, C , and H. Saunders. 1813. A singular case of
Eponym of Crohn's Disease. New instances of stricture and thickening of ileum. Medical Transac-
granulomatous inflammation of the small bowel tions of the Royal College of Physicians, London 4: 16.
were reported in Great Britain, occasionally desig- Crohn B. B., L. Ginzburg, and G. D. Oppenheimer. 1932.
Regional ileitis — a pathological and clinical entity.
nated as Crohn's disease, in 1936. In America the
Journal of the American Medical Association 99:
term "Crohn's disease" was first employed as a syn- 1323-9.
onym by F. Harris and colleagues (1933) and later Dalziel, T. K. 1913. Chronic intestinal enteritis. British
by Hurst of Great Britain. But others have also Medical Journal 2: 1068-70.
claimed priority. In Poland this entity was called Fenwick, S. 1889. Clinical lectures on some obscure dis-
"Lesniowski—Crohn's disease," whereas in Scotland eases of the abdomen. London.
the eponym of "Dalziel's disease" was recorded. H. Goligher, J. C , et al. 1968. Ulcerative colitis. Baltimore.
I. Goldstein designated the condition "Saunders- Golob, M. 1932. Infectious granuloma of the intestines.
Abercrombie—Crohn's ileitis." Medical Journal and Record 135: 390-3.
To some American observers, this entity might Gotlieb, C , and S. Alpert. 1937. Regional jejunitis. Ameri-
well have been called "CGO disease," to include the can Journal of Roentgenology and Radium Therapy
important contributions of not only Crohn, but also 38: 861-83.
Hadfield, G. 1939. The primary histological lesions of re-
Ginzburg and Oppenheimer, who provided 12 of the
gional ileitis. Lancet 2: 773-5.
14 cases constituting the (1932) JAMA paper. What- Hale-White, W. 1888. On simple ulcerative colitis and
ever the "labeling" circumstances, the entity today other rare intestinal ulcers. Guy's Hospital Reports
carries the eponym "Crohn's disease" as the most 45:131.
convenient designation, which is now sanctioned by Harris, R, G. Bell, and H. Brunn. 1933. Chronic cicatriz-
worldwide usage to designate a unique inflamma- ing enteritis: Regional ileitis (Crohn). Surgery, Gyne-
tory process involving any part of the gastrointesti- cology, and Obstetrics 57: 637-45.

VIII.73. Influenza 807
Hawkins, C. 1983. Historical review. In Inflammatory

bowel disease, ed. R. N. Allan et al., Vol. 1: 1-7. vni.73
London.
Kirsner, J. B. 1988. Historical aspects of inflammatory
Influenza
bowel disease. Journal of Clinical Gastroenterology
10: 286-97.
Kirsner, J. B., and R. G. Shorter. 1988. Inflammatory Influenza, also known as flu, grip, and grippe, is a
bowel disease. Philadelphia. disease of humans, pigs, horses, and several other
Lewis, T. 1944. Reflections upon reform in medical educa- mammals, as well as of a number of species of domes-
tion. I. Present state and needs. Lancet 1: 619-21. ticated and wild birds. Among humans it is a very
Lockhart-Mummery, H. E., and B. C. Morson. 1960. contagious respiratory disease characterized by sud-
Crohn's disease (regional enteritis) of the large intes- den onset and symptoms of sore throat, cough, often
tine and its distinction from ulcerative colitis. Gut 1: a runny nose, and (belying the apparent restriction
87-105. of the infection to the respiratory tract) fever, chills,
Lockhart-Mummery, J. P. 1907. The causes of colitis: With headache, weakness, generalized pain in muscles
special reference to its surgical treatment, with an and joints, and prostration. It is difficult to differenti-
account of 36 cases. Lancet 1: 1638.
ate between single cases of influenza and of feverish
Mendeloff, A. I., and B. M. Calkins. 1988. The epide-
miology of idiopathic inflammatory bowel disease.
colds, but when there is a sudden outbreak of symp-
London. toms among a number of people, the correct diagno-
Morris-Gallart, E., and P. D. Sanjmane, eds. 1935. Colitis sis is almost always influenza.
ulcerosa graves non ambianac — etiologia, diagnostica There is at present no specific cure that is effective
y tratemiento. Salvat. La Barcelone. against this viral disease. In mild cases the acute
Moschowitz, E., and A. O. Wilensky. 1923. Nonspecific symptoms disappear in 7 to 10 days, although gen-
granulomata of the intestine. American Journal of eral physical and mental depression may occasion-
Medical Science 166: 48-66. ally persist. Influenzal pneumonia is rare, but often
Nuboer, F. J. 1932. Chronische Phlegmone vas let ileum. fatal. Bronchitis, sinusitis, and bacterial pneumonia
Mededelingen uit het Geneeskundig laboratorium te are among the more common complications, and the
Weltevreden 76: 2989. last can be fatal, but seldom is if properly treated.
Placitelli, G., A. Franchini, M. Mini, and L. Possati. 1958.
Influenza is generally benign, and even in pandemic
La Colite ulcerosa. Rome.
Rappaport, H., F. H. Bergoyne, and F. Smetana. 1951. The
years, the mortality rate is usually low — 1 percent
pathology of regional enteritis. Military Surgeon 109: or less-the disease being a real threat to life for
463-502. only the very young, the immunosuppressed, and
Ross, J. R. 1949. Cicatrizing enterocolitis and gastritis. the elderly. However, this infection is so contagious
Gastroenterology 13: 344. that in most years multitudes contract it, and thus
Shapiro, R. 1939. Regional ileitis. American Journal of the number of deaths in absolute terms is usually
Medical Science 198: 269-92. quite high. Influenza, combined with pneumonia, is
Sullivan, A. J., and C. A. Chandler. 1932. Ulcerative coli- one of the 10 leading causes of death in the United
tis of psychogenic origin: Report of six cases. Yale States in the 1980s. The sequelae of influenza are
Journal of Biology and Medicine 4: 779. often hard to discern and define - prolonged mental
Warren, S., and S. C. Sommers. 1948. Cicatrizing enteritis depression, for instance - but there is evidence that
(regional ileitis) as a pathologic entity. American Jour-
the global pandemic of encephalitis lethargica (par-
nal of Pathology 24: 475-521.
Wells, C. 1952. Ulcerative colitis in Crohn's disease. An-
kinsonism) of the 1920s had its origin in the great
nals of the Royal College of Surgeons 11: 105-20.
pandemic of 1918—19.
Wilks, S. 1859. Morbid appearances in the intestine of
Miss Bankes. London Medical Gazette 2: 264-65.
Wilks S., and W. Moxon. 1875. Lectures on pathological Distribution and Incidence
anatomy, 2d edition, ed. J. and A. Churchill, 408, 762. In seemingly every year, there are at least some
London. cases of influenza in every populated continent and
in most of the large islands of the world. During
epidemics, which occur somewhere almost annually,
the malady sweeps large regions, even entire conti-
nents. During pandemics, a number of which have
occurred every century for several hundred years,
the disease infects a large percentage of the world's

population and, ever since the 1889-90 pandemic, in including immunologically experienced adults. In
all probability a majority of that population. Not the mildest of these pandemics, millions fall ill and
everyone so infected becomes clinically sick, but thousands die.
nonetheless influenza pandemics are among the The cause of the major changes in the virus that
most vast and awesome of all earthly phenomena. set off the pandemics is still a matter of mystery.
The disease strikes so many so quickly and over such Many theories have been devised, including those
vast areas that the eighteenth-century Italians pertaining to the influence of sun spots and such.
blamed it on the influence of heavenly bodies and Currently the three most plausible theories are the
called it influenza. following:
Etiology and Epidemiology 1. The influenza A virus currently circulating

The causative agents of influenza are three myxovi- through the human population undergoes a se-
ruses, the influenza viruses A, B, and C. The B and C ries of mutations, which rapidly and radically
viruses are associated with sporadic epidemics transform the virus into an infection-producing
among children and young adults, and do not cause organism for which human immune systems are
pandemics. The A virus is the cause of most cases unprepared.
during and between pandemics. It exists and has 2. An animal influenza virus abruptly gains the abil-
existed in a number of subtypes, which usually do ity to cause disease in humans, with the same
not induce cross-immunity to one another. In most results.
instances, influenza viruses pass from person to per- 3. A human influenza virus and an animal influenza
son by breath-borne droplets, and from animal to virus recombine ("cross-breed") to produce a new
animal by this and other routes. Although the dis- virus that retains its capacity to infect humans
ease can spread in warm weather, its epidemics but has a surface with which human immune
among humans in the temperate zones usually ap- systems are unfamiliar.
pear in the winters, when people gather together in In the present state of research, the first of these
schools, houses, buses, and so forth under conditions three seems the least likely and the last the most
of poor ventilation. Geographically, the malady likely explanation. Nothing, however, is certain yet,
spreads as fast as its victims travel, which in our and the cause of influenza pandemics remains
time can mean circumnavigation of the globe in a unknown.
few months, with the pandemic veering to the north
and south of the tropics with the changing seasons. History and Geography
Immunology Through the Eighteenth Century
Influenza A virus is distinctive in its genetic instabil- The origins of influenza are unknown. It is not an
ity, which probably makes permanent immunity to infection of our primate relations, and so it is proba-
the disease impossible, no matter how many times it bly not a very old human disease. It has, as far as we
is contracted. This, plus its short incubation period know, no latent state, and it does create a usually
of 1 to 2 days and the ease with which it passes from effective (though short-lived) immunity, and so it
person to person, enables the disease to swing was unlikely to have been common among our Paleo-
around the globe in pandemics and, between them, lithic ancestors or those of our herd animals before
to maintain itself not only in epidemics among the the advent of agriculture, cities, and concentrated
previously unexposed and newborn, but also among populations of humans and domesticated animals. In
the previously exposed and adult majority. Between small populations, it would have burnt itself out by
pandemics the proteins on the shell of the virus killing or immunizing all available victims quickly.
undergo slow but constant genetic change, render- But because the immunity engendered is ephemeral,
ing acquired immunity ever more obsolete. This ge- it does not require the large populations that mea-
netic instability is the likeliest explanation for the sles and smallpox do to maintain itself.
fact that even during pandemics the virus seems to Although influenza could be among the older dis-
change sufficiently to produce repeating waves of eases of civilization, acquired from pigs or ducks or
the infection, often two and three in a given locale. other animals thousands of years ago, there is no
Several times a century, the virus has changed radi- clear evidence of its spread among humans until
cally, rendering obsolete the immunologic defenses Europe's Middle Ages, and no undeniable evidence
of the great majority of humans vis-a-vis influenza, until the fifteenth and sixteenth centuries. Yet,

VIII.73. Influenza 809
since that time, the malady has been our unfailing the efficiency of transatlantic shipping that it swept
companion, never absent for more than a few de- over western Europe and appeared in North Amer-
cades, if that. The association of the disease with Old ica in the same month, December of 1889. It struck
World domesticated animals, and the extreme vul- Nebraska, Saskatchewan, Rio de Janeiro, Buenos
nerability to it of isolated peoples such as Amerindi- Aires, Montevideo, and Singapore in February, Aus-
ans, suggest that it was restricted to the Old World tralia and New Zealand in March. By spring the
until the end of the fifteenth century. In that and the pandemic was firmly established and widespread in
following centuries it spread overseas with Europe- Asia and Africa. Some Africans, who had never seen
ans and their livestock, and may account for much of the disease in their lifetimes, called it a "white
the clinically undefined morbidity and mortality man's disease." Waves of this infection continued to
among the indigenes of Europe's transatlantic and roll across large regions of the world for the rest of
transpacific empires. Large-scale epidemics of influ- the century, and although the mortality rates in this
enza did roll over Europe in 1510, 1557, and 1580. pandemic were quite low, the total of deaths was
The last, the first unambiguously pandemic explo- high. By conservative estimate, 250,000 died in Eu-
sion of the disease, extended into Africa and Asia as rope, and the world total must have been at the very
well. There were further epidemics in Europe in the least two or three times greater. Influenza killed
seventeenth century, but seemingly of only a re- many more than cholera did in the nineteenth cen-
gional nature. tury, but much of the mortality was restricted to the
At least three pandemics of influenza occurred in elderly, and thus its reputation as an unpleasant but
Europe in the eighteenth century - 1729-30, 1732- not dangerous infection was preserved.
3, and 1781-2 - and several epidemics, two of
which - 1761-2 and 1788-9 - may have been exten- Early Twentieth Century
sive enough to be termed pandemics. The pandemic Its history for the first 17 years of the next century
of 1781-2 was, in its geographic spread and the reinforced this view. Although rarely absent for
number of people infected, among the greatest mani- long, influenza attracted little attention until 1918-
festations of disease of all history. Physicians 19, when a pandemic of unprecedented virulence
guessed, for instance, that two-thirds of the people of
appeared. What was probably its first wave rose in
Rome and three-quarters of the population of Brit- the spring of 1918, perhaps first in the United
ain fell ill, and influenza spread widely in North States, attracting little attention because its death
America, the West Indies, and Spanish America. rate was low. Its most ominous characteristic was
that many of the dead were young adults, in contra-
Nineteenth Century distinction to the malady's previous record. That
By the end of the eighteenth century, accelerating spring and summer, this new influenza circumnavi-
population growth, urbanization, and improvements gated the globe, infecting millions and killing hun-
in transportation were changing the world in ways dreds of thousands, and making ever more difficult
that enhanced the transmission of microbes across the waging of wars in Europe and the Middle East.
long distances. There were at least three influenza The name given this new disease was the Spanish
pandemics in the nineteenth century: 1830-1, 1833, flu, not because morbidity and mortality were
and 1889-90, and a number of major epidemics as higher there than elsewhere, but because Spain was
well. Even so, one of the most intriguing aspects of not a belligerent and thus the ravages of the malady
the history of influenza in this century was the long in that country were not screened from world atten-
hiatus between the second and third pandemics. In tion by censorship. As in previous pandemics and
fact, in Europe, from the epidemic of 1847-8 (de- epidemics, morbidity rates were vastly greater than
fined a pandemic by some) to 1889, there were only a mortality rates, and the latter, as a percentage of the
few minor upsurges of this disease. former, were not impressive.
When influenza rose up again in 1889, most physi- In August, that changed, as death rates doubled,
cians had only a textbook acquaintance with the tripled, and more. A second wave arose, sending
disease, but by this time the medical sciences were hundreds of millions to sickbeds, as if they were as
making rapid advances, and public health had be- immunologically inexperienced as children, and kill-
come a matter of governmental concern. The 1889- ing millions. This wave tended to subside toward the
90 pandemic was the first for which we have de- end of the year, but returned again in a third wave
tailed records. It reached Europe from the east in the winter and spring. In both the fall and winter
(hence its nickname, the Russianflu),and such was waves, about half the deaths were in the 20- to 40-

year-old group. Fully 550,000 died in the United in his time and again in the fall of 1918. Unfortu-
States, about 10 times the number of battle deaths of nately, Pfeiffer's bacillus was not the cause, al-
Americans in World War I. though it doubtlessly played a role in many secon-
In remote parts of the world, where influenza had dary infections. Its chief significance is probably
never or rarely reached before, the death rate was that it inveigled many scientists into wasting a lot
often extremely high. In Western Samoa, 7,542 died of time discovering its insignificance. Second, influ-
out of a population of 38,302 in the last 2 months of enza was believed to be an exclusively human dis-
1918. The total of deaths in the world was in excess ease, making it very awkward to work with in the
of 21 million, that number being an estimate made laboratory. Third, bacteriologists of the early de-
in the 1920s before historians and demographers cades of the twentieth century had no means by
sifted through the records of Latin America, Africa, which to see anything as small as the true cause of
and Asia, adding many more - millions, certainly — the disease, the influenza virus.
to the world total. It is possible that the 1918—19 About 1930, Richard E. Shope discovered that he
pandemic was, in terms of absolute numbers, the could transfer a mild influenza-like disease from one
greatest single demographic shock that the human pig to another via a clear liquid from which all
species has ever received. The Black Death and visible organisms had been filtered. (If Pfeiffer's ba-
World Wars I and II killed higher percentages of the cillus was also present in the pigs, they became
populations at risk, but took years to do so and were much sicker, a phenomenon that is one of the sources
not universal in their destruction. The so-called of the theory that the 1918 influenza may have been
Spanish flu did most of its killing in a 6-month the product of synergistic infections.) In 1933, W.
period and reached almost every human population Smith, C. H. Andrewes, and P. P. Laidlaw succeeded
on Earth. Moreover, its impact was even greater in infecting ferrets with a filtrate obtained from a
than these numbers indicate because so many young human with influenza, and after these events, re-
adults died. To this day, we do not know what made searchers knew what to look for. In the following
the 1918—19 influenza such a killer. Theories about years, the A, B, and C viruses were isolated and
wartime deprivation are clearly invalid because the identified and, thanks to the new electron micro-
death rates in well-fed America and Australasia scope, seen and photographed.
were approximately the same as in the nations im- It is possible that more is now known about the
mediately engaged in the fighting. Perhaps as has influenza virus than about any other virus, but its
been suggested, a chance synergy of viral and bacte- changing nature has defeated all efforts thus far to
rial infection produced an exceptionally deadly pneu- make a vaccine against the disease that will be effec-
monia, or perhaps the 1918 virus was so distinctive tive for more than a few years at most. Vaccines
antigenically that it provoked a massive immune were produced in the 1940s to protect the soldiers of
response, choking the victims with inflammation World War II from a repetition of the pandemic that
and edema. We have no way of proving or disproving had killed so many of them in World War I, and
these theories. influenza vaccines developed since have enabled mil-
In 1920, another wave of the disease rolled over lions, particularly the elderly, to live through epi-
the world, and in the United States this was, with demics without illness or with only minor illness.
the exceptions of the two preceding years, the worst But the ability of the A virus to change and some-
for influenza mortality of all time. But morbidity times to change radically - as at the beginning of
and mortality rates soon shrank back to normal lev- the 1957-8 and 1968 pandemics - and to race
els, and the disease lost most of its power to kill around the globe faster than suitable vaccines can
young adults. The medical profession, however, has be produced and delivered to large numbers of peo-
subsequently worried about a resurgence of the ple, has so far frustrated all efforts to abort pan-
killer virus, and has devoted great energy to identify- demics. Vaccines were effective in damping neither
ing it, learning its secrets, and how to disarm it. the pandemic of the so-called Asian flu of 1957-8
nor the Hong Kong flu of 1968.
Prevention and Control At present, a worldwide network of 100 or so cen-
The medical profession, grappling with the great ters, most of them national laboratories, cooperate
pandemic, labored under three major disadvan- under the direction of the World Health Organiza-
tages: First, in the 1890s one of the premier bacteri- tion to identify new strains of influenza virus as
ologists of the world, Richard F. J. Pfeiffer, thought quickly as they appear in order to minimize the time
he had discovered the causative organism, common between the beginning of epidemics and the produc-

VIII.74. Japanese B Encephalitis 811
tion and distribution of relevant vaccines. The effi- mography, 2d edition, ed. C. Fyfe and D. McMaster,
ciency of this organization has been impressive, and 401-31. Edinburgh.
certainly has saved many lives, but influenza is not 1986. Pandemic influenza, 1700-1900. Totowa, N.J.
yet under control. The frustration of flu fighters of Ravenholt, R. T., and William H. Foege. 1982. 1918 influ-
the United States reached a peak in 1976, when a enza, encephalitis lethargica, parkinsonism. Lancet 2:
virus closely resembling Shope's swine virus and 860-64.
Silverstein, Arthur M. 1981. Pure politics and impure sci-
that of the 1918 pandemic began to spread among
ence: The swine flu affair. Baltimore.
soldiers at Fort Dix, New Jersey. The medical profes- Stuart-Harris, Charles. 1981. The epidemiology and pre-
sion and the U.S. government mobilized in order to vention of influenza. American Scientist 69: 166-71.
prevent a recurrence of the disaster that had oc-
curred 60 years before. Scores of millions of dollars
were spent to devise a vaccine, to produce it in quan-
tity, and to deliver it into the arms of millions of
Americans. No pandemic appeared, not even an epi-
demic, and the single long-lasting medical result of VIII.74
this enormous effort seems to have been a number of Japanese B Encephalitis
cases of Guillain-Barre syndrome, a paralytic and
occasionally fatal disorder, which were associated
with the vaccinations. The number of these cases Japanese B encephalitis is a relatively uncommon
was tiny, relative to the tens of millions of doses of disease, even in areas where the infection is en-
the vaccine administered, but the result in litigation demic. The disease is one of several caused by
has been massive. arthropod-borne viruses (arboviruses); carried by
Alfred W. Crosby mosquitoes of the genus Culex, this one is a member
of the family Togaviridae and genus Flavivirus and
Bibliography thus is an RNA virus. The species of Culex that is
Beveridge, W. I. B. 1977. Influenza: The last great plague: the most common insect vector for Japanese B en-
An unfinished story of discovery. New York. cephalitis is Culex tritaeniorhyncus.
Crosby, Alfred W. 1989. America's forgotten pandemic: The The disease was first recognized and described in
influenza of 1918. New York. 1871, and the virus was first isolated in 1935. The
Guerra, Francisco, 1985. La epidemia Americana de influ- infection may appear in epidemic or in sporadic out-
enza en 1493. Revista de Indias 45: 325-47. breaks, and is carried particularly in swine, but also
Hoyle, L. 1968. The influenza viruses. New York. has been isolated from a variety of birds and from
Jordan, Edwin O. 1927. Epidemic influenza: A survey. equine animals. The virus is distributed principally
Chicago. in East and Southeast Asia.
Kaplan, Martin M., and Robert G. Webster. 1977. The
epidemiology of influenza. Scientific American 237:
88-106. Epidemiology
Kilbourne, Edwin D. 1975. The influenza viruses and influ- Epidemic outbreaks of Japanese B encephalitis, like
enza. New York. those of arboviruses in general, tend to occur in
1987. Influenza. New York. regions that are usually dry and arid and, therefore,
Kingsley, M. Stevens. 1918. The pathophysiology of influ- relatively free of viral activity; such areas may accu-
enzal pneumonia in 1918. Perspectives in Biology and mulate a large number of individuals who, because
Medicine 25: 115-25. of lack of previous exposure, are relatively suscepti-
MacDonald, Kristine L., et al. 1987. Toxic shock syn- ble. Then with rain and the appearance of conditions
drome, a newly recognized complication of influenza favorable to the proliferation of the insect vector,
and influenza-like illness. Journal of the American epidemic outbreaks may occur, particularly where
Medical Association 257: 1053-8. there are relatively high population densities of the
Neustadt, Richard E., and Harvey V. Fineberg. 1978. The
human host and of the amplifying hosts such as
swine flu affair: Decision-making on a slippery slope.
Washington, D.C.
equine or porcine animal species. In addition, there
Osborn, June E. 1977. Influenza in America, 1918-1976. is evidence that for some arboviruses a change oc-
New York. curs in the relative virulence of the infecting strain,
Patterson, K. David. 1981. The demographic impact of the which may also account for an epidemic outbreak.
1918-19 influenza pandemic in sub-Saharan Africa: Why, given the presence of Japanese B encephalitis
A preliminary assessment. In African historical de- virus in birds with wide-ranging migratory pat-

terns, the disease remains localized to certain geo- generally decreased and may be elevated in the spi-
graphic areas is not entirely clear, but presumably nal fluid.
has to do with the specificity of the insect vector in
carrying the infectious agent. The mosquito vector, Diagnosis
C. tritaeniorhyncus, is found in rice fields and feeds The definitive diagnosis is made only from studies of
on pigs and birds, as well as human and other hosts. the antibody status of the affected individual, with
However, the Japanese custom of raising pigs in the evidence of the absence of specific antibody at the
fall, after the flooding of rice paddies is over, and of time of onset of the disease followed by a 4-fold or
taking the pigs to market early the following year, greater rise in titer of the antibody during the follow-
may also help to account for the general lack of large ing days or weeks. Complement-fixing antibody is
outbreaks as well as for the usual pattern of sporadic the first to appear in most patients, but hemag-
cases. As might be expected with such a pattern, the glutinating and neutralizing antibodies are usually
few large outbreaks tend to occur in more rural demonstrable shortly thereafter. More recently, anti-
areas, street antibody to the virus is relatively com- body tests usingfluorescein-or enzyme-labeled anti-
mon, and clinical cases account for about 2 percent of body, or the various modifications of these, showing
all of the infections, as judged by antibody surveys. specific rise in titer, are sufficient to establish the
diagnosis. Antigenic variation is common among vi-
Pathology ral isolates, and at least two immunotypes have
Most of the information on the early stages of the been delineated; thus the serodiagnosis must be per-
disease has been gained from studies in the mouse. formed in laboratories that have on hand the several
Pathological features of fatal human cases have subtypes that may be needed for a full serologic
generally been consistent with the experimental analysis of a given case or outbreak.
findings. Early in the disease, focal hemorrhages, The disease is one of the most fatal among arbovir-
congestion, and edema are found in the brain. uses, with case fatality rates of 50 to 70 percent
Microscopically widespread damage to Purkinje having been recorded in outbreaks. Recovery may be
cells of the cerebellum is noted, with pervascular complete, or there may be residual damage to the
inflammation and multiple foci of degeneration and central nervous system; Japanese B encephalitis, in
necrosis. Extraneural evidence of spread of the contrast to other arboviral encephalitides, is accom-
virus is found in the form of hyperplasia of the panied by relatively high rates of complete recovery
germinal centers of the lymph nodes and of the despite the high case fatality rates.
spleen; multiple foci of round-cell infiltration in There is no specific treatment, and supportive care
many organs, including the heart, kidneys, and is the major intervention that can be offered. The
lungs; and, in pregnancy, infiltration of the pla- protective effect of antibody suggests that convales-
centa with corresponding abortion and stillbirth. cent serum or other sources of antibody might have
Multiple lesions in the offspring indicate cross- some therapeutic value, but this has not been sys-
placental passage of the virus. tematically investigated on a suitable scale.
Clinical Manifestations Prevention and Control

The clinical disease consists of the usual signs and Vaccines have been available for many years for
symptoms of encephalitis, and no syndrome has been immunization of humans and of livestock. Live at-
elicited that is specific for Japanese B encephalitis. tenuated vaccines have been available in Japan
Within a few days to several weeks (mean of 10 since 1972, and in China more recently, and their
days) after a bite by a mosquito carrying the virus, effectiveness is shown by seroconversion rates of up
susceptible patients manifest fever and evidence of to 96 percent. Vaccines are prepared by purification
damage to the central nervous system, which may of viral suspensions from mouse brains, or from ham-
include meningism, delirium, drowsiness, confusion, ster kidney cultures, but several newer technologies
stupor, paralyses especially of the facial muscles, are presently under active investigation. Wide-
and, in the most severe cases, coma and death within spread immunization campaigns have been success-
a few days after onset. ful in Japan, Taiwan, and China. At present, the
The cerebrospinal fluid shows the presence of a vaccines are composed principally of the prototype
nonpyogenic infection, with increased numbers of Nakayama strain, and reasonable control of the dis-
mononuclear cells, rarely over 1,000 per cubic milli- ease has taken place. It is therefore unclear how
meter, and elevated protein; sugar is therefore not necessary or desirable the addition of the newer iso-

VIII.75. Lactose Intolerance and Malabsorption 813
lates, with slightly different antigenic specificities, litis in various arthropods collected in Japan in 1946—
would be. 1947. American Journal of Hygiene 51: 36-62.
Currently used vaccines require primary immuni- Umenai, T., et al. 1985. Japanese encephalitis: Current
zation with two injections at 7- to 14-day intervals, a worldwide status. Bulletin of the World Health Organi-
booster within 1 year, and further boosters at 3- to 4- zation 63: 625-31.
year intervals. Fortunately, the vaccine produces
relatively few side reactions, and postvaccinal en-
cephalitis must be exceedingly rare because few if
any reliable reports of this complication following
administration of the vaccine are in evidence. VIII.75
Vector control has been investigated in some de- Lactose Intolerance and
tail. Larvicides and adulticides aimed at the chief
mosquito vector have reduced attack rates in areas Malabsorption
where these have been tested, and programs of con-
trol of insect vectors, coupled with elimination of
aquatic vegetation in irrigation channels and with Lactose malabsorption describes a physiological sit-
spraying of insecticides in livestock pens, have had uation. It is the basis for lactose intolerance. The
some success in China. Under epidemic conditions, inability to digest lactose is a quantitative phenome-
spraying with appropriate insecticides has some- non related to the enzyme lactase and its amount
times been necessary. and activity in the intestine. Lactose intolerance,
Edward H. Kass then, is a clinical definition. It involves the concept
that the individual is unable to tolerate physiologi-
cally the lactose present in milk and other dietary
products because of an inability to digest the carbo-
Bibliography hydrate, due to insufficient activity of the lactase
Buescher, E. L., and W. F. Scherer. 1959. Ecologic studies
enzyme. Intolerance to lactose as a clinical entity
of Japanese encephalitis virus in Japan. IX. Epidemio-
logic correlations and conclusions. American Journal
has been recognized for some time. Early in this
of Tropical Medicine and Hygiene 8: 719-22. century, Abraham Jacoby hinted at the existence of
Buescher, E. L., et al. 1959a. Ecologic studies of Japanese lactose intolerance in speeches to the American Pedi-
encephalitis virus in Japan. IV. Avian infection. atric Society; later, in 1926, John Howland, in his
American Journal of Tropical Medicine and Hygiene presidential address to that same organization, was
8: 678-88. somewhat more explicit when he indicated that
1959b. Ecologic studies of Japanese encephalitis virus in many of the infantile diarrheas were the result of a
Japan. II. Mosquito infection. American Journal of lack of "ferments" necessary for the digestion of car-
Tropical Medicine and Hygiene 8: 651—64. bohydrate (Flatz 1989).
Fukumi, H., et al. 1975. Ecology of Japanese encephalitis More recently, interest of physicians and nutrition-
virus in Japan. I. Mosquito and pig infection with the
ists in the digestion of lactose stimulated reports
virus in relation to human incidences. Tropical Medi-
cine 17: 97-110.
during the late 1950s. One by A. Holzel and col-
Hayashi, K., et al. 1978. Ecology of Japanese encephalitis leagues (1959) reported on a severe diarrhea associ-
virus in Japan, particularly the results of surveys in ated with the ingestion of lactose in two young sib-
every interepidemic season from 1964 to 1976. Tropi- lings who, as a consequence, were "failing to thrive."
cal Medicine 20: 81-96. Another report, by P. Durand (1958), diagnosed two
Hayashi, M. 1934. Uebertragung des Virus von encephali- patients with lactose malabsorption and lactosuria.
tis epidemica auf Affen. Proceedings of the Imperial Since then, innumerable articles and reviews have
Academy of Tokyo 10: 41-4. appeared in the world's literature (Scrimshaw and
Konno, J., et al. 1966. Cyclic outbreaks of Japanese en- Murray 1988). Evaluations of that literature may be
cephalitis among pigs and humans. American Journal obtained by consulting G. Semenza and S. Auricchio
of Epidemiology 84: 292-300. (1989), G. Flatz (1989), and N. Kretchmer (1971).
Mifune, K. 1965. Transmission of Japanese encephalitis
virus to susceptible pigs by mosquitoes of Culex
tritaeniorhynchus after experimental hibernation. En- Lactose: Chemistry, Digestion, and
demic Diseases Bulletin of Nagasaki University 7: Metabolism
178-91. Lactose is a galactoside composed of glucose and
Sabin, A. B. 1950. Search for virus of Japanese B encepha- galactose. This compound is found in the milk of

most mammals, although in marsupials and mono- during the perinatal period. This does not mean,
tremes it appears in conjugated form. It is entirely however, that weaning is directly related to the de-
lacking in the milk of the California sea lion and crease in activity of lactase. There has been no docu-
related pinnipedia of the Pacific Basin. The reason mentation indicating that there is any inductive re-
for the latter is that lactose is synthesized in the lationship between the activity of the enzyme and
mammary gland from two monosaccharides, glucose the ingestion of milk. In fact, all the careful studies
and galactose, by the enzyme galactosyltransferase, indicate that there is no relationship between the
which requires the presence of alpha-lactalbumin - two events (i.e., the ingestion of milk and the activ-
not produced by the mammary glands of the sea lion. ity of lactase).
Thus the concentration of lactose in the milk of pla-
cental animals ranges from a low of zero to a high of Classification
7 percent (Sunshine and Kretchmer 1964). Lactose malabsorption can be classified into three
Lactose is digested in the small intestine by the categories:
lactase (a galactosidase), which is located in the
1. Congenital malabsorption of lactase, a rare phe-
brush border of the epithelial cells of intestinal villi.
nomenon, which has been documented in only a
This enzyme is anchored to the membrane by a hy-
drophobic tail of amino acids. Detailed descriptions few cases.
have recently been published of the intimate in- 2. Primary malabsorption of lactose, a worldwide
tracellular metabolism of lactase (Castillo et al. situation that is encountered in humans after the
1989; Quan et al. 1990). age of 5 to 7 years, and in other animals after
weaning. (This is considered to be a normal phys-
In most mammals the activity of lactose-digesting
iological process, transmitted genetically; indeed
lactase is high during the perinatal period; after
it resembles a classical Mendelian recessive
weaning the activity declines to about 10 percent of
trait.)
its original value. But in certain human groups the
3. An acquired malabsorption of lactose that can be
enzyme activity remains elevated throughout the
encountered at any age in infants and children
lifetime of most of their members (Kretchmer 1977).
under 7 years, as well as in adults who had previ-
Examples of these groups include northern Europe-
ans, people of Magyar-Finnish extraction, and two ously been lactose absorbers. This form can also
be associated with nonspecific and specific diar-
African tribes, the Fulani and the Tussi.
rhea of infancy, drugs that affect the intestinal
mucosa, and diseases such as cystic fibrosis and
Clinical Manifestations gluten-sensitive enteropathy.
The clinical manifestations of lactose intolerance in-
clude increasing abdominal discomfort, borboryg- An interesting phenomenon is that the colonic
mus, flatulence, and finally fermentative diarrhea. flora of the lactose-intolerant individual seems able
Although an inordinate amount of any carbohydrate to adapt to a nonfermentive type of bacteria. A study
in the diet will produce a similar symptomatology, was launched in Nigeria in which six medical stu-
intolerance to lactose is the most prominent of these dents, all proven lactose nondigesters, were fed
clinical syndromes. The basis of this phenomenon is graded doses of 5 grams of lactose to a final amount
primarily the activity of the lactase relative to di- of 50 grams over a 6-month period. At the end of this
etary lactose. The lower the activity, the less the time, all six of the individuals could tolerate the 50
capacity for the hydrolysis of the lactose, although grams of lactose, but were shown to be unable to
other factors - such as intestinal motility and the digest it. Adults who should be intolerant to lactose
presence of other nutrients — also play a role in this can drink a glass, or even a pint, of milk with rela-
phenomenon. tive impunity, but nonetheless manifest no increase
When the capacity of the lactase is exceeded, the in lactase activity and consequently cannot digest
nonhydrolyzed dietary lactose passes into the large the lactose.
bowel where it is fermented by the myriad of colonic
bacteria. This action in turn yields propionic acid, History and Geography
hydrogen, methane, and alcohols, and results in a The ability to digest lactose is a nutritional event
watery diarrhea, the pH of which is acidic. that can be clearly associated with evolutionary pres-
In general, the activity of lactase in the intestine sures. During the Neolithic period, human adults
in almost all mammals by the time of weaning has began to drink milk, probably in association with
decreased to about 10 percent of that encountered the domestication of animals. These ancient pasto-

VIII.75. Lactose Intolerance and Malabsorption 815
ralists who originated in the Euphrates River Valley Table VIII.75.2. Distribution of the adult lactose
were nomadic, constantly in search of new pastures phenotypes in human populations
for their animals. It is assumed that they migrated
in two main directions: to the northwest, toward Population Number of High Low Percent
or country Subgroup subjects LDC LDC low LDC
Europe; and to the southwest, across the then-fertile
Sahara toward east and west Central Africa. The Finland Finns 449 371 78 17
Lapps 521 305 216 41
exact time of these migrations is unknown, but pre- Swedes 91 84 7 8
sumably the nomadic pastoralists of Africa (e.g., the Sweden Swedes 400 396 4 1
Fulani, the Tussi, the Masai, and others) have their Denmark Danes 761 743 18 3
origins in these migrations as do those of northern Britain British 96 90 6 6
Ireland Irish 50 48 2 4
Europe. Netherlands Dutch 14 14 0 0
In the Americas, by contrast, there were no indige- Germany Germans 1872 1596 276 15
nous pastoral groups, and thus, in the Western Hemi- France North 73 56 17 23
South 82 47 35 43
sphere, there was no ingestion of milk after weaning Spain Spaniards 265 225 40 15
until the Europeans arrived. An absence of dietary Switzerland Swiss 64 54 10 16
milk after weaning was also the case in Australia, Austria Austrians 528 422 106 20
Italy North 565 301 264 47
the islands of the Pacific, Japan, and the rest of Asia. South 128 41 78 68
In these regions the individual after weaning ob- Sicily 100 29 71 71
tained calcium from small bones, limestone, dark- Yugoslavia Slovenians 153 99 54 35
green vegetables, and fermented or pressed (and South 51 25 26 51
Hungary Hungarians 707 446 61 37
thus much reduced in lactose) dairy products. Czechoslovakia Czechs 217 189 28 13
Thus the present-day geographic distribution of Poland Poles 296 187 109 37
peoples who can or cannot digest lactose fits with our Former U.S.S.R. Leningrad 248 210 38 15
Estonians 650 467 183 28
historical knowledge of the distribution of ancient Greece Greeks 972 452 520 53
pastoral groups and the milking of their animals. Cyprus Greeks 67 19 48 72
Nonetheless, confusion arises over questions of levels Gypsies European 253 83 170 67
Turkey Turks 470 135 335 71
of lactose intolerance among peoples with no history Morocco Maghrebi 55 12 43 78
of pastoral activity. In the case of a native American Egypt 584 157 427 73
population - the Pima-Papagos, for example - the in- Sudan Arabs 387 179 208 54
ability to digest lactose has been reported at only 60 Beja 303 252 51 17
Other nomads 61 42 19 31
percent (see Tables VIII.75.1 and VIII.75.2). The 40 South 366 92 274 75
Ethiopia 58 6 52 90
Somalia 244 58 186 76
Table VIII.75.1. Lactose absorption and Kenya Bantu 71 19 52 73
Uganda, Rwanda Bantu 114 14 100 88
malabsorption correlated with degree of Indian
Hima, Tussi 70 65 5 7
blood (children ^4 years, and adults) Mixed 75 38 37 49
Central Africa Bantu 112 6 106 95
No. of No. of mal- Percentage South Africa Bantu 57 3 54 95
absorbers absorbers" of malabsorbers Bushmen 65 3 62 95
Mixed 152 26 126 83
Full-blood Indians (100% Pima or all Pima-Papago) Nigeria Ibo, Yoruba 113 12 101 89
3* 59 95 Hausa 48 9 39 81
Fulani (Fulbe) 9 7 2 22
Mixed Anglo (Northern European)-Indian Niger Tuareg 118 103 15 13
Vie Anglo 0 2 100 Senegal Agricultural 131 85 46 35
Peuhl (Fulbe) 29 29 0 0
Ms Anglo 5 16 76 Israel Israeli 272 92 180 66
Vi or Vi Anglo 11 7 39 Arabs 67 13 54 80
Jordan Agricultural 204 43 161 79
Total 16 25 61 Bedouins 162 24
123 39
Saudi Arabia Bedouins 22 17 5 23
"Malabsorbers represent 21 adults (> 18 years), 38 chil- Other Arabs 18 8 10 56
dren (4-18 years). Lebanon 225 48 177 79
6 Syria 75 7 68 91
Ages 4, 4V£, and 6 years.
Arabs Mixed groups 30 5 25 83
Source: Johnson et al. 1977. Lactose malabsorption among Iran Iranians 40 7 33 83
the Pima Indians of Arizona. Gastroenterology 73(6): Afghanistan Afghans 270 47 223 83
1229-1304, p. 1391, by permission of Gastroenterology. Pakistan 467 195 272 58

Table VIII.75.2. (cont.) that the ability to digest lactose is associated only
with a population that has a history of pastoralism.
Population Number of High Low Percent The hereditary pattern for the ability to digest lac-
or country Subgroup subjects LDC LDC low LDC
tose appears to be simple and to follow straightfor-
India North 264 194 70 27 ward Mendelian genetics. The individual who can
Central 125 46 79 63
South 60 20 40 67
digest lactose carries the mutated gene, which in
Indians Overseas 87 22 65 75 this case, is dominant. The lactose nonabsorber car-
Sri Lanka Sinhalese 200 55 145 73 ries a recessive gene. Consequently, the cross be-
Thailand Thai 428 8 420 98 tween lactose malabsorbers always yields progeny
Vietnamese In U.S.A. 31 0 31 100
China Han North 641 49 592 93
who are lactose malabsorbers, thus perpetuating the
Han South 405 17 388 96 absolute inability to digest lactose among a lactose-
Mongols 198 24 174 88 intolerant population.
Kazakhs 195 46 149 76
Uighurs 202 37 165 82
Hui 177 24 153 86
Koreans 198 12 186 94
Summary
Hakka 202 22 180 89 Lactase has been shown in a number of careful inves-
Bai/Zhuang 359 27 332 93 tigations to be the same enzyme in the infant as in
Taiwan 71 0 71 100 the adult who can digest lactose, and in the residual
Chinese Overseas 94 23 71 76
Japan Japanese 66 10 56 85
activity found in the nondigester. In general, the
Indonesia Javanese 53 5 48 91 lactose digester has 10 times more enzymatic activ-
Papua New Guinea Tribals 123 12 111 90 ity than the lactose nondigester. Thus, the bio-
Fiji Fijians 12 0 12 100
Australia Whites 133 127 6 5
chemical genetics of lactose digestion is related to
Aborigines 145 48 97 67 the amount and activity of lactase.
Greenland Eskimo 119 18 101 85 Today, lactose malabsorbers who would like to be
Mixed 108 67 41 38
Canada Whites 16 15 1 6
able to drink milk can purchase various "lactase"
Indians 30 11 19 63 preparations now on the market that "digest" the
U.S.A. Alaska 36 6 30 83 lactose in milk before it is ingested. Others who do
Indians 221 11 210 95 not drink milk can overcome the potential dietary
Whites 1101 887 214 19
Blacks 390 138 252 65
calcium deficiency by consuming fermented milks,
Mexicans 305 147 158 52 pressed cheeses, dark-green vegetables, and small
Mexico Mexicans 401 69 332 83 bones as in sardines.
Colombia Mestizos 45 30 15 33
Chami Indians 24 0 24 100
The worldwide distribution of an inability to digest
Peru Mestizos 94 26 68 72 lactose after weaning in most human adults and all
Bolivia Aymara 31 7 24 77 other mammals argues for this condition to be the
Brazil Whites 53 27 26 49
Nonwhites 31 8 23 74
normal physiological state. The ability to digest lac-
Japanese 20 0 20 100 tose would seem then to be evidence of a genetic
polymorphism. It is only the bias of the milk-oriented
Note: LDC = lactose digestion capacity. societies of northern Europe and North America that
Source: G. Flatz. 1989. The genetic polymorphism of intestinal lactase activity casts lactose malabsorption as an abnormality.
in adult humans. In The metabolic basis of inherited disease, 6th edition, ed. Norman Kretchmer
G. R. Scriver, A. Z. Beaudet, W. S. Sly, and D. Valle, p. 3003. New York. By
permission of McGraw-Hill Book Company.
Bibliography
percent who can drink milk, however, represent the Castillo, R., et al. 1990. Intestinal lactase in the neonatal
genetic penetrance of the pure genetic pool of native rat. Journal of Biological Chemistry 265: 15889-93.
Americans with a gene that affords them the ability Debongnie, J. C , et al. 1975. Absorption of nitrogen and
to digest lactose. Without that genetic penetrance, fat. Archives of the Diseases of Childhood 50: 363-6.
Durand, P. 1958. Idiopathic lactosuria in a patient with
the percentage that could not digest lactose would
chronic diarrhea and acidosis. Minerva Pediatrica 10:
have reached 100. 1083-1147.
Flatz (1989) has compiled a list of figures that Flatz, G. 1989. The genetic polymorphism of intestinal
report the distribution of lactose phenotypes for lactase activity in adult humans. In The metabolic
many populations of the world (see Table VII.75.2). basis of inherited disease, 6th edition, ed. C. R. Scriver
These data support the cultural hypothesis first pro- et al. New York.
mulgated by Frederick Simoons (1970), which states Holzel, A., V. Schwartz, and K. W. Sutcliff. 1959. Defective

VIII.76. Lassa Fever 817
lactose absorption causing malnutrition in infancy.
Lancet 1: 1126-8. VHI.76
Johnson, J., et al. Lactose malabsorption among the Pima
Indians of Arizona. Gastroenterology 73(6): 1299-
Lassa Fever
1304.
Kretchmer, N. 1971. [Memorial lecture] Lactose and lac- Recognition of Africa's major endemic diseases of
tase: A historical perspective. Gastroenterology 61:
human beings was apparently well advanced by
805-13.
1977. The geography and biology of lactose digestion
1900. Malaria, trypanosomiasis, yellow fever, schis-
and malabsorption. Postgraduate Medical Journal 53: tosomiasis, typhoid fever, brucellosis, and a long list
65-72. of other afflictions had been characterized. But then,
Lebenthal, E., et al. 1981. Recurrent abdominal pain and in 1969, a new member of the coterie of major en-
lactose absorption in children. Pediatrics 67: 828-32. demic diseases of Africa entered the scene: Lassa
Quan, R., et al. 1990. Intestinal lactase: Shift in in- fever.
tracellular processing to altered, inactive species in The events leading to the discovery were dra-
the adult rat. Journal of Biological Chemistry 265: matic. A nurse, Laura Wine, in a mission hospital in
15882-8. Lassa, Nigeria, became ill, progressed unfavorably,
Ransome-Kuti, O., et al. 1975. A genetic study of lactose and died, despite the marshaling of antimalarials,
digestion in Nigerian families. Gastroenterology 68: antibiotics, antimicrobial agents, and supportive
431-6.
therapy. This death, as a statistic, would probably
Sahi, T. 1974. The inheritance of selective adult-type lac-
tose malabsorption. Scandinavian Journal of Gastro-
have been labeled "malaria" and thus been regis-
enterology (Supplement 30): 1-73. tered as such in national and World Health Organiza-
Scrimshaw, N. S., and E. B. Murray. 1988. The acceptabil- tion disease records. But another nurse, Charlotte
ity of milk and milk products in populations with high Shaw, who attended the first, also became ill. She
prevalence of lactose intolerance. American Journal of was taken by small plane from Lassa to the Evangel
Clinical Nutrition (Supplement 48(4)): 1083-1147. Hospital in Jos, Nigeria, operated by the Sudan Inte-
Semenza, G., and S. Auricchio. 1989. Small-intestinal rior Mission, where she died while being attended by
disaccharidases. In The metabolic basis of inherited physicians Harold White and Janet Troup, and
disease, 6th edition, ed. C. R. Scriver et al. New York. nurse Lily Pinneo. Again, there was no firm diagno-
Simoons, F. J. 1970. Primary adult lactose intolerance and sis. Pinneo then got sick. Doctors at the hospital
the milking habit: A problem in biologic and cultural were thoroughly alarmed. She was evacuated, via
interrelations. II. A culture-historical hypothesis. Jos and Lagos, to America by plane, and was admit-
American Journal of Digestive Diseases 15: 695—710.
ted to the College of Physicians and Surgeons at
Sunshine, P., and N. Kretchmer. 1964. Intestinal disaccha-
ridases: Absence in two species of sea lions. Science
Columbia University, where she was attended by
144: 850-1. John Frame, E. Leifer, and D. J. Gocke.
Wald, A., et al. 1982. Lactose malabsorption in recurrent The Yale Arbovirus Research Unit in New Haven,
abdominal pain of childhood. Journal of Pediatrics Connecticut, was alerted by Frame, who helped to
100: 65-8. get specimens for the unit. By a combination of seren-
dipity and skill, an agent was isolated — a virus,
unknown hitherto to humans. It was called "Lassa
virus" (Buckley, Casals, and Downs 1970). Two
laboratory-acquired cases occurred in Yale person-
nel working on the virus. One of them, Juan Roman,
died. The other, Jordi Casals, was given immune
plasma from the recently recovered nurse, Pinneo,
and made a full recovery. In due course and with
unfailing collaboration from many services, the
agent was established as belonging to a grouping
including lymphocytic choriomeningitis virus of
nearly worldwide distribution. (Examples are Taca-
ribe virus from bats in Trinidad; Junin virus, the
causative agent of Argentine hemorrhagic fever;
and Machupo virus, causative agent of Bolivian hem-
orrhagic fever.) The grouping of these agents has

Table VIII.76.1. Lassa fever outbreaks: West Africa, mild Lassa cases (McCormick et al. 1987a). This
1969-88 study of several years' duration was conducted by
personnel from the Centers for Disease Control, U.S.
Location Dates Statistics Public Health Service, in two hospitals in central
Lassa and Jos, Jan.-Feb. 1969 3 cases, 2 deaths Sierra Leone. It determined that Lassa was the caus-
Nigeria ative agent (determined by virus isolation) in 10 to
Jos, Nigeria Jan.-Feb. 1970 23 cases, 13 deaths 16 percent of all adult medical hospital admissions
Zorzor, Liberia Mar.—Apr. 1972 10 cases, 4 deaths and in about 30 percent of adult hospital deaths. The
Panguma and Oct. 1970-Oct. 64 cases, 23 deaths fatality rate for 441 hospitalized patients was 16.5
Tongo, Sierra 1972 percent.
Leone Karl M. Johnson and colleagues (1987) have shown
Onitsha, Nigeria Jan. 1974 2 cases, 1 death that mortality is directly associated with level of
Sierra Leone, Feb. 1977-Jan. 441 cases, 76 deaths viremia, although it must be noted that by the time
inland 1979
Vom (near Jos), 1976-7 5 cases, 2 deaths
figures for viremia have been received from the over-
Nigeria seas laboratory, the patient is either recovered or
Bombereke, Feb. 1977 1 case, 1 death dead. Joseph B. McCormick and colleagues (1987b)
Benin estimate the ratio of fatalities in infections in general
to be 1 to 2 percent, a rate lower than estimates based
Note: Seropositive individuals have been detected in Sene- on hospitalized patients. How widely thefindingson
gal, Guinea, Central African Republic, and the Camer- rates and outcome can be extrapolated to other hospi-
oons. tals and other settings in West Africa is not yet
known. Studies simply have not been done to deter-
been officially designated Arenavirus in the family mine this. However, it is clear that when seriously ill
Arenaviridae (Fenner 1976). As portrayed in Table patients are seen, the prognosis is highly unfavor-
VIII.76.1, seven other outbreaks of Lassa fever are able, even when the best of currently recognized
known to have occurred in Africa since 1969. Unfor- therapeutic regimes are applied.
tunately, Nurse Troup, who attended cases in the
1969 outbreak at Jos, became infected through a Virus Morphology, Size, and Structure
finger prick in an outbreak at Jos the following year F. A. Murphy and S. G. Whitfield (1975) have given a
and died. detailed account of the morphology and morpho-
genesis of the virion and have related it to the other
Clinical Manifestations, Morbidity, and members of the Arenavirus group. The virus parti-
Mortality cles, on budding from the cell membrane, may be
High fever associated with malaise, muscle and joint round, oval, or pleomorphic, with mean diameters of
pains, sore throat, retrosternal pain, nausea, mani- 110 to 130 nanometers and with spike-covered enve-
festation of liver involvement, bleeding tendency of lopes. The center of the particle contains variable
variable severity, proteinuria, and erythematous numbers of fine granulations, measuring 20 to 25
maculopapular rash with petechiae are features of nanometers, a characteristic that prompted the
the illness, but not of themselves particularly diag- name Arenavirus. The nucleosome consists of single-
nostic. The presence of an enanthem in the oro- stranded RNA. In 1984, F. Lehmann-Grube fur-
pharynx has been considered by some to have spe- nished a detailed account of the development and
cific diagnostic importance. pathogenetic characteristics of the Arenaviridae.
In early stages, the disease can simulate many
illnesses occurring in Central Africa, prominent Diagnosis
among them malaria (Downs 1975), although ty- Laboratory findings include leukopenia and increas-
phoid fever, rickettsial diseases, brucellosis, hepati- ing thrombocytopenia, proteinuria, and hematuria,
tis (before appearance of jaundice), and even yellow and evidence of coagulation. Diagnostic tests have
fever can also be mimicked. Sporadically occurring been developed. Viremia is a constant feature in
Lassa cases are certainly not often diagnosed. When Lassa cases, and the virus can be isolated and identi-
epidemics arise, the clumping of cases of mysterious fied in cell culture, using procedures that take a week
illness can and has attracted attention, leading to or more to run. By this time, the patient, if indeed a
diagnosis. It has become recognized from studies, Lassa patient, may be in dire straits. A rapid diagnos-
such as one in Sierra Leone, that there are many tic test is sorely needed. Progress has been made in

VIII.76. Lassa Fever 819
survey methodology. Serum specimens from sus- widespread in West Africa and also may be found in
pected patients, taken a few weeks after illness, and East Africa (McCormick et al. 1987). Studies of dis-
those taken in samplings of populations, can be exam- tribution are far from complete.
ined for the presence of antibody to Lassa, using a
special test plate developed in U.S. Army laborato- Control
ries. "Spots" of inactivated antigens are made on a Control must proceed at several levels. At the vil-
test plate, called colloquially a CRELMplate. A drop lage level, community-wide rodent control may be
of serum from an individual is placed on each of the implemented, which should include rodent proofing
"spots" of, respectively, Congo-Crimean fever, Rift of grain storage facilities, general trash cleanup,
Valley fever, and Ebola, Lassa, and Marburg inacti- and rodent poisoning campaigns. At the house-
vated viruses, and incubated. A fluorescein-tagged holder's level, measures should include rodent proof-
anti-human globulin is then added to each drop. De- ing of dwellings, rodent trapping, and rodent poison-
velopment offluorescencein one of the "spots" after ing. At the clinic level, the possibility of Lassa
incubation indicates presence ofhuman antibody, cou- should be considered whenever fever cases are seen,
pled to the signaled antigen. This method has led to and appropriate measures taken to protect the exam-
greater knowledge of several deadly diseases in Af- iner and other patients at the clinic. At the hospital
rica, and is a major step toward understanding the level, attention must be given to rodent control, and
geographic location of these diseases. in addition, diagnosed or suspected Lassa patients
should be isolated, with staff taking full precautions
Treatment to avoid close contact with them. Special precaution-
Treatment modalities are being explored. Ribavirin ary measures are indicated for obstetrical, gyneco-
shows promise of benefits if administered early logical, and surgical services. At the governmental
enough in the course of disease (McCormick et al. level, Lassa should be made a reportable disease,
1987a,b). An early hope in treatment, administra- and at the international level, Lassa must be made a
tion of plasma from recovered cases, has not been reportable disease.
very successful. If given early enough, before a posi- Wilbur G. Downs
tive laboratory diagnosis is possible, it may have
some value. Given later, there have been occasional Bibliography
dramatic recoveries, as in the case of Yale's Jordi Auperin, David D., and Joseph B. McCormick. 1989.
Casals. But there have also been many failures. Re- Nucleotide sequence of the Lassa virus (Josiah strain)
nal shutdown has been a fatal feature of such treat- S genome RNA and amino acid sequence of the N and
ment in some instances. All work with Lassa virus GPC proteins to other arenaviruses. Virology 168:
must be conducted under conditions of highest secu- 421-5.
rity (MMWR 1983), which slows down laboratory Buckley, Sonya M., Jordi Casals, and Wilbur G. Downs.
work. Several human deaths have occurred among 1970. Isolation and antigenic characterization: Lassa
virus. Nature 227:174.
laboratory workers, nonetheless.
Downs, Wilbur G. 1975. Malaria: The great umbrella.
Bulletin of the New York Academy of Medicine 51:
Epidemiology 984-90.
The association with the Arenavirus group helped to Fenner, Frank. 1976. Classification and nomenclature of
orient the studies in Africa, relating to determina- viruses. Second Report of the International Committee
tion of the transmission cycle of the Lassa virus. on Taxonomy of"Viruses: Intervirology 7: 1-116.
Predictably, like its congeners, it was determined to Fuller, John G. 1974. Fever: The hunt for a new killer
be an infection of small rodents, usually house- virus. New York.
frequenting rodents. Praomys (Mastomys) natalen- Johnson, Karl M., et al. 1987. Clinical virology of Lassa
sis in sub-Saharan, equatorial, and southern Africa fever in hospitalized patients. Journal of Infectious
is the most common house-frequenting rodent and Diseases 155: 456-64.
McCormick, Joseph B., et al. 1987a. A case-control study
has been found infected to varying degrees in sev-
of the clinical diagnosis and course of Lassa fever.
eral regions in Africa afflicted with Lassa (Mc- Journal of Infectious Diseases 155: 445—55.
Cormick et al. 1987a,b). The infection in the rodent 1987b. A prospective study of the epidemiology and ecol-
is persistent, with virus in the urine a common fea- ogy of Lassa fever. Journal of Infectious Diseases 155:
ture. As epidemics occurred in other localities in 437-44.
Nigeria, Liberia, and Sierra Leone over the course of MMWR. 1983. Viral hemorrhagic fever: Initial manage-
several years, it became apparent that Lassa virus is ment of suspected and confirmed cases. Morbidity and

Mortality Weekly Report Supplement 32, No. 2S: 27S- dence time is only a matter of a few weeks. The other
39S. 95 percent is stored in bone for an extraordinarily
Murphy, Fred A., and S. G. Whitfield. 1975. Morphology long time, measurable in decades in the adult. If
and morphogenesis of arenaviruses. Bulletin of the absorption ceases, such lead will be leached slowly
World Health Organization 52: 409-19. from the skeleton over a period of many years, and is
Saltzmann, Samuel. 1978. La Figure de Lassa. Editions
then excreted through the kidneys. Lead may be
des Groupes Missionnaires. Annemasse, France.
Vella, Ethelwald L. 1985. Exotic new disease: A review of
transferred to the fetus via the placenta.
the emergent viral hemorrhagic fevers. United King- Methods of exposure to lead as well as the nature
dom Ministry of Defence. Section One: Lassa fever — of toxic episodes are discussed under History and
the multimammate rat disease. Geography.
For many decades the appellation "lead poisoning"
has referred to the clinically apparent symptoms
manifested by this metal's toxic effects on the intes-
VIII.77 tine, brain, and nerves. Before dealing with them in
Lead Poisoning detail, however, the less obvious effects of lead poi-
soning are noted briefly.
Lead can interfere with the physiology of almost
Lead poisoning (plumbism) is denned simply as the every body function. At "low" blood concentration
undesirable health effects induced by that metal. (less than 40 micrograms [/u.g] lead/100 ml blood [dl]),
Many of these, however, are "nonspecific"; that is, there is some evidence that it can impair intellectual
they are similar to or identical with symptoms and capacity development in children, an effect of poten-
signs produced by causes other than lead, and some tially greater significance for a population than the
of the toxic effects are so subtle they require labora- more overt symptoms usually associated with the
tory identification. This historical and geographic concept of lead poisoning. In the mouth, lead may
discussion concerns itself primarily with those overt combine with sulfur produced by local bacteria, pro-
effects obviously apparent upon even casual observa- ducing a linear, black precipitate on the gums suffi-
tion by nonmedical observers, which therefore are ciently apparent and unique to be of diagnostic value.
most likely to appear in the historical record. Princi- Episodes of intense lead exposure may cause tempo-
pal among these are abdominal colic, muscle paraly- rary arrest of long bone growth visible as a horizontal
sis due to lead-damaged nerves, and convulsions. band of radiodensity ("bone lead line").
Lead produces moderate anemia with resulting
Physiology facial pallor by poisoning enzymes necessary for the
Lead gains access to the human body principally formation of hemoglobin, the blood's principal oxy-
through the air we breathe and the substances we gen carrier. Lead excreted through the kidneys can
ingest. Residents of industrialized nations acquire poison the renal cells, eventually terminating in fa-
about half of their "body burden" of lead from pol- tal renal failure. Effects well documented in ani-
luted respired air. Healthy adults only absorb about mals, though less convincingly in humans, include
10 percent of ingested lead, but children may absorb suppression of gonadal function (with consequent
as much as half of the lead they eat or drink. Lead decreased fertility or sterility) as well as carcino-
absorption is enhanced by a low level of calcium in genic and teratogenic activity associated with in-
the diet. Lead may also be absorbed through the creased rates of abortion, stillbirth, and neonatal
skin. Prolonged applications of lead-containing sub- mortality.
stances such as poultices or cosmetics may result in The symptom of lead poisoning most commonly
health-threatening absorption of lead. encountered in the historical literature is abdominal
Absorbed lead is distributed throughout the body pain. Its cause is usually attributed to intestinal
by the blood. The human body's ability to excrete spasm, though the abdominal muscles may partici-
absorbed lead is so limited, however, that normal life pate in the painful, uncontrolled contractions usu-
activities in Western countries will produce lead ab- ally termed "colic." When they are severe and pro-
sorption in excess of the body's excretory capacity. longed, such affected individuals may be driven to
About 5 percent of unexcretable lead is deposited in desperate measures for relief. Similar pain may be
the liver, brain, and other viscera, where its resi- seen in the common forms of diarrhea, but that asso-

VIII.77. Lead Poisoning 821
dated with lead poisoning is accompanied by consti- Because circumstances leading to lead exposure are
pation, and hence the common reference to the ab- of anthropogenic origin, the prevalence of plumbism
dominal pain of lead intoxication as "dry bellyache." correlates with practices and traditions of lead use.
In individual cases such a state could be simulated Predictably, the geographic pattern of such episodes
by inflammation of the gallbladder, pancreas, or has varied with time.
stomach, and by stones in the kidney or bile pas- Although there are few recorded instances of ma-
sages, but these conditions neither would be accom- jor health problems due to lead in antiquity, some
panied by other symptoms or signs of lead toxicity, perspective on the extent of lead poisoning can be
nor would they affect large segments of a population gained by reviewing lead production records. Figure
or occupation. VIII.77.1 represents an approximation calculated by
Lead also has a destructive effect on nerves (pe- C. C. Patterson and others. Because galena is the
ripheral neuropathy), whose ability to transmit the most abundant form of natural lead ore in Europe
electrical impulses to the muscle is then reduced or and Asia, and because its very low solubility pro-
completely blocked, producing muscle paralysis. Pe- duces little toxicity for its miners, one could reason-
culiarly (and diagnostically) the nerves supplying ably surmise that lead poisoning probably was not
those muscles (extensors), which normally raise the common prior to the popularization of the smelting
wrist or foot, are especially commonly affected, caus- process about 3500 B.C.
ing the unique affliction of "wrist drop" (often The cupellation process, discovered about 3000
termed "the dangles" in the past) and "foot drop." B.C., permitted the separation of the small amounts
Serious disturbances of behavior leading to convul- of the commonly "contaminating" silver from the
sions, coma, and death are the most severe and much larger quantities of smelted lead, and was
feared of lead's effects. Children are notoriously followed by a substantial increase in lead production
more susceptible to such brain toxicity, and even a as a by-product of the pursuit of silver in the Mediter-
single episode of convulsions, when not fatal, often ranean area. We only speculate about the degree to
causes permanent, residual cerebral damage. Menin- which lead toxicity affected those involved in lead
gitis, tumors, trauma, and other diseases may result production in the Middle East and Mediterranean
in identical convulsive seizures, and their lead etiol- area during these periods, though the crude nature
ogy may be recognizable in the literature only of the furnace facilities must have exposed many to a
through their association with other features of lead toxigenic degree.
toxicity. Introduction of coinage during Greece's Classical
Finally it should be noted that lead poisoning may Period resulted in a phenomenal increase in silver
cause gout. This condition is due to the reduced (and therefore, lead) production, which was exagger-
ability of the lead-poisoned kidney to excrete uric ated by Roman exploitation to the point of ore ex-
acid, a product of normal protein metabolism. The haustion, leading to a marked reduction of that form
retained uric acid is frequently deposited in the soft of mining after the decline of the Roman Empire.
tissue, often near joints, resulting in exquisitely ten- Reference to lead intoxication can be found in the
der inflammation. The etiology of the renal toxicity various Greek and Roman writers of antiquity (de-
underlying most cases of gout is unknown, but when tails under History and Geography: Historical Antiq-
the kidney injury is caused by lead, it is known as uity). It was then not until the late Middle Ages that
"saturnine gout," in reference to the association of lead production rose again, this time in Europe, with
lead with that planetary god by the ancients. recognition of lead's utility now justifying its acquisi-
A rough correlation exists between the amount of tion for its own sake. Although the Spanish pursuit
lead in the blood and the presence of these various of silver in the New World was second only to that of
signs and symptoms. At lead levels below 40 /ig/dl, gold, the miners' mortality was largely due to factors
clinically evident effects are uncommon, but with other than poisoningfromlead in the ore, and heavy
progressively increasing concentrations above 80 metal toxicity during the silver extraction process
/xg/dl, symptoms become more probable. Many modi- was related primarily to the mercury used after
fying and influencing factors, however, give rise to 1570. It was the Industrial Revolution, with its enor-
diagnostic difficulties. mous surge in lead production, that was responsible
for the recurrent endemics in France, Italy, Spain,
Distribution and Incidence Germany, and especially Great Britain, and later,
The geographic distribution of lead poisoning is their New World colonies. Even so, the 80,000 tons of
global, but it is not of equal frequency everywhere. lead generated annually worldwide at the apex of

10*
c
o
10
Silver flndustrial
o 10 3 production 'evolution
* Exhaustion i n G«rmany|
c of Roman Spanish production
o
Figure VIII.77.1. World lead pro- lead mines of silver
10 2 Introduction
duction during past 5,500 years. Discovery of in New World
of coinage
[Adapted from Roger L. Boeckx. cupellation
1986. Report. Analytical Chemis- 10' Rise and fall Roman Republic
try 58 (February): 275A, reprinted of Athens and Empire
by permission from Analytical
Chemistry, 1986, American Chemi- 10° 5500 50D0 4500 4000 3500 3000 2500 2000 1500 1000 500
cal Society] Corrected " C (solar) years before present
Roman productivity has expanded exponentially to probably limited to the few people directly involved
reach more than 3 million tons worldwide today. in the smelting process.
With this exponential rise has come a staggering
degree of lead exposure in the populations of West- Historical Antiquity
ern nations. In Asia Minor, Cappadocian tablets record lead use
as an exchange item as early as the third millen-
History and Geography nium B.C. By 2000 B.C., not only had the smelting of
Because various cultures indulged in activities pro- lead ore (conversion to and extraction of metallic
ducing serious lead exposure in different periods, lead from the ore compounds) become common
this discussion focuses on those periods specifically knowledge, but also the process of cupellation - the
relevant to lead poisoning. separation of silver from the smelted lead —was
widely practiced, as shown by the use of silver as the
Prehistory principal unit of exchange in Susa, Persia, at that
By definition, this period contains no written record time. Old Testament Biblical references testify that
of lead intoxication, but some concept of the extent of lead had broad utilitarian applications and was
lead use and the degree of presumed lead exposure widely traded even prior to the Israelite departure
by its consumers is made available by the archaeo- from Egypt, though there are no comments on its
logical record. A few lead pieces from Iraq about negative health effects. Early dynastic Egyptians
5000 to 4500 B.C.; multiple lead items at the Troy I used lead for votive statuettes, net sinkers, and cos-
site; lead tumblers from Mesopotamian tombs; and metics. Mycenaeans exploited the later well-known
galena beads in predynastic Egyptian graves from mines at Lavrion near Athens and fashioned the
about 3500 to 3000 B.C.; lead pipes at Ur; leaded product into lead straps. Amulets and loom weights
glazes from Babylon; and leaded bronzes from Thai- from this period have been found in India. Surely
land between 2000 and 1500 B.C.-all imply an such widespread use of lead must have been accom-
active, working knowledge of lead smelting. Arti- panied by lead intoxication on occasion, at least
facts also reveal early experimentation with leaded among the industrial workers and users of certain
bronzes in China's ancient metallurgical centers in lead products including foodwares, but the record
the southwestern provinces by about 1700 B.C. remains silent on such matters, implying a probable
Skeletal lead analyses by several workers, such as failure of recognition of its toxic manifestations.
the study by Philippe Grandjean and others (1979) of Much of our knowledge about the use of lead in the
the Nubian population from as early as 3300 B.C., Greco-Roman period is related to the mines such as
demonstrate negligible quantities of lead stored in the one at Lavrion (called Laurium after the Roman
bone, suggesting that lead toxicity in this period was conquest) near Athens. The hilly terrain of the area

VHI.77. Lead Poisoning 823
is laced with intersecting veins of "argentiferous all its forms clearly exposed the majority of urban
galena," a lead sulfide ore including as much as 0.5 Romans to lead. Roman customs, however, probably
percent silver as a minor element. This silver was resulted in unequal exposure. Poor and middle-class
sought by the Athenians, who referred to Lavrion as citizens of Rome and other major communities closely
a "silver mine," even though they needed to separate shared ingestion of the lead-contaminated water de-
100 to 200 ounces of lead for each ounce of silver livered through the lead-lined aqueducts and pipes of
retrieved from the ore. This same silver was also one the public water systems. The wealthier class, how-
of the sources of Athens's wealth and power, for with ever, additionally contaminated their wine and food
it Themistocles built the navy that defeated the in- through the more extensive use of lead-lined contain-
vading Persians and established Athens as the pre- ers, expensive pewter tableware, and the food addi-
mier Mediterranean sea power. Similar mines were tives described above.
also operated on a number of Mediterranean islands, It is difficult to imagine that the health problems
Asia Minor, and the European continent. Mines associated with excessive lead ingestion had not
have been identified in Spain, France, Italy, and been recognized during this period, and references
Great Britain. Interestingly, the silver component of by contemporary authors indicate many were in-
ores in England and Wales was so low that these deed aware of them. The Greek physician-poet
were mined primarily for their lead content. Nicander is normally credited with the first, clear,
With the generation of huge quantities of metallic unequivocal description of plumbism in the second
lead as a by-product of the silver refinement process, century B.C., when he noted colic, constipation,
the obvious utilitarian value of lead was also ex- paralysis, and pallor resulting from the ingestion of
ploited. Applications included household tableware, the lead compounds litharge and cerusse. Lucretius
storage containers for oil and other fluids, encase- in the following century described "deadly exhala-
ment of iron bars to bind construction stones to- tions of gold and silver mines" and the pallor of
gether, sheathing for ships' hulls, coins, toys, stat- miners' complexions, calling attention to their
ues, bronze and pewter alloys, coffins, tablets, solder, "short life." The Roman architect Vitruvius, also in
and a thousand other purposes. During the three the first century B.C., cautioned that drinking
centuries of its peak production period, the Lavrion water from surface pools in the vicinity of lead
mine is estimated to have yielded over 2 million tons mines was apt to produce muscle cramps and gout.
of ore. The most intensive Roman use of lead related Pliny (first century A.D.) warned against the
to their water system. In addition to lining with deadly fumes of silver mines, calling attention to
sheet lead parts of their extensive aqueductal sys- their lethality by their effect on dogs and advising
tem and cisterns, Romans also rolled such sheets all exposed to such fumes to emulate the miners'
into tubular form and soldered them to produce and smelters' custom of tying an animal bladder
pipes through which the water was distributed. over their faces as a mask. Pliny also identified red •
An even more dangerous application of lead lay in lead as a deadly poison, whereas his contemporary
its use as a food or beverage container lining and, Celsus described an antidote to white lead. Vitru-
even worse, as a food additive. In the absence of vius additionally condemned the use of lead for
sugar, Romans used concentrated fruit juice, com- water conduits, noting that lead fumes poison the
monly grape, as a sweetening and flavoring agent blood, with consequent pallor as seen in lead
(sapa or defrutum). Such juice was concentrated by workers. Emperor Augustus prohibited the use of
boiling in lead-lined containers to avoid the undesir- lead for water pipes, though there is little evidence
able flavor imparted by copper. During the concen- of enforcement of his edict. One of the clearest
tration process lead was leached from the container descriptions of lead poisoning affecting large num-
by the acid fruit juice. Replications of this product bers of the population during late Roman times is
using original Roman recipes are reported to have that by Paul of Aegina, who described an epidemic
resulted in lead concentrations of up to nearly 800 of colic, lower limb paralysis, and epilepsy in Rome
milligrams per liter, about 16,000 times greater and elsewhere during the seventh century. S. C.
than the upper limit for potable water defined by the Gilfillan (1965) speculated that the well-docu-
U.S. Environmental Protection Agency! Eventually mented precipitous decline in numbers of the
Romans acquired such an addiction to the sweet Roman aristocracy during the century following
flavor of lead acetate that it was often made avail- A.D. 60 may have resulted from lead's toxic effects
able as an optional seasoning additive to wine. on fertility (noting that prohibition of wine drink-
This massive production and utilization of lead in ing by women of child-bearing age was lifted about

that time) and believes this may have been a major quantities when the 1703 Treaty of Methuen re-
factor in the decline of the Roman Empire. J. duced its price to less than that of the French prod-
Nriagu (1983) suggests further that lead-contami- ucts. The brandy used to fortify the natural wines
nated wine could explain the bizarre behavior of was often prepared in stills containing lead parts.
many Roman emperors and may be the cause of Such fortified wines are believed to have been re-
Celsus's comment that most of them suffered from sponsible for a concurrent frequency of gout so high
gout. Although some scholars of Roman history that this period is often called "the golden age of
regard the suggestions of Gilfillan and Nriagu as gout" in England.
extrapolations beyond available evidence, wine con- Two eighteenth-century workers - Sir George
sumption by the wealthy does appear to have Baker in England and L. Tanquerel des Planches in
increased during the imperial age, and conformity France — most clearly epitomize publicized recogni-
to contemporary suggestions for its preparation tion of lead ingestion and industrial exposure to lead
would have increased its lead content. as the etiology of specific symptom complexes. In the
region of Devonshire, England, an epidemic of ab-
The Industrial Revolution and Modern Europe dominal colic ("the colic of Devonshire") raged for
With the rapid increase in lead production during decades in the middle of the eighteenth century.
the Industrial Revolution and the explosive growth Occasional writers had noted its relationship to ci-
that followed, including the modern era of lead fuel der drinking, but its absence in the cider-producing
additives, the scene of lead poisoning shifted to the neighboring regions remained puzzling. In 1767,
European stage. During the sixteenth to the eigh- Baker, a Devonshire native, published his report
teenth and even into the nineteenth century, recur- now acknowledged as a milestone in the history of
rent waves of tardily recognized lead poisoning epi- lead poisoning. Baker established the feature that
demics swept the various continental countries and characterized the Devonshire colic: lead contamina-
the British Isles, frequently in temporally overlap- tion of the cider. He had traced the origin of the lead
ping inundations. Most of these were eventually to a type of millstone used in the cider's manufactur-
traced either to industrial exposure to lead or to ing process. The Devonshire millstones were unique
ingestion of lead-contaminated beverages or food. in that they were made in multiple segments bonded
The concept of industrial exposure as a cause of together by lead keys exposed on the stone's surface.
disease was crystallized for eighteenth-century phy- He also noted the custom of cider storage in lead-
sicians by the masterful studies so meticulously re- lined containers and the addition of lead to the cider
corded by Bernardino Ramazzini in 1700 (De Morbis as a flavoring and preservative agent. His publica-
Artificum Diatriba), although he was not the first to tion, clearly indicting lead as the epidemic's cause,
suggest it. His publications established the clear was followed by preventive practices and a gradual
relationship between certain diseases and occupa- subsidence of the epidemic.
tions. Among them were lead poisoning in miners, Similarly, for many decades in the eighteenth and
potters, and painters. early nineteenth centuries, Paris's Charity Hospital
The French epidemic of crampy abdominal pain had become famous for its treatment of patients with
termed the "colic of Poitou" began in 1572, but more the various "dry colic" syndromes. In 1839 Tanque-
than a century passed before the consumption of rel des Planches reported how he had studied these
lead-contaminated wine was identified as its etiol- patients' complaints, scoured their hospital charts,
ogy. A half-century-long endemic of abdominal colic and eventually demonstrated that most were en-
was initiated in Madrid about 1730. The suggestion gaged in an occupation involving unequivocal lead
that lead was its cause was not taken seriously until exposure. His detailed clinical observations included
1797, when the fact was made clear that its distribu- paralysis, encephalomalacia, and such a thorough
tion among the poor was due to their use of badly description of the other items comprising the lead
glazed lead food containers. In the middle of the poisoning syndrome that it can be used as a medical
eighteenth century, Theodore Tronchin realized the teaching exercise today.
"colica pictonum" in Holland constituted poisoning
from the use of water draining from lead roofs and The New World Colonial Period
from lead water pipes. The eighteenth and nine- There was hardly a pause in the spread of the Euro-
teenth centuries also were characterized by British pean colics before they also appeared in the Ameri-
importation of Portuguese port wine in prodigious can colonies. These settlers had arrived in the New

VIIL77. Lead Poisoning 825
World with a restricted hoard of tools and machin- through lead pipes into a lead-lined copper cauldron
ery; malleable lead could be and was employed to in the boiling-house (whose fumes would expose the
create substitutes for a myriad of items manufac- boiling-house workers), and stored in lead contain-
tured out of steel in Europe with consequent opportu- ers, to be distilled later into rum through a lead still.
nities for lead exposure. In addition, the lead-laden rum was used as a work
One such source exposure was the consumption of incentive with subsequent consumption in large
lead-contaminated liquor. The coiled condensation quantities of this lead-contaminated liquor by the
tube (usually called the "worm") of an alcohol still afflicted slaves.
was most easily fashioned out of lead. The distillation In 1745 Benjamin Franklin published Thomas
of fermented sugar products in such a still for rum Cadawaler's treatise on dry gripes in which the role
production caused sufficient lead leaching from the of lead was defined. This knowledge may have been
"worm" to render the rum toxic. By 1685, epidemics of carried to Europe by Franklin because Baker of De-
abdominal colic ("dry bellyache" or "dry gripes") were vonshire quoted Franklin in his well-known 1767
common in North Carolina and Virginia. Upon sug- article. By the mid-eighteenth century, knowledge
gestions from those consumers that their illness about the lead etiology of the dry bellyache was
might be the result of lead-contaminated New En- reaching Barbados. In 1788 John Hunter (Observa-
gland rum, Massachusetts protected its trade market tions on the Diseases of the Army in Jamaica) de-
with remarkable alacrity by enacting the Massachu- tailed dry gripes symptoms and specifically attrib-
setts Bay Law of 1723, prohibiting the use of lead uted them to lead. The condition gradually subsided
parts in a liquor distillation apparatus. Although the in the West Indies during the last quarter of the
law is often hailed as thefirstpublic health law in the century.
colonies, it should be noted there is no evidence of any Another common source of lead poisoning in colo-
serious, objective investigation regarding the role of nial America was houseware, especially those items
lead in the origin of the rum-drinkers' symptoms, nor used in the preparation, serving, or storage of food
does the medical profession seem to have been the and beverages. In England, expensive pewterware,
principal instigator for the law's passage. It appears some with more than 20 percent lead composition,
the legislators were responding primarily to cus- was the symbol of social and economic success, and
tomer complaints, motivated more by trade than by this was emulated in the colonies. Plates and goblets
health concerns. were commonly of pewter in the wealthier colonial
Both the continent and the West Indies had a homes; perishables such as milk, cream, or fruit
similar problem. Whereas slaves on North American juices were stored in lead-lined containers as were
continental plantations developed lead poisoning in- wine, drinking water, and other beverages. Indeed, in
frequently, the afflicted individuals on Caribbean such a wealthy home almost everything the family
island plantations included both Caucasians and ate or drank contained some lead. In a continental
black slaves. Barbados was especially affected, with plantation where access to such lead-contaminated
the literature from the latter seventeenth and much food was tightly controlled, Arthur Aufderheide and
of the eighteenth centuries replete with references colleagues (1981) could demonstrate that the extent
to "dry bellyache," clearly a clinical entity well of differential lead exposure had a socioeconomic ba-
known to both physicians and the laity but of unde- sis. The slave labor force of a 1670-1730 Virginia
termined cause. Jerome Handler and others (1986) plantation had no more lead in their bones than the
provided the chemical support for the diagnosis of average, modern North American does, but the skele-
lead poisoning in the slaves of a Barbadian popula- tons of their wealthy Caucasian masters contained a
tion from the eighteenth century by finding suffi- sixfold greater quantity. Colonists were also exposed
cient lead in their archaeologically excavated bones through their use of lead bottles, funnels, nipple
to predict that at least one-third of them probably shields, dram cups, candlesticks, lamps, pipes, roof
had had lead poisoning symptoms of moderate or gutters, and many other items.
greater severity. Mining also claimed its colonial victims. The east-
The reason for high bone lead values in island ern American mines were largely of the poorly sol-
plantation slaves in contrast to those on continental uble galena ore and generated little morbidity. It
plantations lay in the nature of the product: sugar in was in the western Utah mines, whose ore was pre-
the islands; cotton, fruit, or tobacco on the continent. dominantly lead carbonate, that lead poisoning
The sugar was collected in lead-lined tubs, ducted reached epidemic proportions, with many thousands

of miners suffering from plumbism between 1870 ible utility. No other metal is so easily extracted
and 1900. from the soil and so readily fashioned into unlimited
numbers of needed items. In every age, however,
The Present Era writers sounding the warning of its toxic hazards
Even though we have a more sophisticated under- were ignored or decried. Reasons for such resistance
standing of lead poisoning today, our ongoing use of remain enigmatic.
lead seems to provide new opportunities for expo- It may be that the nonspecificity of the lead intoxi-
sure. Lead encephalopathy acquired by infants nurs- cation syndrome confused earlier diagnosticians be-
ing at the breasts of mothers using lead-containing cause other conditions can simulate some of lead's
cosmetics constituted the fourth most common, fatal, toxic effects. The mine fumes that several Greco-
pediatric malady in Manchuria in 1925. A poisoning Roman period authors held responsible for lead min-
episode from lead fumes occurred in a Baltimore ers' health problems were perhaps the obvious and
neighborhood in 1933 when poor families there unpleasant sulfur dioxide odors emitted by galena
burned discarded battery casings as cheap fuel. Un- ore rather than by lead compounds. Yet Pliny even
til C. C. Patterson (1982) called attention to it re- complained specifically that the practice of "adul-
cently, lead solder was used to seal many food cans. terating" wine (adding lead to improve the flavor)
The common practice of pica (dirt eating), partly produces nerve injury manifested by paralyzed, dan-
biological and partly cultural in origin, has become gling hands. His contemporary, the physician Dios-
especially dangerous for children playing in yards corides, clearly described colic and renal failure re-
whose soils are badly contaminated from inner-city sulting from drinking the lead oxide compound
factory and vehicle-exhausted lead. Chips of lead- called litharge. Most ancient miners were slaves
laden, old paint peeling from their aging houses whose ailments may not have been treated by physi-
constitute a toxic time bomb for the very young. cians. It is, of course, possible that Romans were not
Many surviving victims of childhood lead poisoning exposed to as much lead as we presume today and
in Australia were found to suffer failure of lead- that a lack of concern by Roman physicians simply
poisoned kidneys several decades later. A 1910 reflects a low frequency of lead poisoning in ancient
American pharmacopoeia still listed both a variety times. This can be evaluated objectively only by lead
of therapeutic lead compounds and antidotes to lead analysis of appropriately selected ancient bones. To
poisoning! There is probably no purer example of the date, some of Waldron's (1982) Romano-British ceme-
price exacted by historical ignorance than the tery excavation studies have revealed elevated bone
plumbism rampant among the modern illicit liquor lead values, but further investigations on Italian
producers ("moonshiners") using lead-containing dis- samples with sharply defined socioeconomic status
tillation units (automobile radiators soldered with of the studied individuals will be needed to resolve
lead) in the United States today. this question.
American lead production peaked about 1975, Perhaps even more relevant is the fact that during
with at least half of it converted into automobile fuel most of history the cause-and-effect relationship be-
additive. Recent partial control of automobile ex- tween a specific agent like lead and a specific symp-
haust fumes has been accompanied by a 37 percent tom was only vaguely appreciated by physicians
reduction in average blood lead levels in Americans. whose theoretical concepts did not readily embrace
Statistical data for lead poisoning are difficult to such an association. More concerned with the balance
acquire, but in the United States, 831 adult deaths of postulated body humors, they were apt to attribute
could be identified between 1931 and 1940; whereas a broad range of symptoms to general environmental
in England, Tony Waldron (1982) describes a reduc- (often climatic) disturbances. Even nineteenth-cen-
tion from about 115 deaths annually in 1900 to only tury French naval surgeons accepted lead as the etiol-
an occasional few by 1960. In view of the known ogy of the lead poisoning syndrome but rejected it as
diagnostic inefficiency of lead poisoning, these are the cause of an identical symptom complex in their
surely minimal figures. tropical sailors. They attributed it instead to the ef-
fect of high tropical temperatures, thus delaying rec-
Prevention and Control ognition of its true origin in their custom of shipboard
For many centuries, humanity's flirtation with lead food storage in lead containers.
frequently has been its undoing. Its romance with Surely, lack of a system for regular publication
this pedestrian metal has been inspired not by any and wide dissemination of medical knowledge also
gemlike allure it possesses but, rather, by its irresist- contributed to delay in grasping the etiology of lead

VIII.78. Legionnaires' Disease 827
poisoning. As early as 1656, Samuel Stockhausen, a Patterson, Clair C. 1982. Natural levels of lead in humans.
physician to the lead miners of northern Germany, California Environment Essay, Ser. 3, Institute for
published his realization that their affliction was Environmental Studies, University of North Carolina.
the toxic effect of the lead ore they mined. Forty Chapel Hill.
years later, that observation led his south German Stockhausen, Samuel. 1656. Libellus de lithargyrii fumo
colleague, Eberhard Gockel, to recognize lead con- noxio morbifico, metallico frequentiori morbo vulgo
ditto Die Huettenkatze. Goslar.
tamination of wine as the cause of an identical prob- Waldron, H. A., and D. Stofen. 1974. Subclinical lead
lem in his clerical patients, and it was to be more poisoning. London.
than another century (and many more "colic- Waldron, Tony. 1982. Human bone lead concentrations. In
demics") before the translation of Stockhausen's re- Romano-British cemeteries at Circencester, ed. Alan
port into French enabled Tanquerel to identify the McWhirr, Linda Viner, and Calvin Wells, 203-4.
same problem at Paris's Charity Hospital. Circencester, England.
Josef Eisinger (1982) has noted the recurring need
throughout most of Western history for governments
to enact legislation restricting the population's expo-
sure to lead. Serious and major efforts to reduce lead
exposure, such as the 1971 Lead-Based Poisoning
Prevention Act in the United States and more recent
legislation involving lead air pollution by automo- VIII.78
biles, are phenomena primarily since the 1970s. The Legionnaires' Disease
history of the past two millennia, however, suggests
that our knowledge of lead's potential hazards will
not prevent at least some continuing problems with Legionnaires' disease is an acute infection of hu-
its health effects. mans, principally manifested by pneumonia, that
Arthur C. Aufderheide occurs in a distinctive pattern in epidemics and is
caused by bacteria of the genus Legionella. Typically
Bibliography the incubation period - the interval between expo-
Aufderheide, A. C , et al. 1981. Lead in bone II. Skeletal- sure to the bacterium and the onset of illness - is 2
lead content as an indicator of lifetime lead ingestion to 10 days, with an average of 5 to 6 days, and the
and the social correlates in an archaeological popula- attack rate - the proportion of people exposed to the
tion. American Journal of Physical Anthropology 55: bacterium who become ill - is less than 5 percent.
285-91. Without specific antibiotic treatment, 15 percent or
Boeckx, Roger L. 1986. Report. Analytical Chemistry more of the cases are fatal, although the percentage
58(2): 275A. of fatal cases rises sharply in immunosuppressed
Eisinger, J. 1982. Eberhard Gockel and the colica Picto-
patients.
num. Medical History 26: 279-302.
Gifillan, S. C. 1965. Lead poisoning and the fall of Rome.
Legionnaires' disease is one form of presentation
Journal of Occupational Medicine 7: 53-60. of Legionella infections, which are generally re-
Gockel, Eberhard. 1697. Eine curiose Beschreibung dess ferred to by the umbrella term legionellosis. Another
An 1694.95 und 96 durch Silberglett versussten sau- distinctive clinicoepidemiological pattern of legionel-
ren Weins. ... Ulm. losis is Pontiac fever. Pontiac fever affects 45 to 100
Grandjean, Philippe, O. Vag Nielson, and Irving M. Sha- percent of those exposed and has an incubation pe-
piro. 1979. Lead retention in ancient Nubian and con- riod of 1 to 2 days. Pneumonia does not occur, and all
temporary populations. Journal of Environmental Pa- patients recover. More than 20 species of Legionella
thology and Toxicology 2: 781-7. have been identified, 10 of which are proven causes
Handler, J. S., et al. 1986. Lead contact and poisoning in of legionellosis in humans. The most common agents
Barbados slaves: Historical, chemical, and biological of human infection are Legionella pneumophila, Le-
evidence. Social Science History 10: 399-425.
gionella micdadei, Legionella bozemanii, Legionella
Hirsch, August. 1883-6. Handbook of geographic and his-
torical pathology, 3 vols. London.
dumoffii, and Legionella longbeachae.
McCord, C. P. 1953.1954. Lead and lead poisoning in early Legionellae are distinguished from other bacteria
America. Industrial Medicine and Surgery 22: 393-9, in being weakly staining, gram-negative, aerobic
534-9, 573-7; 23: 27-31, 75-80,120-4,169-72. rods that do not grow on blood agar or metabolize
Nriagu, J. 1983. Lead and lead poisoning in antiquity. New carbohydrates, and have large proportions of
York. branched-chain fatty acids in their cell walls and ma-

jor amounts of ubiquinones with more than 10 iso- (such as corticosteroids) or underlying illness. Noso-
prene units on the side chain. comial (hospital-acquired) legionellosis is an impor-
tant problem, probably because particularly suscepti-
ble people are gathered in a building with water
systems that Legionella can contaminate.
Legionellosis is easily overlooked, but has been
Few children have been shown to have legion-
found essentially wherever it has been sought. The
ellosis, but one prospective study showed that one-
weak staining of Legionella and its failure to grow
on the usual bacterial diagnostic media allowed it to half developed serum antibodies to L. pneumophila
be missed for many years in the evaluation of per- before 4 years of age, indicating that inapparent
sons with pneumonia. Once the right combination of infection may be common, at least at that age. In
staining and other diagnostic culture procedures contrast, studies of adults during Legionnaires' dis-
ease outbreaks have generally shown that fewer
was identified, Legionella was found to cause 1 to 2
percent of the pneumonia cases in the United States, than one-half of the Legionella infections are
inapparent.
or perhaps 25,000 to 50,000 cases annually.
Legionellosis can occur throughout the year but is
Formal surveys of the incidence of legionellosis
most common from June through October in the
have not been done in most countries, but large
Northern Hemisphere. The summer season predomi-
numbers of cases have been identified in Great Brit-
nates even in outbreaks unrelated to air-conditioning
ain and several European countries, and cases have
systems, but whether warmer weather causes the
been reported on all continents.
bacteria to nourish or, rather, humans to increase
contact with their environment is not known. The
Epidemiology and Etiology fact that most bacterial and viral pneumonias are
Legionellae live in unsalty water and are widely dis- most common in the winter makes the seasonality of
tributed in nature. They thrive particularly well at or legionellosis one clue in diagnosis. Legionellosis does
slightly above human body temperature, and thus not seem to spread from one person to another.
are commonly found on the hot water side of potable Travel and certain occupations put people at in-
water systems and in the recirculating water in cool- creased risk of legionellosis. Several outbreaks have
ing towers and other heat exchange devices. occurred in tourist hotels, and a disproportionate
The various ways in which Legionellae can go number of sporadic cases are in people who recently
from their watery environment to infect humans are have traveled overnight. Disease caused by Le-
not all worked out, but one method is clear. Aerosols gionella and serologic evidence of previous Le-
created by some mechanical disturbance of contami- gionella infection are more common in power plant
nated water, such as in the operation of a cooling workers who have close exposure to cooling towers.
tower, can on occasion infect people downwind. It is Other outbreaks have occurred in people who used
likely that, after the aerosol is generated, the drop- compressed air to clean river debris out of a steam
lets of water evaporate, leaving the bacteria air- turbine condenser, and in workers exposed to aero-
borne. Once airborne, they can travel a considerable sols of contaminated grinding fluid in an engine
distance, be inhaled, and then be deposited in the assembly plant.
lungs. Potable water systems also can act as the Legionellosis outbreaks can be stopped by turning
source of legionellosis outbreaks, but it is not known off the machinery that is making infectious aerosols,
whether this occurs through aerosols (as might be disinfecting that machinery, and heating or rechlor-
generated by sinks, showers, or toilets), by coloniza- inating contaminated drinking water. Several chemi-
tion of the throat and then aspiration into the lungs, cal additives that are used in the routine mainte-
by direct inoculation (as into the eye or a wound), or nance of cooling towers and evaporative condensers
by ingestion. can limit the growth of Legionella if used in combina-
Many outbreaks have been recognized, but most tion with regular cleaning. Certain rubber materials
cases occur individually (or sporadically). The risk of used in plumbing washers seem to provide nutrients
Legionella pneumonia (including Legionnaires' dis- for Legionella; using different components may help
ease) increases with age and is two to four times prevent legionellosis associated with drinking wa-
higher in men than in women. No racial predisposi- ter. Maintaining a temperature of 60°C on the hot
tion has been seen. Cigarette smokers are more sus- water side of institutional plumbing systems has
ceptible, as are people whose cellular immune sys- stopped some legionellosis outbreaks by lowering
tem is compromised — for example, by medication the concentration of Legionella sharply.

Immunology Bellevue Stratford Hotel. Within days of the end of
Legionella organisms live inside cells of all types, the convention, reports began to reach Legion head-
from various protozoa and freshwater amoebae in the quarters of conventioneers who had developed pneu-
external environment to various phagocytic cells in monia and died. A massive investigation, begun on
the human body. Given the location of Legionella in- August 3, uncovered 221 cases in Legionnaires who
side cells, it might be expected that cell-mediated im- had attended the convention and others who had
munity is more important than humoral (antibody- been in or near the headquarters' hotel. The earliest
mediated) immunity, and such seems to be the case in case had its onset on July 20, the peak occurrence
legionellosis. extended from July 24 through August 1, and de-
This may explain why people with defective cellu- creasing numbers of cases continued through Au-
lar immunity are particularly susceptible to le- gust 16. Ninety percent of those who became ill
gionellosis and why so few people exposed in an developed pneumonia, and 16 percent died.
epidemic of Legionnaires' disease become sick even Diagnostic tests for all known agents of pneumo-
though usually fewer than 20 percent (and often nia, infectious and otherwise, were negative. The
fewer than 5 percent) have preexisting elevations of epidemiological investigation suggested airborne
titers of specific antibody to Legionella. spread of the agent, because risk of "Legionnaires'
disease," as the press had dubbed it, increased with
Clinical Manifestations and Pathology the amount of time spent in the lobby of the hotel
Two distinct clinical and epidemiological syndromes and on the nearby sidewalk, but was unrelated to
of legionellosis have been identified: Legionnaires' contact with other sick people or animals, eating, or
disease and Pontiac fever. Legionnaires' disease is a participation in specific events at the convention.
multisystem disease, characterized by pneumonia, Those who drank water at the Bellevue Stratford
high fever, chills, muscle aches, chest pain, head- had a higher risk than others, suggesting the possi-
ache, diarrhea, and confusion. Chemical evidence of bility of a waterborne agent, but 49 of the cases had
involvement of the liver and kidneys may also be only been on the sidewalk outside and had drunk no
found. Pneumonia usually worsens over the first water there.
week of illness and resolves gradually thereafter. The outbreak received considerable notoriety and
Without specific antibiotic therapy, the disease is prompted a congressional investigation. The failure
fatal in about 15 to 20 percent of otherwise healthy to find immediately the agent led to much public
people, and in up to 50 percent of those with compro- speculation about toxic chemicals and sabotage, but
mised cellular immunity. It is not readily distin- the answer came through the more usual route of
guished on clinical observation alone from several persistent scientific work.
other forms of bacterial pneumonia. In August, Joseph McDade, who worked on rickett-
Pathological changes are usually confined to the sia at the U.S. Public Health Service Centers for
lungs, which often show a pattern of lobar pneumo- Disease Control, had tested specimens from Legion-
nia. Air sacs (alveoli) are filled with macrophages, naires for evidence of rickettsia by inoculating lung
other inflammatory cells, and fibrin. With the specimens into guinea pigs and, if the animals died,
proper stain, large numbers of Legionella can be putting tissue from them into embryonated eggs.
seen, mostly in the macrophages. The trachea and The experiments were complicated by what seemed
larger airways are generally spared, which may ex- to have been some bacterial contamination, but over-
plain the relative lack of sputum in most cases and all the results appeared clearly negative. In late
the lack of contagiousness. November, McDade received a draft report of the
Pontiac fever is characterized by fever, chills, mus- status of the investigation to that point. He noted
cle aches, and headache. Cough and chest pain are that the liver was involved in many of the cases, a
much less common than in Legionnaires' disease, fact that was reminiscent of Q fever, the rickettsial
and no cases have pneumonia. Victims are very ill infection most commonly associated with pneumo-
for 2 to 7 days, but all recover. nia. After mulling upon that coincidence, he re-
turned to his laboratory over the Christmas holidays
History and Geography to reexamine the specimens from his August experi-
From July 21 through 24, 1976, the Pennsylvania ments. After some hours, he came across a cluster of
Department of the American Legion, a fraternal or- what looked to be large rickettsiae or small bacteria
ganization of military veterans, held its annual in a section of liver from a guinea pig that had been
meeting in Philadelphia, with headquarters in the inoculated with lung tissue from a fatal case of Le-

gionnaires' disease. Repeating the inoculation of could be recovered from the stored lung tissue of
eggs, he was able to grow these organisms in the guinea pigs that had been exposed, unprotected, to
yolk sacs. Using the infected yolk sac suspension as the air in the health department building or to the
the antigen in an indirect fluorescent antibody (IFA) evaporative condenser water. Thus a very different
test, he was then able to show that the serum col- disease-both epidemiologically and clinically-
lected during the field investigation from patients was shown to be caused by a bacterium which, to
who had recovered from Legionnaires' disease (but this day, cannot be distinguished from the one that
not that from unaffected people) had sharply rising caused Legionnaires' disease.
titers of specific antibody to the yolk sac organism - Within a few weeks of the isolation of L. pneu-
indicating convincingly that this (which has since mophila in embryonated eggs, Robert Weaver found
become known as Legionella pneumophila) was the a way to grow it on agar plates. Subsequent improve-
causative agent. ments led to the development of charcoal yeast ex-
In the 11 years before the Legionnaires' disease tract agar, which greatly facilitates the isolation of
outbreak, the Centers for Disease Control had inves- Legionella.
tigated two other large epidemics of respiratory dis- Investigations of legionellosis proceeded both for-
ease for which an agent had not been found. One, in ward and backward in time. In the summer of 1977,
1965, had involved 81 patients at St. Elizabeth's outbreaks of Legionnaires' disease were quickly rec-
Hospital, a psychiatric institution in Washington, ognized in Vermont, Ohio, and Tennessee. In 1978
D.C. John V. Bennett, the epidemiologist who had an outbreak of 44 cases at a hospital in Memphis,
led the original St. Elizabeth's investigation, commu- Tennessee, started shortly after afloodknocked out
nicated to the author in the early fall of 1976 that he the usual cooling tower, and required turning on an
was certain that the two outbreaks were caused by auxiliary that had been out of use for 2 years. Cases
the same agent. Fortunately, serum specimens from clustered downwind from the auxiliary cooling
the St. Elizabeth's outbreak had been stored at the tower but stopped occurring 10 days after it was shut
Centers since 1965. When tested in early January of off. L. pneumophila was isolated from both patients
1977, they unequivocally proved Bennett right. and the cooling tower water, confirming the epi-
In 1968, a remarkable outbreak of a severe, self- demiological evidence that Legionnaires' disease,
limited illness involved 95 of 100 employees in a like Pontiac fever, could be caused by L. pneumo-
health department building in Pontiac, Michigan. phila contamination of heat-rejection devices in air-
Some of the investigators from the Centers for Dis- conditioning systems.
ease Control succumbed also, but only those who en- But air conditioning systems were not the whole
tered the building when the air conditioning system answer. Public health authorities in Scotland and
was turned on. Guinea pigs were placed in the build- Spain were investigating a series of pneumonia
ing without any protection, with antibiotic prophy- cases acquired by Scottish visitors to a hotel in
laxis, or in an isolator that filtered the air, and then Benidorm, Spain, over several seasons. The hotel
were killed to look for evidence of pneumonia or other was not air-conditioned, but the cases proved to be
ill effects. Inspection of the air conditioning system Legionnaires' disease. It would be some time before
showed two major defects. The exhaust from the the source was found.
evaporative condenser discharged on the roof just a Other previously "unsolved" outbreaks were
few feet from the fresh air intake. In addition, the found to have been legionellosis. In 1973, all 10 men
exhaust duct and a horizontal chilled air duct that involved in cleaning a steam turbine condenser at a
was adjacent to the exhaust duct had defects that power plant on the James River in Virginia had
allowed water droplets from the exhaust to puddle in developed what in retrospect seemed to have been
the chilled air duct. Water recirculating in the evapo- Pontiac fever. Testing of stored serum specimens
rative condenser was aerosolized (with or without confirmed this. An outbreak of 78 hospitalized cases
prior attempts to sterilize it) in laboratory tests to of pneumonia in Austin, Minnesota, in the summer
expose guinea pigs in an attempt to induce disease. of 1957 had been investigated at the time. Although
When materials from the 1968 investigation of the records had been preserved, the serum speci-
Pontiac fever were used in the tests that succeeded mens had been lost in a refrigeration mishap. Survi-
for Legionnaires' disease, scientists were intrigued vors were recontacted in 1979, and they and the
to find positive results. Not only did people recover- appropriate controls were bled to confirm the diagno-
ing from Pontiac fever show rising titers of specific sis of Legionnaires' disease in what is to date the
antibody to L. pneumophila, but also L. pneumophila earliest documented epidemic of legionellosis.

In 1979 reports began to appear of agents, some of associated bacteria widely distributed in nature,
which caused pneumonia, that resembled the L. causing pneumonia in humans when particularly
pneumophila type strain in some ways but were susceptible people are exposed by aerosols, or per-
clearly distinct. McDade and colleagues isolated an haps otherwise, to contaminated water. The pres-
organism on artificial media that Hugh Tatlock had ence of running hot water and other thermal pollu-
recovered in 1943 by inoculating into guinea pigs tion, often from industrial processes, favors its
blood from a soldier at Fort Bragg, North Carolina, growth, suggesting that legionellosis may be ex-
who seemed to have a case of "pre-tibial fever," an pected to be particularly common in the developed
illness subsequently shown to be caused by Lepto- world. However, the disease appears to be worldwide
spira. Later that year, A. William Pasculle and colin its distribution.
leagues isolated the "Pittsburgh pneumonia agent" David W. Fraser
in embryonated eggs but could not grow it in artifi-
cial media. Subsequently, the Tatlock organism and Bibliography
the Pittsburgh pneumonia agent were shown to be Balows, Albert, and David W. Fraser, eds. 1979. Interna-
the same, and were named L. micdadei. tional symposium on Legionnaires' disease. Annals of
McDade and colleagues also grew the OLDA Internal Medicine 90: 489-703.
strain on artificial media. OLDA was another organ- Brenner, Don J. 1986. Classification of Legionellaceae:
ism that resembled a rickettsia and had originally Current status and remaining questions. Israel Jour-
been isolated in 1947 by E. B. Jackson, by inoculat- nal of Medical Sciences 22: 620-32.
ing a guinea pig with blood from a patient with fever Broome, Claire V., and David W. Fraser. 1979. Epidemio-
of unknown origin. When characterized in 1979, it logic aspects of legionellosis. Epidemiologic Reviews
1: 1-16.
turned out to be L. pneumophila. It remains the
Dondero, Timothy J., Jr., et al. 1980. An outbreak of Le-
earliest documented isolate of that species. gionnaires' disease associated with a contaminated
In 1959 F. Marilyn Bozeman and colleagues iso- air-conditioning cooling tower. New England Journal
lated a rickettsia-like organism in guinea pigs from of Medicine 302: 365-70.
a navy man who developed pneumonia after practic- Edelstein, P. H. 1987. Laboratory diagnosis of infections
ing with scuba gear in freshwater swimming pools. caused by legionellae. European Journal of Clinical
Lester G. Cordes and colleagues isolated it on artifi- Microbiology 6: 4-10.
cial media in 1979 and showed that it was distinct England, A. C , and D. W. Fraser. 1981. Sporadic and
from L. pneumophila. It was subsequently named L. epidemic nosocomial legionellosis in the United
bozemanii. States. American Journal of Medicine 70: 707-11.
Another line of discovery first reported in 1979 Fisher-Hoch, S. P., M. G. Smith, and J. S. Colbourne. 1982.
had important consequences in defining the biology Legionella pneumophila in hospital hot water cylin-
of Legionella. George K. Morris and his colleagues ders. Lancet 2: 1073.
Fraser, David W., et al. 1977. Legionnaires' disease: De-
reported the recovery of L. pneumophila from envi- scription of an epidemic of pneumonia. New England
ronmental water specimens, collected in the course Journal of Medicine 297:1189-97.
of investigation of outbreaks of Legionnaires' dis- Glick, Thomas H., et al. 1978. Pontiac fever. An epidemic
ease. This quickly led to the discovery that Le- of unknown etiology in a health department: I. Clini-
gionella organisms were widespread in nature, and cal and epidemiologic aspects. American Journal of
could be found in about one-half of cooling towers. It Epidemiology 107: 149-60.
also, for example, led to the discovery of additional Kaufmann, Arnold F , et al. 1981. Pontiac fever: Isolation
Legionella species, not previously recognized to of the etiologic agent (Legionella pneumophila) and
cause human disease. demonstration of its mode of transmission. American
In 1980, John O. H. Tobin reported the first isola- Journal of Epidemiology 114: 337-47.
tion of Legionella from potable water systems, as Kirby, B. D., et al. 1980. Legionnaires' disease: Report of
sixty-five nosocomically acquired cases and review of
part of an investigation of two kidney transplant
the literature. Medicine 59: 188-205.
patients who acquired Legionnaires' disease while McDade Joseph E., et al. 1977. Legionnaires' disease: Isola-
in the same hospital room in England. Subsequent tion of a bacterium and demonstration of its role in
studies in hospitals in England and in the United other respiratory diseases. New England Journal of
State showed the importance of such systems as the Medicine 297: 1197-1203.
sources for dissemination of Legionella. Shands, Kathryn N., et al. 1985. Potable water as a source
As these studies were reported, the picture of Legionnaires' disease. Journal of the American
emerged of Legionella as a group of freshwater- Medical Association 253:1412-16.

Thornsberry, Clyde, et al., eds. 1984. Legionella: Proceed- Epidemiology and Etiology
ings of the 2nd international symposium of the Ameri- All forms of leishmaniasis are zoonoses transmitted
can Society for Microbiology. Washington, D.C. to human beings from wild or domestic animals via
the sandfly (usually Phlebotomus). The leishmanial
form of the parasite lives in reticuloendothelial cells
of the mammalian host where it divides by binary
fission to destroy the host cell. The parasites are
VIII.79 taken up by the sandfly while feeding on the skin of
the host, and in the insect's intestine they develop
Leishmaniasis into leptomonad forms. These divide, producing enor-
mous numbers, and work their way to the pharynx
and buccal cavity. There is a natural restriction of
Leishmaniasis is primarily a skin disease produced individual leishmaniae to specific sandflies, even
by a number of different species of protozoa (genus though a wide variety of these insect species may be
Leishmania). The disease occurs in three basic clini- available.
cal forms, each of which has several variants caused Cutaneous leishmaniasis is caused by several
by different species, subspecies, or strains of the members of the Leishmania tropica species complex.
pathogen. The intermediate host is the sandfly. All produce chronic skin lesions, which tend to ulcer-
ate. Some forms tend to be "urban" and closely
Distribution and Incidence linked to dogs as alternating hosts. Others are "ru-
Cutaneous leishmaniasis (often called "oriental ral," with nonhuman reservoirs including various
sore") is found in Armenia, Azerbaijan, Turkmeni- rodents, marsupials, and foxes. In the Americas,
stan, Uzbekistan (republics of the former Soviet sandflies of the genus Lutzomyia are often vectors.
Union), Afghanistan, India, Iran, much of the Mid- The initial lesion usually heals spontaneously, but
dle East and North Africa, the Sahara, the savanna often leaves a disfiguring scar.
states from Sudan to Senegal, and in Kenya and Mucocutaneous leishmaniasis is caused by Leish-
Ethiopia. In the New World, species of Leishmania mania braziliensis. In the form known as espundia
cause various clinical forms of the disease in Central in Brazil, the initial lesion develops into an infec-
America, the Amazon Basin, the Guyanas, and the tion of the mucosal tissues of the nose and mouth,
Andes, especially Venezuela and Peru. In eastern resulting in gross deformities and sometimes death
South America a form of the disease mainly afflict- from secondary infections. Lutzomyia flies are the
ing children extends from Argentina to Venezuela major vectors. (A clinically similar form, believed
and north through Central America to Mexico. to be caused by L. tropica, has been described in
Mucocutaneous leishmaniasis is restricted to the Ethiopia.)
New World and occurs in Brazil, eastern Peru, Para- Visceral leishmaniasis, or kala-azar, is caused by
guay, Ecuador, Colombia, and Venezuela. at least three members of the Leishmania donovani
Visceral leishmaniasis is found in India, Burma, complex. In visceral leishmaniasis, unlike other
Bangladesh, China, Thailand, Somalia, Chad, Ke- forms of the disease, the organisms parasitize reticu-
nya, Gabon, Sudan, and Niger. A variant occurring loendothelial cells beyond the subcutaneous and
primarily among children is spread over southern mucosal tissue, and a number of internal organs
Europe, North Africa, and the Middle East as well as may be involved. Symptoms include swelling of the
Romania and the southern part of the former Soviet liver and spleen, fever, diarrhea, emaciation, ane-
Union. mia, darkening of the skin, and gross abdominal
As a result of high levels of disease in rodent and enlargement. Mortality in untreated cases has
dog populations, leishmaniasis is so common in en- reached 75 to 95 percent over a 2-year period.
demic areas that it leaves its mark on every inhabit-
ant. Recent estimates indicate that some 12 million Clinical Manifestations and Pathololgy
individuals have one form or another of this infec- Old World cutaneous leishmaniasis has an incuba-
tion. Thus leishmaniasis can be regarded as second tion period of 6 weeks to a year, depending on the
in importance only to malaria among the protozoal species of Leishmania. The lesions may be multiple,
diseases of humans. Although the mortality is low and it is thought that they are the result of multiple
for the skin disease, it is almost always fatal for bites. There is much local induration and possible
kala-azar, an organ variant. lymphatic spread to the regional lymph nodes. Heal-

VIII.79. Leishmaniasis 833
ing is slow, with the formation of scar tissue in a

year or so.
The New World disease takes several different
forms:
1. A self-limiting ulcer of 6 months' duration with-
out metastases, caused by Leishmania tropica
mexicana, is found in the Yucatan. It has a rodent
reservoir in flat, low, rain forests. Figure VIII.79.1. The uta form of leishmaniasis.
2. Espundia, due to L. braziliensis, exists in the jun-ously to malaria, Malta fever, and other diseases. It
gles of Panama through Amazonia to Paraguay. It was in 1900 that W. B. Leishman, working at Net-
starts as a painless ulcer and metastasizes to the tley, noticed the similarity of the parasite to that of
oronasal or anorectal area in 5 to 23 years. The trypanosomiasis, and shortly thereafter Leishman's
host is thought to be the paca (Cuniculus paca), a bodies were discovered to be the cause of kala-azar.
nocturnal American rodent. Leishman published his findings in 1903, yet his
3. A solitary ulcerative lesion known as uta, usually work was duplicated independently by Charles Dono-
found at the base of the nose with no metastasis, van. Leishman's name was given to the entire ge-
exists in the Andean valleys of Peru and Argen- nus, but the agent of kala-azar got its specific name
tina. The agent is Leishmania peruviana, and the from Donovan.
host is the dog. Old World leishmaniasis or oriental sore had long
4. Leproid leishmaniasis is seen in Venezuela. It be- been in northern Africa and India, where it was
gins as a fleshy cutaneous nodule that slowly known geographically as the Delhi boil, Aleppo boil,
spreads over the body without ulcerating and is and so forth. Its agent, L. tropica, was probably seen
difficult to distinguish from leprosy. It is thoughtas early as 1885, but the first clear description was
to be due to an immune response and is very not published until 1898, by Peter Fokitsch Borov-
chronic. sky in a Russian military journal. However, the pa-
In the absence of demonstrable leishmania, reli- per did not become known to the West, and thus
ance rests on the leishmanin skin test, which is posi- credit for the discovery of the organism is often
tive in cutaneous disease when there is a tuberculoid given to James Homer Wright of Baltimore, who in
histology. Generally it becomes positive early and 1903 found it in an ulcer of a child from Armenia.
remains so after healing is complete. Although most The first cases of cutaneous disease in the Ameri-
lesions are self-limiting, antimony, pyrimethamine, cas were described by A. Carini and V. Paranhos in
and amphotericin B are used to treat metastases. A southern Brazil in 1909 - the same year that muco-
persistent positive serology is an important sign of cutaneous leishmaniasis was described as a distinct
continued survival of the parasite, which may live disease, this also in Brazil. Gasper Oliveira de
for decades in asymptomatic individuals. Vianna named the etiologic agent Leishmania bra-
ziliensis in 1911. The visceral form in the Americas
History and Geography was first seen in Paraguay in 1913. Phlebotomus was
Leishmaniasis is an ancient disease of both the Old suspected of being the vector as early as 1911, but
and the New Worlds. Old World cutaneous leish- this was not proven until 1941.
maniasis was first described in English by Alexan- The cutaneous and mucocutaneous form of the
der Russell in the mid-eighteenth century. Designs disease are relatively common problems among peo-
on Indian pottery of the New World clearly show the ple working in heavily forested areas, such as the
disfiguring disease. The pre-Columbian Incas knew original area of Amazonia in Brazil. In Peru the uta
of the dangers of the disease in the lowlands east of form is seen on the lower eastern slopes of the
the Andes where coca grew and thus used captives to Andes. In the Arica area of northern Chile there is
cultivate it. The Spaniards who later took over the an interesting case of what is probably the uta form
coca trade were less aware of the problem, and conse- (Figure VIII.79.1) of this disease dating back about
quently, their labor policies resulted in much disfig- 1,000 years. It is known that contacts were common
urement and death. with the jungle area for trade purposes, and this case
Visceral leishmaniasis was known to nineteenth- is probably an example of an imported exotic disease
century British doctors in India as kala-azar or to the Pacific coast.
Dumdum fever with its symptoms attributed vari- Marvin J. Allison

Bibliography elements. A "bear claw" foot or hand becomes one of
Gade, Daniel W. 1979. Inca and colonial settlement, coca the characteristically maiming and stigmatizing fea-
cultivation and endemic disease in the tropical forest. tures of the leper. Involvement of the nasal cartilage
Journal of Historical Geography 5: 263-79. and vocal cords, common sites for the organism's
Herrer, Aristides, and Howard A. Christensen. 1975. Impli- growth, leads to profound disfiguration of the center
cation of Phlebotomus sand flies as vectors of bar- of the face and also to the raspy, honking voice de-
tonellosis and leishmaniasis as early as 1764. Science scribed in some historical accounts of true leprosy.
190: 154-5.
Jones, T. C, et al. 1987. Epidemiology of America: Cutane-
The early and more subtle physiological changes
ous leishmaniasis due to Leishmania braziliensis. caused by leprosy have been noted consistently only
Journal of Infectious Diseases 156: 73-83. since the nineteenth century. Owing to the involve-
Kean, B. H., Kenneth E. Mott, and Adair J. Russell, eds. ment of nerves supplying the dermis, the heavily
1978. Tropical medicine and parasitology: Classic in- innervated face loses "free play" of expression and
vestigations, Vol. I, 228-70. Ithaca. affect. Eyelashes and the lateral part of the eye-
Lainson, R., and J. J. Shaw. 1978. Epidemiology and ecol- brows disappear long before other, grosser signs be-
ogy of Leishmaniasis in Latin America. Nature (Para- tray infection.
sitology Supplement) 273: 595-600.
Markell, Edward K., Marietta Voge, and David T. John. Distribution and Incidence
1986. Medical parasitology, 6th edition. Philadelphia.In the late twentieth century, leprosy occurs com-
monly only in tropical and subtropical regions, as
Strong, R. P. 1944. Stitts diagnosis, prevention and treat-
ment of tropical disease. 7th edition. Philadelphia. indicated in Map VIII.80.1. There are at least 15
Vianna, Gaspar Oliveira de. 1911. Sobre o tratemento de million lepers worldwide, most of them residing in
leishmaniose tegumentar. Anais Paulistas de Me- Africa, South and Southeast Asia, and South Amer-
dicina e Cirurgia 2: 167—9. ica. However, this geographic distribution of the dis-
ease more likely reflects the poverty of these regions
than it does the possibility that elevated tempera-
tures and humidity facilitate infection. Despite
cheap and effective medication (dapsone) to arrest
VIII.80 the relentless progression of leprosy in infected indi-
Leprosy viduals, the disease continues to spread in the rural
regions of Africa, Southeast Asia, and the Indian
subcontinent. Often because leprosy stigmatizes its
Leprosy occurs naturally only in humans and is victims socially, leading to loss of employment, alien-
caused by infection with Mycobacterium leprae. ation from family and community, and, ultimately,
Known also in the twentieth century as "Hansen's to confinement in a leprosarium, lepers deny infec-
disease," after the Norwegian microbiologist A. G. H. tion or evade treatment as long as they can. In the
Hansen who first isolated the microorganism in 1873, process they ensure transmission of the disease to
true leprosy is a chronic, debilitating, and disfiguring others. Leprosy is normally passed from one individ-
infection. However, the long history of disease attrib- ual to another only with sustained exposure, but the
uted to leprosy undoubtedly includes a broad range of disease continues to spread even in areas served by
skin and systemic afflictions that only resembled lep- Western medical practitioners, because of the high
rosy symptoms. social costs of early identification and treatment.
The leprosy bacillus multiplies quite slowly, usu- In the past, leprosy probably extended as far north
ally in the sheaths of peripheral nerves. Losing sen- as the Arctic Circle. Extensive paleopathological in-
sation in discrete, patchy areas of the skin is often vestigations of medieval gravesites thought to have
the earliest, but ignored, symptom of infection. Lack- belonged to leper colonies have produced evidence of
ing adequate innervation, the affected dermis can be leprosy among Danes and Norwegians of the thir-
damaged without evoking a pain response as, for teenth century. Interestingly, the distribution of lep-
example, by a burn or a cut. Repair of the tissue is rosy in medieval Europe, like that of today, appears
then hindered by poor regulation of local blood sup- to have been rural, and the written or physical evi-
ply. Hence, secondary infection and inflammation of dence of leprosy disappears with urbanization. The
an involved area are common, leading to scarring disappearance of leprosy in Europe historically pro-
and callusing of surviving tissues. This long process gressed gradually northward from the urban Medi-
can result in the loss of fingers, toes, nasal tissue, or terranean areas of Italy and Spain. Cases of leprosy
other parts of the body frequently exposed to the were still reported in England and Scotland during

Map VIII.80.1. Estimated endemicity of leprosy in the world, 1983. (From World Health Organization. 1985. Epidemiology of
leprosy in relation to control: Report of a WHO Study Group. World Health Organization Technical Report Series 716. Ge-
neva.)

the fourteenth and fifteenth centuries, and the dis- mammalian and avian hosts, and, as exemplified by
ease persisted in Scandinavia until the late nine- bovine tuberculosis and avian tuberculosis, a patho-
teenth century, where Hansen discovered the bacil- gen dominant in one host species can successfully
lus that causes the disease. infect an altogether different host. Thus humans
One of the odd features of the geographic distribu- have suffered from bovine tuberculosis transmitted
tion of leprosy is the increased prevalence on islands through contaminated cow's milk and from atypical
or near seacoasts. Late medieval and early modern mycobacterial infections in the form of "scrofula" or
theorists even attributed the cause of the disease to infected lymphatic glands. But among these, only
an exclusively fish diet, an explanation now discred- leprosy and tuberculosis can be successfully trans-
ited. Undoubtedly the low infectivity of the disease mitted from one human to another, although M.
and its association with poverty and poor sanitation leprae is the only one of these genera that cannot be
contribute to the slow spread inland once leprosy is transmitted naturally to species other than humans.
introduced into a region. This feature of leprosy made difficult the search
for a suitable experimental animal for research, and
Epidemiology only during the mid-1960s did medical scientists
It is possible that the history of Mycobacterium tuber- succeed in transmitting the infection to armadillos
culosis, an organism related to leprosy and one that of the American Southwest. In what period of hu-
creates a limited cross-immunity to M. leprae infec- man history M. leprae appeared, and from what
tion, has affected the long-term distribution and inci- other mycobacterial species it evolved are a mystery.
dence of leprosy, as may also have other atypical Paleopathological evidence confirms the existence of
mycobacterial infections such as scrofula and avian true leprosy in the ancient eastern Mediterranean
tuberculosis. Increased population density in urban basin. It was probably African in origin and steadily
areas facilitates the spread of tuberculosis infection, disseminated among human communities from Pleis-
which may have contributed to a declining incidence tocene times onward (Grmek 1983).
of leprosy as cities and large towns appeared. In large The organism usually enters a new human host
regions of West Africa today, leprosy's hold over rural, through respiratory passages or the skin. Because
remote villages increases with distance from a city the period of incubation (i.e., the interval between
(Hunter and Thomas 1984), whereas tuberculosis in- infection and the manifestation of symptoms) is so
fection, evidenced by positive reactions to a tine or long, the actual process of the microorganism's
tuberculin purified protein derivative (PPD) test, ingrowth and dissemination through the body is not
creases dramatically with population density. There well understood. Commonly, early symptoms of dis-
is almost no evidence that leprosy existed in the West- ease appear 3 to 5 years after infection, but clinical
ern Hemisphere, Australia, or Oceanic Islands before evidence of infection may appear in as little as 6
it was introduced from the Old World. months, or as long as 20 years post infection.
This epidemiological relationship between tuber-
culosis and leprosy, however, is obscured in individ- Clinical Manifestations and Pathology
ual patients. For despite cross-immunity, the most Typically leprosy first appears on the skin as a patch
common associated cause of death in leprosaria is or area thickened and differing in color from the
tuberculosis, illustrating how long-sufferers of lep- surrounding skin. It may be darker or lighter in
rosy lose the ability to combat other chronic infec- color, but is usually distinguishable because the
tions. Moreover, geographic determinants of leprosy area is unresponsive to touch or pain. As is true of
infection alone cannot explain the high prevalence other chronic infectious diseases, such as tuberculo-
of leprosy in densely settled eastern India. It could sis, syphilis, or acquired immune deficiency syn-
be, however, that more successful control of tubercu- drome, the clinical features of leprosy can vary from
losis in the region permitted the persistence of lep- one sufferer to another. Leprosy is in fact described
rosy and that stigmatization of lepers effectively de- as a "bipolar" disease because of two very different
layed treatment of the illness by medical and public clinical forms of the illness, with "mixed" or "indeter-
health authorities. minate" reactions to infection possible but less fre-
quent. The intermediate type is sometimes called
Etiology "borderline" as well. Individuals whose clinical
M. leprae belongs to a large group of intracellular course vacillates between the two polar types are
bacterial pathogens widely distributed in nature. also viewed as intermediate.
Members of the family Mycobacteriaceae can infect In tuberculoid leprosy, one of the polar types, the

Vm.80. Leprosy 837
areas of "patchy anesthesia" on the skin heal rela- historical diagnosis of leprosy. Thus the more subtle
tively quickly after injury, but new areas appear, changes of early leprosy, such as the loss of the
more extensive and severe, and the untreated dis- lateral third of the eyebrows, the hoarse voice, the
ease involves peripheral nerves to such an extent areas of patchy anesthesia, and the loss of free play
that desensitized skin cannot be protected from in facial musculature - all features of the diagnostic
burns, exposure, or other insults to the body surface. procedure described by tenth-century Persian physi-
Even though tuberculoid leprosy is thought to be cian Avicenna - provide more assurance of a correct
milder than lepromatous leprosy, possibly because of diagnosis of leprosy than does simply loathesome
a stronger immune response to infection, the secon- appearance.
dary infections after skin injury make it a serious Untreated, the established leprosy infection today
disease. usually progresses slowly, although there are peri-
In the "leonine facies" of lepromatous leprosy, the ods of rapid worsening in a person's overall ability to
other polar type, the reaction on the skin surface is contain the disease. During these periods of exacer-
dramatic and severely disfiguring, because the bation, severe pain can be caused by involvement of
intermediate healing of involved skin produces the nerves, and nodules on the skin may appear
thick, corrugated scar tissue. The lesions are often rapidly and in crops of lesions. It is rare to die,
teeming with infective bacilli. The two clinical however, from unchecked Hansen's disease; secon-
forms are not caused by morphologically distin- dary infection usually leads to the patient's demise.
guishable forms of M. leprae. Thus either a strong
or a weak immunologic response (if this difference Immunology
is the "cause" of the two forms of disease) produces Because leprosy is caused by an intracellular patho-
crippling and disfigurement. gen, production of circulating humoral antibodies
The leonine form is more distinctive by sight and (the immunoglobulins) is of little use in combatting
thus is more frequent in historical accounts closely the infection of cells and the multiplication of the
describing leprosy. Chinese surgeon Hua T'o's de- organism in human tissues. Cell-mediated, or T-cell,
scription (around A.D. 150) is a good one: immunity is thus the principal bodily means of com-
bating leprosy. Individuals in whom the expression
The skin is first numb without sensation, gradually red
of cell-mediated immunity is compromised or poorly
spots appear on it, when it is swollen and ulcerated with-
out any pus. And later the disease develops to such an developed, such as pregnant women and children
extent that the eyebrows fall, the eyes may become blind, younger than 2 years of age, are at greater risk for
the lips deformed and the voice hoarse. The patient may both infection (when initially exposed) and progres-
also experience ringing in his ears and the soles of his feet sion of the disease unimpeded by the immune sys-
develop rotted holes; his finger joints may become dislo- tem. Others with intact cellular immunity can live
cated and the bridge of his nose flattened. (Skisnes 1973) almost 20 years before the first serious, debilitating
consequences of infection occur. It is not known to
On the other hand, exaggerated, grossly disfigur- what extent recurrent viral infection, which also
ing ulceration of face and limbs is not necessarily challenges cellular immunity, may hasten the onset
caused by leprosy. Syphilis, repeated frostbite injury,
of clinical leprosy.
and diabetes could also account for the features given
Genetic factors may further mediate the clinical
in this eighteenth-century Japanese description:
expression of leprosy among those already infected,
[I]t is useless to attempt to cure a patient whose eyes have predisposing some individuals to a more or less rapid
a yellow hue [a reflection of either liver damage or the course of the disease, or perhaps influencing the
destruction of red blood cells], whose fingernails have no appearance of severe, lepromatous leprosy rather
white crescents at the bottom, whose hands are wholly than the milder tuberculoid form. Nevertheless,
anesthetic, whose palm or sole bleeds, whose eyeballs are there are only a limited number of cases in which
ulcerated, whose penis is putrified, whose hands or feet some clear genetic determinant of susceptibility can
are clawed, whose skin is spotted with black, whose fin- be differentiated from the socioeconomic factors me-
gers have melted off leavingfrog-footshaped ends, whose diating exposure to the agent.
body hairs fall off, whose nose is gone, whose bones are
poisoned and putrified. (Skisnes 1973)
In addition, secondary infection by many nonin- The history of leprosy has been dominated by three
fectious diseases such as psoriasis, pellagra, eczema, questions or problems. One question concerns stig-
and lupus erythematosis could easily have led to this matization. Most ancient societies identified some

individuals as "lepers," and the leper was stigma- ated fear of contagion lepers generated. Lepers had
tized, although surely lepers as a group included to be identifiable at a distance, leading to the cre-
many suffering from something besides Hansen's ation of legendary symbols of the leper: a yellow
disease. Stigmatization of the leper has persisted cross sewn to their cape or vestment; a clapper or
into the late twentieth century despite advances and bell to warn those who might pass by too closely; a
refinements in the medical diagnosis and treatment long pole in order to point to items they wished to
of leprosy. The second problem focuses on medical purchase, or to retrieve an alms cup placed closer to
evidence for leprosy's changing incidence and preva- a road than lepers were allowed to go.
lence over time, particularly in western European The stigmatization of lepers, however, was not
history during the period between 500 and 1500 of limited to Western tradition, and in most societies of
the present era. Finally, the world distribution of the past those labeled as lepers were denied legal
leprosy and failures to impede its spread have rights in addition to being socially ostracized. In
emerged as a historical problem of the past 250 traditions of both East Asia and the Indian subconti-
years. nent, marriage to a leper or the offspring of a leper
In the Old Testament Book of Leviticus, the dis- was prohibited, and, as in Western tradition, the
ease zara'ath or tsara'ath was identified by priests disease was often attributed to moral causes (sin) as
and its victims were cast "outside the camp" as un- well as to contagion. Interesting in this regard is the
clean and uncleansable. They were viewed as both iconographic representation of the leper in Tibetan
chosen and rejected by God and, consequently, not art, a man covered with vesicles and ulcers, which
exiled altogether from the community, as were crimi- parallels Western depictions of Job as a man covered
nals, but rather made to live apart as if the living by sores in punishment by God for his sins. The
dead. Thus, central problems posed by the disease stereotype of the leper as filthy, rotten, nauseating,
zara'ath involved, on the one hand, the spiritual and repulsive is so strong that most "hansenolo-
identity of diseased individuals who, although proba- gists" today advocate rejection of the name "leprosy"
bly morally "tainted," were not, apparently, person- in favor of Hansen's disease. The only exception to
ally responsible for their disease; and on the other this pattern of stigmatization seems to be in Islamic
hand, the delegation of the process of making the society, where the leper is neither exiled nor consid-
diagnosis to religious, not medical, authorities. ered perverse, promiscuous, or otherwise morally
Because the opprobrium attached to leprosy was repulsive (Dols 1983).
handled dramatically by writers of the Biblical Old In contrast to ancient Chinese texts of approxi-
Testament and because this Judaeo-Christian tradi- mately the same period, in which leprosy destroying
tion was of central importance to western European the center of the face is well described, the clinical
history for the next 2,000 years, stigmatization of evidence for leprosy in the ancient Mediterranean is
the leper was derived from religious, medical, and meager. Nowhere in the Biblical tradition is there
social responses to individuals carrying the diagno- more than a general description of the disease that
sis. Thus, during the High Middle Ages (A.D. 1100- created such a severe response. Hippocratic texts
1300), lepers were identified by priests or other spiri- provide no evidence that true leprosy existed in an-
tual authorities, and then separated from the gen- cient Greece, but the Hippocratic, Greek word lepra,
eral community, often ritualistically. Considered probably describing psoriasis, gave origin to the dis-
"dead to society," last rites and services might be ease's name. Thus a coherent and powerful tradition
said in the leper's presence, sometimes as the victim in the West stigmatizing the leper was begun in
stood symbolically in a grave. Thereafter the per- what appears to have been the absence of any orga-
son's access to his or her city or village was severely nized and reasonably accurate medical description of
limited. Italian cities, for example, posted guards at how these sufferers could be identified. Indeed, the
the city gates to identify lepers and deny them en- earliest clinical description of leprosy in the West
trance except under carefully controlled circum- appears neither in the Hippocratic corpus (written
stances. Leprosaria, or isolation hospitals to house in Greek between 400 and 100 B.C.) nor in the 20
lepers, were constructed at church or communal ex- surviving volumes of the works of the great second-
pense, although medical services to these facilities century Greek physician, Galen, but rather in the
were limited. Where public services were less well writings of the tenth-century Persian physician Avi-
organized, lepers had to depend upon begging or cenna, and it is his Canon of Medicine that provides
alms. the description upon which medieval European phy-
Laws in western Europe illustrated the exagger- sicians relied.

VIII.80. Leprosy 839
The decline of leprosy in Europe coincided with Clay, Rotha Mary. 1909. The medieval hospitals of En-
increasing medical sophistication in diagnosing what gland. London.
we might recognize as leprosy. This decline may be Clark, George A., et al. 1987. The evolution of mycobac-
due in part to an increase in another mycobacterial terial disease in human populations: A reevaluation.
disease such as tuberculosis; to improvements in liv- Current Anthropology 28: 45-62.
ing standards; to high catastrophic mortality from Demaitre, Luke. 1985. The description and diagnosis of
leprosy by fourteenth-century physicians. Bulletin of
plague and other epidemics, effectively reducing the the History of Medicine 59: 327-44.
number of lepers in the general population; or to the Dols, Michael W. 1983. The leper in medieval Islamic
simple fact that medical authorities began to share society. Speculum 4: 891-916.
the burden of diagnosis with religious and communal Ell, Stephen R. 1984. Blood and sexuality in medieval
leaders. Surely other skin infections and afflictions leprosy. Janus 71:153-64.
that might earlier have been taken for leprosy were Grmek, Mirko D. 1983. Les Maladies a I'aube de la civili-
better recognized in the late Middle Ages. Nonethe- sation occidentale: Recherches sur la realite patho-
less true leprosy certainly existed in Europe, as the logique dans le monde grec prehistorique, archaique et
exhumations of medieval skeletal materials from classique. Paris.
northern Europe have well illustrated (M0ller- Gron, K. 1973. Leprosy in literature and art. International
Christensen 1961; Andersen 1969; Steinbock 1976). Journal of Leprosy 41: 249—83.
Knowledge of leprosy in modern medical terms Gussow, Z., and G. S. Tracy. 1970. Stigma and the leprosy
phenomenon: The social history of a disease in the
evolved during the nineteenth century, coincident nineteenth and twentieth centuries. Bulletin of the
with development of the germ theory of disease. Dur- History of Medicine 44: 425—49.
ing this period, the precise description of the clinical Hunter, John M., and Morris O. Thomas. 1984. Hypothesis
characteristics of lepromatous leprosy by Danish phy- of leprosy, tuberculosis, and urbanization in Africa.
sician Daniel C. Danielssen in the 1840s; the discov- Social Science and Medicine 19: 26—57.
ery of the microorganism by Hansen in 1873; and M0ller-Christensen, V. 1961. Bone changes in leprosy.
widespread attention to the contemporary geograph- Copenhagen.
ic distribution of leprosy in European colonial territo- Palmer, Richard J. 1982. The church, leprosy and plague
ries served to identify the disease as a contagious in Medieval and Early Modern Europe. In The church
tropical infection. As such it was believed to be eradi- and healing: Studies in church history, No. 19. ed. W.
cable by Western medical efforts in public health in- J. Shields. Oxford.
tervention. Methods of quarantine and isolation were Richards, Peter. 1977. The medieval leper and his northern
heirs. Cambridge.
enthusiastically employed, despite skepticism about 1971. Leprosy in Tibetan art and religion. International
these methods in general public health control. Journal of Leprosy 39: 60-65.
In the same year that Hansen found the causal Skisnes, Olaf K. 1973. Notes from the history of leprosy.
organism of leprosy, a devoted Catholic priest, Fa- International Journal of Leprosy 41: 220-37.
ther Damien de Veuster, drew worldwide attention Steinbock, R. T. 1976. Paleopathological diagnosis and
in an attempt to humanize the treatment of leprosy interpretation. Springfield, 111.
by going to live among lepers in Hawaii. But he may World Health Organization. 1985. Epidemiology of leprosy
have underscored fear of the contagion of leprosy in relation to control: Report of a WHO Study Group.
because he eventually contracted the disease. Thus Technical report series 716. Geneva.
in modern times, increasing medical knowledge of
the incidence and prevalence of M. leprae may have
served to increase alarm and fear as leprosy was
"discovered" to be the resilient global problem it
remains to this day.
Ann G. Carmichael
Bibliography
Andersen, J. G. 1969. Studies in the mediaeval diagnosis
of leprosy in Denmark. Danish Medical Bulletin (Sup-
plement) 16:1-142.
Brody, Saul Nathanial. 1974. The disease of the soul: A
study in the moral association of leprosy in medieval
literature. Ithaca.

VHI.81
Leptospirosis
The kind of leptospirosis manifested by severe jaun-

dice was first described as a human disease in 1886
by A. Weil. Named Weil's disease the following year,
the term was meant to designate a distinctive infec-
tious jaundice, and it would not be known until
much later that leptospirosis was caused by numer-
ous leptospires that triggered various clinical syn-
dromes. The first of the causative pathogens were
independently discovered in 1915 by R. Inada among
Japanese mine workers and by P. Uhlenhut and W.
Fromme among German soldiers. Leptospira, a ge- Figure VIII.81.1. Leptospires on darkfield.(From O.
nus of the family Treponemataceae, order Spiro- Gsell. 1978. Leptospires and relapsing fever. In Hand-
chaetales, is a fine threadlike organism with hooked book of Clinical Neurology, Part III, Chapter 18, 395-
ends (see Figure VIII.81.1) that is pathogenic for 418, by permission of Elsevier Science Publishing.)
humans and other mammals, producing meningitis,
hepatitis, and nephritis both separately and to-
gether. In the past, the disease killed between 15
and 40 percent of those infected. Modern treatment In most of the world, leptospirosis is an occupa-
has reduced mortality to about 5 percent. As a tional disease. Field workers and those who work
zoonosis, the disease is generally maintained in ro- around farm animals are at risk, as are employees of
dent reservoirs. slaughter houses and poultry and fish production
plants, and persons employed in sewers, mines, and
in other wet places infested with rodents. Infected
Etiology and Epidemiology wild animals such as rats and mice are the source of
Leptospires are obligate aerobes and classified sero- infection for domesticated animals, especially dogs
logically as a bacterium, subdivided into two species. (Leptospira canicola), pigs (Leptospira pomona), and
One is Leptospira biflexa, which includes the various cattle (Leptospira hardjo), who may in turn infect
water spirochetes, whereas the other, Leptospira in- humans.
terrogans, embraces the parasitic strains. The spe- As Table VIII.81.1 indicates, localized leptospi-
cies interrogans (so named because of an appearance rosis infections produced by one or another strain of
like a question mark) is now subdivided by the main the pathogen occur across the globe. The pig-raising
antigen into 187 serotypes or serovars. Human lepto- areas of the European alpine region, northern Aus-
spirosis generally results from direct or indirect ex- tralia, and parts of Argentina see one form of the
posure to the urine of infected animals, although it disease caused by L. pomona and Leptospira hyos or
can also be transmitted by handling infected animal tarassovi and called swineherd's disease. Similarly,
tissue, by animal bites, and by the ingestion of con- the sugarcane plantation regions of East Asia and
taminated food and water. The leptospires can enter rice-growing regions of Spain and Italy harbor other
the body through breaks in the skin, as well as forms, which are the result of infection byfieldmice.
through the lining of the mouth, nose, and eyes. Local names for the various forms of leptospirosis
Persons of all ages are susceptible to the infection, often reflect the circumstances under which it is
and although the disease may occur at any time, it is contracted. Thus there is "harvest" or "swamp" fe-
most often seen during warmer weather and periods ver, caused by Leptospira grippotyphosa. In Ger-
of heavy rainfall. Its presence in mud and swamps many, agricultural workers contracted "field fever";
has often placed soldiers at special risk. As a rule, it in Silesia, there was "mud fever"; in Russia, "water
appears as isolated cases, but it can also manifest fever"; and in Germany and Switzerland, "pea pick-
itself in small clusters and even in large outbreaks, ers disease." On the other hand, leptospirosis can
depending on the type and the circumstances of its also be an urban disease carried by the ubiquitous
transmission. Rattus norwegicus, as well as by dogs.

VTII.81. Leptospirosis 841
Table VIII.81.1. Serologic classification of leptospires
Important serogroups Principal human diseases Rare serogroups

1. L. icterohaemorrhagiae Morbus Weil 10. L. pyrogenes
2. L. bataviae Indonesian Weil, 11. L.javanica
ricefieldfever
3. L. canicola canicola fever 12. L. ballum
4. L. grippotyphosa field or swamp fever 13. L. celledoni
5. L.pomona swineherd's disease 14. L. cynopteri
6. L. hyos = tarassovi swineherd's disease 15. L. panama
7. L. australis cane fever 16. L. shermani
8. L. autumnalis Japanese autumnal fever 17. L. semeranga
9. L. hebdomadis 7-day fever 18. L. andamana
19. L. sejroe, including serovarL.
hardjo
Source: 0. Gsell. 1978. Leptospiroses and relapsing fever. In Handbook of Clinical Neurology, Part III, Chapter 18, 397.
New York: Elsevier Science Publishing, by permission of publisher.
Clinical Manifestations requires hemodialysis or peritoneal dialysis, and in-

Figure VIII.81.2 shows the phases of leptospirosis fusions or transfusions may be necessary as well.
and the relevant diagnostic procedures. The first
phase of the disease is characterized by an acute History and Geography
onset of high fever, headache, malaise, conjunctival Much of the history of leptospirosis appears as an
reddening, muscle pain, often meningism, renal irri- effort to separate leptospiral jaundice and meningi-
tation, hypotonia, and relative bradycardia (see Ta- tis from other infections. The clinical portion of this
ble VIII.81.2). In the second stage, there is danger of history began with Weil's description of the disease
organ involvement, which is accompanied by the in 1886; the bacteriologic phase began with isolation
appearance of specific antibodies in the serum. The
disease frequently causes the liver to become en- Approximate time
scale {weeks)
4-
larged and painful, and can be life-threatening when Incubation period Acute Convalescent
renal damage is severe. Icterus, when it occurs, can Inoculationn ||22-2O
-2
stage
(jaundice)
stage
be very intense and last for several weeks. Lepto- days meningitis
spirosis also causes kidney damage, although the AAy\ N

/Fever I
most common second-stage symptom is serosal men- leptospires present
ingitis, and less frequently encephalomyelitis or neu- Blood
CSF
ritis. Swineherds' meningitis is particularly well Urine
known (Gsell 1952). Meningitis symptoms usually Antibody normal
subside completely in the third week. titres hiqh
As Figure VIII.81.2 indicates, there can be other

damage from the disease, but only rarely. When it Laboratory
low
investigations and
A early treatment
delayed
causes death, postmortem findings reveal renal and specimens required

lal Isolation of strain
hepatic failure represented by renal tubular necro- from -blood —
CSF
ses, hemoglobinemia, and liver cell necrosis with
Ibi Seroloqy -2nd - — 3rd etc
general jaundice and anemia. Hemorrhages can be
found in almost any organ, and in muscles and subcu- Phases leprospiroemio-*
I [ leptospiruria and immunity -
taneous tissue.
Figure VIII.81.2. Phases and relevant diagnostic proce-
Treatment dures of leptospiroses. (Reproduced with slight modifica-
Antibiotics are quite effective against leptospires tion from L. H. Turner 1973, in O. Gsell. 1978. Lepto-
but only if employed within the first 3 or, at the spiroses and relapsing fever. In Handbook of Clinical
most, 4 days. After this, efforts should be directed at Neurology, Part III, Chapter 18, 395-419; 399, by permis-
avoiding complications. Severe kidney insufficiency sion of Elsevier Science Publishing.)

Table VIII.81.2. Symptoms occurring in and L. hyos were discovered to be of the same
leptospiroses serotype and also carried by the pig. Numerous
other serovars have been discovered subsequently,
Symptom % cases and after 1950 a new classification of the serotypes
Fever 100 was accepted which classified the clinical groups
Headaches 96 into malignant and benign human leptospires, while
Biphasic fever 96 in serology it permitted the allocation of animal and
Meningitis serosa 90—96 human leptospires to different serovars. In looking
Pathological urinary sediment 84 back on a century of research on leptospirosis, it
Conjunct, hyperaemia 60 seems remarkable that serious and widespread epi-
Pharyngitis 60 demics have been so infrequent. Today the incidence
Hypotonia 38 of the disease has been reduced in developed coun-
Myalgias, arthralgias 28 tries, probably because of a decrease in the rodent
Exanthema 14
populations and because of improved human hy-
Icterus 1—2
giene in the presence of domestic animals.
Duration of fever Otto R. Gsell
Up to 8 days 77
9-14 days 16 Bibliography-
15-19 days 7 Alston, J. M., and J. C. Broom. 1958. Leptospiroses in man
Leukopenia under 6000 and animal. London.
First phase 30 Faine, S. 1982. Guidelines for the control of leptospirosis.
Second phase 43 World Health Organization Offset Publication No. 67.
Gsell, O. 1952. Leptospirosen. In Handbuch der Inneren
Leukocytosis upwards of 9000 Medizen, 4th edition, 21-45. Berlin.
First phase 25 1974. Leptospirosen. Klinik der Gegenwart, Vol. 2, ed. H.
Second phase 25 E. Bock, W. Gerock, and F. Hartmann. Munchen.
Shift to the left in blood formula 1978. Leptospiroses and relapsing fever. In Handbook of
First phase 81 Clinical Neurology, Part III: 395-419. New York.
Second phase 72 1984. History of leptospiroses: 100 years. Zentralblatt
fiir Bakteriologie und Hygiene A257: 473-8.
Source: O. Gsell. 1978. Leptospiroses and relapsing fever. 1990. Leptospiroses. Zentralblatt fiir Bakteriologie und
In Handbook of Clinical Neurology, Part III, Chapter 18, Hygiene 281: 109-26.
399. New York: Elsevier Science Publishing, by permis- Symposium of the leptospiroses, December 1952. 1953.
sion of the publisher. Washington, D.C.
Turner, L. H. 1973. Leptospiroses III. British Medical Jour-
of t h e pathogenic g e r m s in 1915 by Inada a n d nal 1: 537-40.
Uhlenhut and Fromme. In 1918, H. Noguchi gave
the name Leptospira to the newly discovered bacte-
ria. During the years 1917-18 Y. Indo, H. Ito, and H.
Wani found cases of the disease that were not charac-
terized by jaundice — described as the 7-day fever
"Nanukayami" which has the field mouse as a car-
rier. In the following decades, numerous different
serotypes were found throughout the world. Among
these are Leptospira pyrogenes (Indonesia, 1923),
Leptospira autumnalis (Japan, 1925), Leptospira ba-
taviae (Indonesia, 1926), L. grippotyphosa (Russia,
1928), Leptospira andaman (Andaman Islands,
1931), L. canicola (Netherlands, 1933), Leptospira
australis as well as L. pomona (Australia, 1937), and
Leptospira hebdomadis hardjo (Great Britain, 1968).
In Switzerland during the year 1944, L. pomona
was found to be the cause of swineherds disease with
the pig as its carrier, and 4 years later L. tarassovi

VIII.82. Leukemia 843
are released into the bloodstream at a rate consistent

VIII.82 with the body's needs and the death of old cells. The
Leukemia exception is the lymphocytes: These are allowed to
leave the bone marrow as immature cells, but they
mature in the lymph system (thymus, spleen, lymph
Leukemia, commonly known as cancer of the blood, nodes, and so forth) before entering the bloodstream.
describes a group of malignant disorders that arise In normal health, immature stem cells or blasts are
in the blood-forming cells. The bone marrow, where present in the circulating blood only in very small
the cells of the blood are made, malfunctions to pro- numbers, and healthy bone marrow does not contain
duce abnormal white cells (leukemic cells) in an un- more than 5 percent of the total cell population.
controlled manner to the detriment of all the other From 6 weeks until about 6 to 7 months in utero,
essential blood cells. Blood consists of a clear fluid liver and the spleen are the main organs involved in
(plasma), containing chemical substances essential blood formation. Thereafter, the bone marrow takes
to the body's needs, and three types of blood cells. over. In infants, practically all the bones are in-
The red blood cells (erythrocytes) are by far the most volved, but in adults the production is limited to the
numerous; their main function is to transport oxy- vertebrae, ribs, sternum, skull, sacrum, pelvis, and
gen to all the tissues of the body. They contain hemo- the proximal ends of the femur. Because the entire
globin, an iron-rich protein that gives the blood its blood cell formation, growth, maintenance, destruc-
red color. A reduction in hemoglobin concentration tion, and replacement cycle is most efficiently orga-
is known as anemia. The white blood cells, leuko- nized, it follows that any abnormal reproduction of
cytes, of which there are three major groups, namely any type of cell will disrupt the blood cell balance
monocytes, granulocytes, and lymphocytes, play dif- and, in the absence of a self-regulating mechanism,
ferent roles in defending the body against infection. will affect the body's general health.
Platelets help to control bleeding. Every day at least 200 billion red cells, 10 billion
white cells, and over 400 billion platelets are pro-
duced in the marrow. The averagel life-span of the
Hematopoiesis cells varies according to the cell type, and ranges
Blood cell formation, known as hematopoiesis, starts from 1 to 2 days for white cells, to about 7 days for
in the bone marrow, the spongy interior of the large platelets, to 120 days for red cells. In normal circulat-
bones, with a pool of immature or undifferentiated ing blood there are approximately 1,000 red cells to
cells known as pluripotent stem cells, which contain each white cell. But in leukemia, the normal produc-
the characteristics of all the major blood cell lines. tion of blood cells fails. In all but its rarest form, one
These cells divide, either producing themselves ex- or more of the types of white blood cells reproduces
actly or producing more specialized cells that contain abnormally and creates useless, immature blast cells
the characteristics of only one of the two major cell or poorly developed cells of inferior quality. These
lines: One of these two specialized cells, known as the leukemic cells begin to overpopulate the bone mar-
mixed myeloid progenitor cell, consists of the progeni- row, spill into the bloodstream and the lymph system,
tor cells to the red blood cells, the monocytes and and infiltrate vital organs and glands, causing them
granulocytes (white cells), and the platelets. The to enlarge and malfunction. Because the bone mar-
other, the lymphoid stem cell, produces the lympho- row is severely impaired, it is unable to maintain
cytes that make up about 30 percent of the circulating production of sufficient levels of red cells and plate-
white blood cells. The two types of lymphocytes - T lets. As a consequence, the whole balance of the blood
cells and B cells - have different functions: The T cell population is seriously disturbed, and the body's
cells attack and destroy virus-infected cells, foreign defense mechanisms provided by the white blood cells
tissue, and cancer cells; B cells produce antibodies, and the platelets are rendered ineffective.
which are proteins that help destroy infectious
agents. The two types of white cells interact in com- Classification of the Leukemias
plex ways to regulate the immune response. Leukemia types are classified according to the type
The production process is continual through divi- of white cell that is affected. The two main types of
sion and differentiation, with cell characteristics be- the disease are myeloid (also called granulocytic or
coming increasingly denned with each division. The myelogenous) and lymphatic (or lymphocytic). These
result is that cells are "committed" to evolution into two main types are derived from the two major cell
one specific cell type, and thus, as mature cells, they lines: the mixed myeloid progenitor cell line, which

produces the white blood cell monocytes or granulo- The specific types of leukemia are very different in
cytes; and the lymphoid cell line, which gives rise to their age patterns and presentation:
the lymphocytes. These are further subdivided into 1. Acute myeloid leukemia (AML) is the major
acute (progressing rapidly) and chronic (progressing form of leukemia. Its rate of incidence increases with
slowly). In the acute form, there is abnormal growth age, yet it also occurs in early infancy and in those in
of immature or blast cells whereas in chronic leuke- their early 20s. With a mean estimated presentation
mia, more mature cells proliferate, although abnor- at around the age of 40 years, the disease affects
mal immature cells may also be present. The follow- both sexes equally.
ing are the diseases that mainly arise: 2. Chronic myeloid leukemia (CML) is considered
1. Acute myeloid leukemia (AML), also called an "adult" leukemia, attacking those in the 30- to
acute myelogenous leukemia, acute myelocytic leu- 50-year age bracket, although it also presents in the
kemia, acute myeloblastic leukemia, and acute older age groups. It, too, has an equal rate of inci-
granulocytic leukemia, is synonymous with the dence in males and females.
group known as acute nonlymphocytic leukemia 3. Acute lymphoblastic leukemia (ALL) is often
(ANLL), which includes some of the rarer subtypes referred to as "childhood leukemia" for the reason
of the disease (e.g., monocytic leukemia). AML in- that it accounts for 85 percent of leukemia in chil-
volves the neutrophils (one of the granulocytes) that dren and only 15 percent of cases in adults. ALL has
stem from the myeloid progenitor cell line. been reported in all races and all geographic areas;
2. Chronic myeloid leukemia (CML), also called yet, for every child with leukemia there are about 10
chronic myelogenous leukemia, chronic myelocytic adults with it.
leukemia, and chronic granulocytic leukemia (CGL), 4. Chronic lymphocytic leukemia (CLL) is primar-
produces excessive numbers of granulocytes that ac- ily a disease of the elderly; it rarely presents in
cumulate in the bone marrow and blood stream. anyone below the age of 40. It is more common in
3. Acute lymphoblastic leukemia (ALL), also males than females, with a male/female ratio of 2:1.
known as acute lymphocytic leukemia and acute The estimated incidence of all cases of leukemia in
lymphatic leukemia, arises as a result of abnormal the developed countries of the world is 10 per
immature lymphocytes, which proliferate in the 100,000 of population, the most common now being
bone marrow and the bloodstream and affect the CLL including the lymphoproliferative disorders,
lymphocytes (the B cells and T cells) stemming from followed by AML and its subgroups, then CML,
the lymphoid cell line. and lastly ALL. Incidence rates vary in some
4. Chronic lymphocytic leukemia (CLL), also countries of the world and among some ethnic
known as chronic lymphatic leukemia and chronic groups, but no variation is of great significance.
lymphogenous leukemia, produces an abnormal in- The male/female incidence ratio is about 1.7:1.
crease in lymphocytes that lack their infection-
fighting ability. It is the major type of a group of Etiology
diseases known as lymphoproliferative disorders, The etiology of leukemia is at present unknown. The
which includes such rarer forms of leukemia as basic question is what causes a healthy cell to
hairy cell leukemia and adult T cell leukemia. change to become malignant and to proliferate in
that state. The consensus of opinion is that the dis-
Distribution and Incidence ease results from the interaction of a number of
Leukemia occurs worldwide and represents just over factors, including environmental agents, and investi-
5 percent of all cancers. The disease does not present gations are being pursued on the following:
in a regular pattern, and its comparative rarity
helps to explain its irregularity. Leukemia can 1. Genetic factors, involving chromosomal abnor-
strike anyone, at any time, and at any age. The malities and changes.
difficulties in collecting statistics relating to leuke- 2. Disorders of the immune system (the body's de-
mia in populations throughout the world are due not fense system against infection).
only to the different methods of reporting cases and 3. Exposure to ionizing radiation from a single large
identifying the true leukemia cell-type specificity, dose or from repeated small doses.
but also to the variable standards and access to medi- 4. Chemicals that suppress bone marrow function.
cal care. Comparing the incidence of leukemia and 5. Infection - viruses: Retroviruses are known to
other cancers on a worldwide basis can therefore cause leukemia and lymphomas in certain animal
present problems. species but not in humans, although recently a

type of RNA virus has been isolated from patients a cause. The identification of possible contributory
with adult T cell leukemia known as human T cell factors within the environment is one approach, al-
leukemia virus HTLV1. though the prime concentration is on what influ-
ences the basic cells and genes to change and begin
Epidemiology the malignant process. The most established etio-
As the cause of leukemia remains obscure, epide- logic factor in human leukemias is ionizing radia-
miology has assumed an importance in two direction. The atom bombs dropped on Hiroshima and
tions: first, the incidence, age, and sex differences in Nagasaki in 1945, for example, brought a rise in the
the various forms of the disease related to their incidence of leukemia, which began about 3 years
geographic presentation, and second, the hunt for after the atomic attack and reached a peak at 6
etiologic clues. years, but then slowly declined to a normal inci-
One of the first epidemiology studies on leukemia dence of the disease at 20 years. On investigation it
was by W. R. Gowers, based upon 154 cases and was found that the greatest incidence was among
published in London in 1879. The study comprised those closest to the explosion, whereas at 2,000 me-
age and sex data collected at a time when leukemia ters or more the risk of leukemia was no greater
was recognized only as a chronic disease. It offered than among unirradiated people.
few etiologic clues other than exposure to malaria, Altogether some 250 cases of leukemia occurred
which was then not confined to tropical countries. between 1946 and 1965 in the 183,000 people
Toward the close of the nineteenth century, a exposed to radiation in Hiroshima and Nagasaki.
small number of cases of leukemia in its acute form From this information it followed that only a small
were reported in Europe, and attention was focused proportion of those irradiated developed leukemia,
on this new form of the disease, particularly in Amer- and this led to the suggestion of individual suscepti-
ica. George Dock of the University of Michigan was a bility. Later, public concern about nuclear power
leading investigator of the complicated aspects of causing leukemia was heightened by the number of
acute leukemia and its rapid onset. The literature, clusters of cases of the disease reported in areas
which Dock reviewed extensively in 1903, regarded surrounding nuclear power stations. Indeed many
infection and "some microscopic germ" as suspects. questions have been raised on this issue, particu-
The infective theory of acute leukemia was fur- larly because childhood cases appear to be more
ther discussed in a 1917 publication in the British prominent in these reported clusters. The pattern —
Journal of Children's Diseases by G. Ward, who had which became apparent in the aftermath of the
collected a series of 1,457 cases of leukemia. This attacks on Hiroshima and Nagasaki - seems to
work added to the knowledge of the age-sex distribu- emerge in these clusters as well; for if nuclear
tion of the disease and suggested that although power stations are emitting radiation, relatively
acute leukemia resembled an infectious disease in few people are actually affected - again raising the
many respects (e.g., the feverlike symptoms it etiologic question of possible susceptibility.
caused), there was little evidence to suggest that it The issue of genetic susceptibility was studied by
was by nature infectious or that it was hereditary. Frederick Gunz, a distinguished research physician
Leukemia tends to present in an irregular pat- at Sydney Hospital in Australia, whose biological
tern, evidenced by the number of "clusters" of cases approach to epidemiology resulted in his publica-
that are regularly reported, clusters being defined as tions in 1974 and 1975 on the genetics of human
more cases of the disease than would be expected to leukemia. Gunz concluded that evidence from family
occur in a specific area. The first report of a cluster of studies reinforced the theory of a genetic basis in
leukemia cases came from Paris in 1922, where four some people for chronic lymphatic leukemia in par-
patients living within a short distance of one an- ticular. Gunz also reported that certain chemicals,
other were diagnosed with acute leukemia in a pe- notably benzene along with viruses, were identified
riod of 7 weeks. It was the commonly held view that as triggering factors in some animal leukemias, but
the cause was the water from a canal in the area. In evidence for such a conclusion in human leukemia
this event, as with most clusters, the pattern was of remained elusive.
normal or less than normal incidence of the disease A major epidemiology study embracing a popula-
both before and after the appearance of the cluster of tion base of some 20 million people was started in
cases. 1984 in England and Wales, at the University of
Because of the sudden presentation of clusters of Leeds, by the Leukaemia Research Fund. This com-
the disease, investigations are often launched to find puterized program with diagnostic check controls

will be of major importance in assessing current of York, England, introduced a solution of arsenic
trends in the presentation of the disease. trioxide for the cure of agues, remittent fevers, and
headaches. In addition, it became a general tonic for
Clinical Manifestations and Pathology animals and humans alike, and in 1865 a German
Some of the first symptoms of acute leukemia are physician prescribed this solution in the treatment
similar to those of common infectious illness. All the of a woman with chronic myeloid leukemia. The
leukemias share common signs and symptoms aris- patient became temporarily restored to health, and
ing from the infiltration of the bone marrow, with as a result, arsenic became the first agent of some
leukemic cells replacing the normal tissues. The lack beneficial use in the treatment of certain forms of
of red cells causes fatigue and anemia, the lack of leukemia, causing a shrinkage of the enlarged
normal white cells results in infections and fever, and spleen and lymph nodes and a reduction in the leuke-
the lack of platelets produces bleeding and bruising. mic cells.
The lymph nodes, spleen, and liver may become en- The discovery in 1895 of X-rays by Wilhelm
larged as they are infiltrated with leukemic cells. Rontgen soon led to X-ray therapy of leukemias with
Bone or joint pains are associated symptoms, and results similar to those produced by arsenic. How-
purpura is often present. Although the basic features ever, X-ray therapy had a greater advantage be-
of the leukemias are common, marked differences cause it was discovered to have the ability to prevent
exist between the acute and chronic leukemias in cell division and to inhibit cell growth. On the other
their mode of presentation. In the acute leukemias, hand, patients could eventually become resistant to
influenza-type symptoms and fever (present for only treatment with X-rays. Thus William Osier com-
days or weeks) signal the sudden and rapid progress mented in 1914 that he had not seen any striking
of the acute form of the disease. Weakness, exhaus- permanent improvement in patients who had under-
tion, enlargement of the lymph nodes, abnormal gone X-ray therapy, and C. E. Forkner of Cornell
bleeding (from the gums for example), and a tendency University, New York, writing on the etiology of
to bruise easily are some of the chief symptoms. leukemia in 1938, stated that although much could
By contrast, the symptoms of chronic leukemias be done to add to the comfort of patients with chronic
are generally far more subtle. It is not uncommon for forms of leukemia, acute leukemia did not respond
the disease to be discovered accidentally when a to any form of therapy.
blood test is carried out for an unrelated reason. The In 1946, two American research groups reported
most common symptoms are loss of energy, tired- on nitrogen mustard therapy, which arose from the
ness, fever, night sweats, and loss of appetite. There poisonous mustard gas research study initiated dur-
may also be enlargement of the liver and spleen and ing World War II. It was found that the chemical
the lymph nodes. analogues of the gas could cause depression of the
Leukemia can be diagnosed only by microscopic blood cells, and that some patients in cases of leuke-
examination of the blood and the bone marrow. A mia and lymphoma who had become resistant to X-
blood test may show low hemoglobin, low levels of ray therapy responded to treatment with this agent.
normal white cells, and a low platelet count; and This new treatment triggered intensive efforts to
leukemic blast cells may be present. A bone marrow find less toxic and more specific therapeutic agents.
biopsy will confirm the diagnosis of leukemia and The result was the introduction of chemotherapy.
the predominant cell type involved, which will en- The aim of all treatment of leukemia is to achieve a
able the leukemia to be correctly classified. prolonged remission of the disease, a state in which
all clinical signs of abnormal blood cells disappear
Treatment and the normal balance of less than 5 percent of
The remedies for leukemia in the nineteenth cen- blasts in the bone marrow is restored.
tury were few, and none was useful in controlling the Chemotherapy is the form of induction therapy
disease for any length of time. In the first 50 years used to effect a remission. A variety of drugs are
following its recognition (Bennett 1845), leukemia used to attack the leukemic cells in diverse ways,
was generally accepted as a chronic disease, and the and they are often given in combination to enhance
limited therapeutics in the armory of the general the efficacy of treatment. However, as these drugs
physician were applied. Quinine was used for com- can affect both the leukemic and normal cells, their
bating fever; morphine and opium, for diarrhea; doses and the sequence of their use must be con-
iron, for anemia; iodine, for external use as an trolled with great care. Usually combinations of
antibacterial; and arsenic. In 1786, Thomas Fowler drugs belonging to different groups of chemical com-

pounds are used to attack leukemic cells at different ber 1845, a month before Rudolph Virchow pub-
stages of their growth to prevent leukemic cells from lished his findings under the title Weisses Blut. Two
becoming resistant to the therapy. years later, Virchow named the disease leukemia,
Radiotherapy by deep X-irradiation may also be Greek for "white blood," and Bennett in 1851 called
given; and in certain instances it is used to attack it leucocythemia, Greek for "white cell blood." Both
leukemic cells that may accumulate in certain areas men, who were keen observers and in the early
of the body - for example, in the central nervous stages of what were to become distinguished careers
system, the testis, and the eye - and for which che- in medicine, made their observations at the autopsy
motherapy is less effective. The treatment and table. However, it is unlikely that the disease was
choice of drugs differ for each of the main types of new in 1845, for there had been earlier reports of
the disease. The slowly progressing chronic leuke- what was described as peculiar conditions of the
mias are less responsive to the currently available blood, pus in the blood, and "milky" blood, with some
therapies than are the acute leukemias, although in symptoms compatible with those of leukemia. David
nearly all cases modern therapy can effect remis- Craigie in Edinburgh and Alexandre Donne in
sion. The next stage is to keep the patient in remis- Paris, among others, were physicians who in the
sion through a second level of treatment known as decade previously were alert to something odd in the
consolidation therapy, to be followed by maintenance condition of the blood of certain patients.
therapy, which aims to destroy any remaining or The microscope at that time was a crude instru-
undetected leukemic cells. Antibiotics are available ment, and there was no satisfactory means of illumi-
to treat infections, to which the immunosuppressed nating the specimens being observed. In fact, what is
patient has an increased susceptibility. Complete re- remarkable is that the disease was recognized at all,
mission does not always mean cure because some when one considers its rarity, on the one hand, and
residual leukemic cells may still be present and re- the continual epidemics of infectious diseases as well
main undetected even by means of microscopic ex- as chronic ailments of the last century which occu-
amination and will multiply over a period of time. If pied the medical profession, on the other. But after
leukemic cell growth recurs, treatment is restarted recognition, reports of suspected or actual cases of
to achieve a second remission. Survival rates differ leukemia began to appear in the literature, slowly
for each type of leukemia. The most encouraging revealing its worldwide distribution. Case reports
results are achieved in children with acute lympho- from Europe and America also indicated the ineffec-
blastic leukemia; over half of those diagnosed are tual nature of any known therapy.
now long-term survivors. Two breakthroughs occurred in the last half of the
A further form of treatment in suitable cases is nineteenth century. The first was the discovery by
bone marrow transplantation. This new therapy in- Ernst Neumann in 1868 of the importance of the
volves high-dose chemotherapy and total body irra- bone marrow in the formation of blood; a year later,
diation followed by an infusion of bone marrow from he published his report on the changes in the bone
either a suitable donor (an allogeneic transplant) or marrow in leukemia, which introduced the term
from the patient's own marrow taken and stored myelogenous leukemia. The second came in 1877,
during remission (an autograft transplant). Apart when Paul Ehrlich, a medical student at the time,
from suitable donor availability, a major complica- developed a stain that permitted the cells to be
tion at present is graft-versus-host disease resulting clearly defined. By then, the microscope had been
from the reaction of the infused marrow with the improved, and the new technique of staining en-
recipient and, in autologous transplant, the risk of abled features of the blood to be studied that had
residual disease still being present in the marrow. hitherto been unseen or unsuspected.
This form of therapy has been responsible for the Thus began a new era in hematology, but it was to
control of the disease in cases where other means be nearly 70 years before any progress was to be
would not have been successful. made in the treatment of leukemia. This began with
the realization that folic acid was important to blood
History and Geography cell formation, and that its lack caused anemia and,
Leukemia was identified as a new disease in 1845 by significantly, a decrease in the white cells. Ensuing
two independent observers. John Hughes Bennett, experiments showed that some preparations contain-
lecturer in clinical medicine and pathologist to the ing folic acid inhibited growth of experimental tu-
Royal Infirmary at Edinburgh, published his obser- mors, whereas other observations indicated that it
vations in the Edinburgh Medical Journal of Octo- might stimulate the growth of leukemic cells. This

led a group of researchers in the United States to Garrison, F. H., and L. T. Morton. 1970. A medical bibliog-
develop a series of new drugs that were designed as raphy. 3d edition. London.
antagonists of folic acid for trial in the treatment of Gunz, F. W. 1974. Genetics of human leukaemia. Series
human cancers. Aminopterin was one of these new Haematologica 7: 164-91.
drugs and was used with much success in the treat- Hoffbrand, A. V, and J. E. Pettit. 1985. Essential haema-
ment of acute leukemia by Sidney Farber and his tology. Oxford.
Leukaemia Research Fund of Britain. Various publica-
group at Boston Children's Hospital in the late
tions.
1940s. Much research followed in a quest for new Leukemia Society of America. Various publications.
and more successful drugs to combat leukemia, with Linet, M. 1985. The leukaemias: Epidemiological aspects.
the result that by the late 1980s there was an estab- New York.
lished armamentarium of drugs used mostly in com- Metcalf, D. 1989. Haemopoietic growth factors (1) & (11).
bination to achieve a remission and to maintain it. Lancet i: 825-7, 885-6.
Leukemia is a disease of major interest in both Osier, W. 1914. The principles and practice of medicine, 8th
hematology and cancer research where much prog- edition. Oxford.
ress has been and is still being made, measured in U.S. Department of Health and Human Services. National
terms of patient survival. Moreover, the outstanding Cancer Institute. 1985. Research report - Leukemia.
"problem areas" of research are now more clearly Washington, D.C.
denned and recognized, and current research efforts Virchow, R. 1858. Cellular pathology. New York.
Wintrobe, M. M. 1980. Blood pure and eloquent. New York.
(in both pure and applied settings) within the fields
of cell and molecular biology, immunology, cytogenet-
ics, and virology are directed toward investigating
such problems as the following:
1. Application of molecular mechanisms in therapy VIII.83
to destroy leukemic cells
2. Role of viruses in influencing the development of Lupus Erythematosus
the disease
3. Nature of environmental triggers of leukemia
4. How to achieve earlier recognition of leukemia Lupus erythematosus (LE) is a clinical syndrome
5. How to understand the scientific basis for remis- that has multiple, but largely unknown causes. It
sion and thus how it can be maintained exhibits an extremely broad spectrum of symptoms,
6. How to eliminate residual disease and it can range in severity from being potentially
fatal within a few weeks to eliciting minor indolent
It is hoped that improved therapy for both adult symptoms which, prior to immunologic testing, are
and childhood cases will result from these complex virtually undiagnosable. When limited to the skin,
and concentrated research efforts and that survival it is called discoid lupus erythematosus (DLE); when
rates will be increased even more. Virchow wrote the viscera are symptomatically affected, it is
the following in 1858: "I do not wish by any means to termed systemic lupus erythematosus (SLE). The in-
infer that the disease in question [leukemia] is abso- citing causes activate immunologic mechanisms
lutely incurable; I hope on the contrary that for it too that mediate the pathological, predominantly in-
remedies will at length be discovered." Today there flammatory, tissue responses.
is optimism that Virchow's hope will be realized.
Gordon J. Filler History
Medical use of the term lupus has been traced to the
Bibliography fifteenth century, when it designated a variety of
Ackerknecht, E. H. 1953. Rudolf Virchow: Doctor, states- cancer. The term was reintroduced by London physi-
man, anthropologist. Madison, Wis. cian Robert Willan in 1808 to designate cutaneous
Bennett, J. H. 1845. Case of hypertrophy of the spleen and
tuberculosis, particularly when it affected the face.
liver in which death took place from suppuration of
the blood. Edinburgh Medical Journal 64: 413-23.
Cutaneous tuberculosis eventually received the syn-
International Agency for Research on Cancer. 1982. Can- onym lupus vulgaris. In 1851 P. L. Alph6e Cazenave
cer incidence in five continents, Vol. IV. Lyons. of Paris used the term lupus erythemateaux to de-
Doll, R. 1966. The incidence of leukaemia and the signifi- scribe the condition that came to be called discoid
cance of environmental factors. In Lectures on Haema- lupus erythematosus (DLE) by Vienna's Moriz
tology, ed. F. G. J. Hayhoe, 138-51. Cambridge. Kaposi in 1872 (Jarcho 1957). During 1866-70,

VIII.83. Lupus Erythematosus 849
Kaposi diagnosed this disease in 22 patients and SLE. Recent data indicate that even with the
concluded that it was more common and more severe current longer life expectancy of SLE patients, only
in women. All 3 deaths occurred among his 15 fe- about 40 percent ever have the "butterfly" facial
male patients. Although one of these had pulmonary rash, and that an eruption occurs somewhere on the
tuberculosis, and cutaneous tuberculosis was com- body in about 75 percent of the cases. The concept
mon, Kaposi believed that DLE is not related to that DLE and SLE are manifestations of the same
tuberculosis. Such a causal relationship, however, disease was first proposed by Harry Keil in 1937,
came to be advocated, particularly by French derma- but two decades passed before the concept became
tologists, and remained under discussion until the generally accepted.
1930s. During the 5 years in which Kaposi saw 22 SLE was perceived to be rare and uniformly fatal
cases of DLE, 279 cases of lupus vulgaris were seen because only the most severe cases identified by
in the same department (Kaposi 1872). One genera- their rash were being diagnosed. For example, at the
tion later, among 30,000 dermatologic patients seen University Hospital in Prague there were just eight
in Manchester, England, between 1893 and 1913, a cases from 1897 to 1908. At the Johns Hopkins Hospi-
diagnosis of DLE was made in 142 instances (0.47 tal, only three cases were diagnosed between 1919
percent), and lupus vulgaris in 1.5 percent. Of the and 1923. In fact among 7,500 autopsies of cases
DLE cases, 66 percent were female, ranging in age above 13 years of age reviewed at the same hospital
from 15 to 63 years, whereas males ranged in age in 1936, there were just five instances of SLE. Five
from 8 to 66 years. cases were diagnosed at the Mayo Clinic between
Kaposi (1872) used the term disseminated lupus 1918 and 1921 (Goeckerman 1923), but, as the dis-
erythematosus, but referred thereby to cases with ease became more familiar, 132 cases were recog-
widespread skin lesions rather than visceral involve- nized during the decade 1938 to 1947 (Montgomery
ment. Nevertheless, he described some cases having and McCreight 1949).
fever, pleuropneumonia, arthralgia, and arthritis. In 1948, Malcolm Hargraves, a hematologist at
Recognition developed slowly that various visceral the Mayo Clinic, reported a discovery, which he said
manifestations are attributes of the systemic disease "has been called an L.E. cell in our laboratory be-
rather than coincidences. From 1894 to 1903, Wil- cause of its frequent appearance in the bone marrow
liam Osier saw 29 patients (17 aged 3-15 years; 12 in cases of acute disseminated L.E." (Hargraves
aged 18-57 years), who had an "erythema with vis- 1969). In the next 4 years, numerous modifications
ceral lesions." He is credited with having provided of Hargrave's procedure were devised in various labo-
the first clear descriptions of systemic lupus eryth- ratories to make demonstration of the LE cell easier
ematosus (SLE) although, by modern criteria, the and more reliable.
diagnosis that resulted from those descriptions does In 1954 it was discovered that the formation of LE
not fit all of the cases. cells results from a reaction between a factor in the
Osier (1904) added involvement of the kidneys serum and leukocyte nuclei. This led in 1957 to the
and central nervous system to the description of development of a quantifiable test of this antigen-
Kaposi, whereas Alfred Kraus and Carl Bohac antibody reaction. The determination of antinuclear
(1908-9) recognized that pneumonia belongs to the antibodies (ANA) has gradually replaced the LE cell
syndrome. Before the 1940s, most publications on as the principal diagnostic test for SLE. These tests
lupus erythematosus were written by dermatolo- have greatly increased case finding and thereby
gists, and consequently, skin lesions were consid- have led to the recognition that SLE exhibits a broad
ered essential to satisfy the diagnosis. Emanual range of severity. Nevertheless, the ANA test may
Libman and Benjamin Sacks (1923) described four cause confusion because many circumstances induce
cases of noninfectious endocarditis (heart inflamma- ANA reactions, at least in low titer. In North Amer-
tion) of which three had the skin lesions of LE. A ica and Europe, "false positive" reactions are most
review of 11 cases of Libman—Sacks endocarditis in often due either to a drug or to another connective
1932 found that 5 lacked the skin eruption. George tissue disease, whereas in tropical Africa they have
Belote and H. S. Ratner (1936) concluded that this been related to endemic malaria.
form of heart disease nevertheless is a manifesta- The next advance was the standardization of crite-
tion of SLE. Leukopenia and sensitivity to sunlight ria for the diagnosis of SLE. For this purpose, a
were convincingly related to SLE in 1939, but it committee of American rheumatologists in 1971 pub-
was only in the 1940s that it became accepted that lished a battery of clinical and laboratory findings of
a skin eruption is not a necessary component of which a specified number had to be present for the

diagnosis to be probable. This schema was well re- commonly used drugs in this category are azathio-
ceived, and a modification prepared in 1982 has been prine and cyclophosphamide (Wagner 1976). This
adopted in many countries (Tan et al. 1982). type of treatment is reserved for severe renal involve-
ment and refractoriness to corticosteroid therapy.
Drug-Induced SLE Modern therapy has not only improved the quality
A syndrome that was indistinguishable from SLE of life of the SLE patient but has also greatly pro-
was recognized at the Cleveland Clinic in 1954 in longed his or her survival. Before the advent of corti-
patients who were taking the antihypertensive drug costeroids, one-half of these patients died within 2 to
hydralazine. Since then, many drugs have been sus- 3 years of being diagnosed. Now the mean survival
pected or have been proven potentially to have such of 15 years after diagnosis has reached 75 percent.
an effect. By far the most consistent SLE-inducing Two factors in addition to the therapeutic agents
agent is procainamide; this drug, used to treat car- cited above help to account for this improvement: (1)
diac arrhythmias, was first reported to induce SLE better antibiotic therapy for potentially fatal bacte-
in 1962. After 6 months of therapy, ANA develop in rial infections; and (2) recognition of much milder
at least half of these cases; and after 1 year, a quar- cases for which a more benign course is likely even
ter of the cases may exhibit symptoms of SLE. In with minimal therapy.
patient populations in which potentially lupus- Mortality is influenced by race and sex. According
inducing drugs, such as procainamide, hydralazine, to U.S. data for 1968 to 1976, the annual mortality
phenytoin, and isoniazid are widely used, about 10 rate, relative to 1.0 for white males, was 1.6 for
percent of the cases of SLE are drug-induced (Lee, black males; 3.7 for white females; and 10.5 for black
Rivero, and Siegel 1966). Drug-induced SLE is rela- females (Gordon, Stolley, and Schinar 1981).
tively benign. The female preponderance is dimin-
ished and its most frequent symptoms are pleurisy Epidemiology, Distribution, and Incidence
and arthralgia. Fever, leukopenia, and skin lesions Reviews of the proportion of cases of DLE in the
occur about half as frequently as in idiopathic SLE; clientele of dermatology clinics began to be reported
renal involvement and pericarditis are rare, and cen- at the beginning of this century. An incidence of
tral nervous system involvement does not occur. between 0.25 percent and 0.75 percent has been con-
Only the development of ANA warrants close obser- sistently found in various parts of the world (Gahan
vation. If it is possible to discontinue the inciting 1942). The early belief that the disease is rare in the
drug after symptoms have developed, those symp- tropics and among black populations has been dis-
toms will disappear within several weeks. proved in Africa and in the United States (Rothfield
et al. 1963; Findlay and Lups 1967).
Treatment and Mortality The only epidemiological conclusion about SLE
In the 1940s it was generally acknowledged that reached until the 1950s was that the disease occurs
there was no effective treatment for either DLE or predominantly in young women. In 1952 an ethnic
SLE. The initial breakthrough occurred in 1949, predisposition was postulated, based on the observa-
with the discovery that the corticosteroids cortisone tion of the often deleterious effect of sun exposure:
and corticotropin can exert a dramatic suppression Redheaded, freckled persons with an inability to tan
of most symptoms of SLE. Prednisone, a synthetic were deemed most susceptible (Brunsting 1952).
derivative of cortisone, was introduced in 1955 and This conclusion was contradicted, however, by M.
has become the most commonly used orally adminis- Siegel and his colleagues (1964), whose epidemio-
tered corticosteroid (Urman and Rothfield 1977). logical data indicated that SLE is actually more
Only the cutaneous and renal manifestations are common among blacks. Studies in San Francisco
frequently refractory. In 1951, quinacrine, an anti- (Fessel 1974) and Baltimore (Hochberg 1987) sub-
malarial drug, was found to be effective against stantiated this increased susceptibility of blacks, par-
DLE. Soon thereafter, the antimalarials chloroquine ticularly among black women. National data from
and hydroxychloroquine were found similarly use- Veterans Administration hospitals have confirmed
ful, and the latter is now principally employed. In the racial difference among men as well (Siegel and
SLE the antimalarials are also most effective Lee 1973). Unlike infectious diseases such as rheu-
against the rash, but they may also ameliorate some matic fever or tuberculosis, the occurrence of SLE
visceral symptoms. The third major therapeutic cate- appears not to be related to socioeconomic factors. In
gory is the immunosuppressive drugs. The first to be terms of total population, the annual incidence of
tried was nitrogen mustard, in 1950. Now the most SLE in the United States has been estimated at

VIII.83. Lupus Erythematosus 851
about 5 per 100,000, with black females about three Bibliography
times more susceptible and black males two times Beck, J. S. 1969. Antinuclear antibodies: Methods of detec-
more susceptible than their white counterparts. The tion and significance. Mayo Clinic Proceedings 44:
mean age of onset is 28 to 30 years, but the prepon- 600-19.
derance of female patients varies with age. About Belote, G. H., and H. S. Ratner. 1936. The so-called
twice as many females as males suffer from the dis- Libman-Sacks syndrome: Its relation to dermatology.
Archives of Dermatology and Syphilology 33: 642—64.
ease during the first decade of life and from the sev-
Brunsting, L. A. 1952. Disseminated (systemic) lupus
enth decade on. But between ages 20 and 40, there erythematosus. Proceedings of the Staff of the Mayo
are 8 female patients for every male. Clinic 27: 410-12.
The prevalence, sex ratio, and mortality rates for Fessel, W. J. 1974. Systemic lupus erythematosus in the
SLE in northern Europe resemble those of U.S. community. Incidence, prevalence, outcome and first
white populations (Helve 1985; Hochberg 1987). In symptoms; the high prevalence in black women. Ar-
other parts of the world, as recognition of the disease chives of Internal Medicine 134: 1027-35.
has increased, more cases are being diagnosed. For Findlay, G. H., and J. G. Lups. 1967. The incidence and
example, SLE was rarely diagnosed in India before pathogenesis of chronic discoid lupus erythematosus:
1970, but from 1974 to 1985, 181 cases were seen in An analysis of 191 consecutive cases from the Trans-
one hospital in New Delhi (Malaviya et al. 1987). vaal. South African Medical Journal 41: 694-8.
Studies in Hawaii (Serdula and Rhoads 1979) and Frank, A. O. 1980. Apparent predisposition to systemic
lupus erythematosus in Chinese patients in West Ma-
Malaysia (Frank 1980) indicate greater susceptibil- laysia. Annals of the Rheumatic Diseases 39: 266-9.
ity of Chinese than other ethnic groups, and the Gahan, E. 1942. Geographic distribution of lupus erythe-
death rate due to SLE for Oriental women in the matosus. Archives ofDermatology and Syphilology 45:
United States (nearly three times that of white 1133-7.
women) is similar to that of black women (Kaslow Goeckerman, W. H. 1923. Lupus erythematosus as a sys-
1982). The prevalence of SLE among Polynesians temic disease. Journal of the American Medical Asso-
also exceeds that of Caucasians (Serdula and Rhoads ciation. 80: 542-7.
1979; Hart, Grigor, and Caughey 1983). Gordon, M. F., P. D. Stolley, and R. Schinar. 1981. Trends
In the predominantly black population of Jamaica, in recent systemic lupus erythematosus mortality
SLE constitutes a remarkably large proportion of rates. Arthritis and Rheumatism 24: 762-76.
treated rheumatic diseases. Indeed, 22 percent of all Greenwood, B. M., E. M. Herrick, and E. J. Holbrow. 1970.
outpatients and 37 percent of inpatients with rheu- Speckled antinuclear factor in African sera. Clinical
and Experimental Immunology 7: 75—83.
matic disease suffer from SLE (Wilson and Hughes Hargraves, M. M. 1969. Discovery of the LE cell and its
1979). In view of the prevalence of SLE among non- morphology. Mayo Clinic Proceedings 44: 579—99.
white populations elsewhere, the apparent rarity of Hart, H. H., R. R. Grigor, and D. E. Caughey. 1983. Ethnic
the disease among African blacks has been perplex- difference in the- prevalence of systemic lupus ery-
ing. The first case was reported from Senegal in thematosus. Annals of the Rheumatic Diseases 42:
1960. Between 1967 and 1978, only 21 cases were 529-32.
recorded in Kampala, Uganda. A 5-year prospective Helve, T. 1985. Prevalence and mortality rates of systemic
analysis of cases of polyarthritis in Zimbabwe re- lupus erythematosus and causes of death in SLE pa-
ported in 1969 found no case of SLE, whereas an- tients in Finland. Scandinavian Journal of Rheuma-
other study during 1979-84 discovered 31 cases (30 tology 14: 43-6.
female, ages 13 to 46 years) (Taylor and Stein 1986). Hench, P. S., et al. 1950. Effects of cortisone acetate and
The possibility of differences in susceptibility of vari- pituitary ACTH on rheumatoid arthritis, rheumatic
fever and certain other conditions. Archives of Inter-
ous African ethnic groups must be considered. Dur- nal Medicine 85: 545-666.
ing 1960-72, for example, 130 cases of SLE were Hochberg, M. C. 1985. The incidence of systemic lupus
admitted to two hospitals in Cape Town, South Af- erythematosus in Baltimore, Maryland, 1970-1977.
rica. These included 86 "coloureds" (mainly Indian), Arthritis and Rheumatism 28: 80-6.
36 whites, and only 8 "Bantu." In terms of each 1987. Mortality from systemic lupus erythematosus in
1,000 female admissions, this meant a rate of 4.9 England and Wales, 1974-1983. British Journal of
"coloured," 3.8 "Bantu," and 2.3 white (Jessop and Rheumatism 26: 437-41.
Meyers 1973). The data from much of the world Jarcho, S. 1957. Notes on the early modern history of lupus
remain inadequate to draw firm conclusions about erythematosus. Journal of the Mount Sinai Hospital
ethnic and other possible variables related to SLE. 24: 939-44.
Thomas G. Benedek Jessop S., and O. L. Meyers. 1973. Systemic lupus erythe-
matosus. South African Medical Journal 47: 222—5.

Kaposi, M. 1872. Neue Beitrage zur Kenntniss des Lupus Wagner, L. 1976. Immunosuppressive agents in lupus ne-
erythematosus. Archiv fiir Dermatologie und Syphilis phritis: A critical analysis. Medicine 55: 239-50.
4: 18-41. Wilson, W. A., and G. R. Hughes. 1979. Rheumatic disease in
Kaslow, R. A. 1982. High rate of death caused by systemic Jamaica. Annals of the Rheumatic Diseases 38: 320-5.
lupus erythematosus among U.S. residents of Asian
descent. Arthritis and Rheumatism 2: 414—18.
Keil, H. 1937. Conception of lupus erythematosus and
variants. Archives ofDermatology and Syphilology 36:
729-57.
Kraus, A., and C. Bohac. 1908. Bericht uber acht Falle von
VIII.84
Lupus erythematodes acutus. Archiv fiir Derma- Lyme Borreliosis
tologie und Syphilis 43: 117-56.
Lee, S. L., I. Rivero, and M. Siegel. 1966. Activation of (Lyme Disease)
systemic lupus erythematosus by drugs. Archives of
Internal Medicine 117: 620-6.
Libman, E., and B. Sacks. 1924. A hitherto undescribed Lyme borreliosis is a tick-borne spirochetal bacterial
form of valvular and mural endocarditis. Transac- disease caused by Borrelia burgdorferi. Lyme borreli-
tions of the Association of American Physicians 38: osis is a systemic illness with potential involvement
46-61. of the skin, neurological, cardiac, and articular sys-
MacLeod, J. M. 1913. Discussion on the nature, varieties, tems. It can mimic a variety of other diseases such as
causes and treatment of lupus erythematosus. British juvenile rheumatoid arthritis, multiple sclerosis,
Medical Journal 2: 313-19. and syphilis.
Malaviya, A. N., et al. 1987. Systemic connective tissue
diseases in India - IX. Survival in systemic lupus
erythematosus. Journal of the Association of Physi-
Epidemiology
cians of India 36: 509-11. The disease is the most frequently diagnosed tick-
Montgomery, H., and W. G. McCreight. 1949. Dissemi- transmitted illness in the United States. The three
nated lupus erythematosus. Archives of Dermatology major geographic loci of Lyme disease in the United
and Syphilology 60: 356-72. States are the Northeast and middle Atlantic coastal
Osier, W. 1904. On the visceral manifestations of the regions, the upper Midwest, and the Pacific North-
erythema group of skin diseases. American Journal of west. The disease is found in Europe, Australia, the
the Medical Sciences 127: 1-23, 751-4. former U.S.S.R., China, Japan, and several African
Page, F. 1951. Treatment of lupus erythematosus with countries. The vector of Lyme disease is the tick,
mepacrine. Lancet 2: 755—8. Ixodes dammini, or related Ixodes ticks such as pa-
Rose, E., and D. M. Pillsbury. 1939. Acute disseminated cificus, scapularis, or ricinus. B. burgdorferi has
lupus erythematosus — a systemic disease. Annals of been found in other ticks such as the Dermacentor
Internal Medicine 12: 951-63.
variabilis, Amblyomma americanum, and Haema-
Rothfield, N. F., et al. 1963. Chronic discoid lupus
erythematosus: A study of 65 patients and 65 controls. physalis leporispalustris; however, transmission has
New England Journal of Medicine 269:1155-61. not been proved.
Serdula, M. K., and G. G. Rhoads. 1979. Frequency of B. burgdorferi has been found in horseflies, deer-
systemic lupus erythematosus in different ethnic flies, and mosquitoes, but proof that these insects
groups in Hawaii. Arthritis and Rheumatism 22: are possible secondary vectors has not been estab-
328-33. lished. The reservoirs of B. burgdorferi occur in ani-
Siegel, M., and S. L. Lee. 1973. The epidemiology of sys- mals parasitized by infected ticks. The Ixodes tick is
temic erythematosus. Seminars in Arthritis andRheu- a three-host tick with a life cycle of 2 years. Adult
matism 3: 1—54. ticks mate and feed primarily on deer in late fall; the
Tan, E. M., et al. 1982. The 1982 revised criteria for the female deposits eggs on the ground, which produce
classification of systemic lupus erythematosus. Arthri- larvae that are active late the following summer.
tis and Rheumatism 25: 1271-7. The tiny larvae obtain a blood meal from infected
Taylor, H. G., and C. M. Stein. 1986. Systemic lupus
erythematosus. Annals of the Rheumatic Diseases 45:
rodents such as white-footed mice, shrews, chip-
645-8. munks, and squirrels, which are primary reservoirs
Urman, J. D., and N. F. Rothfield. 1977. Corticosteroid for B. burgdorferi. Ground foraging birds are also
treatment in systemic lupus erythematosus: Survival important hosts for the larvae and nymphs. After a
studies. Journal of the American Medical Association blood meal, the larvae molt to a nymphal form,
238: 2272-6. which is active the following spring and early to

VIII.84. Lyme Borreliosis (Lyme Disease) 853
midsummer. It seeks an animal host, obtains a blood ease and begins as a small flat (macule) or swollen
meal, and molts to an adult stage to complete the 2- (papule) spot at the site of the tick bite and then
year life cycle. The animal hosts can include hu- expands to a very large (10 to 20 centimeters) oval or
mans, dogs, deer, cows, horses, raccoons, cats, round lesion with a red to pink outer border and a
skunks, black bears, and Virginia opossums. very clear central area. Viable B. burgdorferi occa-
Each developmental stage of the tick requires feed- sionally can be cultured in the advancing margins.
ing once and may take several days. B. burgdorferi Blood-borne spread of the spirochete may produce
is transmitted to the host during the blood meal. The multiple, secondary lesions days to weeks later. The
longer the time of attachment of the infected tick to rash persists for a few days to weeks, and is usually
the host, the greater probability of transmission. unaccompanied by systemic symptoms, although oc-
casionally fever, chills, and fatigue may occur. Be-
Etiology cause the rash can be asymptomatic or on areas of
The detection of B. burgdorferi in human tissue or the body that may not be observed, many people may
body fluids is the most reliable technique to prove go undiagnosed. More than 20 percent of adults who
the cause of an infectious disease. In Lyme borre- have Lyme borreliosis will not remember having the
liosis, cultivation of the organism has been difficult, rash, and the percentage is much higher in children.
probably because of slow growth of B. burgdorferi Stage II of Lyme borreliosis may involve the neuro-
and its low density in body tissues. logical system. Of patients, 10 to 15 percent may have
An alternative method to establish proof of infec- this involvement and present with a meningitis-type
tion by B. burgdorferi relies on the detection of its picture or have cranial nerve palsies. The most com-
antibody. In early Lyme borreliosis, the immunoglo- monly involved cranial nerve is the seventh (facial)
bulin (Ig) M form of the antibody response appears nerve, which results in an inability to control prop-
first, peaks 3 to 6 weeks after exposure, and then erly the facial musculature. In individuals with men-
declines. The IgG then becomes detectable and is ingeal irritation, episodic headaches, neck pain, and
present in late-stage disease states. However, anti- stiffness may occur. Cerebrospinal fluid analysis fre-
bodies are frequently not detectable in the early quently shows a predominance of mononuclear white
stages of the disease by current techniques. In the blood cells. Occasional patients with stroke syn-
late stages of the disease, they are almost always dromes including hemiparesis as well as cases mim-
positive. Other spirochetal diseases, such as yaws, icking multiple sclerosis or encephalitis have been
pinta, or syphilis, may give false-positive results, reported. Individuals may have associated confusion,
but can be excluded by clinical evaluation. agitation and disorientation, and memory loss. The
symptoms and signs may wax and wane over weeks
Clinical Manifestations and months.
Lyme borreliosis is a multisystem disease. Its pri- Heart involvement is rare as part of Stage II mani-
mary target organs include the skin initially and festations of Lyme borreliosis. Cardiac manifesta-
later, potentially, the neurological, cardiac, and ar- tions are commonly detected only as first-degree
ticular systems. Lyme borreliosis is categorized in heart block on electrocardiographic tracings, al-
three phases. Arbitrarily: though some patients can have a more serious
second- or third-degree heart block and present with
Stage I involves the dermatologic system and is diag- episodic fainting spells. Both the neurological and
nosed by the classic rash, erythema chronicum cardiac manifestations may occur within weeks to
migrans (ECM). months or even longer after infection with the B.
Stage II involves the neurological or cardiac system burgdorferi organism, and they can occur without
months to years after exposure to the organism. any antecedent rash.
Stage III, involving the joints, also can occur months
The most common late manifestation of Lyme
to years after the initial exposure.
borreliosis is arthritis. It usually occurs several
These three stages may overlap and occasionally can months after the tick bite, but the range is 1 week
present simultaneously. Moreover, any of these to over 10 years after exposure. It is usually an
stages may occur in the absence of the others. oligoarticular form of arthritis (fewer than four
Erythema chronicum migrans (ECM) is pathogno- joints) involving the large joints such as the knee or
monic for Stage I Lyme borreliosis. The average ankle. The attacks may last from a few days to
incubation period is 1 to 3 weeks (range: 3 days to 16 several months. Some individuals will have recur-
weeks). This rash is a diagnostic marker of the dis- rence with variable periods of remission between

attacks. The intensity of articular involvement is len C. Steere revealed an associated rash (ECM) in
variable, because some patients complain only of 25 percent of patients. He named the syndrome
aches (arthralgias), whereas others demonstrate Lyme disease in honor of the town in which it was
joint swelling {arthritis). In children the symptoms first observed.
and signs of Stage III Lyme borreliosis can mimic In 1977 it was observed that an /. dammini tick
juvenile rheumatoid arthritis. Antibody testing to bite preceded the ECM rash on a human subject.
B. burgdorferi can provide valuable clues to diagno- Willy Burgdorfer and his colleagues (1982) isolated
sis of Lyme borreliosis in those individuals who a spirochete from the midgut of the /. dammini tick;
present with Stage II or III without antecedent this spirochete was subsequently named Borrelia
history of ECM or tick bite exposure. burgdorferi. The following year, Steere isolated the
B. burgdorferi infection can be spread transpla- spirochete from blood, skin, and spinal fluid from
centally in humans. Infections during pregnancy patients with the Lyme disease syndrome and con-
can result in spontaneous abortion, premature deliv- cluded that it was the causative agent. Also, in 1983
ery, low birth weight, and congenital malformation. in West Germany, H. W. Pfister and his colleagues
These complications are similar to those caused by (1984) concluded that B. burgdorferi isolated in spi-
the spirochete Treponema pallidum, the causative nal fluid from a patient with lymphocytic meningo-
agent of syphilis. radiculitis (Bannwarth's syndrome) was causative,
Lyme borreliosis is treated with antibiotics. The and they implied that the original description of 13
best results are achieved with prompt administra- patients provided by A. Bannwarth (1941) may have
tion of oral antibiotics at the time of initial infection been due to the same organism. Dermatologist
(Stage I). The duration of the rash and associated Klaus Weber and his colleagues (1984), working in
symptoms is abbreviated by a 3-week course of oral West Germany, noted an elevation of IgG antibodies
tetracycline, penicillin, or erythromycin therapy. In in the blood of patients with the skin lesion acro-
Stage III Lyme borreliosis, 3 weeks of parenteral dermatitis chronica atrophicans (AC A). AC A is an
penicillin or ceftriaxone are the drugs of choice. The uncommon late dermatologic manifestation of Lyme
earlier antibiotics are instituted, the more likely a borreliosis. The first description of ACA was given
cure may be achieved. A delay in starting antibiotics by the German physician Alfred Buchwald (1883),
may result in lifelong, intermittent or even chronic, and may have been the first reported case of Lyme
residual symptoms from the disease. borreliosis.
Robert D. Leff
History
In 1909, in Stockholm, Swedish dermatologist Bibliography
Arvid Afzelius (1910) described a rash (which he Afzelius, A. 1910. Verhandlungen der dermatologischen
labeled erythema migrans) on a female patient Gesellschaft zu Stockholm on October 28, 1909. Ar-
chives of Dermatology and Syphilis 101: 404.
following a bite from an Ixodes tick. In 1913 an Anderson, John. 1988. Mammalian and avian reservoirs of
Austrian physician described a similar lesion on a Borrelia burgdorferi. In Lyme disease and related dis-
patient and labeled it erythema chronicum migrans orders, ed. Jorge Benach and Edward Bosler, 180-91.
(ECM). Recognition that ECM was associated with New York.
systemic symptoms occurred in France in 1922. Bannwarth, A. 1941. Chronische lymphozytare Meningi-
Investigators described patients with tick bites who tis, entziindliche Polyneuritis und "Rheumatismus."
developed subsequent erythema migrans and lym- Archive von Psychiatry und Nervenkrankheit 113:
phocytic meningoradiculitis (nervous system in- 284-376.
volvement). In 1934 a German dentist described six Buchwald, A. 1883. Ein Fall von diffuser idiopathischer
patients with erythema migrans and associated Hautatrophie. Archives of Dermatology and Syphilis
joint symptoms. And in 1951 beneficial effects of 10: 553-6.
penicillin in the treatment of a patient with ECM Burgdorfer, Willy, et al. 1982. Lyme disease - a tick-borne
spirochetosis. Science 216: IB, 1317-19.
and meningitis suggested a bacterial etiology.
Craft, Joseph E., and Allen C. Steere. 1986. Lyme disease.
In the United States the first documented case of In New frontiers in pediatric rheumatology, Proceed-
ECM occurred in a grouse hunter in Wisconsin in ings of a symposium held on June 2, 1985 at the
1969. In 1975, two homemakers reported to the Con- College of Physicians and Surgeons of Columbia Uni-
necticut State Health Department that several chil- versity, New York, 38-42. New York.
dren living close together in Lyme, Connecticut, had Garin, Bujadoux C. 1922. Paralysie par les tiques. Journal
developed arthritis. A following investigation by Al- of Medicine Lyon 71: 765-7.

VIII.85. Malaria 855
Hellerstrom, S. 1930. Erythema chronicum migrans Af- with sweating, subsiding fever, a sense of relief, and,
zelii. Acta Dermatology Venereology (Stockholm) 11: often, sleep. Between the early paroxysms the in-
315-21. fected person may feel quite well; as the disease
Johnson, Russell. 1988. Lyme borreliosis: A disease that progresses, however, the patient may be increas-
has come into its own. Laboratory Medicine: 34—40. ingly burdened by symptoms, even in the periods
Lipschiitz, B. 1913. Ueber eine seltene erythemform
between febrile paroxysms. Although infection by
(erythema chronicum migrans). Archives Dermatol-
ogy and Syphilis 118: 349-56.
any species may have serious, even fatal, conse-
Magnarelli, Louis. 1986. The etiologic agent of Lyme dis- quences, P. falciparum infection is particularly dan-
ease in deer flies, horse flies, and mosquitoes. Journal gerous because of complications associated with this
of Infectious Diseases 154(2): 355-8. parasite.
Markowitz, Lauri E., et al. 1986. Lyme disease during The term malaria, from the Italian mala and aria
pregnancy. Journal of the American Medical Associa- ("bad air"), was certainly in use in Italy by the seven-
tion 255(24): 3394-6. teenth century to refer to the cause of intermittent
Pfister, H. W., et al. 1984. The spirochetal etiology of fevers thought to result from exposure to marsh air
lymphocytic meningoradiculitis of Bannwarth (Bann- or miasma. Horace Walpole wrote home from Italy in
warth's syndrome). Journal of Neurology 231: 141-4. 1740 about "[a] horrid thing called mal'aria, that
Stadelmann R. 1934. Ein Beitrag zum Krankheitsbild des comes to Rome every summer and kills one." This is
Erythema chronicum migrans Lipschiitz. Ph.D. disser-
said to be the first use of the term in English, and it
tation, Marburg.
Steere, Allen C , and Stephen E. Malawista. 1985. Lyme
may well have been the first appearance of the word
disease. In Textbook of rheumatology, Vol. 2,2d edition, in print (Russell et al. 1963). However, Walpole and
ed. William N. Kelley et al., 1557-63. Philadelphia. other writers of the eighteenth century, and later,
Weber, Klaus, et al. 1984. European erythema migrans used the term to refer to the presumed cause rather
disease and related disorders. Yale Journal of Biology than the disease. It was only after the pathogenic
and Medicine 57: 463-71. agents were identified at the end of the nineteenth
century that usage shifted so that the term "ma-
laria" came to refer to the disease rather than the
agent.
Etiology
VIII.85 Protozoa assigned to the genus Plasmodium are
Malaria parasitic in many species of vertebrate animals in-
cluding birds, reptiles, amphibians, and mammals.
Most Old and New World primate species serve as
Malaria is the disease resulting from infection by one hosts for plasmodia, and some of these parasites are
or more of four species of protozoan parasites of the closely related to the species established in human
genus Plasmodium. These parasites are normally populations. It is generally accepted that the human
transmitted from one human host to the next by the malaria parasites evolved in association with early
bite of an infected female mosquito of the genus human beings, perhaps differentiating into the four
Anopheles. Although malaria has receded from many species recognized today in the mid-Pleistocene
temperate regions in this century, the disease contin- (Garnham 1966; Bruce-Chwatt and Zulueta 1980).
ues to be a major cause of morbidity and mortality in All of the mammalian plasmodia have similar
many tropical and subtropical countries. Three of the two-phase life cycles: an asexual (schizogonic) phase
species — Plasmodium viuax, Plasmodium falcipa- in the vertebrate host and a sexual (sporogonic)
rum, and Plasmodium malariae - are widely distrib- phase in female Anopheles mosquitoes. These cycles
uted; the fourth, Plasmodium ovale, is principally a reflect ancient anopheline and vertebrate host-
parasite of tropical Africa. P. vivax (the agent of be- parasite relationships that seem to date from at
nign tertian malaria) and P. falciparum (causing ma- least the Oligocene.
lignant tertian malaria) are responsible for the great The sexual phase in the mosquito is initiated as
majority of cases and deaths attributed to malaria the female anopheline takes a blood meal from a
throughout the world. human or other vertebrate host. Parasites in in-
Malaria is characteristically paroxysmal, and of- gested red blood cells are released as male and fe-
ten periodic. The classical clinical episode begins male gametes in the stomach of the mosquito. Fu-
with chills, extends through a bout of fever, and ends sion of the gametes produces a zygote, which, after

rapid development, migrates and encysts in the stom- P. falciparum parasites, on the other hand, are
ach wall. At maturity, after some 10 to 20 days, this much more limited in time of survival; if the disease
oocyst releases thousands of sporozoites, motile is left untreated and is not fatal, P. falciparum infec-
forms that migrate to the salivary glands. When the tion will terminate spontaneously without relapse,
now infective mosquito bites and probes for verte- usually in less than a year. Instead of developing as
brate blood, many of these sporozoites are likely to trophozoites, small numbers of red cell merozoites
be injected into the new host in released saliva. The differentiate as male and female forms (gameto-
duration of the sexual or sporogonic phase of the cytes). These circulate in erythrocytes and may even-
cycle is controlled principally by environmental tem- tually be ingested by a female Anopheles mosquito -
perature and humidity. P. vivax requires a minimum to begin a new sexual phase of the life cycle.
temperature of 16°C; P. falciparum, at least 18°C. Although malaria transmission normally follows
The duration of P. vivax sporogony is 9 to 16 days and the bite of the infected mosquito, several other
that of P. falciparum, 12 to 24 days, when environ- routes have been recorded, including congenital
mental temperatures range between 20° and 25°C transmission and direct transfer of parasites by
(Bruce-Chwatt 1987). blood transfusion or by contaminated needles shared
Most of the sporozoites injected by the biting mos- by drug abusers. Before the advent of antibiotic ther-
quito are phagocytosed, but some, traveling in the apy, malaria infections were also sometimes induced
bloodstream, reach the liver, enter parenchymal by injection for therapeutic purposes - for example,
cells, and (as tissue schizonts) proceed by nuclear to produce high fevers in the treatment of late-stage
division to form large numbers (10,000 to 20,000) of syphilis.
merozoites. Eventually, about 6 to 16 days after ini-
tial infection, the preerythrocytic schizont ruptures, Distribution and Incidence
releasing its merozoites into the bloodstream. Those Although the eradication campaigns of the 1950s
merozoites that escape phagocytosis invade red and 1960s contributed to substantial declines in the
blood cells and, as trophozoites, initiate the erythro- incidence of malaria in many countries, and to the
cytic portion of the asexual phase. The trophozoite elimination of transmission in some, malaria per-
form breaks down the hemoglobin of the host sists as a major contributor to ill health in vast areas
erythrocyte, leaving hematin pigment as a digestive of the tropical and subtropical world. Reported cases
product. As it grows, the parasite (now called an of malaria are increasing from year to year, espe-
erythrocytic schizont) divides, producing 8 to 24 me- cially in areas of Asia and the Americas undergoing
rozoites, depending on the species. For the human agricultural colonization with forest clearing and
malaria parasites, schizogony in the red cell lasts pioneering of unexploited lands. Eradication cam-
about 48 hours or, for P. malariae, about 72 hours. paigns have given way to long-term control pro-
When the schizont reaches maturity, the erythrocyte grams in most areas where the disease remains en-
bursts and the merozoites are released. Again some demic, and in some countries control is now being
will be phagocytosed whereas others will invade un- linked to or integrated with systems of primary
infected red cells. Erythrocytic schizogony may then healthcare (Bruce-Chwatt 1987; Hilton 1987).
continue through repeated cycles with increasing The present global situation has been categorized
synchronism, manifest as clinical periodicity. As a by David Clyde (1987) as follows:
consequence, more and more red cells are parasi-
tized and destroyed. Immune responses or therapeu- 1. Areas where malaria never existed or disap-
tic intervention can check the process short of pro- peared spontaneously (with a current population
found anemia, complications, and death. totaling some 1.3 billion)
Following clinical recovery, P. vivax and its close 2. Areas where control and eradication campaigns,
relative P. ovale are capable of causing relapse, even in combination with other factors, have elimi-
after several years. Recrudescence of quartan ma- nated endemic malaria in recent years (popula-
laria (P. malariae infection) may occur after many tion about 800 million)
years, even 30 or more years after initial infection. P. 3. Areas under continuing control, including most
vivax and P. ovale infections can persist because of endemic countries of Asia and the Americas (popu-
the survival in the host liver of dormant stages capa- lation about 2.2 billion)
ble of reinitiating erythrocytic schizogony. Recrudes- 4. Areas with little or no organized control, mainly
cent P. malariae infection appears to be due to long- in Africa south of the Sahara (population about
term survival of erythrocytic-stage parasites. 400 million)

Table VIII.85.1. Malaria in 1984

No. of cases reported
to the World Health Population at risk Estimated incidence per
Geographic areas Organization (millions) 1,000 population at risk
The Americas 914,000 179 11.8

Europe, including Turkey and 60,000 47 2.1
former Soviet Union
Africa south of the Sahara 5,000,000° 385 202.6
North Africa and western Asia 305,000 166 5.4
Central and South Asia 2,711,000 844 10.5
Eastern Asia and Oceania 1,300,000 1,069 7.5
Total 10,290,000
"Estimated; mainly clinical diagnoses.

Source: Adapted from World Health Organization data and Clyde (1987, tables 1 and 2).
foci of autochthonous transmission persist in this

Reported cases, and estimates for Africa south of
region.
the Sahara, are summarized in Table VIII.85.1 for
Central and South Asia. Malaria remains endemic
1984, together with incidence estimates. The total of
in most countries of the region. P. vivax is predomi-
some 10 million cases probably represents less than
10 percent of actual cases for that year because of nant, but P. falciparum is also important, and this
reporting and surveillance deficiencies. Clyde (1987) species appears to be increasing in relative preva-
believes that the infected population in 1984 may lence (Spencer 1986).
Eastern Asia and Oceania. The northeastern area of
actually have exceeded 100 million in a population
at risk of 2.6 billion. Malaria-related deaths are also Asia, including Japan, is free of transmission, as
are many of the smaller islands and island groups
poorly reported; David Hilton (1987) notes that
in Oceania. Endemic foci persist in some of the
worldwide estimates of deaths are still in the range
larger island areas (e.g., the Philippines, the Solo-
of hundreds of thousands every year.
mon Islands, Papua New Guinea, and Indonesia)
The Americas. The United States, Canada, and most and in most of mainland Southeast Asia and
countries of the Caribbean are essentially free of China. P. vivax prevails in China, where the inci-
malaria transmission and report only small num- dence is steadily declining. In Thailand, which is
bers of imported cases. Costa Rica, Panama, and also experiencing a decline in incidence, P.
several southern South American countries are falciparum is somewhat more prevalent than P.
also nearly free of local transmission. Haiti and vivax.
the Dominican Republic report only P. falciparum
cases, although in substantial numbers. P. vivax is Epidemiology and Control
the prevailing species in Mexico, Central Amer- Malaria transmission in any locale depends upon
ica, and northern South America, although many the complex interactions of parasites; vector mosqui-
P. falciparum cases are also reported, especially toes; physical, socioeconomic, and environmental fac-
from Brazil, Colombia, and Ecuador. tors; and human biology, demography, and behavior.
Europe, Turkey, and the former Soviet Union. Ma- The four species of plasmodia differ in many bio-
laria is no longer endemic in Europe and the So- logical characteristics. Each species, for example,
viet Union, but Turkey still reports some autoch- has somewhat different environmental temperature
thonous cases. requirements for sporogony; each is different in
Africa south of the Sahara. About 90 percent of the many features of its schizogonia cycle, and as a conse-
population in this region is still at risk, and trans- quence, each has distinctive clinical manifestations.
mission is high in many areas, especially in rural P. falciparum differs so much from the other three
West Africa (Spencer 1986). P. falciparum is the species (of the subgenus Plasmodium) that it has
predominant species. been assigned to its own subgenus, Laverania
North Africa and western Asia. Only a few small (Garnham 1966). Within each species, variation in

strains is also important. Differences in strains influ- Malaria endemicity is classified on the basis of
ence sporogonic development in mosquitoes, viru- spleen or parasite rates:
lence and thus the clinical course, and the develop-
1. Hypoendemic malaria: spleen or parasite rates up
ment of resistance to antimalarial drugs.
to 10 percent in 2- to 9-year-old children
The presence of anopheline mosquitoes capable of
2. Mesoendemic malaria: spleen or parasite rates of
supporting sporogony is fundamental for natural ma-
11 to 50 percent in 2- to 9-year-olds
laria transmission. Although more than 400 species
3. Hyperendemic malaria: spleen or parasite rates
of Anopheles have been described, natural sporozoite
over 50 percent in 2- to 9-year-olds together with
infections have been found in only about 67 species,
a high adult spleen rate
and only some 30 species are recognized as important
4. Holoendemic malaria: spleen or parasite rates
vectors (Spencer 1986). Usually, in any endemic area,
over 75 percent in 2- to 9-year-olds with low adult
only one, two, or three vector species are responsible
spleen rates and high infant parasite rates
for most of the malaria transmission. Parasite species
and strain differences affect anopheline receptivity to In a pioneering work, George Macdonald (1957)
infection. Vector competence for transmission is also attempted to fit many of the variables noted above
influenced by mosquito population densities, flight into an epidemiological model. His ideas continue to
ranges, feeding and resting habits, blood meal prefer- be influential in contemporary malariology despite
ences (anthropophilic for human blood; zoophilic for many advances in epidemiological and mathemati-
animal blood), blood meal frequencies, and the life- cal modeling sophistication. Macdonald's principles
span of the female anopheline. In recent decades, in denning stable and unstable malaria, for exam-
resistance to insecticides has also become a major ple, continue to be helpful in studies of epidemiolo-
vector-related determinant of transmission. gical patterns. Stable malaria is characteristically
Vector, parasite, and host interactions are pro- endemic, often hyper- or holoendemic. There is little
foundly affected by factors in the environment. seasonal change; transmission continues through
Physical factors, such as temperature, rainfall, and most or all of the year; epidemics of malaria are very
humidity, control mosquito survival and the dura- unlikely to occur; and most of the population, except
tion of sporogony. Other factors such as latitude, infants, has some immunity as a result of experience
altitude, and landscape characteristics (natural or with the disease. Control under these circumstances
human-modified) influence mosquito breeding, vec- is likely to be very difficult. Malaria in much of
tor densities, and vector survival, as well as many tropical Africa south of the Sahara corresponds to
kinds of human behavior. In addition, features of the Macdonald's stable extreme.
social and economic environment contribute in Unstable malaria may be endemic, but transmis-
many ways to patterns of transmission. sion varies from year to year and may be strictly
Age, gender, and a variety of human demographic seasonal, reflecting the strong seasonal change typi-
variables, together with genetic factors, immune cal in unstable areas. Seasonal epidemics may occur,
mechanisms, and health conditions (e.g., nutritional collective immunity varies and may be low, and chil-
status, pregnancy, and concurrent infections), consti- dren as well as infants may be nonimmune. Control
tute the final host-related set of determinants in the is relatively easy, and indeed, many of the countries
malaria epidemiological complex that must be well only recently freed from endemic malaria were in
understood before fully effective control can be insti- the unstable category.
tuted in any setting.
The incidence and prevalence of clinical cases may Immunity
be useful measures for describing the status of ma- Acquired and innate immunity are important fac-
laria in an area, but parasite and spleen rates are tors in the epidemiology of malaria. Innate resis-
even more helpful for determining the level of tance has been recognized in some human popula-
endemicity - spleen rates particularly, because en- tions. In parts of Central and West Africa, many
larged spleens are indicative of past or recent active individuals lack the Duffy blood group antigens Fya
erythrocytic schizogony. The spleen rate is the propor- and Fyb and are thus resistant to P. vivax infection.
tion of persons, usually children 2 to 9 years old, Generally, in these areas, P. ovale replaces P. vivax as
with enlarged spleens at a particular time, whereas the prevailing cause of benign tertian malaria. In
the parasite rate is the proportion of persons in a endemic P. falciparum areas of Africa, those individu-
population with microscopically confirmed para- als heterozygous for hemoglobin AS or sickle trait
sitemia at a particular time. are more likely to survive malignant tertian ma-

laria than are hemoglobin A homozygotes. The per- clinical picture may never develop. Mixed infections
sistence of sickle-cell disease (in hemoglobin SS of two or even three species may produce atypical
homozygotes), with its unfortunate consequences, is and confusing clinical manifestations.
balanced by the substantial advantage conferred by These clinical events are related to the behavior of
the AS condition, but only as long as P. falciparum the parasites in the bloodstream. The onset of chill
remains endemic in the area. Several other hemoglo- reflects the escape of parasites and metabolic prod-
bin variants have been thought to provide some pro- ucts from great numbers of ruptured red cells. By
tection against P. falciparum infection; it is known the end of the paroxysm, the parasites will have
that persistent hemoglobin F (fetal Hb) delays de- invaded new red cells to initiate another generation
velopment of falciparum parasites (Bruce-Chwatt of erythrocytic schizogony. With each cycle of inva-
1987). Another genetic condition, deficiency of the sion, multiplication, and rupture, more red cells are
red blood cell enzyme glucose 6-phosphate dehydro- destroyed. In the absence of treatment and immune
genase (G6PD), also provides a degree of protection defenses, severe anemia may develop, particularly
against falciparum infection. in falciparum malaria. The spleen enlarges during
Acquired immunity in malaria is species-specific the acute episode, in part because of its function in
and also specific to stage, that is, to the sporozoite, to filtering out of the bloodstream the detritus result-
the asexual forms in the blood, or to the sexual ing from red cell destruction. The liver may also
stages (Clyde 1987). In endemic areas, newborns increase in size.
may be protected for a few months by maternal anti- Although malaria caused by the other three spe-
bodies that have crossed the placenta. After this cies may be fatal, most of the serious complications
phase of protection, however, infants and toddlers and deaths are caused by P. falciparum. This species
are especially vulnerable; most of the severe ill- can invade a high proportion of the total red cell
nesses and deaths due to malaria in endemic regions mass, and the parasitized cells tend to agglutinate,
occur in these early years. Older children and adults occluding capillaries in almost any organ. These oc-
gradually acquire immunity with repeated exposure clusions are considered to underlie cerebral, gastro-
to infection. This partial immunity (premunition) is intestinal, adrenal, and other complications in
sustained in the presence of low densities of para- falciparum malaria. Cerebral malaria begins with
sites in the blood. In premune individuals the spleen headache and may progress to convulsions, delir-
may remain enlarged; hence the spleen rate may be ium, and coma. Gastrointestinal complications re-
relatively high in an adult population despite a low semble bacillary dysentery or cholera.
parasite rate. With prolonged exposure and infec- The initial uncomplicated and untreated episode
tion, however, as in a holoendemic area, eventual of malaria usually lasts 2 to 4 weeks (about twice as
spleen scarring and shrinkage leads to a low adult long for P. malariae). Relapses commonly occur in
spleen rate. Attenuated malaria certainly contrib- untreated malaria. Drug-resistant strains of P.
utes to impaired resistance to other diseases; thus falciparum may also cause relapses after inadequate
improved malaria control in endemic areas gener- treatment.
ally results in declines in morbidity and mortality Blackwater fever is a distinctive intravascular
from all causes (Bruce-Chwatt 1987). hemolytic disorder associated with longstanding and
repeated falciparum malaria infection, especially in
Clinical Manifestations and Pathology hyper- and holoendemic areas. The incidence of
The classical malaria paroxysm is initiated by a blackwater fever has fallen considerably in the sec-
chill, lasting up to an hour and often accompanied by ond half of this century as malaria control has im-
headache, nausea, and vomiting. The chill is fol- proved and as drug prophylaxis and treatment has
lowed by a period of spiking fever lasting several expanded from an earlier dependence on quinine.
hours. The subsiding fever is accompanied by sweat- Quinine is not an essential etiologic factor, but the
ing, often profuse. The relieved patient may drift off onset of blackwater fever has often been noted to
to sleep, to awaken feeling relatively well. The early follow the administration of therapeutic doses of the
paroxysms may be asynchronous.' As the clinical epi- drug. It is also known that the disorder rarely occurs
sode progresses, P. malariae paroxysms occur about in persons who have taken quinine regularly as a
every 72 hours {quartan periodicity), whereas those prophylactic. Blackwater fever is characterized by
of the other three species occur with tertian (48- abrupt onset, chill, fever, jaundice, nausea, vomit-
hour) periodicity. P. falciparum infection is less ing, and red or dark-brown urine containing hemo-
likely to become clearly synchronous, and the classic globin. The case mortality rate, resulting principally

from anuria and uremia, usually falls between 10 Western Hemisphere remained free of the disease
and 30 percent. until contact (Dunn 1965).
In the first two centuries after 1492, malaria para-
History and Geography sites must have been introduced many times from
Since at least the mid-Pleistocene, many thousands Europe and Africa. Anopheline vectors were at
of generations of humans have been parasitized by hand, species native to the Americas. Together with
the plasmodia (Garnham 1966). Species very similar smallpox, measles, and other infectious diseases
to the human plasmodia have also been described brought across the Atlantic from the Old World,
from gorillas and chimpanzees; indeed the relation- malaria soon began to contribute to the depopula-
ships of the malaria parasites of humankind and the tion of the indigenous peoples, especially those of the
African apes are extremely close (Dunn 1966; lowland American tropics (Borah and Cook 1963;
Garnham 1966). It is therefore certain that human Crosby 1973; McNeill 1976).
malaria is an Old World disease in its origins. There From its early, usually coastal, sites of introduc-
has, however, been some debate about the timing of tion, malaria spread widely in North, Central, and
malaria's appearance in the Western Hemisphere South America, limited principally by altitude and
(McNeill 1976). Some have suggested that malaria latitude - that is, by factors controlling the distribu-
was present in the New World long before the time of tion of vector mosquitoes. By the nineteenth century
European contact, but a strong case can be made in North America, the disease was prevalent in
that the hemisphere was malaria-free until the end much of the Mississippi Valley; seasonal transmis-
of the fifteenth century (Dunn 1965; McNeill 1976). sion occurred even in the northernmost areas of the
Malaria could have reached the New World before Mississippi basin (Ackerknecht 1945). Malaria trans-
1492 only as an infection of migrants from northeast mission, unstable and seasonal, also extended into
Asia or by pre-Columbian sea-borne introductions. the northeastern United States, well north in Califor-
The possibility that humans brought malaria over- nia, and far to the south in South America. By the
land into North America from Siberia can almost eighteenth and nineteenth centuries, malaria had
certainly be discounted; conditions for malaria trans- also become established as a stable endemic disease
mission were unsuitable in the far north during and in the American subtropics and tropics, including
after the Pleistocene, as they are today. It is equally most of the islands of the Caribbean.
unlikely that the Vikings could have introduced ma- The Old World gave malaria to the New; the New
laria in the centuries before Columbus. These voyag- World, however, provided the first effective remedy
ers came from regions of Europe and the North Atlan- for the disease. It is recorded that a sample of
tic (Greenland, Iceland) presumably free of malaria cinchona bark, taken from a Peruvian tree as a me-
at that time, and they seem to have visited northeast- dicinal, was carried to Europe in 1632 by a Spanish
ern North American coasts that were north of any priest (Russell et al. 1963). The bark was soon discov-
possible receptive anopheline mosquito populations. ered to provide relief from certain intermittent fe-
Similarly, any voyagers landing on American shores vers. This therapeutic action allowed Richard Mor-
from the central or eastern Pacific could not have ton and Thomas Sydenham in England in 1666, and
carried the parasites with them because islands in Francesco Torti in Italy in 1712, to begin the process
that region are free of anopheline vectors and thus of of defining malaria as a clinical entity separable
locally transmitted malaria. Voyagers reaching from other fevers, which failed to respond to
American coasts from eastern Asia (e.g., fishermen cinchona (Russell et al. 1963). By the end of the
adrift from Japan) could conceivably have introduced seventeenth century, cinchona bark was an impor-
malaria, but this possibility too is remote. tant export product from Peru, well established in
Moreover, and more to the point, colonial records the treatment of intermittent fevers.
indicate that malaria was almost certainly unknown The human malaria parasites have evolved in asso-
to the indigenous peoples of the Americas. It is also ciation with their evolving hosts and have followed
evident that some areas that supported large pre- the human species through most, but not all, of its
Columbian populations soon became dangerously dispersal in Africa, Asia, and Europe. Transmission,
malarious after European contact (McNeill 1976). dependent on suitable anopheline mosquitoes, has
The absence in aboriginal American populations of always been limited by all those environmental condi-
any of the blood genetic polymorphisms associated tions, influenced by latitude and altitude, that con-
with malaria elsewhere in the world is another kind trol vector breeding and survival.
of evidence consistent with the conclusion that the The antiquity of the hnman-Plasmodium associa-

tion in the Old World is symbolized, biologically, by many, southern Scandinavia, Poland, and Russia
the existence in modern populations of some of the (Bruce-Chwatt and Zulueta 1980).
blood genetic polymorphisms. Early texts - Chinese, Through all of these centuries the record of ma-
Hindu, Chaldean, Greek - give us other evidence of laria's human impact in Asia and Africa is fragmen-
this ancient association (Russell et al. 1963; McNeill tary. With the onset of European colonization, how-
1976; Bruce-Chwatt and Zulueta 1980). Malaria was ever, it soon became obvious that endemic malaria
probably endemic in Greece by the fourth century, was a threat almost everywhere in the Old World
B.C.; Hippocrates described the types of periodicity of tropics, especially to the colonizers (who were, of
intermittent fevers - quotidian, tertian, quartan - course, generally nonimmune upon arrival in the
and took note of the enlargement of spleens in those tropics). The beginnings of tropical medicine and
who lived in low, marshy districts. In Italy, too, the modern malariology are entangled in this recogni-
intermittent fevers were well known, for example, to tion (Dunn 1984).
Cicero, and well described by Celsus, Pliny the Elder, The modern era in malariology began in the last
and Galen (Russell et al. 1963). two decades of the nineteenth century with the iden-
Malaria was certainly a disease of some impor- tification of the causal parasites and the recognition
tance in the centuries of Roman domination of Eu- of the role of anopheline mosquitoes as vectors.
rope and the Mediterranean basin. However, in their These discoveries provided the rationale for new
review of malaria in early classical times, especially strategies in malaria control, developed during the
in relation to military operations, L. J. Bruce- first third of the twentieth century. Malaria control
Chwatt and J. de Zulueta (1980) reached the conclu- itself was not a new concept; nor was the control of
sion that malaria was much less destructive than it mosquitoes a new idea at this time. Humankind had
has been in recent centuries, primarily because P. sought from ancient times to control biting mosqui-
falciparum was absent or rare and the other species toes as pests (Russell et al. 1963). The new rationale,
were less intensely transmitted. The conclude that P. however, provided for much more specific vector con-
falciparum failed to spread in those centuries be- trol, directed principally at those anophelines that
cause Anopheles atroparvus was refractory as a vec- proved to be important in transmission. Malaria con-
tor for the falciparum strains then introduced from trol was further strengthened in the 1930s with the
time to time by travelers. A. atroparvus, basically a introduction of synthetic antimalarials, useful not
zoophilic species, was also a poor vector for P. ma- only in treatment but also in prophylaxis. The 1940s
lariae and P. vivax. By late classical times, however, brought further advances in chemotherapy together
it appears that two other anopheline species, with the first of the residual insecticides, DDT.
Anopheles labranchiae and Anopheles sacharovi, By the late 1940s and early 1950s, the resources
had been introduced and dispersed along the coasts for treatment and control of malaria appeared to be
of southern Europe from their North African and sufficiently formidable to justify attempts at na-
Asian origins. These anthropophilic species were tional eradication in a few countries (e.g., Venezu-
much more effective as vectors for all three of the ela, Italy, the United States). Early success in local
species of plasmodia. By the final centuries of the or aerial eradication, based on residual spraying,
Roman Empire, malaria was a more lethal force and together with concerns about the emergence of
may have contributed to the social, political, and anopheline resistance to DDT and other insecticides,
cultural decline that had set in. led to a decision in 1955 to commit the World Health
After the fall of the Roman Empire, the history of Organization to malaria eradication. This commit-
malaria in Europe and the Mediterranean region is ment pushed many countries into supposedly time-
obscure for many centuries (Bruce-Chwatt and limited eradication campaigns, often with consider-
Zulueta 1980). With few exceptions medieval medi- able WHO financial and adivsory support. Some of
cal writers provide only sketchy and confusing ac- these campaigns were successful, especially in coun-
counts of cases and outbreaks that may have been tries with unstable malaria, but others faltered after
due to malaria. During the Renaissance, the histori- dramatic initial reductions in incidence. By the end
cal record is clearer and richer, but malaria appears of the eradication era, in the early 1970s, some hun-
not to have represented a major problem to society in dreds of millions of people were living in areas
those centuries. It is not until the seventeenth and where campaigns had eliminated endemic malaria
eighteenth centuries that malaria became resurgent (Clyde 1987), but in many other areas malaria con-
in Europe, not only in the south but, in periodic tinued to prevail, forcing a return to long-term con-
outbreaks, as far north as the Netherlands, Ger- trol strategies.

In 1980 the World Health Organization began to Russell, P. F., et al. 1963. Practical malariology, 2d edition.
recommend that malaria control be coordinated with London.
primary health care. The experiences, especially the Spencer, Harrison C. 1986. Epidemiology of malaria. In
difficulties, of the eradication years also made it im- Clinics in tropical medicine and communicable dis-
perative that modern malaria control be strongly sup- eases, Vol. 1: Malaria, 1—28.
ported by epidemiologicalfieldwork with recognition
of local variability in transmission patterns and of
sociocultural, economic, and human behavioral influ-
ences on transmission and control (Bruce-Chwatt
1987). Malaria control and therapy continues to be VIII.86
complicated by mosquito resistance to insecticides
and by parasite resistance to drugs. Vaccine develop- Marburg Virus Disease
ment proceeds, although slowly. The problems posed
by malaria persist, but they are not insoluble. Ma-
laria will remain endemic in many countries in the History
twenty-first century, but the prospects are good for In 1967, a disease outbreak occurred in a laboratory
steady improvement in control. in Marburg, Germany, where the kidneys of
Frederick L. Dunn cercopithecoid (Green African; vervet) monkeys
were being taken out for preparation of cell cul-
tures. Twenty-seven laboratory workers (including
Bibliography a worker in Yugoslavia) fell ill with a grave illness,
Ackerknecht, E. H. 1945. Malaria in the Upper Missis- and seven died. There were four secondary cases in
sippi Valley, 1860-1900. Bulletin of the History of total (including the wife of an infected laboratory
Medicine, Supplement No. 4.
Borah, Woodrow W., and Sherburne F. Cook. 1963. The
worker in Yugoslavia secondarily infected by sex-
aboriginal population of Central Mexico on the eve of ual intercourse), but none fatal. Early suspicions
the Spanish Conquest. Ibero-Americana No. 45. focused on yellow fever, but this was soon ruled out
Bruce-Chwatt, L. J. 1987. Malaria and its control: Present (Casals 1971). In due course, a virus was isolated
situation and future prospects. Annual Review of Pub- and found to be quite distinct from any other
lic Health 8: 75-110. known viruses. Electron micrographs revealed a
Bruce-Chwatt, L. J., and J. de Zulueta. 1980. The rise and virus with bizarre morphology of a type never seen
fall of malaria in Europe: A historico-epidemiological before (Peters, Muller, and Slenckza 1971). Pictures
study. London. taken resembled photographs of a bowl of spaghetti.
Clyde, David F. 1987. Recent trends in the epidemiology The agent was named Marburg virus and the
and control of malaria. Epidemiologic Reviews 9: disease Marburg disease. Strict monkey quaran-
219-43. tines were initiated. No further cases were seen in
Crosby, Alfred W., Jr. 1973. The Columbian exchange: Bio-
laboratory workers.
logical and cultural consequences of 1492. Westport,
Conn. An intensive and extensive series of field studies
Dunn, Frederick L. 1965. On the antiquity of malaria in were initiated in East Africa, which had been the
the Western Hemisphere. Human Biology 37: 385-93. monkeys' homeland (Henderson et al. 1971; Hennes-
1966. Patterns of parasitism in primates: Phylogenetic sen 1971; Kalter 1971). No virus recoveries were
and ecological interpretations, with particular refer- made from any of the monkeys examined. In later
ence to the Hominoidea. Folia Primatologica 4: 329- years, serologic studies involving humans and pri-
45. mates, and also rodents, have been carried out in
1984. Social determinants in tropical disease. In Tropi- many regions, as can be seen in Table VIII.86.1.
cal and geographical medicine, ed. K. S. Warren and ThefirstMarburg cases seen in Africa occurred in
A. A. F. Mahmoud, 1086-96. New York. February of 1975. A young Australian couple tour-
Garnham, P. C. C. 1966. Malaria parasites and other ing in Rhodesia (Zimbabwe) became ill by the time
haemosporidia. Oxford.
Hilton, David. 1987. Malaria: A new battle plan. Contact
they got to South Africa. They were admitted to a
95: 1-5. major hospital in Johannesburg where the young
Macdonald, George. 1957. The epidemiology and control of man died and the young lady recovered. A nurse
malaria. London. tending them also sickened and recovered. After the
McNeill, William H. 1976. Plagues and peoples. Garden disease was determined to be Marburg, a thorough
City, N.Y. epidemiological inquest was carried out all along the

VIII.86. Marburg Virus Disease 863
Table VIII.86.1. Serologic studies of Marburg virus in humans and other primates
No. No. Percent
Study area Date examined positive positive Remarks
Humans
Senegal: northern provinces 1977 159 0 0
Central African Republic 1980 499 7 1.4 several regions
Liberia 1982 400+ 4 1 several regions
Gabon 1982 253 0 0
Kenya 1982 58 0 0
Cameroons 1982 1517 15 1 several regions
Sudan: northern provinces 1979-82 231 0 0 very desert region
Sudan: central provinces 1979-82 240 0 0 savannah regions
Sudan: southern provinces 1979-82 176 1 0.6 agri and forest
Kenya 1983 741 0 0 several regions
Kenya 1983 1899 8 4.2 several regions
Liberia 1986 215 2 2
Nigeria 1988 1677 29 1.1 several regions
Primates
Kenya 1981 136 4 3 vervet monkeys
Kenya 1981 184 1 0.6 baboons
Gabon 1982 48 0 0 chimpanzees
route of passage of the victims, concentrating par- capsid core of approximately 280 A width (Peters et
ticular attention on every locale where they spent a al. 1971). Marburg virus was shown (Casals 1971) to
night. Animal, insect, and human populations were be unrelated to the many arboviruses against which
sampled. No evidence of endemic disease was found it was tested, and most closely resembles the Ebola
(Gear et al. 1975). virus agent discovered in 1976. In fact, both Marburg
On January 14,1980, a 58-year-old man from west- and Ebola viruses have since been placed in a new
ern Kenya was seen in a Nairobi hospital. He died 6 family, Filoviridae (Kiley et al. 1982), which includes
hours after admission, and a physician who attended but the two members thus far.
him also became ill but recovered. A Marburg virus It was discovered that the Marburg virus could be
was isolated from his blood (Centers for Disease Con- inactivated by gamma irradiation (Elliot, McCor-
trol 1980). Subsequent epidemiological investiga- mick, and Johnson 1982); this finding made the
tions carried on in western Kenya produced a posi- preparation of inactivated diagnostic reagents possi-
tive finding: Antibodies against the Marburg virus ble. Cultivation of Marburg in cell culture has al-
were found in two vervet monkeys from among lowed observation of growth and multiplication tak-
many primates examined. ing place in a number of mammalian and avian cell
The latest episode involved a boy in Kenya in 1987 types. A cytopathic effect on cells was observed in
who became infected in a visit to a park in the Cercopithecus kidney cell lines, and human amnion
western part of Kenya. The boy died. There were no cell lines (Hoffmann and Kunz 1971).
secondary cases reported. Immunoglobulin responses have been studied
(Wulff and Johnson 1979), measured by immunofluo-
Etiology rescence. Immunoglobulin M antibodies appear in
Electron microscopic examination of blood, liver, and sera of patients infected with Marburg virus 4 to 7
spleen of guinea pigs infected with materials from days after onset of illness. Titers peak 1 to 2 weeks
patients show a long, viruslike agent, quite unlike later, and by 1 to 2 months have decreased consider-
any virus particle ever before visualized. The parti- ably. Antiviral IgG antibodies appear at the same
cles vary in length, up to several microns. The width time as or a little later than IgM antibodies and
of the particles is also variable, with limits of 720 to persist much longer (Wulff and Johnson 1979). In
1100 A (7,200 to 11,000 nanometers). There is an autopsy material, antigenic material is present in
outer shell, an intermediate clear zone, and a nucleo- large amounts, and can be demonstrated as late as 3

hours after death by use of immunofluorescent tech- Ebola virus infection is considerably more fatal in
niques (Wulff, Slenczka, and Gear 1978). humans than is the Marburg virus. In the four secon-
dary Marburg cases studied, it was clear that their
Clinical Manifestations and Diagnosis clinical course was less severe than that seen in
The incubation period following exposure varied primary cases, and there was no mortality.
from 5 to 7 days. In six cases for which data are
available, death occurred between days 7 and 16. Treatment and Prophylaxis
The onset was indicated by malaise, myalgia, and No effective therapy has been found. In one case in a
often prostration (Martini 1971). Vomiting fre- London treatment center, therapy was instituted us-
quently occurred by the third day, and conjunctivitis ing interferon in conjunction with immune plasma.
by the fourth, by which time the temperature had The patient, a secondary exposure case, recovered.
reached 40°C. A rash occurred on the fifth day, was Further clinical trials on human beings await fur-
macular in type, and progressed usually to a maculo- ther cases.
papular rash that later coalesced into a more diffuse Basic methods for the management of patients
rash. In severe cases, a diffuse dark livid erythema with suspected viral hemorrhagic fever include
developed on face, trunk, and extremities. An strict isolation and precaution in examination and
enanthem of the soft palate developed at the same in taking specimens from patients, as well as in
time as the rash. Spleen and liver were not palpable. handling material from suspect cases in the labora-
Lymph node enlargement was noted in the nuchal tory. Such procedures are not readily applicable in
region and the axillae. A diarrhea appeared, often bush clinics in many parts of Africa. Further precau-
with blood in the stools. The South African cases tions are necessary in the movement of suspected
differed only in that there were no enanthem and no cases internationally and in the shipment of speci-
lymph node enlargement. mens internationally (Simpson 1977; Centers for Dis-
The above description was declared by several cli- ease Control 1988).
nicians to make diagnosis easy. This may be true Prophylaxis and control await further epidemio-
when there is a clustering of cases, and epidemiolo- logical information on animal reservoirs of disease,
gists are on the alert; however, in much of Africa, modes of transmission from animal reservoirs (if
the occurrence of single cases, however severe, indeed there are animal reservoirs) to humans, and
would not be likely to arouse suspicion. Moreover, modes of persistence of the virus in nature.
during the first 5 to 6 days, the symptoms could be Wilbur G. Downs
mistaken for those of many other diseases. Labora-
tory diagnosis is accomplished by means of immuno-
fluorescence techniques, by electron microscopic ex- Bibliography
amination of a serum sample from a patient, which Casals, J. 1971. Absence of a serological relationship be-
tween the Marburg virus and some arboviruses. In
has been centrifuged and placed on a grid (Wulff et
Marburg virus disease, ed. G. A. Martini and R.
al. 1978), and by inoculation of laboratory animals. Siegert, 98-104. New York.
None of these methods is readily accessible in the Elliot, L. H., J. B. McCormick, and K. M. Johnson. 1982.
usual field situation; yet early diagnosis is impera- Inactivation of Lassa, Marburg and Ebola viruses by
tive in order to abort a possible developing epidemic. gamma irradiation. Journal of Clinical Microbiology
16: 704-8.
Mortality Evans, A. S., ed. 1978. Viral infections of humans: Epi-
Because descriptions of Marburg virus pathology are demiology and control, 2d edition. New York.
equally applicable to Ebola virus, some pathologists Fields, B. N., ed. 1985. Virology. New York.
feel that the findings are not distinctive enough to Gear, J. H. S. 1988. CRC handbook of viral and rickettsial
permit a positive diagnosis of either on the basis of fevers. Boca Raton, Fla.
Gear, J. H. S., et al. 1975. Outbreak of Marburg virus
pathology alone, especially in regions where there
disease in Johannesburg. British Medical Journal, No-
are many causes of fever and death. vember 29: 489-93.
Guinea pigs and rhesus and vervet monkeys are Haas, R., and G. Maass. 1971. Experimental infection of
susceptible to the virus. The infection is fatal for the monkeys with the Marburg virus. In Marburg virus
monkeys and, often but not always, fatal for the disease, ed. G. A. Martini and R. Siegert, 136—43. New
guinea pigs. Guinea pigs that recover may have per- York.
sistent virus in serum and urine for several weeks. Henderson, B. E., et al. 1971. Epidemiological studies in
The same has been observed for human beings. Uganda relating to the "Marburg" agent. In Marburg

VIII.87. Mastoiditis 865
virus disease, ed. G. A. Martini and R. Siegert, 166—

76. New York. VIIL87
Hennessen, W. 1971. Epidemiology of Marburg virus dis-
ease. In Marburg virus disease, ed. G. A. Martini and
Mastoiditis
R. Siegert, 161-5. New York.
Hoffmann, H., and C. Kunz. 1971. Cultivation of the Mar-
burg virus (Rhabdovirus simiae) in cell cultures. In Infections of the middle ear and mastoid encompass a
Marburg virus disease, ed. G. A. Martini and R. spectrum of potentially serious medical conditions
Siegert, 112-16. New York. and sequelae. Decreased hearing from ear infections
Isaacson, M. 1988. Marburg and Ebola virus infections. In may have a lifelong impact on speech, learning, and
CRC handbook of viral and rickettsial fevers, ed. social and vocational development, causing these con-
J. H. S. Gear, 185-97. Boca Raton, Fla. ditions to remain a major health concern. Because of
Johnson, K. M. 1978. African hemorrhagic fevers due to the anatomic relationship of the middle ear and mas-
Marburg and Ebola viruses. In Viral infections of hu- toid to the middle and posterior cranial compart-
mans: Epidemiology and control, ed. A. S. Evans, 9 5 - ments, life-threatening complications may occur.
103. New York.
Kalter, S. S. 1971. A serological survey of primate sera for
antibody to the Marburg virus. In Marburg virus dis- Classification
ease, ed. G. A. Martini and R. Siegert, 177-87. New
Inflammatory diseases of the middle ear and mas-
York.
toid are categorized according to the underlying dis-
Kiley, M. P., et al. 1982. Filoviridae: A taxonomic home for
Marburg and Ebola viruses? Intervirology 18: 24-32. ease process and location:
Martini, G. A. 1971. Marburg virus disease, clinical syn- 1. Acute suppurative otitis media (AOM) is char-
drome. In Marburg virus disease, ed. G. A. Martini acterized by obstruction of the eustachian tube,
and R. Siegert, 1-9. New York. allowing the retention and suppuration of retained
Murphy, F. M. 1985. Marburg and Ebola viruses. In Virol- secretions. AOM is the medical term associated
ogy, ed. B. N. Fields, Chapter 47. New York. with, most commonly, the acute ear infection of
Peters D., G. Muller, and W. Slenckza. 1971. Morphology, childhood. Generally the course of this infection is
development and classification of the Marburg virus. self-limited, with or without medical treatment,
In Marburg virus disease, ed. G. A. Martini and R. and the retained infected secretions are discharged
Siegert, 68-83. New York. through either the eustachian tube or a ruptured
Siegert, R., and W. Slenckza. 1971. Laboratory diagnosis tympanic membrane.
and pathogenesis. In Marburg virus disease, ed. G. A.
Martini and R. Siegert, 157-60. New York.
Acute coalescent mastoiditis can result from fail-
Siegert, R., H.-L. Shu, and W. Slenczka. 1968. Zur Diagnos-
ure of these processes to evacuate the abscess. Co-
tic und Pathogenese der Infektion mit Marburg-virus. alescence of disease within the mastoid leads to pus
Hygiene Institut ofPhilipps University (Marburg Uni- under pressure and ultimately dissolution of sur-
versity) MarburglLahn: 1827-30. rounding bone. This condition may require urgent
Simpson, D. I. H. 1977. Marburg andEbola virus infections: surgical evacuation because the infection is capable
A guide for their diagnosis, management and control. of spreading to local and regional structures.
WHO Offset Publication No. 36, Geneva. 1-28. 3. Otitis media with effusion (OME) is an inflam-
U.S. Public Health Service. Centers for Disease Control. matory condition of the middle ear in which serous
1988. Management of patients with suspected viral or mucoid fluid accumulates. Both AOM and OME
hemorrhagic fever. Morbidity and Mortality Weekly are precursor conditions to tympanic membrane re-
Report 37 (Feb. 26): 1-15.
tractions and perforations. Ongoing eustachian tube
Wulff, H., and K. M. Johnson. 1979. Immunoglobulin M
and G responses measured by immunofluorescence in
dysfunction predisposes to persistent retained secre-
patients with Lassa or Marburg infections. Bulletin of tions in the ear and recurrent acute attacks of otitis
the World Health Organization 57: 631-5. media. A small percentage of these patients develop
Wulff, H., W. Slenczka, and J. S. S. Gear. 1978. Early a chronic tympanic membrane perforation which, in
detection of antigen and estimation of virus yield in most cases, allows eventual aeration of the middle
specimens from patients with Marburg virus disease. ear and mastoid air-cell spaces and resolution of the
Bulletin of the World Health Organization 56: 633-9. underlying disease process.
4. Chronic suppurative otitis media (CSOM) is
defined as an ear with a tympanic membrane
perforation. Benign CSOM is characterized by a dry
tympanic membrane perforation, unassociated with

active infection. Active CSOM is the result of entrance into school. The incidence of uncomplicated
intermittent bacterial infection often in the pres- AOM is not significantly different in boys from that
ence of ingrown skin in the middle ear and mastoid in girls. Mastoiditis, however, would appear to be
cavities. This skin ingrowth is known as cholestea- more common among males.
toma formation. Primary acquired cholesteatoma Studies of eastern coast American children have
occurs through a tympanic membrane retraction demonstrated a higher incidence of middle ear infec-
into the attic of the middle-ear space, with a tions in Hispanic and Caucasian children than in
subsequent potential for extension into the middle black children. The higher incidence of middle ear
ear and mastoid air-cell systems. Secondary ac- and mastoid infections in certain peoples is not
quired cholesteatoma is denned as skin growth readily explained. Variability in eustachian tube
through a tympanic membrane perforation into the size, orientation, and function among racial groups
ear. has been suggested as being responsible for differ-
ences in disease incidence. Genetic predisposition to
Distribution and Incidence middle ear infection and associated complications
Surveys of large pediatric populations demonstrate has also been demonstrated. Down syndrome, cleft
that 80 percent of all children will experience one or palate, and other craniofacial anomalies are also
more episodes of AOM by the age of 6. Together associated with a high risk of developing AOM,
AOM, OME, and CSOM comprise one of the most OME, and CSOM.
common disease entities affecting human popula- The severity of otitic infections is related to factors
tions. Indeed, AOM is thought to be the most com- such as extremes of climate (temperature, humidity,
mon disease treated with antibiotics. and altitude) and poverty with attendant crowded
Prevalence studies have demonstrated an extraor- living conditions, inadequate hygiene, and poor sani-
dinarily high incidence of complicated infections of tation. There is a well-recognized seasonal variance
the middle ear in African, American Indian, Alas- in the incidence of AOM. During the winter months,
kan and Canadian Eskimo, Australian aboriginal, outpatient visits for AOM are approximately 4-fold
and New Zealand Maori pediatric populations, sug- higher than in the summer months. Although in-
gesting that disease-manifesting tissue destruction take of mother's milk and avoidance of cigarette
of the middle-ear and mastoid structures is much smoke appear to confer some protection against
more prevalent in these areas. By contrast, studies OME, no effect on the incidence of suppurative com-
of children in different geographic areas indicate plications has been shown.
that the incidence of uncomplicated disease in the
middle ear is similar in all areas. Etiology
The incidence of complicated infections producing Eustachian tube dysfunction is the most important
mastoiditis has dramatically declined since the ad- factor in the pathogenesis of middle ear infections.
vent of antibiotics in the 1930s and 1940s. Prior to The most commonly cited problem is an abnormal
that time, acute coalescent mastoiditis complicated palatal-muscle, eustachian-tube vector, which com-
AOM in approximately 20 percent of the cases. Ini- monly occurs in young children. With adolescent
tially, antibiotics cut into mortality rates from mas- growth, descent of the soft-palate-muscle sling rela-
toiditis, but overall moribidity remained unchanged. tive to the eustachian tube orifice improves the eu-
By the 1950s, however, the incidence of acute mas- stachian tube opening. However, poor tubal function
toiditis resulting from AOM had declined to 3 per- may persist with mucosal disease (allergic, in-
cent. Current reports indicate that mastoiditis and flammatory, immunologic impairment, or immotile
other infectious complications will develop in less cilia), extrinsic compression (enlarged adenoid or
than 0.5 percent of cases of AOM. nasopharyngeal tumor), or palatal muscle dysfunc-
tion (cleft palate and other craniofacial anomalies).
Epidemiology Persistent eustachian-tube dysfunction induces a
A variety of host and environmental factors, as well relative negative pressure in the middle-ear space.
as infectious etiologic agents, have been linked to The lack of aeration and the accumulation of effu-
infection of the middle ear and mastoid. AOM occurs sions provide an environment conducive to the devel-
most commonly between 6 and 24 months of age. opment of OME or AOM.
Subsequently, the incidence of AOM declines with Bacteriologic studies identify Streptococcus pneu-
age except for a limited reversal of the downward moniae and Hemophilus influenzae most frequently
trend between 5 and 6 years of age, the time of as the pathogenic organisms in AOM. Group A beta-

VHI.87. Mastoiditis 867
hemolytic streptococcus, Staphylococcus aureus, and CSOM in its active form often presents with foul-
Branhamella catarrhalis are less frequent causes of smelling drainage and longstanding hearing loss.
AOM. Gram-negative enteric bacilli are isolated on Otoscopy reveals tympanic membrane retraction,
occasion in infants up to 6 weeks of age with AOM. perforation or hyalinization, and often, evidence of
When AOM continues beyond 2 weeks as a result bony erosion, with the development of a cystlike
of inadequate antimicrobial therapy, progressive mass called cholesteatoma. Development of pain in
thickening of the mucosa lining the middle ear ob- such an ear is a foreboding sign, as it often repre-
structs free drainage of purulent secretions, thereby sents the obstruction of drainage of the infection,
permitting bone destruction and extension of infec- and pus under pressure. Local complications of
tion. This process may eventuate in mastoiditis and CSOM include bone erosion producing hearing loss,
possibly other local or intracranial extensions of sup- facial nerve dysfunction, sensorineural hearing loss,
puration. ringing sounds in the ear, and vestibular distur-
bances. On occasion, infection will extend into the
Immunology bony skull or into the soft tissues of the neck and
The respiratory mucosal membrane that lines the scalp, either through normal preformed pathways
middle-ear space and mastoid air cells is an immuno- such as vascular channels, or through progressive
logic defense consisting of constantly renewed mucus bone destruction. Catastrophic intracranial compli-
that contains lysozyme, a potent, bacteria-dissolving cations include abscesses, abnormal fluid accumula-
enzyme. In response to an invading organism, production, lateral sinus thrombosis, meningitis, and brain
tion of mucus is increased. Inflammatory dilation of herniation.
vessels, white blood cell migration, and proteolytic
enzyme and antibody deposition contribute to the Pathology
formation of mucopurulent (containing both mucus Pathological findings associated with AOM demon-
and pus) secretions. All of the major classes of strate inflammatory changes in the lining of the
immunoglobulins have been identified in middle-ear middle ear as well as suppurative exudates in the
effusions of patients with AOM. A significant type- middle-ear cleft. The quantity of the exudate in-
specific antibody response in the serum to the bacte- creases with time and exerts pressure on the tym-
ria responsible for AOM has been demonstrated. The panic membrane. The bulging tympanic membrane
presence of this type-specific antibody in middle-ear may rupture spontaneously in the central or mar-
effusions is associated with clearance of mucopuru- ginal portions. Marginal perforations are more
lent secretions and an early return to normal middle- likely to lead to ingrowth of skin and the formation
ear function. of a secondary acquired cholesteatoma. Primary ac-
The incidence of otitis media and attendant compli- quired cholesteatomas arise in retraction pockets of
cations is higher in individuals with congenital or the tympanic membrane that are induced by eusta-
acquired immunologic deficiencies. The presence of chian tube dysfunction. Cholesteatoma can also
a concomitant malignancy, the use of immunosup- arise from congenital or traumatic implantation of
pressive drugs, uncontrolled diabetes, and previous skin into the middle ear as well as from abnormal
irradiation are also associated with a higher risk of changes in the middle-ear mucosal lining in re-
developing AOM and related complications. sponse to inflammation.
Suppurative AOM persisting beyond 2 weeks can
Clinical Manifestations initiate the development of acute coalescent mas-
The onset of AOM in childhood is often associated toiditis. The progressive thickening of the mucosa of
with fever, lethargy, and irritability. Older children the middle ear begins to obstruct the drainage of
may experience earaches and decreased hearing. Ex- mucopus through the eustachian tube. Stoppage of
amination with a hand-held otoscope demonstrates blood in the veins and the high acidity of that blood
tympanic membrane redness, opacity, bulging, and promote demineralization and the loss of bony parti-
poor mobility when pneumatic pressure is applied. tions. As a consequence, separate air cells of the mas-
However, there is considerable variability in the toid coalesce into large cavitiesfilledwith mucopuru-
symptoms and signs of acute otitis media. lent secretions and thickened mucosal granulations.
OME is often characterized by hearing loss and a The erosion of bone, however, may not be confined to
history of recurrent episodes of AOM. Otoscopic find- the air cell partitions within the mastoid bone. Other
ings usually consist of fluid visible behind a re- portions of the temporal bone including the posterior
tracted tympanic membrane. wall of the external canal, the mastoid cortex, and the

thin, bony plates separating air cells from the subject of otology. It was the first book to contain an
sigmoid sinus and dura may likewise be eroded. Ex- account of the structure, function, and diseases of
tension of the infection beyond the mucosal lining of the ear, whereas earlier works were devoted to
the middle ear and mastoid air cells may produce an purely normal otologic anatomy. In this work,
intracranial complication, generally by passage of DuVerney described infectious aural pathology and
the infection along preformed bony pathways or the mechanisms producing earache, otorrhea, and
through inflamed veins in intact bone. hearing loss. He was the first to describe extension
of tympanic cavity infection posteriorly to the mas-
History and Geography toid air cells to produce the characteristic symptoms
Antiquity Through the Sixteenth Century andfindingsof mastoiditis.
It is likely that humanity has always suffered from Noteworthy contributions were made by Antonio
acute infections of the middle ear and attendant Valsalva (1704), who still believed that aural suppu-
suppurative complications such as mastoiditis. Stud- ration was secondary to cerebral abscess formation
ies of 2,600-year-old Egyptian mummies reveal per- and was not the primary lesion. He did, however,
forations of the tympanic membrane and destruction suggest a method for removing purulence from the
of the mastoid air-cell system. Evidence of suppura- ear. This procedure consisted of blowing out strongly
tive destruction of the mastoid is also apparent in while holding the mouth and nose firmly closed,
skeletal specimens from early Persian populations thus forcing air to pass into the middle ear by way of
(1900 B.C. to 800 B.C.). the eustachian tube. He suggested this maneuver as
Hippocrates appreciated the potential seriousness a means of expelling pus in cases of otitis. Valsalva's
of otitic complications and noted that "acute pain of student Giovanni Morgagni, in his great work On
the ear with continued high fever is to be dreaded for the Sites and Causes ofDisease (1761), revealed post-
the patient may become delirious and die." Early in mortem evidence that demonstrated that aural sup-
the Roman era, the Roman physician Aulus Cornel- puration was the primary source of lethal, intra-
ius Celsus observed that "inflammation and pain to cranial abscesses.
the ear lead sometimes to insanity and death." The In the early eighteenth century, Jean Petit of Paris
Arabian physician Avicenna related suppuration of performed what is generally believed to have been
the ear and mastoid with the brain, reasoning incor- the first successful operation on the mastoid for the
rectly that the ear discharge was caused by the brain evacuation of pus. He demonstrated recovery "after
disease. For centuries, middle-ear and mastoid infec- the compact layer had been taken away with gouge
tions producing discharges from the ear were consid- and mallet." He stressed the need for early drainage
ered virtually normal conditions because they oc- of mastoid abscesses because of the potential for
curred so frequently. "accidents which may supervene and render the dis-
Although the seriousness of ear suppuration was ease infinitely complicated and fatal."
appreciated much earlier, the concept of opening the S. Stevenson and D. Guthrie, in their History of
mastoid to relieve infection did not occur until the Otolaryngology (1949), describe how, in 1776, a Prus-
sixteenth century. The great medieval surgeon sian military surgeon apparently treated a painful,
Ambroise Pare was called to the bed of Francis II of swollen, draining mastoid by removing a portion of
France. Pare found the young king febrile and deliri- the overlying mastoid cortex. The surgeon was proba-
ous with a discharging ear. He proposed to drain the bly unaware of Petit's work, and the authors quote
pus through an opening in the lateral skull. The boy- him saying, "Perhaps this is no new discovery, but
king's bride, Mary, Queen of Scots, consented. How- for me it is quite new."
ever, the king's mother, Catherine de Medici, refused Performance of the mastoidectomy operation suf-
to let the surgery take place, causing Mary to lose fered a setback when the procedure was performed on
her first husband and throne while she was only 18 Baron von Berger, personal physician to the King of
years old. Denmark. The baron, hearing of the success of Petit
and others, persuaded a surgeon to operate upon his
Seventeenth Through Eighteenth Century mastoid to relieve tinnitus and hearing loss. The op-
Notable advances in understanding the pathophysi- eration was performed before the importance of surgi-
ology of aural suppuration were made in the late cal asepsis was realized, and resulted in a wound
seventeenth century. Joseph DuVerney wrote Traits infection. The baron died of meningitis 12 days later,
de I'Organe de VOuie (1683), which is generally re- and the mastoidectomy operation fell into disrepute
garded to be the first monograph published on the until the middle of the nineteenth century.

VIII.87. Mastoiditis 869
France was one of the first countries to remove failure to address disease deeper within the middle
otology from the sphere of the general surgeon and ear recesses and mastoid invariably resulted in re-
to give it a place of its own. One of the first to currence of otorrhea. In 1873 he proposed extensions
specialize in this discipline was Jean Marie Gaspard of Schwartze's simple mastoidectomy to treat surgi-
Itard. Itard was a military surgeon in Paris who cally these problematic areas.
carried out extensive study of otologic physiology Following a similar line of reasoning, Ernst von
and pathology, and published a textbook on these Kiister and Ernst von Bergmann, in papers read
subjects, Traite des Maladies de I'Orielle et de I'Audi- before the German Surgical Society in 1889, recom-
tion, in 1821. He exposed many errors of his predeces- mended extending Schwartze's mastoidectomy proce-
sors, particularly their opening of the mastoid cavity dures to include removal of the posterior wall of the
as a cure for deafness. Like Itard, Jean Antoine external canal and middle ear structures "to clear
Saissy, a Parisian surgeon, was strongly opposed to away all disease and so fully to expose the source of
puncturing the tympanic membrane for aural suppu- the suppuration that the pus is nowhere checked at
ration as recommended by his predecessors. Instead, its outflow." This extended procedure became known
he treated middle ear and mastoid suppuration by as the radical mastoidectomy.
rinsing through a eustachian catheter. He described Prior to these remarkable advances in the surgical
the technique in his Essai sur les maladies de treatment of mastoiditis, the "mastoid operations"
Voreille interne (1829). frequently failed because of delayed surgical inter-
In 1853, Sir William Wilde of Dublin - father of vention in cases in which infections had already
the poet Oscar Wilde - published the medical classic extended beyond the mastoid process to involve in-
Practical Observations on Aural Surgery and the Na- tracranial structures. George Shambaugh, Jr., has
ture and Treatment of Diseases of the Ear. In this noted that these patients died most likely despite,
publication he recommended incision of the mastoid not because of, their mastoid operation (Shambaugh
through the skin and periosteum for fluctuant mas- and Glasscock 1980). Many surgeons trained before
toiditis when symptoms and findings were life- 1870 were unable to absorb and practice Listerian
threatening. doctrines, and this fact may have contributed to an
The nineteenth century saw the successful employ- overly conservative approach to surgical procedures.
ment of ether in a surgical operation by William Properly indicated and performed, mastoidectomy
Thomas Green Morton in 1846 and the introduction for a well-localized coalescent infection proved to be
of chloroform by James Young Simpson in 1847. extremely effective in removing the risk of serious
These, coupled with bacteriologic discoveries made complication from an abscess within the mastoid
by Louis Pasteur and the work of Joseph Lister on and in preventing continued aural suppuration. The
antisepsis, the invention of the electric light by addition of techniques for exteriorizing infectious
Thomas Edison, and the work of Rudolph Virchow in processes in the less accessible apex of the temporal
cellular pathology, had profound effects upon the bone, as well as progress in making earlier diagnosis
development of otologic surgery for suppuration. of mastoiditis, capped this important phase of oto-
James Hinton, a London surgeon, and Hermann logic surgery for aural suppuration.
Hugo Rudolf Schwartze of Halle are credited with In many cases of chronic otorrhea treated with
establishing the specific indications and method of radical mastoidectomy, previous infection had de-
simple mastoidectomy. This operation involved re- stroyed the middle-ear sound-conducting system.
moval of the bony cortex overlying the mastoid air Removal of the tympanic membrane and ossicular
cells. The insight and work of Schwartze led to the remnants was necessary in order to extirpate the
first systematic account of the operation as a scien- infection completely. However, it soon became appar-
tific procedure to be performed when specific indica- ent that in a subset of cases of chronic otorrhea, the
tions were present and according to a definite plan. infectious process did not involve the inferior
His rationale was so convincing that by the end of portions of the tympanic membrane or ossicular
the nineteenth century, the operation had attained chain. In 1899, Otto Korner demonstrated that, in
widespread acceptance and had overcome more than selected cases, the majority of the tympanic mem-
a century of prejudice against it. brane and ossicular chain could be left intact
In 1861 the German surgeon Anton von Troltsch during radical mastoidectomy, thus maintaining
had reported successful treatment of a case of appar- the preoperative hearing level.
ent mastoiditis with a postauricular incision and In 1910 Gustav Bondy formally devised the modi-
wound exploration. He subsequently recognized that fied radical mastoidectomy for cases in which the

inferior portion of the tympanic membrane (pars construction was introduced by William J. House in
tensa) and the ossicular chain remained intact. He 1966. C. L. Pennington and R. E. Wehrs are credited
demonstrated that the removal of the superior bone with refinement of this technique for reestablishing
overlying infected cholesteatoma adequately exte- ossicular continuity between the tympanic mem-
riorized and exposed disease while preserving hear- brane and the cochlea.
ing. Despite the successful demonstration of this less In 1954 B. W. Armstrong reintroduced a proce-
radical approach in selected patients, otologic sur- dure, first suggested by Adam Politzer in 1869, to
geons were slow to accept Bondy's procedure. Most reverse the effects of eustachian tube dysfunction.
likely, the preoccupation with preventing intracra- The procedure entails a limited incision of the tym-
nial suppurative complications forestalled accep- panic membrane and insertion of a tympanostomy
tance of this less aggressive approach. Shambaugh tube. Theoretically, a functioning tympanostomy
and others in America and abroad recognized the tube exerts a prophylactic effect by maintaining am-
utility of the Bondy procedure, and it finally gained bient pressure within the middle ear and mastoid
widespread acceptance by the 1930s. and providing aeration and drainage of retained
A marked decline in the need for mastoid opera- middle-ear secretions. Tympanostomy tubes appear
tions developed with the use of sulfanilamide and to be beneficial in restoring hearing and preventing
penicillin. The favorable results that were achieved middle-ear infections and structural deterioration
with the use of these antibiotics in many cases en- while in place.
couraged their application at earlier stages of severe This review of the historical development of
infections including mastoiditis. At first, otologic otology reports an evolution in the understanding
surgeons were hesitant to abandon the established and management of aural infections. Interestingly,
surgical drainage procedures for mastoiditis, fearing current principles of the surgical treatment of
that antibiotics would mask the clinical picture and chronic ear infections recapitulate this evolution.
lead to late complications. It soon became evident, The essential principles and objectives upon which
however, that if antibiotics could be given before modern surgical procedures are based are (1) removal
localized collections of pus were established, fewer of irreversibly infected tissue and restoration of
complications requiring surgical intervention would middle-ear and mastoid aeration; (2) preservation of
result. Nonetheless, modern-day physicians have rec- normal anatomic contours, and avoidance of an open
ognized that too low a dose of an antibiotic given for cavity, when possible, by maintaining the external
too brief a time, or the use of a less effective antibi- ear canal wall; and (3) restoration of the middle-ear
otic in the early stages of otitis media, may indeed sound-transformer mechanism in order to produce
mask a developing mastoiditis. usable postoperative hearing.
Interest in hearing-preservation in conjunction The historical lessons learned by otologists under-
with surgical treatment of chronic ear infections con- score the importance of adequate surgical exposure
tinued to grow. The German surgeons F. Zollner and and removal of irreversibly infected tissue followed
H. Wullstein share credit for performing the first by regular, indefinite postoperative follow-up in or-
successful repairs of the tympanic membrane using der to maintain a safe, dry ear.
free skin grafting techniques in 1951. The ability to John L. Kemink, John K. Niparko, and
repair perforations of the tympanic membrane and Steven A. Telian
seal the middle ear reduced the likelihood of persis-
tent aural suppuration and associated mastoid and
intracranial complications. Bibliography
The emphasis on preservation and restoration of Armstrong, B. W. 1954. New treatment for chronic secre-
hearing in conjunction with the management of tory otitis media. American Medical Association Ar-
chronic ear infections has fostered the development of chives of Otolaryngology 59: 653—4.
methods of ossicular reconstruction since the 1950s. Bluestone, C , and S. Stool. 1983. Pediatric otolaryngology.
Techniques in ossicular reconstruction are designed Philadelphia.
Bergmann, Ernst von. 1888. Krankenvorstellung: Geheil-
to simulate the middle-ear sound-conducting mecha-
ter Hirnabszess. Berliner Klinische Wochenschrift 25:
nism. Alloplastic prostheses made of polyethylene 1054-6.
and Teflon and bioceramic materials have produced Bondy, Gustav. 1910. Totalaufmeisselung mit Erhaltung
mixed results with respect to long-term hearing and von Trommelfell und Gehorknochetchen. Miinchener
prosthesis stability and acceptance. Ohrenheilkunde 44: 15-23.
The incus interposition technique of ossicular re- Clements, D. 1978. Otitis media and hearing loss in a

VUI.88. Measles 871
small aboriginal community. Medical Journal of Aus- Wullstein, H. 1952. Funktionelle Operationen im Mitte-
tralia 1: 665-7. lohr mit Hilfe des freien spaltlappen Transplantates.
DuVerney, Guichard Joseph. 1683. Traitt I'organe de Archiv fur Ohren- Nasen- und Kehlkopfheilkunde
I'ouie; contenant la structure, les usages et les maladies vereinigt mit Zeitschrift fur Hals- Nasen- und
de toutes les parties de I'oreille. Paris. Ohrenheilkunde 161: 422-35.
Hinton, James. 1847a. Atlas of the membrana tympani. Zollner, F. 1952. Plastische Eingriffe an den Laby-
London. rinthfenstern. Archiv fur Ohren- Nasen- und Kehl-
1847b. The questions of aural surgery. London. kopfheilkunde vereinigt mit Zeitschrift fiir Hals-
House, W. J., M. E. Patterson, and F. H. Linthicum, Jr. Nasen- und Ohrenheilkunde 161: 414-22.
1966. Incus homografts in chronic ear surgery. Ar-
chives of Otolaryngology 84: 148-53.
Hughes, G. 1985. Textbook of clinical otology. New York.
Itard, Jean Marie Gaspard. 1821. Traits des maladies de
I'oreille et de I'audition, 2 vols. Paris.
VIII.88
Kuster, Ernst Georg Ferdinand von. 1889. Ueber die
Grundsatze der Behandlung von Eiterungen in starr- Measles
wandigen Holen, mit besonderer Berucksichtigung des
Empyems der Pleura. Deutsche Medizinische Wochen-
schrift 15: 254-7. Measles (rubeola; hard measles; red measles; 9-day
Morgagni, Giovanni Batista. 1966. On the sites and causes measles; morbilli) is a common, acute, viral infec-
of disease, trans. B. Alexander. New York. tious disease, principally of children, with world-
Palva, T., and K. Palkinen. 1959. Mastoiditis. Journal of
wide distribution, that is clinically characterized by
Laryngology and Otology 73: 573.
Pennington, C. L. 1973. Incus interposition techniques.
fever and a typical red, blotchy rash combined with
Annals of Otology, Rhinology and Laryngology 82: cough, coryza, or conjunctivitis. It is a vaccine-
518-31. preventable disease, and its vaccine is one of the
Politzer, Adam. 1878-82. Lehrbuch der Ohrenheilkunde, 2 vaccines included in the Expanded Programme on
vols. Stuttgart. Immunization (EPI) of the World Health Organiza-
Saissy, Jean Antoine. 1829. Essai sur les maladies de tion (WHO). The disease is known by many local
I'oreille interne. Paris. names throughout the world.
Schuknecht, H. 1974. Pathology of the ear. Cambridge.
Schwartze, Hermann Hugo Rudolf, and Adolph Eysell. Etiology and Epidemiology
1873. Ueber die kunstliche Eroffnung des Warzenfor- Measles is caused by a virus, which is in the genus
satzes. Archiv fur Ohren- Nasen- und Kehlkopfheil- Morbillivirus of the family Paramyxoviridae. Al-
kunde vereinigt mit Zeitschrift fur Hals- Nasen- und though the virus does not survive drying on a sur-
Ohrenheilkunde 1: 157-87. face, it can survive drying in microdroplets in the
Shambaugh, G., and M. Glasscock. 1980. Surgery of the
air.
ear. Philadelphia.
Sonnenschein, R. 1936. The development of mastoidec-
Measles is one of the most highly communicable
tomy. Annals of Medical History 8: 500. diseases, transmitted by contact of susceptible indi-
Stevenson, S., and D. Guthrie. 1949. History of otolaryn- viduals with the nose and throat secretions of in-
gology. Edinburgh. fected persons, primarily by droplet spread. Infec-
Teele, D., S. Pelton, and J. Klein. 1981. Bacteriology of tion also occurs by direct contact, and by indirect
acute otitis media unresponsive to initial antimicro- contact through freshly soiled articles and airborne
bial therapy. Journal of Pediatrics 98: 537. transmission. There is no reservoir for measles other
Timmermans, F., and S. Gerson. 1980. Chronic granuloma- than human beings, which means that a continuous
tous otitis media in Inuit children. Canadian Medical chain of susceptible contacts is necessary to sustain
Association Journal 122: 545. transmission. The period of communicability is from
Valsalva, Antonio Maria. 1704. De aure humana tractatus. slightly before the beginning of the prodromal phase
Bologna.
of the disease to 4 days after the start of the rash.
Wehrs, R. E. 1972. Three years' experience with the
homograft tympanic membrane. Transactions of the
There is no carrier state. Measles has an incubation
American Academy of Ophthalmology and Otolaryn- period from time of exposure to onset of fever of
gology 76: 142-6. about 10 days with a range from 8 to 13 days. The
Wilde, Sir William Robert Wills. 1853. Practical observa- incubation period from time of exposure to rash on-
tions on aural surgery and the nature and treatment of set is about 14 days.
diseases of the ear. London. In populated areas with no or low vaccination cov-

erage, measles is primarily an endemic disease of the outside. In some countries, such as the United
children, with epidemics occurring every 2 to 5 States, a national goal of measles elimination has
years. In such areas, the greatest incidence is in been adopted, and impressive progress toward its
children under 2 years of age. Epidemic measles has control has been achieved.
a winter-spring seasonality in temperate climates
and a less marked hot-dry seasonality in equatorial Immunology
regions. This seasonality may be primarily the re- Infants usually have a passive immunity to measles
sult of the indirect effect of climate on socioeconomic as a result of maternal antibodies acquired transpla-
conditions and population movements. In more re- centally from immune mothers. This passive immu-
mote isolated populations, measles is not endemic nity protects the infant from measles infection for 6
and disease is dependent upon introduction of the to 9 months, depending on the amount of maternal
virus from the outside, at which time an epidemic antibody acquired.
may occur, affecting all age groups born since the Measles infection induces a lifelong immunity.
last epidemic. There is no evidence for a gender Several methods for confirming infection and immu-
difference with respect to incidence or severity of nity have been developed, including the following:
measles, or a racial difference with respect to inci- serologic tests,fluorescentantibody techniques, and
dence. Differences in severity among certain popula- isolation of the virus from patients during the acute
tions are most likely the result of nutritional and phase of the disease.
environmental factors. A single dose of live attenuated measles virus
Measles mortality is highest in the very young vaccine confers long-term, probably lifelong, immu-
and the very old. In malnourished children in the nity in over 95 percent of susceptible individuals.
developing world, the case fatality rate may be as The optimal age for vaccination is related to the
high as 5 to 10 percent or more. Some studies have persistence of passive immunity from maternal anti-
indicated that multiple cases within a family group bodies and patterns of disease transmission. For de-
may lead to higher mortality rates. veloped countries with low incidence, such as the
United States, vaccination at 15 months of age is
Distribution and Incidence recommended, whereas in developing countries the
Measles has a worldwide distribution, and the Ex- Expanded Programme on Immunization recom-
panded Programme on Immunization of the World mends vaccination at 9 months of age.
Health Organization maintains an information sys- Measles vaccine may confer immunity if given
tem on reported cases and vaccination coverage in within 72 hours of exposure; and immune globulin
member countries. Because of underreporting, world- (IG), if given within 6 days of exposure, may provide
wide reported measles incidence represents only a a limited-duration protection from measles, owing to
small fraction of an estimated 50 million cases and passively acquired antibodies from the immune
1.5 million deaths caused annually by measles in globulin.
developing countries. It should be emphasized that
reported incidence is subject to completeness of re- Clinical Manifestations and Pathology
porting and also to a general trend of improving The prodromal phase of measles disease typically
disease surveillance. Measles vaccination as part of includes symptoms and signs of fever, cough, coryza,
the Expanded Programme on Immunization, with and conjunctivitis. During this stage, small whitish
global coverage estimated at 55 percent for children specks on reddened areas of the mucosal lining of the
under 1 year of age (52 percent in developing coun- mouth called Koplik's spots are diagnostic of mea-
tries), is currently averting over 40 million cases sles. The prodromal period continues for 3 to 7 days
and over 1 million deaths resulting from the disease until the characteristic blotchy reddish rash ap-
each year in Third World countries. pears. This rash usually appears first on the head
In populated areas where measles is both endemic and then spreads down the body and outward to the
and epidemic, over 90 percent of the adult popula- limbs, lasting about 4 to 7 days. After its peak, in
tion will show serologic evidence of prior infection. uncomplicated cases, all the symptoms and signs
In remote or island populations where measles is not begin to recede and the rash fades in the same order
endemic, a significant proportion of the population it appeared.
can be susceptible, which may produce large out- Complications due to viral replication or secon-
breaks when the measles virus is introduced from dary bacterial infection may occur, however, and

VIII.88. Measles 873
result in middle-ear infections and pneumonia. Diar- lier. Rhazes used the word hasbah for measles and
rhea may also complicate measles and, in the devel- believed that "the measles arise from very bad
oping world, is one of the most important causes of blood." He considered the disease "more to be
measles-associated mortality. Neurological involve- dreaded than smallpox." Around the year 1000,
ment may also occur, resulting in encephalitis dur- Avicenna of Baghdad also wrote about measles, and
ing or soon after the acute illness or in the rare translators of his writings are said to have intro-
subacute sclerosing panencephalitis (SSPE) after a duced the term rubeola for the disease.
lengthy incubation period. Measles is uncommon During medieval times, measles was referred to
during pregnancy, and the limited data available do by the Latin term morbilli, the diminutive of
not appear to demonstrate clearly any increased risk morbus, meaning the "little disease." August Hirsch
of fetal mortality or congenital malformations. (1883-6) notes that measles was also called rubeola,
rossalia, rosagia, as well as the colloquial names
History and Geography fersa or sofersa (Milanese), mesles and later measles
(English), maal and masern (German), and the
Ancient Times Through the Eighteenth masura or spots (Sanskrit). The derivation of the
Century English name "measles" is in some doubt. One sug-
The origin of measles is unknown. Francis Black gestion is that it may have come from the Latin term
(1976) has noted that populations of a sufficient size miscellus or misella, a diminutive of the Latin miser,
to allow for a continuous chain of susceptibles re- meaning "miserable" - a term given to those suffer-
quired to sustain measles transmission would not ing from leprosy. The sores on the legs of leprosy
have developed until sometime after 2500 B.C. He patients were known as mesles, and John of Gaddes-
has suggested that measles may have arisen as an den in the early fourteenth century unjustifiably
adaptation of one of the other viruses of the same coupled these mesles with the disease morbilli of
genus (which includes rinderpest and canine distem- medical authors. Eventually the term "measles" lost
per). It is interesting to note that Hippocrates, writ- its connection with leprosy.
ing in the fourth century B.C., did not describe a Measles, smallpox, and other rash illnesses contin-
rash illness that would be consistent with measles, ued to be confused in Europe during the Middle
even though his recorded case histories document Ages. The seventeenth-century physician and epide-
the existence of many other infections in ancient miologist Thomas Sydenham studied measles epi-
Greece. demics in 1670 and 1674 and made observations on
The history of measles is confused with that of the clinical features of the illness and its complica-
smallpox in much of the early literature. Although tions. He is generally credited with differentiating
records are scanty, major unidentified epidemics and describing measles in northern Europe, and his
with high mortality rates spread through the Roman famous descriptions of the disease in "Of Measles in
Empire in A.D. 165-80 and again in 251-66. Wil- the Year 1670" and "On the Measles" were published
liam McNeill (1976) has noted that there are some in Process Integri in 1692. The first clear demonstra-
suggestive circumstances that make it tempting to tion that measles was an infectious disease is attrib-
believe that these two "demographic disasters" sig- uted to Francis Home who, in 1758, attempted to
naled the arrival of measles and smallpox. In China, prevent the illness and provide immunity by placing
two major epidemics with high mortality were re- blood from measles patients beneath the skin or into
corded in A.D. 161-2 and 310-12, but again there is the nose of susceptible persons. Numerous measles
uncertainty of the diseases, and McNeill states that, epidemics were reported in the seventeenth and eigh-
given the fragmentary and imperfect data, it is possi- teenth centuries in the English medical literature.
ble to conclude only that "some time between A.D.
37 and A.D. 653 diseases like smallpox and measles Nineteenth Century
arrived in China." The Persian physician known as The most famous epidemiological study of measles
Rhazes is generally credited with the first authentic was conducted by Peter Panum and reported in his
written record of measles by differentiating the two classic Observations Made During the Epidemic of
diseases in approximately A.D. 910 in his Treatise Measles on the Faroe Islands in the Year 1846 (1940).
on the Small-Pox and Measles. Rhazes, however, Measles attacked about 6,100 islanders during 1846
quoted previous writers, including the famous He- and was associated with the deaths of 102 of the
brew physician El Yahudi, who lived 300 years ear- 7,864 inhabitants, who had been completely free of

the disease for 65 years. Panum confirmed the respi- settings where populations were well nourished and
ratory route of transmission, the incubation period, where better medical care was available, the mortal-
and the lifelong immunity acquired from previous ity rate was much lower, as noted in the outbreak of
infection. Hirsch (1883-6) built on Panum's work measles in southern Greenland in 1951 where, in
and recorded the universal geographic distribution one district, 4,257 persons out of a population of
of measles by noting accounts of epidemics that had about 4,400 contracted measles and 77 deaths oc-
occurred in most parts of the world. He noted that curred (Christensen et al. 1953).
measles reached the Western Hemisphere soon after Not until 1896 did Henry Koplik publish a descrip-
the arrival of the first European colonists and fol- tion of Koplik's spots, although apparently their sig-
lowed the westward movement of the settlers. He nificance was independently recognized about a cen-
suggested that introduction of the disease into the tury earlier by John Quier in Jamaica and Richard
Australian continent occurred in 1854 after first ap- Hazeltine in Maine.
pearing in the Hawaiian Islands in 1848.
A particularly vivid account of the dramatic 1876 Prevention and Control
measles epidemic in Fiji quoted by Hirsch illustrates Research leading to the development of current mea-
the conditions that accounted for the relatively high sles vaccines began around the beginning of this
mortality: century. John Anderson and Joseph Goldberger
(1911) demonstrated that the illness was caused by a
Later in the epidemic, when it is said to be like plague, ... virus, by injecting filtered material from patients
the people, seized with fear, had abandoned their sick. ... with acute diseases into monkeys. Harry Plotz
The people chose swampy sites for their dwellings, and (1938) and Geoffrey Rake and Morris Shaffer (1940)
whether they kept close shut up in huts without ventila- reported the cultivation of measles virus in tissue
tion, or rushed into the streams and remained in the water culture. In 1954, with the advent of reliable tissue
during the height of the illness, the consequences were
equally fatal. The excessive mortality resulted from terror
culture techniques, J. F. Enders and T. C. Peebles
at the mysterious seizure, and [from] the want of the were able to isolate the measles virus. Subsequent
commonest aids during illness. . . . Thousands were car- research by S. L. Katz, M. J. Milanovic, and J. F.
ried off by want of nourishment and care, as well as by Enders (1958) resulted in the development of an
dysentery and congestion of the lungs. . . . attenuated strain of measles vaccine which was pro-
duced in 1958. In 1963, after field trials, the attenu-
It was especially dramatic when measles struck a ated ("live") measles vaccine was licensed for gen-
"virgin soil" population that had no prior or recent eral use in the United States. An inactivated
exposure to measles disease or measles vaccine, and ("killed") measles vaccine was also developed, but
thus the outbreak affected most persons. With re- was shown to be inferior and is no longer available.
gard to the introduction of measles by the Spaniards With the establishment of the World Health Orga-
from the Old World into the Amerindian populations nization Expanded Programme on Immunization in
of the New World, McNeill (1976) noted that "mea- 1974, measles vaccine has been introduced into the
sles followed hard upon the heels of smallpox, spread- national immunization programs of most countries.
ing through Mexico and Peru in 1530-1. Deaths The current levels of immunization coverage for mea-
were frequent, as is to be expected when such a sles vaccine show wide geographic variation. Except
disease encounters a virgin population dense enough for more remote isolated populations where the oc-
to keep the chain of infection going." High mortality currence of measles disease is not endemic and is
was also reported in measles epidemics that oc- subject to infrequent introduction of virus, the geo-
curred in virgin soil island populations in the Pacific graphic occurrence in the world today is related to
Ocean in the nineteenth century: 40,000 deaths out the immunization coverage with measles vaccine. In
of a population of 150,000 in Hawaii in 1848, 20,000 countries with sustained, large-scale immunization
deaths comprising 20 to 25 percent of the population programs and reliable disease surveillance, the im-
of Fiji in 1874, and 645 deaths out of 8,845 cases in pact of control efforts has been documented through
Samoa in 1911. High mortality in these settings was decreasing numbers of reported cases. Global mea-
likely due to some of the same factors that result in sles eradication is considered to be technically possi-
high mortality rates among unvaccinated individu- ble, but it is increasingly recognized that extremely
als in many areas of the developing world today, high immunization coverage levels will be necessary
including lack of supportive care, lack of treatment to achieve such a goal.
for complications, and malnutrition. In virgin soil Robert J. Kim-Farley

Vffl.89. Meningitis 875
This chapter was written in the author's private capacity. No rougeole. Bulletin de I'Academie de Medecine de Paris
official support or endorsement by the Centers for Disease Con- 119: 598-601.
trol is intended or should be inferred. Rake, Geoffrey, and M. F. Schaefer. 1940. Studies on mea-
sles. I. The use of the chorio-allantois of the developing
Bibliography chicken embryo. Journal of Immunology 38:177—200.
Anderson, J. R, and J. Goldberger. 1911. Experimental Wilson, G. S. 1962. Measles as a universal disease. Ameri-
measles in the monkey. Public Health Reports 26: can Journal of Diseases of Children 103: 49-53.
847-8,887-95.
Benenson, Abram S., ed. 1985. Control of communicable
disease in man. Washington, D.C.
Bett, Walter R., ed. 1954. The history and conquest of
common diseases. Norman, Okla.
Black, Francis. 1976. Measles. In Viral infections of hu- VIII.89
mans: Epidemiology and control, ed. Alfred S. Evans,
451-69. New York. Meningitis
Caufield, E. 1943. Early measles epidemics in America.
Yale Journal of Biology and Medicine 15: 521-6.
Centers for Disease Control. 1987. Measles - United Meningitis is an acute inflammation of the menin-
States, 1986. Morbidity and Mortality Weekly Report ges, the membranes covering the brain and spinal
36: 301-5. cord. The disease is usually the result of bacterial
Christensen, Pov Elo, et al. 1953. An epidemic of measles infection, but a number of viruses, fungi, and other
in southern Greenland, 1951. Acta Medica Scandi- microbial agents can also cause it. Meningitis can
navica 6: 448. develop as well from noninfectious conditions such
Enders, J. R, and T. C. Peebles. 1954. Propagation in
as tumors, lead poisoning, and reactions to vaccines.
tissue cultures of cytopathogenic agents from patients
Meningococcal meningitis, caused by a bacterium,
with measles. Proceedings of the Society for Experi-
mental Biology and Medicine 86: 277-86.
Neisseria meningitidis, is the only form that occurs
Expanded Programme on Immunization. 1986. Update: in major epidemics. Also called cerebrospinal menin-
Measles - spots that kill. Geneva. gitis (CSM), it has been known in the past as "spot-
Feigin, Ralph D., and James D. Cherry, eds. 1981. Text- ted fever," cerebrospinal fever, typhus cerebralis,
book ofpediatric infectious diseases. Philadelphia. and meningitis epidemica. Aseptic meningitis refers
Gastel, Barbara. 1973. Measles: A potentially finite his- to inflammations of the meninges without detect-
tory. Journal of the History of Medicine 28: 34-44. able bacterial involvement. The most common
Goerka, H. 1956. The life and scientific works of Mr. John causes are any of a number of viruses.
Quier. West Indian Medical Journal 5: 23.
Hirsch, August. 1883—6. Handbook of geographical and
historical pathology, 3 vols. London.
Home, Francis. 1759. Medical facts and experiments.
London.
Many species of bacteria can cause meningitis, but
Howe, G. Melvyn, ed. 1977. A world geography of human over 80 percent of all cases in developed countries in
diseases. London. recent years have been due to only three: N. mening-
Katz, S. L., M. V. Milanovic, and J. F. Enders. 1958. Propa- itidis, Hemophilus influenzae, and Streptococcus
gation of measles virus in cultures of chick embryo (Diplococcus) pneumoniae. Other common members
cells. Proceedings of the Society for Experimental Biol- of the human bacterialflorasuch as Escherichia coli
ogy and Medicine 97: 23-9. and various streptococci and staphylococci can also
Koplik, Henry. 1896. The diagnosis of the invasion of mea- produce meningitis under special circumstances, as
sles from a study of the exanthema as it appears on can members of the genera Listeria, Pseudomonas,
the buccal mucous membrane. Archives of Pediatrics and Proteus. Meningitis sometimes develops as a
13: 918-22. complication of tuberculosis.
Major, Ralph H. 1945. Classic descriptions of disease.
Aseptic meningitis is usually the result of viral
Springfield, 111.
McNeill, William H. 1976. Plagues and peoples. Garden
infection. Among the many types of viruses that can
City, N.Y. be involved are mumps, echovirus, poliovirus, cox-
Panum, P. L. 1940. Observations made during the epidemic sackievirus, herpes simplex, herpes zoster, hepatitis,
of measles on the Faroe Islands in the year 1846. New measles, rubella, and several mosquito-borne agents
York. of encephalitis. Fungi, most commonly Cryptococcus,
Plotz, Harry. 1938. Culture 'in vitro' du virus de la are other possible agents.

Laboratory study is necessary to determine the Immunology
cause of any particular case of meningitis, so it is N. meningitidis stimulates the production of sero-
generally difficult to be certain of the exact etiology type-specific antibodies in persons who have experi-
of past meningitis cases or epidemics. However, de- enced infection. The antibodies in most serogroups
spite the current relative significance of Hemophilus develop against the polysaccharides of the bacterial
and Streptococcus, Neisseria is the most important capsule, but the basis for antigenicity in serogroup B
pathogen for meningococcal meningitis; it is the is unclear. Infants can acquire passive immunity
only type that commonly occurs in major epidemics, from their mothers and be protected for a few months.
and is the most likely to attack adults. Vaccines are available for protection against several
N. meningitidis is a nonmotile, gram-negative serogroups, including A, C, Y, and W-135.
coccus closely related to the organism that causes
gonorrhea. Its protective capsule is composed of one Clinical Manifestations and Pathology
of several possible large sugar polymers (polysaccha- Infection with N. meningitidis can result in one of
rides), which provide the basis for assigning a given three conditions. In the large majority of cases, bacte-
specimen into 1 of about 13 currently recognized ria are carried in the nose and pharynx without any
serogroups. Serogroups B, C, W-135, and Y have symptoms or with just a sore throat. Serious disease
been especially active in the Americas in recent develops only if the bacteria reach the bloodstream.
years; group A organisms are the most likely to This can produce fulminating blood infection or
cause large-scale epidemics and have historically meningococcemia, which is characterized by sudden
been very prevalent in Africa. Serogroups can be prostration, high fever, skin blotches (ecchymoses),
divided into serotypes; these finer distinctions are and collapse. Most of these cases are fatal unless
often crucial in tracing connected cases or determin- promptly treated, and death may ensue in a matter
ing if a given outbreak has a common origin. Hu- of hours, before the meninges become involved.
mans are the only natural host. Meningitis, however, is the more common result,
N. meningitidis is a common inhabitant of the occurring when bacteria travel through the blood to
mucosal membranes of the nose and throat, where it infect the membranes of the brain and spinal cord.
normally causes no harm. As many as 5 to 50 per- Fever, violent headache, stiff neck, and vomiting are
cent of a population may be asymptomatic carriers typical symptoms, and, as in meningococcemia,
without any cases of meningitis developing, but such many victims show a petechial rash due to blockage
carriers are crucial to the spread of the disease. The of small blood vessels. A thick, purulent exudate
organism is transmitted by droplets sneezed or covers the brain, and arthritis, cardiac damage, and
coughed from the noses and throats of carriers or, shock may develop. Coma, convulsions, and delirium
less commonly, meningitis patients. It is very suscep- are frequent, and death rates for untreated cases
tible to desiccation and to sunlight, so close and range from 50 to 90 percent. Even in epidemic condi-
prolonged contact is favorable to propagation. tions, however, only a small minority of persons har-
The majority of victims, especially in sporadic boring the organism develop clinical disease. It is
cases and small outbreaks, are children under age 5. not known why most people remain healthy carriers
Among adults, new military recruits crowded into whereas others become desperately ill. Individual
barracks have traditionally been prime targets. susceptibility, damage to mucous membranes, and
Throughout the nineteenth and twentieth centuries, concomitant infections with other bacteria may all
wartime mobilization in Europe and America was play a role.
always accompanied by sharp increases in meningi- Diagnosis is based on clinical signs and the recov-
tis case rates. ery of pathogens from the cerebrospinal fluid or, in
Meningitis is a highly seasonal disease. In temper- meningococcemia, from the blood. Culture of organ-
ate regions, a large preponderance of cases develop isms from throat swabs is used to monitor carrier
in the winter and early spring. The reasons for this rates and circulating strains.
are not clear, but indoor living, crowding, and the Therapy was revolutionized with the introduction
effects of cold temperature and low humidity on po- of sulfa drugs in the late 1930s, and sulfonamides
tential hosts' mucous membranes may all play a were widely used as a prophylaxis for exposed popu-
role. Epidemics in sub-Saharan Africa develop dur- lations. The appearance and spread of sulfonamide-
ing the cool, dry season, when people travel more resistant bacteria after 1963 has forced a shift in
and sleep indoors to keep warm. African outbreaks preventive tactics, but the pathogen is still very
tend to end abruptly when the rains come. sensitive to treatment with penicillin. Military re-

VHI.89. Meningitis 877
cruits are routinely vaccinated in most countries, and Ohio in 1808, in New York State and Pennsylva-
and extensive inoculation campaigns have helped nia in 1809, among American troops during the War
control epidemics in Africa. Better ventilation and of 1812, and were described as "sinking typhus" or
reductions in crowding in living and sleeping areas "spotted fever" in New England from 1814 to 1816.
are useful in barracks and other institutional set- Relatively little more was heard about this deadly
tings. Prophylaxis with rifampin is helpful in reduc- and apparently quite new disease until the years
ing carrier rates and preventing outbreaks after 1837 through 1842, when a series of outbreaks oc-
cases have occurred in specific populations, as, for curred in French garrisons, and civilians also came
example, children in day-care centers. under attack in some nearby towns. Thus epidemics
in Algeria from 1840 to 1847 began among French
History and Geography troops, but caused many deaths among the indige-
Meningococcal and other forms of meningitis occur nous Moslem population as well, especially in the
throughout the world. Meningitis is endemic in tropi- Algiers and Constantine areas during 1846 and
cal and temperate regions and in both urban and 1847. Meningitis was also widespread in southern
rural settings, and sporadic cases and small epidem- Italy from 1839 to 1845, and there were scattered
ics can develop anywhere. In this century, epidemic reports from Corfu, Ireland, and especially Denmark
cerebrospinal meningitis (CSM) has repeatedly cut a in the period 1845 to 1848. There was also a series of
wide swath throughout African savanna country in small epidemics in the United States in the 1840s,
a belt south of the Sahara; these unusual epidemics primarily in the South.
are caused by serotype A of N. meningitidis. The first recorded major epidemic of CSM began in
Sweden in 1854, starting in Goteborg in the late
Antiquity Through the Nineteenth Century winter and slowly spreading to the north and east
Meningitis was not described in a form recognized as during the next five winters. It died out in the sum-
definitive until after 1800, so the antiquity of the mers and resumed a slow, irregular progress during
disease is unknown. Mention of "epidemic convul- winters, reaching 61° north in 1857 and 63° north in
sion" in tenth-century China and a possible descrip- 1858. The epidemic declined in 1859, with scattered
tion by T. Willis in England in 1684 could indicate cases reported in the next several years and a small
earlier recognition of meningococcal meningitis. flare-up in the years 1865 to 1867. Government re-
There are many other possible references to meningi- turns showed a total of 4,158 meningitis deaths from
tis outbreaks in European medical literature of the 1854 to 1860 and 419 in 1865-7.
sixteenth, seventeenth, and eighteenth centuries. An During the 1860s, numerous small but deadly epi-
episode described in Munster in 1788 could well have demics occurred in Germany, the Netherlands, En-
been meningococcal meningitis. Indeed, although the gland, France, Italy, Portugal, Austria, Hungary,
first clear clinical description was of cases in Geneva Greece, Turkey, Poland, and Russia. There were nu-
in 1805, it seems highly unlikely that meningitis of merous outbreaks in the United States during the
meningococcal or other etiology is really such a new same decade, with both Union and Confederate
infection in humans. troops suffering during the Civil War. In the United
In the early months of 1805, a small epidemic of States and elsewhere, recruits and small children
CSM was described in Geneva by Gaspard Vieus- continued to be the most common victims. Scattered
seux. Most victims were infants and children. Clini- cases and sporadic outbreaks continued for the rest
cal accounts, complemented by autopsy studies by A. of the century, with flurries of activity in the mid-
Matthey, establish the identity of the disease. In 18808 and at the end of the century.
March 1806, a cluster of 13 or 14 cases were de-
scribed in Medfield, Massachusetts. As in Switzer- Twentieth Century
land, the victims were infants and children. Nine There was a new burst of meningitis activity in the
patients died, despite frantic application of an array first decade of the twentieth century. The first cases
of depletive and stimulating therapies. The case de- from Australia were recorded in 1900-1. Portugal
scriptions and five autopsies confirmed a diagnosis had more than 5,000 cases from 1901 to 1905; a
of CSM. An epidemic of apparent meningitis af- series of North American epidemics from 1904 to
flicted British troops in Sicily in 1808, and French 1907 involved much of the United States and Can-
garrisons in Grenoble and Paris were struck in early ada, with 2,755 patients in New York alone in 1905.
1814. In North America, meningitis epidemics were A severe epidemic in Silesia caused almost 10,000
reported in Canada in 1807, in Virginia, Kentucky, cases from 1905 to 1908.

For most of the twentieth century, meningitis in lingering in Tanganyika until 1919. Both territo-
the developed countries has followed a pattern of ries, as well as neighboring Uganda, had dramatic
small, local epidemics and scattered cases, mostly surges during World War II. In North Africa, Algeria
among children. The two world wars caused major and Egypt experienced meningitis epidemics in the
spurts as military authorities crammed large num- nineteenth century, and the disease has been re-
bers of recruits into crowded barracks. In England ported throughout the region in recent decades. Mo-
and Wales, for example, cases rose from a few hun- rocco had over 6,000 cases in 1967.
dred a year prior to World War I to a peak of more The classic area for epidemic CSM, however, has
than 3,500 by 1915. Similarly, annual cases and been the savanna zone south of the Sahara Desert
deaths rose more than fivefold in the early 1940s, from Sudan to Senegal. This "CSM belt" has been
with over 23,000 cases in 1940 and 1941. But except swept by a series of great epidemics during the twen-
for a peak of almost 1,300 cases in 1974, there have tieth century. Indeed, there the disease has behaved
been fewer than 1,000 cases a year reported since in a very different fashion, advancing on a regular
the early 1950s. front and killing tens of thousands of people in a
For the United States, there were 5,839 cases and season. Only the Swedish epidemic of the 1850s
2,279 deaths among soldiers during World War I. In seems to have displayed a similar broad geographic
1942 and 1943, however, although there were 13,922 pattern. In both places, macroscopic examination in-
military cases, thanks to new therapy there were dicated that the disease advanced in a regular man-
only 559 deaths. Moreover, except for a spurt to ner from season to season, but also that actual cases
about 14 cases per 100,000 people in 1942, civilian were scattered widely within the afflicted zone in a
case rates in the United States have remained under totally unpredictable manner. The epidemic hopped
4 per 100,000 since the late 1930s. Total meningo- about, skipping many large communities and some-
coccal infections have rarely exceeded 3,000 a year, times striking hard at small, relatively isolated
but reported cases of aseptic meningitis have risen places. Areas struck in one CSM season were usu-
steadily and have totaled two to four times the ally spared in the next.
meningococcal figure during the 1980s. The reasons for the unusual behavior of CSM in
The situation in non-Western countries is quite the African "CSM belt" are unclear. Open grassland
different. Incidence rates tend to be much higher, country facilitates mobility, and much of the region
and there are still major epidemics like those that has a fairly dense population. A long, cool dry season
afflicted Sweden and Silesia in the past. For exam- creates dusty conditions and may dry out mucous
ple, China has experienced three major epidemics of membranes of the nose and throat while it also al-
serogroup A meningococcal meningitis since 1949, lows people to travel easily and encourages them to
with peak incidence rates of 50 to 400 per 100,000 in sleep indoors. Housing is often crowded and poorly
1959, 1967, and 1977. During the 1963-9 epidemic, ventilated. Perhaps the savanna dry season is analo-
which coincided with the upheavals of the Cultural gous to the Swedish winter; people are forced to
Revolution, there were more than 3 million cases congregate indoors, and the seasonal low humidity
and 166,000 deaths. in Africa was replicated in Sweden by home heating.
Africa has had two kinds of experience with the The Swedish outbreaks ceased every year with the
disease. In most of the continent, meningitis is a arrival of spring, whereas the sub-Saharan zone ex-
sporadic disease that behaves much as it does in the periences relief with the first rains.
West, although often with higher incidence and fatal- Although there has been a tendency, exemplified
ity rates. Much of north, central, east and southern in the studies of the British colonial physician B. B.
Africa falls into this pattern. In South Africa, scat- Waddy, to view the entire savanna belt as a single
tered cases were reported in the 1880s. Mining com- epidemiological unit, there have been distinct geo-
pounds have had favorable conditions for meningi- graphic zones of CSM. Thus the disease did not
tis, with newly hired African workers forced to live spread in great waves from southern Sudan across
in conditions similar to those of military recruits. the grasslands to West Africa. Epidemics in south-
CSM is endemic in east Africa, producing a few ern Sudan and northern Uganda, especially destruc-
hundred cases in most countries in recent years. tive in the late 1920s, have been independent of
On the other hand, there has been at least one developments in central and northern Sudan. And,
terrible epidemic. In 1913 CSM swept Kenya and with an exception in 1934 and 1935, central Suda-
Tanganyika, killing over 20,000 people in Kenya nese epidemics have not been linked to those in
alone and, partly as a result of military activity, Chad and westward.

VIII.89. Meningitis 879
The antiquity of meningitis in the savanna zone is entire CSM belt, despite the advent of sulfa and
not known, but some evidence exists that the disease penicillin therapy and vaccines against serogroup A
had occurred in central Sudan and the densely popu- pathogens.
lated Hausa country of northern Nigeria by the The puzzlingly late discovery of meningitis as a
1880s. Small outbreaks in troops in Senegal in the clinical entity did not retard development of knowl-
1890s and in the Gold Coast (Ghana) in 1900 did not edge of its etiology. The sporadic nature of outbreaks
afflict wide regions. The first of the great West Afri- and the apparent lack of transmissibility of infection
can epidemics began in northern Nigeria in early by victims led many nineteenth-century writers to
1905. It spread westward as far as French Sudan believe that the disease was not contagious and was
(Mali) and northwest Ghana in 1906, lingering in somehow linked to climate or environmental condi-
these places until the rains of 1908. British authori- tions such as crowding. By about 1860, however, it
ties guessed the 3-year death toll in Ghana at some was widely assumed that there was some sort of
34,000; case mortality was estimated at 80 percent. specific poison or agent involved. In 1887 an Aus-
Total deaths in the 1905-8 epidemic are not known, trian pathologist, Anton Weichselbaum, described
but there clearly was a major disaster. the meningococcus under the name Diplococcus in-
The second CSM cycle in the western savanna tracellularis meningitidis. This organism was sus-
began in northwest Ghana in 1919, spread to Upper pected of being the primary pathogen for many
Volta (Burkina Faso) in 1920, and swept northern years, but its role was not proven until studies done
Nigeria and Niger from 1921 to 1924. Weak political in 1904 and 1905 in connection with the great
and medical infrastructures precluded accurate esti- Silesian epidemic. By 1910 it was recognized that
mates of cases or deaths, but the death toll in one the meningococcus was responsible for epidemics
northern Nigerian province, Sokoto, was put at over and that other bacteria could cause sporadic cases.
45,000 in 1921 alone, and French officials assumed Lumbar puncture, introduced in 1891 by Heinrich
that at least 15,000 persons died in Niger over the 4- Quincke, provided an easy method to get cerebro-
year period. spinal fluid for study, and was sometimes used to
The third great cycle of CSM activity in West provide relief from the terrible headaches caused by
Africa began in 1935, when Chad was attacked by the disease. The crucial epidemiological role of
an epidemic that had raged during the previous year asymptomatic carriers was appreciated by the turn
in the Kordofan and Darfur provinces of central Su- of the century.
dan. This was the first and only time that a clear After 1905, inspired by success against diphthe-
pattern of east-west spread from Sudan has been ria, there were many attempts to develop a therapeu-
demonstrated. Carriers brought infection westward tic serum. Some early successes were reported, espe-
during the rainy seasons to Chad, to northern Nige- cially in France, but by 1909 it was clear that there
ria, and thence to Niger, with disastrous epidemics were important serologic differences among strains.
developing in early 1937. CSM hit Upper Volta in Workers in Britain, the United States, and France
1938 and Mali and northern Ghana in 1939, and had established four major serogroups by the end of
local outbreaks continued through 1941. Mortality World War I. Vaccine therapy remained of limited
statistics are very unreliable, but even with the ad- value, but in the absence of anything else, it was
vent of sulfa drugs, several tens of thousands died. frequently tried. In the 1930s, French efforts to pro-
CSM was again epidemic in the years 1943-7, with tect Africans against serogroup A by vaccination
major outbreaks reported from Chad to Senegal. Up- had inconclusive results, and similar British trials
per Volta, western Niger, and northwest Ghana were in Sudan were unsuccessful.
especially seriously afflicted. The development of sulfa drugs in the 1930s revo-
Another cycle of epidemics developed in 1949 from lutionized meningitis therapy. Gerhardt Domagk
foci in northern Ghana, northern Nigeria, and Up- published on one such drug in 1935; French workers
per Volta, spreading eastward as far as Sudan by at the Institut Pasteur introduced a more effective
1952. By this time, meningococcal meningitis had active form, sulfanilamide, later in the same year.
become well established throughout the region, and Clinical trials showed the almost miraculous impact
geographic patterns of spread were much less dis- of sulfanilamide on meningococcal infections in
tinct. At least 250,000 and perhaps a million or more 1937. This drug, one of a group of chemicals called
people died of CSM in West Africa between 1905 and sulfonamides, reduced case-fatality rates from be-
the end of the colonial period in 1960. The disease tween 50 and 80 percent to 20 percent and less, and
remains a very serious public health problem in the saved many thousands of lives during the meningi-

tis epidemics of World War II. Sulfa drugs were suc- Bibliography
cessfully used for prophylaxis and to reduce carrier Centers for Disease Control. 1986. Summary of notifiable
rates by the U.S. Army beginning in 1943; the tech- diseases, United States, 1986. Atlanta.
nique was widely adopted for troops and during out- Danielson, L., and E. Mann. 1983. The first American
breaks. account of cerebrospinal meningitis. Reviews of Infec-
tious Diseases 5: 967-72. [Reprint of 1806 article.]
The advent of this class of "wonder drugs" had an
Dowling, Harry F. 1977. Fighting infection: Conquests of
especially dramatic impact in the CSM belt of Af- the twentieth century. Cambridge, Mass.
rica, where they were introduced in early 1938 in Hirsch, August. 1886. Handbook of geographical and his-
the midst of major epidemics in Sudan and West torical pathology, Vol. III. London.
Africa. Prior to this date, Africans had been well Lapeyssonie, L. 1963. La Meningite cerebro-spinale en
aware that European therapy was useless. Preven- Afrique. Bulletin of The World Health Organization 28
tive measures seemed equally futile and were often (Supplement).
arbitrary and very harsh. Victims were usually quar- Netter, Arnold, and Robert Debr6. 1911. La Meningite
antined, and cordons were sometimes thrown c&rtbrospinale. Paris.
around whole villages and districts. Such efforts dis- Patterson, K. David, and Gerald W. Hartwig. 1984.
rupted trade and care of the sick, but, given the key Cerebrospinal meningitis in West Africa and Sudan in
role of asymptomatic carriers and the use of bush the twentieth century. Los Angeles.
paths to avoid police checkpoints, they did nothing Solente, Lucy. 1938. Histoire de 1 evolution des meningites
c6r6bro-spinales aigues. Rivue de Midicine 55:18—29.
to impede the spread of the disease. Annoying proce-
Vedros, Neylan A., ed. 1987. Evolution of meningococcal
dures like "nasopharyngeal disinfection" of travel- disease, 2 vols. Boca Raton, Fla.
ers in Chad or destroying houses or removing their Waddy, B. B. 1957. African epidemic cerebro-spinal menin-
roofs in Sudan did not encourage African coopera- gitis. Journal of Tropical Medicine and Hygiene 60:
tion with colonial medical authorities. Indeed, Afri- 179-89, 218-23.
cans very sensibly tried to hide cases, preferring not
to add government public health measures to the
burdens of an epidemic. Sulfa drugs were, however,
extremely effective. Africans responded pragmati-
cally to this new treatment and, seeing death rates
plummet, eagerly began to report cases and seek VIII.90
treatment for themselves and their children. In
many areas, a shortage of medical workers forced Milk Sickness (Tremetol
authorities to give supplies of drugs to chiefs to pass Poisoning)
along to the sick. This and the introduction of drug
prophylaxis meant that CSM, in sharp contrast to
earlier decades, was overreported during the 1940s Milk sickness, usually called milksick by early
and 1950s. nineteenth-century American pioneers, denotes
In 1963 sulfa-resistant strains of N. meningitis what we now know to be poisoning by milk from
were detected by U.S. military doctors and the spread cows that have eaten either the white snakeroot or
of such strains has forced an end to sulfa prophylaxis. the rayless goldenrod plants. The white snakeroot,
Penicillin therapy is still very effective, but this anti- common in the Midwest and upper South, is a
biotic has no preventive value. Vaccines against member of the Compositae called Eupatorium
serogroup C and A organisms were introduced in urticaefolium. It is also known as white sanicle,
1971 and 1973, respectively. Improved vaccines for squaw weed, snake weed, pool wort, and deer wort.
these and other serogroups have been developed in A shade-loving plant, it is frequently seen growing
recent years, although there is still no protection on roadsides, in damp open areas of the woods, or
against serogroup B bacteria. Meningitis will proba- on the shaded north side of ridges. The rayless
bly remain a public health problem, especially in goldenrod, Haplopappus heterophyllus, is the cause
underdeveloped countries. Death occurs in about 5 of the disease in southwestern states, such as
percent of all cases, even with prompt treatment. Arizona and New Mexico.
Poverty, logistical problems, and financial difficulties Milk sickness has been called variously alkali poi-
make meningitis a continuing threat in the tradi- soning, puking disease, sick stomach, the slows or
tional CSM belt of Africa. sloes, stiff joints, swamp sickness, tires, and trem-
K. David Patterson bles (when it occurs in animals). It is now known as

VIII.90. Milk Sickness (Tremetol Poisoning) 881
tremetol poisoning after an identified toxic ingredi- from the soil. Still others incriminated various poi-
ent of the white snakeroot and rayless goldenrod. sonous minerals and springs. Nonetheless there was
Tremetol, obtained from the leaves and stems of no definite identification of one specific toxic plant
these plants by extraction with ether, is an unsatu- during the nineteenth century. In the 1880s, the
rated alcohol with the empirical formula C16H22O3. In medical revolution following the discoveries of Louis
consistency and odor, it resembles turpentine. Pasteur in France and Robert Koch in Germany led
to the expectation that many obscure diseases such
Distribution and Incidence as milk sickness would prove to be of bacterial etiol-
Milk sickness was unknown in Europe or in any ogy. This expectation appeared to have been realized
other region of the world except North America. It when Edwin Jordan and Norman Harris (1909) re-
appeared in North Carolina as early as the Ameri- ported that Bacillus lactimorbi was the cause of milk
can Revolution near a mountain ridge named Milk sickness in humans and trembles in cattle. Needless
Sick. Its highest incidence was in dry years when to say, they were wrong.
cows wandered from their brown pastures into the Beginning in 1905, however, Edwin Moseley of
woods in search of forage. As more forests were what is now Bowling Green State University in Ohio
cleared so that cattle had more adequate pasture, began a scientific study of the white snakeroot that
and as fences were built, the incidence of milk sick- lasted for over three decades. In careful animal-
ness decreased rapidly. feeding trials, he established the toxic dose of snake-
The disease wrought havoc in the Midwest, espe- root for animals at 6 to 10 percent body weight. He
cially in Illinois, Indiana, and Ohio, and in the upper also found that the stems were less poisonous than
southern states of Kentucky, North Carolina, Tennes- the leaves and that neither freezing nor drying de-
see, and Virginia. Milk sickness was, in some years stroyed the poison. His book, published in 1941, is
and some localities, the most important obstacle to the definitive work on milk sickness.
settlement by the pioneers. Beginning about 1815, a Finally James Couch (1928) reported that he had
flood of pioneers moved west. As they penetrated the isolated three poisonous substances from the white
forest wilderness of the Midwest they all too fre- snakeroot: a volatile oil and a resin acid that did not
quently came upon evidence of epidemics of the dis- produce trembles, and an oily liquid with the charac-
ease as several villages were abandoned. Physicians teristics of a secondary alcohol that did. The last he
in Kentucky and Tennessee described milk sickness identified as C16H22O3 and, drawing on the Latin
as being so widespread that the Kentucky legisla- tremere meaning "tremble," named it tremetol.
ture appointed a committee in 1827 to investigate its Heating reduces somewhat the toxicity of poi-
cause. A few years later, the state medical society of soned milk, and oxidation readily destroys the toxic
Indiana also attempted a similar investigation. In- properties of tremetol. Because only a small number
terestingly, in that state it has been noted that of cows are likely to be secreting toxic milk at one
"Evansville, Indiana, owes its prominent posi- time, human illness is seen chiefly when milk from a
tion . . . today, in part at least, [to] the fact that its single animal or herd is consumed. It is now thought
early competitor, Darlington, was abandoned" be- that the dilution that occurs in the usual dairy collec-
cause of milk sickness (Snively 1967). tion and distribution of milk from a large milk
source, rather than pasteurization, is the reason for
Epidemiology and Etiology the failure of milk sickness to develop in urban ar-
In 1811, an anonymous author wrote that milk sick- eas. For that reason, milk sickness has become ex-
ness was a true poisoning because it involved no tremely rare. Moreover, in rural areas, farmers are
fever. He also believed that it was caused by poison- now well aware that to avoid trembles or milk sick-
ous milk that had a peculiar taste and smell. The ness, one need only abandon woodland grazing, for
source of the poison, he wrote, was vegetation eaten the white snakeroot is a woodland plant and almost
by the cows. He further advised that finding the never found in bright and open pastures.
offending plant would remove a major stumbling
block to emigration westward. Clinical Manifestations
In the years that followed, the theories as to the When milk sickness occurs in animals, chiefly cattle,
cause of milk sickness were numerous. One sug- it is called trembles. The animals suffer from an-
gested that the cause was arsenic; another claimed it orexia, weakness, falling, stiffness, and trembling.
was a mysterious soil organism, whereas another In humans the symptoms of milk sickness include
attributed the disease to a mysterious exhalation anorexia, listlessness, severe constipation, a n d -

most important of all, and underlying most of the that white snakeroot caused trembles and milk sick-
symptoms - profound acidosis; the latter, if un- ness, she had a calf fed several bunches of the root.
treated, leads to coma and death. Because of the The calf developed typical trembles, enforcing her
acidosis, the breath smells of acetone, described in conviction that she had found the cause of milk sick-
the past as an overpowering "fetor." The weakness is ness. John Rowe, a farmer of Fayette County, Ohio,
thought to be due chiefly to hypoglycemia, and wrote in 1838 that he had discovered through simi-
death, to ketoacidosis and marked fatty degenera- lar experimentation that trembles was caused by
tion of the liver, kidney, and muscles. The disease ingestion of white snakeroot.
can be chronic or latent, and is likely to recur if the During the second half of the nineteenth century,
patient is subjected to fatigue, starvation, inter- milk sickness occurred sporadically, which made se-
current infection, or vigorous exercise. quential observations difficult to make, and the rea-
The lethargy that characterizes the patient who son for its cause was lost in the widely held medical
has not completely recovered from an attack of milk belief in miasmas and exhalations from the ground.
sickness helped give it the name of slows (or sloes). Moreover, because milk sickness was limited to the
Abraham Lincoln knew it by that name, and, an- Midwest, upper South, and Southwest, influential
noyed by the desultory progress of the Army of the eastern physicians tended to ignore it or even dis-
Potomac in the early months of the Civil War, he once count the possibility that it really existed as a dis-
tartly remarked that General McClellan "seemed to ease sui generis.
have the slows." Nonetheless, the solution was eventually found
when attention was turned back to the poisonous
History and Geography plant theory advanced during the first half of the
Milk sickness has vanished from the list of major century. Although many plants were suspected, such
concerns of modern Americans. Although endemic as poison ivy, water hemlock, Virginia creeper, coral-
in the Midwest and upper South, it had never been berry, spurge, mushrooms, and march marigold, scru-
seen elsewhere in the United States, in Europe, or in tiny finally centered once again on white snakeroot.
any other continent. The settlers along the Atlantic Yet it was not until 1928 that the white snakeroot
seaboard knew nothing of it, and if the Indians or was established with certainty as the cause of milk
their cattle suffered from the disease, they did not sickness - over a century after the anonymous 1811
inform the early settlers. Not until the pioneers be- article appeared.
gan to push westward beyond the Alleghenies did The question that Snively has asked remains:
the disease attract attention. "How could a disease, perhaps the leading cause of
The first sporadic cases to be recognized occurred death and disability in the Midwest and Upper
in North Carolina in the years preceding the Revolu- South for over two centuries, go unrecognized by the
tion. It was generally known that on the western medical profession at large until 1928?"
side of the Allegheny Mountains from Georgia to the Thomas E. Cone, Jr.
Great Lakes a disorder called trembles prevailed
among cattle, and that wherever it appeared, the Bibliography
settlers were likely to get a disease, which from its Anon. 1811. Disease in Ohio ascribed to some deleterious
most prominent symptom received at first the name quality in milk of cows. Medical Repository [N.Y.] 3:
"sick stomach" and from a theory concerning its 92-4.
cause that of "milk sickness." Couch, James F. 1928. Milk sickness, result of richweed
In 1811, the Medical Repository of New York con- poisoning. Journal of the American Medical Associa-
tained an anonymous report entitled "Disease in tion 91: 234-6.
Ohio, Ascribed to Some Deleterious Quality in the Furbee, Louanna, and William D. Snively, Jr. 1968. Milk
Milk of Cows." This appears to be the earliest surviv- sickness, 1811-1966: A bibliography. Journal of the
ing reference to a disease that was to become a History of Medicine 23: 276-85.
Hartmann, Alexis F, Sr., et al. 1963. Tremetol poisoning —
frequent cause of death and a major source of misery
not yet extinct. Journal of the American Medical Asso-
and mystification in the rural South and Midwest ciation 185: 706-9.
through a large part of the nineteenth century. Jordan, Edwin O., and Norman MacL. Harris. 1909. Milk
William Snively and Louanna Furbee (1956) de- sickness. Journal of Infectious Diseases 6: 401-91.
scribed a discovery made in 1834 by Anna Pierce Jordan, Philip D. 1944. Milk sickness in the western coun-
Hobbs, a pioneer doctor, in southeastern Illinois. try together with an account of the death of Lincoln's
Having learned from a Shawnee medicine woman mother. Ohio State Medical Journal 40: 848-51.

Vm.91. Multiple Sclerosis 883
McKeever, George E. 1976. Milk sickness: A disease of the century, and in 1916 J. W. Dawson gave an exhaus-
Middle West. Michigan Medicine 72: 775-80. tive account of the pathology of the disease which
Moseley, Edwin L. 1941. Milk sickness caused by white has remained a standard reference.
snakeroot. Ann Arbor, Mich. Three personal accounts of multiple sclerosis by
Snively, William D., Jr. 1967. Mystery of the milksick. sufferers are worth reading for the insights that
Minnesota Medicine 50: 469-76. they give into its course and its consequences. The
Snively, William D., Jr., and Louanna Furbee. 1956. Dis-
first two take the form of diaries, one written in the
covery of the cause of milk sickness. Journal of the
American Medical Association 196: 1055-60.
nineteenth century by Augustus d'Este, one of King
George Ill's illegitimate grandsons, and the other
early in the twentieth century by a young naturalist
who used the pseudonym W. N. P. Barbellion (Bar-
bellion 1919; Firth 1948). The third, a well-illus-
trated account of the visual experience of optic neuri-
VHI.91 tis (one of the common manifestations of multiple
Multiple Sclerosis sclerosis the main symptoms of which are well de-
scribed by d'Este), was recently provided by Peter
MacKarell (1986), a professional painter who was
Multiple sclerosis is a disease of the central nervous afflicted by it.
system characterized clinically by recurring epi- The geography of multiple sclerosis is interesting
sodes of neurological disturbance which, especially because it is strange and because understanding it
early in the course of the disease, tend to remit may provide a crucial clue to the nature of the dis-
spontaneously, although as time goes by there is ease (see Matthews et al. 1985; McDonald 1986).
often a gradual accumulation of disability. The Geographic peculiarities were first noted 85 years
course of the disease is quite variable, at one ex- ago when Byron Bramwell argued that the higher
treme lasting for 50 years without the development incidence of multiple sclerosis in his practice in Edin-
of significant disability, and at the other terminat- burgh than that of neurologists in New York re-
ing fatally in a matter of months. Overall, about one flected a real difference in frequency between the
quarter of patients remain able to work for up to 15 two cities.
years after the first recognized clinical manifesta- Forty years ago, the notion of the relevance of
tion, and the mean duration of life is approximately genetic background as well as latitude was pointed
25 years from that time. Nevertheless, because the out by Geoffrey Dean on the basis of the lower preva-
disease commonly affects young adults and produces lence of multiple sclerosis among Boers than among
disability in the prime of life, the economic burden is British descendants in South Africa; in both groups
heavy, in the United States averaging $15,000 per the prevalence of the disease in Africa was the same
annum per family with a member afflicted (Inman as in their countries of origin. The idea that genetic
1983 data, cited in McDonald and Silberberg, eds. background was important also received support
1986, 180). from the discovery of the rarity of multiple sclerosis
among the Japanese. In the past 20 years, strenuous
Overview efforts have been made to determine the conse-
Multiple sclerosis is a remarkable disease. It was quences of migration at different ages from areas of
first clearly described more than 120 years ago in a high to low prevalence, and vice versa. These studies
way which we would recognize as a modern, patho- support the general idea of an interaction between
logically based account that discusses the clinical latitude and genetic factors determining the geo-
features of the illness and their possible patho- graphic distribution of the disease.
physiology (Charcot 1868). It is only since the early
1970s, however, that real progress has been made in Pathology
understanding its nature, course, and pathogenesis. The characteristic lesion of multiple sclerosis is the
It was discussed in treatises on pathology by R. Cars- plaque of demyelination - a patch varying from a
well (1838) and J. Cruveilhier (1835-42), and more few cubic millimeters to many cubic centimeters in
knowledge was added by E. Rindfleisch (1873), but which the myelin sheath of nerve fibers is destroyed,
the French school did most to delineate the disease. leaving the axons relatively intact. Small plaques
Good descriptions were appearing in standard text- are oriented around small veins (the venules),
books of neurology before the end of the nineteenth though this orientation is often obscured in large

lesions. The venules in areas of active demyelina- ate zones, though it does occur infrequently in the
tion, as judged by the presence of inflammatory cells tropics and in other racial groups. Because the course
and myelin breakdown products, are surrounded by of the disease is so prolonged and the manifestations
cells derived from the immune system. Such cells are so variable, it is difficult to determine its true
are also present in the substance of the brain itself- incidence, and prevalence rates are generally used to
in the lesions, especially at the edges, where it has compare the frequency of the disease in different
been suggested that they may play a role in limiting populations. Females are affected about twice as com-
the spread of damage. monly as men. The average age of onset is 30 years
The outstanding feature of the chronic lesion is old, and it rarely starts over the age of 60 or before
the formation of a fibrous scar as a result of prolifera- puberty. In Caucasoid populations, approximately 10
tion of the astrocytes, one of the supporting cells of percent of patients have an affected relative. The
the central nervous system. Remyelination, at least concordance rate in twins (i.e., the frequency with
in most cases coming to post mortem, is scanty, al- which both members of a twin pair have the disease)
though it is an open question whether it may be is about 30 percent for identical twins and 2 percent
more extensive early in the course of the disease. for nonidentical twins, the latter being similar to the
The plaques are distributed asymmetrically frequency in siblings. The difference in concordance
throughout the brain and spinal cord, but there are rate between identical and nonidentical twins pro-
certain sites of predilection which determine the char- vides strong evidence for the implication of a genetic
acteristic clinical pattern of the disease. The impor- factor in the etiology of the disease, but the rather low
tant functional consequence of demyelination is concordance rate in identical twins suggests that an
block of electrical conduction in the nerve fibers environmental factor is also involved. Further evi-
which leads to many of the clinical features of the dence implicating both environmental and genetic
disease. factors comes from a consideration of the geography
and epidemiology of the disease.
In at least 80 percent of patients, the disease follows Geography and Epidemiology
a relapsing and remitting course, often in the later There are two relevant geographic aspects: the distri-
stages entering a steadily progressive phase. Fully bution of the disease and the distribution of its ge-
5 to 10 percent of patients experience a steadily netic associations. Among Caucasoids the preva-
progressive course from onset. The typical episode of lence of multiple sclerosis is generally higher in
neurological disturbance develops over a matter of higher latitudes. In the United Kingdom, for exam-
days or a week or two, persists for a few weeks, then ple, the prevalence in the Orkney and Shetland Is-
resolves over a month or two. Common manifesta- lands is 309 per 100,000, in northern Scotland 178
tions include reversible episodes of visual loss (optic per 100,000, and in the south of England 100 per
neuritis), sensory disturbance or weakness in the 100,000. It must be pointed out, however, that these
trunk or limbs, vertigo, and bladder disturbance. prevalence studies have been conducted at different
Obvious disturbance of intellectual function is un- times, and the reliability of ascertainment varies.
common, except in severe cases. Recently, however, Nevertheless, data from other regions suggest that
subtle defects have been demonstrated early in the the trends are real: Multiple sclerosis is more com-
course of the disease. mon in the northern United States and Canada than
Certain special clinical patterns are of interest. in the southern United States, and in the more tem-
Steadily progressive spastic weakness is more com- perate south of New Zealand and Australia than in
mon in late-onset cases (older than 40 years). In their northern portions.
Orientals generally, severe and persistent visual The influence of migration on risk has been stud-
loss and limb weakness are particularly common. In ied in several populations. Migration from high
the same group, a curious form of spasmodic disorder prevalence (e.g., northern Europe and the northern
of the limbs is also frequent. The reasons for these United States) to low prevalence areas (e.g., Israel,
well-documented ethnic differences in the pattern of South Africa, or the southern United States) before
clinical involvement are unknown. puberty appears to decrease the risk of developing
the disease, while migration after puberty does not.
Distribution and Incidence The total number of patients involved in these stud-
Multiple sclerosis affects principally individuals of ies is small, but the consistency of the results sug-
northern European Caucasoid origin living in temper- gests that the observation is significant. Studies of

VIII.91. Multiple Sclerosis 885
migration from low-risk to high-risk zones (Vietnam real differences in the frequency of the disease in
to Paris, New British Commonwealth to the Old) are different ethnic groups, again suggesting the opera-
based on even smaller numbers, though they have tion of a genetic factor in determining susceptibility.
yielded concordant results. These observations pro-
vide further, albeit rather weak, evidence for the Genetics
operation of an environmental factor in the etiology The most intensively studied genetic associations of
of multiple sclerosis, although this would seem to be multiple sclerosis are those within the human leuko-
the case if the risk of developing the disease is influ- cyte antigen (HLA) region of the sixth chromosome.
enced by where individuals spend their first 15 The most frequent association in Caucasoid popula-
years. tions is with HLA-DR2, though others, including
On the face of it, stronger evidence comes from the DQwl, have been reported. The strength of the asso-
study of apparent clusters of cases in the Faroe Is- ciations varies in different population groups. R. J.
lands in the North Sea. No cases had been identified Swingler and D. A. S. Compston (1986), though cau-
in the Faroe Islands prior to World War II. But be- tious in interpreting their data, have reported that in
tween 1943 and 1973, there were 32 cases; there the United Kingdom the north-south gradient of
have been no new cases since. Although it cannot be prevalence of multiple sclerosis is mirrored by a simi-
certain that cases prior to 1943 were not missed, the lar gradient in the frequency of DR2 in the control
balance of evidence is in favor of there being an population. In the New World, G. C. Ebers and D.
unusual run of them in the 30 years after that date. Bulman (1986) have shown that in the United States
J. F. Kurtzke and K. Hyllested (1986) have analyzed the areas of highest prevalence correspond with the
the data minutely and have suggested that there areas of immigration from Finland and Scandinavia
were two mini-epidemics within the main one. In (where there is a high frequency of DR2), and D. C. G.
addition, they have pointed out that the pattern of Skegg and colleagues (1987) have shown that multi-
presentation of the cases suggests a point source ple sclerosis is three times less common in the north
epidemic and, noting that the places of residence of than in the south of New Zealand - the latter a site of
the patients were close to the location of army camps preferential migration for the Scots, who have a par-
during World War II, have proposed that an infection ticularly high frequency of DR2.
was introduced by the British troops occupying the There are fewer data for non-Caucasoid popula-
islands during that period. C. M. Poser and P. L. tions. In a small study, multiple sclerosis was found
Hibberd (1988) have challenged these conclusions. to be associated with the Dw2 (related to DR2) in
Nonetheless, the overall clustering of cases is strik- blacks in Philadelphia. Among the Arabs, multiple
ing and probably a phenomenon of biological signifi- sclerosis is associated with DR2 in some groups, and
cance, indicating exposure to a newly introduced DR4 in others. No HLA association has been found
environmental agent in the early 1940s. Other examin the Japanese and Israelis.
ples of clustering have been reported but are less It should be noted that multiple sclerosis is rare in
convincing. two populations in which DR2 is common: the Hun-
Multiple sclerosis is much less frequent in non- garian Gypsies (of whom 56 percent of controls are
Caucasoid populations. No postmortem-proved case DR2 positive) as well as the Maoris - raising the
has yet been described in African blacks, and preva- possibility of the existence of an overriding genetic
lence of the disease is lower in American blacks than protective effect. Protective genes have also been
in whites living in the same areas. The disease is postulated in Mongoloid and Caucasoid populations.
similarly rare among American Indians, the Maoris Moreover, current research suggests that multiple
in New Zealand, the gypsies in Hungary, and Orien- sclerosis may be associated with peculiarities in the
tals living in California and Washington State but structure of certain genes in the HLA region.
not in the larger populations they live among. Multi- What is one to make of this mass of confusing and
ple sclerosis is also rare among the Japanese in Ja- sometimes conflicting data? The frequency with
pan; among the Chinese in Taiwan, China, and which some association with the HLA system is found
Hong Kong; and among Indians living in India. It is suggests that the observations are significant. Yet it
so far unreported in the Eskimo. In many of these is clear that none of the factors so far identified alone
groups (but not Orientals in the United States and confer susceptibility to the disease. The simplest ex-
Japan), problems of ascertainment may have led to a planation would be that DR2 is acting as a marker for
significant underestimate of the true frequency of another gene (or genes) conferring susceptibility, and
the disease. Nevertheless, it is clear that there are that other genetic factors are involved as well.

Other possible genetic associations have been little (Johnson 1982). There are, however, a number of
studied, although there is evidence for an association important clinical and pathological differences be-
with genes concerned with the control of antibody tween visna and multiple sclerosis, including the
structure located on the fourteenth chromosome. A consistent failure to isolate, reproducibly from the
consistent pattern has not yet emerged. What is com- latter, a virus or fragments of one.
mon to all the genetic associations so far identified is The second plausible mechanism involves the de-
that they are concerned in one way or another with velopment of an autoimmune form of demyelination
the genetic control of the immune response. (after complete elimination of the virus) in mice inocu-
lated intracerebrally with corona virus (Watanabe,
Pathogenesis and Etiology Wege, and Ter Meulen 1983). The limitations of this
In considering how the geographic, epidemiological, model are that it is not known whether the process
genetic, and pathological data might fit together, it occurs after a natural route of infection, and whether
must be stressed that there is no wholly satisfactory in appropriate strains of animals a spontaneously
framework within which to incorporate all the data. relapsing and remitting disease can develop.
In conclusion, a solution to the problem of the
nature and cause of multiple sclerosis would seem to
Pathogenesis be within sight. When we understand the reasons for
Much evidence has accumulated suggesting an im- the peculiar distribution of the disease, we are also
munologic basis for the disorder in patients with likely to understand its etiology and pathogenesis.
multiple sclerosis. There is abnormal synthesis of W. I. McDonald
antibodies, both inside and outside the brain; there
are changes in the number and functional activity of
peripheral blood lymphocyte subsets in active dis- Bibliography
ease; and there are immune-competent cells around Barbellion, W. N. P. 1919. The journal of a disappointed
the venules in the lesions and in the brain itself. The man. London.
occurrence of such changes in the retina (where Carswell, R. 1838. Pathological anatomy: Illustrations of
there is no myelin) is evidence that the vascular the elementary forms of disease. London.
Charcot, J. M. 1968. Histologie de la sclerose en plaques.
events are not secondary to myelin breakdown pro- Gazette Hopital (Paris) 41: 554-5, 557-8, 566.
duced in some other way. This, combined with the Cruveilhier, J. 1835—42. Anatomie pathologique du corps
results of recent functional vascular studies and humain: Descriptions avec figures lithographiees et
other evidence, suggests that a vascular change is a colorizes: Des diverses alterations morbides dont le
critical early event in development of the new lesion. corps humain est susceptible. Paris.
Dawson, J. W. 1916. The histology of disseminated sclero-
Etiology sis. Transactions of the Royal Society ofEdinburgh 50:
517-740.
These processes provide a plausible though incom- Ebers, G. C, and D. Bulman. 1986. The geography of MS
plete explanation for the development of the lesions reflects genetic susceptibility. Neurology 36 (Supple-
in established multiple sclerosis. What of its initia- ment 1): 108.
tion? There is good evidence from family studies and Firth, D. 1948. The case of Augustus d'Esti. Cambridge.
epidemiology that an environmental trigger, proba- Johnson, R. T. 1982. Viral infections of the nervous system.
bly infective, is required in the genetically suscepti- New York.
ble individual. The most likely infective agent would Kurtzke, J. F., and K. Hyllested. 1986. Multiple sclerosis
be a virus, though interest in spirochetes has been in the Faroe Islands. II. Clinical update, transmission
revived recently on rather slender grounds. and the nature of MS. Neurology 36: 307-28.
Two possible mechanisms for demyelination fol- MacKarell, P. 1986. Interior journey and beyond: An art-
lowing viral infection are now known that occur only ist's view of optic neuritis. In Optic neuritis, ed. R. F.
in genetically susceptible hosts. With visna, a retro- Plant and G. T. Hess. Cambridge.
Matthews, W. B., etal. 1985. McAlpine's multiple sclerosis.
virus infection of certain strains of sheep, there are London.
recurring episodes of demyelination of the central McDonald, W. I. 1986. The mystery of the origin of multi-
nervous system dependent on a direct attack of the ple sclerosis. Gowers Lecture. Journal of Neurology,
virus; the remissions are due to the formation of Neurosurgery, and Psychiatry 49: 113—23.
neutralizing antibodies, whereas the exacerbations McDonald, W. I., and D. H. Silberberg, eds. 1986. Multiple
are due to mutations that lead to the loss of antibody sclerosis. London.
control and renewed multiplication of the virus Poser, C. M., and P. L. Hibberd. 1988. Analysis of the

VIII.92. Mumps 887
epidemic of multiple sclerosis in the Faroe Islands. II. wards, the period of greatest infectivity is about 48
Biostatistical aspects. Neuroepidemiology 7: 181-9. hours before salivary gland involvement. There is no
Rindfleisch, E. 1873. A manual of pathological histology, carrier state. Mumps has an incubation period from
Vol. III. London. time of exposure to onset of salivary gland swelling
Skegg, D. C. G., et al. 1987. Occurrence of multiple sclero- of about 18 days with a range of 2 to 3 weeks.
sis in the north and south of New Zealand. Journal of In populated areas with no or low vaccination cov-
Neurology, Neurosurgery and Psychiatry 50: 134-9.
erage, mumps is primarily an endemic disease of
Swingler, R. J., and D. A. S. Compston. 1986. The distribu-
tion of multiple sclerosis in the United Kingdom. Jour-
children, with epidemics occurring in closely associ-
nal of Neurology, Neurosurgery and Psychiatry 49: ated groups such as schools. Its peak incidence is
115-24. found in the age group 6 to 10 years, and mumps is
Watanabe, R., H. Wege, and V. Ter Meulen. 1983. Active rare before 2 years of age. Outbreaks may occur at
transfer of EAE-like lesions from rats with corona intervals ranging from 2 to 7 years. There is a con-
virus-induced demyelinating encephalomyelitis. Na- centration of cases in the cooler seasons in temper-
ture 305: 150-3. ate climates, and there is no apparent seasonality in
tropical areas. In more remote isolated populations,
mumps is not endemic, and disease depends upon
introduction of the virus from the outside, at which
time an epidemic may occur, affecting all age groups
VIII.92 born since the previous epidemic. There is no evi-
dence for a sex or racial difference in incidence of
Mumps mumps, although clinically apparent mumps may be
more common in males than in females.
Mumps (infectious parotitis; epidemic parotitis) is a Distribution and Incidence
common, acute, viral infectious disease, principally Serologic surveys as well as recorded outbreaks have
of children, with worldwide distribution. It is fre- demonstrated the existence of mumps throughout
quently clinically characterized by fever and painful the world. Mumps is not a reportable disease in most
enlargement of one or more salivary glands. Inappar- countries, is underreported even in countries where
ent infection is common and occurs in about one- it is a notifiable disease, and may be clinically
third of infections. Sometimes postpubertal males inapparent in 30 to 40 percent of infections. In popu-
with mumps may develop painful swelling of the lated areas where mumps is both endemic and epi-
testicles, usually only on one side, with sterility andemic, over 80 percent of the adult population will
extremely rare complication. Mumps is a vaccine- show serologic evidence of prior infection. In remote
preventable disease, but the vaccine is not yet or island populations where mumps is not endemic,
widely used on a global basis. a significant proportion of the population can be
susceptible which may lead to large outbreaks when
Etiology and Epidemiology the mumps virus is introduced from the outside.
Mumps is caused by the mumps virus, a member of In some countries, such as the United States, where
the genus Paramyxovirus of the family Paramyxo- mumps is a reportable disease and mumps vaccine
viridae. Mumps virus has an irregular spherical has been extensively used (often in combination with
shape averaging about 200 nanometers in diameter measles and rubella vaccine), there have been impres-
and contains a single-stranded RNA genome. sive declines in reported cases of mumps.
Mumps is a contagious disease, only slightly less
contagious than rubella and measles, transmitted Immunology
from infected persons to susceptible individuals by Infants usually have a passive immunity to mumps
droplet spread and by direct contact with saliva. because of maternal antibodies acquired transpla-
Mumps virus has also been shown to be transmitted centally from their immune mothers. This passive
across the placenta to the fetus. There is no natural immunity protects the infant from mumps infection
reservoir for mumps other than human beings, for about 6 months, depending on the amount of
which means that a continuous chain of susceptible maternal antibody acquired.
contacts is necessary to sustain transmission. Al- Mumps infection in both clinically apparent and
though the period of communicability may be from 6 inapparent cases induces a lifelong immunity. Be-
days before salivary gland symptoms to 9 days after- cause a significant percentage of mumps infections

are clinically inapparent, persons may develop im- History and Geography
munity without recognizing they have been infected. In the fifth century B.C., Hippocrates is believed to
Several serologic tests for confirming infection or have first recognized mumps as a distinct clinical
immunity have been developed, and it is also possi- entity in his work Epidemics I. He described an
ble to isolate the virus from patients during the outbreak of an illness on the island of Thasus, noting
acute phase of the disease. Skin tests for immunity that "swelling appeared about the ears, in many on
are not considered reliable. either side, and in the greatest number on both
A single dose of live attenuated mumps virus vac- sides . . . in some instances earlier, and in others
cine confers long-term, probably lifelong, immunity later, inflammations with pain seized sometimes one
in over 90 percent of susceptible individuals. of the testicles, and sometimes both." Greek and
Roman medical writers of antiquity as well as medi-
Clinical Manifestations and Pathology eval practitioners at various times recorded cases of
The prodromal phase of mumps disease may be ab- mumps-like illnesses, but there was relatively little
sent or include symptoms of low-grade fever, loss of study of the disease. Outbreaks of mumps in Paris in
appetite, malaise, and headache. Salivary gland the sixteenth century were recorded by Guillaume
swelling will often follow the prodromal period de Baillou. In 1755 Richard Russell described
within a day, although it sometimes will not begin mumps and expressed his opinion that the disease
for a week or more. The salivary gland swelling was communicable.
progresses to maximum size in 1 to 3 days. The Mumps is called Ziegenpeter or Bauerwetzel in Ger-
gland is painful and tender to the touch. Typically man and oreillons in French. The origin of the term
both the parotid salivary glands are affected, usu- "mumps" is unclear although it may come from the
ally with one gland enlarging a few days after the English noun mump, meaning a "lump," or the En-
other; hence the name "infectious or epidemic paro- glish verb mump, meaning "to be sulky," or even
titis." One-sided parotid gland involvement occurs perhaps from the pattern of mumbling speech in
in approximately one-fourth of patients who have individuals with significant salivary gland swelling.
salivary gland involvement. The fever may last for a In 1790, Robert Hamilton presented a very full
variable period (from 1 to 6 days), and the parotid description of mumps to the Royal Society of
gland enlargement may be present for 6 to 10 days. Edinburgh. He emphasized that orchitis was a
It should be emphasized that approximately one- manifestation of mumps and suggested that some
third of mumps cases may go unrecognized or be mumps patients had symptoms of central nervous
completely asymptomatic. system involvement. In the beginning of the eigh-
A common manifestation of mumps in approxi- teenth century, interest in the study of epidemics
mately 20 to 30 percent of postpubertal males is helped to establish the communicability and wide
painful testicular swelling (orchitis), usually one- geographic distribution of the disease.
sided. Sterility is an extremely rare outcome of August Hirsch collected references to some 150
testicular involvement on both sides, which occurs epidemics occurring between 1714 and 1859 in tem-
in only approximately 2 percent of cases. The next perate latitudes in both hemispheres as well as in
most common manifestation of mumps is central cold, subtropical, and equatorial regions. He specifi-
nervous system involvement in the form of a usually cally mentioned accounts of outbreaks that had oc-
benign meningitis, which may occur in about 10 curred in diverse countries and places: "Iceland, the
percent of all infections. Uncommon manifestations Faroe Islands, Lapland, Alaska, Egypt, Arabia, In-
of mumps include involvement and sometimes pain- dia, Malay Archipelago, Polynesia, the West Coast of
ful swelling of other glands such as the ovaries, Africa, Mexico, the West Indies, Peru, Italy, Sweden,
breasts, thyroid, and pancreas. Mumps-associated Prussian Saxony, Schleswig and Holstein, the depart-
complications are rare and may include encephali- ments of Dusseldorf and Treves, the Cologne depart-
tis, neuritis, arthritis, nephritis, hepatitis, pericard- ment, Martinique, Canton Zurich, Denmark, Lower
itis, and hematologic complications. Deafness, usu- Bavaria, Central Franconia, the quondam Duchy of
ally one-sided and often permanent, is reported to Nassau, New York, Halle, Moscow, Bombay, and Ber-
occur once per 20,000 cases of mumps. Although lin." He also stated that during the American Civil
increased fetal mortality has been reported in War, 11,216 cases among Confederate troops were
women who contracted mumps during the first tri- reported during the first year of the war and 13,429
mester, there is no evidence that mumps in preg- cases during the second year. He concluded that
nancy increases the risk of fetal malformations. mumps "occurs in widest diffusion over the globe, no

VIII.92. Mumps 889
part of the world being exempt from this strange Benenson, Abram S., ed. 1985. Control of communicable
malady." diseases in man. Washington, D.C.
Data have also demonstrated the occurrence of epi- Bett, Walter R., ed. 1954. The history and conquest of
demic mumps in the closely associated populations of common diseases. Norman, Okla.
prisons, orphanages, boarding schools, garrisons, and Bunyak, E. B., and Hilleman, M. R. 1966. Live attenuated
ships. Indeed, Haven Emerson noted that mumps was mumps virus vaccine. I. Vaccine development. Pro-
ceedings of the Society of Experimental Biology and
the most important disease in terms of days lost from Medicine 123: 768-75.
active duty in the American Expeditionary Force in Evans, Alfred S., ed. 1976. Viral infections of humans:
France during World War I; and Surgeon General T. Epidemiology and control. New York.
Parran of the U.S. Public Health Service stated in Gordon, John E., and Ralph H. Heeren. 1940. The epi-
1940 that mumps was one of the most disabling of the demiology of mumps. American Journal of the Medical
acute infections among armed forces recruits, ex- Sciences 200: 412-28.
ceeded only by the venereal diseases. Habel, K. 1945. Cultivation of mumps virus in the develop-
Despite earlier animal experiments suggesting ing chick embryo and its application to studies of
that the fluid of the salivary glands was infective, immunity to mumps in man. Public Health Reports
C. D. Johnson and E. W. Goodpasture were not able 60: 201-12.
to prove conclusively the viral etiology of mumps Hamilton, Robert. 1790. An account of a distemper, by the
until 1934. They demonstrated that mumps was common people in England vulgarly called the mumps.
Transactions of the Royal Society of Edinburgh 2:
caused by a filtrable virus in saliva by transmitting 59-72.
mumps from patients to rhesus monkeys. In 1945 K. Henle, G., and F. Deinhardt. 1955. Propagation and pri-
Habel successfully cultivated mumps virus in chick mary isolation of mumps virus in tissue culture. Pro-
embryos. In 1948 G. Henle and associates experimen- ceedings of the Society of Experimental Biology and
tally confirmed the significant percentage of clini- Medicine 89: 556-60.
cally inapparent infections by deliberately exposing Henle, G., et al. 1948. Isolation of mumps virus from
15 susceptible subjects to mumps, then following human beings with induced apparent or inapparent
their clinical condition, isolating the virus, and per- infections. Journal of Experimental Medicine 88: 223.
forming serologic studies. In 1951, an experimental Hirsch, August. 1886. Handbook of historical and geo-
killed-virus vaccine was used in humans. A live graphical pathology, trans. Charles Creighton. Lon-
mumps virus vaccine has been used in the former don.
U.S.S.R. since the early 1960s. In 1966 E. B. Buynak Johnson, C. D., and E. W. Goodpasture. 1934. An investiga-
tion of the etiology of mumps. Journal ofExperimental
and M. R. Hilleman reported on the development of Medicine 59: 1-19.
a live attenuated mumps virus vaccine, and they, Krugman, S., and S. L. Katz. 1981. Infectious diseases of
R. E. Weibel, and others conducted a successful trial children. St. Louis.
of the vaccine, which led to its licensure in 1967 in Major, Ralph H. 1945. Classic descriptions of disease.
the United States. Springfield, 111.
The worldwide geographic distribution of mumps U.S. Public Health Service. Centers for Disease Control.
is well documented, even in Hirsch's collection of 1987. Mumps - United States, 1985-1986. Morbidity
some 150 epidemics noted earlier. In populous coun- and Mortality Weekly Report 36: 151-5.
tries without any sustained, large-scale immuniza- Weibel, R. E., et al. 1967. Live attenuated mumps-virus
tion programs, mumps is widespread. In island or vaccine. III. Clinical and serologic aspects in a field
remote communities, large numbers of susceptible evaluation. New England Journal ofMedicine 245—51.
persons may exist. In countries with sustained,
large-scale immunization programs, the impact of
control efforts has been documented through decreas-
ing numbers of cases of reported mumps.
Robert J. Kim-Farley
This chapter was written in the author's private capacity. No
official support or endorsement by the Centers for Disease Con-
trol is intended or should be inferred.
Bibliography
Amstey, Marvin S., ed. 1984. Virus infection in pregnancy.
New York.

because, although he is weak, his muscles may ap-
VIII.93 pear to be unusually well developed. This pseudohy-
Muscular Dystrophy pertrophy is due to the infiltration of muscle and
replacement of muscle fibers by fat and connective
tissue. As the disease progresses, muscle fibers in-
The muscular dystrophies are a group of genetically creasingly appear abnormal microscopically, and oth-
determined, almost exclusively pediatric diseases. ers disappear. The upper extremities are affected
Generally, the earlier the age at which symptoms later but in the same fashion as the pelvic girdle and
begin, the poorer is the prognosis. Because of a con- lower limbs. Smooth muscle (e.g., intestinal tract,
siderable overlap of manifestations and rates of pro- bladder) is not affected. As a result of subnormal
gression and, until recently, the lack of any biochem- stress on the developing skeleton from the weak
ical test, their classification is still unsettled. As a musculature, ossification of long bones is delayed,
group, the principal differential diagnosis of the mus- and the mineral content of bones is deficient. Once
cular dystrophies is from the muscular atrophies. In weakness has resulted in confinement to wheelchair
the former, the primary defect is in the voluntary or bed, contractures of extremity joints and kyphosco-
muscle fibers; in the latter, it is in the innervation of liosis (deformity of the vertebral column) supervene.
muscles. A moderate degree of mental retardation frequently
is an associated problem. Death is generally due to
respiratory failure before the age of 20.
Classification The defective gene of DMD was identified in 1986.
The most common of the dystrophies and the first to Soon thereafter it was discovered that this genetic
be described was that delineated by Guillaume B. A. abnormality causes a deficiency of a protein, now
Duchenne, a French neurologist, in 1868. Duchenne called dystrophin, in the membrane of muscle fibers.
muscular dystrophy (DMD) is a sex-linked recessive Although this substance normally constitutes only
disorder. Consequently, it clinically affects only 0.002 percent of the total muscle protein, its defi-
males and is inherited through female carriers of the ciency can now be detected and can serve as a spe-
gene. Although affected boys have abnormally ele- cific diagnostic test.
vated concentrations of muscle cell enzymes such as At the other extreme from DMD in the spectrum
creatine phosphokinase in their blood, this abnor- of severity, there is facio-scapulo-humeral dystrophy
mality is also found in about three-fourths of the (FSHD), which was described by the French neurolo-
asymptomatic female carriers. DMD appears to have gists Louis T. Landouzy and Joseph J. Dejerine in
a rather uniform incidence worldwide, with a mean 1884. Onset usually occurs during adolescence, but
incidence estimated to be about 1 case per 4,000 live can be much later. Its incidence has been estimated
male births, or 15 to 33 cases per 100,000. Most to be from 5 percent to 50 percent of the incidence of
surveys have been of predominantly Caucasian popu- DMD. Inheritance is autosomal dominant, and
lations, but the results of a study in Japan were FSHD occurs equally in both sexes. As the name
consistent with the others. A family history of DMD indicates, the muscles of the face and shoulder girdle
can be obtained in only about one-third of cases. The are affected first. Sometimes only facial muscles are
others are attributed to either a previously unex- involved. An affected person may be unable to close
pressed carrier state or to a new mutation. the eyelids completely or to purse the lips. Muscular
Cases can be identified during the first week of life involvement progresses downward to the pelvic gir-
by an excessive concentration of creatine phospho- dle and legs, but it may become arrested at any time.
kinase in the blood, although the infant appears to Reproduction is not impaired. Death from sudden
be normal. The boy learns to walk somewhat late, heart failure occurs in some cases. So far there is no
falls easily, and has difficulty in getting up again. effective treatment for the underlying abnormality
The gait gradually becomes broad based and wad- of any of the muscular dystrophies.
dling. Nevertheless, the diagnosis usually is not Thomas G. Benedek
made before the age of 5 years. Unless the boy has
been identified by biochemical screening during in- Bibliography
fancy and the parents receive genetic counseling, Drummond, L. M. 1979. Creatine phosphokinase levels in
their risk of producing additional dystrophic chil- the newborn and their use in screening for Duchenne
dren remains high. muscular dystrophy. Archives of Disease in Childhood
The appearance of the child may be perplexing 54: 362-66.

VIII.94. Myasthenia Gravis 891
Emery, A. E. 1980. Duchenne muscular dystrophy: Ge- be uniformly distributed throughout the United
netic aspects, carrier detection and antenatal diagno- States, and probably is uniformly distributed
sis. British Medical Bulletin 36: 117-22. throughout the world. There is no difference be-
Gardner-Medwin, D. 1980. Clinical features and classifica- tween city and country in the incidence of myas-
tion of the muscular dystrophies. British Medical Bul- thenia gravis, and the age-specific death rates for
letin 36: 109-15. the United States, based on a survey of 675 death
Hoffman, E. P., et al. 1988. Characterization of dystrophin
certificates listing myasthenia gravis as the primary
in muscle biopsy specimens from patients with Du-
chenne's or Becker's muscular dystrophy. New En-
cause of death, showed that 90 percent of the dece-
gland Journal of Medicine 318: 1363-8. dents were older than 15 years of age. For this popu-
Hyser, C. L., and J. R. Mendell. 1988. Recent advances in lation the age-specific death rate is less than 1 per
Duchenne and Becker muscular dystrophy. Neuro- million until age 35, when there is a steady increase
logic Clinics 6: 429-53. in the incidence of death for myasthenia gravis up to
Kakulas, B. A., and R. D. Adams. 1985. Diseases of muscle, age 75. There appears to be a twin-peaked incidence,
4th edition. Philadelphia. with females peaking between the ages of 15 and 24,
Kazadov, V. M., et al. 1974. The facio-scapulo-limb (or the and men peaking between ages 40 and 60. But if all
facioscapulohumeral) type of muscular dystrophy: ages are considered together, the sex ratio is proba-
Clinical and genetic study of 200 cases. European bly close to 1. Morbidity data in surveys of the
Neurology 11: 236-60. United States, Canada, England, Norway, and Ice-
Leth, A., et al. 1985. Progressive muscular dystrophy in
land over a 10-year period using retrospective analy-
Denmark. Acta Paediatrica Scandinavica 74: 881-5.
Tangsrud, S. E. 1989. Child neuromuscular disease in
sis show that the incidence of myasthenia is proba-
southern Norway: The prevalence and incidence of bly 0.2 to 0.5 per 100,000, with the prevalence being
Duchenne muscular dystrophy. Acta Paediatrica Scan- 3 to 6 per 100,000. In other words, the prevalence is
dinavica 78: 881-5. approximately 10 times the incidence.
Etiology and Immunology

The overwhelming evidence is that myasthenia
gravis is due to an immune system dysfunction that
VIII.94 produces an autodirected antibody against the
acetylcholine receptor in the postsynaptic mem-
Myasthenia Gravis brane of the neuromuscular junction. The evidence
is clinical, laboratory, serologic, and therapeutic.
Myasthenia gravis is a disorder of skeletal muscle The clinical evidence that myasthenia is an auto-
characterized by weakness and easy fatigability due immune disease is based on the association of myas-
to autoimmune destruction of the acetylcholine re- thenia with vaccination, insect sting, infection, or
ceptor in the postsynaptic membrane of the neuro- trauma; and its association with autoimmune dis-
muscular junction. eases such as hypothyroidism, systemic lupus, and
polymyositis. Many laboratory abnormalities point
Distribution and Incidence to the immune system dysfunction in myasthenia
The disease has a worldwide distribution and has gravis. These include serologic abnormalities, in-
been identified as the primary cause of death at the creased incidence of a specific human leukocyte anti-
average annual rate of 1.5 per million in the United gen (HLA-B8) in certain types of disease, histologic
States. If cases coded as contributory or as a compli- abnormalities of thymus and skeletal muscle, and
cation are included, then the total would be 2 to 2.5. abnormal responsiveness of lymphocytes to mito-
This seems to be the safest method of reckoning the gens. Antinuclear antibodies are positive in uncom-
actual incidence of myasthenia gravis, and previous plicated myasthenia in about 18 percent of cases and
estimates of 1 in 1,600 of the population probably in 54 percent of myasthenic patients who have
vastly overestimate the incidence of myasthenia. thymoma, a tumor derived from elements of the thy-
There is no difference between whites and non- mus. Antistriated muscle antibodies are present in
whites, and there is no difference in nationality. The about 11 percent of patients with uncomplicated
death rate is slightly higher for women than men. In myasthenia and in all patients who have myas-
age-adjusted death rates for all ages, there is no thenia associated with thymoma. Perhaps the most
appreciable difference in nine geographic regions of important serologic test in myasthenia is the IgG
the United States. Thus myasthenia gravis seems to antibody directed against the acetylcholine receptor.

This antibody is probably positive in 70 to 95 percent is unmistakable and is usually associated with bilat-
of clinically diagnosed myasthenic patients and is eral ptosis, weakness of the face, and difficulty in
the cause of the weakness and easy fatigability in smiling, chewing, and talking. The clinical diagnosis
the disease. Myasthenia gravis can be readily pro- is confirmed by demonstrating electrical defects in
duced in animals by immunizing them against their transmission at the neuromuscular junction, respon-
acetylcholine receptor. Experimental autoimmune siveness to anticholinesterase drugs, or the presence
myasthenia gravis usually develops 2 to 3 weeks of the anti-acetylcholine receptor antibody circulat-
after immunization with the receptor and has all the ing in the patient's blood. The consistent pathology
features of human myasthenia gravis. Myasthenia found in every patient is autoimmune destruction of
gravis responds to all of the manipulations against the postsynaptic receptor, simplification of the
the immune system that one would expect to see if postsynaptic membrane, widening of the synaptic
the disease were of autoimmune origin. Thymec- gap, and reduction in the acetylcholine receptor num-
tomy is effective, as are prednisone, Cytoxan, bers and efficiency. Thymic pathology is also present
plasma exchange, and any other treatment that neu- in myasthenia gravis. Approximately 80 percent of
tralizes the effect of excessive autoimmunity. patients have germinal centers and enlarged thy-
mus, and about 10 percent of patients have a thymic
Clinical Manifestations tumor, a thymoma.
The single most important clinical feature of myas-
thenia gravis is weakness of skeletal muscle wors- History
ened by exercise and relieved by rest. Without this
feature there can be no diagnosis. Weakness with Seventeenth Century
easy fatigability is the only constant in this disease; Although myasthenia gravis was not described with
all other features are variable. For instance, the weak- any pretense of completeness as a clinical entity
ness is usually worse in the afternoon and evening, until the last quarter of the nineteenth century, a
although some patients are weaker in the morning reference by Thomas Willis, an astute seventeenth-
when they first awaken. Usually the muscles sup- century English clinician, indicates that Willis
plied by the cranial nerves are the first and most probably knew of the disease and recognized the
severely affected, with resultant diplopia, ophthal- chief symptom of asthenia of the voluntary muscles
moplegia, dysphagia, dysphonia, dyspnea, and dys- with recovery after rest. The description of weakness
mimia. The disease may involve proximal lower- and in his patients occurs in his book on the physiology
upper-extremity muscles. In rare instances, however, and pathology of disease with illustrated cases, De
proximal muscles weaken first. Involvement of indi- anima brutorum (1672), published in two separate
vidual muscles may be symmetrical, but is often editions the same year in Oxford and in London. The
asymmetrical with a dominant leg and arm usually book was translated into English by S. Pordage in
weaker than a nondominant counterpart. Myasthe- 1683 and published as "Two Discourses Concerning
nia gravis can also present as weakness of a single the Souls of Brutes" in Willis's Practice of Physick
muscle - for example, the external rectus or superior (London 1684). The significant part is as follows:
oblique in one eye - or as a single complaint - for in- There follows another kind of this disease i.e., the palsy,
stance, jaw ptosis from inability to close the mouth. It depending on the want and fewness of spirits in which
can also present as a symptom seemingly unrelated although motion be not deficient in any part or member
to the neuromuscular system - for instance, burning wholly, yet it is not performed in any but the weakly and
eyes from exposure to keratitis, from incomplete eye depravedly only. For though the distempered are free from
closure during sleep, or a sore throat on awakening want of motion they are not able however to move their
from mouth breathing during sleep. The disease may member strongly or to bear any weight. Moreover, in ev-
affect people at any age or of either sex and varies in ery motor endeavor, they labor with a trembling of their
severity from mild nonprogressive disease involving limbs which is only a defect of debility and of a broken
strength in the mode of power.
the eyes only (ocular form) to severe cases that may
be rapidly fatal such as acute myasthenia gravis af- He then goes on to say that the patients with this
flicting older men. affliction, although languishing in their limbs, are
well in their stomachs and have a good and laudable
Diagnosis and Pathology pulse and urine. "Yet, they are as if they were inner-
No two myasthenic patients look alike or have the vated and cannot stand upright and dare scarce en-
same signs and symptoms. The classical appearance ter upon local motions, or if they do cannot perform

VIII.94. Myasthenia Gravis 893
them long. Yea, some without any notable sickness into remission, and it was natural for Erb to attri-
are for a long time fixed in their bed as if they were bute the improvement to his electrical treatment.
everyday about to die" Willis then goes on to state Erb's second case was Magdalene Meisel, a peasant
what has been often quoted: 30 years of age, first seen in 1870. Her symptoms
were double vision, ptosis, dysphagia, and weakness.
At this time I have under my charge a prudent and honest She died suddenly at night, and no autopsy was
woman who for many years have been obnoxious to this
done. She had clear-cut exacerbations and remis-
sort of spurious palsy, not only in her members, but also in
her tongue. She for sometimes can speak freely and sions. The third patient reported by Erb, August
readily enough, but after she has spoke long or hastily or Thai, a merchant, age 47 years, had difficulty hold-
eagerly, she is not able to speak a word but becomes mute ing his head up, and showed bilateral ptosis and
as afish,nor can she recover the use of her voice under an facial weakness.
hour or two. Subsequently, a score more cases were reported by
1893, when Samuel V. Goldflam reported a detailed
Thus did Willis note that his patients developed study of myasthenia gravis. Goldflam mentions all
general, "although partial paralysis," and that they of the currently accepted clinical signs and symp-
were not able to move their members strongly or toms of the disease, which he summarized as follows:
bear any weight. This seems to be a description of
myasthenia gravis, although, of course, we will 1. The disease occurs in early life.
never really know. 2. Both sexes are equally affected.
3. It is a disease of the motor system.
4. Chewing, swallowing, and eye movements are
Nineteenth Century
most affected at first, followed by involvement of
Nearly 200 years were to pass from the time of Willis
trunk extremity.
before myasthenia gravis was again mentioned in
5. Trunk involvement is usually but not necessarily
the medical literature. The next recorded observa-
always symmetrical.
tion appears to have been made by an English physi-
6. Most patients are worse in the afternoon and eve-
cian, Samuel Wilks in 1877, one of the physicians to
ning and are improved by rest.
Guy's Hospital, London, who, when describing some
cases of bulbar paralysis, described a patient with Goldflam also mentioned that daily exacerbations
symptoms slightly similar to myasthenia gravis. He and remissions may occur, and that death may be
talked about a woman who could scarcely walk and due to respiratory impairment, and may occur sud-
had defective extraocular movement. Her speech denly. His article in many ways is the most impor-
was slow and deliberate, and she fatigued easily. tant ever written in the history of myasthenia
Subsequently, she developed trouble swallowing and gravis.
was unable to cough and died of respiratory paraly- The next major advance occurred a year later, in
sis. This is an incomplete discussion, but is the first an 1894 paper by F. Galle. He was the first to ana-
fatal case of myasthenia gravis ever described in the lyze the reaction of muscles in myasthenia gravis to
medical literature. This report by Wilks was of some electrical stimulation and to name the disease. He
importance because the patient was autopsied and also suggested physostigmine as a form of drug treat-
no abnormality could be found in the nervous sys- ment, but he does not seem to have followed up on
tem, indicating that the patient's trouble was due to this important point; it was left to Mary Walker, 40
some kind of functional defect. years later, to demonstrate the therapeutic value of
The first really complete report of myasthenia physostigmine.
gravis was given by Wilhelm W. Erb in 1879; he
described a patient, age 55, who was seen in 1868,11 Twentieth Century
years prior to the publication of the case record. The Modern studies of the pathological physiology of
patient's illness had developed over a period of four myasthenia gravis started with the work of A. M.
months, and the first principal symptoms, which Harvey (1948), and a series of illustrious colleagues,
were clearly described, included ptosis, neck weak- including Richard Masland, D. Grob, and T. R.
ness, and dysphagia. Some atrophy was noticed in Johns. These men recognized the characteristic re-
the neck muscles, and the patient seemed to respond sponse of the evoked muscle action potential to re-
to faradism (induced current). The patient was proba- petitive stimulation of nerve, thereby localizing the
bly one of the first to be treated by Erb with electric- defect of myasthenia gravis to the neuromuscular
ity. The patient, George Fuss, a day laborer, went junction.

In 1964, E. Elmquist and colleagues, using mi- Harvey, A. M. 1948. Some preliminary observations on the
croelectrode techniques on human intercostal mus- clinical course of myasthenia gravis before and after
cle, seemed to show that there was too little thymectomy. Bulletin of the New York Academy of
acetylcholine in each quantum released from the Medicine 24: 505-22.
nerve terminal, an abnormality that could be ex- Lindstrom, J. M., et al. 1976. Antibody to acetylcholine
plained by the presence of a false transmitter or by receptor in myasthenia gravis: Prevalence, clinical cor-
relates and diagnostic value. Neurology 26: 1054—9.
an abnormal binding or packaging of acetylcholine
Lisak, R. P., and R. L. Barchi. 1982. Myasthenia gravis.
quanta. This particular finding, as it subsequently London.
turned out, was in error, and we now know that the Mann, J. D., T. R. Johns, and J. F. Campa. 1976. Long-
postsynaptic membrane is poorly sensitive to in- term administration of corticosteroids in myasthenia
fused acetylcholine and that the defect in myas- gravis. Neurology 26: 729.
thenia gravis has nothing to do with any presynaptic Newsom-Davis, J. 1979. Plasma exchange in myasthenia
defect. In fact, presynaptic release of acetylcholine gravis. Plasma Therapy 1: 17.
in my asthenia gravis is normal. Osserman, K. E. 1958. Myasthenia gravis. New York.
In the meanwhile, evidence was accumulating that Patrick, J., and J. M. Lindstrom. 1973. Autoimmune re-
there was an immunologic disorder in myasthenia. sponse to acetylcholine receptor. Science 180: 871—2.
This was first suggested by D. W. Smithers in 1959, Patten, B. M. 1978. Myasthenia gravis. Muscle and Nerve
who recognized the histological parallel between the 1: 190.
Schwab, R. S., and C. C. Leland. 1953. Sex and age in
thymus in myasthenia and the thyroid gland in thy-
myasthenia gravis as critical factors in incidence and
roiditis. The following year, J. A. Simpson drew atten- remission. Journal of the American Medical Associa-
tion to the increased frequency, in myasthenia gravis, tion 153: 1270.
of other diseases regarded as autoimmune, especially Simpson, J. A. 1966. Myasthenia gravis as an autoim-
rheumatoid arthritis. But the major advance oc- mune disease: Clinical aspects. Annals of the New
curred in 1973, when J. Patrick and J. M. Lindstrom York Academy of Sciences 135: 506-16.
injected rabbits with acetylcholine receptors purified Vincent, A. 1980. Immunology of acetylcholine receptor in
from electric eel, intending to make antibodies to the relation to myasthenia gravis. Physiological Reviews
acetylcholine receptor. In the process, they induced 60: 756.
and recognized experimental autoimmune myasthe- Walker, M. B. 1934. Treatment of myasthenia gravis with
nia gravis. This led to experiments indicating the na- physostigmine. Lancet 1: 1200.
ture of the human disease. We now know that the Whitaker, J. N. 1980. Myasthenia gravis and autoim-
munity. Advances in Internal Medicine 26: 489.
disease is caused by a circulating antibody directed
against the acetylcholine receptor and that treat-
ments directed against the abnormal antibody are
effective in modifying the clinical signs and symp-
toms of myasthenia gravis.
Bernard M. Patten
Bibliography
Blalock, A., et al. 1941. The treatment of myasthenia
gravis by removal of the thymus gland. Journal of the
American Medical Association 117: 1529.
Brunner, N. E., T. Namba, and D. Grob. 1972. Cortico-
steroids in management of severe, generalized myas-
thenia gravis: Effectiveness and comparison with
corticotropin therapy. Neurology 22: 603-10.
Elmquist, D., and J. O. Josefsson. 1962. The nature of the
neuromuscular block produced by neomycin. Acta
Physiologica Scandinavica 54: 105—10.
Grob, D., and A. M. Harvey. 1951. Effect of adrenocorti-
cotropic hormone (ACTH) and cortisone administra-
tion in patients with myasthenia gravis and report of
onset of myasthenia gravis during prolonged corti-
sone administration. Johns Hopkins Medical Journal
91: 125-36.

VTII.96. Onchocerciasis 895
In the 700,000 square-kilometers of the Volta Basin
vm.95 region alone, the World Health Organization esti-
mated that in the early 1970s, about 1 million of the
Nematode Infections 10 million inhabitants were infected, with about
70,000 classified as "economically blind." In north-
The roughly 500,00 species in the phylum Nemathel- ern Ghana alone, surveys in the early 1950s deter-
minthes, the nematodes or roundworms, include mined that about 30,000 people, roughly 3 percent of
both free-living forms and important parasites of the population, were totally blind because of oncho-
plants and animals. Many species of nematodes cerciasis. In some West African villages, adult blind-
parasitize humans, and several of them are major ness rates of from 10 to 30 percent have been ob-
public health problems in poor countries, especially served. Conversely, dermatologic symptoms predomi-
in the tropics. Some species reside as adults in the nate in Arabia, and ocular involvement is rare.
intestine; others are found in the blood and tissues.
SeeAscariasis,Dracunculiasis,Enterobiasis,Filaria-
sis, Onchocerciasis, Strongyloidiasis, Trichinosis, Clinical Manifestations, Diagnosis, and
and Trichuriasis. Treatment
K. David Patterson O. volvulus, one of several filarial worms that are
important human parasites, lives in the cutaneous
and subcutaneous tissues. Humans are the only de-
finitive host; there is no animal reservoir. Numbers
of adult worms, the females of which may reach a
length of 50 centimeters, live in large coiled masses,
VIII.96 which usually become surrounded by fibrotic tissue
Onchocerciasis generated by the host. In these nodules, which may
reach the size of a walnut and are often easily visible
on the head, trunk, hips, or legs, the adults can live
Onchocerciasis is caused by a filarial nematode, the and breed for as long as 16 years. Thousands of
roundworm Onchocerca volvulus. Humans are in- larvae, the microfilariae, emerge from the nodules
fected by larval microfilariae transmitted by blood- and migrate in the tissues of the skin. Host immune
feeding female flies of the genus Simulium. Symp- reactions to dead or dying microfilariae cause vari-
toms include skin damage, extreme itching, and ous forms of dermatologic destruction, including loss
ocular lesions, which can lead to permanent blind- of elasticity, depigmentation, and thickening of the
ness. Synonyms include river blindness in West skin. These changes are complicated by the host's
Africa, sowda in Yemen, and enfermedad de Robles reaction to the extreme pruritis caused by the aller-
in Latin America. gic reactions to the worm proteins; the victim may
scratch him- or herself incessantly in a vain attempt
Distribution and Incidence to relieve the tormenting itch. This condition is some-
Onchocerciasis is widely distributed in Africa south times called "craw-craw" in West Africa. Wandering
of the Sahara, especially in the savanna grasslands microfilariae can also cause damage to the lym-
from Senegal to Sudan. Its range extends southward phatic system and inguinal swellings known as
into Kenya, Zaire, and Malawi. The region encom- "hanging groin." Microfilariae that reach the eye
passing the headwaters of the Volta River system in cause the most damage. Larvae dying in various
northern Ghana, northeastern Ivory Coast, southern ocular tissues cause cumulative lesions that, over a
Burkina Faso (Upper Volta), and adjacent territories period of one to several years, can lead to progressive
has been a major center for the disease. Onchocer- loss of sight and total blindness. There appear to be
ciasis was almost certainly indigenous to Africa, but distinct geographic strains, which help to explain
it has been transmitted by the slave trade to the different pathological pictures in parts of the para-
Arabian Peninsula (Saudi Arabia and Yemen) and to site's range; for example, in forest regions of Camer-
the Caribbean basin, where scattered foci exist in oon a smaller percentage of infected persons experi-
Mexico, Guatemala, Colombia, Venezuela, Ecuador, ence ocular complications than do inhabitants of the
and Brazil. The disease has a patchy distribution savanna.
within its range; infection rates in particular vil- Diagnosis is by detection of nodules, by micro-
lages may range from zero to virtually 100 percent. scopic demonstration of microfilariae in skin snips,

and, in recent years, by a number of immunologic meters of a stream with suitable breeding sites. The
tests. Therapy includes surgical removal of nodules, term "river blindness" accurately reflects the geo-
which has been widely practiced in Latin America to graphic distribution of the disease.
combat eye damage, and various drugs to kill the Onchocerciasis often has dramatic effects on hu-
wandering microfilariae. The first drug to be widely man activities and settlement patterns. In many
used was diethylcarbamiazine (DEC), but in heavily heavily infested areas, notably in the headwaters of
infected people it may cause serious side effects the Volta River, swarming flies, tormenting skin in-
when the immune system reacts to the allergens festation, and progressive blindness among a signifi-
released by large numbers of dying worms. Dermato- cant proportion of the population have resulted in
logic complications of DEC can be severe, but these progressive abandonment of rich, well-watered farm-
are treatable with antihistamines and corticoste- lands near the rivers. Depopulation of river valleys
roids; ophthalmologic complications are less com- due to onchocerciasis has been going on for decades in
mon but more dangerous. Suramin, a drug used to much of northern Ghana, with people being forced to
combat trypanosomiasis, is effective against both cultivate crowded and eroding lands away from the
microfilariae and adult worms, but it has serious streams. In many areas, land-hungry people were set-
side effects and, like DEC, is too dangerous to use in tling the river valleys in the early twentieth century,
mass campaigns. Some success has been reported but, as John Hunter has shown in his classic study of
with antihelminthics like mebendazole, but only Nangodi on the Red Volta, in recent decades the line
ivermectin, a microfilaricide introduced in the early of settlement has been retreating from the rivers. It is
1980s, seems safe and effective enough for wide- possible that a cycle of colonization and retreat, with
spread use in rural areas of developing countries. farmers caught between malnutrition and land short-
ages on the one hand and the perils of onchocerciasis
Etiology and Epidemiology on the other, has been going on for centuries in parts
The vectors and intermediate hosts of the pathogen of the Volta basin.
are blood-feeding flies of the genus Simulium, espe-
cially members of the species complex Simulium History
damnosum. These annoying and appropriately As stated above, onchocerciasis is almost certainly a
named insects, sometimes called buffalo gnats, are disease that originated in Africa and has spread to
close relatives of the familiar "black flies" of the Arabia and the New World as an unintended by-
northern United States and southern Canada. The product of the slave trade. Skin lesions caused by
females bite people, cattle, goats, wild animals, or onchocerciasis were first described by J. O'Neill, who
birds to obtain blood meals. Flies feeding on infected detected microfilariae from Africans in the Gold
humans may ingest microfilariae. These migrate Coast (modern Ghana) suffering from the tormenting
from the insect's stomach to the muscles of the tho- itch of "craw-craw." The organism was first described
rax, where they undergo about a 1-week developmen- in 1893 by the eminent German parasitologist K. G.
tal process before migrating to the salivary glands. Friedrich Rudolf Leuckart, who studied adults in nod-
Here, as infective larvae, they await the opportunity ules extracted from Gold Coast Africans by a mission-
to enter a new host when the fly feeds again. Once ary. In 1916 the disease was first recognized in the
this happens, the larvae wander briefly in the skin Americas when the Guatemalan investigator Rodolfo
before settling down in clumps to mature, breed, and Robles discovered onchocerciasis in the highlands of
produce microfilariae. his country. Robles linked nodules to eye disease and
Simulium females lay eggs on rocks and vegetation suggested that the distribution of infection impli-
in swiftly flowing, richly oxygenated water. Ripples cated two species of Simulium as vectors. D. B.
around rocks, bridge abutments, and dam spillways Blacklock, working in Sierra Leone, showed in 1926
provide favorable conditions for the larval develop- that S. damnosum was the vector. In 1931 J. Hissette,
ment of the vector. There is no transovarial transmis- working in the Belgian Congo, linked onchocerciasis
sion, so newly emerged adults must acquire oncho- with blindness for the first time in Africa, but despite
cerca in a blood meal. Adult flies have extensive confirmation in the Sudan a year later, colonial doc-
flight ranges: Infected females aided by winds and tors generally considered onchocerciasis only a skin
weather fronts can move hundreds of kilometers to disease. Just before World War II, French doctors in
establish new foci of disease. However, because of the what is now Burkina Faso began to link the disease
vector's breeding preferences, most flies and hence with mass blindness and river valley abandonment.
most onchocerciasis cases are found within a few kilo- Their colleagues across the frontier in the British

VIII.97. Ophthalmia (Conjunctivitis and Trachoma) 897
Gold Coast did not make a similar discovery until Bibliography
1949. Although British physicians and administra- Hunter, John M. 1966. River blindness in Nangodi, North-
tors were aware of river valley depopulation, oncho- ern Ghana: A hypothesis of cyclical advance and re-
cerciasis, and substantial blindness in the northern treat. Geographical Review 66: 398-416.
part of the colony, they did not link these phenomena, 1981. Progress and concerns in the World Health Organi-
zation Onchocerciasis Control Program in West Af-
partly because doctors who became interested in the
rica. Social Science and Medicine 15D: 261-75.
problem in the 1930s were repeatedly distracted by Kean, B. H., Kenneth E. Mott, and Adair J. Russell. 1978.
other duties or transferred. After the war, the associa- Tropical medicine and parasitology: Classic investiga-
tion was finally made, especially in a crucial 1949 tions, Vol. 2, 444-57. Ithaca, N.Y.
report by B. B. Waddy. A series of investigations in Patterson, K. David. 1978. River blindness in Northern
the 1950s confirmed the widespread incidence and Ghana, 1900-1950. In Disease in African history: An
serious consequences of the disease in a number of introductory survey and case studies, ed. Gerald W.
African countries, and Latin American foci were de- Hartwig and K. David Patterson, 88-117. Durham,
limited. N.C.
Puyelo, R., and M. M. Holstein. 1950. L'Onchocercose
Control humaine en Afrique noire frangaise: Maladie sociale.
In 1975 the World Health Organization, supported Medicine Tropicale 10: 397-510.
by a number of donor and afflicted countries, began Waddy, B. B. 1969. Prospects for the control of onchocer-
ciasis in Africa. Bulletin of the World Health Organiza-
the Onchocerciasis Control Programme, an ambi-
tion 40: 843-58.
tious and expensive 20-year effort to eliminate
onchocerciasis in the entire Volta Basin. The basic
strategy was to kill fly larvae by aerial spraying of
an organophosphate called Abate (generic name:
temephos) over breeding sites scattered over a huge
and repeatedly extended portion of West Africa. The VIII.97
absence of an effective agent to kill adult flies has
not prevented tremendous success in reducing and Ophthalmia (Conjunctivitis
sometimes eliminating Simulium populations. Al- and Trachoma)
though treatment of victims was less successful un-
til very recently because existing drugs were too
dangerous for mass use, the vector control program, In its broadest sense, ophthalmia is an inflammation
though costly and constantly faced with the problem of the eye, especially of the conjunctiva of the eye.
of reintroduction of adult flies from places beyond The term derives from the Greek word ophthalmos
the limits of the control program, has resulted in (the eye). Hence, almost any disease that attacked
dramatic declines in biting rates, infection, and the eye was called ophthalmia in many Greco-
blindness in most of the region. Recently, treatment Roman and later European sources until the begin-
of thousands of victims with ivermectin, a safe and ning of the twentieth century. As medical knowledge
effective microfilaricide, has helped to reduce blind- was refined, defining terms were attached, such as
ness among infected persons and has reduced the "purulent ophthalmia," "neonatorum ophthalmia,"
chances that a feeding fly would ingest infective or "Egyptian ophthalmia." The problem for histori-
microfilariae. The absence of an agent to kill adult ans attempting to define eye diseases in the past is
worms and the logistical and financial difficulties of that the term "ophthalmia" meant many diseases
the massive larviciding campaign make total eradi- that attack the eyes or that manifest symptoms in
cation unlikely, but vector control and microfilarici- the eye, and that blindness due to "ophthalmia" had
dal treatment can reduce the number of infected many causes. Two important causes of ophthalmia
persons and lessen or eliminate severe clinical symp- were trachoma and conjunctivitis; this essay is lim-
toms. Success at this level could help make thou- ited to these.
sands of square kilometers of valuable farmland safe Trachoma (also called granular conjunctivitis and
for use in many regions of Africa. It is, however, Egyptian ophthalmia) has been defined as a conta-
clear that there must be a long-term commitment to gious keratonconjunctivitis caused by Chlamydia
the campaign for many years into the future, or trachomatis (serotypes A, B, Ba, and C). It is charac-
river blindness will reconquer its old haunts. terized by the formation of inflammatory granula-
K. David Patterson tions on the inner eyelid, severe scarring of the eye

in the fourth stage, and blindness (but not in all Egypt still led the list of areas where a majority of
cases). It was one of the leading causes of blindness the population was affected. Because a dry climate
in the past, and still blinds millions in Asia, the seems to affect incidence, among the highest rates of
Middle East, and Africa (Bietti and Werner 1967; infection are the countries of North Africa and the
Rodger 1981; Insler 1987). Muslim Middle East - that is, from Morocco to
Conjunctivitis (purulent ophthalmia) may appear Egypt and the Sudan in North Africa, and from the
with trachoma and may complicate the progression of Red Sea to Turkey and Iran in the Middle East. It is
the disease so that blindness rather than healing also widespread in Asia, with 20 to 50 percent of the
occurs. Although conjunctivitis may denote any in- population infected in Burma, Pakistan, India,
flammation of the conjunctiva ("the mucous mem- China, Southwest Asia, Indonesia, and Borneo.
brane lining the inner surface of the eyelids and cover- These rates also occur in Africa south of the Sahara,
ing the frontpart of the eyeball"), bacteria often infect except for West Africa, where the incidence falls
the conjunctiva at the same time as does trachoma, below 20 percent. Similar trachoma rates continue
thus causing an acute bacterial conjunctivitis. In the along the Mediterranean coast of Europe, in Eastern
Middle East, for example, "spring and fall epidemics Europe, parts of Russia, Korea, Japan, Australia,
of gonococcal and Koch—Weeks conjunctivitis ac- New Zealand (among the Maoris), and the Pacific
count for much of the corneal scarring seen in these Islands. In the Western Hemisphere, Brazil and Mex-
populations" (Thygeson 1964). If trachoma attacks as ico have the highest incidences, but trachoma also
well, the two in combination may blind many indi- infects Indians and Mexican-Americans in the south-
viduals. Viruses can also cause conjunctivitis, and western United States. Sporadic cases appear in
historical descriptions that stress mild cases of parts of Europe, the Philippines, and some Central
ophthalmia often point to a viral or bacterial conjunc- and South American countries. The disease is practi-
tivitis. By contrast, the more severe ophthalmia that cally extinct in Canada, Switzerland, Austria, and
scarred the eye or permanently blinded individuals northern Europe - that is, in the countries with the
was often trachoma. It was almost impossible to iden- highest standards of living and sanitary conditions
tify the various forms of conjunctivitis before twen- and without pockets of extreme poverty. Where liv-
tieth-century scientific methods of testing, but even ing conditions have improved, trachoma has de-
at present, in desert and tropical areas, forms of bacte- clined or disappeared (Bietti and Werner, 1967). It is,
rial and viral conjunctivitis are still confused with however, a disease that still afflicts the impover-
trachoma, with which they often occur. ished who live in crowded conditions in the desert
Ophthalmia neonatorum is a term used for eye and tropical regions of Africa, the Middle East, Asia,
disease in newborns since the Greeks, but vague and Latin America (Bietti and Werner 1967; Rodger
historical references make it difficult to identify the 1981).
actual disease. Blindness in newborns may be due to
various infections acquired in the birth canal. Before Etiology and Epidemiology
the twentieth century, ocular gonorrhea may have Trachoma generally requires prolonged contact
been the major cause of blindness in newborns, but among individuals in filthy and overcrowded living
in the twentieth century (at least in the industrial- conditions for transmission. In endemic areas, infec-
ized nations) chlamydial infection is the most com- tionfirstoccurs in childhood as a result of close family
mon type of ophthalmia neonatorum (Thygeson contact. Transmission may be from mother to baby,
1971; Rodger 1981; Insler 1987). from eye to eye, by fingers, and by eye-seeking flies.
In urban slums or poor villages where people live
Distribution and Incidence crowded together under unsanitary conditions, garb-
Trachoma remains widespread in the twentieth cen- age and raw sewage attractfliesthat breed copiously.
tury. Two estimates place the number of victims As the insects swarm on the faces of infants and
worldwide at 400 million to 500 million, with mil- children, they feed on the infected eye discharges of
lions suffering from sight defects and perhaps 2 mil- those with trachoma and carry it to the eyes of other
lion totally blinded (Bietti and Werner 1967; Rodger victims. Most children in endemic areas have tra-
1981). choma at an early age, but hosting the disease in
In 1935 Adalbert Fuchs found that the greatest childhood does not provide a lifelong immunity.
frequency of the disease was in Egypt, "where 98 Trachoma transmission may also occur by direct
percent of schoolchildren in the fourth grade are touch, by the contamination of clothing or bedding,
afflicted by trachoma" (Fuchs 1962). In the 1960s, possibly by bathing in pools in which people swim

VIII.97. Ophthalmia (Conjunctivitis and Trachoma) 899
and wash, and by sexual means. According to B. R. inflammation mainly of the upper tarsal conjunctiva
Jones: with the formation of follicles" and then of papillae
with the "follicles appearing like sago grains." The
[I]n the vast majority of cases infection (with the TRIC
agent) is transmitted from person to person by intimate pannus increases toward the apex of the cornea.
sexual contact involving at various times genital, rectal, Because the red vessels in the cornea are dilated,
oral or other mucosal surfaces. No doubt it can be directly they are visible to the naked eye. In severe cases,
transferred to the eye during such activities. However, in because a secondary bacterial infection may worsen
the vast majority of cases it appears to be transferred to a the appearance of the eye, there will be purulent and
genital mucosal area, and then by means of transferring a copious secretions. In dark-skinned populations the
genital discharge by hand, or other vectors, it reaches the conjunctiva may take on pigment, which remains
eye. (Cited by Rodger 1981) after the healing stage. The duration is 6 months to
Factors that contribute to the severity of trachoma several years.
are ocular irritants and bacterial conjunctivitis. It is Stage 3 (cicatrizing trachoma) is the scarring and
most prevalent where the climate is hot and dry, and healing stage. The follicles rupture, and scar tissue
low humidity leads to excessive drying of the con- forms on the undersurface of the upper lids. Scar
junctiva. Winds and dust, along with smoke in un- tissue also appears elsewhere on the conjunctiva. At
ventilated huts, further irritate the eyes. Bacterial first, the scars are pink but later turn white. It is not
infections, particularly the seasonal outbreak of bac- uncommon for a new infection of C. trachomatis to
terial purulent conjunctivitis, often cause the worst occur at this stage and to start the process all over
cases. Frederick Rodger (1981) suspects that such again. Thus Stages 2 and 3 may coexist for many
infections are "related to the peak period of reproduc- years and may be further complicated by repeated
tion of theflypopulation." bacterial infections. With each new attack, more
scar tissue appears, and an ever-increasing pannus
covers the cornea. This phase may be several years
Clinical Manifestations and Pathology
in duration.
Trachoma Stage 4 (healed trachoma) is the final stage of the
The clinical features of trachoma are usually divided disease in which healing has been completed without
into four stages, following the classification system any signs of inflammation, and the disease is no
of A. F. MacCallan published in 1931: longer infectious. Trachomatous scarring remains,
Stage 1 (incipient trachoma) is characterized by however, and may deform the upper lid and cause
increasing redness of the conjunctiva lining the up- opaqueness in the cornea. The thickening of the up-
per lids and covering the tarsal plate. Magnification per lids gives a "hooded appearance to the eyes." Be-
reveals many small red dots in the congested con- cause scarring of the upper lids involves the tarsal
junctiva. As the organism proliferates, larger pale plate, which buckles, twists, and inturns, these fea-
follicles appear. Both features then spread across the tures indicate a past trachoma. When the inturning
upper conjunctival surface. A minimal exudate oc- occurs, the lashes often rub on the cornea (trichiasis),
curs, which may be more profuse if there is a secon- causing constant irritation and tearing until the cor-
dary bacterial infection. This stage is difficult to neal surface is scarred. Ulcers may develop, and bacte-
distinguish from the similar follicles of folliculosis rial infection of the ulcers can lead to blindness. An-
and follicular conjunctivitis. Another characteristic other complication may be drying of the conjunctiva
of this acute stage is that the upper part of the and cornea. The combination of corneal scarring,
cornea becomes edematous and infiltrated with in- opacification, and vascularization plus secondary bac-
flammatory cells that invade the upper part of the terial infections all account for impaired vision and
cornea from its edge. In the last phase of incipient blindness (Thygeson 1964; Yanoff and Fine 1975;
trachoma, pannus ("an abnormal membranelike vas- Grayson 1979; and Rodger 1981).
cularization of the cornea, due to granulation of the
eyelids") appears in the upper cornea. Rarely does Conjunctivitis
pannus appear in the lower cornea, and then only Simple acute conjunctivitis is a common eye infec-
with pannus in the upper cornea. The duration of tion, caused by a variety of microorganisms. Its most
Stage 1 is several weeks to several months. characteristic sign is the red or bloodshot eye. In
Stage 2 (established trachoma) marks the increase mild cases, there may be a "feeling of roughness or
of all the symptoms established in Stage 1 and is sand in the eyes," but in se

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The Cambridge World History of Human Disease

Cambridge Histories Online © Cambridge University Press, 2008

Arthur C. Aufderheide Stanley Engerman William McNeill

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

CAMBRIDGE UNIVERSITY PRESS

© Cambridge University Press 1993

This book is in copyright. Subject to statutory exception and

First published 1993

Reprinted 1994 (thrice), 1995, 1999

Printed in the United States of America

Typeset in Century Schoolbook

Library of Congress Cataloguing-in-Publication Data is available

ISBN 0-521-33286-9 hardback

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

List of tables, figures, and maps page xn 111.2. Immunology 126

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

VIII.3. Ainhum 561 VIII.29. Clonorchiasis 654

Cambridge Histories Online © Cambridge University Press, 2008

Vffl.57. Gallstones (Cholelithiasis) 738 VIII.83. Lupus Erythematosus 848

Cambridge Histories Online © Cambridge University Press, 2008

VIII. 109. Pneumonia 938 VIII. 135. Syphilis, Nonvenereal 1033

Cambridge Histories Online © Cambridge University Press, 2008

Tables IV.4.1. Abridged life table for Sweden,

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

HI.8.1. Annual consumption of VI.3.1. Mortality rates for the urban

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Geoffrey C. Ainsworth Georges C. Benjamin Kenneth J. Carpenter

Marvin J. Allison Surinder M. Bhardwaj K. Codell Carter

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008

Cambridge Histories Online © Cambridge University Press, 2008