MMM

.l

fermions. Even though the composite fer- 14. J. K. Jain, ibid. 63,199 (1989).
15. To see how multiplication by the Jastrow factor at-
mions are quantum mechanical particles taches 2m vortices to each electron, fix all z. in the
with a true many-body character, they Jastrow factor except z1 As z1 traverses in a closed
may be treated, for most purposes, as or- loop around any other electron, it acquires a phase of
dinary noninteracting fermions moving in 4m1r, that is, it sees 2m vortices on all other electrons.
2.0 . 16. N. Trivedi and J. K. Jain, Mod. Phys. Lett. B 5, 503
an effective magnetic field. They form (1991).
quasi-LLs, execute cyclotron motion, and 17. G. Dev and J. K. Jain, Phys. Rev. Lett. 69, 2843
fill a Fermi sea. The formation of compos- (1992).
9.0 9.5 18. X. G. Wu, G. Dev, J. K. Jain, ibid. 71, 153 (1993); X.
l.0-B ite fermions lies at the root of the FQHE G. Wu and J. K. Jain, preprint.
and several other fascinating experimental 19. E. H. Rezayi and A. H. MacDonald, Phys. Rev. B 44,
phenomena. 8395 (1991); M. Kasner and W. Apel, ibid. 48,11435
(1993); E. H. Rezayi and N. Read, Phys. Rev. Lett.
0.0 0.2 72, 900 (1994).
Magnetic field (T)
REFERENCES AND NOTES 20. V. J. Goldman et al., Phys. Rev. Lett. 65, 907 (1990).
21. J. K. Jain, S. A. Kivelson, N. Trivedi, ibid. 64, 1297
Fig. 4. The resistance R = V34/121 for the magnet- 1. E. H. Hall, Am. J. Math 2, 287 (1879). (1 990).
ic focusing sample shown in the inset. (A) Focus- 2. K. von Klitzing, G. Dorda, M. Pepper, Phys. Rev. Lett. 22. B. l. Halperin, P. A. Lee, N. Read, Phys. Rev. B 47,
45, 494 (1980). 7312 (1993).
ing peaks of electrons near B = 0, and (B) focus- 3. D. C. Tsui et al., ibid. 48,1559 (1982). 23. R. R. Du et al., Phys. Rev. Lett. 70, 2944 (1993).
ing peaks of composite fermions near B* = 0 (that 4. See L. D. Landau and E. M. Lifshitz, Quantum Me- 24. Also see, l. V. Kukushkin, R. J. Haug, K. von Klitzing,
is, near v = 1/2). The scales of B and B* differ by chanics (Addison-Wesley, Reading, MA, 1965), pp. K. Ploog, ibid. 72, 736 (1994).
a factor of about \/2. A qualitative difference be- 424-426. 25. D. R. Leadley et al., ibid., p. 1906.

Downloaded from www.sciencemag.org on November 29, 2013

tween the positive and negative B* (that is, be- 5. R. B. Laughlin, Phys. Rev. B 23, 5632 (1981). 26. R. R. Du, H. L. Stormer, D. C. Tsui, L. N. Pfeiffer, K.
6. _ , Phys. Rev. Lett. 50,1395 (1983). W. West, Solid State Commun. 90, 71 (1994).
tween v > 1/2 and v < 1/2) is evident, as is the 7. For example, G. Fano, F. Ortolani, E. Colombo, Phys. 27. H. W. Jiang, H. L. Stormer, D. C. Tsui, L. N. Pfeiffer,
one-to-one correspondence between several Rev. B 34, 2670 (1986); F. D. M. Haldane and E. H. K. W. West, Phys. Rev. B 40, 12013 (1989); R. L.
composite fermion and electron focusing peaks. Rezayi, Phys. Rev. Lett. 54, 237 (1985). Willett et al., Phys. Rev. Lett. 65, 112 (1990).
[Reprinted from (30) with permission of Goldman 8. F. D. M. Haldane, Phys. Rev. Lett. 51, 605 (1983). 28. R. L. Willett, R. R. Ruel, K. W. West, L. N. Pfeiffer,
et al.] 9. B. l. Halpenn, ibid. 52,1583 (1984). Phys. Rev. Lett. 71, 3846 (1993).
10. See J. K. Jain, Adv. Phys. 41,105 (1992). 29. W. Kang et al., ibid., p. 3850.
11. S. M. Girvin and A. H. MacDonald, Phys. Rev. Lett. 30. V. J. Goldman et al., ibid. 72, 2065 (1994).
the lattice; some of the most relevant com- 58,1252 (1987). 31. V. J. Goldman, unpublished figure.
12. S. C. Zhang et al., ibid. 62, 82 (1989). 32. Financial support from the National Science Founda-
mensurate orbits are shown in the figure. 13. N. Read, ibid., p. 86. tion under grant DMR93-18739 is acknowledged.
Similar dimensional resonances of compos-
ite fermions show up near B* = 0. Goldman
et al. (30) observed magnetic focusing of
composite fermions near v = 1/2. The ex-
perimental setup is shown in Fig. 4.; the The Sverdlovsk Anthrax
current flows from 1 to 2, and the voltage is
measured between 3 and 4. Near B = 0, a
number of quasi-periodic peaks are observed
Outbreak of 1979
(Fig. 4B), which occur at those values of B Matthew Meselson,* Jeanne Guillemin, Martin Hugh-Jones,
where the electrons coming straight out of
the left constriction are focused into the Alexander Langmuir,t llona Popova, Alexis Shelokov,
right constriction, possibly after several Olga Yampolskaya
specular reflections from the gate. Similar
quasi-periodic structure was observed near In April and May 1979, an unusual anthrax epidemic occurred in Sverdlovsk, Union of
B* = 0 (Fig. 4A). The close correspon- Soviet Socialist Republics. Soviet officials attributed it to consumption of contaminated
dence between the electron and the com- meat. U.S. agencies attributed it to inhalation of spores accidentally released at a military
posite fermion peaks is evident in both Figs. microbiology facility in the city. Epidemiological data show that most victims worked or
3 and 4. These experiments confirm the lived in a narrow zone extending from the military facility to the southern city limit. Farther
existence of composite fermions in the south, livestock died of anthrax along the zone's extended axis. The zone paralleled the
compressible region near v = 1/2 by dem- northerly wind that prevailed shortly before the outbreak. It is concluded that the escape
onstrating that the dynamics of the charge of an aerosol of anthrax pathogen at the military facility caused the outbreak.
carriers are described by the effective field
B* rather than the external field B. Thus,
the composite fermion framework has not
only provided a simple "one-step" explana- Anthrax is an acute disease that primarily and legal journals reported an anthrax out-
tion of the FQHE, it has also helped reveal affects domesticated and wild herbivores break among livestock south of the city in
the nontrivial nature of the metallic state at and is caused by the spore-forming bacteri- the spring of 1979 and stated that people
even-denominator fractions. um Bacillus anthracis. Human anthrax re- developed gastrointestinal anthrax after
sults from cutaneous infection or, more eating contaminated meat and cutaneous
Conclusion rarely, from ingestion or inhalation of the anthrax after contact with diseased animals
pathogen from contaminated animal prod- (5-7). The epidemic has occasioned intense
The following picture has finally emerged. ucts (1). Anthrax has also caused concern international debate and speculation as to
First, electrons form LLs because of quan- as a possible agent of biological warfare (2). whether it was natural or accidental and, if
tization of their kinetic energy. This re- Early in 1980, reports appeared in the accidental, whether it resulted from activi-
sults in the IQHE. Within the lowest LL, Western press of an anthrax epidemic in ties prohibited by the Biological Weapons
in a range of filling factor, electrons min- Sverdlovsk, a city of 1.2 million people Convention of 1972 (8).
imize their interaction energy by capturing 1400 km east of Moscow (3, 4). Later that In 1986, one of the present authors
vortices and transforming into composite year, articles in Soviet medical, veterinary, (M.M.) renewed previously unsuccessful re-
1202 SCIENCE * VOL. 266 * 18 NOVEMBER 1994
 Table 1. Case data. Case numbers for fatalities are as they appear on the administrative list. Case
numbers for survivors are arbitrary. Days of onset and death are counted from 1 April 1979. Abbrevia-
tions: 0, onset; D, death; R, residence; W, workplace; unidentified man; ?, not known; ma, mid-April;
s, survivor; c, cutaneous survivor; +, in high-risk zone; -, outside high-risk zone; a, had two residences,
o 20- one in Compound 32; p, pensioner; r, daytime military reservist at Compound 32; u, unemployed.
Patients 25, 29, 48, and 87 were home on vacation during the first week of April.
0
15-
Case Age/sex O/D R/W Case Age/sex O/D R/W
E 10 no. no.
z
5_
* ?/m ?/? ?/? 51 31//m 10/15 -?
32 40/m ?/? -? 40 37/m 12/15 +/+
67 26/m ?/? +/+ 36 68/f ?/16 a/p
1 2 3 4 5 6 68 32/f ?/? +/+ 35 52/m 13/16 +/+
lime (weeks) 8 60/f ?/8 +/+ 34 43/m 14/16 -/+
18 38/m 6/8 -/? 38 69/f 14/16 +/p
Fig. 1. Time course of the epidemic: onsets of 16 40/m ?/9 +/+ 39 49/m 14/16 +/+
fatal cases by week. The first week begins on 4 66 55/f ?/9 -/? 41 41 /f ?/17 +/p
April 1979, the date of the first onset we recorded. 1 44/m 6/9 +/+ 42 43/m 15/18 -/+
Lighter shading represents cases for which the 2 46/m 6/9 +/+ 43 39/m 15/19 +/u
onset date is unknown and is estimated by sub- 5 66/m 7/9 -/+ 44 47/m 15/21 -/?
tracting 3 days from the date of death. 49 51 /m 8/9 +/+ 45 45/m ?/22 +/+
21 49/m ?/10 -/? 46 39/m 20/23 -/+
4 54/f 5/10 +/+ 47 41//m 21/24 /
quests to Soviet officials to bring indepen- 6 40/m 7/10 -/? 52 42/m 21/24
20 39/m 7/10 /- 53 47/m 22/24 -/-
dent scientists to Sverdlovsk to investigate. 17 67/f 8/10 +/+ 48 57/f 15/25 +/-
This resulted in an invitation to come to 9 72/f 9/10 +/p 54 50/f 17/25 -/?
Moscow for discussions with four physicians 7 52/f ?/11 +/+ 55 31 /m 23/25 +/+
who had gone to Sverdlovsk to deal with the 19 64/f ?/11 -/? 57 31//m 27/28 -/r
outbreak (including another of the present 22 27/m ?/11 +/+ 58 32/m 29/30 -/+
authors, O.Y., who was a clinician in the 23 43/m ?/1 1 -/r 59 55/m 27/31 -/+
3 48/f 4/11 -/+ 60 33/m 25/33 -/r
intensive care unit set aside to treat the 10 27/m 9/11 +/- 61 42/m 34/40 -/+
victims). In 1988, two of these Soviet phy- 65 72/m 9/11 +/p 62 29/m 39/40 +/+
sicians visited the United States, where they 15 48/f 6/12 +/+ 63 25/m 37/42 -/+
gave formal presentations and participated 25 46/m 10/12 -/ 64 28/m 42/46 -/?
in discussions with private and government 12 38/m 11/12 -/+ 90 28/m ?/s -/+
specialists. According to their account, con- 11 27/m 12/12 -/r 82 68/f 13/s +/+
26 67/m 9/13 +/p 80 49/m 14/c +/-
taminated animals and meat from an 13 24/f 10/13 +/+ 84 55/f ma/c -/+
epizootic south of the city starting in late 24 65/f 10/13 +/p 85 40/f ma/s +/+
March 1979 caused 96 cases of human an- 28 47/m 11/13 +/+ 89 50/f 34/s +/-
thrax with onsets from 4 April to 18 May. Of 14 49/m 12/13 -/+ 86 28/m 37/s /
these cases, 79 were said to be gastrointesti- 27 64/m 10/14 +/+ 81 29/m 38/s +/+
nal and 17 cutaneous, with 64 deaths among 31 42/m 11/14 -/r 83 45/m 41 /s +/+
30 52/m 12/14 +/+ 87 41 /m 42/s +/-
the former and none among the latter (9). 29 45/m 13/14 +/+ 88 37/m 45/s +/+
The impression left on those of the 50 72/f ?/15 +/p
present authors who took part in the U.S.
meetings (J.G., A.L., M.M., and A.S.) was
that a plausible case had been made but (10). These included interviews with Sver- investigation (13). The results of that in-
that additional epidemiological and patho- dlovsk physicians who questioned the food- vestigation have not yet appeared.
anatomical evidence was needed. Further borne explanation of the epidemic and with Pathoanatomical evidence that the fatal
requests by M.M. for an invitation led to an officials at the military microbiology facili- cases were inhalatory, recently published by
on-site study in Sverdlovsk, initiated there ty. These officials said that in 1979 they Russian pathologists who performed autop-
in June 1992, and a return visit in August had been developing an improved vaccine sies during the epidemic (14-16), is sum-
1993. against anthrax but knew of no escape of marized in an earlier report from the present
Starting in 1990, several articles about anthrax pathogen. Late in 1991, Russian study (17). Here we report epidemiological
the epidemic appeared in the Russian press President Boris Yeltsin, who in 1979 was findings that confirm that the pathogen was
the chief Communist Party official of the airborne, and we identify the location and
M. Meselson is in the Department of Molecular and Cel- Sverdlovsk region, directed his Counsellor date of its escape into the atmosphere.
lular Biology, Harvard University, Cambridge, MA 02138, for Ecology and Health to determine the
USA. J. Guillemin is in the Department of Sociology, Bos-
ton College, Chestnut Hill, MA 02167, USA. M. Hugh- origin of the epidemic (11). In May 1992, Sources of Information
Jones is in the School of Veterinary Medicine, Louisiana Yeltsin was quoted as saying that "the KGB
State University, Baton Rouge, LA 70803, USA. A. Lang- admitted that our military developments Local medical officials told us that hospital
muir is in the School of Hygiene and Public Health, Johns and public health records of the epidemic
Hopkins University, Baltimore, MD 21205, USA. I. Pop- were the cause" (12). No further informa-
ova is in the Social and Political Sciences Division, Ural tion was provided. Subsequently, the chair- had been confiscated by the KGB. We nev-
State University, Ekaterinburg 620083, Russia. A. She- man of the committee created by Yeltsin to ertheless were able to assemble detailed in-
lokov is in the Govemment Services Division, Salk Insti- oversee biological and chemical disarma- formation on many patients from a variety
tute, San Antonio, TX 78228, USA. 0. Yampolskaya is in
the Botkin Hospital, Moscow 125101, Russia. ment expressed doubt that the infection of sources. (i) An administrative list giving
*To whom correspondence should be addressed. originated at the military facility and stated names, birth years, and residence addresses
tDeceased 22 November 1993. that his committee would conduct its own of 68 people who died, compiled from KGB
SCIENCE * VOL. 266 * 18 NOVEMBER 1994 1203
records and used by the Russian govern- markers, giving names and dates of birth dresses, and, in some cases, workplaces or
ment to compensate families of the de- and death, that we inspected in the ceme- diagnoses (or both) of approximately 110
ceased ( 18). Comparison with other sources tery sector set aside for the anthrax victims. patients who were apparently screened for
of information, including those listed be- These include 61 markers with names that anthrax, 48 of whom are indicated to have
low, indicates that the administrative list are also on the administrative list and 5 died. Of the latter, 46 are on the adminis-
may include most or all of those who died of with illegible or missing name plates. (iv) trative list. (vi) Full clinical case histories of
anthrax. (ii) Household interviews with rel- Pathologists' notes regarding 42 autopsies 5 survivors hospitalized in May 1979.
atives and friends of 43 people on the ad- that resulted in a diagnosis of anthrax (14- Current street and regional maps were
ministrative list and with 9 survivors or 17). All but 1 of the 42, an unidentified purchased in Sverdlovsk, which is known
their relatives (or both). The interviews man, are on the administrative list. The again by its prerevolutionary name of Eka-
(directed by J.G.) were designed to identify notes include name, age, and dates of onset, terinburg. The city is the seat of an admin-
the workplaces and other whereabouts of admission, death, and autopsy. (v) Various istrative region, or oblast, named Sverd-
patients before their illness. (iii) Grave hospital lists, with names, residence ad- lovskaya. The city itself is divided among a
number of districts, or rayon, the most
southerly being Chkalovskiy rayon. A satel-
lite photograph of the city taken 31 August
1988 was purchased from SPOT Image Cor-
poration (Reston, Virginia). Archived me-
teorological data from the city's Koltsovo
airport were obtained from the National
Center for Atmospheric Research (Boulder,
Colorado).
Case Data
Table 1 presents information on 66 pa-
tients who died and 11 who survived. The
fatalities include the unidentified man
and all people named on the administra-
tive list, except for three patients for
whom recent reexamination of preserved
autopsy specimens does not support a di-
agnosis of anthrax (19). For survivors, di-
agnoses of anthrax are supported by clin-
ical case histories or hospital lists or both
and by household interviews.
Overall, 55 of the 77 tabulated patients
are men, whose mean age was 42. The mean

Fig. 2. Probable locations of patients when ex-

posed. The part of the city shown in the photo-
graph is enclosed by a rectangle in the inset. Case
numbers, in red, correspond to those in Table 1
and indicate probable daytime locations of pa-
tients during the period 2 to 6 April 1979. Of the 66
patients mapped as explained in the text, 62
mapped in the area shown. This distribution may
be somewhat biased against residence locations,
because daytime workers not on vacation who
both resided and worked in the high-risk zone are
mapped at their workplaces. Proceeding from
north to south, Compound 19, Compound 32,
and the ceramics factory are outlined in yellow.
The five patients residing in Compound 32 are
mapped at their apartments. Within the com-
pound, the placement of an additional, part-time
resident and of the five reservists is arbitrary, as is
that of the five residents and a nonresident em-
ployee in Compound 19. Patients known to have
worked in the ceramics pipe shop are mapped in
the eastern part of the factory area, where the pipe
shop is located. Calculated contours of constant
dosage are shown in black. Approximately 7000
people lived in the area bounded by the outermost
contour of constant dosage, Compound 32, and
the ceramics factory. The terrain slopes gently
downward by about 40 m from Compound 19 to
the ceramics factory.
1204 SCIENCE * VOL. 266 * 18 NOVEMBER 1994
 -- ill il- - 9 ---- 1

age for women was 55. No man was younger Public Health Response man anthrax is not considered contagious,
than 24, and only two women, aged 24 and nor was there any evidence of person-to-
32, were under 40. Recorded onsets span a Public health measures were initially direct- person transmission. In the part of Chka-
period of nearly 6 weeks, 4 April to 15 May, ed by an emergency commission formed in lovskiy rayon where most patients resided,
with a mean time between onset and death Chkalovskiy rayon, where most patients building exteriors and trees were washed
of 3 days (Table 1 and Fig. 1). lived and worked. On or about 10 April, by local fire brigades, stray dogs were shot
Approximately 60% of the 33 men for overall direction was assumed by a commis- by police, and several previously unpaved
whom we have relevant information were sion that was constituted at oblast level and streets were asphalted. Newspaper articles
described as moderate or heavy smokers and included the USSR Deputy Minister of and posters warned of the risk of anthrax
nearly half as moderate or heavy drinkers. Health. Military personnel participated lit- from consumption of uninspected meat and
None of the women was said to have tle if at all in the implementation of med- contact with sick animals. Uninspected
smoked or to have consumed alcohol more ical and public health measures. meat in vehicles entering the city from the
than occasionally. Few patients were report- Before the bacteriological confirmation south was confiscated and burned at high-
ed to have had serious preexisting medical of anthrax, on 11 April (14), patients were way checkpoints.
conditions. Among the 35 men whose oc- taken to hospitals served by the ambulance Starting in mid-April, a voluntary im-
cupation in 1979 we could determine, the or polyclinic of first contact. Starting on 12 munization program using a live nonencap-
most common occupation was welder, ac- April, most patients presenting with high sulated spore vaccine (designated STI) was
counting for 7. fever or other indications of possible an- carried out for healthy persons 18 to 55
In descending order of frequency, symp- thrax or who died at home or elsewhere of years old served by clinics in Chkalovskiy
toms reported in household interviews in- suspected anthrax were taken to city hospi- rayon. Posters urged citizens to obtain "pro-
cluded fever, dyspnea, cough, headache, tal No. 40, where separate areas were des- phylactic immunization against anthrax" at
vomiting, chills, weakness, abdominal pain, ignated for screening suspect cases and for designated times and places. Of the 59,000
and chest pain. Two of the survivors inter- treating nonsystemic cutaneous cases, for people considered eligible, about 80% were
viewed reported having had cutaneous an- intensive care, and for autopsy. Bodies of vaccinated at least once.
thrax, one on the back of the neck, the those who died were placed in coffins with
other on the shoulder. Hospitalized pa- chlorinated lime and buried in a single sec- Geographical Distribution of
tients were treated with penicillin, ceph- tor of a city cemetery. Medical and sanita- Human Cases
alosporin, chloramphenicol, anti-anthrax tion teams recruited from local hospitals
globulin, corticosteroids, osmoregulatory and factories visited homes of suspected and Most of the 77 tabulated patients lived and
solutions, and artificial respiration. The confirmed cases throughout the city, where worked in the southern area of the city
average hospital stay was 1 to 2 days for they conducted medical interviews, dis- shown in Fig. 2. Of the 66 patients for
fatal cases and approximately 3 weeks for pensed prophylactic tetracycline to pa- whom we have both residence and work-
survivors. To the best of our knowledge, tients' households, disinfected kitchens and place locations, 9 lived and regularly
no human anthrax has occurred in the sick rooms, and took meat and environmen- worked outside of this area. Interviews with
Sverdlovsk region since 1979. tal samples for bacteriological testing. Hu- relatives and friends revealed that five of
these nine had attended military reserve
classes during the first week of April 1979 at
Fig. 3. Villages with animal 603 Compound 32, an army base in the affected
anthrax. Six villages where area. Respondents stated and, in one case,
livestock died of anthrax in showed diary notes establishing that the
April 1979 are A, Rudniy; B, first day of attendance was Monday, 2
Bolshoye Sedelnikovo; C, April, that classes began at 0830, and that
Maloye Sedelnikovo; D, Per- participants returned home each evening.
vomaiskiy; E, Kashino; and F, Assuming that the reservists were exposed
Abramovo. Settled areas are
shown in gray, roads in white, while at or near Compound 32, this must
lakes in blue, and calculated have occurred during the daytime in the
contours of constant dosage week of 2 April.
in black. In order to locate the high-risk area
more precisely, we prepared a map showing
probable daytime locations of the 66 pa-
56040' tients during the week of 2 April. Those
with residence or work addresses in military
compounds or attending reserve classes
were placed in the appropriate military
compound; night workers, pensioners, un-
employed people, and vacationers were
placed at their homes; and all other workers
were placed at their workplaces. This
mapped 57 patients in a narrow zone ap-
proximately 4 km long, extending from the
military microbiology facility to the south-
em city limit. The remaining nine worked
outside this zone, but three of them resided
within it. Placing the latter at their resi-
dences gives the distribution shown in Fig.
56020' 2, with 60 of the 66 mapped cases in the
SCIENCE * VOL. 266 * 18 NOVEMBER 1994 1205
 -. i

high-risk zone, 2 cases east of it, and 4 cases south of the city in early spring 1979. A ined in order to identify times when the
north or east of the area of the figure. Of detailed report of a commission of veteri- wind direction was parallel to the center-
these six patients who both worked and narians and local officials describes the line of human and animal cases. During the
lived outside the high-risk zone, three had epizootic in Abramovo, a village of approx- time that the reservists who contracted an-
occupations (truck driver, pipe layer, and imately 100 houses 50 km south-southeast thrax were at Compound 32, but before the
telephone worker) that might have taken of Compound 19. The report, dated 25 first recorded human onsets, this occurred
them there, one was temporarily working in April 1979, records the deaths or forced only on Monday, 2 April, when northerly
Chkalovskiy rayon, one was on vacation, slaughter of seven sheep and a cow with winds from the sector 320° to 350° were
and inadequate information was available anthrax that was confirmed by veterinary reported throughout the period 0400 to
for another. examination. The first such losses were of 1900 local time (Fig. 4).
At the northern end of the high-risk two sheep on 5 April, followed by two more During the rest of April, winds from this
zone is the military microbiology facility, on each of the next 2 days, another on 8 sector seldom occurred, accounting for few-
Compound 19, followed to the south by April, and a cow on 10 April, all belonging er than 2% of reports. During the period of
Compound 32. Both compounds include to different private owners. These losses northerly wind on 2 April, which followed
numerous buildings, with four- and five- were substantiated by interviews we con- the passage of a cold front, the wind speed
story apartment houses for about 5000 peo- ducted with owners of six of the sheep that was 4 to 6 m s 1, the temperature -10° to
ple at the former and 10,000 at the latter. died. Respondents said there had been no -30C, the relative humidity 50 to 66%, the
The administrative list includes five people human anthrax in the village. During a sky cloudless, and the midday sun 390 above
who lived in Compound 19 and five who livestock immunization program started on the horizon. These conditions of insolation
lived in Compound 32. All of the latter 10 April, 298 sheep were given anti-an- and wind speed indicate that the atmo-
resided in four adjacent apartment buildings thrax serum or vaccine or both. The attack sphere near the surface was of neutral sta-
in the eastern part of the compound. Inter- rate among sheep at Abramovo therefore bility (21). As is consistent with this, tem-
views in Compound 32 indicated that all of appears to have been approximately 2%. perature measurements at 500 to 1000 m
its residents who died of anthrax are on the In addition, we obtained veterinary re- indicated a slightly stable atmosphere at
administrative list. Interviews were not ports of bacteriological tests positive for 0400 and 1000 hours, becoming neutral by
conducted in Compound 19. anthrax in samples from three sheep from 1600.
Adjacent to Compound 32 and extend- three farms in the village of Kashino, one
ing south-southeast for about 1.5 km is a sheep from Pervomaisky, and a cow from Discussion
residential neighborhood with a 1979 pop- Rudniy, the earliest samples being received
ulation density of approximately 10,000 per for testing on 6 April. Although other doc- We have presented evidence that (i) most
square kilometer, composed of small single- uments cite the forced slaughter of a sheep people who contracted anthrax worked,
story private houses and a few apartment in Rudniy on 28 March and the death of lived, or attended daytime military reserve
houses, shops, and schools. Just south of this another in Abramovo on 3 April, the ear- classes during the first week of April 1979
is a ceramics factory that had about 1500 liest livestock losses for which we have in a narrow zone, with its northern end in a
daytime employees. Of the 18 tabulated documentation of a diagnosis of anthrax are military microbiology facility in the city
patients who were employees there, 10 those in Abramovo on 5 April. and its other end near the city limit 4 km to
worked in a large unpartitioned building Altogether, Soviet publications (6, 7) the south; (ii) livestock died of anthrax in
where ceramic pipe was made and which and the documents we obtained cite out- villages located along the extended axis of
had a daytime work force of about 450. The breaks of anthrax among livestock in six this same zone, out to a distance of 50 km;
attack rate at the ceramics factory therefore villages: Rudniy, Bolshoye Sedelnikovo, (iii) a northerly wind parallel to the high-
appears to be 1 to 2%. Still farther south are Maloye Sedelnikovo, Pervomaiskiy, Kash- risk zone prevailed during most of the day
several smaller factories, apartment build- ino, and Abramovo. All six villages lie on Monday, 2 April, the first day that the
ings, private houses, schools, and shops, along the extended axis of the high-risk military reservists who contracted anthrax
beyond which begins open countryside with zone of human anthrax (Fig. 3). The cen- were within the zone; and (iv) the first
patches of woodland. terline of human and livestock cases has a cases of human and animal anthrax ap-
compass bearing of 3300 + 100. peared 2 to 3 days thereafter.
Animal Anthrax We conclude that the outbreak resulted
Meteorology from the windbome spread of an aerosol of
Anthrax has been enzootic in Sverd- anthrax pathogen, that the source was at
lovskaya oblast since before the 1917 revo- Surface (10 m) observations reported at the military microbiology facility, and that
lution (20). Local officials recalled an out- 3-hour intervals from Koltsovo airport, 10 the escape of pathogen occurred during the
break of anthrax among sheep and cattle km east of the ceramics factory, were exam- day on Monday, 2 April. The epidemic is
the largest documented outbreak of human
inhalation anthrax.
Fig. 4. Wind directions 2 April 3April 4 Apnil The narrowness of the zone of human
and speeds reported and animal anthrax and the infrequency of
from Koltsovo airport for northerly winds parallel to the zone after 2
the period 2 to 4 April April suggest that most or all infections
1979. Numbers at the 19019 resulted from the escape of anthrax patho-
downwind end of each 222. 13 gen on that day. Owing to the inefficiency
line are local standard 2700 V 16 of aerosol deposition and resuspension (22,
times. Inner and outer 16'2-T/ 23), few if any inhalatory infections are
concentric circles desig- 4,13 10,13
nate wind speeds of 2.5 116, 10 likely to have resulted from secondary aero-
and 5.0 m s-1, respec- 19 sols on subsequent days. A single date of
tively. Zero wind speed inhalatory infection is also consistent with
was reported for 0400 on 3 April and for 0100 and 0400 on 4 Apr1l. No data were reported for 0700. the steady decline of onsets of fatal cases in
1 206 SCIENCE * VOL. 266 * 18 NOVEMBER 1994
 ..li .l Il Il

successive weeks of the epidemic. 0.2, and 0.1 X 10-8 Q spore minutes per nine spores. According to the Gaussian
Accepting 2 April as the only date of cubic meter (Fig. 3), where Q is the number plume model we have used, this dose would
inhalatory exposure, the longest incubation of spores released as aerosol at the source. be inhaled by individuals breathing 0.03 m3
period for fatal cases was 43 days and the The number of spores inhaled is the dosage min 1 at the pipe shop if the aerosol re-
modal incubation period was 9 to 10 days. multiplied by the breathing rate. On the leased at the source contained 4 X 1 O0
This is longer than the incubation period of innermost contour of Fig. 2, for example, a spores. In contrast, a release 150 times larg-
2 to 6 days that has been estimated from person breathing 0.03 m3 min1, as for a er is estimated if the calculation is based on
very limited data for humans (24). Experi- man engaged in light work (33), would an LD50 of 4.5 X 104 spores, which has
ments with nonhuman primates have inhale 3 X 10` Q spores. been obtained for rhesus monkeys by other
shown, however, that anthrax spores can The calculated dosage at Abramovo is investigators (37), and if it is assumed that
remain viable in the lungs for many weeks more than an order of magnitude lower spores act independently in pathogenesis
and that the average incubation period de- than that at the ceramics factory. This sug- and that all individuals are equally suscep-
pends inversely on dose, with individual gests that sheep, reported to be more sus- tible (38). This estimate would be lowered
incubation periods ranging between 2 and ceptible to inhalation anthrax than are if allowance were made for nonuniform sus-
approximately 90 days (25, 26). monkeys (34), are also more susceptible ceptibility. If these divergent estimates
The absence of inhalation anthrax pa- than humans. bracket the actual value, the weight (39) of
tients younger than 24 remains unex- It has been suggested that if Compound spores released as aerosol could have been
plained. Although nothing suggests a lack 19 was the source, there would have been as little as a few milligrams or as much as
of children or young adults in Chkalovskiy many more cases in its close vicinity than nearly a gram.
rayon in 1979, they may have been under- farther downwind (13). This expectation In sum, the narrow zone of human and
represented in the aerosol plume. Alterna- may be misleading, for as a cloud moves animal anthrax cases extending downwind
tively, older people may have been more downwind it also widens. The total cross- from Compound 19 shows that the out-
susceptible, which may also explain the lack wind-integrated dosage will therefore de- break resulted from an aerosol that originat-
of young people in epidemics of inhalation crease more slowly with distance than does ed there. It remains to be learned what
anthrax early in this century in Russian the dosage along the centerline. In the activities were being conducted at the com-
rural communities (27). present case, whereas the calculated center- pound and what caused the release of the
It may be asked if the geographical dis- line dosage decreases by a factor of 40 be- pathogen.
tribution of cases is consistent with the dis- tween 0.3 and 3 km downwind, the cross-
tribution expected for an aerosol of anthrax wind-integrated dosage decreases by a factor REFERENCES AND NOTES
spores released at Compound 19 under the of only 4. Depending on the dose-response 1. P. S. Brachman, in Bacterial Infections of Humans:
daytime atmospheric conditions of 2 April relation, the crosswind-integrated attack Epidemiology and Control, A. S. Evans and P. S.
1979. Contours of constant dosage were cal- rate may decrease even more slowly than Brachman, Eds. (Plenum, New York, ed. 2, 1991),
culated from a Gaussian plume model of this. Considering, in addition, the lack of pp. 75-86.
2. Health Aspects of Chemical and Biological Weapons
atmospheric dispersion, with standard devi- information regarding the exact locations of (World Health Organization, Geneva, Switzerland,
ations given by Briggs for neutral atmospher- people in Compounds 19 and 32 at the time 1970).
ic stability in open country (21), a wind of exposure, the distribution of cases is not 3. Posev (Frankfurt) 1, 7 (1980).
4. B. Gwertzman, New York Times, 19 March 1980, p.
speed of 5 m s- l, a nominal release height of inconsistent with a source at Compound 19. 1.
10 m, and no limit to vertical mixing (Figs. More detailed comparison of the geo- 5. I. S. Bezdenezhnykh and V. N. Nikiforov, Zh. Mikro-
2 and 3). The aerosol is assumed to consist graphical distribution of cases with the cal- biol. Epidemiol. Immunobiol. 1980 (no. 5), 111
of particles of diameter <5 Kum, as can be culated distribution of dosage would require (1980).
6. Veterinariya 1980 (no. 10), 3 (1980).
produced, for example, by a laboratory aero- knowledge of the precise locations of indi- 7. Chelovek i Zakon 117 (no. 9), 70 (1980).
sol generator (28), and to have a negligible viduals in relation to the plume, the num- 8. Defense Intelligence Agency, "Soviet biological war-
infectivity decay rate (<0.001 min'l) (2) ber of spores released as aerosol, and the fare threat," DST-1610F-057-86 (U.S. Department
of Defense, Washington, DC, 1986); L. H. Gelb, New
and a deposition velocity <0.5 cm sol, relation between dosage and response for York Times Magazine, 29 November 1981, p. 31; J.
which is insufficient to cause appreciable the particular spore preparation, aerosol, P. P. Robinson, Arms Control 3, 41 (1982).
reduction of dosage at downwind distances and population at risk. 9. R. J. Smith and P. J. Hilts, Washington Post, 13 April
By far the largest reported study of the 1988, p. 1; M. Meselson, Fed. Am. Sci. Public Inter-
less than 50 km (29-31 ). Dosage contours est Rep. 41, 1 (September 1988); I. S. Bezdenezh-
are not shown closer than 300 m to the dose-response relation for inhalation an- nykh, P. N. Burgasov, V. N. Nikiforov, unpublished
putative source, as the dosage at shorter thrax in primates used 1236 cynomolgus manuscript, "An Epidemiological Analysis of an Out-
distances depends sensitively on the effec- monkeys exposed to an aerosol of the Vol- break of Anthrax in Sverdlovsk" (U.S. Department of
State Language Service, translation 126894, Sep-
tive release height of the aerosol and the lum 1B strain of B. anthracis (26, 35). This tember 1988).
configuration of nearby buildings. provided data that, when fitted to a log- 10. N. Zhenova, Literatumaya Gazeta (Moscow), 22 Au-
People indoors will be exposed to the normal distribution of susceptibility to in- gust 1990, p. 12; ibid., 2 October 1991, p. 6; S.
Parfenov, Rodina (Moscow), May 1990, p. 21; Pash-
same total dosage as those outside if filtra- fection, gave a median lethal dose (LD50) of kov, Isvestiya (Moscow), 1 1 November 1991, p. 8; V.
tion, deposition, and infectivity decay of 4100 spores and a slope of 0.7 probits per Chelikov, Komsomolskaya Pravda (Moscow), 20
the aerosol are negligible. The negligibility log dose (26, 36). This LD50 may be com- November 1991, p. 4.
11. N. Zhenova, Literatumaya Gazeta (Moscow), 13 No-
of these factors is supported by the absence pared with an LD50 of 2500 spores obtained vember 1991, p. 2.
of significant dosage reduction in field stud- in an experiment done under identical con- 12. D. Muratov, Yu. Sorokin, V. Fronin, Komsomolskaya
ies of protection afforded by tightly con- ditions with 200 rhesus monkeys (35) and Pravda (Moscow), 27 May 1992, p. 2.
structed buildings against an outside spore with a U.S. Defense Department estimate 13. L. Chernenko, Rossiyskiye Vesti (Moscow), 22 Sep-
tember 1992, p. 2.
aerosol (32). that the LD50 for humans is between 8000 14. A. A. Abramova and L. M. Grinberg, Arkh. Patol. 55
The calculated contours of constant dos- and 10,000 spores (8). For a log-normal (no. 1), 12 (1993).
age, like the zone of high human and ani- distribution with LD50 = 8000 and slope = 15. _ , ibid., p. 18.
16. L. M. Grinberg and A. A. Abramova, ibid., p. 23.
mal risk, are long and narrow. Contours are 0.7, the dose causing 2% fatalities, as re- 17. F. A. Abramova, L. M. Grinberg, 0. V. Yampolskaya,
shown at 10, 5, and 1 X 10`8 Q spore corded at the ceramics pipe shop, approxi- D. H. Walker, Proc. Natl. Acad. Sci. U.S.A. 90, 2291
minutes per cubic meter (Fig. 2) and at 0.5, mately 2.8 km downwind of the source, is (1993).
SCIENCE * VOL. 266 * 18 NOVEMBER 1994 1207
 .M ... ..l ...

18. Russian Federation, statute 2667-1 (4 April 1992). 28. J. V. Jemski and G. B. Phillips, in Methods of Animal 38. H. A. Druett, Nature 170, 288 (1952).
19. L. Grinberg, personal communication. Experimentation, W. 1. Gay, Ed. (Academic Press, 39. R. Scherrer and V. E. Shull, Can. J. Microbiol. 33,
20. V. M. Popugaylo, R. P. Sukhanova, M. I. Kukhto, in New York, 1965), pp. 273-341. 304 (1987).
Current Problems of Anthrax Prophylaxis in the 29. A. C. Chamberlain, Proc. R. Soc. London A 296, 45 40. We thank A. V. Yablokov, Counsellor to the Presi-
USSR (Moscow, 1974), p. 50. (1967). dent of Russia for Ecology and Health, for letters of
21. S. R. Hanna, G. A. Briggs, R. P. Hosker, Handbook 30. T. W. Horst, in Atmospheric Sulfur Deposition, D. S. introduction; Ural State University and its then rec-
on Atmospheric Diffusion (U.S. Department of Ener- Shriner, C. R. Richmond, S. E. Lindberg, Eds. (Ann tor, P. E. Suetin, for inviting us to Ekaterinburg; S.
gy Report No. DOE/TIC-1 1223, Washington, DC, Arbor Science, Ann Arbor, Ml, 1980), pp. 275-283. F. Borisov, V. A. Shchepetkin, and A. P. Tiutiunnik
1982). 31. A. Bovallius and P. Anas, in Proceedings of the 1st for assistance and advice; members of the Ekater-
22. D. E. Davids and A. R. Lejeune, Secondary Aerosol International Conference on Aerobiology, Interna- inburg medical community and the Sverdlovskaya
Hazard in the Field (Defence Research Establish- tional Association for Aerobiology, Munich, West Oblast Sanitary Epidemiological Service for discus-
ment Suffield Report No. 321, Ralston, Alberta, Can- Germany, 13 to 15 August 1978, A. W. Frankland, E. sions, notes, and documents; interview respon-
ada, 1981). Stix, H. Ziegler, Eds. (Erich Schmidt, Berlin, 1980), dents for their cooperation; P. N. Burgasov, USSR
23. A. Birenzvige, Inhalation Hazard from Reaerosolized pp. 227-231. Deputy Minister of Health at the time of the out-
Biological Agents: A Review (U.S. Army Chemical 32. G. A. Cristy and C. V. Chester, Emergency Protec- break, for documents regarding livestock deaths;
Research, Development and Engineering Center Re- tion Against Aerosols (Report No. ORNL-5519, Oak and People's Deputy L. P. Mishustina for the ad-
port No. TR-413, Aberdeen, MD, 1992). Ridge National Laboratory, Oak Ridge, TN, July ministrative list of those who died. I. V. Belaeva
24. P. S. Brachman, S. A. Plotkin, F. H. Bumford, M. M. 1981). assisted with interviews. We also thank B. Ring, W.
Atchison, Am. J. Hyg. 72, 6 (1960). 33. D. S. Ditmer and R. M. Grebe, Eds., Handbook of H. Bossert, P. J. M. Cannone, M. T. Collins, S. R.
25. D. W. Henderson, S. Peacock, F. C. Belton, J. Hyg. Respiration (Saunders, Philadelphia, 1958). Hanna, J. V. Jemski, D. Joseph, H. F. Judson, M.
54, 28 (1956); C. A. Gleiser, C. C. Berdjis, H. A. 34. G. A. Young, M. R. Zelle, R. E. Lincoln, J. Infect. Dis. M. Kaplan, J. Medema, C. R. Replogle, R. Stafford,
Hartman, W. S. Gochenour, Br. J. Exp. Pathol. 44, 79, 233 (1946). J. H. Steele, and E. D. Sverdlov. Supported by
416 (1963). 35. J. V. Jemski, personal communication. grants to M.M. from the John D. and Catherine T.
26. H. N. Glassman, Bacteriol. Rev. 30, 657 (1966). 36. C. I. Bliss, Ann. Appl. Biol. 22,134 (1935). MacArthur Foundation and the Carnegie Corpora-
27. A. V. Elkina, Zh. Mikrobiol. Epidemiol. Immunobiol. 37. H. A. Druett, D. W. Henderson, L. Packman, S. J. tion of New York. This article is dedicated to Alex-
1971 (no. 9), 112 (1971). Peacock, J. Hyg. 51, 359 (1953). ander Langmuir.

* RESEARCH ARTICLE 80-kD complex suggested that either the

complex was a homodimer or that an un-
known TCR chain was involved that may
affect T cell maturation. A glycosylated
Analysis and Expression of a chain of 33 kD (gp33) is paired with TCRP
proteins in a TCR,-transfected immature T
Cloned Pre-T Cell Receptor Gene cell line (SCB.29) from severe combined
immunodeficient (SCID) mice (12), but
could not be identified in normal thymo-
Claude Saint-Ruf,* Katharina Ungewiss,* Marcus Groettrup, cytes (12, 13). The gp33-TCR3 complex of
Ludovica Bruno, Hans Joerg Fehling, Harald von Boehmer SCB.29 cells is associated with CD3 pro-
teins (8, 12) and cross-linking of TCR
chains initiates Ca2+ mobilization. This
The T cell antigen receptor (TCR) P3 chain regulates early T cell development in the suggested that this TCR, complex could be
absence of the TCRoL chain. The developmentally controlled gene described here responsible for the developmental progres-
encodes the pre-TCRa (pTcx) chain, which covalently associates with TCRf and with sion observed in TCRP transgenic, rear-
the CD3 proteins forms a pre-TCR complex that transduces signals in immature rangement-deficient mice, whereas the
thymocytes. Unlike the X5 pre-B cell receptor protein, the pTcx chain is a type I TCRP GPI-linked monomer could repre-
transmembrane protein whose cytoplasmic tail contains two potential phosphorylation sent a transgenic artifact (14, 15). We have
sites and a Src homology 3 (SH3)-domain binding sequence. Pre-TCRa transfection now cloned the gene encoding gp33 and
experiments indicated that surface expression of the pre-TCR is controlled by addi- examined its structure and expression. Be-
tional developmentally regulated proteins. Identification of the pTa gene represents an cause of its properties, the gp33 protein was
essential step in the structure-function analysis of the pre-TCR complex. named the pre-TCRa (pTax) chain.
Pre-T cell receptor a (pTa) expression
in immature T cells. The pTa chain can be
identified by two-dimensional (diagonal)
T cell development takes place in discrete chains, are sufficient to promote early T cell gel electrophoresis, in which the disulfide-
steps during which the TCR genes are rear- development (6-8). Although such mice linked pTao protein under reducing condi-
ranged and expressed in temporal order. are still rearrangement-defective, their im- tions migrates away from the diagonal just
During development of TCRax-expressing mature thymocytes (which express neither underneath the TCR, protein (12) (Figs. 1
cells the TCRP gene is rearranged and ex- the CD4 nor CD8 proteins) begin to express and 2). The analytical method was scaled
pressed before the TCRao gene (1, 2). With- CD4 and CD8 coreceptors, transcripts of the up to obtain sufficient amounts of pTa
out TCR rearrangement the development of TCRcx locus become detectable (7), and the protein for microsequencing. In a first at-
T cells is arrested at an early stage (3-5). By number of thymocytes increases (6-8). In- tempt a 20-amino-acid-long NH2-terminal
introducing TCRP transgenes into mice troduction of TCRP transgenes into normal sequence was obtained; a peptide of the 18
that are defective for rearrangement of an- mice suppresses rearrangement of endoge- NH2-terminal residues was synthesized and
tigen receptor genes, it was shown that nous TCRP genes (9, 10). The TCRI trans- injected into rabbits to obtain a pTa-spe-
TCRP proteins, in the absence of TCRa gene is expressed on the cell surface in the cific antiserum. The antiserum was tested
absence of TCRaL proteins in both normal for binding to the pTao protein. To this end
C. Saint-Ruf is at the Unite INSERM 373, Institut (11) as well as in rearrangement-defective lysates from the TCRax-negative SCB.29
Necker, 75730 Paris, Cedex 15, France. K. Ungewiss,
M. Groettrup, L. Bruno, H. J. Fehling, and H. von Boe-
mice (7, 8, 12) in an 80-kD disulfied-linked cell line as well as the TCRcx3-expressing
hmer are at the Basel Institute for Immunology, CH- complex and as a glycosyl-phosphatidylino- B6.2.16BW hybridoma (12) were precipi-
4005 Basel, Switzerland. sitol (GPI)-linked 40-kD monomer. tated with the monoclonal antibody (mAb)
'The first two authors contributed equally to this work. The presence of the TCRB chain in the F23.1 to V38 proteins (16). Precipitates
1208 SCIENCE * VOL. 266 * 18 NOVEMBER 1994