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OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi
CONTENTS
1 Introduction 1
Life in space and time 4
Phenotype = genotype + environment + life history + epigenetics 4
Evolution is the change over time in the world of living things 5
Biological classification and nomenclature 6
Dogmas: central and peripheral 9
The structure of DNA 9
Transcription and translation 12
The structures of proteins 12
Statics and dynamics 17
Systems biology 17
The human genome 19
Variation in human genome sequences 20
The human genome and medicine 21
Databases in molecular biology 28
Observables and data archives 29
A database without effective modes of access is merely a data graveyard 29
Information flow in bioinformatics 31
Curation, annotation, and quality control 32
The World Wide Web 33
Electronic publication 34
Computers and computer science 34
Programming 35
Après moi, le déluge? Sorry—too late! 38
How much sequencing power is there in the world? 41
How does the amount of data in bioinformatics compare with other large scientific
information archives? 41
Recommended reading 42
Exercises and Problems 43
viii Contents
Contents ix
x Contents
Contents xi
xii Contents
Contents xiii
xiv Contents
Conclusions 399
Index 400
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi
On June 26, 2000, the sciences of biology and to prevent Celera—or anyone else—from applying
medicine changed forever. Prime Minister of the for patents.
United Kingdom Tony Blair and President of The academic groups lined up against Celera were
the United States Bill Clinton held a joint press a collaborating group of laboratories based primar-
conference, linked via satellite, to announce the ily but not exclusively in the UK and USA. These
completion of the draft of the Human Genome. The included the Wellcome Trust Sanger Institute in Eng-
New York Times ran a banner headline: ‘Genetic land; Washington University in St. Louis, Missouri;
Code of Human Life is Cracked by Scientists’. The the Whitehead Institute at the Massachusetts Institute
sequence of 3 billion bases was the culmination of of Technology in Cambridge, Massachusetts; Baylor
over a decade of work, during which the goal was College of Medicine in Houston, Texas; the Joint
always clearly in sight and the only questions were Genome Institute at Lawrence Livermore National
how fast the technology could progress and how Laboratory in Livermore, California; and the RIKEN
generously the funding would flow. The Table shows Genomic Sciences Center, now in Yokahama, Japan.
some of the landmarks along the way. Both sides could dip into deep pockets. Celera had
Next to the politicians stood the scientists. The its original venture capitalists; its current parent com-
late John Sulston (later Sir John, CH, FRS), Direc- pany, the PE Corporation; and, after going public,
tor of the Wellcome Trust Sanger Institute in the anyone who cared to take a flutter. The UK Medical
UK, had been a key player since the beginning of Research Council and The Wellcome Trust supported
high-throughput sequencing methods. He had grown the Sanger Institute. The US National Institutes of
with the project from the earliest ‘one man and a Health and Department of Energy supported the US
dog’ stages to the large international consortium. academic labs.
In the US, appearing with President Clinton were On June 26, 2000 the contestants agreed to declare
Francis Collins, director of the US National Human the race a tie, or at least a carefully out-of-focus
Genome Research Institute, representing the US pub- photo finish.
licly funded efforts; and J. Craig Venter, President The sequencing of the human genome ranks
and Chief Scientific Officer of Celera Genomics Cor- with the Manhattan project that produced atomic
poration, representing the commercial sector. It is weapons during the Second World War, and the
difficult to introduce these two without thinking, ‘In space program that sent people to the moon, as one
this corner . . . and in this corner . . . ’. Although never of the great bursts of technological achievement of
actually coming to blows, there was certainly intense the last century. These projects share a grounding in
competition, in the later stages a race. fundamental science, and large-scale and expensive
The race was more than an effort to finish first and engineering development and support. For biology,
to receive scientific credit for priority. It was a race neither the attitudes nor the budgets will ever be
after which the contestants would be tested not for the same. Soon a ‘one man and a dog project’ will
whether they had taken drugs, but whether they and refer only to an afternoon’s undergraduate practical
others could discover them. Clinical applications experiment in sequencing and comparison of two
were a prime motive for support of the Human mammalian genomes.
Genome Project. Once the courts had held that The human genome is only one of the many
gene sequences were patentable—with enormous complete genome sequences known. Taken together,
potential payoffs for drugs and diagnostic tools based genome sequences from organisms distributed widely
on them—the commercial sector rushed to submit among the branches of the tree of life give us a
patents on sets of sequences that they determined, sense, only hinted at before, of the very great unity
and the academic groups rushed to place each bit of in detail of all life on Earth. These results have
sequence that they determined into the public domain changed our perceptions, much as the first pictures
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi
of Earth from space engendered a unified view of Computing is an essential component of the first
our planet. three of these; CRISPR is spawning bioinformatics
support.
Molecular biology has seen four major break- Where will this lead? We can study the present as
throughs since the previous edition of this book thoroughly as we wish, and the past as extensively as
appeared: we can. What of the future? Molecular biologists used
to be like astronomers, in that we could observe our
• Explosive growth in next-generation genome
subjects but not affect them. This is no longer true:
sequencing
we now have the ability, and the challenge, of direct
• Consistent successful prediction of protein struc- control over living things, including but not limited
ture from amino acid sequence to ourselves.
• Achievement of atomic resolution in cryo-electron A gratifying consequence of this progress is its con-
microscopy tributions to medicine, agriculture, and technology.
• CRISPR for genome editing. A better understanding of life processes empowers us
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi
to deal with them when they go wrong, and even to lengthier answers or in some cases calculations. The
improve them when they do not. third category, ‘weblems,’ require access to the World
The human genome is fundamentally about Wide Web. Weblems are designed to give readers
information, and computers were essential both practice with the tools required for further study and
for the determination of the sequence and for the research in the field.
applications to biology and medicine that are flowing Examples and problems appear in the text.
from it. Computing contributed not only the raw Weblems are on the Online Resource Centre, a
capacity for processing and storage of data, but also website companion to the book.
the mathematically sophisticated methods required Some computing, based on the widely available
to achieve the results. The marriage of biology and language PERL, is introduced in this book. PERL
computer science has created a new field called is a relatively simple but extremely effective
bioinformatics. programming language. It is one of the languages
Today bioinformatics is an applied science. popular in the bioinformatics community. Similar
Computers have been an essential component of
the projects that determine sequence, structure, and
other types of data. We use computer programs to PERL, PYTHON, and RUBY
make inferences from the data archives of molecular
biology and medicine, to make connections among
As languages, PERL, PYTHON, and RUBY have roughly
them, and to derive useful and interesting predictions.
equivalent ranges of expression. However, applica-
This book is aimed at students and practising
tions of bioinformatics have begun to coalesce around
scientists who need to know how to access the
PYTHON: PYTHON arguably has a richer literature,
data archives, including but not limited to those of
both in training material and in available program mod-
genomes and proteins, how to use the tools that
ules (see, for example, http://rosalind.info/problems/
have been developed to work with these archives, locations/).
and the kinds of questions that these data and tools Nevertheless sample programs in the text are in PERL.
can answer. In fact, there are a lot of sources of this There are two reasons for this. The main one is that PERL
information. Sites treating topics in bioinformatics programs are more self-contained. PYTHON programs
sprawl out all over the Web. Our challenge is to select tend to invoke external ‘black boxes’ and are therefore
an essential core of this material and to describe it, less perspicuous. It is also true that PYTHON is divided
together with the necessary biological background, between PYTHON 2 and PYTHON 3—which to choose?
clearly and coherently, at an introductory level. Unfortunately they are not fully compatible. It is likely
It is assumed that the reader already has some that PYTHON 3 will eventually take over, but a large
knowledge of modern molecular biology, and some amount of legacy software exerts a viscous drag. Also,
facility at using a computer. The purpose of this book presenting PERL programs in the book has the advantage
is to build on and develop this background. It is that readers can be asked to provide PYTHON or RUBY
suitable as a textbook for advanced undergraduates versions as exercises!1
or beginning postgraduate students. Many worked- PERL, PYTHON, and RUBY each has an extensive
out examples are integrated into the text, and refer- repertoire of available components utilizable as ‘stand-
ences to useful websites and recommended reading alone’ modules, or for combination into novel programs:
are provided. A useful list of biomedical courses on- https://bioperl.org, https://biopython.org and https://
line appears at https://www.science.co.il/biomedical/ bioruby.org, and ‘Cookbooks’: Christiansen, T. & Tork-
ington, N. (2009). Perl cookbook 2nd edn; Beazley, D.
Courses.php.
& Jones, B.K. (2013). Python cookbook 3rd edn; and
Problems test and consolidate understanding, pro-
Carlson, L. & Richardson, L. (2015). Ruby cookbook 2nd
vide opportunities to practise skills, and explore addi-
edn; all published by O’Reilly Media, Sebastopol, CA.
tional topics. Three types of problems supplement the
texts of the chapters. Exercises are short and straight- 1 For a comment about PERL to PYTHON conversion see
languages include PYTHON and RUBY (see Box on The most striking change in attitude has been
previous page); each of these has its adherents. a refocus on integration; that is, of trying to see
Examples of simple programs appear in the context life processes as unified systems. As I wrote at the
of biological problems. Many simple programming end of Introduction to Protein Science: Architecture,
tasks are assigned as exercises, problems, or weblems Function and Genomics, ‘During the last century,
at the ends of the chapters. molecular biologists have been taking living things
Bioinformatics has grown, explosively, since the apart. Our task now is to understand how to put
first edition of this book appeared. Underlying this them back together.’ We have large amounts of data.
surge are the multiplication and growth of data Now we want to see how they interrelate. At the heart
streams. In addition to genomics, these include, but of life processes are complicated patterns of interac-
are not limited to, transcriptomics, metabolomics, tion among the components, in space and in time.
and regulatory networks. The human genome, To understand these patterns, the field has moved
available in draft form when the first edition towards combining information into networks, and
appeared, is now complete. Large-scale human analysing their structures and dynamics. Many tools
genome sequencing projects are underway. Joining are now available for storing, visualizing, analysing,
these results are the complete genomes of hundreds and comparing networks. Contemporary bioinfor-
of other eukaryote species, very large numbers of matics could not do without them.
prokaryotes, and many other organelle and viral Research and applications require that the data be
sequences. The extension to metagenomics—the available in useful form. It is not enough to make the
survey of distributions of sequences in a region of data public. The information must be subjected to
the land or ocean, or the human body—is a recent quality control, annotation, and a logical structure
development but a copious producer of data. These must be imposed on it to make information retrieval
data illuminate one another. One story that they tell possible. For this we are indebted to the institutions
is about unsuspected underlying unities of all living that archive, curate, organize, and distribute the data.
things, despite the obvious and profound differences A trend has seen mergers of these groups into col-
in morphology and lifestyle. laborative projects spanning the continents. In accord
These genome data are the harvest of new and with the need to integrate the study of different types
more powerful DNA sequencing methods. Of course of data, we are moving in the direction of a large-
particular attention is focused on human genomes: scale unified biological data archive and repository.
several hundred thousand individual genomes are Conversely, individual scientists will be able to define
known. The goal of the US$1000 human genome has ‘virtual databanks’ tailoring access to the information
been achieved. This enterprise continues to grow: it to suit particular needs and interests.
is likely that during the lifetimes of many readers, Major changes in information distribution involve
human genome sequencing will be nearly universal the transition from paper to electronic libraries. The
in many countries. implications for scientific research are only a part
Genomic sequences are supplemented by other of the great social revolution that has flowed from
data streams. Patterns of gene expression, and the development of the Web; comparable to, if not
networks of regulatory interactions, show how cells exceeding, the one impelled by the printing press
and organisms implement the information in the 500 years ago. Only connect.
DNA. The potential for the life of an organism is The natural habitat of bioinformatics is the Web.
contained in its genome, but it would be impossible To achieve their scientific goals most projects begin by
to deduce a biography from it. Genomes are not identifying the relevant data on one or more websites;
formulae or scripts. It is in the RNAs and proteins, analysing them, usually applying tools available on
and their interactions amongst themselves and the Web; and reaching robustly justified conclusions;
with DNA, that we must seek the set of life’s ultimately leading to a publication also distributed on
activities, tragic and comic, contingent on and the Web. However, a serious problem with the Web
responsive to developmental programmes and/or the is its volatility. Sites come and go, leaving trails of
environment. dead links in their wake. Databases proliferate. Many
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi
new databases represent different ways of ‘slicing and available tools rather than creating new ones.
dicing’ information from other resources. Changes Many programs are freely available. As with
in a source database may trickle down slowly—or the data, the challenges are often to recombine
not at all—to derived resources. The resulting lack available programs. Constructing a cart requires
of consistency is a serious problem. not reinventing wheels, but assembling them.
It is necessary to try to find a few gateways that
Practitioners of bioinformatics must assimilate these
are stable: not only continuing to exist but also kept
attitudes and reflect them in their training.
up-to-date in both their contents and links. I have
Accordingly, there is somewhat more mention of
suggested some such sites, but many others are just
topics from computer science in this edition than in
as good. The problem is not to create a long list
the previous ones. This is in part because of critical
of useful sites—this has been done many times, and
comments received, but also because it is easier to use
is relatively easy—but to create a short one—this
these tools than before. Instead of needing to write a
is much harder! The site https://www.science.co.il/
sophisticated program, it is often possible to find an
biomedical/databases/ is comprehensive but useful.
available distributed one, or even a web server.
All research in contemporary biology and medicine
Indeed, one of the arguments for the suggestion
depends on data, and on programs to retrieve and
that sophisticated programming skills are not gener-
analyse them. There is consensus that all biomedical
ally required is the great panoply of freely available
scientists must achieve a minimum of programming
programs, written by acknowledged professionals.
skills, but there is vigorous debate over what this
What is essential is developing skill in using these
minimum level should be. In the preface to the fourth
programs, and in intelligent interpretion of the results
edition I wrote: ‘The point of view expressed in this
that they produce.
book is that molecular biologists based primarily
This is the goal of the problems and projects in the
in a “wet” lab must dip no more than their toes
the text and in the Online Resource Centre. Many of
into the stream; those based primarily at a computer
them are ‘weblems’ based on data and facilities on the
must wade in up to their waist perhaps; but only
web. Some are programming exercises. Some of these
those specializing in computer science and software
involve modifying programs. Such challenges can be
development must undergo total immersion.’ Today,
more focused than writing programs from scratch.
this appears as a gross understatement, given that:
Moreover, such exercises better exemplify situations
1. The growth in the amounts, and kinds, of that arise in actual research.
data. Traditional input streams, such as DNA Some of the exercises, problems, and weblems,
sequences; and novel ones, such as tissue- although not requiring any programming, can be
dependent inventories of RNAs (transcriptomics), solved more easily by writing short programs. Read-
produce torrential output. There is danger in ers are encouraged to try this approach whenever
adopting too-casual an attitude. appropriate.
The minimal computing skills essential for a
2. A revolution in approach to data has been the
biomedical scientist would also include facility
recognition that the structure of data is as impor-
with using social media for communication (it is
tant as the values (it would be going a bit too far
assumed that readers are familiar with Facebook and
to say more important).
YouTube, but there are others that are in use for
3. Different ways to recombine data provide novel communication among scientists), and the ability to
approaches. An example would be to combine create a website. Studying from this book and the
genome sequences with signatures of protein func- Online Resource Centre affords an opportunity to
tion to assign roles to gene products. practise these skills. You might, for instance, ‘turn in’
4. The data have elicited new sets of tools for the answers to homework assignments by gathering
analysis and application. The breadth of the them into a Web page. Questions about statements
software literature is so encompassing that that you and the other students found unclear in
research applications tend to involve the selecting your instructor’s lectures—or, conceivably, even in
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi
this book—could be shared and discussed in a blog. Bioinformatics is one of them. I have also written
Indeed, there is now a trend to integrating websites about genomics, and about proteins, in companion
and social media. However, there are security issues. volumes also published by Oxford University
Your instructor might be unhappy if everyone copied Press: Introduction to Protein Science: Architecture,
the answers to the exercises from the first student Function, and Genomics and Introduction to
to post them. A class taught from this book would Genomics. As a result, this book is focused more
afford a fine opportunity to explore the possibilities tightly on the applied science of bioinformatics.
and challenges. Readers are urged to put the books together
There are many different possible points of for a more rounded appreciation of the pageant
view from which to present molecular biology. of life.
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi
• Chapter 1 sets the stage and introduces all of the paper to electronic form. This transition has many
major players: DNA and protein sequences and consequences, both intellectual and practical. It
structures, genomes and proteomes, databases and has had profound effects on research in bio-
information retrieval, the World Wide Web, and informatics.
computer programming. Before developing indi- • Chapter 7 treats the topics of artificial intelligence
vidual topics in detail it is important to see the and machine learning. Few activities, even outside
framework of their interactions. science, have escaped applications of these meth-
• Chapter 2 presents the background of genetics ods. They are playing a role of growing importance
and genomes, and the development of DNA in molecular biology.
sequencing. • Chapter 8 introduces systems biology. The key idea
• Chapter 3 contains a survey and some important of systems biology is integration: how do all the
examples of genome sequencing. pieces fit together? How do they interact? How
• Chapter 4 treats the analysis of relationships among do the individual molecules and processes together
sequences: alignments and phylogenetic trees. create a whole that so far transcends the pieces in
These methods underlie some of the major compu- self-sufficiency?
tational challenges of bioinformatics: detecting • Chapter 9 describes metabolic pathways. The
distant relatives, understanding relationships activities of individual enzymes are the subject
among genomes of different organisms, and tracing matter of classical biochemistry. Understanding
the course of evolution at the species and molecular their controls has been a goal of molecular biology,
levels. revealing a variety of mechanisms at the levels
• Chapter 5 moves into three dimensions, treating of transcription, translation, post-translational
protein structure and folding. Sequence and struc- modifications, and the interaction of inhibitors
ture must be seen as full partners, with bioinfor- and allosteric effectors with enzymes themselves.
matics developing methods for moving back and The integration of these controls is a development
forth between them as fluently as possible. Under- of systems biology, as a continuation of Chapter 8.
standing protein structures in detail is essential • Chapter 10 deals with more general control
for determining their functions and mechanisms mechanisms, including gene expression. Control
of action, and for clinical and pharmacological of gene expression is involved in responses to
applications. stimuli and changes in the cell’s environment,
• Chapter 6 describes the current state of the and governs short- and long-term developmental
scientific literature as it makes the transition from processes.
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi
ACKNOWLEDGEMENTS
I am grateful to many colleagues for discussions and T. Madden, J. Magré, M. McFall-Ngai, J. McInerney,
advice during the preparation of this book, and to the P. Miller, C. Mitchell, J. Moult, E. Nacheva, C.
universities of Uppsala, Umeå, Rome ‘Tor Vergata’, Notredame, C. Ouzounis, A.P. Pandurangan, H.
Bologna, and Cambridge for the opportunity to try Parfrey, D. Parkinson, A. Pastore, M. Peitsch,
out this material. D. Penny, J. Pettitt, C.A. Praul, C. Ravarani, S.
I thank S. Adhya, D.J. Abraham, S. Aparicio, Reikine, F.W. Roberts, G.D. Rose, P.B. Rosenthal,
M.M. Babu, T. Baglin, D. Baker, S. Balaji, M. B. Rost, B. Santhanam, E.J. Simon, M. Segal,
Bashton, A. Bateman, A. Bench, J.M. Bollinger, V. O. Skovegaard, G. Slodkowicz, E.L. Sonnham-
Bonazzi, M. Brand, A. Brazma, A. Buckle, C. Cantor, mer, R. Srinivasan, R. Staden, J. Sulston, I.
R.W. Carrell, S. Chavali, C. Chothia, D. Crowther, Tickle, A. Tramontano, A.A. Travers, A.R. Venki-
T. Dafforn, A. P. Diz, I. Dodd, R.B. Eckhardt, taraman, G. Vriend, P. Welsch, J.C. Whisstock,
J.G. Ferry, R. Foley, A. Friday, M. Galperin, M. Wildersten, A.S. Wilkins, S.H. White,
M.B. Gerstein, T. Gibson, J. Gough, J. Irving, B. V.E. Womble, and E.B. Ziff for advice and critical
Jorden, J. Karn, K. Karplus, P. Klappa, A.S. Kon- reading.
agurthu, E.V. Koonin, M. Krichevsky, P. Lawrence,
E.L. Lesk, M.E. Lesk, V.E. Lesk, V.I. Lesk, A. Lister, A.M.L.
L. Lo Conte, D.A. Lomas, A.D. MacKerell Jr, Cambridge, July 2018
OUP CORRECTED PROOF – FINAL, 23/4/2019, SPi
Exploring the Variety of Random
Documents with Different Content
The Project Gutenberg eBook of Race Riot
This ebook is for the use of anyone anywhere in the United States
and most other parts of the world at no cost and with almost no
restrictions whatsoever. You may copy it, give it away or re-use it
under the terms of the Project Gutenberg License included with this
ebook or online at www.gutenberg.org. If you are not located in the
United States, you will have to check the laws of the country where
you are located before using this eBook.
Language: English
Watts ran off after the mob chasing the natives, perhaps with some
idea of explaining, more likely not—he was in a half mindless rage of
excitement with the whiskey and the fighting. McCullough was left
alone with Tallant and the two natives. The native woman seemed
unhurt, she was picking herself up and examining the infant, which
still whimpered. Tallant was unconscious. McCullough picked him up
and carried him into the house.
His wife was standing white-faced at the door.
"Get some water," he said. He laid Tallant on a cot and began to
wipe off his face. There was a scalp cut where Watts' boot had
clipped him, most of the blood was coming from that; but it was
high and it did not feel like a fracture. Presently Tallant groaned and
shook his head and opened his eyes. The pupils did not look bad.
"How do you feel?" McCullough asked.
"Rough," Tallant mumbled. "Rough. Side ... hurts...."
McCullough pulled up the shirt and looked. There was a swelling
purplish bruise on the chest. He touched it gently and drew a gasp
of pain.
"Looks like maybe you got a cracked rib," he said. "Get me some
tape, will you, Mary?" He took the roll of tape and wound it tightly
about Tallant's chest.
"That'll hold till you get to a doctor," he said.
Tallant drew a light experimental breath. "Feels better," he said.
"What the hell happened anyway?"
McCullough told him.
"That's bad," Tallant said. "That fool Watts could touch off a real riot,
there's plenty more around here with no more brains than he has,
and just spoiling for trouble. Somebody ought to get the marshal's
office working on it before things get out of hand." He took the wet
rag he had been holding to his head away and examined the cut
with squeamish fingers. "Have to get this stitched up too, I guess,
before it sets up hard. Look, could you back my truck out into the
street? I don't feel up to driving, but if I get it in the street, it can
take me in to the dispensary on auto, and I can call Administration
from there."
There were very few private vehicles in Port Knakvik, or indeed
anywhere on Centaurus II; but Tallant, who was an electrician, had
a company panel which he drove to and from the job. Though it was
chemically powered—the new inductor station was the first nuclear
installation on the planet—it had the same cybernetic controls as any
Earthside vehicle. They worked fine on paved roads. On Knakvik
streets, however—
"I don't know," McCullough said dubiously, "You think you can make
it on auto? Suppose you get stalled?"
Port Knakvik lay on a silty alluvial plain. In the downtown area, the
streets were stabilized, but back along the river where the shanties
of the construction workers sprawled, they were simply ruts
punctuated at frequent intervals by chuckholes where churning
wheels had ripped off the overburden, exposing the bottomless
muck beneath.
"I'd go with you," McCullough said, "except I kind of hate to leave
Mary and the kids right now—I tell you, maybe I could find
somebody else. You lay down for a minute, take it easy, I'll look
around."
Tallant seemed to have guessed right about the riot, there were
people running by outside toward a commotion at the lower end of
the street where the native shanties clustered. McCullough saw a
man he knew from the job. "Hey, George," he called, "you got time
to do a little favor?" He explained about Tallant.
The man had not yet been in any fighting, he was simply curious
about what was going on, and this was part of it. "Sure, John," he
said. "Be glad to."
They helped Tallant into the truck. George backed it out into the
street on manual. "What's the dispensary coordinates?" he asked.
"Three-two-three, oh-one-five, local," Tallant told him.
George pushed the keys and they started off toward town.
McCullough turned to see what he could make out of the excitement
at the other end of the street. There were two columns of smoke
billowing up now, and scattered shots. Two men came back up the
street helping another with his trouser leg split away and a bloody
bandage about his thigh.
"What's it all about, John?" A man called across the street to him.
"Don't know. Fighting with the natives, I guess. Henry Watts and
some other fellows chased a couple of them down there. Looks like
they mean to clean the whole bunch out."
"Dammit, that's not right," the man across the street said. "The
natives got a right to live too, they had a village here before we
came. Somebody ought to do something about it."
"Pete Tallant just went into town to tell the marshal."
"Yeah, well, I wouldn't holler copper on my neighbors myself, but I
won't have anything to do with killing those poor natives either. They
can get along without me." The man went back in his house and
closed the door.
McCullough walked a few steps out into the street to get a better
view. The riot was none of his business, and he had no intention of
getting mixed up in it, but the idea of the fighting excited him and
made him nervous. He could not see much, except that there was a
lot of activity.
He shook his head helplessly. My God, he thought, all this from two
men with nothing to do on a Sunday afternoon but get half-drunk
and start arguing....
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