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"A new way of thinking about illness . . a igi pr spetive on the persistence of human vulnerabilitWy. -Peter D. Kramer, author of Listening PtoPza

The New Science of

Darwinian Medicine

Acclaim for

Randolph M. Nesse and George C. Williams's

WHY WE GET SICK

"This is the most important book written about issues in biomedi-

cine in the last fifty years. When the world's leading evolutionary

biologist (Williams) teams up with a thoughtful physician

(Nesse), the product is a gripping exploration of why our bodies

respond the way they do to injury and disease."

-Michael S. Gazzaniga, Ph.D.,

director, Center for Neuroscience,

University of California at Davis

"Darwinian medicine . . . holds that there are evolutionary expla-

nations for human disease and physical frailties, just as for

everything else in biology, and that these insights can inspire

better treatments.... In Why We Qet Sick ... two proponents

of Darwinian medicine lay out the ambitious reach of the

adventurous new discipline."

-The New York Times Magazine

"Every so often, a book comes along that has the power to

change the way we live and die. This splendid book is one, and

it could well revolutionize the way physicians are taught, the

way they practice, and even the way parents watch over their

child with a fever or a cough."

-Professor Robert Ornstein,

author of The Psychology of Consciousness

"Would you accept that eating certain kinds of red meat could help ward off heart attacks? That taking aspirin when you are sick could make things worse? That mothers should sleep right next to their infants to prevent sudden infant death? You might after hearing how your prehistoric ancestors lived, according to a small but growing tribe of 'Darwinian medicine' thinkers. They argue that for too long physicians have ignored the forces that shaped us over evolutionary eons.... Such ideas are ... controversial, but that's the point."

-Wall Street Journal

"Why We Qet Sick is certain to be recognized as one of the most important books of the decade, and what's more, it's beautifully written."

-Roger Lewin, author of Human Evolution, 3rd Edition

"Why We Qet Sick offers both a provocative challenge to medi- cine and a thoughtful discussion of how evolutionary theory applies to people."

-Business Week

Randolph M. Nesse, M.D. George C. Williams, Ph.D.

WHY WE GET SICK

Randolph M. Nesse, M.D., is a practicing physician and professor and associate chair for education and academic affairs in the Department of Psychiatry at the University of Michigan Medical School.

George C. Williams, Ph.D., is a professor emeritus of ecology and evolution at the State University at Stony Brook and editor of The Quarterly Review of Biology.

WHY WE GET SICK The New Science

of Darwinian Medicine

Randolph M. Nesse, M.D.

George C. Williams, Ph.D.

VINTAGE BOOKS

A Division of Random House, Inc.

New York

FIRST VINTAGE BOOKS EDITION, JANUARY 1996

Copyright ) 1994 by Randolph M. Nesse, M.D., and George C. Williams, Ph.D.

All rights reserved under International and Pan-American Copyright Conventions. Published in the United States by Vintage Books,

a division of Random House, Inc., New York, and simultaneously in Canada by Random House of Canada Limited, Toronto. Originally published

in hardcover by Times Books, a division of Random House, Inc., New York, in 1995.

Grateful acknowledgment is made to the following for permission to reprint previously published material:

Lawrence M. Crapo and James F. Fries, M.D.: Two charts from Vitality and Aging by Lawrence M. Crapo and James F. Fries, M.D.

(W. H. Freeman & Company, San Francisco, 1981). Reprinted by permission.

Harcourt Brace & Company: Chart 12-1 from Life: An Introduction to Biology by George C. Simpson, Colin S. Pittendrigh,

and Lewis H. Tiffany. Copyright C 1957 by George C. Simpson, Colin S. Pittendrigh, and Lewis H. Tiffany. Copyright renewed 1985

by Anne R. Simpson, Joan Simpson Burns, Ralph Tiffany, Helen Vishniac, and Elizabeth Leonie S. Wurr.

Reprinted by permission of Harcourt Brace & Company.

The Library of Congress has cataloged the Times Books edition as follows:

Nesse, Randolph M. Why we get sick: the new science of Darwinian medicine

Randolph M. Nesse and George C. Williams.-1st ed. p. cm.

Includes bibliographical references and index. ISBN 0-8129-2224-7

1. Medicine-Philosophy. 2. Human evolution. 3. Human biology. 4. Adaptation (Physiology)

I. Williams, George C. (George Christopher), 1926- II. Title. R723.N387 1995

610'.1-dc2O 94-27651 Vintage ISBN: 0-679-74674-9

Illustrations by Jared M. Brown

Manufactured in the United States of America 10 9 8 7

ACKNOWLEDGMENTS

Q - ur work has benefited enormously from comments made by many colleagues and friends who know more than we do about certain aspects of medicine and evolu- tion. We have not always had the sense to take their

advice, so don't blame them for our mistakes. Among those who have offered comments or other suggestions on the manuscript are: James Abelson, M.D., Ph.D., Laura Betzig, Ph.D., Helena Cronin, Ph.D., Lyubica Dabich, M.D., Wayne Davis, Ph.D., William Ens- minger, M.D., Paul Ewald, Ph.D., Joseph Fantone, M.D., Rosalind Fantone, R.N., Robert Fekety, M.D., Linda Garfield, M.D., Robert Green, M.D., Daniel Hrdy, M.D., Sarah Hrdy, Ph.D., Matt Kluger, Ph.D., Isaac Marks, M.D., Steven Myers, M.D., James Neel, M.D., Ph.D., Margie Profet, M.A., Robert Smuts, M.A., William Solo- man, M.D., Paul Turke, Ph.D., Alan Weder, M.D., Brant Wenegrat, M.D., and Elizabeth Young, M.D. For help in finding references we especially thank Doris Williams, Jeanette Underhill, M.D., and Joann Tobin. A sabbatical provided by The University of Michigan with support from John Greden, M.D., and George Curtis, M.D., made it possible for Randolph Nesse to work on the manuscript at Stanford University, where Brant Wenegrat, M.D., and Anne O'Reilly offered hospitality beyond measure. Barbara Polcyn's loyal and effective secretarial support was wonderful. We are grateful to our agent, John Brockman, for convincing us that we could present serious new science in a book for a general audience and for handling negotiations and publishing details with great effectiveness, and to Barbara Williams for persuading us to take John Brockman seri- ously. The style and structure of the book are much improved thanks to detailed editing by Margaret Nesse and by our editor at Times Books, Elizabeth Rapoport.

v

ACKNOWLEDGMENTS

Our greatest debt is to those who made us realize that we had a reason to write this book. They are the pioneers and visionaries whose ideas and investigations form the heart of the now flourishing field of Darwinian medicine. Some, like Paul Ewald and Margie Profet, figure prominently in several places in our text. Others are mentioned more briefly or merely have their publications listed in our endnotes. We are confident that, over the next few years, they will all be getting growing shares of the recognition they richly deserve.

vi

CONTENTS

Acknowledgments v Preface ix

1. The Mystery of Disease 3 2. Evolution by Natural Selection 13 3. Signs and Symptoms of Infectious Disease 26 4. An Arms Race Without End 49 5. Injury 66 6. Toxins: New, Old, and Everywhere 77 7. Genes and Disease: Defects, Quirks,

and Compromises 91 8. Aging as the Fountain of Youth 107 9. Legacies of Evolutionary History 123

10. Diseases of Civilization 143 11. Allergy 158 12. Cancer 171 13. Sex and Reproduction 182 14. Are Mental Disorders Diseases? 207 15. The Evolution of Medicine 234

Notes 251 Index 273

vii

PREFACE

W xe first met and discovered our shared interests in 1985 at a meeting of a group that later developed into the Human Behavior and Evolution Society. One of us (Nesse) was a physician in the Department

of Psychiatry at the University of Michigan Medical School. Frustra- tion with psychiatry's lack of theoretical foundation and fascination with the extraordinary progress that evolutionary ideas had brought to the field of animal behavior had led to his association with the University of Michigan Evolution and Human Behavior Program. Colleagues in that interdisciplinary group, on hearing about his long- term interest in the evolutionary origins of aging, suggested a 1957 paper by a biologist named George Williams. The paper was a reve- lation. Aging had an evolutionary explanation. Why not anxiety disorders or schizophrenia? Thanks to subsequent years of conversa- tions with evolutionists, especially Williams, and with medical school residents and faculty, he has found that an evolutionary per- spective on patients' disorders has become steadily more natural and useful.

The other author (Williams) has divided his career between marine ecological research and theoretical studies on evolution. His interest in medical applications of evolutionary ideas was aroused by reading a 1980 article by Paul Ewald in The Journal of Theoretical Biol- ogy, "Evolutionary Biology and the Treatment of the Signs and Symptoms of Infectious Disease." Ewald's work suggested that evo- lutionary ideas might well have significance for many medical prob- lems, not just those that arise from infection. Williams' general knowledge of evolutionary genetics included many principles with obvious implications for genetic diseases, and his early work on the evolution of the aging process suggested a basic relevance of evolu- tion to gerontology.

ix

PREFACE

We convinced each other, shortly after we met, that the potential contribution of evolutionary biology to medical progress was impor- tant enough to justify a real effort to bring this idea to others. We decided to put our reasoning and some obvious examples into print as a way of stimulating other workers to explore many other possi- bilities. After our jointly written article, "The Dawn of Darwinian Medicine," published in The Quarterly Review of Biology in March 1991, drew a favorable reception from the press as well as colleagues in both medicine and evolutionary biology, we decided that it could easily be expanded into a book that would interest a wide range of readers.

Charles Darwin's theory of natural selection as the explanation for the functional design of organisms is the foundation of almost everything in this book. The discussion centers on the concept of adaptation by natural selection: adaptations by which we combat pathogens, adaptations of pathogens that counter our adaptations, maladaptive but necessary costs of our adaptations, maladaptative mismatches between our body's design and our current environ- ments, and so on.

As we wrote, we kept discovering new ways in which Darwinism can aid the progress of medicine. We gradually realized that Darwin- ian medicine is not just a few ideas, but a whole new field, with excit- ing new developments arising at an ever-increasing rate. However, we must emphasize that Darwinian medicine is still in its infancy. The examples of Darwinian thinking applied to medical problems should not be taken as authoritative conclusions or medical advice. They are designed only to illustrate the use of evolutionary thinking in medi- cine, not to instruct people on how to protect their health or treat their diseases. This is not to say that we believe Darwinian medicine is merely a theoretical endeavor. Far from it! We have every expecta- tion that the pursuit of evolutionary questions will demonstrably improve human health. That will require effort, money, and time. In the meanwhile, we hope this book will stimulate people to think about their illnesses in a different way, to ask questions of their doc- tors, perhaps even argue with them, but certainly not to ignore their instructions.

Having made that disclaimer, we will also make a few others. This book does not arise from a disapproval of current medical research or practice in Western industrialized nations. It is based on the convic- tion that medical research and practice would be even better if ques-

x

PREFACE

tions of adaptation and historical causation were routinely considered along with those of immediate physical and chemical causation. We are urging not an alternative to modern medical practice but rather an additional perspective from a well-established body of scientific knowledge that has been largely neglected by the medical profession. We would be very much against Darwinian medicine being viewed as a kind of alternative cult opposed to some supposed orthodoxy. It is likewise not our purpose to make political recommendations, although we believe that some of our reasoning might prove impor- tant to those who formulate health care or environmental policies.

In addition to trying to make this book interesting and informa- tive to a wide audience, we have tried to make it a preliminary but sci- entifically valid guide for physicians and researchers who are asking evolutionary questions in their own areas of expertise. We well real- ize that many medical professionals have already been asking such questions. Often, however, they have done so apologetically, treating their own ideas not as serious hypotheses but as mere speculations undeserving of serious inquiry. We challenge this attitude as strongly as possible and hope that the examples in this book will make many scientists realize that their evolutionary hypotheses are legitimate and deserve scientific testing, in ways that may be easier and more deci- sive than they suspect. This book does not offer formal instruction on how to test evolutionary hypotheses, but it does give many exam- ples of such testing.

We hope readers will realize that this meager book can provide only a brief glimpse of a few current evolutionary ideas in relation to a select list of medical examples. Medicine is now such a huge field that no one can master more than a small part of it. Even specialties such as internal medicine are quickly splitting into subspecialties, such as cardiology, and into subsubspecialties. Neither of us claims to have mastered more than a small fraction of the knowledge encom- passed by modern medicine. We are well aware that any discussion of such a wide range of topics as is found in this book must of neces- sity be superficial and oversimplified. We hope that this will not seri- ously mislead anyone and that specialists will forgive us for any minor inaccuracies they may find. These risks seem worth it because of the potential utility of a broad overview of Darwinian medicine and because we believe that readers will derive real pleasure from an evolutionary understanding of their bodies' functioning, and occa- sional malfunctioning.

xi

WHY WE GET SICK

1

THE MYSTERY OF

DISEASE

hy, in a body of such exquisite design, are there aW /thousand flaws and frailties that make us vulnerable to disease? If evolution by natural selection can shape sophisticated mechanisms such as the eye,

heart, and brain, why hasn't it shaped ways to prevent nearsighted- ness, heart attacks, and Alzheimer's disease? If our immune system can recognize and attack a million foreign proteins, why do we still get pneumonia? If a coil of DNA can reliably encode plans for an adult organism with ten trillion specialized cells, each in its proper place, why can't we grow a replacement for a damaged finger? If we can live a hundred years, why not two hundred?

We know more and more about why individuals get specific dis- eases but still understand little about why diseases exist at all. We know that a high-at diet causes heart disease and sun exposure causes skin cancer, but why do we crave fat and sunshine despite their dan- gers? Why can't our bodies repair clogged arteries and sun-damaged skin? Why does sunburn hurt? Why does anything hurt? And why are we, after millions of years, still prone to streptococcal infection?

The great mystery of medicine is the presence, in a machine of exquisite design, of what seem to be flaws, frailties, and makeshift mechanisms that give rise to most disease. An evolutionary approach

3

WHY WE GET SICK

transforms this mystery into a series of answerable questions: Why hasn't the Darwinian process of natural selection steadily eliminated the genes that make us susceptible to disease? Why hasn't it selected for genes that would perfect our ability to resist damage and enhance repairs so as to eliminate aging? The common answer-that natural selection just isn't powerful enough-is usually wrong. Instead, as we will see, the body is a bundle of careful compromises.

The body's simplest structures reveal exquisite designs unmatched by any human creations. Take bones. Their tubular form maximizes strength and flexibility while minimizing weight. Pound for pound, they are stronger than solid steel bars. Specific bones are masterfully shaped to serve their functions-thick at the vulnerable ends, stud- ded with surface protrusions where they increase muscle leverage, and grooved to provide safe pathways for delicate nerves and arteries. The thickness of individual bones increases wherever strength is needed. Wherever they bend, more bone is deposited. Even the hol- low space inside the bones is useful: it provides a safe nursery for new blood cells.

Physiology is still more impressive. Consider the artificial kidney machine, bulky as a refrigerator yet still a poor substitute that per- forms only a few of the functions of its natural counterpart. Or take the best man-made heart valves. They last only a few years and crush some red blood cells with each closure, while natural valves gently open and close two and a half billion times over a lifetime. Or con- sider our brains, with their capacity to encode the smallest details of life that, decades later, can be recalled in a fraction of a second. No computer can come close.

The body's regulatory systems are equally admirable. Take, for instance, the scores of hormones that coordinate every aspect of life, from appetite to childbirth. Controlled by level upon level of feed- back loops, they are far more complex than any man-made chemical factory. Or consider the intricate wiring of the sensorimotor system. An image falls onto the retina; each cell transmits its signal via the optic nerve to a brain center that decodes shape, color, and move- ment, then to other brain centers that link with memory banks to determine that the image is that of a snake, then to fear centers and decision centers that motivate and initiate action, then to motor nerves that contract exactly the right muscles to jerk the hand away- all this in a fraction of a second.

4

THE MYSTERY OF DISEASE

Bones, physiology, the nervous system-the body has thousands of consummate designs that elicit our wonder and admiration. By con- trast, however, many aspects of the body seem amazingly crude. For instance, the tube that carries food to the stomach crosses the tube that carries air to the lungs, so that every time we swallow, the airway must be closed off lest we choke. Or consider nearsightedness. If you are one of the unlucky 25 percent who have the genes for it, you are almost cer- tain to become nearsighted and thus unlikely to recognize a tiger until you are nearly its dinner. Why haven't these genes been eliminated? Or take atherosclerosis. An intricate network of arteries carries just the right amount of blood to every part of the body. Yet many of us develop cholesterol deposits on the walls of our arteries, and the result- ing blockage in blood flow causes heart attacks and strokes. It is as if a Mercedes-Benz designer specified a plastic soda straw for the fuel line!

Dozens of other bodily designs seem equally inept. Each may be considered a medical mystery. Why do so many of us have allergies? The immune system is useful, of course, but why can't it leave pollen alone? For that matter, why does the immune system sometimes attack our own tissues to cause multiple sclerosis, rheumatic fever, arthritis, diabetes, and lupus erythematosus? And then there is nau- sea in pregnancy. How incomprehensible that nausea and vomiting should so often plague future mothers at the very time when they are assuming the burden of nourishing their developing babies! And how are we to understand aging, the ultimate example of a universal occurrence that seems functionally incomprehensible?

Even our behavior and emotions seem to have been shaped by a prankster. Why do we crave the very foods that are bad for us but have less desire for pure grains and vegetables? Why do we keep eat ing when we know we are too fat? And why is our willpower so weak in its attempts to restrain our desires? Why are male and female sex- ual responses so uncoordinated, instead of being shaped for maxi- mum mutual satisfaction? Why are so many of us constantly anxious, spending our lives, as Mark Twain said, "suffering from tragedies that never occur"? Finally, why do we find happiness so elusive, with the achievement of each long-pursued goal yielding not contentment, but only a new desire for something still less attainable? The design of our bodies is simultaneously extraordinarily precise and unbeliev- ably slipshod. It is as if the best engineers in the universe took every seventh day off and turned the work over to bumbling amateurs.

5

WHY WE GET SICK

Two KINDS OF CAUSES

T w o resolve this paradox, we must discover the evolutionary causes for each disease. By now it is obvious that these evo- lutionary causes of disease are different from the causes most people think of. Consider heart attacks. Eating fatty

foods and having genes that predispose to atherosclerosis are major causes of heart attacks. These are what biologists call proximate ("near") causes. We are more interested here in the evolutionary causes, those that reach further back to why we are designed the way we are. In studying heart attacks, the evolutionist wants to know why natural selection hasn't eliminated the genes that promote fat craving and cholesterol deposition. Proximate explanations address how the body works and why some people get a disease and others don't. Evolutionary explanations show why humans, in general, are suscep- tible to some diseases and not to others. We want to know why some parts of the human body are so prone to failure, why we get some dis- eases and not others.

When proximate and evolutionary explanations are carefully dis- tinguished, many questions in biology make more sense. A proxi- mate explanation describes a trait-its anatomy, physiology, and biochemistry, as well as its development from the genetic instruc- tions provided by a bit of DNA in the fertilized egg to the adult indi- vidual. An evolutionary explanation is about why the DNA specifies the trait in the first place and why we have DNA that encodes for one kind of structure and not some other. Proximate and evolutionary explanations are not alternatives-both are needed to understand every trait. A proximate explanation for the external ear would include information about how it focuses sound, the tissues it is made of, its arteries and nerves, and how it develops from the embryo to the adult form. Even if we know all this, however, we still need an evolutionary explanation of how its structure gives creatures with ears an advantage, why those that lack the structure are at a dis- advantage, and what ancestral structures were gradually shaped by natural selection to give the ear its current form. To take another example, a proximate explanation of taste buds describes their struc- ture and chemistry, how they detect salt, sweet, sour, and bitter, and how they transform this information into impulses that travel via

6

THE MYSTERY OF DISEASE

neurons to the brain. An evolutionary explanation of taste buds shows why they detect saltiness, acidity, sweetness, and bitterness instead of other chemical characteristics, and how the capacities to detect these characteristics help the bearer to cope with life.

Proximate explanations answer "what?" and "how?" questions about structure and mechanism; evolutionary explanations answer "why?" questions about origins and functions. Most medical research seeks proximate explanations about how some part of the body works or how a disease disrupts this function. The other half of biology, the half that tries to explain what things are for and how they got there, has been neglected in medicine. Not entirely, of course. A primary task of physiology is to find out what each organ normally does; the whole field of biochemistry is devoted to understanding how metabolic mech- anisms work and what they are for. But in clinical medicine, the search for evolutionary explanations of disease has been halfhearted at best. Since disease is often assumed to be necessarily abnormal, the study of its evolution may seem preposterous. But an evolutionary approach to disease studies not the evolution of the disease but the design charac- teristics that make us susceptible to the disease. The apparent flaws in the body's design, like everything else in nature, can be fully under- stood only with evolutionary as well as proximate explanations.

Are evolutionary explanations mere speculations, of intellectual interest only? Not at all. For instance, consider morning sickness. If, as Seattle researcher Margie Profet has suggested, the nausea, vomit- ing, and food aversions that often accompany early pregnancy evolved to protect the developing fetus from toxins, then the symp- toms should begin when fetal-tissue differentiation begins, should decrease as the fetus becomes less vulnerable, and should lead to avoidance of foods that contain the substances most likely to inter- fere with fetal development. As we will see, substantial evidence matches these predictions.

Evolutionary hypotheses thus predict what to expect in proximate mechanisms. For instance, if we hypothesize that the low iron levels associated with infection are not a cause of the infection but a part of the body's defenses, we can predict that giving a patient iron may worsen the infection-as indeed it can. Trying to determine the evolu- tionary origins of disease is much more than a fascinating intellectual pursuit; it is also a vital yet underused tool in our quest to understand, prevent, and treat disease.

7

WHY WE GET SICK

THE CAUSES OF DISEASEE -xperts on various diseases often ask themselves why a par, ticular disease exists at all, and they often have some good ideas. In many cases, however, they confuse evolutionary with proximate explanations, or do not know how to go

about testing their ideas, or are simply reluctant to propose explana- tions that seem outside the mainstream. These difficulties can per- haps be reduced with the help of a formal framework for Darwinian medicine. To this end, we propose six categories of evolutionary explanations of disease. Each of these will be described at length in later chapters, but this brief overview illustrates the logic of the enter- prise and provides an overview of the terrain ahead.

1. Defenses

D efenses are not actually explanations of disease, but because They are so often confused with other manifestations of disease we list them here. A fair-skinned person with severe pneumonia may take on a dusky hue and have a deep cough. These two signs of pneu- monia represent entirely different categories, one a manifestation of a defect, the other a defense. The skin is blue because hemoglobin is darker in color when it lacks oxygen. This manifestation of pneumo- nia is like a clank in a car's transmission. It isn't a preprogrammed response to the problem, it is just a happenstance result with no par- ticular utility. A cough, on the other hand, is a defense. It results from a complex mechanism designed specifically to expel foreign material in the respiratory tract. When we cough, a coordinated pat- tern of movements involving the diaphragm, chest muscles, and voice box propels mucus and foreign matter up the trachea and into the back of the throat, where it can be expelled or swallowed to the stomach, where acid destroys most bacteria. Cough is not a happen- stance response to a bodily defect; it is a coordinated defense shaped by natural selection and activated when specialized sensors detect cues that indicate the presence of a specific threat. It is, like the light on a car's dashboard that turns on automatically when the gas tank is nearly empty, not a problem itself but a protective response to a problem.

8

THE MYSTERY OF DISEASE

This distinction between defenses and defects is not merely of aca- demic interest. For someone who is sick it can be crucial. Correcting a defect is almost always a good thing. If you can do something to make the clanking in the transmission stop or the pneumonia patient's skin turn warm pink, it is almost always beneficial. But eliminating a defense by blocking it can be catastrophic. Cut the wire to the light that indicates a low fuel supply, and you are more likely to run out of gas. Block your cough excessively, and you may die of pneumonia.

2. Infection

G iven that some bacteria and viruses treat us mainly as meals, we Gcan think of them as enemies. Unfortunately, they are not just simple pests put here to bedevil us but sophisticated opponents. We have evolved defenses to counter their threats. They have evolved ways to overcome our defenses or even to use them to their own ben- efit. This endlessly escalating arms race explains why we cannot erad- icate all infections and also explains some autoimmune diseases. We expand greatly on these topics in the next two chapters.

3. Novel Environments

O ur bodies were designed over the course of millions of years for Olives spent in small groups hunting and gathering on the plains of Africa. Natural selection has not had time to revise our bodies for coping with fatty diets, automobiles, drugs, artificial lights, and cen- tral heating. From this mismatch between our design and our envi- ronment arises much, perhaps most, preventable modern disease. The current epidemics of heart disease and breast cancer are tragic examples.

4. Genes

S ome of our genes are perpetuated despite the fact that they cause disease. Some of their effects are "quirks" that were harmless

when we lived in a more natural environment. For instance, most of the genes that predispose to heart disease were harmless until we began overindulging on fatty diets. The genes that cause nearsighted- ness cause problems only in cultures where children do close work

9

WHY WE GET SICK

early in life. Some of the genes that cause aging were subject to little selection when average life spans were shorter.

Many other genes that cause disease have actually been selected for because they provide benefits, either to the bearer or to other individuals with the gene in other combinations. For instance, the gene that causes sickle-cell disease also prevents malaria. In addition to this well-known example, many others are discussed in later chap- ters, including sexually antagonistic genes that benefit fathers at the expense of mothers or vice versa.

Our genetic code is constantly being disrupted by mutations. On very rare occasions these changes in DNA are beneficial, but much more commonly they create disease. Such damaged genes are con- stantly being eliminated or kept to a minimum by natural selection. For this reason defective genes with no compensating benefit are not a common cause of disease.

Finally, there are "outlaw" genes that facilitate their own trans- mission at the expense of the individual and thus bluntly demon- strate that selection acts ultimately to benefit genes, not individuals or species. Because selection among individuals is a potent evolu- tionary force, outlaw genes are also an uncommon cause of disease.

5. Design Compromises

Just as there are costs associated with many genes that offer an over- Jall benefit, there are costs associated with every major structural change preserved by natural selection. Walking upright gives us the ability to carry food and babies, but it predisposes us to back prob- lems. Many of the body's apparent design flaws aren't mistakes, just compromises. To better understand disease, we need to understand the hidden benefits of apparent mistakes in design.

6. Evolutionary Legacies

E volution is an incremental process. It can't make huge jumps, Only small changes, each of which must be immediately beneficial. Major changes are difficult to accomplish even for human engineers. Fires occurred when a popular line of pickup truck was struck from the side because the gasoline tanks were located outside the frame. But to locate the tanks within the frame would require a major redesign of

10

THE MYSTERY OF DISEASE

everything now there, which could cause new problems and require new compromises. Even human engineers can be constrained by his- torical legacies. Similarly, our food passes through a tube in front of the windpipe, and must cross it to get to the stomach, thus exposing us to the danger of choking. It would be more sensible to relocate the nostrils to somewhere on the neck, but that will never happen, as we explain in Chapter 9.

WHAT WE ARE NOT SAYINGB -efore we discuss the details of the above causes of disease, we would like to try to forestall several potentially danger- ous misunderstandings. First of all, our enterprise has noth- ing to do with eugenics or Social Darwinism. We are not

interested here in whether the human gene pool is getting better or worse, and we are emphatically not advocating actions to improve the species. We are not even particularly interested in most genetic differences between people, but much more in the genetic material that we all have in common.

An evolutionary perspective on disease does not change the ancient goals of medicine carved on a statue honoring physician E. L. Trudeau's work at Saranac Lake: "To cure, sometimes, To help, often, To console, always." The goal of medicine has always been (and, in our belief, always should be) to help the sick, not the species. Confusion regarding this point has justified much mischief. At the beginning of the century, Social Darwinist ideology helped to justify withholding medical care from the poor and letting capitalist giants battle irrespective of effects on individuals. These beliefs were inti- mately linked to those of the eugenicists, who advocated sterilization of certain groups in order to improve the species (or race!). Such ide- ology has long ago earned a well-deserved ill repute. It made metaphorical use of some of the terminology of Darwinism but no use of the theory as biologists understand it. We are by no means advocating that medicine should assist natural selection, nor do we suggest that biology can guide moral decisions. We would never argue that any disease is good, even though we will offer many exam- ples in which pathology is associated with some unappreciated bene-

11

WHY WE GET SICK

fit. Darwinism gives no moral guidelines about how we should live or how doctors should practice medicine. A Darwinian perspective on medicine can, however, help us to understand the evolutionary ori- gins of disease, and this knowledge will prove profoundly useful in achieving the legitimate goals of medicine.

12

2

EVOLUTION BY NATURAL SELECTION

Now, as each of the parts of the body, like every other instrument, is for the sake of some purpose, viz. some action, it is evident that the body as a whole must exist for the sake of some complex action.

-Aristotle

he solutions to the mysteries discussed in Chapter 1 are to be found in the workings of natural selection. The process is fundamentally very simple: natural selection occurs whenever genetically influenced variation among individu-

als affects their survival and reproduction. If a gene codes for charac- teristics that result in fewer viable offspring in future generations, that gene is gradually eliminated. For instance, genetic mutations that increase vulnerability to infection, or cause foolish risk taking or lack of interest in sex, will never become common. On the other hand, genes that cause resistance to infection, appropriate risk taking, and success in choosing fertile mates are likely to spread in the gene pool, even if they have substantial costs.

A classic example is the spread of a gene for dark wing color in a British moth population living downwind from major sources of air pollution. Pale moths were conspicuous on smoke-darkened trees and easily caught by birds, while a rare mutant form of moth whose color more closely matched that of the bark escaped the predators'

13

WHY WE GET SICK

beaks. As the tree trunks became darker, the mutant gene spread rapidly and largely displaced the gene for pale wing color. That is all there is to it. Natural selection involves no plan, no goal, and no direction-just genes increasing and decreasing in frequency depend- ing on whether individuals with those genes have, relative to other individuals, greater or lesser reproductive success.

The simplicity of natural selection has been obscured by many misconceptions. For instance, Herbert Spencer's nineteenth-century catch phrase "survival of the fittest" is widely thought to summarize the process, but it actually promotes several misunderstandings. First of all, survival is of no consequence in and of itself. This is why nat- ural selection has created some organisms, such as salmon and annual plants, that reproduce only once, then die. Survival increases fitness only insofar as it increases later reproduction. Genes that increase lifetime reproduction will be selected for even if they result in reduced longevity. Conversely, a gene that decreases total lifetime reproduction will obviously be eliminated by selection even if it increases an individual's survival.

Further confusion arises from the ambiguous meaning of "fittest." The fittest individual, in the biological sense, is not necessarily the healthiest, strongest, or fastest. In today's world, and many of those of the past, individuals of outstanding athletic accomplishment need not be the ones who produce the most grandchildren, a measure that should be roughly correlated with fitness. To someone who under- stands natural selection, it is no surprise that parents are so con- cerned about their children's reproduction.

A gene or an individual cannot be called "fit" in isolation but only with reference to a particular species in a particular environment. Even in a single environment, every gene involves compromises. Con- sider a gene that makes rabbits more fearful and thereby helps to keep them from the jaws of foxes. Imagine that half of the rabbits in a field have this gene. Because they do more hiding and less eating, these timid rabbits might be, on average, a bit less well fed than their bolder companions. If, hunkered down in the March snow waiting for spring, two thirds of them starve to death while this is the fate of only one third of the rabbits who lack the gene for fearfulness, then, come spring, only a third of the rabbits will have the gene for fearfulness. It has been selected against. It might be nearly eliminated by a few harsh winters. Milder winters or an increased number of foxes could have the opposite effect. It all depends on the current environment.

14

EVOLUTION BY NATURAL SELECTION

NATURAL SELECTION BENEFITS GENES, NOT GROUPS

M [any people have seen the nature film in which droves of starving lemmings jump eagerly to a watery death

as a resonant voice explains that when food becomes scarce, some lemmings sacrifice themselves so that

there will be enough food for at least some of the group to survive. A few decades ago, such "group selection" explanations were taken seriously by professional biologists, but not now. To see why, com- pare two imaginary lemmings. One is a noble fellow who, upon sens- ing that the population is about to outrun its food supply, quickly jumps to his death in the nearest stream. The other is a selfish lout who waits for the noble ones to do away with themselves and then eats as much food as he can get, mates as often as possible, and has as many offspring as possible. What would happen to the genes that code for the behavior of sacrificing oneself for the benefit of the group? No matter how beneficial they might be for the species, they would be eliminated.

So how can we explain the observations of apparently suicidal lemmings? When food becomes scarce in late winter, lemmings migrate, rushing along in large groups that do not always stop when they encounter waters created by early snowmelt. Drownings are, however, rather uncommon. To get the footage they wanted, the makers of the film apparently had to use brooms to surreptitiously herd the lemmings into the water, a dramatic example of the human preference for altering reality rather than theory when the two con- flict! There are special circumstances in which selection at the group level can outweigh the usually stronger force of selection at the level of the individual, but they do not apply very often.