Second, disease results from exposure to novel factors that were not present in the environment in which we evolved. Given enough time, the body can adapt to almost anything, but the ten thousand years since the beginnings of civilization are not nearly enough time, and we suffer accordingly. Infectious agents evolve so fast that our defenses are always a step behind. Third, disease results from design compromises, such as upright posture with its associated back problems. Fourth, we are not the only species with adaptations produced and maintained by natural selection, which works just as hard for pathogens trying to eat us and the organisms we want to eat. In conflicts with these organisms, as in baseball, you can’t win ’em all. Finally, disease results from unfortunate historical legacies. If the organism had been designed with the possibility of fresh starts and major changes, there would be better ways of preventing many diseases. Alas, every successive generation of the human body must function well, with no chance to go back and start afresh.
The human body turns out to be both fragile and robust. Like all products of organic evolution, it is a bundle of compromises, each of which offers an advantage, but often at the price of susceptibility to disease. These susceptibilities cannot be eliminated by any duration of natural selection, for it is the very power of natural selection that created them.
RESEARCH
Many questions confront the infant enterprise of Darwinian medicine. What is its long-range goal? How should we go about analyzing a disease from an evolutionary viewpoint? How should hypotheses be formulated and tested? Who will pay for this research? Who will do the research and in what academic departments or other agencies? Why has it taken so long to get this enterprise started?
We begin with the long-range goal. What will medical textbooks look like when evolutionary studies of disease are well established? Current textbooks summarize what is known about a disorder under traditional headings: signs and symptoms of the disease, laboratory findings, differential diagnosis, course, complications, epidemiology, etiology, pathophysiology, treatment, and outcome. Such descriptions fall one category short. A comprehensive discussion of a disease must also provide an evolutionary explanation. While some current textbooks have a sentence or two about the advantages of the sickle-cell gene or the benefits of cough or fever, none of them systematically addresses the evolutionary forces acting on genes that cause disease, the novel aspects of environment that cause disease, or the details of the host-parasite arms race. Every textbook description of a disease should have, in our opinion, a section devoted to its evolutionary aspects. This section should address the following questions:
1. Which aspects of the syndrome are direct manifestations of the disease, and which are actually defenses?
2. If the disease has a genetic component, why do the responsible genes persist?
3. Do novel environmental factors contribute to the disease?
4. If the disease is related to infection, which aspects of the disease benefit the host, which benefit the pathogen, and which benefit neither? What strategies does the pathogen use to outflank our defenses, and what special defenses do we have against these strategies?
5. What design compromises or historical legacies account for our susceptibility to this disease?
Such questions immediately suggest important but neglected research on many diseases. Even the common cold offers many opportunities. What are the effects of taking or not taking aspirin? What are the effects of using nasal inhalers or decongestant medication? To use the categories of Chapter 3, is rhinorrhea (runny nose) a defense, a means the virus uses to spread itself, or both? For the most part, these projects have yet to be undertaken despite their conceptual simplicity and their obvious practical implications for us all.
Take something far more chronic and complicated, plantar fasciitis. More often known as heel spurs, this common disorder causes intense pain on the inside edge of the heel, especially first thing in the morning. The proximate cause is inflammation at the point where the heel attaches to the plantar fascia, a band of tough tissue that connects the front and rear of the foot like the string on a bow, supporting the arch of the foot. With every footstep it stretches, bearing the weight of the body thousands of times every day. Why does this fascia fail so often? The easy answer is that natural selection cannot shape a tissue strong enough to do the job—but by now this explanation should be suspect. Somewhat more plausible is the possibility that we began walking on two feet so recently that there has not been enough time for natural selection to strengthen the fascia sufficiently. The problem with this explanation is that plantar fasciitis is common and crippling. Like nearsightedness, it would, in the natural environment, so drastically decrease fitness that it would be strongly selected against. Some experts say plantar fasciitis arises in people who walk with their toes pointed out, a conformation that puts increased stress on the tissue. But then why do we walk that way? Is it the modern habit of wearing shoes? But many people who have never worn shoes also walk with their toes pointed outward.
Two clues suggest that plantar fasciitis may result from environmental novelty. First, exercises that stretch the plantar fascia to make it longer and more resilient are effective in relieving the problem. Second, many of us do something hunter-gatherers don’t: we sit in chairs all day. Most hunter-gatherers walk for hours each day, instead of compressing their exercise into an efficient aerobic workout. When they aren’t walking, they don’t use chairs, they squat, a position that steadily stretches the plantar fascia. No plantar fasciitis and physical therapy for them, just squatting and walking for hours each day. This hypothesis, that plantar fasciitis results from prolonged sitting that allows the fascia to contract and that the disorder can be prevented and relieved by squatting and other stretching of the fascia, can readily be tested with epidemiological data and straightforward treatment studies.
Another good challenge for Darwinian medicine is the current controversy about whether it is wise to take antioxidants such as vitamin C, vitamin E, and beta-carotene. Folklore has long credited these agents with reducing heart disease, cancer, and even the effects of aging. Controlled studies are increasingly supporting these claims, especially for the prevention of atherosclerosis, although a major study in 1994 reported that beta-carotene appeared to increase the risk of cancer in some people. The agents are still deemed controversial, and many physicians studying them recommend caution until larger studies can assess their risks as well as benefits. We agree with this general conservatism but hope that an evolutionary view can speed the process. Earlier in this book we noted that natural selection seems to have resulted in high levels of several of the body’s own antioxidants even though they cause disease. Uric acid levels are higher in species that live longer and are so high in humans that we are susceptible to gout. It appears that natural selection has acted to increase the human levels of uric acid, superoxide dismutase, and perhaps bilirubin and other substances as well, because they are antioxidants that slow some effects of aging in a species that has greatly increased its life span in just the past few hundred thousand years.
Why doesn’t the body have antioxidant levels that are already optimal? It is possible that our antiaging mechanisms are still catching up with the recent increase in our life span. It is also possible that the costs of high levels of antioxidants (perhaps decreases in our resistance to infection or toxins?) have restricted them to levels that were optimal for a normal Stone Age lifetime of thirty or forty years. These possibilities suggest that adding extra antioxidants to the diet may have benefits that exceed the costs. In contrast to the many cases in which an evolutionary view argues against excessive intervention, here it supports the active pursuit of strategies that may prevent some effects of aging. A major part of such studies should be a search for other antioxidants in the body and an assessment of their costs and benefits. It would be interesting to see if people with high uric acid levels have costs other than gout and whether they show fewer signs of aging than other people. It
will also be important to look for similar costs and benefits in our primate relatives. With this knowledge we will be in a better position to decide who will benefit from taking antioxidants and what the side effects might be.
This book contains suggestions for dozens of studies, many of which seem to us to be fine topics for Ph.D. theses and some of which offer challenges enough for a whole career. Pursuing them will be difficult, however, because no government agency presently supports such projects. Existing funding committees are reluctant to provide support because their mandate is to provide funds to study the proximate mechanisms and treatment of particular diseases. Furthermore, few members of such committees know anything about the formulation or testing of evolutionary ideas, and some are likely to have misgivings based on fundamental misconceptions about the scientific status of evolutionary hypotheses. The system used to assign funding priorities ensures that even a few people with such misgivings can eliminate the chances of funding.
Asking biochemists or epidemiologists to judge proposals to test evolutionary hypotheses is like asking mineral chemists to judge proposals on continental drift. Darwinian medicine needs its own funding panels staffed by reviewers who know the concepts and methods of evolutionary biology. Realistically, the prospects are poor for major government funding soon. The best hope for rapid growth of the field lies in the vision of private donors or foundations that could create institutes to support the development of Darwinian medicine. Even moderate support of this sort could quickly change the course of medicine, just as prior investments in biochemical and genetic research are now transforming our lives. As René Dubos noted in 1965:
In many ways, the present situation of organismic biology and especially of environmental medicine is very similar to that of the physicochemical sciences related to medicine around 1900. At that time there was no place in the United States dedicated to the pursuit of physicochemical biology, and the scholars who were interested in this field were treated as second-class citizens in the medical community. Fortunately, a few philanthropists were made aware of this situation, and they endowed new kinds of research facilities to change the trend. The Rockefeller Institute is probably the most typical example of a conscious and successful attempt to provide a basis of physicochemical knowledge for the art of medicine.… Organismic and especially environmental medicine constitute today virgin territories even less developed than was physicochemical biology 50 years ago. They will remain undeveloped unless a systematic effort is made to give them academic recognition and to provide adequate facilities for their exploration.
WHY DID IT TAKE SO LONG?
Why has it taken more than a hundred years to apply Darwin’s theory systematically to disease? Historicans of science will eventually address this question, but from this close perspective several explanations seem likely: the supposed difficulty in formulating and testing evolutionary hypotheses about disease, the recency of some advances in evolutionary biology, and some peculiarities of the field of medicine. Biologists have long tried to figure out the evolutionary origins and functions for organismic characteristics, but it has taken a surprisingly long time to realize that this enterprise is fundamentally different from trying to figure out the structure of organisms and how they work. Harvard biologist Ernst Mayr, in The Growth of Biological Thought, traces the parallel development of the two biologies. Medicine, while at the forefront of proximate biology, has been curiously late in addressing evolutionary questions. This is, no doubt, in part simply because the questions and goals are so different. It takes a wrenching shift to stop asking why an individual has a particular disease and to ask instead what characteristics of a species make all of its members susceptible to that disease. It has seemed a bit odd until now even to ask how something maladaptive like disease might have been shaped by natural selection. Furthermore, medicine is a practical enterprise, and it hasn’t been immediately obvious how evolutionary explanations might help us prevent or treat disease. We hope this book convinces many people that seeking evolutionary explanations for disease is both possible and of substantial practical value.
If we are to assign blame for the tardiness of medicine in making use of relevant ideas in evolutionary biology, it rests as much with evolutionary biologists as with the medical profession. It took evolutionists an inexcusably long time to formulate the relevant ideas. Given the powerful insights of Darwin, Wallace, and a few others in the middle of the nineteenth century, and the Mendelian revolution in genetics in the early years of the twentieth, why was it not until Fisher’s book of 1930 that we had the first fruitful idea about why the number of boys and girls born is nearly equal? Why was it not until Medawar’s midcentury work that we had any idea why there is such a thing as senescence? Why was it not until Hamilton’s publications in 1964 that there was any realization that kinship would have some relevance to evolution? Why was it not until the 1970s and 1980s that we had useful ideas on how parasites and hosts, or plants and herbivores, influence each other’s evolution? We believe that the answers to these and related questions will be found in a persistent antipathy to evolutionary ideas in general and to adaptation and natural selection in particular (even among some biologists). Meanwhile, we will simply note that medical researchers can hardly be blamed for failing to use the ideas of other sorts of scientists before those scientists developed them.
Medical scientists may also hesitate to consider functional hypotheses because of their indoctrination in the experimental method. Most of them were taught early, firmly—and wrongly—that science progresses only by means of experiment. But many scientific advances begin with a theory, and much testing of hypotheses does not rely on the experimental method. Geology, for instance, cannot replay the history of the earth, but it nonetheless can reach firm conclusions about how basins and ranges got that way. Like evolutionary hypotheses, geological hypotheses are tested by explaining available evidence and by predicting new findings that have not yet been sought in the existing record.
Finally, medicine, like other branches of science, is especially wary of ideas that in any way resemble recently overcome mistakes. Medicine fought for years to exclude vitalism, the idea that organisms were imbued with a mysterious “life force,” so it continues to attack anything that is even vaguely similar. Likewise, teleology of a naive and erroneous sort keeps reappearing and must be expelled. Many people recollect from freshman philosophy class that teleology is the mistake of trying to explain something on the basis of its purpose or goal. This admonition is wise if it establishes an awareness that future conditions cannot influence the present. It is unwise if it also implies that present plans for the future cannot affect present processes and, through them, future conditions. Present plans may include printed recipes for baking cakes or the information in the DNA of bird’s eggs. Functional explanations in biology imply not future influences on the present but a prolonged cycling of reproduction and selection. A bird embryo develops wing rudiments in the egg because earlier individuals that failed to do so left no descendants. Adult birds lay eggs in which embryos develop wing rudiments for the same reason. In this sense, a bird’s wing rudiments are preparation for its future but are caused by its past history. Evolutionary explanations based on a trait’s function do not imply that evolution involves any consciousness, active planning, or goal-directedness. While medicine is wise to be on guard against sliding back into discredited teleological reasoning, this wariness has prevented it from taking full advantage of the solid advances in mainstream evolutionary science. Through its efforts to keep from being dragged back, medicine has, paradoxically, been left behind.
MEDICAL EDUCATION
Medical education is similarly in trouble because of trying to guard against the old mistakes. The origins of its current quandary lie in the solution to a previous one. Early in this century, the Carnegie Foundation sponsored an extensive investigation of medical education by Abraham Flexner. In his cross-country travels, he reported a haphazard system of medical app
renticeship in which physicians, good and bad, took on assistants who, one way or another, learned something about medicine. Doctors’ formal study of basic science was sporadic, and even their knowledge of basic anatomy and physiology was inconsistent. The Flexner report, published in 1910, formed the basis of new accreditation standards that required medical schools to provide future physicians with a foundation in basic science.
On this count, medical schools have far exceeded Flexner’s hopes. In fact, one wonders what Flexner would say if he could see today’s medical curricula. Now medical students are not only exposed to basic sciences, they are inundated with the latest advances by teachers who are subspecialist basic science researchers. At curriculum meetings in every medical school there are battles for students’ time and minds. The microbiologists want more lab time, the anatomists want more too. The pathologists feel they cannot possibly fit their material into a mere forty hours of lecture. The pharmacologists say they will continue flunking 30 percent of the class until they get enough time to cover all the new drugs. The epidemiologists and biochemists and physiologists and psychiatrists and neuroscience experts all want more time, and certainly the students must keep up with the latest advances in genetics. Then they need to learn enough statistics and scientific methodology to be able to read the research literature. And they must somehow learn, before they start their work on the wards, how to talk with patients, how to do a physical exam, how to write up a patient report, how to draw blood, do a culture, a spinal tap, a Pap smear, measure eyeball pressure, examine urine and blood, and, and,… The amounts of knowledge and the lists of tasks are overwhelming, but all must be completed in the first two years of medical school.
Why We Get Sick Page 29