Introduction

While evolution by natural selection has long been a foundation for biomedical science, it has recently gained new power to explain many aspects of disease. This progress results largely from the disciplined application of what has been called the adaptationist program. This increasingly significant research paradigm can predict otherwise unsuspected facets of human biology and it provides new insights into the causes of medical disorders.

The interaction between evolutionary theory and the field and laboratory work of biologists was exemplary in the work of Darwin and has continued ever since. It has become a conspicuous part of biology in the last two decades, often in the special form recognized as the adaptationist program. Adherents of this program, when confronted with a biological phenomenon, try to envision it as an aspect of an adaptation. An adaptation is some sort of biological machinery or process shaped by natural selection to help solve one or more problems faced by the organism. The phenomenon may be interpreted as a necessary component of the imagined machinery, or as an unavoidable cost of the machinery, or some incidental manifestation of its operation. The prediction is then made, or at least implied, that other necessary components must be there, and that an appropriate investigation will disclose their presence. Thus, the adaptationist program predicts otherwise unsuspected adaptive processes that can be searched for and, if found, described. The adaptationist program has been enormously fruitful in the fields of ecology, and animal behavior, and in the study of life cycles.

Evolutionary Biology

Traditionally medical education stresses physics, chemistry and those branches of biology that deal with proximate, i.e. immediate mechanisms. Application of this knowledge to biology and medicine has resulted in impressive advances in the prevention and treatment of human diseases. Evolutionary biology, however, has not been emphasized in medical curricula. This is unfortunate, because new applications of evolutionary principles to medical problems show that advances would be even more rapid if medical professionals were as attuned to Darwin as they have been to Pasteur.

In one sense, physics and chemistry may furnish a complete explanation of all events in the human body, from subatomic aspects of cellular metabolism, to the mechanical characteristics of the skeletal system, to the cognitive mechanisms that regulate behavior. For instance, there are seven vertebrae in the neck. Can physics and chemistry explain this? Yes, In an important sense. These vertebrae arise by a series of developmental events of a material nature, very much the realm of the proximate sciences of physiology and embryology. In another important sense, however, the answer is no. A complete explanation of how seven vertebrae are normally produced by a human zygote leaves untouched the question of why that zygote’s DNA should be so programmed. Why is it not organized to produce six or eight cervical vertebrae? And why should the zygote be capable of producing a functionally adequate neck at all? These last two questions find their answers in the Darwinian concepts of phylogeny and natural selection, respectively. Such answers are not alternatives to answers from physiology and embryology, they are answers to different kinds of questions.

An evolutionary explanation of the history and current utility of some feature of some organism always implies more than the observations that suggested the explanation. Theimplications constitute predictions of the results of investigations and may thereby lead to new discoveries. The relentless operation of mutation pressure, Mendelian genetics, selection, and other Darwinian factors for hundreds of millions of years in every lineage means that organisms must have certain features and not others.

The most universally reliable expectation is of a near maximum for a gene’s ability to get itself replicated. An intuitively useful, if not entirely accurate restatement, is that selection maximizes the abilities of organisms to gain genetic representation in future generations. This is substantively different from older “wisdom of the body” or “survival of the fittest” notions, and can lead to different and counter intuitive expectations.

Selection need not maximize fitness in the vernacular sense of strength, health, and longevity. It does not necessarily enhance the welfare of the species or the happiness of the individual. In fact, many of the capacities for suffering seem to have been shaped by natural selection to serve special adaptive functions.

“The core of Darwinian medicine is the search to find for each disease an evolutionary as well as a proximate explanation.”

A New Perspective on Health and Disease

The recent radical “Darwinian” approach to medicine seeks to explain diseases a d their symptoms as a leg of evolution. Can darwinism lead to better treatments? Should we treat the symptoms or disease, or are they there to aid recovery? Can phobias, panic attacks and morning sickness be of any advantage to people who suffer from them? Might common diseases of old age such as Alzheimer’s and osteoarthritis be associated with a genetic advantage In youth? Is the phenomenon of the couch potato an unavoidable legacy of our past life as hunters and gatherers?

Such questions are far from rhetorical. In fact, they are central to an ambitious new movement In medical research which threatens to overturn many of the conventional wisdoms at the heart of medicine. The underlying message is uncontroversial enough: human beings and their illnesses are the products of a long evolutionary history. Yet, modern medicine, for all its high-technology treatments and preventive strategies, has so far largely ignored this fact. And the few researchers who haven’t, have been scattered across the world, working in disparate. pockets of medical science. Now these quiet revolutionaries are linking their ideas together and the discipline they are forging has acquired a name: Darwinian Medicine.

Modern medicine is founded on reductionism. Organisms are viewed as a collection of organs, not as functional wholes, and still less as members of a species. Diseases and their symptoms are considered as discrete defects of the body that can and must be eliminated. Evolution is not an issue.

In 1991, the scope of this approach was questioned by Randolph Nesse and George Williams in a paper which served as a rallying call to those with an evolutionary theme to their biomedical research. Nesse works as a psychiatrist at the University of Michigan, and Willliams is an evolutionary biologist at the State University of New York.

The core of Darwinian medicine is the search to find for each disease an evolutionary as well as a proximate explanation. For instance, infection is not just the outcome of an encounter with a pathogenic microorganism but an arms race between host and parasite. Trauma is not just a question of damaged tissue, but an interplay of protective mechanisms and repair processes that have been shaped by natural selection. Genes that cause diseases are not just the product of harmful mutations, but may be selected for benefits we have yet to discover. Cancer, heart disease and other “diseases of civilization” are not just the product of metabolism gone awry, but the result of today’s humans living in conditions different to those for which they evolved. In other words, Darwinian medicine considers disease from the viewpoint of the species not the individual human.

Underpinning Darwinian medicine is the theory that evolutionary adaptation may have apparently negative as well as positive consequences. In a sense any adaptation should be seen as a compromise. Back pains are commonly the price of bipedal posture, for example; the price of effective tissue repair is cancer; the price of a powerful immune system is immune disorders; the price of anxiety, which is an adaptive response to danger, is panic disorder. Natural selection is a powerful force, but it is not all powerful. Organisms are not perfect machines, but cobbled-together compromises.

“Darwinian medicine considers disease from the viewpoint of the species not the individual human. ”

Infectious Diseases

Even when making a transition from another species to human hosts, an infectious agent has a long evolutionary history that must have maximized its ability to achieve its own survival and reproduction despite elaborate host defenses. Parasites interact with their hosts in complex ways, and a first step towards understanding this interaction is use of a valid classification of the associated phenomena.

The process and dynamics of infection-what we see as the symptoms-are complex, however, and modern medicine has tended to take a narrow look at them. Darwinian medicine argues that the human body’s response to infection is likely to be an adaptation that helps to fight the disease.

Although doctors are aware of the beneficial effects of certain symptoms, such as coughing induced by pneumonia, many symptoms are regarded as harmful and are routinely treated sometimes to the detriment of the patient. Fever is the best example. Long suspected as having adaptive value, fever has only recently been revealed as a beneficial response to infection. The response is triggered by bacterial toxins, and the resulting increase in body temperature is hostile to the invading microorganisms. Reduce the fever-using aspirin, for instance-and the disease may last longer, as has been recently demonstrated in the case of chicken pox.

Another defense is sequestration of iron. Plasma iron, levels may fall to 20 percent of normal during initial stages of infections, as iron is bound more tightly to protein and sequestered in the liver. The plasma iron decrease has sometimes been viewed as a deficiency to be treated by dietary supplements. In fact, the sequestration of iron deprives’ bacteria of a vital mineral a works synergistically. The prescription of aspirin and an iron supplement for infection blocks two interdependent evolved defensive systems.

There are dangers o.. blocking other defensive systems as well. For instance, routine prescription or anti diarrheal agents for shigellosis causes delayed recovery, increases complications , and slows eradication of the bacteria from the bowel.

A theoretical framework for interpreting the host-parasite conflict encourages much needed investigations of such treatments. Nonetheless, there are times when it is useful to interfere with the body’s defenses. They were evolved for Stone Age conditions, and technological substitutes may be preferable. Severe cough may do more harm than good if antibiotics can quickly suppress an infection. But decisions about the appropriate use of such technologies should be informed by an understanding of the evolutionary nature of the host-parasite contest.

The Host-Parasite Arms Race

Bacterial pathogens may complete a million cycles of fission within the lifetime of one human host, and there may be more pathogens in one individual than the earth’s human population. Even in one host, a pathogen can be expected to produce highly improbable mutations many times and to evolve significantly in response to even minute selection forces.

This could happen even if the bacterial populations and rates of reproduction were one percent of what they actually are. Populations of protozoans and some parasitic helminths may also evolve important changes during their residence within one host. It has been realized for many years that some bacteria rapidly acquire high levels of antibiotic resistance and that resistant strains can locally replace susceptible ones in a few weeks.

Mutation is another but slower way to produce genetic diversity within a host. Only quite early in a host’s incubation of a bacterial pathogen, when the total count is in the millions or less, is the pathogen likely to be genetically homogeneous. Thereafter, various mutants will be competing with the ancestral type. The great majority of these mutations will be eliminated by selection, but a small minority will increase competitive ability and survive. Whatever its origin, the clone that more rapidly converts host tissues into more of itself will come to predominate within the host. The expected steady increase in virulence will be reversed only as a result of improved host defense either natural or artificial.

“Whatever its origin, the clone that more rapidly converts host tissues into more of itself will come to predominate within the host. ”

Mechanical Damage

Healing of mechanical damage is less complex than eliminating an infection, because it is not a contest between two organisms with divergent interests.

An evolutionary perspective suggests the value of distinguishing among several kinds of repair mechanisms and secondary adjustments. Repairs include both rebuilding of damaged tissues and other processes that indirectly aid in repair.

Increased temperature associated with inflammation might be one example of indirect aid along with mechanisms that restrict use of damaged parts, such as pain and swelling. Their initiation by injury is presumably optimized for Stone Age conditions. Now, artificial restraints and advice from physicians may substitute for pain to discourage activity. Swelling that is bothersome or physiologically costly can often be safely blocked by medication and local cooling.

As a specific example consider the usual sprained ankle. Blood escapes from damaged tissues to cause a bruise. This and increased extra vascular fluid contribute to local swelling. Histamine and other diffusible products of the injured tissues initiate the process that attracts phagocytes and other mobile cells, some of which start removing damaged structures and synthesizing their replacements.

An evolutionary biologist and adaptation-conscious physiologists and pathologists would ask a number of questions about the patho physiology of a sprain. To what extent is swelling merely an incidental result of the trauma, and to what extent is it an adaptation to immobilize the joint or to otherwise favor healing? What harmful consequences may result from limiting swelling? What is the role of each cell type in the repair program and how are these roles coordinated for the efficient achievement of the repair? Are the repair processes influenced by temperature, and is healing fastest at a certain temperature? What exactly is the mechanism that results in pain, and is the pain adjusted to the expected need for immobilization under normal conditions of human ecology? Is local pain supplemented by more general injury induced effects on motivation (lethargy and malaise)?

Reliable answers to such questions would facilitate design of a program of therapy. Evolved mechanisms that produce pain or malaise can be suppressed in favor of artificial substitutes: splints, wrappings, wheelchairs, and sick-leave.

Cellular mechanisms of repair and related processes that facilitate their action should be augmented unless there is reason to think them already optimal. Thus, the assumption that the increased temperature is adaptive would preclude routine application of ice unless well-designed studies confirmed its benefits.

There can be no sharp distinctions among injury, injurious wear and tear from abnormal usage, and normal wear and tear but an evolutionary perspective can aid in deciding what uses are normal. For instance, osteoarthritis mainly affects those joints that received increased use an loading with upright posture-especially the back, knees, and ankles. Sitting for long periods dramatically compresses the lumbar disks and can be regarded as abnormal usage. An example is carpal tunnel syndrome caused by hypertrophy of the fascia over the median nerve at the wrist. It results from repeated wrist twistings of the sort that are often necessary for carpenters.

Some adaptations for the avoidance of injury are analogous to hygienic precautions against infectious diseases. The actual mechanisms of injury avoidance and infection avoidance are quite different, of course, but in both cases we are prepared to avoid some kinds of modern dangers much better than others. For instance, tissue damage elicits spinal reflexes that cause withdrawal before the information even reaches the brain. Likewise, defensive action is initiated when specialized sensors detect pressure, excessive strain, or thermal stress.

Cognitive and Behavioral Adaptations

Other forms of adaptation to prevent injury are cognitive and behavioral. For instance, snakes and other objects of common phobias are by no means random, but seem to represent “prepared fears” of stimuli associated with danger in previous generations. Similarly, the changes associated with a panic attack are not an autonomic storm, but a carefully coordinated pattern that is adaptive in life-threatening situations. Psychological and physiological responses to danger are particularly intriguing since their adaptive significance and evolutionary origins have long been recognized, but they also contribute to the etiology of various diseases.

Why do stress responses cause disease? And why, if stress responses make the organism function more effectively, hasn’t natural selection shaped continuous expression of these responses?

One reason is that stress arousal is calorically expensive, and another is that an organism in a state of arousal may be less capable or dealing effectively with everyday tasks. A third explanation is the possibility that certain useful components of the stress response also interfere with metabolism or damage bodily tissues. Such components will be retained by natural selection only if their expression can be restricted to situations when the damage or disruption they cause will be more than outweighed by the benefits they offer-in short, if expression can be limited to emergency situations.

The stress response is an example of an inducible defense. An analysis of its costs and benefits may help to explain why extended states of stress cause disease. Some physiological changes are components of the stress response precisely because they cause damage. Increased secretion of adrenal steroids has long been associated with stress, but many of their actions seem to be the opposite of what one would expect. For instance, steroids decrease inflammation and increase susceptibility to infection, but the opposite would seem appropriate in the face of danger. An adaptive view of the functions of the adrenal cortex suggests that they may have been shaped by natural selection specifically to protect the body against other components of the stress response.

“Psychological and physiological responses to danger are particularly intriguing since their adaptive significance and evolutionary origins have long been recognized, but they also contribute to the etiology of various diseases.”

The Environment of Evolutionary Adaptedness

Adaptations are produced and maintained only in the range of environments in which selection takes place.

For humans, the physical environment of evolutionary adaptiveness is probably that of the Pleistocene savannah (10,000-1,700,000 years ago). The socioeconomic environment consisted of small groups of relatives hunting, gathering, mating, raising children, and responding to threats and opportunities provided by neighboring boring groups. The unique’ ability to use culture to adapt to diverse and changing environments enabled human populations to grow enormously, spread widely, and adapt technologically to a great range of conditions.

In the past ten thousand years, we have largely created our own environments, by the domestication of plants and animals and by the industrial and technological revolutions. These advances have led to the virtual elimination, in many parts of the world, of many of the most enduring and prominent agents of selection, such as starvation, parasites and infectious diseases.

There can be no doubt that people are, on the average, substantially healthier to a greater age than their predecessors. Yet many of the diseases now confronted by medicine in technological societies are “diseases of civilization”. They are either caused by differences between our current environment and the environment we evolved to live in, or they are aspects of senescence that have been uncovered by preventing earlier causes of mortality. The effects of recent increases in mean life span have changed medicine more than many people realize. For instance, since 1900, 80 percent of mortality from causes other than senescence in the United States has been eliminated.

When dealing with specific diseases that result from novel aspects of our environment, it is necessary to emphasize again that our health has i been immensely improved by medical advances and other environmental changes. Current rates of mortality and morbidity in economically advanced societies allow no challenge to this conclusion. What follows is not to advocate a return to any earlier way of life, but only the recognition that some net improvements of modern civilization are mixed blessings.

Diseases of Civilization – Genetic Quirks

There are strong genetic predisposing factors for many of the diseases of modern civilization. Examples include obesity, myopia, hypertension, substance abuse, atherosclerosis, and adult-onset diabetes mellitus. These genetic factors have often been characterized as “defects” but they might better be called “quirks” since they have probably been of little biological detriment (or possibly of some benefit) until recent generations when individuals have been exposed to certain novel circumstances.

A genetic tendency to overeat sweets is of little consequence when sugar is scarce and extensive exercise is involved in meeting basic needs; if famines are frequent, it might even be advantageous. A preference for fats will mainly be adaptive when calories and fat are scarce and few people live into their sixties. The strong genetic factors in myopia and dyslexia will remain latent until literacy becomes a necessary accomplishment. It will be valuable to understand the nature of the genetic variations that make some individuals especially susceptible to these diseases. An adaptive analysis reveals the fundamental distinction between such genetic quirks (genes of little cost in the natural environment), genes that impose costs that are worth their biological benefits, and true genetic defects that are necessarily rare and maintained by population pressure.

Myopia is a good example of a disease of civilization, one that shows much genetic variability. Teikare et al. showed high levels of concordance for both monozygotic and dizygotic twins in respect to myopia, and Karlsson found evidence for a strong single-locus effect. This evidence for genetic control is hardly evidence against decisive environmental causation.

A serious handicap with a high heritability, such as myopia, could not possibly persist under natural conditions. Corrective lenses were invented far too recently to have allowed a substantial increase in genes that cause myopia. This argument is supported by the dramatic myopia increase in native groups newly subjected to formal education in childhood. Myopia may be a fine example of a disease that is strongly heritable, but is seen only in a special environment.

Recent research on the development of myopia in experimental animals has revealed an exquisite adaptation: eye growth is regulated by the kind of usage and the quality of retinal images received. Each eye grows independently and different parts grow differently to keep images in focus. The strong genetic factor in myopia most likely reflects differences in the sensitivity of the mechanism that regulates eye growth. None of the experimental data derive from human subjects, and conflicts among some results even within the same species indicate that many issues await resolution. Still, an evolutionary approach gives reason to be optimistic about the possibility of preventing or reducing myopia. For example, could it be that the burden or myopia ‘ , Id be dramatically reduces if children’s books had large print and wide margins, and if schools made more frequent use of larger more distant reading materials such as posters and blackboards?

The Hunter-Gatherer life Style Versus Modern Life

The most obvious differences in life-style between pre agricultural and modern times are in exercise and diet. Much ill health stems from over consumption, particularly of saturated fat and salt. The problem, however, goes deeper; the evolutionary perspective shows it is also a predictable outcome of the human genetic makeup. Designed by natural selection as hunter gatherers, humans are programmed to store fat reserves when possible, against lean times. A tendency to minimize physical activity when it is not absolutely necessary might be an adaptation to conserve those stores-the couch potato might be an evolutionary inevitability.

Another interesting example in this line of thought is Eaton’s research in cancer related to life-style changes other than diet. He argues, for instance, that changes in reproductive patterns in Western women mean that they have up to a hundred times increased risk of breast cancer and increased risk of endometrial and ovarian cancers compared with women who still have a hunter gatherer life-style. The increased risk is a consequence of a combination of earlier menarche, later first birth, fewer births and later menopause; in addition, modern women breast-feed for much shorter times. One consequence of these differences is that during their lifetime, hunter gatherer women ovulate on average 158 times, while the average for modern affluent women is 451 times.

Eaton acknowledges that altering this pattern will not be simple. “Increasing the popularity of breast feeding has a good chance of being accepted” he says, “but the other factors would have to be addressed mainly through hormonal therapy that mimics the hunter-gatherer reproductive pattern, rather than seeking to restore the pattern itself’. For instance, hormone therapy should induce early maturation of mammary ducts, decrease ovulatory frequency, and lower the level of the reproductive hormone gonadotropin in the blood. Each of these features is associated with low incidence of female cancers.

Patterns of child rearing and acculturation have changed so dramatically that many children may not receive the minimum amounts of certain kinds of stimulation. Psychiatrists and psychologists have appropriately emphasized the importance of the early mother-child interaction andattachment and studies continue about the psychological and intellectual effects of extended early exposure to daycare by strangers. Less emphasis has been given to such factors as family size, loss of availability of extended family, and lack of consistent early exposure to groups of peers. The hunter-gatherer child, playing with other children in a clearing between huts under the casual supervision of several related adults, may be having developmentally significant experiences that are not available to a child in even the best daycare center or single-family dwelling.

The Dawn of Darwinian Medicine

Disease looks different from an evolutionary perspective. Infection is not a happenstance encounter with another organism, but an arms race between host and parasite, with extraordinary elaborations of weapons, strategies, defenses and counter-defenses. Trauma is not a mere matter of damaged tissues but of the failure of protective mechanisms, the yielding of the soma at weak spots, and repair processes that have been shaped and constrained by natural selection. Genes that cause disease are not just the result of mutation, but may be selected for known or unknown benefits, such as the vigor in youth that may result from genes that later cause aging. Environmental abnormalities, not limited to changes in the last few generations, are major causes of common diseases, often in interaction with genetic “quirks” that are harmless in the environment of evolutionary adaptedness. For all these causes of disease an evolutionary perspective adds another dimension to proximate explanations.

We are only at the dawn of Darwinian medicine. Although evolutionary theory has long been the foundation for many branches of biology, adaptationists analyses are just beginning to be applied in medicine. We expect them to grow rapidly in number and explanatory power, and to make major contributions to future progress in the understanding of disease.

One might ask why this is happening now, but it may be more edifying to ask why evolutionary theory was not fully applied to medicine decades ago. This will eventually be a topic for historians of science, but the present guess is that the delay resulted mainly because scientific medicine arose during the heyday of logical positivism, with its condemnation of all implications of purpose. This was transmitted to many physicians, who remain suspicious of adaptationist arguments. Another reason, also worthy of the attention of historians of science, is the surprising slowness of evolutionary biologists to provide useful theory. The historians may well marvel that the role of kinship in evolution was not seriously examined until 1964. While some branches of biology gave made rapid strides as a result of testing evolutionary as well as proximate explanations, the evolutionary approach has so far provided few benefits to medicine.

Conclusion

Many people seem to think that an adaptionist approach is based on the assumption that organisms are perfect. This is a misconception. It is true that the adaptionist holds the power of selection in high regard and is skeptical of explanations that take quick refuge in proposed defects in the organism. Paradoxically, however, the adaptationist is also particularly able to appreciate the adaptive compromises that are responsible for much disease. Walking upright has a price in back problems. The capacity for tissue repair has a price of cancer. The immune response has a price of immune disorders. The price of anxiety is panic disorder. In each ;; case, natural selection has done the best it can, weighing benefits against costs. Wherever the balance point, however, there will be disease. The adaptationist does not view the body as a perfect creation, but as a bundle of compromises. By understanding them, we will better understand disease.

“The adaptationist does not view the body as a perfect creation, but as a bundle of compromises. “