Abstract: Darwinian principles have been remarkably successful in explaining otherwise puzzling features of the living world. The human body surely qualifies as a part of the living world. It would therefore be surprising if Darwinian principles were not helpful in explaining how our bodies work, and why they so often fail to work as we think they should. However, only recently have evolutionary biologists teamed up with physicians to try to understand the evolutionary causes of "why we get sick". The result is the new science of "Darwinian Medicine". This talk is a brief introduction to this exciting new field of research.

Introduction: What is "Darwinian Medicine"?

At present Darwinian Medicine is largely theoretical. It takes as its point of departure the oft-repeated saying by the geneticist Theodosius Dobzhansky: "Nothing in biology makes sense except in the light of evolution." Evolutionary biology is the theoretical foundation for all biology, and biology is the foundation for all medicine, so it is natural that there should be a connection. But it has taken a long time to appreciate this fact because of the very different time perspectives typically adopted by physicians and medical researchers, on the one hand, and evolutionary biologists, on the other. The immediate and primary aim of medical research is to understand the human body's anatomical and physiological mechanisms as they currently exist, and to devise treatments to counter whatever malfunctions may arise. Medical research focuses on the proximate causes of illness, i.e., those causes operating on and in presently existing individuals. Evolutionary biologists, on the other hand, want to know why any organism has the characteristics it does in the first place. They seek the ultimate causes of an organism's characteristics in its evolutionary history. Present organisms have the basic characteristics they do because their ancestors acquired these characteristics. Darwinian evolutionary biology does this by asking how a small set of processes leads organisms to have the characteristics they do.

At least some of the traits of living things can be explained by noting that such characteristics conferred a survival or reproductive advantage on their ancestors. In other words, such characteristics are a result of natural selection. A key strategy in framing Darwinian explanations has come to be called "The Adaptationist Program". Essentially this means that when trying to explain some widespread biological characteristic, ask what adaptive function this characteristic has, or might have had in the past, and then seek a plausible selectionist explanation of this function. Of course, there is no guarantee beforehand that every characteristic is adaptive, or that a plausible selectionist explanation will be forthcoming. But as a research strategy the Adaptationist Program has enjoyed a great deal of success.

Despite its success, however, no Darwinian believes that all features of all organisms are adaptations. Selection is not the only evolutionary force at work shaping organisms. Chance, historicity, and constraints combine with natural selection to shape organisms. The result is that while all organisms are incredibly well-adapted in some respects, in others they represent "trade-offs" and compromises, jury-rigged contraptions that succeed despite, rather than because of, the way they are constructed. Taking into account the various ways in which evolution designs organisms helps to explain why the human body is simultaneously a glorious work of art and a Rube Goldberg device that seems patched together by craftsmen lacking both wisdom and foresight. I will follow Ness and Williams in distinguishing evolutionary explanations for human ailments into the following categories: evolved defenses, conflicts with other organisms, novel environments, trade-offs, and design flaws. I will conclude with some remarks on the future of Darwinian Medicine.

Evolved Defenses

Some of the body's "ailments" are in fact evolved defenses brought about by natural selection. These are physiological mechanisms that, although associated with unpleasant experiences, aid the body in its own self-defense. Some evolved defenses have fairly obvious survival value. Pain is unpleasant, perhaps by definition, and most people go to great lengths to avoid it. This is, in fact, the purpose of pain: to steer us away from those activities that are harmful to the body. The rare individuals who cannot feel pain lack the crucial mechanism for avoiding dangerous experiences, and generally don't live past 30. Coughing, vomiting, and diarrhea are evolved defenses designed to expel dangerous material from the body. The benefit of vomiting after ingesting a toxic substance is obvious. The benefit of vomiting on other occasions is less obvious. Such responses work according to the "smoke-detector" principle. A smoke detector may issue many false alarms (e.g., from burned toast), which are merely annoyances. One could avoid these false alarms by removing the batteries from the smoke detector, but then in the case of a real fire you might die. Likewise, the penalty for not responding to ingestion of a toxic substance is far greater than the minor inconveniences associated with the body's many false alarms at relatively innocuous substances.

Pain, coughing, vomiting, and diarrhea serve plausible defensive purposes. Less obvious is the utility of fever. Why should your internal body temperature rise when you have the flu? One explanation that has a good deal of support in its favor is that the elevated body temperature associated with fever apparently facilitates the destruction of pathogens. Studies have shown that "cold-blooded" lizards, when infected, move to warmer places until their bodies are several degrees above their usual temperature. If prevented from moving to the warmer part of their cage, they are at increased risk of death from the infection. Similarly, in a study of elderly rats, no longer achieve the high fevers of their younger lab companions, these rats tended to seek hotter environments when challenged by infection. Closer to home, a study of humans suggested that individuals suffering from a flu-induced fever recovered more quickly from the flu than individuals who took fever-reducing medications. One consequence of this finding is that parents who give fever-reducing medications to their children, while decreasing the discomfort of the child, may actually be inhibiting the child's body from most effectively fighting the infection.

Morning sickness has long been a puzzle: Why should a woman undergoing the already difficult process of bringing a child to term be saddled with nausea as well? Can nature really be that cruel? Perhaps not. The onset of nausea coincides closely with the period of rapid tissue differentiation of the fetus, when development is most vulnerable to interference by toxins. Nauseated women tend to restrict their intake of strong-tasting, potentially harmful substances. This has led researchers to speculate that the nausea of morning sickness is an evolved adaptation which protects the fetus from exposure to toxins. As it turns out, studies have shown that women with more nausea are also less likely to suffer miscarriages. Although this does not prove that the proposed explanation is correct, it is nonetheless highly suggestive. It also suggests that blocking nausea with drugs could result in higher miscarriage rates or more birth defects.

There is no reason to restrict the list of evolved defenses to the purely "physical". Some psychological problems, as well, are probably the result of evolved defenses. Many people suffer from severe anxiety disorder, characterized by terror at the prospect of speaking in public and the like, and treatments are widely available for this. But some degree of anxiety is useful. Feelings of anxiety evolved as a defensive mechanism in dangerous situations in which avoidance and/or rapid escape might mean the difference between life and death. Too little anxiety can be as bad as too much. One study evaluated the benefits of fear in guppies. Guppies were placed into a tank with a smallmouth bass, their reactions observed, and then divided into three groups: timid, ordinary, or bold. The timid hid, the ordinary simply swam away, and the bold stood their ground and eyed the bass. Each group of guppies was then left alone in the tank with the bass. After 60 hours, 40% of the timid guppies had survived, compared to only 15% of the ordinary guppies. All of the bold guppies ended up aiding in the transmission of bass genes rather than their own. Some animals presumably can afford to be bold. Guppies, alas, are not such an animal. What about humans? Is it possible to suffer from too little anxiety? It is difficult to know how widespread a problem this is, since few people come to psychiatrists complaining of insufficient apprehension, but it has been suggested that if sought, the pathologically nonanxious are likely to be found in abundance in emergency rooms, jails, and unemployment lines.

It is important to keep in mind that identifying something as an adaptation does not in itself specify who the beneficiary of the adaptation is. Take sneezing, for example. It may be an adaptation serving the organism sneezing, as a way of expelling foreign invaders. Or it may be a way in which the invader manipulates the host to help it makes its way to another host as quickly as possible. It has been suggested that the excessive salivation and increased aggressiveness associated with rabies infection serves a similar function. If it turned out that an increased libido is associated with certain venereal diseases, this would not be at all surprising when viewed from an evolutionary perspective.

Conflicts with Other Organisms

We share the world with an incredible variety of living things, some of which would like to eat us, if they could. Most of us no longer face danger on a daily basis from large carnivores. But threats from internal enemies is much like it has always been. We share not only our planet but also our bodies with an incredible variety of living things, some of which do not have our own best interests at heart. These are called pathogens. Although our bodies have evolved defenses against many pathogens, it cannot provide us with perfect protection against all, because pathogens have their own evolutionary agendas, and tend to evolve countermeasures much faster than we can erect defenses. E. coli may evolve more in a day than the human species does in a millennium, and thus may rapidly evolve countermeasures to any defenses that we evolve or artificially introduce. Antibiotic resistance is a classic example of natural selection in action in our own bodies. Bacteria that happen to have genes that allow them to prosper despite the presence of an antibiotic spread rapidly, rendering the administration of antibiotics ineffectual.

Conflicts with other organisms are not limited to pathogens, or to other species like large carnivores. They can arise within the same species, and indeed within the same family. Parent-offspring conflicts are the most obvious. Although obviously genetically related, a mother's genetic interests and those of her child are not identical. While it may be in the mother's genetic interests to become pregnant again when the child is a couple of years old, it may be in the child's interest that she continue to lactate. Likewise, it may be in the genetic interests of a woman that she conserve some of her reproductive resources while pregnant for subsequent offspring. But it may be in the genetic interests of a fetus that it secure as much nourishment from its mother as possible. Thus, from the mother's standpoint the optimal size of a fetus may be a bit smaller than that which would best serve the fetus. Consequently, an "arms race" can develop between mother and fetus over her blood pressure and levels of blood sugar, resulting in hypertension and diabetes during pregnancy.

Coping with Novelty

Evolutionists remind us again and again that there is no such thing as an adaptation simpliciter. All adaptations are relative to particular environments. What is beneficial in one environment may not be so in another. This simple insight helps to explain a host of human ailments. Anthropologists studying human evolution refer to our "Environment of Evolutionary Adaptedness" -- i.e., the hypothetical set of environments in which 99.9% of human evolution took place. Although accounts of the EEA differ in the details, one thing is certain: it was quite unlike modern industrialized urban existence. And so the threats to health and well-being were different as well. Whereas for most of human existence the most common causes of death would be accidents, starvation, predation, and infectious disease, now the most common threats are heart attacks, strokes, and other complications of atherosclerosis, cancer, and the health hazards associated with obesity.

Ironically, it is because we were so well adapted to pre-modern environments that we have so many of the latter problems now. On the African savanna, fat, salt, and sugar were scarce and precious resources, and it would have been impossible to ingest too much of any of these. But individuals who had a tendency to consume large amounts of fat when given the rare opportunity to do so had a selective advantage over their more svelte companions when famines occurred. We are the descendants of these well-adapted individuals, and we retain their fondness for fat, salt, and sugar. It is no coincidence that it is precisely these nutrients that are found in such density in the foods sold so successfully by fast-food restaurants. But in our environment, where these nutrients are available in abundance, the problem now is to curb our tendencies to consume them. Many do not succeed. The result is heart attacks resulting from atherosclerosis, a problem that was rare before this century and remains rare among contemporary hunter-gatherers. We know what we ought to do -- limit fat intake, eat lots of vegetables, exercise -- but evolved tendencies tend to subvert our intellects and wills.

In a different way, change of life-style may also be responsible for the much higher incidence of breast cancer among American women than among their ancestors. Depending on which data are selected, women today are somewhere between 10 and 100 times more likely to be stricken with breast cancer than their ancestors were. Why? For most of human pre-history we lived a hunting and foraging existence. Among contemporary hunter-gatherers, menstruation begins later, the first child is born earlier, there are more children altogether, they are breast-fed for years rather than months, and menopause comes somewhat earlier. During each menstrual cycle a woman's body is flooded with estrogen, a hormone that has been linked to breast cancer. It has been estimated that American women today experience 3.5 times as many menstrual cycles than their ancestors did 10,000 years ago, so the higher incidence of breast cancer may well be related to just such life-style factors.

Trade-Offs

Every well-built machine is a congery of compromises. The flashy sports car (e.g., the Dodge Viper I lust after) that does 0 to 60 in under six seconds is a fuel hog. The economy car (e.g., my Toyota Tercel) that gets great gas mileage will have to patiently wait its turn when trying to merge into freeway traffic. Likewise, trade-offs and compromises are built into every biological adaptation. One could have arm bones three times their current thickness that would never break, but one would need more massive shoulder muscles to lift them, and human beings would be condemned to a never-ending quest for calcium and protein to support such structures. Our hearing could be much more sensitive than it is, but only at the cost of being bombarded with irrelevant noises that preclude concentration on what really matters. In general, our bodies are the result of millions of years of evolutionary compromises selected to get the greatest reproductive benefit at the lowest cost. Walking upright permits us to run faster, see farther, handle tools, and hold babies. Suffering from lower back pain is the price we pay for the greater benefits received.

At the genetic level such trade-offs also exist. If a given gene offers a net reproductive advantage, it will tend to increase in frequency in a population even if it causes vulnerability to disease. It is only the net reproductive consequences that matter, not the factors that lead to this result. The most famous example of a genetically-based biological trade-off concerns sickle-cell anemia. Individuals with two copies of the sickle cell gene have defective blood cells, suffer terrible pain, and die young. Individuals with two copies of the "normal" (unsickled) gene are at high risk of death from malaria. But individuals with one of each gene enjoy "heterozygote superiority" and are protected from malaria, while avoiding the fatal consequences of sickle cell anemia. Where malaria is prevalent, such individuals are actually fitter than those completely lacking the sickle-cell gene. Despite being lethal in homozygous form, in heterozygous form it is beneficial. Of course, individuals carrying the sickle-cell gene may pass it on to their offspring, some of whom may be homozygous for the gene. This is the "cost" of increased malarial resistance.

It is quite possible that other genetic diseases may be linked to benefits conferred by such heterozygote superiority. Cystic fibrosis kills one out of 2,500 Caucasians. So one might expect the responsible genes to be eliminated from the gene pool. And yet they endure. Animal studies indicate that animals with just one copy of the cystic fibrosis gene may be more resistant to the effects of the cholera bacterium. Since there are many more people with a single, resistance-conferring copy of the gene than with a disease-causing double dose, the gene is stably passed from generation to generation. Another study suggests that the cystic fibrosis gene decreases the chances of acquiring a typhoid fever infection, which once had a 15 percent mortality rate. The influence of such pleiotropic genes (those having multiple effects) may be responsible for a number of human ailments.

A final, tragic possible example of a trade-off, concerns cancer. Every sexually produced organism begins as a fertilized egg. Cell division iterated over and over again results in a multicellular organism with tissues differentiated for specific functions. Many of these tissues retain the ability to undergo cell division to repair damage. In other words, cell division is the very essence of building and maintaining a complex functional organism. In reproduction, the instructions for building a multicellular organism with tissue differentiation are passed along to form the next generation. The instructions that get passed along have to encode directions for dividing at the right time, in the right way, for stopping at the right moment, and for starting and stopping again as needed. Given the complexity of the task, and the number of opportunities for the cellular machinery to get derailed, the really difficult question becomes not why anyone gets cancer, but rather how anyone avoids this fate. The very process that permits our existence in the first place also brings an untimely demise to some of us in the end.

Design Flaws

Finally, there are characteristics that can only be explained by an utter lack of foresight on the part of evolution. Nature programs often convey the impression that organisms have been "fine-tuned" by natural selection to be virtually perfect for their particular ways of life. Such shows emphasize the often incredible adaptations that characterize so many species of plants and animals. But a closer look reveals that all is not perfect. Rather than being perfectly crafted instruments for the propagation of their genetic material, organisms are the products of chance, historicity, and constraints, as well as of natural selection. The result is that while organisms are incredibly well-adapted in some respects, in others they represent "trade-offs" and compromises, jury-rigged contraptions that succeed despite, rather than because of, the way they are constructed. Some examples will help to make this clearer.

The eye has always elicited awe from anyone who has studied its structure carefully. The clear tissue of the cornea curves just the right amount, the iris expands and contracts to modulate the amount of light entering, the lens adjusts to distance, so that the optimal quantity of light focuses exactly on the surface of the retina, etc. It seems to be so carefully crafted that it is hard to imagine how its design could be improved upon. In the 19th century this conviction reached its zenith in William Paley's Natural Theology (1802), which took the eye as the basis for an argument for the existence of an all-wise, all-powerful Intelligent Designer. A closer look at the vertebrate eye, however, may lead one to a different conclusion. Blood vessels and nerves traverse the inside of the retina, and then dive through an opening in the retinal wall on their way to the optic nerve. This creates a blind spot at their point of exit, and some distortion as photons have to make their way through the tangle of blood vessels and nerves before striking the retinal wall. It may not be a large distortion, but the vertebrate eye is clearly not designed as well as it could be. This arrangement also fails to anchor the retina securely to the inside of the eye, so that retinal detachment sometimes occurs (e.g., in boxers). The "backwards" wiring of vertebrate eyes is a good example of (i) bad luck and (ii) historical constraints. Hundreds of millions of years ago the layer of cells that happened to become light sensitive in our ancestors was positioned "incorrectly," but because it provided a selective advantage, it was retained and evolved into the modern backwards-wired vertebrate eye. Even though a better design existed in an abstract "morphospace" (i.e., the space of biologically possible forms), once evolution of the eye started down a certain path, backing up (i.e., going back to a relatively less advantageous form) and starting over, became impossible. Squid eyes, on the other hand, are designed more sensibly, with nerves running on the outside, reducing distortion and securing the retina so that it cannot detach. Were squid to take up boxing, one would see far fewer prematurely terminated careers due to detached retinae.

A second example makes much the same point. For vertebrates, choking to death on ingested food is a constant danger. The simple act of swallowing can be life-threatening because our respiratory and food passages intersect. Thanks to the epiglottis we usually manage to inhale air into our lungs and take food into the stomach rather than vice versa without difficulty, but mistakes happen all too often. Although it would be a better design to have completely separate pathways for respiration and for ingestion of food, we are stuck with an evolutionary legacy from our lungfish forebears. In an early lungfish ancestor the opening for breathing air was located sensibly at the top of the snout, with the opening for ingestion of food below that. But then the passageway for respiration crossed the passageway for food, leading to the original traffic-control problem whose unfortunate consequences we still face today. It would of course be better if natural selection could start over from scratch and redesign us more optimally. But evolution is like a ratchet that only moves in one direction. As a result, we can only take precautions like chewing our food thoroughly and staying away from people telling jokes while we are eating.

Conclusions: The Evolution of Medicine

In the concluding pages of the Origin of Species, Darwin predicted that his work would lead to far more important research in the distant future, especially concerning human beings. Darwin's prediction is being fulfilled. At present Darwinian medicine exists mainly at the level of theory, but the insights of Darwinian medicine could work a profound transformation in practice of medicine in the next century. By shifting focus to the traits that make us vulnerable to disease, medicine might be in a better position to develop treatments that effectively mitigate the consequences of disease. At the very least, taking a gene's-eye evolutionary point of view helps to dispel some mysteries about health and sickness. Evolution is not concerned to maximize the health or well-being of organisms. It is only concerned with successful genetic replication, and what serves this purpose is only contingently related to the health and well-being of the organism serving as the temporary vehicle for the genes. What is good for our genes is not necessarily good for us, and even when our interests and our genes' interests coincide, the genes of other organisms can often subvert ours with their own agendas. Without appreciating the evolutionary dynamics of health and disease, it is impossible to correctly understand the origin, persistence, and options for treating the ills affecting the human body.

Recommended Reading

Print Sources

Ewald, P.W. (1994), Evolution of Infectious Disease (Oxford University Press)..

McGuire, M.T., and Troisi, A. (1998), Darwinian Psychiatry (Cambridge, MA: Harvard University Press).

Nesse, R. and Williams, G.C. (1994), Why We Get Sick: The New Science of Darwinian Medicine (New York: Vintage Books).

Stearns, S. (ed.) (1998), Evolution in Health and Disease (Oxford University Press).

Trevathan, W.R., Smith, E.O., and McKenna, J.J. (eds.) (1999), Evolutionary Medicine (Oxford University Press).

Williams, G.C., and Nesse, R.M. (1991), "The Dawn of Darwinian Medicine," Quarterly Review of Biology 66:1-22.

Online Resources

Randolph M. Nesse, "What is Darwinian Medicine?" http://www.chester.ac.uk/~djones/HCS/PHD1/TEXTS/read2.htm

Randolph M. Nesse and George C. Williams, "Evolution and the Origins of Disease"
http://www.sciam.com/1998/1198issue/1198nesse.html

Lori Oliwenstein, "Dr. Darwin," Discover (October, 1995) http://www.people.virginia.edu/~rjh9u/darwmed.html