Evolution and the Origins of Disease by Randolph M

The principles of evolution by natural selection are finally beginning to inform medicine Evolution and the Origins of Disease by Randolph M. Nesse and George C. Williams houghtful contemplation of the human body elicits awe—in equal measure with perplexity. The eye, for instance, has long been an object of wonder, T with the clear, living tissue of the cornea curving just the right amount, the iris adjusting to brightness and the lens to distance, so that the optimal quantity of light focuses exactly on the surface of the retina. Admiration of such apparent perfection soon gives way, however, to consternation. Contrary to any sensible design, blood vessels and nerves traverse the inside of the retina, creating a blind spot at their point of exit. The body is a bundle of such jarring contradictions. For each exquisite heart valve, we have a wisdom tooth. Strands of DNA direct the development of the 10 trillion cells that make up a human adult but then permit his or her steady deterioration and eventual death. Our immune system can identify and destroy a million kinds of foreign matter, yet many bacteria can still kill us. These contradictions make it appear as if the body was designed by a team of superb engineers with occasional interventions by Rube Goldberg. In fact, such seeming incongruities make sense but only when we investigate the origins of the body’s vulnerabilities while keeping in mind the wise words of distinguished geneti- cist Theodosius Dobzhansky: “Nothing in biology makes sense except in the light of evolution.” Evolutionary biology is, of course, the scientific foundation for all biology, and biology is the foundation for all medicine. To a surprising degree, however, evolutionary bi- 86 Scientific American November 1998 Copyright 1998 Scientific American, Inc. Constraints Example: The design of the human eye leads to a blind spot and allows for detached retinas. The squid eye is free of such problems. AIG KIEFER TIONS BY CR SQUID RETINA HUMAN RETINA A USTR ILL Defenses Example: Symptoms such as cough or fever are not defects but in fact are the body’s defenses in action. Trade-offs Example: Overdesign of any one system, such as a pair of unbreak- able arms, would upset the entire organism’s functioning. Conflicts Example: Human beings are in con- stant battle with other organisms that have been fine-tuned by evolution. CHERS, INC. O RESEAR T HO Cholera bacterium CNRI/SPL/P Novel environments Example: The human body has only recently adopted its current environment, filled with former rarities such as high-fat foods. CE A URIE GR A L Copyright 1998 Scientific American, Inc. Scientific American November 1998 87 ture facilitates the destruction of patho- DEATH gens. Work by Matthew J. Kluger of the Lovelace Institute in Albuquerque, N.M., has shown that even cold-blooded liz- ards, when infected, move to warmer places until their bodies are several de- grees above their usual temperature. If prevented from moving to the warm COST part of their cage, they are at increased risk of death from the infection. In a similar study by Evelyn Satinoff of the MINOR University of Delaware, elderly rats, INCONVENIENCE who can no longer achieve the high fevers of their younger lab companions, SEVERE NO also instinctively sought hotter environ- RESPONSE SEVERE ments when challenged by infection. WITH NO RESPONSE REAL WITH REAL A reduced level of iron in the blood is THREAT THREAT another misunderstood defense mecha- JOHNNY JOHNSON nism. People suffering from chronic in- MUCH SUFFERING is unnecessary but inevitable fection often have decreased levels of because of the smoke-detector nature of our defens- blood iron. Although such low iron is es. The cost of a false alarm—a strong reaction such sometimes blamed for the illness, it ac- as vomiting in the absence of a true threat to life—is tually is a protective response: during temporary unpleasantness. But the cost of no alarm infection, iron is sequestered in the liver, in the presence of a true threat, such as a food toxin, which prevents invading bacteria from could mean death. A lack of defensive response dur- AIG KIEFER getting adequate supplies of this vital CR ing pregnancy, for example, could kill the fetus. element. Morning sickness has long been con- ology is just now being recognized as a cell gene, which also protects against sidered an unfortunate side effect of basic medical science. The enterprise of malaria. Finally, the process of natural pregnancy. The nausea, however, coin- studying medical problems in an evolu- selection is constrained in ways that cides with the period of rapid tissue dif- tionary context has been termed Dar- leave us with suboptimal design features, ferentiation of the fetus, when develop- winian medicine. Most medical research as in the case of the mammalian eye. ment is most vulnerable to interference tries to explain the causes of an individ- by toxins. And nauseated women tend ual’s disease and seeks therapies to cure Evolved Defenses to restrict their intake of strong-tasting, or relieve deleterious conditions. These potentially harmful substances. These efforts are traditionally based on con- erhaps the most obviously useful de- observations led independent research- sideration of proximate issues, the Pfense mechanism is coughing; peo- er Margie Profet to hypothesize that the straightforward study of the body’s ple who cannot clear foreign matter nausea of pregnancy is an adaptation anatomic and physiological mecha- from their lungs are likely to die from whereby the mother protects the fetus nisms as they currently exist. In con- pneumonia. The capacity for pain is also from exposure to toxins. Profet tested trast, Darwinian medicine asks why the certainly beneficial. The rare individu- this idea by examining pregnancy out- body is designed in a way that makes als who cannot feel pain fail even to ex- comes. Sure enough, women with more us all vulnerable to problems like can- perience discomfort from staying in the nausea were less likely to suffer miscar- cer, atherosclerosis, depression and same position for long periods. Their riages. (This evidence supports the hy- choking, thus offering a broader con- unnatural stillness impairs the blood pothesis but is hardly conclusive. If Pro- text in which to conduct research. supply to their joints, which then dete- fet is correct, further research should The evolutionary explanations for the riorate. Such pain-free people usually die discover that pregnant females of many body’s flaws fall into surprisingly few by early adulthood from tissue damage species show changes in food prefer- categories. First, some discomforting and infections. Cough or pain is usually ences. Her theory also predicts an in- conditions, such as pain, fever, cough, interpreted as disease or trauma but is crease in birth defects among offspring vomiting and anxiety, are actually nei- actually part of the solution rather than of women who have little or no morn- ther diseases nor design defects but rath- the problem. These defensive capabili- ing sickness and thus eat a wider vari- er are evolved defenses. Second, conflicts ties, shaped by natural selection, are ety of foods during pregnancy.) with other organisms—Escherichia coli kept in reserve until needed. Another common condition, anxiety, or crocodiles, for instance—are a fact Less widely recognized as defenses are obviously originated as a defense in of life. Third, some circumstances, such fever, nausea, vomiting, diarrhea, anxi- dangerous situations by promoting es- as the ready availability of dietary fats, ety, fatigue, sneezing and inflammation. cape and avoidance. A 1992 study by are so recent that natural selection has Even some physicians remain unaware Lee A. Dugatkin of the University of not yet had a chance to deal with them. of fever’s utility. No mere increase in Louisville evaluated the benefits of fear Fourth, the body may fall victim to trade- metabolic rate, fever is a carefully regu- in guppies. He grouped them as timid, offs between a trait’s benefits and its lated rise in the set point of the body’s ordinary or bold, depending on their costs; a textbook example is the sickle thermostat. The higher body tempera- reaction to the presence of smallmouth 88 Scientific American November 1998 Evolution and the Origins of Disease Copyright 1998 Scientific American, Inc. bass. The timid hid, the ordinary sim- birth defects, by interfering with the ing defenses is so often free of tragic con- ply swam away, and the bold main- mother’s defensive nausea. sequences. Because most defensive reac- tained their ground and eyed the bass. Another obstacle to perceiving the tions occur in response to insignificant Each guppy group was then left alone benefits of defenses arises from the ob- threats, interference is usually harmless; in a tank with a bass. After 60 hours, servation that many individuals regu- the vast majority of alarms that are 40 percent of the timid guppies had larly experience seemingly worthless re- stopped by removing the battery from survived, as had only 15 percent of the actions of anxiety, pain, fever, diarrhea the smoke alarm are false ones, so this ordinary fish. The entire complement of or nausea. The explanation requires an strategy may seem reasonable. Until, bold guppies, on the other hand, wound analysis of the regulation of defensive re- that is, a real fire occurs. up aiding the transmission of bass genes sponses in terms of signal-detection the- rather than their own. ory. A circulating toxin may come from Conflicts with Other Organisms Selection for genes promoting anxious something in the stomach. An organ- behaviors implies that there should be ism can expel it by vomiting, but only atural selection is unable to pro- people who experience too much anxi- at a price.

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