Editorial
DARWINIAN (EVOLUTIONARY) MEDICINE
Charles R. Darwin may have had the most profound influence on biology of anyone who has ever lived. He was born February 12, 1809 (the same day as Abraham Lincoln) and died in 1882.' His three major contributions concerning evolution were The Origin of Species (1859), The Descent of Man and Selection in Relation to Sex (1871), and Expressions of the Emotions in Man and Animals (1872). Recent reviews concerning aspects of Darwinian medicine have been written by Oliweinstein,2 Nesse and Williams,3 Profet,4 and Wright.s I have drawn heavily upon these publications and their excellent bibliographies of original publications. Particularly, the book by Nesse and Williams3 has been seminal, and the examples given in this editorial are largely derived from that book.
Interestingly, the evolutionary theory was advanced earlier by other individuals, pecifically Darwin's own grandfather, Erasmus Darwin, and Jean Baptiste Lamarck. However, Darwin and A. R. Wallace were the first to recognize how natural selection could account for evolution, thereby getting the credit for this still controversial theory. In clinical medicine, most practitioners face the consequences of evolution on a daily basis, namely the development of bacterial resistance to antibiotics. Berkowitz6 has recently reviewed the problem. Many of the signs, symptoms, and diseases related to evolutionary medicine must be considered conjecture. While some hypotheses are readily testable, others are difficult or impossible to prove. However, for those individuals whose constant question to everything around them is why or how, these suppositions are intriguing.
Oliweinstein2 credits Williams with the first suggestion of a Darwinian approach to medicine. He wrote a paper in the 1950s proposing an evolutionary framework for senescence. More recently, Ewald looked at various symptoms of infectious disease from an evolutionary standpoint.2°3 Williams and Nesse7 reviewed Darwinian medicine, subsequently collaborating in a more extensive consideration defming Darwinian medicine as "the hunt for evolutionary explanations of vulnerability to disease."3 Mechanisms such as salivation, tearing, coughing, sneezing, vomiting, and diarrhea expel noxious substances and microbiologic agents. Our natural repugnance toward garbage, feces, vomitus, and purulence is a defense against contagion. The IgE system, as manifested by allergic tearing, sneezing, coughing, vomiting, and diarrhea, no doubt has some function, perhaps that of eliminating toxins and poisons and possibly protecting us from parasites.
Before the introduction of antibiotics, iatrogenic malaria was an effective treatment for syphilis, a disease that is rare where malaria is common. Among metabolic diseases that may have benefits as well as costs is phenylketonuria, in which there may be reduction in the miscarriage rate of the female heterozygote. The homozygote, however, cannot metabolize phenylalanine and will survive only with strict dietary restriction. Myopia is thought to be a result of an interaction between genes and the increasing close work characteristic of literate societies. Among the groups in which the emergence of myopia has been observed are the Eskimos, who were seldom nearsighted until more recent times, when they began to attend schools.
Modern women, who menstruate earlier than their forebears, have an estimated 3½ times more menstrual cycles than women 10,000 years ago. The increased estrogen with each cycle may relate to the 10 to 100 times greater likelihood of breast cancer in modern women. Grand multiparous women have less breast cancer than women with fewer pregnancies.
Profet4 has promulgated the hypothesis that pregnancy (morning) sickness is protective.
During the first trimester when the fetus is most susceptible to toxins (teratogens), the pregnant woman avoids those foods and agents (odors, for example) more likely to be associated with toxins. Individuals who have less pregnancy sickness have more miscarriages. Drugs that reduce pregnancy sickness may be associated with a greater number of fetal anomalies. Children's avoidance of possible toxins in vegetables such as onions, garlic, broccoli, okra, brussels sprouts, and turnips may also be related to this mechanism. However, why is there no "lactation sickness," ie, the same sort of avoidance in women who breast-feed their infants?
In malaria, sickle cell carriers (heterozygotes) are better able to remove infected blood cells, and thus resist the disease. Unfortunately, homozygotes have sickle cell anemia. Similarly, glucose-6-phosphate dehydrogenase deficiency causes red blood cells to burst when malarial parasites use oxygen. However, hemolysis can also be caused by oxidizing drugs such as quinine, primaquine, salicylates, sulfonamides, nitrofurans, phenacetin, naphthalene, and some vitamin K derivatives. Heterozygotes for cystic fibrosis may be more resistant to diarrhea (cholera) or asthma, but homozygotes have cystic fibrosis. The X-linked mental retardation syndrome (fragile X syndrome) causes mental retardation in 1 in 2,000 males, but the gene may persist because the heterozygotic female shows increased fertility. DR3 is associated with childhood-onset diabetes mellitus but may reduce miscarriage in the mother. Tay-Sachs disease, which kills all homozygotes before reproduction and is heterozygotic in 3% to 11% of Ashkenazic Jews, may protect against tuberculosis. Elevated uric acid protects against oxidation, a factor in senescence, and it has also been suggested that individuals with elevated serum uric acid have increased mental ability, though elevated uric acid levels are also associated with gout. Hemochromatosis may help women avoid iron deficiency anemia, but men can accumulate excessive iron with deleterious effects. X-linked color blindness enables individuals to see camouflage better than those without this defect,' which is found in approximately 6.0% of Europeans, 4.9% of Asians, and 3.1 % of Native Americans.9 Since prehistoric males were the hunters, it would have been of no advantage for the females to have this characteristic. It has been suggested that good specialty choices for color-blind physicians would be psychiatry and neurology, while anesthesiology, emergency medicine, and dermatology might represent problems.10
Insect bites can lead to malaria, Rocky Mountain spotted fever, borreliosis, and other infectious diseases. If the bites were not itchy and an annoyance, would we avoid them? Daily bathing is a recent custom, with weekly or less frequent baths common 100 years ago. Infrequent bathing was even more common several hundred years ago. Today's excessive bathing removes the natural surface lipids that maintain hydration of the outer layers of the skin, preventing dryness and itching (winter itch). Perhaps over the next few thousand years, human skin will become oilier as a protection against frequent bathing. Pigmentation gives protection against sun damage. Darkly pigmented individuals are less likely to have skin cancer, and albinos have a markedly increased incidence. However, in patients with xeroderma pigmentosum, an inherited disorder associated with pronounced sun sensitivity, defective deoxyribonucleic acid repair after ultraviolet injury, and a marked increase in skin cancer, skin cancers develop regardless of pigmentation.11 Thus, increased melanin pigmentation may have evolved for other reasons, such as camouflage and heat absorption.12
Ephelides (freckles) and lentigines (liver spots) may represent abortive attempts at increased pigmentation. Next to pigmentation, thickness of the outer layer of the skin (stratum corneum) is the most effective mechanism for protection from sun damage. Are actinic keratoses an attempt to thicken the stratum corneum and protect from sun damage?
These ideas are stimulating and encourage our perennial questioning of why and how. Thinking about disease in this way will undoubtedly lead to more examples of Darwinian (evolutionary) medicine and theories of mechanisms for disease.
J. Graham Smith, Jr., MD Editor
References
1. Browne J: Charles Darwin, Voyaging. New York, Knopf, Vol 1, 1995, p 6
2. Oliweinstein L: Darwin. Discover 1995; 16:111-117
3. Nesse RM, Williams GC: Why We Get Sick. New York, Random House, 1994 4. Profet M: Protecting Your Baby-To-Be. Reading, Mass, Addison-Wesley, 1995 5. Wright R: The Moral Animal. New York, Vintage, 1994 6. Berkowitz FE: Antibiotic resistance in bacteria. South Med J 1995; 88:797-804
7. Williams GC, Nesse RM: The dawn of Darwinian medicine. Q Rev Biol 1991; 66:1-22 8. Morgan MJ, Adam A, Mollon JD: Dichromats detect colour-camouflaged objects that are not detected by trichromats. Proc R Soc Lond B Biol Sci 1992; 248:291-295 9. Reichel E: Hereditary cone dysfunction syndromes. Principles and Practice of Ophthalmology. Albert DM, Jakobiec FA (eds). Philadelphia, WB Sounders Co, Vol 2, 1994, pp 1238-1249
10. Currier RD: A two- and-a-half color rainbow: color blindness in physicians. Arch Neurol 1994; 51:1090-1092 11. Kraemer KH: Xeroderma pigmentosum knockouts. Lancet 1996; 347:278-279
12. Morison WL: What is the function of melanin? Arch Dermatol 1985; 121:1160-1163