Why We Get Sick

by Randolph M. Nesse

  2 The sequestration of iron as a defense against bacterial pathogens is discussed by E. D. Weinberg in Physiological Reviews, 64:65–102 (1984). The treatment of malaria with iron chelating agents is reported by V. Gordeuk et al. in The New England Journal of Medicine, 327:1473–7 (1992).

  3 For a wide-ranging review of progress in bringing evolution to bear on microbiology, see Parasite-Host Associations: Coexistence or Conflict, edited by C. A. Toft et al. (New York: Oxford Univ. Press, 1991). A still-valuable general review of host-parasite coevolution is P. W. Price’s Evolutionary Biology of Parasites (Princeton, N.J.: Princeton Univ. Press, 1980).

  4 Behavioral defenses against parasites are discussed by B. L. Hart in Neuroscience and Biobehavioral Reviews, 14:273–94 (1990). The functions of pain and the shortened lives of those who lack it are described by Ronald Melzack in The Puzzle of Pain (New York: Basic Books, 1973).

  5 The biocidal action of tears is discussed by S. Hassoun in Allergie et Immunologie, 25:98–100 (1993), and that of saliva by D. J. Smith and M. A. Taubman in Critical Reviews of Oral Biology and Medicine, 4:335–41 (1993).

  6 A relevant article on nasal sprays is provided by R. Dockhorn and collaborators in Journal of Allergy and Clinical Immunology, 90:1076–82(1992).

  7 Important works on the psychology of food aversions and related defenses are provided by M. E. P. Seligman in Psychological Review, 77:406–18 (1970), and by John Garcia and F.R. Ervin in Communications in Behavioral Biology, (A)1:389–415 (1968).

  8 The diarrhea article is by H. L. DuPont and R. B. Hornick in Journal of the American Medical Association, 226:1525–8 (1973).

  9 Profet’s theory is presented in Quarterly Review of Biology, 68:335–86 (1993). Strassman’s paper was presented to the 1994 Human Behavior and Evolution Society.

  10 A good general introduction to immunology is Chapter 16 of Life: The Science of Biology, 3rd ed., by W. K. Purves, G. H. Orians, and H. C. Heller (Sunderland, Mass.: Sinauer, 1992).

  11 Many dramatic examples of the ravages of parasitic diseases are described, and some pictured, by Michael Katz et al. in Parasitic Diseases, 2nd ed. (New York: Springer, 1989).

  12 Hemoglobin increase in compensation for decreased lung function is described on pages 307 and 418 of A. J. Vander et al.’s Human Physiology: The Mechanisms of Body Function, 5th ed. (New York: McGraw-Hill, 1990.

  13 For a readable and authoritative introduction to deceptive strategies used by pathogens, see Ursula W. Goodenough’s article in American Scientist, 79:344–55 (1991). Specifically antimalarial strategies are discussed by D. J. Roberts et al. in Nature, 357:689–92 (1992). A wealth of material on autoimmune disease is provided by The Autoimmune Diseases, vol. 2, edited by N. R. Rose and I. R. Mackay (San Diego: Academic, 1992). See especially the introductory chapter by Rose and Mackay. The relationship between obsessive-compulsive disorder and Sydenham’s chorea is discussed by Judith Rapaport on pages 83–89 of Scientific American (March 1989).

  14 Reactions and overreactions to a bacterial toxin are discussed by E. K. LeGrand in Journal of the American Veterinary Medical Association, 197:454–6(1990).

  15 The best evolutionary perspective on AIDS is in P. W. Ewald’s Evolution of Infectious Disease (New York: Oxford Univ. Press, 1993). See also B. R. Levins’s article on pp. 101–11 of AIDS, the Modern Plague, edited by P. A. Distler et al. (Blacksburg, Va.: Presidential Symposium, Virginia Polytechnic Institute and State University, 1993).

  16 Viral alteration of host cell structure is discussed by Shmuel Wolf et al. in Science, 246:377–9 (1989). Fungal castration of plants is reviewed by Keith Clay in Trends in Ecology and Evolution, 6:162–6 (1991). Behavior manipulation by the rabies virus is discussed by G. M. Baer in The Natural History of Rabies (New York: Academic, 1973). A general review of manipulation of host behavior by parasites is provided by A. P. Dobson in The Quarterly Review of Biology, 63:139–65 (1988). Many medically important examples of host manipulation are discussed by Heven in The Host-Invader Interplay, edited by H. Van den Bossche (Amsterdam: Elsevier/North Holland, 1980).

  17 Ewald’s article, mentioned in our Preface, is “Evolutionary Biology and the Treatment of Signs and Symptoms of Infectious Disease,” Journal of Theoretical Biology, 86:169–76. It forms the basis for Table 3–1. Professional conferences on evolutionary approaches to medicine include one in Boston at the February 1993 meeting of the American Association for the Advancement of Science, another at the London School of Economics in June 1993.

  Chapter 4. An Arms Race Without End

  1 The classic work on biological arms races is Richard Dawkins and J. L. Krebbs’ article in Proceedings of the Royal Society of London, 6105:489–511. Alice’s race with the Red Queen is in Chapter 2 of Through the Looking Glass by Lewis Carroll.

  2 The account of President Coolidge’s son’s death and its emotional and political effects is taken from p. 14 of an article by R. S. Robins and M. Dorn in Politics and the Life Sciences, 12:3–17 (1993).

  3 A superb popular account of the nature and power of natural selection is Richard Dawkins’ The Blind Watchmaker (New York: W. W. Norton, 1986).

  4 Evidence of devastation of native populations by introduced diseases is summarized by R. M. Anderson and R. M. May’s Infectious Diseases of Humans (New York: Oxford Univ. Press, 1991) and by F. L. Black in Science, 258:1739–40 (1992).

  5 The quotation is from M. L. Cohen’s article in Science, 257:1050–5 (1992). Useful recent reviews of bacterial resistance to antibiotics are provided by J. P. W. Young and B. R. Levin in their article in Genes in Ecology, edited by R. J. Berry et al. (Boston: Blackwell Scientific, 1991) and by S. B. Levy’s The Antibiotic Paradox: How Miracle Drugs Are Destroying the Miracle (New York: Plenum, 1992). See also Rick Weiss in Science, 255:148–50. The use of antibiotics in livestock is discussed by S. B. Levy in The New England Journal of Medicine, 323:335–37, 1990. Our data on tuberculosis are mainly from B. R. Bloom and C. J. L. Murray in Science, 257:1055–64. The 1969 quote from the Surgeon General is in Bloom’s article. H. C. Neu’s work is in Science, 257:1064–73 (1992). The article by Ridley and Low is in The Atlantic, 272(3):76–86 (September 1993).

  6 Three examples of authoritative statements on an inevitable evolutionary reduction of virulence provide epigraphs for the first chapter of Paul W. Ewald’s book cited for p. 45. One not cited by Ewald is the distinguished population geneticist Theodosius Dobzhansky’s assertion that parasitism “is a form of relationship which is unstable in the evolutionary sense, and … it will tend to disappear and be replaced by cooperation and mutualism,” Genetics and the Origin of Species, 3rd ed. (New York: Columbia Univ. Press, 1951, p. 285). Genetic diversity of HIV within a host is documented by several writers in Science, 254:941, 963–9 (1991); 255:1134–7 (1992). Genetic diversity of a parasitic helminth population in a single host is documented by M. Mulvey et al. in Evolution, 45:1628–40 (1991). The data on fluke infections of fig wasps are in E. A. Herre’s article in Science, 259:1442–5 (1993).

  7 There is a large literature on the different effects of selection within and between populations. The special case of selection on parasites within and between hosts is modeled by R. L. Anderson and R. L. May’s book cited for p. 52. J. J. Bull and I. J. Molineux’s experimental verification of the expected increase in virulence of a virus that had its fitness decoupled from that of its host is presented in Evolution, 46:882–95 (1992). Other important works are R. B. Johnson’s in Journal of Theoretical Biology, 122:19–24 (1986), and S. A. Frank’s in Proceedings of the Royal Society of London, B259:195–7 (1992).

  8 Our favorite account of the Semmelweis story is the 1909 classic by William J. Sinclair, Semmelweis, His Life and His Doctrine (Manchester: The University Press).

  9 A good introduction to mimicry is provided by J. R. G. Turner’s article on pp. 141–61 of The Biology of Butterflies, edited by R. I. Vane-Wright and P. R. Ackery (London and Orlando: Academic, 1984). Works on molecular mimicry and related phenomena are cite
d for pp 43–44.

  10 Most of our information on the effects of novel environments on infection is from R. M. Krause’s article in Science, 257:1073–8 (1992). Detailed data on the Ebola virus are provided by P. H. Sureau’s article in Reviews of Infectious Diseases, 11 (4):790s-793s (1989).

  Chapter 5. Injury

  1 The quotation at the beginning of the chapter is from Chapter 6 of Mark Twain’s The Adventures of Huckleberry Finn.

  2 John Garcia’s classic work, with F. R. Ervin, is cited for p. 37.

  3 The work on monkeys’ conditioned fear of snakes is by Susan Mineka and collaborators in Animal Learning and Behavior, 8:653–63 (1980).

  4 Repair of mechanical damage is discussed by P. L. McNeil in American Scientist, 79:222–35, and by Natalie Angier in The New York Times, November 9, 1993, pp. C1, C14.

  5 Many of the special aspects of burn healing are discussed in Burn Care and Rehabilitation: Principles and Practice, edited by R. L. Richard and M. J. Staley (Philadelphia: F. A. Davis, 1994). See especially Chapter 5, by D. G. Greenhalgh and M. J. Staley.

  6 The trout-hatchery story and a general discussion of damage by sunlight are provided by Alfred Perlmutter in Science, 133:1081–2 (1961).

  7 UV-B effects on Langerhans cells are discussed by M. Vermeer et al. in Journal of Investigative Dermatology, 97:729–34 (1991). An epidemiological study of the increase in melanoma rates is provided by J. M. Elwood and collaborators in International Journal of Epidemiology, 19:801–10 (1990). A less technical discussion, with emphasis on immunological aspects of melanoma, is David Concal’s in New Scientist, 134:23–8 (1991). Interactions between the nervous system and Langerhans cells are discussed by J. Hosoi et al. in Nature, 159–63 (1993). The role of sunscreens in causing excess exposure to UV-A is discussed by P. M. Farr and B. L. Diffey in The Lancet, 1(8635):429–31 (1989). Eye damage by sunlight is discussed by L. Semes in Optometry Clinics, 1(2):28–34 (1991). The beneficial effects of sunscreen use are reported by S. C. Thompson and collaborators in The New England Journal of Medicine, 329:1147–51 (1993).

  8 The work of R. J. Goss in the Journal of Theoretical Biology, 159: 241–60 is a good introduction to the literature and current controversies on the evolution of regeneration.

  Chapter 6. Toxins: New, Old, and Everywhere

  1 Works by McNeil and by Angier, cited for pp. 69–70, are relevant to the sort of damage the whisky caused to Don Birnham’s stomach.

  2 An introduction to the work of Bruce Ames et al. is provided in a 1991 response by Ames and L. S. Gold to criticisms of their earlier work (Science, 251:607–8). Timothy Johns’ With Bitter Herbs They Shall Eat It (Tucson: Univ. of Arizona Press, 1990), reviews many aspects of human ecology in relation to plant toxins. It also details a fascinating history of human dealings with potatoes and their toxins, and of medicinal uses of plant toxins. A more technical work is Toxic Plants, edited by A. D. Kinghorn (New York: Columbia Univ. Press, 1979). An early but unexcelled review of chemical defenses in arthropods is by Thomas Eisner on pp. 157–217 of Chemical Ecology, edited by Ernest Sondheimer and J. B. Simeone (New York: Academic, 1970). The first serious discussion of trade-offs between chemical defenses and other values, such as rapidity of development, was by G. H. Orians and D. H. Janzen in the American Naturalist, 108:581–92 (1974). For a dramatic account of plant defenses, with details of electrical signaling and rapid adaptation, see Paul Simons’ The Action Plant (Boston: Blackwell, 1992). It includes a discussion of the role of aspirinlike hormones in plants.

  3 Our interpretation of nectar toxins is based on D. F. Rhoades and J. C. Bergdahl’s article in American Naturalist, 117:798–803 (1981).

  4 A dramatic account of the consequences of fungal toxins for human life is provided by Mary K. Matossian’s Poisons of the Past: Molds, Epidemics, and History (New Haven: Yale Univ. Press, 1989).

  5 The high incidence of PTC tasting in the Peruvian Andes is documented by R. M. Barruto and coauthors in Human Biology, 47:193–9 (1975). The study of oxylate kidney stones is that of G. C. Curhan et al. in The New England Journal of Medicine, 328:833–8 (1993). Our kidney-stone discussion is also based on that of S. B. Eaton and D. A. Nelson, “Calcium in Evolutionary Perspective,” in American Journal of Clinical Nutrition, 54:281s-287s. For a wide-ranging review of the evolution of chemical and other defense mechanisms, see D. H. Janzen’s article on pages 145–64 of Physiological Ecology: An Evolutionary Approach to Resource Use, edited by C. R. Townsend and Peter Calow (Oxford: Blackwell, 1981).

  6 Maize processing is described by S. H. Katz et al., in Science, 184:765–73(1973).

  7 The information on tannins in acorns and the detoxification of arum by cooking is from pp. 63–5 in Timothy Johns’s book cited for pp. 78–80.

  8 The toxicity of disease-resistant potatoes is discussed on pages 106–59 of Johns’s book cited for pages 78–80.

  9 Bacterial resistance to antibiotics in people with dental fillings is discussed by A. O. Summers et al. in Antimicrobial Agents and Chemotherapy, 37:825–34 (1993). Examples of unrealistic arguments on environmental toxins can be found in Biosphere Politics (New York: Crown, 1991) and other works by Jeremy Rifkin.

  10 The antiteratogen theory of morning sickness is presented by Margie Profet on pp. 327–65 of The Adapted Mind, edited by J. H. Barkow et al. (New York: Oxford Univ. Press, 1992).

  11 The reluctance of regulatory agencies to take fetal sensitivities into account is discussed by Ann Gibbons in Science, 254:25 (1991).

  Chapter 7. Genes and Disease: Defects, Quirks, and Compromises

  1 A recent general treatment of medical genetics is T. D. Gelehrter and F. S. Collins’ Principles of Medical Genetics (Baltimore: Williams &. Wilkins, 1990). A number of articles describing advances in the understanding of genetic diseases and progress in gene therapy were published in 1992 and 1993 in Science (256:773–313, 258:744–5, 260:926–32). For a vivid personal view of the development of modern medical genetics and wise commentary on its implications, we recommend James Neel’s Physician to the Genome (New York: Wiley, 1994). Another thoughtful treatment of the ethics of genetic counseling can be found in Genetic Disorders and the Fetus, edited by Aubrey Milunsky (Baltimore: Johns Hopkins Univ. Press, 1992); see especially the chapter by J. C. Fletcher and D. C. Wertz.

  2 Selection against unfavorable genes, their rate of loss by such selection, their expected equilibrium frequencies in populations, and related quantities can be related to one another algebraically, as explained by any textbook of population genetics, such as J. Maynard Smith’s Evolutionary Genetics (New York: Oxford Univ. Press, 1989). Our presentation in this chapter is greatly simplified. Huntington’s Disease, edited by P. S. Harper (London: Saunders, 1991), summarizes the history and epidemiology of this condition. It would be difficult to find a modern textbook of genetics or evolution that does not discuss the sickle-cell gene. Our favorite treatment is by Jared Diamond in Natural History, June 1988, pp. 10–13.

  3 Our information on G6PD deficiency is from an article by Ernest Beutler in The New England Journal of Medicine, 324:169–74 (1991). The quotation from F. S. Collins is from his article in Science, 774 (1992). Complications in cystic fibrosis genetics are reviewed by Gina Kolata in The New York Times, November 16, 1993, pp. C1, C3, and related evolutionary problems by Natalie Angier in The New York Times, June 1, 1994, p. B9. Contributions to the study of Tay-Sachs disease are offered by B. Spyropoulos and Jared Diamond in Nature, 331:666 (1989); by S. J. O’Brien in Current Biology, 1:209–11 (1991); and by N. C. Myrianthopoulos and Michael Melnick in “Tay-Sachs Disease: Screening and Prevention,” in Palm Springs International Conference on Tay-Sachs Disease edited by M. M. Kaback (New York: Liss, 1977). Our information on the human fragile-X syndrome is from F. Vogel et al.’s article in Human Genetics, 86:25–32 (1990). Jared Diamond has written a number of nicely reasoned articles on hidden benefits of genes that cause disease. Some of these are in Discover, November 1989, pp. 72–8, and in Natural History, June 1988, p
p. 10–13, and February 1990, pp. 26–30, Worthy examples of the voluminous literature on the genetic aspects of disease and health are Teresa Costa et al.’s article in American Journal of Human Genetics, 21:321–42 (1985), and in a group of five articles on anthropological aspects of genetic disease in American Journal of Physical Anthropology, 62(1) (1983).

  4 The effect of PKU on miscarriage rates is discussed by L. I. Woolf et al. in Annals of Human Genetics, 38:461–9 (1975). A recent statement of Richard Dawkins’ idea that a body is the genes’ way of making more genes is his The Selfish Gene, new ed. (New York: Oxford Univ. Press, 1989).

  5 The fitness effects of the T-locus in mice are discussed by Patricia Franks and Sarah Lenington in Behavioral Ecology and Sociobiology, 18:395–404 (1986). Medical aspects of mitochondrial DNA are discussed by Angus Clarke in Journal of Medical Genetics, 27:451–6 (1990). For general treatments of intragenomic conflict, see Leda Cosmides et al.’s classic work in Journal of Theoretical Biology, 89:83–129 (1981), and David Haig and Alan Grafen’s article in Journal of Theoretical Biology, 153:531–58 (1991).

  6 Familial and environmental aspects of cardiac malfunction are discussed by M. P. Stern on pp. 93–104 in Genetic Epidemiology of Coronary Heart Disease: Past, Present, and Future, edited by M. P. Stern (New York: Liss, 1984).

  7 Piggy’s extreme dependence on his glasses, and the tragic results of their damage and spiteful theft, are depicted in Chapters 10 and 11 of Lord of the Flies by William Golding. The quotation is from Chapter 11. The sudden emergence of myopia in the children of urbanized Eskimos is documented by F. A. Young et al. in American Journal of Ophthalmology, 46:676–85 (1969). General discussions of the genetics and etiology of myopia are provided by Elio Raviola and T. N. Wiesel’s article in The New England Journal of Medicine, 312:1609–15 (1985); by B. J. Curtin’s The Myopias (Philadelphia: Harper & Row, 1988); and by G. R. Bock and Kate Widdows in Myopia and the Control of Eye Growth (Chichester, New York: Wiley, 1990). A brief summary of recent research is provided by Jane E. Brody in The New York Times, June 1, 1994, p. C10.