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Unformatted text preview: Copyright 2004 by the Genetics Society of America Perspectives Anecdotal, Historical and Critical Commentaries on Genetics Edited by James F. Crow and William F. Dove Two Lessons From the Interface of Genetics and Medicine Anthony C. Allison 1 SurroMed, Menlo Park, California 94025 Thoughts are but dreams till their effects be tried. W illiam S hakespeare , The Rape of Lucrece W HILE growing up in Kenya, I became interested whereas in the majority of carriers sickling is observed only when blood is strongly deoxygenated in vitro , for in natural history, anthropology, and medicine. Natural history included Darwinism, and at Oxford Uni- example, in the presence of a reducing agent. The modern phase of research on sickle-cell disease versity after World War II, I learned what was then a novel concept: that natural selection results from began in 1949. Linus Pauling recalled how in 1945 he heard from W. B. Castle, a Harvard physician, about changes in gene frequencies in populations. The theo- retical basis of population genetics and of the effects of sickle cells and the need for deoxygenation to produce them. It immediately occurred to me that sickle-cell ane- selection had been provided by R. A. Fisher and J. B. S. Haldane in England and by Sewall Wright in the United mia must be a disease of the hemoglobin molecule. . . . the molecules line up to form long thin strands . . . States. My parallel interest was the diversity of indige- nous peoples in East Africa, who belong to several lin- which would cause the cell to be deformed into the shape of a sickle or crescent ( Pauling 1994, p. xvii). guistic and cultural groups. An attack of malaria forcibly directed my attention toward parasitic diseases and the This remarkable insight was confirmed when it was shown in his laboratory that hemoglobin (Hb) from need for doing something to relieve tropical maladies. The wish to participate in such a worthwhile task pro- patients with sickle-cell disease has a lower negative charge at physiological pH than does normal adult Hb vided motivation for a career in medical research. These rather diverse interests coincided to produce my first ( Pauling et al. 1949). The Hbs were designated S and A; the Hb from patients with sickle-cell disease was major scientific contribution, which was published in 1954, 50 years ago. nearly all of the S type (apart from a minor component of fetal Hb). In parents and siblings there was a nearly equal amount of HbS and HbA, leading to the conclu- THE DISCOVERY THAT SICKLE-CELL sion that they were AS heterozygotes, whereas the pa- HETEROZYGOTES ARE RESISTANT TO MALARIA tients were SS homozygotes. This interpretation was con- firmed by family studies published in the same year James Herrick, a Chicago physician, observed sickle ( Beet 1949; Neel 1949)....
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