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ANCIENT GENOMES, WISE BODIES, UNHEALTHY PEOPLE: LIMITS OF A GENETIC PARADIGM IN BIOLOGY AND MEDICINE RICHARD C. STROHMAN* The reality (of disease) is the inability of one person's homeostasis, conditioned by his genotype and a lifetime ofspecial experiences, to maintain equilibrium; neither genes nor environment 'cause' disease, it is simply that the organism is unsuited for adaptive action in one, or several environments .—Barton Childs. [1] Introduction This review explores the possibility that the medical sciences are in crisis. Medical research has depended most heavily on a genetic view of life that has yielded remarkable progress in our understanding of the fundamental mechanisms of biology, including evolution. However, increased understanding of cellular, hereditary, and evolutionary mechanisms has progressively revealed important deficiencies in the genetic paradigm of biology. While cellular mechanisms now are amply understood , and further progress is expected, a mechanistic view alone will severely limit advances in our understanding of the cell or organism viewed at a behavioral level—viewed whole. Fundamental biological research is beginning to struggle with these limits and is seeking new The research for this report was supported by a generous grant from Health Net, an HMO, in conjunction with their development ofthe Wellness Lectureship at the University of California. The author thanks his colleagues for their creative comments on various phases of this review: professors Ranu Nandi, Harry Rubin, Terry Speed, Richard Steinhardt, and Leon Wofsy; Dr. Stewart Wolf for encouragement and wise counsel; Zorik Avanessian, Bryan Ellison, and Jon Wells who assisted in his class; Perspectives in Biology and Medicine, where much of the literature review initially took place; and professor Peter Duesberg for allowing him to see a prepublication copy of his review on oncogenes and HIV-AIDS and instructions on both. *Professor emeritus, Molecular and Cell Biology, University of California, Life Sciences Addition, Berkeley, California 94720.© 1993 by The University of Chicago. All rights reserved. 0031-5982/93/3701-0850$01.00 112 Richard C. Strohman ¦ Limits of a Genetic Paradigm conceptual approaches to the enormous complexity of living cells. In many ways, contemporary biology is rediscovering earlier insights about differences in complexity between living and nonliving systems, and is attempting to place individual genetic events in a larger cellular and organismal context [2—9]. At the same time large segments of applied medical and behavioral research continue to emphasize a genetic paradigm , continue to regard complex human phenotype as genetically derived , and have become somewhat estranged from the evolving views of mainstream academic research (see ref. [10] for examples of modern medical/genetic emphasis). This estrangement has had a negative impact not only on academic medical research and teaching, but on medical practice itself. Here we examine the basis for the separation of medical -oriented research from mainstream biology, and the influence of this separation on health and medical practice. Substantial evidence from diverse studies now points to the possibility that most human diseases in the Western world are manageable and that we are reaching a plateau in our attempts to extend life. Life span is a species constant [11, 12], and in the United States we appear now to be rapidly approaching a maximum life expectancy of age 85 [13]. Even the elimination of the most serious premature killers—cancer and cardiovascular diseases—is predicted to provide a mere two to three years of additional life for the population at large [14, 15]. Advances in molecular genetics are not expected to increase life expectancy because monogenic diseases remain stable at only 2 percent of total diseases, and because the afflictions of older people tend to be multifactorial, polygenic [16], and therefore ultimately beyond the reach of applied molecular genetics. That is to say, progeroid syndromes have a genetic basis fundamentally different from that of the simple monogenic diseases afflicting mostly younger people [17]. In the latter cases, but not in the former, modern molecular biology is seen as sufficient to provide a successful genetic analysis and even therapy based on a linear [single gene —» single disease] format [18, 19]. Gene doners, armed with advanced statistical devices, attempt to redefine common polygenic diseases in terms of genetic tendency [20-22]. Behavioral scholars of various backgrounds try to apply monogenic...


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