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THE HUMAN GENOME PROJECT: HAS BLIND REDUCTIONISM GONE TOO FAR? ALFRED I. TAUBER and SAHOTRA SARKAR* Introduction The Human Genome Project (HGP) is now well under way. An internationally coordinated effort, its ultimate aim is to sequence the entire human genome, producing a string of As, Ts, Gs, and Cs that would fill 13 sets of Encylopaedia Britannica [I]. This is the largest and most expensive biology project ever proposed, let alone undertaken. In the United States, where most of the effort has so far been concentrated, the program has been split between the Department of Energy (DOE), whose original interest arose from the possible utility of direct DNA analysis to detect radiation-induced mutations, and the National Institutes of Health (NIH) [2]. From its first conception, the feasibility and advisability of the project have been vigorously debated. After 3 years of discussion, an almost universal consensus has emerged in favor of a comprehensive mapping program to locate genes precisely on chromosomes (as opposed to total sequencing). This is expected to have immediate benefits for molecular studies of human genetic disease, especially for diagnosis (prenatal, preclinical, carrier), of single-locus, multifactorial , and chromosome disorders [3, 4]. Most would not argue the merits of that issue, but the question of complete sequencing is still to be resolved , since not all agree that such a goal "will yield a harvest of information that will drive the research enterprise for at least the next 100 years" [5]. The purpose of this article is, first, to evaluate critically the scientific merit of the project; second, to very briefly suggest that the project is the culmination of a research program within biology that, for 2 centuThis article is dedicated to the memory of Salvador Luria. It is contribution BTBG 91-1 from the Boston Theoretical Biology Group, Boston University. ?Departments of Philosophy, Pathology, and Medicine, Boston University, 80 East Concord Street, Boston, Massachusetts 02118-2394.© 1992 by The University of Chicago. AU rights reserved. 003 1-5982/92/3502-0776$0 1 .00 220 Alfred I. Tauber and Sahotra Sarkar ¦ Human Genome Project ries, has been fundamentally reductionist; and, third, to conclude that the doubts raised about the scientific merits of the project may well illustrate the limitations of such reductionist approaches in biology (and, perhaps even more strongly, in medicine) at present. This is not an exhaustive review of the history of HGP or of all the controversies surrounding its purpose, economics, or politics. These are already receiving systematic treatment [6—8] and are considered here only when directly relevant to this article's immediate aims. Fact, Fiction, and Fancy in the Scientific Aims ofHGP The main proponents of HGP have come from the top echelons of the molecular biology establishment. Some have been nothing short of elegiac about the project. For instance, James Watson has argued that sequencing the human genome is analogous to placing a man on the moon [9]. For such strident public advocacy, Watson has been rewarded with the czarship of the program, as it emerged as a somewhat coherent whole after fierce federal interdepartmental fighting between mid-1985, when it was first articulated as a realizable public objective [10], and late 1988, when some advisory committees were formed at the NIH [H]. Initially, the DOE and NIH vied for control of the project, but they eventually reached a compromise, encapsulated in an unorthodox "Memorandum of Understanding" [12] that explicitly recognized the DOE's interest in what, most naturally, should have been an NIH or NSF project. More important than such organizational compromises, by 1989 a consensus about scientific strategy had also emerged among the HGP's proponents. This consensus, presented as a report to Congress in January 1990 [13], was that sequencing the human genome was a worthwhile end, but that before the entire genome was actually sequenced, the next 5 years should be devoted to the construction of genetic linkage maps, physical maps, and DNA sequencing technique development. The linkage map is expected to identify and locate genes that are now recognized only by their phenotypic effects. In addition, assembly of the physical map appears to require the linkage studies, although the strategic order of these studies is...

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