Livemiore cosmid map of chromosome 19. now under construction. Tom Caskey 

 reviewed progress on understanding mutations in the HPRT locus, and Sherman 

 Weissman reviewed data on the HLA locus. David Botstein. as always exuding volcanic 

 enthusiasm peppered with sharp humor, speculated about pushing the restriction 

 fragment length polymorphism (RFLP) techniques to their limits — perhaps enough to 

 detect mutations in the range of 10^ per base pair per generation. Unfortunately, this 

 was still shy of what would be needed to detect mutations among the Hiroshima- 

 Nagasaki survivors, unless an unrealistically massive effort were mounted. Ray White 

 talked about applying RFLP methods to the Y chromosomes originating from a single 

 Mormon progenitor of 1850 (who by now has thousands of male descendants) to 

 examine changes in the part of the Y chromosome outside the pseudoautosomal 

 region — a part of the genome where changes should accumulate. 



Edwin Southern wound up the .scientific session by addressing the gap between 

 cytogenetic detection and molecular methods, and his presence was noted by more than 

 one participant as a moderating influence on the intellectual pyrotechnics. Southern's 

 discussion of measuring uv-induced mutations might be seen to presage the radiation 

 hybrid mapping methods brought to fruition in 1988 by David Cox and Richard Myers, 

 although the two approaches are quite independent in origin. 



Michael Gough returned from Alta to Washington to work on the OTA report on 

 detecting heritable mutations. The report had been requested by Congress in anti- 

 cipation that controversies over Agent Orange, radiation exposure during atmospheric 

 testing in the 1950s, and exposure to mutagenic chemicals might find their way to court, 

 where a neutral as.sessment of the technical feasibility of detecting mutations would be 

 essential. Gough directed preparation of Technologies for Detecting Heritable 

 Mutations in Human Beings until he left OTA in 1985 (U.S. Congress, 1986). Several 

 Alta participants served either as contractors or as advisory panel members for that 

 study. Charles DeLisi, then newly appointed director of the Office of Health and 

 Environmental Research at DOE, read a draft of this report in October 1985, and while 

 reading it first had the idea for a dedicated human genome project (DeLisi, 1988). The 

 Alta meeting is thus the bridge from DOE"s traditional interest in detection of mutations 

 to DeLisi 's push for a Human Genome Initiative, and provides one of several historical 

 links between genome projects and another massive technical undertaking of the 20th 

 century — the Manhattan project. 



Acknowledgements 



Thanks go to the many Alta participants and others who reviewed drafts of this 

 historical sketch — Elbert Branscomb, Charies Cantor, Charles DeLisi, Michael Gough, 

 Mortimer Mendelsohn, Richard Myers, Maynard Olson, David Smith, and Ray White — 

 and to those who helped provide background in interviews (see Ref. (4)). 



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