and 5, 1984. in Hiroshima, at which new DNA analytical tools were deemed second 

 highest priority for human mutations research, just behind establishing ceil lines from 

 atomic bomb survivors, their progeny, and controls. Those attending the Alta meeting in 

 December (see Table 1 ) were drawn from a variety of backgrounds, and many had 

 never met each other. Most said in interviews later that they came to the meeting quite 

 skeptical, but left thinking it had been one of the best scientific meetings they ever 

 attended (Interviews, 1987. 1988). 



The principal conclusion of the meeting was. ironically, that methods were incapable of 

 measuring mutations with sufficient sensitivity, unless an enormously large, complex, 

 and expensive program were undertaken. Technical obstacles thus thwarted attainment 

 of the main goal of the meeting, yet the meeting left a profusion of new ideas in its 

 wake, some of which later washed ashore to be incorporated into various genome 

 projects. Five years later, there is still no sensitive assay for human heritable mutations, 

 but there are genome programs at NIH. at DOE, and in several foreign nations. 



Excitement about the new methods blossomed at Alta despite, or perhaps because of, 

 the wintry isolation. As Mortimer Mendelsohn noted in his internal report to DOE: 



It was clear from the outset that the ingredients for a successful meeting [were 

 present]. . . and the result far exceeded expectation. Once the point of the 

 exerci.se was clear to everyone, a remarkable atmosphere of cooperation and 

 mutual creativity pervaded the meeting. Excitement was infectious and ideas 

 flowed rapidly from every direction, with many ideas surviving to the end. 

 (Mendelsohn, 1985). 



John Mulvihill began the meeting by reviewing epidemiological studies of human 

 mutations. Studies that could theoretically have detected a threefold increase in 

 mutations had not found any. James Neel spoke about measurement of mutations among 

 Hiroshima-Nagasaki survivors, estimating that the likely mutation rate was 10 '^ per 

 base pair per generation (or roughly 30 new mutations per genome per generation), 

 indistinguishable from that of Japanese controls and in the same general range as that 

 estimated by epidemiological methods and detection of protein variants among other 

 "normal" populations. Several of the technical consultants commented on the passionate 

 devotion Neel brought to the study of Hiroshima and Nagasaki victims, and how his 

 demeanor set the tone for lively and cooperative exchanges throughout the meeting. 



Existing methods had failed to detect an anticipated increase in mutations among the 

 more than 12.000 children of Hirsohima-Nagasaki survivors (whose parents received an 

 average 43 rad). Calculations showed that to measure a 30% increase in the mutation 

 rate, roughly what would be expected from the average dose, one would have to 

 examine 4.5 x 10'" bp in the children, and 4 to 5 times more in the parents (Delahanty, 

 1986). In fact, the DNA methods were at least an order of magnitude short of being able 

 to detect the expected impact from atomic bomb exposure among survivors; they could 

 only detect differences expected from radiation exposure well above the lethal dose 

 (and hence not measurable). The question was whether there were new technical means 



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