234 MUTATIONS 



he pointed out that the extent of exposure and time of exposure arc 

 very heterogeneous in our population. But his main thesis was that 

 we can already prove that substantial contribution to spontaneous 

 mutation rate can be pinned down to certain chemical mutagens and, 

 in particular, caffeine. 



Goldstein: I didn't say that we could assert that. I said that this was 

 a possibility. 



Zamenhoj: All right, it is a possibility. Later, he tried to develop a 

 formula for calculating to what extent spontaneous mutation rate 

 could be accounted for by chemical mutagens; there were several 

 assumptions necessary in developing such a formula and therefore 

 this formula was subject to criticism. Nevertheless, it does not appear 

 doubtful that the greatest danger would be during sensitive periods in 

 pregnancy; in females after birth there seemed to be less danger, 

 whereas in males, the danger is before birth as well as after birth, and 

 of course, we don't know which of the two periods is more impor- 

 tant. 



Dr. Goldstein then classified drugs as to the extent of exposure, and 

 divided them, rightly, into three categories: drugs to which people 

 are exposed only occasionally and briefly ; those to which special 

 groups of people are exposed for long periods of time but other people 

 not at all; and those to which practically all the population is ex- 

 posed, for a long time. 



Then a most interesting discussion developed, which I would like 

 to quote here because it clarifies much of our thinking. Dr. Goldstein 

 invited Dr. Novick to devise a standard test for estimating the danger 

 of chemical mutagens, but Dr. Novick has declined the invitation 

 because there could be no such standard test ; further discussion showed 

 why there could not be one. 



Dr. Atwood suggested that the least we could do was to test whether 

 a given chemical was radiomimetic, and Dr. Glass suggested that we 

 use tissue culture for this purpose, as he already has done for yS- 

 propiolactone. Dr. Neel pointed out that we all agree that human tissue 

 would be the best, but human tissue is the most difficult to study. The 

 problem here, as presented to Dr. Novick, was whether we could find 

 any other system, such as a bacterial system, which could serve as a 

 good test system, though one realizes that there are difficulties in extra- 

 polating from bacteria to man. 



Dr. Lederberg suggested that, just for a list of suspected chemical 

 mutagens, the use of Novick and Szilard's chemostat seems to be most 

 appropriate, but no more than for a list of suspects. Human tissue 

 should be used and should be of more value, but there is another 



