226 MUTATIONS 



criticism. We are permitted to believe, without indulging in utter 

 fantasy, that much or all of the spontaneous mutation rate in man 

 could be ascribed to caffeine; that this at least should generate some 

 concern that would motivate doing much more extensive tests for 

 mutagenic effect of caffeine in experimental situations closer to man, 

 for example, mammals such as mice, and, indeed, if there is anything 

 to this, even if a small fraction of residual effect can be extracted from 

 the calculations that are described here, we should be at least as 

 alarmed about caffeine as a mutagenic agent in man as we are about 

 radiation. 



There are many hundreds of thousands of people who are greatly 

 exercised and involved in radiation mutagenesis, and there are 

 possibly one, two, or three, if that many, people who are equally 

 involved in mutagenesis by these agents. 



I would like to make another point; that is, the argument runs in 

 another direction. Another very important contribution that Novick 

 and Szilard made in the same system was the discovery of anti- 

 mutagens. They could take untreated cultures and reduce the spon- 

 taneous mutation rate in certain loci by growing these organisms in 

 the presence of adenosine. If we are so concerned about mutagenesis 

 in man that we are willing to place serious constraints, at considerable 

 cost and political effort, on industrial development in order to save 

 the penalty of some few per cent increase over the background rate, 

 we are equally well committing a drastic sin of omission in neglecting 

 to conduct vigorous research on the possible reduction of the spon- 

 taneous rate by the use of such agents, which could accomplish very 

 much more. 



Russell: I thoroughly agree. And since there is some evidence, from 

 the Drosophila data cited here, that caffeine is mutagenic in spermatids 

 and spermatozoa, where no replication is going on, it should be worth- 

 while to test for dominant lethals in mice, both in males and females. 

 If an effect is found, then, first of all, it would confirm that caffeine 

 can act when there is no replication going on, and, at the same time — 



Lederberg: I think you would agree that this is a rather weak experi- 

 ment, and even if it showed no results whatsoever, the issue should 

 not be in any sense considered closed. 



Russell: Oh, certainly, a negative result would not rule out the 

 possibility of a mutagenic effect. But if the Drosophila results are 

 valid, something may show up in a dominant lethal test on mammals. 



Atwood: Isn't the radiation sensitive volume for dominant lethals 

 the biggest of anything that you can measure? 



