218 MUTATIONS 



that you find in bacteria is the same time scale that we are to apply 

 to man, or whether the time scale is in some way linked to the 

 division time in bacteria. This is a very important aspect. If it is really 

 per hour, as will be shown in the next calculation, one gets extremely 

 high estimates for the effect of caffeine in the 30-year exposure in man. 



Lederberg: Isn't it a question of the mutation rate in man, expressed 

 per cell per hour, compared with the mutation rate in bacteria per cell 

 per hour, for the range of mutations you are concerned about? 



Novick: Not for the range. Josh, but for the mutation you're talk- 

 ing about. 



Lederberg: If you have information to suggest that the radiation 

 equivalence for caffeine differs widely from the different loci in bac- 

 teria, that would have to be taken into account. 



Novick: Yes, we do. 



Lederberg: We would then have to concern ourselves with not only 

 the over-all mutational rate, but also with the mutation spectrum of 

 human tissues compared to the bacterial situation. I think we're al- 

 ways more concerned about those that occur frequently. As long as any 

 substantial fractions of mutation rates are at the high range, the 

 problem hasn't changed one bit. 



Benzer: You can at least calculate the mutation to T5 resistance in 

 man. 



Novick: Right, or T6. I think the thing here is that one will come 

 out with an embarrassingly high figure for mutational equivalence. 

 The important thing right now is that I don't want to see that as the 

 basis for assuming the spermatogonia are not sensitive to mutagenesis 

 during the adult period. 



Goldstein: I still don't feel we have reached a clarification of this 

 matter of time. If you propose that the effect of the mutagen is per 

 hour, per cell, and you then propose to take that same figure per 

 hour, per cell — forgetting for the moment whether the gene you chose 

 is a good one or a bad one — are you going to transfer that to man 

 and say that the estimate is likely to be the same per hour per bac- 

 terial cell as per spermatogonial cell, or are you going to translate 

 it into a time scale that would make the hour in bacteria equivalent to 

 ten days in man or something like that? 



Novick: The absolute value has no meaning. What we compare is the 

 ratio between the spontaneous mutation rate and the induced mutation 

 rate. We are going to compare the mutation rate produced by caffeine 

 with that produced by X-rays, but its actual value has no meaning. 



Neel: Would it not be appropriate to let Dr. Goldstein go ahead 



