216 MUTATIONS 



lower organisms. We have no data in man. If we are going to try to 

 make any extrapolations, it will have to be done on assumptions that 

 we know are false. The alternative is to stop here until we get evidence 

 in man. I think nobody would suggest doing that. 



Freese: But you don't have to make these assumptions. If you merely 

 make the assumption that the genetic material in different species is 

 equal or similar, and if you make the further assumption that the 

 enzymatic pool of different species is similar, that is sufficient. 



Lederberg: I have suggested a solution; that is to say, to put the 

 dilemma, to start with, in so far as these considerations bear on the 

 estimation of caffeine mutagenesis — 



Benzer: Assumptions that don't bear on the question should be cut 

 out. 



Lederberg: Perhaps so. 



Benzer: Why perhaps? What is the point of an assumption? 



Neel: May I suggest that we permit Dr. Goldstein to develop his 

 argument and then attack him when he has built up his case? In my 

 opinion, he has been unusually careful in setting forth his assumptions, 

 and they are no more nor less than have been employed frequently in 

 the past ten or twenty years in making certain extrapolations. 



Benzer: The conclusions would be no more valid, by the same token. 



Goldstein: The fourth assumption is one that I mentioned earlier — 

 that caffeine mutagenesis is a linear function of dose. We have to 

 postulate this, because all the evidence that we have from lower 

 organisms is obtained at a concentration which is orders of magnitude 

 higher than the concentrations of caffeine to which man is exposed. 



Novick: I think the assumption is a good one, because our experi- 

 ments showed that it is linear down to 10 mg/1 and extrapolates 

 through zero, 



Goldstein: I think that there is at least some evidence on assump- 

 tion 5. It is probably true that caffeine has free access to the gonads, 

 at least in the adult gonads and possibly in the fetal, although our 

 data on this are still incomplete.* 



For assumption 6, there are two alternatives. One is that the effect 

 of caffeine exposure is linear with time, regardless of replication cycles. 

 My comment is simply that this probably is true of chemically reactive 

 agents which have been demonstrated to be mutagenic in vitro, but it 



* Addendum : We have now shown that caffeine equihbrates freely between 

 blood and gonads in the human male and female, and also that the concentration 

 of caffeine in the human fetus at 6 to 8 weeks gestation is the same as in maternal 

 blood plasma. Goldstein, A., and R. Warren. Passage of caffeine into human 

 gonadal and fetal tissue. Biochem. Pharmacol, in press (1962). 



