220 MUTATIONS 



10"^ as the total probability of mutation per hour per sperm. Then, 

 using assumption 6a, and multiplying by the number of hours in 30 

 years (2.6 X 10'^), we obtain approximately 4 mutations per sperm 

 at the end of 30 years due to caffeine exposure. In terms of radiation 

 equivalent, we take 90 r per hour reduced by the same factor of about 

 100 to obtain 0.8 r per hour, which, on a 30-year basis, comes to about 

 200,000 r. Therefore, as you predicted, you come out with very high 

 estimates. 



Obviously, we are not to accept these estimates. I believe the main 

 trouble here was using time rather than cell divisions as a basis for 

 extrapolating from bacteria to man. Another trouble may be that we 

 have chosen this T5 gene which may be entirely inapplicable to the 

 situation in man's genes. 



Novick: In the same paper, there is the same T6 resistance, which 

 gives a figure ten times less than that. 



Atwood: So it's only 20,000 r; is that right? 



Goldstein: Yes, 20,000 instead of 200,000. 



Atwood: That's not much better. 



Goldstein: Perhaps we can do the other type of calculation based on 

 assumption 6b, and then compare the two results. 



Novick: I'm sorry, but I would like to make the further point that 

 this paper also described the effect of caffeine on bacteria growing 

 anaerobically. From these results you would have concluded that the 

 radiation equivalent of caffeine is negligible since X-rays are still very 

 mutagenic under anaerobic conditions. Here it appears that it de- 

 pends upon whether you view man as an aerobic coli or an anaerobic 

 coli. 



Lederberg: By what factor must you reduce the observed rate 

 aerobically? 



Novick: From 10 down to .5, a factor of 20, at least. 



Goldstein: To calculate the effect of caffeine per cell division cycle 

 rather than per hour, we proceed as follows. We start with the same 

 rate per hour in bacteria but with a generation time of approximately 

 5.5 hours. Per cell division, this gives a caffeine-induced rate of about 

 10"^. Reducing this by a factor of about 100, to get down to the mean 

 concentration of 1 mg/1 in man, we have approximately 10"^ induced 

 mutations per gene per cell per division cycle. 



This would be the value of p in the equation I presented this 

 morning (p. 180). Using the parameters derived there, we can 

 calculate a caffeine-induced mutant frequency of 0.15 per cent in sperm 

 or ova at puberty, caused entirely by exposure during the fetal period. 



