182 MUTATIONS 



various periods in human life for genetic hazard due to the exposure 

 to chemical mutagens. It is essential to establish, for example, whether 

 the fetal period is so important in the establishment of mutation (as 

 Dr. Atwood suggested the other day) that this would be a time for 

 concentrated antimutagenic efforts. It is very easy to take special 

 care to see that women in the first three months of pregnancy are not 

 exposed to mutagenic agents. This is a great deal simpler than worry- 

 ing about the exposure to all mutagenic agents throughout our life- 

 time. If, on the other hand, it turns out that this period in human 

 life is not so important after all, but is soon outweighed by the accumu- 

 lation of mutants in the germ line, it necessitates quite a different 

 approach. 



The only way to find this is to have some estimates of the numerical 

 terms, of the four terms in this equation, which represent four distinct 

 periods in human life. 



Novick: But isn't your clone inclusion going to be determined by 

 whether or not you are going to assume that mutations occur at a 

 constant rate per generation or per unit of time? 



Goldstein: Yes, and I have already made that assumption. 



Novick: If you assume per generation, the early period is going to be 

 very important. If you assume per unit of time, then all time will be 

 equally important. 



Goldstein: 1 think it won't turn out that way. Let's try to find what 

 actually is known about this. 



Neel: One point of clarification. Your m4 term refers to the divisions 

 of the meiotic cycle? 



Goldstein: Yes. 



Atwood: Two divisions. 



Goldstein: From the stem cell to the final sperm. 



Neel: Good. I didn't understand it that way. This is fixed, then, at 

 only two divisions. 



Lederberg: Not necessarily only two. This is the actual number of 

 terminal divisions of a cell which will give only spermatocytes as 

 progeny; that is, at a certain point, a stem cell will divide in such a 

 way that all the subsequent progeny of that cell become sperm, rather 

 than continuing to divide to maintain the stem line. That represents 

 the number of divisions after a cell leaves the stem line. I think that 

 is the best way to put it. It may be more than two; in fact, it probably 

 is. There is a little earlier time of determination. 



Neel: In any case, this is a small number. 



Goldstein: Let me ask a specific question. Do we know anything for 

 certain about the mean generation time in the stem line? 



