184 MUTATIONS 



value, 34; in other words, at 3400 days, which is ten years. That brings 

 us back to Dr. Atwood's statement that the events in the very early 

 fetal period are about equivalent to ten years of later life. 



However, if, as I have suggested, the mean generation time in the 

 stem line were 12 days, the position is entirely different. In one year 

 in the male, we have already reached the equivalent exposure that we 

 have in the fetal period, and everything after that is a continuous age 

 effect. It does make a difference in estimating the importance of the 

 exposure during the adult life. 



Novick: Or if it occurs at a constant rate per hour, which is the 

 opposite extreme. 



Goldstein: Now let us return to our equation and substitute into it 

 our known and assumed values for the several terms. We then obtain 



P = y2 (30 + 400 + t/12+4 ) (10^) p 



in the male, and 



P = y2 (30 + + 0+2) (lO-*) p 



in the female. 



If these terms are even approximately correct, it follows that in the 

 male the contribution of events during fetal life is very small com- 

 pared with later events. This is true even at puberty, and the signifi- 

 cance of what happened during fetal life becomes even less by the usual 

 reproductive age. Moreover, the contribution of the period during 

 which a sperm clone develops from the stem line is entirely negligible. 

 The equation predicts a strong age dependence for the frequency of 

 mutant sperm. Even if the estimate of stem cell generations during 

 childhood were greatly exaggerated, the contribution of the first post- 

 pubertal year would equal that of the fetal period and the same age 

 dependence would subsequently be seen. In the female, on the other 

 hand, the dominant contribution is from the fetal period, and no age 

 effect whatsoever should be manifested unless, indeed, an unrecognized 

 stem cell mechanism is operative in the female as in the male. It should 

 perhaps be emphasized again that I am speaking only about mutagens 

 whose action is upon the replication or division process. 



There is a point that I wanted to bring up in connection with the 

 question of the female oocytes remaining dormant for many, many 

 years. One could ask the question whether, during this period, there is, 

 in fact, turnover of DNA or some kind of continuing replication and 

 degeneration of cells. There is a recent paper by Bennett and Skip- 

 per (9) demonstrating the conservation of DNA in the liver and brain 



