224 MUTATIONS 



being given? You would, presumably, give us two different doubling 

 doses, according to the rate — 



Russell: I wouldn't give you a single one, to begin with. I think 

 you would have to get one for each locus, and then you would be 

 subject to the possibility of qualitative differences. It seems to me, 

 until we know a good deal more, we may be talking about doubling 

 the frequency of apples when we are measuring oranges. 



Lederberg: Are you suggesting that we should ignore the problem of 

 radiation mutagenesis in man? 



Russell: Not at all. 



Lederberg: I thought not. 



Russell: I think we should talk in terms of absolute effect, the effect 

 produced by radiation. At the present time, it is very hard to relate 

 this quantitatively to the spontaneous rate. 



Glass: Theoretically, Bill, I think your position is wrong. What you 

 are really saying is that we have no basis for arriving at an average 

 figure, but a population of mice or human beings which is sensitive to 

 radiation must have some over-all doubling dose. 



Atwood: Certainly, an acute irradiation can't have a doubling dose, 

 because you would have to choose at w'hat age you would want to take 

 the spontaneous mutant frequency to be doubled, and, if it is 

 different with ages, as we think it must be — 



Russell: Let me give you another example. One of the estimates of 

 doubling dose that has been used is based on irradiation of Drosophila 

 spermatozoa. In the mouse, we find that irradiation of spermatozoa 

 gives a high frequency of deficiencies which involve two closely 

 linked loci in our test. We haven't found any spontaneous occurrences 

 of this kind yet, so the doubling dose for this particular effect must be 

 extremely low. 



Here we have a type of mutation which, in spermatozoa, is easily 

 induced, but which has not yet been observed to occur spontaneously. 

 I think we need to know a good deal more before we can compare 

 radiation-induced and spontaneous mutation in a meaningful way. It 

 is highly misleading, I believe, to try to put our present inadequate 

 knowledge into one single doubling dose estimate. 



Neel: Does that answer your question. Dr. Novick? 



Novick: Yes. 



Lederberg: I think we all understand the problem. 



Russell: With regard to tests of mutagens in mice, I should like to 

 say that some experiments would not be tedious. If a chemical muta- 

 gen is hkely to do whatever it is that causes dominant lethals, we have 



