PROBLEMS OF MEASUREMENT OF MUTATION RATES 35 



given red cell has the P^- decay taken place in relation to when you 

 see it in the aberrant cell? 



Atwood: I have been told that nearly all the P^^ effect is ac- 

 complished in the first week after injection. 



Lederberg: If you put in effect a pulse, then how long after that do 

 you first see the aberrant cells? 



Atwood: About two weeks. 



Lederberg: I mean, at what stage of development were these cells 

 at the time the P^- was put in? 



Atwood: Probably near the end, because they appeared in two 

 weeks or less. I don't know how much less, but in about two weeks 

 there was an elevation of the exceptional cells. 



Lederberg: So it is not unreasonable that this is a time of determi- 

 nation of the surface antigen, either with disintegration in RNA or 

 DNA, for that matter. You may be getting chromosome breakage 

 effects such as Pardee was talking about (21). 



Atwood: Well, chromosome breakage is a leading hypothesis. It 

 would explain it perfectly if we had not done the experiments with the 

 Dolichos. 



Lederberg: No, that's not out, either, because you had a cell that 

 was just starting to make Ai, and Ao was then the stage in the 

 amount of the production of Ai. 



Atwood: Yes, that would explain it; that amounts to a hypothesis 

 about the formation of the antigen. I don't know whether or not Ai 

 is made by finishing off an A2. 



Lederberg: Well, Ao may be a lot of Ai, or conversely, Ai may be a 

 lot of Ao, but in either case you could get this result by doing a com- 

 plete job of manufacture. 



Auerbach: Wouldn't you then need selection against them, because 

 this peak disappeared? 



Lederberg: Well, these are the cells, and this is a phenotypic effect. 

 This is not taking place in the stem line, you see. 



Atwood: The nice thing about chromosome breakage is that you 

 could imagine that the cell with chromosome losses might still be 

 able to mature from within the clone leading to red cells, but not be 

 able to survive in the stem line. 



Neel: Isn't there a complication in the quantitative treatment of 

 this problem that has not been mentioned? 



Atwood: What is that? 



Neel: The maximum anemia in a polycythemic following treat- 



