PROBLEMS OF MEASUREMENT OF MUTATION RATES 33 



Cotterman: I would say that this idea of what you call bi-specific 

 antibody is quite tenable. I have had some evidence of this in studies 

 of these bi-agglutinins on different animal species, and I believe it is 

 something you've got to find. 



Atwood: Scheinberg is not convinced that this idea is right. He 

 thinks it has something to do with the site number. By that, I mean 

 the number of agglutinogen sites per cell, which he assumes is greater 

 for human cells than for pigeon cells. Consequently, if this residuum 

 of isolated pigeon cells is a fraction having the lowest site number, so 

 that it is inagglutinable because of insufficient cell to cell binding, 

 then, if human cells are smaller and have more sites they might become 

 attached. 



Lederberg: There is nothing here that says that the two ends of the 

 individual lectin have to have different qualitative specificities. 



Atwood: No, not in Scheinberg's explanation. 



Freeze: Isn't it possible that the initial rise after the P^^ treatment 

 is due to the incorporation of the P^- into RNA, the subsequent decay 

 preventing the formation of A-antigen? After some time, new RNA 

 is made and the antigen can be produced again. 



Atwood: Yes, or if you say that it kills certain specific RNA 

 molecular species — 



Freese: No, it need not be specific. 



Lederberg: It may be some of the RNA in some of the cells. 



Atwood: The reason I would reject the idea at first is that this 

 implies that you would have killed the cell by a number of other means 

 as well. If you have enough P^^ activity in the RNA to prevent the 

 antigen synthesis, the cell probably would not mature since other 

 syntheses would also be blocked. But I see this is not necessarily 

 right. A certain proportion of the cells would escape all the other 

 damage and have only the antigen knocked out. Perhaps we are seeing 

 a small enough proportion to be accounted for in that way. 



Freese: There may be much more incorporation into RNA than into 

 DNA; thus transient effects may be more pronounced than killing. 



Lederberg: Much of this depends on the timing. When is the antigen 

 synthesized in the developing erythrocyte? 



Atwood: We don't know for man, although I think it could be 

 found out quickly. In the pigeon, the bone marrow cells of both 

 white and red cell series are equally agglutinable by Phaseolus as the 

 peripheral red cells, so there is no difference (34). The phenotype 

 runs throughout in the pigeon. 



Lederberg: It is probably not true of human leukocytes, is it? 



Atwood: I don't know. 



