214 DISCUSSION 



Simonsen: I have never been able to find it in mice. 



Hildemann: Is Dr. Simonsen's hypothesis not really a negation of 

 clonal selection theory, in the sense that all lymphoid cells are supposed 

 to be capable of reacting to strong isoantigens ? It seems to me that 

 once you admit that a given lymphoid cell is competent to respond to a 

 number of antigens, then clonal selection loses much of its merit. 



Simonsen: I hope I made it clear that the clonal selection in the 

 original version in which Burnet proposed it — that is to say, a hetero- 

 geneous population of immunologically competent cells consisting of 

 many small clones each with a different reactivity — seems to me very 

 difficult to fit in with these results ; whereas I think they fit well with 

 the modifications I have made of the concepts of Lederberg and Burnet, 

 i.e. that all immunologically competent cells are originally endowed 

 with the same reactivity but some reactivities are maintained better 

 than others, that mutational losses affect certain loci of spontaneous 

 activity more frequently than others, and therefore you do in fact end 

 up with a sort of heterogeneous population where all have to respond 

 to certain antigens, but to other antigens only some would respond. 



Medawar: The original Burnet hypothesis of the multiplicity of 

 clones was devised for, and had the merit of, explaining the pheno- 

 menon of immunological tolerance, which it does very simply and 

 neatly, but its subsequent modifications and readjustments lose that 

 virtue, it appears to me, without gaining any other virtues in 

 compensation. 



Simonsen: I think that the modification I have mentioned gives a 

 plausible explanation for why tolerance is induced with differential 

 ease, but of course it doesn't contribute at all to the basic question of 

 what tolerance means to the individual cell. 



Woodruff: Surely there is one very great gain from a point of view of 

 credibility in Simonsen's interpretation as distinct from the Burnet 

 "Mark I", in that it eHminates the Calvinistic element in Burnet, the 

 awful predestination of the cells ! 



Silvers: Most clonal selection theories of antibody formation are 

 expressed in terms ofgene mutation and I do not understand why this is 

 the case. As far as I am aware most biologists don't explain differenti- 

 ation in terms of gene mutations. I like to consider it in terms of the 

 segregation of cytoplasmic components which are unequally distri- 



