154 MUTATIONS 



are 1 and 2, and the original was AT and responded in a certain way, 

 giving a certain mutation pattern with your chemicals, when you 

 change the neighbors this may alter the pattern. 



Lederberg: Indeed it should, and there should be two alternatives, 

 you see. There should be no more than four patterns all together. 

 Using the very subtle criterion — and you have indicated how subtle 

 it is, because there are no fewer than 25 conceivable possibilities of 

 the pattern of response to the whole battery of tests — 



Goodgal: But his prediction is that there will be more than four. 

 Atwood: Oh, no! 



Lederberg: If there are more than four, they are not nucleotide 

 substitutions. 



Zamenhoj: The effect of neighbors, Seymour, could be the presence 

 of clusters of purines or pyrimidines which may exist in nucleic acid. 

 That is why I asked you the question before as to whether you ob- 

 served any mutation from coldness to hotness. Is it as easy to produce 

 it as it is an ordinary mutation, or do you need several mutational 

 steps to change this pattern from coldness to hotness? If you find that 

 you never observe such mutations, that may mean that the change 

 necessary to produce this effect may really be a very complex one. 



Benzer: I think what you are proposing is that we start with the 

 standard type, and you want to pick up a mutant which is going to 

 affect the mutation rate at a neighboring point — is that right? 



Zamenhoj: No, I am asking how easy is it to change the chronic 

 cold into chronic hot. Is the change as frequent as ordinary mutation? 

 Benzer: How do you propose to change it if not by mutation at other 

 points? 



Zamenhoj: Yes, but perhaps you need mutation at many points, and 

 therefore such a change from cold to hot would be rare. 



Benzer: If these changes themselves give you a mutant, you cannot 

 detect the occurrence of an additional adjacent mutation, except by 

 testing every single particle genetically against every other one. If 

 they themselves do not register as mutants, they are invisible. 

 Zamenhoj: That's what I mean, invisible mutation. 

 Atwood: You could guess that a point might be subject to invisible 

 mutation by seeing that its mutants form only two reversion classes 

 instead of three. Then, you could infer a fourth state that is wild type, 

 like the first one. Both wild-type states should occur among the 

 revertants, so if a case of this sort were found it would be worthwhile 

 screening the revertants for hotness in nearby sites. 



Benzer: If I understand you. Dr. Zamenhof, the reason you propose 

 this is as a direct demonstration of neighbor interaction. 



