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DISCUSSION 



Hayes: \Vliat was the mutation rate at the lower level of selection, 

 i.e. at 30 [xg./ml.? 



Gyorffy: That was 2-5 X 10-«. 



Stocker: In the case where you used low concentrations to screen, so 

 that a high proportion of the colonies formed were "persistors", i.e. they 

 were not resistant on retest, did you find any evidence of fluctuation, i.e. 

 was there marked variation between replicate cultures grown from small 

 inocula, as to number of persistor colonies formed ? One theoretically 

 possible explanation for persistors is that they are cells which result from 

 a mutation-like process which occurs very rapidly in each direction, so 

 that there is correlation, persisting for a small number of generations 

 only, between the phenotypes of the parent and the descendants; in 

 which case one might perhaps expect to find some degree of fluctuation 

 in a test of that sort. 



Gyorffy: We did not observe fluctuation; but mostly we used the 

 higher degree of resistance, because repeated retesting gives rise to a 

 great deal of difficulty at lower concentrations. 



Cavalli-Sforza : Dr. Stocker's remark might be amplified by saying 

 that not only a high back-mutation rate, but also a low selective value, 

 i.e. a low growth rate of the mutant might easily be responsible for 

 unstable resistance. It is important to think in terms of gro\vi:h rates also, 

 because that is so much more likely to be effective from the kinetical 

 point of view than the mutation rate. 



Knox: We have heard a great deal about the role of DNA in deter- 

 mining genetic characteristics and so on, but we have not heard anything 

 about the role of the protein in the gene. Is it the view of the geneticists 

 that a gene is a naked DNA or that it is a DNA with some protein fitted 

 to it in some specific way? If so, it is conceivable that a good deal of this 

 controversy as to what is an unstable mutant and what is an adaptive 

 change might actually be due to some change occurring in the protein 

 part of the gene itself. If that were the case, then the DNA in such a 

 system might be normal, but there might be not just a purely adapta- 

 tional change in the enzyme of the cell, but some change in the protein 



