Discussion 195 



However, we know that with auxotrophic mutants you can get not only 

 mutations giving rise to an all-or-none appearance or disappearance of 

 an enzyme, but also mutations causing wide quantitative variations in 

 the amount present, and other mutations causing qualitative variations 

 in the value of an enzyme. Hence, the number of loci affecting resistance 

 to a given drug does not have to be nearly as large as the number of 

 steps of resistance that can be distinguished, since various alleles at a 

 single locus could be expected to produce different degrees of resistance. 



Cavalli-Sforza : There is a widespread impression that the gradual type 

 of adaptation is likely to be physiological rather than genetic. I tend to 

 hold another view : I don't see any reason why the gradual adaptation 

 should be easily physiological. Dr. Demerec, in the early stages of his 

 work when he started the genetic analysis of bacterial drug resistance, 

 called the gradual and the abrupt types of adaptation "penicillin and 

 streptomycin patterns". Whether some drug tested on some organism 

 is going to show one or the other pattern depends entirely on the relative 

 frequency of the various types of resistance mutations that can occur. 

 If mutations that have a small effect are more frequent, then you are 

 more likely to have the penicillin type, i.e. the gradual type of adapta- 

 tion; and that is likely to be the most frequent case, because it seems 

 reasonable to expect that mutations having small effects are more fre- 

 quent than those having large effects. There has been an accumulation 

 of data showing that gradual adaptation also is indeed of genetic origin. 

 There is evidence from indirect selection, such as the data on 

 chloramphenicol resistance — first step only — and Yudkin's evidence on 

 multistep adaptation to proflavine, which shows that in the case of the 

 chloramphenicol and proflavine systems of "gradual" adaptation you 

 do have genetic adaptation. There is all the evidence from recombina- 

 tion, and transformation data, showing that "gradual" adaptation is 

 due to nuclear genes having small effects, which effects can add together 

 to give a big one ultimately. 



Hotchkiss : We have studied what we call lysis transformation, in a 

 mixed culture having penicillin-sensitive organisms which were strepto- 

 mycin-resistant, mixed with penicillin-resistant organisms which were 

 streptomycin-sensitive. When this mixed culture was grown in peni- 

 cillin, the penicillin-sensitive cells were killed. Thereupon they lysed, 

 DNA was released, and this DNA interacted with the surviving resistant 

 culture so that streptomycin resistance was introduced into that culture. 

 Therefore, we had a compiling of information; when these cells died, 

 they passed on a high proportion of their information. Now consider 

 what couM happen if this were one of the cases such as Prof. Cavalli- 

 Sforza has seen, for let us say a drug which kills. Suppose one compo- 

 nent is penicillin-resistant to 5 [ig. and another is penicillin-resistant to 

 10 [ig. If we introduce 10 [ig. of the drug, the former will be killed, and 

 if these are independent factors, there could now appear transformant 

 "tens plus fives", that might well be resistant to 200 ij.g. This would 

 now be a mechanism for fairly efficient compilation, within a culture, of 

 all the properties that were present. If we bear in mind that some of 

 these might be of the latent type, they would not be easily recognized 



