42 Discussion 



instance that mutants have to multiply in competition with the wild type. 

 This is not a gratuitous assumption, it is something which you can test 

 directly; if the mutant multiplies much more slowly than the normal, 

 then the method is difficult to apply. 



Lederberg: A control is needed in such a case, i.e. an artificial recon- 

 struction of a mutant which you know was produced ; you then put it in 

 with the wild type to show that 3^ou can select it under those conditions. 

 If you then fail to obtain similar mutants without making artificial 

 mixtures you can conclude that no mutants of that type are present in 

 untreated cultures. I emphasize of that type, because this consideration 

 of differential growth rate might still come in, but you would certainly 

 have to stretch the genetical hyjiothesis quite far to get selection. 



Yudkin: Prof. Cavalli-Sforza said that mutants would be expected 

 necessarily to be at a disadvantage, compared with the natural types. 

 When we are dealing with drugs like some of the antibiotics which may 

 occur in nature, it is reasonable to suggest that the resistant mutants 

 grow more slowly than the wild type, for otherwise the sensitive strains 

 would have disappeared at some time. But when we are dealing with 

 drugs like proflavine, which the bacteria are most unlikely to have 

 encountered in nature, then there is no reason to suppose that the 

 resistant mutants have a gro^vth disadvantage. 



Cavalli-Sforza: I don't think that the fact that the particular strain 

 has had experience before of one particular drug is very important. 



Any mutation that arises in an otherwise homogeneous population of 

 cells has a fitness value relative to the normal type, which of course 



^ W ^ \ r ^ \ rr 



Fig. 1. (Cavalli-Sforza). An oversimplified picture of the 

 process of genetic adaptation taking place automatically in a 

 culture kept under fairly constant conditions, in terms of the 

 distribution of fitness values of mutations arising in tlie popu- 

 lation at various stages. It shows why most mutations are 

 likely to be "unfavourable." The abscissa gives tlie fitness 

 value of a mutation; the ordinate, the frequency of mutations 

 having given fitness values. Arrows indicate the lapse of 

 generations. The stippled area represents the proportion of 

 mutations which are "favourable", i.e. have positive fitness; 

 the white area the proportion of "unfavourable" ones. 



depends on the specific environment considered. Different mutations 

 will presumably show different fitness values; a few may have a fitness 

 value of zero or nearly so (if we thus describe the absence of advantage 

 or disadvantage in respect to the normal type, e.g. the mutant grows and 

 dies at the same rate as the normal) ; others may have a positive fitness 

 value (i.e. they are "favourable" mutations), and the rest a negative 

 fitness value ("unfavourable" mutations) (Fig. 1)*. If a bacterial strain 

 * For greater clarity Fig. 1 was added in proof. 



