206 Discussion 



I am, however, quite happy about the phage Tl, which rapidly kills 

 sensitive cells. 



Lederberg: An analogous example may be seen in that if you take 

 diploids which are heterozygous for streptomycin resistance and sensi- 

 tivity, these can be prevented from measurable growth by about 5 

 units of streptomycin. Nevertheless, if those cells are plated in medium 

 containing that level of streptomycin, there is an appreciable yield of 

 segregants, which are streptomycin-resistant, and can grow out, which 

 suggests that they can escape into this new genotype, so to speak. 

 What I am not certain of here is how precisely that multiplication is 

 inhibited. 



Hayes: The only way to work with sodium azide in this kind of 

 experiment was to make the assumption that a dose which inhibited 

 division of the sensitive parent also prevented further development of 

 the heterozygote. I quite agree that this assumption may be incorrect. 

 The only check was that on an agar slide, with the drug included, no 

 multiplication of any sensitive cell was observed. 



Lederberg: With phage the action is all-or-none, i.e. you have a bac- 

 tericidal effect of phage if it is absorbed at all. 



Pollock: It would be interesting to do this kind of analysis with a 

 mutation which involves loss of the power to form an enzyme. You 

 postulated there being a dilution out of an enzyme after it ceased to be 

 produced. It is quite possible that, following a loss mutation, there 

 might arise an inability to form an enzyme-forming system ; which would 

 mean that it would be the enzyme-forming system rather than the 

 enzyme molecule which would be diluted out, and it might take a very 

 long time indeed before cells lost their resistance. 



Hayes: The trouble about this kind of experimentation is that you 

 are restricted to certain characters; for instance, you could not esti- 

 mate the phenotypic expression of sulphonamide resistance under these 

 circumstances because, as Hotchkiss has already pointed out, the cells 

 can still continue to divide after application of the drug. You must have 

 something at the very least which will stop any further division. 



Lederberg: Have you some information on the expression of strepto- 

 mycin resistance? 



Hayes: No, but we are going to study this. 



Davis: There are some definite advantages in using streptomycin, in 

 that it is the one agent that is bactericidal without any growth of the cell. 

 In addition, the rate of bactericidal action increases practically linearly 

 in proportion to the concentration of the drug. 



Hayes: Yes, it is ideal; and there are also Lederberg's results with 

 diploids to serve as comparison. We just have not been able to obtain an 

 Hfr strain yet which will transfer the streptomycin locus to the zygote. 



Davis: Are you at all surprised at the speed with which the phenotypic 

 delay is overcome in these cases? For instance, in phage resistance 

 presumably a cell is resistant when it no longer has on its surface any 

 units which the phage can attack. And from electron micrographs a 

 sensitive cell appears to have a great many such units. Yet you find that 

 resistance is phenotypically expressed within a generation or two. This 



