Discussion 293 



types of rearrangement that are changes in quahty of existing material. 

 Is that a fair statement, Prof. Westergaard? 



W ester gaard: That is a fair statement. 



Hughes: Reverting to mutation in bacteria from mutation molecules, 

 I have got the impression that Lederberg believes that mutation may be 

 increased by organisms being sent through the long form or the L cycle. 

 I also think that is probably so. Do you hold the view, Prof. Lederberg, 

 that the mutagenic agents do in fact send organisms through that cycle 

 and that that does increase mutation rates? Certainly, some of the 

 chemotherapeutic agents would then fit in very nicely. 



Lederberg: I have questioned whether the action of any mutagenic 

 agent has to be considered as the immediate consequence of a chemical 

 reaction between a molecule of a mutagen and a specific nucleotide in 

 the DNA strain, or whether there is a somewhat more general pathology 

 of the cell during the recovery, from which you may get chromosome 

 breakage or other alterations. I do not insist that these are mutually 

 exclusive alternatives; to a very large degree the question is still open 

 as to the exact timing of localization and fixation of mutagenic effects. 



Knox: If antibiotics are capable of acting as weak mutagenic agents, 

 is there any information about the effect of antibiotics on a whole range 

 of mutations in bacteria ? For example, if you take a fairly mutagenic 

 concentration of streptomycin, does it increase mutation rates? 



Westergaard: This has l3een shown in the case of streptomycin by 

 Japanese workers {see Sevag, Reid and Reynolds (1955), loc. cit., p. 85; 

 also Christensen, J. J. (1956), In Antibiotics and Agriculture, Pm6?. 

 Nat. Acad. Sci., Wash., 397, 73). 



Knox: Does this depend on the sensitivity of resistance of the bacteria? 



Westergaard: That was not studied, but it is an interesting point. I 

 should like to try it with azaserine. 



Lederberg : It is quite clear that there are types of metabolic disturb- 

 ances which can greatly influence mutation rate, and which therefore by 

 extension might apply to certain antibiotics. For example, the mutant 

 strains of Esch. coli which are defective in the synthesis of thymine, and 

 may be grown under conditions of thymine deprivation, have a very high 

 rate of mutation for all sorts of biochemical deficiencies and reversions 

 as well. One can easily imagine equally non-specific metabolic inter- 

 ferences by antibiotics. Newcombe found a rather small mutagenic 

 effect of streptomycin for phage resistance. 



Westergaard: There is also the Japanese work. Is there any evidence 

 of phenocopies being induced in bacteria by different treatments ? 



Lederberg: I myself have been guilty of using the term once for the 

 suppression of compatibility status of compatible cultures. I think a 

 Lac+ genotype which is grown in the absence of an inducer and thereby 

 fails to form the specific enzymes is a phenocopy of a lactose-sensitive. 

 The examples are so numerous that they are almost trivial because all the 

 characters that we use in bacteria are in a sense physiological responses 

 which are dependent on their environment for their expression. 



