288 M. Westergaard 



back-mutation test, back mutations are induced only by 

 radiation and by strongly alkylating agents, whereas many 

 stable chemicals such as phenols or urethane, which induce 

 chromosome breakage in plants and animals, are inactive 

 (Jensen et at., 1951; Kolmark and Westergaard, 1955). 



In terms of our model, how may the results of chemical 

 mutagenesis and phenocopy induction help to identify the 

 different mechanisms of variation in bacteria? Has variation 

 in bacteria, for instance drug resistance, been enhanced by 

 these chemicals which in higher organisms are known to pro- 

 duce only phenocopies, but not mutations? If so, can the 

 variants induced by such treatments be transduced, trans- 

 formed or recombined? One has somxctimes the impression 

 that "mutations" in bacteria can be induced by almost any 

 kind of treatment. However, it may well be that several of 

 these "mutations" are not nuclear, but "receptor events" or 

 "translation events". Only genetical breeding experiments 

 can give the final answer, but circumstantial evidence may be 

 obtained by use of chosen chemicals. 



There is also the possibility that the antibiotics against 

 which drug resistance is built up are themselves inducers 

 either of nuclear mutations, cytoplasmic changes or "pheno- 

 copies ". I think it is possible that they are, but that this is not 

 particularly relevant for understanding the origin of drug 

 resistance. Most antibiotics are probably weak, unspecific 

 chemical mutagens. There is good evidence that strepto- 

 mycin can affect the chloroplasts of green plants and it would 

 be very interesting to study the effect of other antibiotics on 

 the induction of phenocopies in, for instance, Drosophila. 

 However, although the induction of phenocopies may be 

 specific, the result, the phenocopy, seems to be a non-adaptive 

 change. I think we all agree on one thing, namely that what 

 we are seeking in order to explain the origin of drug resistance 

 are mechanisms which can give rise to an adaptive system, 

 in the ecological and evolutionary sense of the word. Hence, 

 although the possible mutagenic properties of many drugs 

 and antibiotics may have important perspectives for other 



