158 MUTATIONS 



pharmacological chemicals: mustard gas, because it resembles X-rays 

 in the kind of burns it produces; alkylating agents, because of their 

 carcinostatic properties; various alkaloids, because of their medicinal 

 uses. Other substances were then tried, and are still being tried, be- 

 cause of their ability to fit into theories of how a mutagen may act. 

 Formaldehyde was used because of the belief that a protein is the 

 carrier of genetic information. Since the discovery that a nucleic acid 

 plays this role, tests have been made with various substances that react 

 with amino acids, particularly certain analogues of purine and pyrimi- 

 dine. In the history of chemical mutagenesis, the wrong theories have 

 often led to the selection of good mutagens, and this warns us to be 

 cautious. It means that if we have a theory about mutagenesis, choose 

 a chemical on the basis of this theory, and find it to be mutagenic, we 

 do not necessarily prove the theory. 



The discussion of the action of mutagens brought out the fact that, 

 in two stranded phages as well as in bacteria, treatment with a mutagen 

 produces mosaic plaques or colonies, indicating that both strands of 

 DNA give rise to progeny. Zamenhof found no mosaics among auxo- 

 trophs of Escherichia coli induced at frequencies up to 10 per cent by 

 heat treatment and interpreted their absence to mean that under the 

 conditions of the experiment the heat treatment eliminated one of 

 the two DNA strands. Lederberg expressed the opinion that the 

 bacterium is far too complex a genetic entity to be suitable for experi- 

 ments on mutagenesis and pointed out that the available information 

 about the structure of DNA cannot eliminate the possibility that at 

 some stage of the bacterial life cycle DNA may be single-stranded. 



During the discussion of the action of the mutagens Freese presented 

 his ingenious models interpreting the types of change induced in 

 phage T4 DNA by treatment with purine and pyrimidine analogues 

 and certain other potent chemical mutagens. Mutations induced by 

 a direct effect on DNA may be due to mistakes in incorporation or 

 mistakes in replication. Two types of changes may occur: transitions, 

 that is, replacements of a purine by a purine, or a pyrimidine by a 

 pyrimidine; and transversions, that is, replacements of a purine by a 

 pyrimidine or vice versa. The discussion clearly indicated that Freese's 

 models constitute a good start in the right direction, although most of 

 the processes involved in mutagenesis are too complex and still not 

 sufficiently well known to be explained in terms of simple models. In 

 organisms higher than phages, where the genetic material seems to be 

 better protected against changes in its immediate environment, the 

 complexity of mutagenesis is likely to be greater. Freese, in the course 



