420 RADIATION BIOLOGY 



tion of E. coll is hindered to various degrees by regulation of the supply of 

 an essential nutrient, the frequency of mutations per unit of time remains 

 constant. In other words, within a given length of time, as many 

 mutants arise, on the average, in a line of bacteria that has undergone 

 few divisions as in one that has undergone many, and this principle holds 

 over a very wide range of proliferation rates. (A "line" in this case 

 would signify a succession of individual bacteria produced one from the 

 other by cell division, with just one of the two products of each cell 

 division always being taken for the continuance of the line.) However 

 (according to a personal communication from Szilard), when proliferation 

 is reduced to zero, by the complete cutting off of the supply of the minimal 

 constituent, mutations also cease, or nearly cease, to occur. The latter 

 result may perhaps be used in reconciling the apparent contradiction 

 between Zamenhof's findings and those of Novick and Szilard. 



By analogy with the findings of Lederberg et at. (1952) on crossable 

 strains of E. coli, in which genetic changes of an apparently similar kind 

 could be shown by Mendelian analysis to involve individual genes, we 

 may infer that the mutations dealt with by Novick and Szilard were in all 

 probability gene mutations. Their finding of the independence between 

 mutation frequency and reproduction rate within a wide range of the 

 latter therefore implies that these mutations consisted of changes in 

 already completed genes, rather than in the construction of new genes. 

 Why then is it that the mutations occurred only when at least a little 

 reproductive activity was going on? It is evident from the results that, 

 as long as any proliferation at a rate above a certain minimal one is being 

 attempted, but not in its absence, there is a steady stream of metabolic 

 processes of some kind, not otherwise occurring, which result in occa- 

 sional mutations. It is conceivable that these processes, in acting to 

 cause a mutation, alter or rearrange gene material which, but for the 

 mutation itself, would have remained in place just as it had been. But it 

 would seem at least as likely that, in connection with these metabolic 

 processes, a continual turnover and replacement of at least some of the 

 gene parts is normally occurring, at a rate independent of the over-all 

 growth, and that in the course of this replacement missteps occasionally 

 occur, whereby a new gene part is substituted which is different, or which 

 becomes arranged and connected up differently, from the old one that it 

 replaces. The hypothetical normal replacement process might even 

 involve a kind of gene reproduction itself. For if, as has sometimes been 

 postulated, the gene produces its effects on the protoplasm by means of 

 the building of partial or complete gene replicas, which become loosed into 

 the cell, all the original gene material might not invariably stay behind in 

 the chromosome while the newly built material emigrated, but a part or 

 all of the old and of the new gene material might sometimes change places. 

 In that case the mutations might after all consist in missteps in an actual 



