THE GENE MUTATION RATE— DOSAGE RELATION 303 



is the more interesting. It would indicate that those spots which are 

 more vulnerable in the finished gene are also more prone to be effectively 

 disturbed during the process of gene construction. It is not surprising, 

 however, that the unfinished gene should be more labile in general than 

 the finished one; that is, that it should be more susceptible to having 

 mutational disturbances caused in its synthesis by the relatively mild 

 influences that operate in non-radiated material.* 



If the above general view of the spontaneous gene-mutation process 

 has validity, it is not at all strange that high-energy radiation also in- 

 duces the occurrence of gene mutation, for it not only releases energy at 

 a far higher level than necessary for such a result but in virtually as 

 many different forms as it would naturally be encountered in, and more 

 besides. Indeed, such a chaos of different, molecularly more or less 

 localized reactions must arise in irradiated protoplasm, both as direct 

 results of the ionizations and activations on the molecules hit, and as 

 secondary, tertiary, etc., consequences of the varied combinations into 

 which these products later enter, that it would be strange if those reac- 

 tions which, in non-radiated material, result in spontaneous mutations 

 were not included among those here arising. In addition, the gene itself 

 could be struck directly by a fast particle, with results that might resem- 

 ble those brought about by the intermediation of mutagenic substances. 

 In all this welter of effects and of possibilities, the tracing of the more 

 usual trains of mutational processes, in physicochemical terms, is a mat- 

 ter of the greatest difficulty. This field is only now opening up, as a re- 

 sult of studies of chemical influences upon the occurrence of gene mu- 

 tation, both with and without radiation. 



On the Proportionality between Induced Gene 

 Mutations and Ionizations 



Before referring to some of the specific findings along these lines, let 

 us consider the question of how the production of mutations is affected 

 by changes in the dose of radiation. Since the doctoral thesis presented 



* While this manusciipt was in press, results were reported by Novick and Szilard 

 {Proc. Natl. Acad. ScL, 36: 708-719, 1950), showing that in Escherichia coli growing 

 at a given temperature spontaneous mutations continue at the same rate regardless 

 of the rate of growth and multiplication (varied by controlling the amount of some 

 minimal nutrient available for them), provided they are able to multiply at all. 

 Here, then, the changes must be in the "old" gene; however, we do not know how 

 much turnover of material it is undergoing. A paper by Maale and Watson {Proc. 

 Natl. Acad. Sci., 37: 507-513, 1951) reports results on phage "tagged" with P^- which 

 may be interpreted by assuming that at least the phosphorus in the genetic material 

 of the phage does undergo exchange apart from reproduction, but other interpreta- 

 tions of these results are possible. 



