312 GENE MUTATIONS CAUSED BY RADIATION 



least, have done so by the intermediation of the activations, or groups 

 of activations, which the ionizations occasioned. If then such activa- 

 tions were, under other circumstances, induced more directly, the mu- 

 tations Avould in that case arise in the absence of ionization. 



The Inapplicability of the Target Hypothesis in 

 Its Simplified Form 



The target hypothesis, in the simplified form in which it has usually 

 been applied by those sponsoring its application to problems of muta- 

 genesis, has admitted only ionizations, not activations, as causes of the 

 mutations induced by high-energy radiation. As we have seen above, 

 it appears premature at present to assume the effect to be so limited. 

 We may now examine some of the other premises which have been set 

 up on the target hypothesis. 



One of these premises is that every ionization within the genetic ma- 

 terial results in a gene mutation, thus making it possible to calculate 

 the volume of the gene. When such calculations are made, however, it 

 is found, in Drosophila, that only about one in seven hundred or more 

 ionizations occurring within the volume of a chromosome when it is in a 

 condensed stage (a stage of relatively high susceptibility) is followed by 

 a gene mutation of some detectable kind— lethal, detrimental, or visible. 

 A similar figure is arrived at if we estimate the maximum volume of 

 that part of a condensed chromosome including but one gene and then 

 compare the frequency of ionization induced by a given dose within such 

 a volume with the frequency with which those individual genes that 

 have been studied give detectable mutations on application of the same 

 dose. This result would lead, on the target hypothesis, to the conclusion 

 that the genetic material itself occupied only about a seven-hundredth 

 of the volume of the condensed chromosome. 



Now such a conclusion appears on the face of it very improbable. 

 Recent work renders it more so, if we agree that the evidence concerning 

 the "transforming substance" in bacteria points strongly to the conclu- 

 sion that the genetic material is composed, in part at least, of nucleic 

 acid. Not only is the nucleic acid content of a chromosome very high, 

 but the work of Mirsky and Ris has shown that the amount of desoxy- 

 ribonucleic acid (which usually forms the great bulk of the nucleic acid 

 of condensed chromosomes) is constant and proportional to the num- 

 ber of genomes, throughout the somatic and germinal cells, despite the 

 great variations in amount of other nuclear and cytoplasmic material. 

 In view of this, it would be strange if only a minute fraction of this des- 

 oxyribonucleic acid were genetic in nature. But if we discard this alter- 



