INAPPLICABILITY OF TARGET HYPOTHESIS 313 



native it would follow that a considerable proportion of the ionizations 

 which occur within the genetic material fail to cause a mutation in it. 



What now about the complementary premise of the target hypothesis 

 of radiation mutations, according to which virtually no ionizations or 

 activations induced outside the genetic material result in mutations? In 

 this connection it should be admitted to begin with that, in Drosophila, 

 there is good reason to believe most of the mutagenic effect usually to 

 be rather narrowly localized, not merely in a molar but also in a micro- 

 scopic sense, even though this does not necessarily mean on an atomic 

 or molecular scale. The molar localization was first shown in the experi- 

 ments of Kerkis (31). These showed that the mutation rate induced in 

 flies which had only the posterior half of the body irradiated with x-rays 

 was the same as in those whose whole body was irradiated, whereas if 

 only the anterior half was irradiated there was no appreciable effect. 

 Later Timofeeff-Ressovsky (72, 73) showed that irradiation of the super- 

 ficial tissues with x-rays too soft to penetrate to the gonads was without 

 mutagenic influence on the germ cells. 



That this principle extends down to a microscopic scale is indicated, 

 for one thing, by the close similarity of the x-ray-induced gene-mutation 

 rate in the relatively condensed chromosomes of late oocytes and in those 

 of mature spermatozoa in the male [Muller, R. M. Valencia, and J. I. 

 Valencia (58)].* In the oocytes there is much accessible nucleoplasm 

 and cytoplasm which could serve as absorptive media for the mutagenic 

 effects of the radiation if, indeed, they can be transmitted to the chromo- 

 somes over microscopically visible distances. In the sperm, on the other 

 hand, packed tightly as they are, the amount of such extrachromosomal 

 material is far more limited. At the same time, in the sperm, both cell 

 and nuclear boundaries would usually be interposed in the way of the 

 supposed transmission. And since the sperm in this stage are dormant 

 their amount of exchange with the medium is likely to be at a minimum. 

 Similar considerations apply to sperm in the receptacles of the female, 

 which have been found to have about the same mutation rate [Muller 

 (40)]. 



More critical evidence of the microscopic or ultramicroscopic locali- 

 zation of most of the mutagenic effects of high-energy radiation is given 

 by the results of Zimmer and Timofeeff-Ressovsky (81), showing the 

 lesser effectiveness of neutrons than of x-rays and gamma rays in pro- 

 ducing lethal mutations, and the contrasting results of Giles (18, 19), 



* The work on the production of mutations in Drosophila by high-energy radia- 

 tion, referred to in this section, was supported by a grant from the American Cancer 

 Society, on recommendation of the Committee on Growth of the National Research 

 Council. 



