530 RADIATION BIOLOGY 



The finding that the sensitive region, in the sense used by Blackwood, 

 Lea, and Catcheside, represents an entire group of genes rather than 

 only one gene makes the more unacceptable the conclusion of Lea and 

 Catcheside that its volume as calculated by them corresponds fairly 

 closely with the size of the actual genes concerned. For if it is difficult 

 to conceive of one gene as being of such small size as calculated on this 

 view, it is considerably more difficult to imagine a group of genes as 

 occupying this space. It thereby becomes evident that the physical vol- 

 umes dealt with are much larger than calculated and that, in comple- 

 mentary fashion, there is a far smaller chance than unity for an ionization 

 or activation within this space to result in a mutation. Thus the calcu- 

 lated volume cannot be translated into terms of real physical dimensions 

 without knowledge of the probability, for the given set of conditions, 

 that an ionization in the given region will be effective. Moreover, it 

 should be recognized that even this probability represents only an average 

 for the entire region and that within this region it must be subject to local 

 variations, perhaps diminishing so gradually toward its outskirts as to 

 make the size of the region, like the height of the earth's atmosphere, 

 only arbitrarily definable. 



The assumption that virtually every ionization within a given volume 

 (or within the gene itself) causes mutation of the gene is not the only 

 questionable premise of the target hypothesis. The idea that activations 

 of a merely excitational, nonionizing nature are without effect in the pro- 

 duction of mutations is still more improbable since it is contradicted by 

 the results from ultraviolet, from experiments with temperature alone, 

 and from those with chemicals. However, the much greater mutagenic 

 efficiency of ionizing radiation, for a given amount of absorbed energy, 

 indicates (as discussed on pp. 538-539) that, in comparison with indi- 

 vidual ionizations, individual excitations may be of very minor importance 

 in accounting for the mutagenic effects of ionizing radiation itself. 



More vulnerable still is the assumption of the detectability of virtually 

 all mutations. It is a demonstrated fact that most mutations have effects 

 which are very difficult to detect (see Chap. 7). Moreover, even the 

 same gene can mutate to alleles of very different detectability. When 

 the different alleles of one original gene are obtained, they are often found 

 to differ in the frequency of mutations which they show because their 

 mutations differ either in detectability or in frequency, or both, with the 

 result that these alleles have been calculated to have radically different 

 sensitive volumes. 



Finally, the assumption that ionizations or activations which occur out- 

 side the gene or outside some definite sensitive volume are never (or with 

 negligible frequency) capable of causing mutations in it has in certain 

 instances been demonstrated to be fallacious. Here again the results on 

 inactivation of enzymes and viruses have proved misleading, even though 



