MANNER OF PRODUCTION OF MUTATIONS 529 



volume, as calculated on the target hypothesis, forms only a thousandth 

 of the bulk of the chromosome. But it points up the question, is this 

 because few ionizations within the genes are effective in causing a detec- 

 table mutation or because the genes comprise so small a proportion of the 

 chromatin? Moreover, it is to be noted that, if some ionizations which 

 originate outside the chromatin can cause mutations also, the proportion 

 of ionizations inside the chromatin which cause mutations is lowered still 

 further. 



That not every ionization within the assumed sensitive region is sure 

 to produce a mutation is directly proved by the long-known fact that 

 the yield of mutations, for a given dose, varies according to other circum- 

 stances than the radiation (Muller, 1932, 1937, 1940, 1941a, 1952a). 

 Thus in Drosophila, point mutations are produced in the germ cells of 

 some ordinary interphase stages with only about a third or half the 

 frequency of their production in spermatozoa. Different stocks and 

 species also differ in their sensitivity to the effect. Again, as will be 

 noted in Sects. 15-17, various externally applied agents cause drastic 

 changes in the induced-mutation frequency. It seems much more likely 

 that these differences are caused by conditions which alter the likelihood 

 of a given ionization or activation being effective rather than by shrink- 

 age and swelling of a supposititious sensitive volume. But, if our inter- 

 pretation is correct, the sensitive volume as calculated would not be a 

 spatially fixed and definable thing and would have meaning only as a 

 mathematical description of the end result. The term used for it would 

 therefore be a misnomer. 



It is of importance to note that, when the qualification is introduced 

 that the ionizations within a given sensitive region have less than a 100 

 per cent chance of being effective. Lea's size-effectiveness tables require 

 a change in the scale of the coordinate representing size. For it is the 

 number of effective ions not the total number present which counts, and 

 in this case a larger particle is required to have a given number of effec- 

 tive ions than if every ion were effective. Thus it turns out that, under 

 these circumstances, larger volumes than those calculated by Lea are 

 required in order to fulfill the condition that neutrons have only two- 

 thirds the apparent mutagenic efficiency of X rays. In fact, their increase 

 in size must be about the same, factorially, as the decrease in the chance 

 of an ionization being effective (e.g., a one-fifth chance of being effective 

 implies a volume about five times as great). In view of these consider- 

 ations, it is evident that the agreement between the volume arrived at by 

 Lea on the basis of the relative efficiencies of radiation of different specific 

 ionizations and that obtained from the absolute efficiency of X rays is no 

 indication of the correctness of this calculated volume since a decrease in 

 the probability of an ionization being effective will affect both calculations 

 in much the same way. 



