INAPPLICABILITY OF TARGET HYPOTHESIS 315 



branching of its effect like that of a bomb [Aluller (44)], be able to cause 

 more than one genetic change in its neighborhood. 



At this point a few words concerning the history of the target hypothe- 

 sis may be in place. It does not seem to be generally realized that this 

 hypothesis, although now so popular, is over a quarter of a century old, 

 or that it i was originated by the British biophysicist J. A. Crowther. 

 When Crowther (9) proposed it in 1924, he used it as a means of in- 

 terpreting the relation of the frequency of inhibition of mitosis to the 

 dose of x-rays that had been observed by Strangeways and Oakley in 

 1923 in cells of tissue cultures. Crowther found that these results might 

 be accounted for by assuming that the inhibition of mitosis was caused 

 by a single ionization produced in a particle about the size of a centro- 

 some. In a later paper (10) he proceeded to show, in connection with 

 results on the survival of x-rayed protozoa, how not only the size of 

 sensitive body but also the number of ionizations in it which are neces- 

 sary to produce a given effect, when more than one ionization is neces- 

 sary, can be calculated from the observed frequency-dosage curve. 

 Crowther was, however, duly cautious in the drawing of actual biologi- 

 cal conclusions from the use of the brilliant analytical method which he 

 had proposed, for he realized that the premises employed might be in- 

 applicable in the given cases. 



It was realized by the present author that this method might be ap- 

 plied to his own and his coworkers' data, for the calculation of gene size, 

 and, in collaboration with Mott-Smith, such calculations were carried 

 out in 1930 [see Muller (45)]. The results were not published at the 

 time, however, since we thought it very unlikely that all the required 

 premises should be valid at once. However, in 1931 and 1932 the phys- 

 icist O. Blackwood of the University of Pittsburgh published results on 

 the size of the sensitive volume or '^nucleus" of the gene, calculated by 

 the application of Crowther's method to the data of the Texas group of 

 Drosophila workers. 



In and about 1935 Timofeeff-Ressovsky and his coworkers, as well 

 as Haskins and others, revived the method or some modification of it, 

 again using it for the calculation of gene size [see, for instance, Timofeeff- 

 Ressovsky and Zimmer (74)]. The present writer, however, has from 

 the time of the first application of the method to this problem warned 

 against its usage in this connection both in publications (42, 43, 44, 45, 

 53) and in the Gene Conferences held at Copenhagen (1936) and Spa 

 (1938). After the first of these conferences, Timofeeff and his coworkers 

 greatly moderated their original position, so as to admit the points that 

 the calculated "sensitive volume" changes with conditions outside the 

 gene, with the gene and allele studied, and with the type of mutation 



