418 RADIATION BIOLOGY 



specific effect in slightly increasing the mutation frequency has relatively 

 seldom been demonstrated in Drosophila, even when such highly detri- 

 mental concentrations of chemicals are fed as to kill the great majority 

 of them (Muller, 1928d), is probably due to the germ cells in multi- 

 cellular animals being held protected in such a well-regulated somatic 

 system that under many conditions death of the body as a whole occurs 

 before the germ cells are allowed to have their metabolism greatly dis- 

 turbed. Abnormal temperatures, unlike many chemicals, however, can- 

 not be kept out of any part of such a small organism as a fly.^ 



18. INFLUENCE OF NORMAL METABOLIC PROCESSES 

 ON THE OCCURRENCE OF GENE MUTATIONS 



It would be of much interest to know the effects, if any, on the "spon- 

 taneous" gene mutation frequency which are exerted by the differences in 

 metabolic processes and biochemical conditions generally which normally 

 exist between different cells of the same organism, and between cells 

 at different stages in the cell cycle, and in the life cycle of the whole 

 individual. 



In an approach to problems of this kind in Drosophila evidence was 

 obtained by the present writer (1946a, b, but with the details still unpub- 

 hshed) that the occurrence of the great majority of spontaneous gene 

 mutations in the germ cells, or cells of the germinal line, is concentrated 

 into two relatively short periods of germ-track history. These are: 

 (1) that of very early embryogeny, the so-called "early cleavage" stage 

 when nuclear divisions are taking place in rapid succession; and (2) some 

 period shortly antecedent to fertihzation, either that in which the germ 

 cells are undergoing their spurt of proliferation as gonia, just prior to 

 their maturation, or the protracted maturation period itself, or both 

 taken together. In the long intervening period of larval and adult life, 

 in which by far the greater part of germ-cell existence is spent, very few 

 mutations occur. This was shown by the fact that it made no per- 

 ceptible difference in the final, total frequency of mutations whether or 

 not this period is prolonged to several times its usual length, whether this 

 prolongation takes place in the larval or adult stage, or whether the 

 individual is starving or actively metabolizing and reproducing during 

 that time. In addition to these two periods* there is in the germ cells of 

 the male one other period when spontaneous mutations occur at a per- 



^ Since the foregoing material was written, Novick and Szilard (1952) have reported 

 distinct influences on the frequency of mutations in E. coli to be exerted by diverse 

 substances, including some organic compounds of common occurrence in organisms, 

 and others related to these. These important results, the obtaining of which was 

 made possible by the use of their chemostat, have come to hand too late for considera- 

 tion here. 



