154 



now receive a possible interpretation 

 in terms of the gene-transmuting 

 property of X-rays; we may more ap- 

 propriately confine ourselves here to 

 matters which can more strictly be 

 demonstrated to be genetic. 



Further facts concerning the nature 

 of the gene may emerge from a study 

 of the comparative effects of varied 

 dosages of X-rays, and of X-rays ad- 

 ministered at different points in the 

 life cycle and under varied conditions. 

 In the experiments herein reported, 

 several different dosages were made 

 use of, and while the figures are not 

 yet quite conclusive they make it 

 probable that, within the limits used, 

 the number of recessive lethals does 

 not vary directly with the X-ray 

 energy absorbed, but more nearly with 

 the square root of the latter. Should 

 this lack of exact proportionality be 

 confirmed, then, as Dr. Irving Lang- 

 muir has pointed out to me, we should 

 have to conclude that these mutations 

 are not caused directly by single 

 quanta of X-ray energy that happen 

 to be absorbed at some critical spot. 

 If the transnuting effect were thus 

 relatively indirect there would be a 

 greater likelihood of its being influ- 

 enceable by other physico-chemical 

 agencies as well, but our problems 

 would tend to become more com- 

 plicated. There is, however, some 

 danger in using the total of lethal 

 mutations produced by X-rays as an 

 index of gene mutations occurring in 

 single loci, for some lethals, involving 

 changes in crossover frequency, are 

 probably associated with rearrange- 

 ments of chromosome regions, and 

 such changes would be much less likely 

 than "point mutations" to depend on 

 single quanta. A re-examination of the 

 effect of different dosages must there- 

 fore be carried out, in which the dif- 

 ferent types of mutations are clearly 

 distinguished from one another. When 



MULLER 



this question is settled, for a wide 

 range of dosages and developmental 

 stages, we shall also be in a position 

 to decide whether or not the minute 

 amounts of gamma radiation present 

 in nature cause the ordinary mutations 

 which occur in wild and in cultivated 

 organisms in the absence of artificially 

 administered X-ray treatment. 



As a beginning in the study of the 

 effect of varying other conditions, 

 upon the frequency of the mutations 

 produced by X-rays, a comparison has 

 been made between the mutation fre- 

 quencies following the raying of 

 sperm in the male and in the female 

 receptacles, and from germ cells that 

 were in different portions of the male 

 genital system at the time of raying. 

 No decisive differences have been ob- 

 served. It is found, in addition, that 

 aging the sperm after treatment, be- 

 fore fertilization, causes no noticeable 

 alteration in the frequency of detec- 

 table mutations. Therefore the death 

 rate of the mutant sperm is no higher 

 than that of the unaffected ones; more- 

 over, the mutations can not be re- 

 garded as secondary effects of any 

 semi-lethal physiological changes 

 which might be supposed to have oc- 

 curred more intensely in some ("more 

 highly susceptible") spermatozoa than 

 in others. 



Despite the "negative results" just 

 mentioned, however, it is already cer- 

 tain that differences in X-ray influ- 

 ences, by themselves, are not suflicient 

 to account for all variations in muta- 

 tion frequency, for the present X-ray 

 work comes on the heels of the deter- 

 mination of mutation rate being de- 

 pendent upon temperature (work as 

 yet unpublished). This relation had 

 first been made probable by work of 

 Altenburg and the writer in 1918, but 

 was not finally established until the 

 completion of some experiments in 

 1926. These gave the first definite evi- 



