430 MAMMALIAN RADIATION GENETICS 



measurable end effect: the reproductive rate. The difficulty of esti- 

 mating theoretically the combined effects of the complex of variables 

 emphasizes the need for experimental work in population genetics, such 

 as that being done on Drosophila by Wallace (22), in order to collect 

 empirical data. In mammals there is still much to be done, in fact al- 

 most everything, on the preliminary problem of measuring the radiation- 

 induced mutation rate. In the next section, some of our present experi- 

 ments and the results of earlier investigations are outlined and discussed. 



Experimental Work 

 gene mutations 



Mutations produced by x-rays have been reported in mice by Snell 

 (15) and Hertwig (7, 9, 10), but the data are not adequate for a reli- 

 able estimate of mutation rate. The difficulties encountered in trying 

 to measure mutation rates in mice, as compared with Drosophila, are 

 very great and not, as is often supposed, due solely to the slower re- 

 productive rate of mice and to the greater space and labor required to 

 raise them. In Drosophila, the most reliable and most easily deter- 

 minable mutation rates are those based on lethal mutations on the 

 X-chromosome. These rates are obtained by a well-known method, 

 devised by Muller, which makes use of sex-linked genes, acting as 

 markers, and chromosome inversions which suppress crossing over. 

 Neither of these being, as yet, available in the mouse, Muller's method 

 cannot be used. Sex-linked lethals could be detected by observing a 

 disturbed sex ratio in the offspring of daughters of irradiated males, but 

 this would be far more tedious and relatively uncertain unless further 

 extensive tests were made. 



It would be out of place here to consider in detail the possible ways 

 of measuring mutation rates in other whole groups of genes. For our 

 present research at Oak Ridge they have been rejected in favor of a 

 method for obtaining mutation rates at specific loci. This consists es- 

 sentially of mating irradiated wild-type mice, and non-irradiated con- 

 trols, to a strain homozygous for as many known recessive genes as can be 

 managed practicably. A mutation at any of the loci represented by the 

 recessives will then be detected in the first generation. The method has 

 not been suggested before, for mice, presumably because of the rela- 

 tively large number of animals needed. It was calculated, however, 

 that, with the facilities offered by the Atomic Energy Commission, reli- 

 able mutation rates might be obtained in a reasonable time if they were 

 not lower, or much lower, than the Drosophila rates. 



The method has several advantages. All mutations are detected in 

 the first generation, whereas methods for obtaining autosomal recessive 



