8 BIOLOGICAL EFFECTS OF ATOMIC RADIATION 



tion damage, are discussed with some overlapping under three headings: (1) mutation, 

 (2) phenotypic effects of mutant genes, and (3) the behavior of genes in populations. 



1. Mutation 



We need to know the rates of spontaneous occurrence of mutation in specified categories 

 and how these are influenced by radiation. To a considerable degree, information concerning 

 these rates — especially the induced ones — will have to be deduced from what is known of 

 organisms other than man. Such a process of extrapolation is not wholly satisfactory; the 

 errors in so doing will be minimized if we have at least one mammal for comparison. We 

 feel that experiments now under way with mice to determine mutation rates for specific loci 

 as well as over-all rates for certain categories of mutations should be continued and expanded 

 as rapidly as is feasible. The results will, however, give us more confidence if they are comple- 

 mented with comparative data from a wide variety of organisms, including other mammals, 

 since there is already evidence that different species may differ widely in spontaneous muta- 

 tion frequencies and that individuals within one species likewise differ. The genetic control 

 of such differences in mutation rate is itself in need of further study. 



Most of the questions concerning radiation-induced mutations also need to be answered 

 for mutations induced by other agents — abnormally high temperatures, ultra-violet light, 

 various chemicals, etc. Although it seems reasonable to suppose that the germ cells of man 

 are well protected from extraneous chemical substances to which large numbers of persons 

 are exposed through ingestion, inhalation, or otherwise, it is nevertheless conceivable that 

 some such substances as industrial and automobile fumes, foods and food additives, tobacco, 

 drugs, antibiotics, hormones, cosmetics, contraceptives, and agents of chemical warfare may 

 be important as possible sources of genetic damage to man. Chemical mutagens and anti- 

 mutagens come within the special interests assigned to this Committee, since what is learned 

 from their study may contribute materially to knowledge of the basic mutation process and 

 the effects of ionizing radiations. This is especially emphasized by recent studies indicating 

 that radiation-induced mutations may arise indirectly by way of intermediate chemical modi- 

 fications of the cellular environment. It is also important to determine whether all these vari- 

 ous agents produce similar spectra of mutations and especially the extent to which radiation- 

 induced mutations are like "spontaneous" ones in the severity of their effects on the organism. 



The degree to which mammalian germ cells in vivo may be protected from chemicals 

 known to be mutagenic to microorganisms, to mammalian cells in culture, or to invertebrates 

 in which the cells can be directly exposed, should be investigated in an experimental mammal 

 such as the mouse. 



Whatever organisms are used, the direct studies on mutation will need to take into 

 account and elucidate the effect of such factors as age, sex, and physiological condition of 

 the treated organism; cell type, stage of mitotic or meiotic cycle and the condition of the 

 chromosomes; the exact type of mutant effect scored, especially how many different genes 

 are concerned, and how sensitive the selected index is; the degree to which the technique is 

 objective and free from personal bias; and the extent to which strain differences affect the 

 results through the action of mutator or antimutator genes, or otherwise. 



There are several different methods of study that lead to estimates of mutation rates for 

 single loci, for all loci having a particular effect (e.g., lethals), for loci lying in a particular 

 chromosome or chromosome region, or for the total effect per treated gamete. All are useful. 



