GENETIC EFFECTS 11 



be hoped that human material so exposed in the future will be less prevalent than it now is. 

 There should therefore be no delay. 



In addition to making effective use of all currently available methods and techniques 

 for the study of human genetics, investigators should be given constant encouragement in 

 searching for new approaches. It is conceivable, for example, that entirely new methods of 

 directly investigating human chromosomes can be found. It would be of great value to have 

 biological means of estimating accumulated radiation exposure in man. This might be pos- 

 sible by some method of quantitatively determining accumulated chromosome breaks. Im- 

 proved methods of measuring physiological age would be most useful in investigating the 

 relation of induced mutations, including chromosomal breaks and rearrangements, to the 

 aging process. 



2. Phenotypic Effects 



It is obvious that mutations are of importance to human populations because they lead 

 to significant variations in developing individuals. The extent of damage due to unfavorable 

 mutant genes will depend on two factors: their frequency in the population and the harm they 

 do to individuals. 



In both respects, there are serious difficulties in making estimates. In the latter regard, 

 it is misleading in some connections to attempt it in numerical terms. How, for example, does 

 one measure quantitatively the relative importance of a still-birth, a feeble-minded child, and 

 a death during adolescence? One may rate such things in the order of their significance either 

 for society or for the families of the affected individuals, but clearly no simple numerical 

 formulation can describe the relative human values. (The following contribution by Sewall 

 Wright presents one suggestion as to how problems of this kind might be approached. ) 



While an over-all figure must in this sense be inadequate, it is still possible and desirable 

 to get estimates on the relative frequencies of different types of mutant abnormalities, as 

 expressed in rather broad categories (e.g., early or late embryonic deaths, infant deaths, 

 mental defects, sterility, etc.). Much genetic damage is of course not observed by the usual 

 direct methods. As pointed out in the United Nations report referred to earlier, it is probable 

 that the magnitude of this fraction of undetected genetic damage in man can be estimated 

 through careful comparison of the children of cousin marriages with those of parents less 

 closely related. Until reliable data of these kinds become available for man, estimates will 

 have to be based in part on information from other organisms. 



There are certain general properties of mutant genes that are in need of more study. 

 Our 1956 report emphasized that many radiation-induced mutants would exert their chief 

 effects through small dominant effects. This question of the degree of dominance, and its 

 variation among loci, needs additional study because, among other reasons, of its bearing 

 on the number of generations in which mutations will persist in populations. 



Although the magnitudes of the selective disadvantages of heterozygotes for mutant 

 genes usually called recessive may be small and therefore difficult to detect, they may never- 

 theless be of such overriding importance in the elimination of deleterious genes as to deserve 

 especially thorough investigation. And for the same reasons it is essential to know the fre- 

 quency and importance of loci for which there are selective advantages of heterozygotes — 

 that is, "over-dominance." Several instances are now known in man in which it has become 



