Mutational Loads and Their Consequences 



249 



place in these cells, which remain relatively 

 quiescent for decades before becoming ova. 

 Not only is germinal selection against mu- 

 tants via mitosis absent in women, but there 

 is evidence suggesting that as oocytes age 

 they become disproportionately sensitive to 

 mutation (at least to nondisjunction that 

 leads to the presence of extra whole chro- 

 mosomes, polysemy, and probably to chro- 

 mosome loss, also). 



While there is no doubt, in principle, that 

 exposure to radiation has produced point 

 mutants in the somatic and germ lines of 

 man, this has not been easy to demonstrate 

 in practice, for two main reasons. The first 

 is that the point mutants expected are not 

 qualitatively different from those which 

 would occur spontaneously, and the second 

 is that the quantitative effect, although large 

 in total, is, in any one generation, small 

 enough to be masked by the general varia- 

 bility of human genotypes and environment. 

 However, by means of the use of improved 

 statistical methods, the evidence is becom- 

 ing stronger and stronger that radiation has 

 produced such genetic effects. On the other 

 hand, there is clear proof that radiation can 

 cause structural changes in human chromo- 

 somes. With the recent perfection of cyto- 

 logical methods for studying human chro- 

 mosomes, and the evidence that aneusomy 

 is a relatively frequent event in oocytes, it is 



Hkely that additional evidence will be forth- 

 coming relative to the numbers and kinds of 

 gross chromosomal mutations which differ- 

 ent doses and kinds of radiation can induce 

 in man. 



In conclusion two more points need to be 

 made. In our discussion of the genetic ef- 

 fects of low doses of radiation, we have recog- 

 nized a danger which is not likely to be 

 calamitous to the human gene pool. How- 

 ever, the very high dosages which are possible 

 in a nuclear war could be disastrous. For 

 if 500 r is given the whole body in a short 

 period of time, the chances are 50% that the 

 person will die in a few months. If a person 

 survived this period, his life expectancy would 

 be reduced by some years, probably because 

 of somatic mutations, and children conceived 

 after exposure would be handicapped by 

 many detrimental mutants. It is even 

 possible, but not probable, that we could re- 

 ceive enough radiation in a nuclear war to 

 destroy the human species. Finally, it 

 should be realized that we are being con- 

 stantly exposed to manmade mutagenic 

 chemicals. It is very probable that we are 

 getting less germ-line mutagenic effect from 

 chemicals than from radiation; on the other 

 hand, however, it is possible that we are 

 having more somatic mutants produced by 

 chemical substances than by present radi- 

 ation exposure. 



SUMMARY AND CONCLUSIONS 



Cross-fertilizing species carry a large load of mutants in heterozygous condition. The vast 

 majority of these are detrimental when homozygous and, to a lesser extent, when heterozy- 

 gous, although there are also some mutants that are heterotic. Other things being equal, 

 all mutants are equally harmful in that all are eliminated from the population only via the 

 genetic death of their carriers. For rare mutants, more detriment and more genetic deaths 

 occur in heterozygotes than in homozygotes. Persistence of mutants in the population is 

 inversely related to their effect upon reproductive potential. Mutants with the smallest 

 detriment to reproductive potential cause the greatest total amount of human suffering. 



Mutation is the current price paid by a population for the possibility of having a greater 

 reproductive potential in the same or a different environment in the future. So, despite the 

 rarity, in a given environment, of mutants which increase reproductive potential, mutation 

 provides the raw materials for evolution. 



