EFFECT OF AN INCREASE IN MUTATION RATE 325 



There would of course be a great many more individuals who, though 

 suffering some damage, had not met actual elimination; in fact the num- 

 ber of these in the given case may be estimated at something of the 

 order of one or two hundred descendants slightly affected, for every 

 hundred of the treated generation. These effects then are inappreci- 

 able only because they are hidden from us by the veils of space, time, 

 and circumstance. 



Even if highly accurate measurements could be made, in organisms 

 with easily controlled breeding, nutrition, etc., of the amount of depres- 

 sion of viability caused in one or in a few generations as a result of one 

 or a few generations of application of a mutagenic agent, this would not 

 give us a reliable means of estimating the total amount of genetic dam- 

 age done by the given exposure, if all generations were considered. 

 Neither would it allow us to determine what the condition of the popu- 

 lation at equilibrium would be, if the agent were applied in the same 

 strength, generation after generation, indefinitely. The answer to these 

 questions depends not only on the total effect that finds expression in 

 one or a few generations after treatment, but also on the amount and 

 type of distribution of the mutational damage among different loci. If, 

 for example, most of the damage was caused by a relatively few mu- 

 tations, with individually marked expression, the mutant genes con- 

 cerned would be eliminated more quickly by natural selection and the 

 effects would sooner die away, and so the total damage throughout 

 all generations would be much smaller than if the observed effect had 

 been divided among a great many mutations with individually small 

 action. Keeping watch of the viability for a few generations would 

 hardl}^ give a delicate enough means of measuring the curve of decay 

 of the effect. To obtain the needed information, highly controlled 

 breeding and genetic analysis would be called for, in which a sample of 

 the mutant genes was "caught," as it were, in the homozygous condi- 

 tion, and then carefully tested, with the use of exactly regulated genetic 

 and environmental backgrounds, for the ascertainment of the amount of 

 effect which the given genes had on viability when they were in hetero- 

 zygous condition [Muller (53)]. This sort of thing has not been done 

 even for Drosophila, and would be a major project in that organism. 



It might be thought that in view of the uncertainties even in Dro- 

 sophila the situation as regards man would be pure guesswork. Yet the 

 information that has been brought forward by various investigators on 

 spontaneous mutation frequencies at a number of specific loci in man, 

 taken together with a number of considerations of comparative genetics, 

 makes it feasible to form an approximate estimate of the probable spon- 

 taneous mutation rate in man, and of the consequent genetic depression 



