168 MUTATIONS 



are injected, or given in the food, they have to pass through a number 

 of membranes and through Hving substance, which destroys them to 

 a large extent." 



Neel and Schull (42), at about the same time, wrote: "Moreover, be- 

 cause of the elaborate mechanisms which maintain the chemical con- 

 stancies of the human body during life, it seems unlikely that exposure 

 to various chemical agents exerts a very large influence on human 

 mutation rates, but the situation with respect to certain types of 

 radiation which can penetrate the body with ease is potentially quite 

 different." 



At the other extreme, I may point to Barthelmess (5) , at the Botani- 

 cal Institute in Munich, who three years ago wrote a review on the 

 genetic hazards of drugs in medicinal use. After presenting a very 

 thorough literature survey, he concluded that all drugs may be po- 

 tentially hazardous to the germ line of man. Therefore, he argued, the 

 routine toxicity testing of all drugs should include assays of mutagenic 

 activity before approval is given for use in the human population. 



Just as it may be dangerous to underestimate the possibility that 

 chemical agents can cause genetic damage in man, so is it probably 

 wrong to cry wolf about every drug to which we are exposed. I shall 

 raise for discussion later the practicability of developing meaningful 

 tests for mutagenic activity. The real problem is to see whether any 

 basis exists for choosing, among all drugs and other chemicals to 

 which man is exposed, those few that are most likely to present a 

 genetic hazard, and to concentrate further research energies upon them. 



My entire presentation here today may well be subjected to the 

 criticism that it is premature, that it makes much out of little. 

 Indeed, I hope such a criticism turns out to be valid. But it must be 

 pointed out that we are quite properly concerned about genetic effects 

 of radiation, despite the fact that there is as yet only slim evidence 

 for such genetic (in contradistinction to somatic) effects in man. Yet 

 we do not hesitate to extrapolate from a variety of other species and 

 we assume that the chemical behavior of man's genetic apparatus is 

 not wholly unique. It is true that there is even less evidence (i.e., none 

 at all) for an effect of any chemical mutagen in man or, for that 

 matter, in any mammalian organism, except for a very few experi- 

 ments with alkylating agents in mice. However, it would seem improper 

 to dismiss chemical mutagenesis in man merely because the data 

 thus far are weaker than in the case of radiation. Experimental evi- 

 dence leads to practical concern, but it is also true that concern often 

 leads to experiments that yield new evidence. 



