176 MUTATIONS 



the human race has been exposed to a changing chemical environment 

 for a genetically significant period of time, i.e., for thousands of 

 generations. The development of agriculture, for example, provided new 

 kinds of foods as major items of diet which were not available before. 

 The discovery of fermentation introduced a wholly new organic com- 

 pound to which man was not previously exposed. Certain religious 

 customs have created special exposures to exogenous substances, for 

 example, the peyotl rites among some American Indians. 



Medication goes back to the days of prehistory. Professor Dunlop 

 in Edinburgh used to begin his course in therapeutics by saying that 

 the main feature which distinguishes man from the lower animals 

 is his desire to take medicine. Man has always sought in nature reme- 

 dies for his physical and mental ills. Particularly prized have been 

 psychic stimulants. For example, caffeine, being the main stimulant 

 alkaloid of tea, was in use as a stimulant at least as long ago as 

 2500 B.C. in China. This is more than a hundred and fifty generations, 

 a long time for man, and an absolute minimum estimate of the 

 duration of exposure. 



It follows from all this that we have to regard the human race as 

 extremely heterogeneous, both in space and in time, with respect to 

 exposure to exogenous compounds. Were some of these even weakly 

 mutagenic, continuous exposure over a long period of time might have 

 had some significant effect upon the human germ plasm. 



Although some of these exposures have gone on for hundreds of 

 generations and more, an extraordinary change has occurred in very 

 recent times. The total exposure to exogenous compounds in our 

 environment has increased explosively primarily as a result of de- 

 velopments in synthetic organic chemistry and its offshoot, the phar- 

 maceutical industry. This remarkable state of affairs had its inception 

 only in the middle of the last century, or not more than three or four 

 generations ago. Thus all of us are exposed with regularity to com- 

 pounds which did not even exist a short while ago, while the number 

 and variety of these compounds and the extent of exposure continues 

 to increase with great rapidity. If any of them had significant muta- 

 genic activity some doubt would be cast upon the concept that we have 

 attained a stable genetic equilibrium in man. Moreover, the question 

 of "spontaneous" mutation in man must be viewed against the 

 background of this exposure to compounds which might possibly be 

 mutagenic. We heard something the other day about estimation of the 

 spontaneous mutation rate in man. There is a considerable genetic 



