MUTAGENESIS 79 



of substances for mutagenic action, is pharmacological. Mustard gas 

 was discovered because, pharmacologically, it resembles X-rays in the 

 kind of burns it produces. Then followed a whole list of similar sub- 

 stances. Simply on pharmacological principles, other substances were 

 found to be mutagenic; for instance, allyl zsothiocyanate was tested 

 because it was vesicant. In 1947, I got a letter from a German Ph.D. 

 student who sent me a sealed little vial with a chemical in it, and 

 thought it should be tried because it was vesicant. I had so much else 

 to do that I forgot all about it. Then, about ten years later, ethylene 

 imine turned out to be a good mutagen and this somehow seemed to 

 ring a bell, so I hunted through my chemical cupboard, and there was 

 this little vial. It was ethylene imine which had already been suggested 

 on purely pharmacological grounds. 



Pharmacological research is still the source of an ever-increasing 

 number of the so-called alkylating agents that produce mutations. All 

 of them are also carcinostatic, but this correlation is one-sided and 

 somewhat biased. What happens usually is that when a substance is 

 found to be carcinostatic, it is turned over to a geneticist, mainly the 

 Fahmys (21) at the Chester-Beatty Institute in London, and then it 

 is tested for mutagenicity. Usually it is found to be mutagenic. I think 

 the connecting link between the two properties is the ability to break 

 chromosomes. 



Also on pharmacological grounds, a number of alkaloids have been 

 tested successfully for mutagenic ability. Oehlkers (57) in Germany 

 produced chromosome rearrangements with scopolamine, morphine, 

 and similar substances. Clark (11) in Australia detected another group 

 of mutagenic alkaloids on pharmacological grounds, this time the sug- 

 gestion came from veterinary medicine. Certain pyrrolizidine alkaloids, 

 for instance heliotrin, are of concern to sheep breeders because they 

 cause liver disease in sheep. He tested some of them on Drosophila 

 and obtained very high mutation frequencies indeed. I want to give 

 this simply as a suggestion that there may be whole groups of sub- 

 stances that have never been tapped for mutagens. 



After this, I come to substances which were discovered because 

 of theories as to how a mutagen should act. One of the theories which 

 was developed in connection with the alkylating agents was the idea 

 that cross-linkage is necessary for mutation. This idea came from 

 wool research, where it had been found that some of these substances 

 cross-link protein fibers. Then the cancer workers found a very im- 

 pressive correlation between the number of functional groups in these 

 compounds and their carcinostatic ability. In fact, Professor Haddow 



