MUTAGENESIS 81 



years and has not been substantiated as yet in my opinion. This is 

 Gershenson's claim that he had produced mutations in Drosophila by 

 adding thymonucleic acid to the medium (27j. Rapoport tried to re- 

 peat this, and somebody in Muller's laboratory tried to repeat it, but 

 without success. Now, however, when genetics has again started in 

 Russia, Gershenson has made the same claim on the basis of data 

 which I did not find very convincing. However, he wrote to me about 

 it and sent me a sample of his calf nucleic acid, and assured me that 

 if we tested it the way he did, it would prove mutagenic. I think 

 somebody in our laboratory will try it. 



After this, then, come the mutagens which were tested on the basis 

 of our knowledge, or what we believe is our knowledge now", that DNA 

 is the important part of the genetic material. The other day I was 

 looking through some old notes I made on this point. I was amused 

 to see that immediately after Avery had published his first data on 

 transformation — I believe it was in 1944 — Muller wrote to me sug- 

 gesting that somebody should test deoxyribonuclease for mutagenic 

 ability. I was busy with other chemicals then, and this suggestion was 

 not followed up at the time. Last year Kaufman (39) had the same 

 idea, and DNAase did, indeed, turn out to be mutagenic for Drosophila. 



Then, finally, nitrous acid has come back again, and this time on 

 the basis of what we think is a correct theory of how it acts on DNA 

 and RNA (28). It has been used with very spectacular success. 



There is one conclusion which I think one should draw from all 

 this; in the history of chemical mutagenesis, the wrong theories have 

 very often led to the selection of very good mutagens. I think this 

 should warn us to be cautious, for it means that if we have a theory 

 about mutagenesis and, on the basis of this theory, choose a mutagen, 

 and it acts, this does not prove the theory. It doesn't disprove it, but 

 it doesn't go very far toward proving it. Ethylene imine was used with 

 success on the basis of at least three different theories. 



Perhaps there is a practical question here, but I don't know whether 

 you want to discuss it; that is, what mutagens one should choose for 

 future work. Apparently there is a vast array already to choose from, 

 and I am convinced that there are whole additional groups of sub- 

 stances that contain mutagens. I think, from a practical point of view, 

 one should look for mutagens among substances which are likely either 

 to cause damage by producing mutations or to be helpful in inducing 

 mutations where they can be useful; for instance, in microorganisms. 



However, from a theoretical point of view, I think the choice of 

 mutagen depends on the attitude one has to the study of mutations. It 



