MUTAGENS OF POTENTIAL SIGNIFICANCE 189 



go to tissue culture techniques, or ultimately the clinician, have some 

 idea what to look for. 



Neel: We're with you. Dr. Novick. All you can do is form a basis 

 for suspicion. From the knowledge around this table of the test systems 

 available, which are the best ones for formulating this basis for 

 suspicion? 



Novick: Dr. Auerbach pointed out, if not yesterday, at earlier talks 

 I have heard her give, that, clearly, one should demonstrate this is a 

 genetic change and should have a system where one can demonstrate 

 that the effect is indeed a genetic one. 



Atwood: I would like to augment your remarks about caffeine. The 

 mutagenicity of caffeine, I think, was first discovered in Ojihiostoma by 

 Kihlman. 



Auerbach: Yes. 



Atwood: I tried it in Neurospora under conditions that I thought 

 were the best; that is, they assured detection of mutants at any locus 

 because I used the recessive lethal method. It is not mutagenic by this 

 criterion at all, despite the fact that it was used in growing Neurospora 

 in a race tube, at a concentration that reduced the growth rate to two- 

 thirds of the normal value, and it even created a peculiar morphology 

 of the thing as it grew. Yet, at the end, no mutants had accumulated 

 whatever. 



Novick: The same thing is true with bacteriophage. 



Lederberg: I think you're putting the cart before the horse in asking 

 this question about drugs. In so far as we have grave suspicions con- 

 cerning an agent which is very widely used, namely, caffeine, I don't 

 see how we can possibly want to distract ourselves by very serious 

 consideration of a wide variety of other pharmacological agents until 

 we dispose of this one. 



Also, I don't know that there is ever any technique that is going to 

 tell us about the mutagenic effect of any chemical as applied to the 

 human population, if we're going to be making a variety of extrapola- 

 tions from a variety of sources. If we were all agreed with respect to 

 the mutagenicity of a given compound in Neurospora, E. coli, and 

 Drosophila, I think that we would consider it very hazardous to 

 assume it was not mutagenic in man. If we do find these discrepancies, 

 we can ask the question, on which side of the fence does man happen 

 to fall? 



I think, as a preliminary screening test for the likelihood of the very 

 general effect of a compound, the accumulation of bacterial mutants 

 in the chemostat is unquestionably the most satisfactory and most 



