PROBLEMS OF MEASUREMENT OF MUTATION RATES 71 



Atwood: If you have a treatment that gives no apparent killing 

 and gives a high rate of total auxotrophy, let's say 10"*, well, if the 

 actual number of auxotrophs formed carries with it a thousand times 

 that many lethals, you wouldn't detect it, because you would still 

 have less than 1 per cent of the bacteria killed, and nobody detects 

 that difference by plating. You would still say there is no killing with 

 this mutagen. 



Goodgal: Yes, essentially, that is correct. 



Atwood: So that you can't tell an irreparable recessive lethal except 

 by a special method such as trying to stabilize the diploid. 



Neel: Those of us who work with man are intrigued by this dis- 

 cussion of how difficult it is to define a lethal in bacteria. At the risk 

 of being overly sweeping, I have the feeling that the range of muta- 

 tions with which we can work in man is so restricted in one way or 

 another, and that the range with which you work in bacteria is, 

 perhaps, so restricted in its way, that any attempt to compare mutation 

 rates in two species is premature at the present time. 



Auerbach: But one doesn't compare the over-all rates. One usually 

 compares mutation frequencies at individual loci, or what one thinks 

 are individual loci. 



Neel: My remarks apply to individual loci, as best we can come 

 to grips with them in man. 



Auerbach: Yes, but I don't really see the difference; once you can 

 recognize a mutation at an individual locus, it doesn't matter whether it 

 is an eye color in Drosophila or hemophilia in man. 



Neel: You mentioned hemophilia in man. It is a fact that what 

 was hemophilia ten years ago is now one-third another disease that 

 we call Christmas disease. In man we never know when we are 

 working with a single locus, and we never know how much of the 

 mutation spectrum at that locus we are picking up. 



Auerbach: I think that many of these difficulties disappear when 

 one considers individual loci rather than the whole genome. One can- 

 not compare all mutations in man with all mutations in Drosophila; 

 this is meaningless. 



Neel: I wish I felt as confident as Dr. Auerbach, that these difficulties 

 disappear when we talk of the individual locus. 



Auerbach: Some of them disappear. I think Kim has enumerated 

 those which remain, but I think the additional ones which you made 

 will largely disappear if one restricts oneself to a comparison of 

 mutation frequencies at what one thinks are known loci. I know 

 that the estimate of mutation frequency to hemophilia has changed, 

 but only by a factor of 2 or 3. 



