Discussion 59 



it is formed, it comes to a point where the block takes place by the drug ; 

 if that is at a very late stage in the formation of the genie material this 

 can split off and convey information for subsequent replication, but is 

 incomplete in so far as the whole information is not available for subse- 

 quent replication. In subsequent replication the drug does not enter into 

 the picture at all. That explains why one can get resistance forming in 

 one generation and also quite abruptly. There may be many flaws in 

 that picture, and I am putting it forward only as a basis for discussion : 

 that it may be the means whereby the information can be transmitted for 

 subsequent formation of genie material which is not affected by the drug. 



Lederberg: This model is one of a number of formal schemes which can 

 be elaborated to explain the fact that the initial genetic changes (if they 

 arose) were being produced by the drug. I think that if we had many 

 examples where we could unambiguously show that these initial "catas- 

 trophes" w^ere produced by the drug, we would then avidly seek details 

 of the models in which they would exist. But I think the whole point 

 we have been discussing is not the ways in which this might happen, if it 

 happened, but whether it happens at all. Prof. Cavalli-Sforza, for 

 example, has shown that we can get these alterations in the copies of the 

 template which occur without the drug ever having been present in 

 those cells. I know there will not be unanimous agreement on this ; there 

 will be those here who will continue to insist that there are local effects 

 which are in fact induced by the drug, but I don't think even that is 

 Prof. Hinshelwood's model of what is going on, and he has a rather more 

 subtle understanding of the inductive effects that might come into play. 

 We may come to a time when we know just what reagent to use, when 

 we can create specific blocks in replication of particular genes in the 

 genetic material, but so far we have not found such reagents. 



Hotchkiss: It should require a high degree of specificity indeed, to 

 cause a block at one particular unit, when all of it seems to be made of 

 DNA in which the chemist can as yet discern no specificity except that 

 implied in the genie action. 



Alexander: I w^onder whether Dr. Demerec's point that he finds this 

 sharp distinction is as decisive as it seems (between bacteria which have 

 mutated and those which have not). The time interval in bacterial 

 development is so short that it might be possible that this is a directed 

 mutation, directed by the physiological state of the cell. There may be 

 some similarity in the carcinogenic process, because once a tumour cell 

 has been produced this is a clear case of mutation, yet there is a long 

 interval in which we have to produce an unnatural physiological condi- 

 tion in the animal before this occurs; in some cases this is done with 

 chemicals which are mutagens. But the most decisive proof that a 

 mutagen is not always necessary comes from the experiments by the 

 Oppenheimers, who found that the introduction of an unnatural en- 

 vironment, namely a thin film of any sort, will eventually after a year or 

 so create the condition where tumour cells grow. So there one can make 

 a good case that the mutation which has given rise to the tumour cell 

 has come as a response to an unnatural physiological environment. The 

 same situation might also arise in bacteria, but since cell division and 



