60 Discussion 



bacterial growi:h is so quick, one may not detect this intermediate stage 

 by the methods used. One may only detect the end-effect when the final 

 mutational response to the changed environment has already taken place. 

 If the time interval could be narrowed within division times, one might 

 then find a gradual adaptation finishing eventually in a mutation. 



Demerec: The evidence accumulated by geneticists working with vari- 

 ous organisms indicates that, as a rule, mutations produce discrete rather 

 than gradual effects ; and the findings of research with antibiotics con- 

 form with this general picture. 



The experiment discussed in my presentation was not designed to 

 show whether or not the drug, in this case streptomycin, induces muta- 

 tion. It was designed to show that resistance to a low concentration of 

 the drug develops in discrete steps. The critical experiments, as men- 

 tioned by Lederberg, in studying whether mutation to resistance origi- 

 nates independently of the drug, are those where the drug has not been 

 used, such as the experiment which was discussed by Cavalli-Sforza this 

 morning, and also a replica plating experiment which was done by 

 Lederberg. 



Yudkin: Dr. Demerec, I think we all agree that what you have shown 

 once more is that genetic changes do occur. I don't think that either of 

 the two examples mentioned prove that induction or adaptation did 

 not occur, and I suggest that e.g. the outgrowth of resistant papillae or 

 parts of a colony may indeed have occurred through induction between 

 the drug and some of the bacteria which, when they become resistant, 

 obviously grow much faster. 



Another argument used in favour of drug resistance originating only 

 through genetic change is the chemotherapeutic one, i.e. the use of a 

 combination of drugs is much more effective than the use of the drugs 

 singly. And surely Sir Cyril would say that for a bacterium to become 

 adapted to a combination of drugs must be very much more difficult 

 than for it to become adapted to a single drug. 



Davis: I would question Dr. Alexander's statement that cancer is 

 clearly caused by mutation. I would agree that a cancer results from 

 inheritable change in a somatic cell; but the inheritable properties of 

 somatic cells, after all, are determined in part by the process of differ- 

 entiation, and in this process something in the environment directs 

 gradual changes that are inheritable. It would therefore seem reasonable 

 to consider the gradual process of carcinogenesis as an aberration of 

 differentiation. 



As Dr. Pontecorvo pointed out, geneticists would not deny the possi- 

 bility that the environment can direct an inheritable change, for they 

 would then be denying the process of differentiation. Unfortunately, 

 our understanding of differentiation is very primitive compared with 

 our understanding of gene mutations. It has long been hoped that 

 unicellular organisms would be helpful, since it is in principle quite 

 conceivable that one could find chemical or physical agents that would 

 cause such directed inheritable changes in these organisms. However, 

 few cases that fit this category have been observed, and none in bacteria. 

 The burden of proof still rests on those who would claim that drug 



