44 Discussion 



Hinshelwood has performed a service in focussing on this interesting and 

 neglected area of biology. However, the real rub comes in his claim that 

 such reversible adaptive resistance, if carried through enough generations 

 will gradually develop (by some process other than random mutation 

 plus selection) into a stable, inheritable resistance. Most biologists 

 would be sceptical about the existence of such gradual, non-mutational 

 stabilization of an adaptation; and I feel that the experiments cited in 

 support of this concept are all compatible with mutation and selection. 



One further comment: as Sir Charles Harington pointed out in his 

 introduction, the general interest in drug resistance and the raison d'etre 

 of this symposium have arisen from the practical importance of the 

 problem. I would like to emphasize that the problem to which he refers 

 is the emergence of strains with an inheritable increase in resistance. 

 This is what is ordinarily meant by drug resistance. The problem of the 

 adaptive and other non-inheritable physiological factors affecting the 

 observed level of resistance of a cell is also interesting — but it is not the 

 problem of drug resistance. 



Pontecorvo: This last point which Prof. Davis has made is precisely 

 the one I meant when I mentioned what has been done in higher 

 organisms, particularly by Waddington. The experiment there is to 

 expose embryos of flies to a certain concentration of drug at certain 

 critical periods in development : a proportion of them develop into ab- 

 normal adults. Breeding is selective, i.e. only from the abnormal adults. 

 After a few generations abnormal adults develop even without treatment 

 or with a reduced one. In this case it is quite evident from the procedure 

 of the experiment that what has happened is that there was initially, 

 let us call it "physiological", variability: some individuals responded, 

 some did not. A genetic mechanism which can be pin-pointed to particu- 

 lar regions of the chromosome set has taken over later on. That is 

 precisely the transition from one mechanism to the other. It would be 

 important to see whether this transition can or cannot be favoured by 

 means other than selection by the stimulus ; so far, I am not convinced 

 that there has been any proof one way or the other. 



Gyorffy: To raise a point concerning definition: we need to make a 

 distinction between the terms "heritable" and "genetic"; they are not 

 synonymous, and we must take care in using them, because "heritable" 

 or "hereditary" means transmissible or transmitted from one generation 

 to another ; and "genetic " implies control by the genotype, by genes ; and 

 it is well known that all modifications are non-genetic changes. The 

 "Dauermodificationen", which very often occur in micro-organisms, are 

 "inherited" through a number of generations although they are not 

 genetic changes. Another complication is that each bacterial cell in 

 itself represents one generation, and if it is modified as by environmental 

 influence it may be "inherited" through a number of generations. That 

 again is not a real genetic change. I wonder whether we really are able, 

 in the usual experiments, to differentiate by the criterion of the term 

 "heritable" between a genetic change and a Dauermodification. The 

 term "heritable" seems to me somewhat ambiguous, and it will be better 

 when we no longer use this term in microbial genetics but use instead 



