ASPECTS OF THE PROBLEM OF DRUG 

 RESISTANCE IN BACTERIA 



A. C. R. Dean and Sir Cyril Hinshelwood 



Physical Chemistry Laboratory, Oxford 



General Observations 



In presenting this brief review of our present ideas on the 

 subject of drug resistance it may be well to begin by mention- 

 ing views which have at one time or another been attributed 

 to us, but which we have never held and of which no expres- 

 sion could be quoted from any of our publications. 



We have never doubted that the essential characters of a 

 cell are inherent in the structure of certain fundamental units 

 including (though not necessarily exclusively) the deoxy- 

 ribonucleic acid (DNA). We do not suppose these basic 

 structures to be easily susceptible to change, and indeed in 

 our experience easily provoked changes are normally destruc- 

 tive. The maintenance of species characters is of course a 

 matter of the copying of the genetic patterns, and if and when 

 these have been changed the heredity will be changed. We 

 have never denied that structural mutations leading to 

 increased drug resistance or improved utilization of nutrient 

 sources can and do occur, or the obvious consequence that the 

 mutants so arising would be rapidly selected in the appro- 

 priate environment. 



On the other hand, we have contested the assumption that 

 random mutation and selection is the sole mechanism (or 

 perhaps even the major mechanism) for adaptation to new 

 media or for the development of drug resistance. We have 

 proposed more direct mechanisms, and quoted what appears 

 to us to be good experimental evidence that in various specific 

 examples these mechanisms operate. 



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