Penicillin-induced Penicillin Resistance 91 



Speculative Discussion 



This symposium will undoubtedly contain many discus- 

 sions on the extent to which drug resistance may depend in 

 the first place upon a spontaneous change within an organism 

 (followed by selection) or upon a change specifically induced 

 in the organism by some factor in the environment. A study 

 of the development of the penicillinase type of penicillin 

 resistance in B. cereus, where changes in resistance can be 

 followed accurately at a biochemical level, has shown that 

 both types can occur, even within the same population of 

 individuals. It is vital, however, to recognize that the speci- 

 fically induced change (enzyme induction) is due to an 

 increase in the activity of an enzyme-forming system which 

 itself does not appear to play any part — however indirect — 

 in stimulating its own production. It is biochemically stable, 

 but genetically transitory. Although the antibiotic antidote 

 (penicillinase) developed in both types is identical, its mode of 

 acquisition and its genetic stability are quite different. Once 

 this distinction is accepted (but not before), it is permissible 

 to ask whether after all there may be some connexion between 

 the two types of phenomenon. 



In a speculative discussion (Pollock, 1953) ways have been 

 suggested by which enzyme induction by specific environ- 

 mental factors might theoretically lead to a stable heritable 

 change in an organism. It was argued that a necessary pre- 

 requisite for such an event would be that the external inducer 

 should, by some means (however indirectly), stimulate the 

 cell to form more of the inducer itself (or its biological equi- 

 valent). This attempt was influenced by what was felt to be a 

 need to adapt the theoretical speculations of Hinshelwood 

 (1946) towards the established facts of induced enzyme 

 synthesis. Now although the synthesis or activation of bio- 

 logically important molecules (e.g. formation of certain 

 polysaccharides or activation of many proteinase precursors) 

 in some subcellular systems often runs an autocatalytic course 

 because the reaction is stimulated by its own product, it 



