Drug Resistance in Bacteria 5 



Before outlining the proposed mechanisms and sum- 

 marizing this evidence another point should be made clear. 

 The primary concern of the work has been to explore the 

 problem of the way in which cell reactions are co-ordinated, 

 and the manner in which adjustments in the cell economy can 

 take place, not to assert the relative importance of this or 

 that evolutionary mechanism. A sound judgement on this 

 latter question will probably be reached only when the 

 number of examples studied is considerably greater than it 

 is at present. 



In quoting the kinds of evidence on which our current 

 views are based we shall group together examples of adapta- 

 tion to drugs and certain examples of adaptation to new sub- 

 strates. The mechanisms will be often, though not always, 

 the same. The addition of a drug to the medium often im- 

 pedes certain essential enzyme reactions and so imposes a 

 new reaction pattern on the cell. This is not unlike what 

 happens when an unfamiliar substrate has to be used. On the 

 other hand, drug resistance could arise, as in some cases phage 

 resistance seems to, by a mutation leading to a deficiency 

 whereby receptors for the drug in the cell are extirpated. In 

 such a case the analogy with enzymic adaptation would be 

 absent. 



In its essentials the mechanism of adaptive change which 

 we believe to operate in certain examples is the following. 

 Although the major characters are determined by the basic 

 gene structures, their quantitative expression is a function 

 not merely of what structures are present but of the propor- 

 tions in which they occur in the cell. When the medium is 

 changed so that some parts of the reaction sequence are im- 

 peded relatively to others, corresponding changes in the rela- 

 tive proportions of the major cell constituents must occur. 

 If division is governed even approximately by the attainment 

 of a threshold amount of some key substance (and DNA seems 

 to be roughly an invariant in this respect), then it is easily 

 shown that the cell composition adjusts itself automatically 

 to give an optimum growth rate. 



