Drug Resistance in Bacteria 9 



in a drug-free medium. As training proceeds reversion takes 

 place less readily until eventually the adaptation appears to 

 be relatively stable. This pattern of behaviour is seen in the 

 adaptation of Aerohacter aerogenes to proflavine (Davies, 

 Hinshelwood and Pryce, 1944, 1945; Pryce and Hinshelwood, 

 1947), and to sulphanilamide (Davies and Hinshelwood, 1943). 

 Reversion when it does take place need not be complete but 

 a lower level of immunity, the "equilibrium state", may be 

 reached and held for a considerable time. 



The stability, however, is never absolute. For example. 

 Dean and Hinshelwood (1954a) have trained Aerohacter 

 aerogenes to moderately high concentrations of proflavine, 

 propamidine and chloramphenicol and have subcultured these 

 trained strains for a very long time (about 1,000 generations) 

 in the drug medium. The adaptations, although of consider- 

 able stability, were eventually lost on long-continued sub- 

 culture in a drug-free medium, thus emphasizing the fact that 

 arguments from stable heredity cannot by themselves be used 

 to disprove the theory of environmental response. Moreover, 

 the entire pattern of events in these and in the earlier drug ex- 

 periments was more easily explained by an adaptive hypothesis 

 than by a theory involving mutations and reverse mutations. 



Similar results have been obtained with Aerohacter aerogenes 

 and acetate and with Bact. coli mutahile and lactose as sole 

 carbon sources. In the latter example although it has been 

 relatively easy to detrain the Lac^ strains partially (Dean 

 and Hinshelwood, 1954c) complete reversion to the Lac~ state 

 has proved more difficult. It has, however, been achieved in 

 one or two cases (Dean and Hinshelwood, unpublished). 



Mass -Number Relations 



If the only cells to develop and multiply in a given medium 

 are pre-existent mutants, the bulk of the population remaining 

 inert, then there can be no increase in the mass of the culture 

 as a whole without a corresponding increase in the number of 

 cells. If the average size of a mutant is nearly equal to that 



