16 A. C. R. Dean and Sir Cyril Hinshelwood 



at lower pH values. In the proflavine experiments concen- 

 tration levels of 42 and 63 mg./l. were reached in 98 and 

 185 minutes respectively. In the first case the pH was un- 

 changed at the end of the experiment and in the second case 

 it had dropped from 7-0 to 6-7. Controls in which the cells 

 were inoculated directly into media adjusted to the pH 

 reached at the end of the respective experiments and con- 

 taining 42 and 63 mg./l. of drug respectively had lags of 

 380 and 1,300 minutes respectively. 



In experiments with sodium azide, concentrations of 263 

 and 430 mg./l. were reached in two experiments lasting for 

 130 and 245 minutes respectively. Controls put up as in the 

 proflavine experiments had lags of 3,000 minutes and infinity 

 respectively. 



There can be little doubt that these experiments involve 

 the adjustment of the cells to the adverse environment since 

 the time intervals are too short for any extensive selection of 

 pre-existing resistant mutants. This "physiological" adapta- 

 tion, is however, unstable on subculture. Continued subcul- 

 ture in the drug media stabilizes it. In this process there 

 would be time for selection. It would, however, be rather 

 surprising if there were two quite distinct mechanisms 

 involved in the development of a resistance and the gradual 

 stabilization of that same degree of resistance to the same 

 drug by the same organism. This matter is under further 

 investigation. 



Binding or Adsorption of Drugs by Resistant and Non- 

 Resistant Cells 



Proflavine-resistant cells of Bad. lactis aerogenes take up 

 from solution not less but more proflavine than those of the 

 non-resistant strain from which they have been derived 

 (Peacocke and Hinshelwood, 1948). On the other hand, 

 certain phage-resistant forms of Esch. coli B take up no phage, 

 in contrast with the corresponding sensitive forms for which 

 Brenner (1955) determined the adsorption isotherms. Eagle 



