54 M. Demerec 



Discussion 



Experimental evidence shows that resistance to drugs 

 originates in discrete steps, and that a high degree of resist- 

 ance may either be built up through successive changes or be 

 attained in a one-step change. The pattern followed is charac- 

 teristic of the drug. Two patterns have been recognized : the 

 "penicillin" pattern, in which high resistance is reached only 

 through multi-step changes; and the "streptomycin" pattern, 

 in which high resistance may arise either by multiple steps or 

 in a single step (Demerec, 1948). Recombination, transform- 

 ation, and transduction analyses all show that the trans- 

 mission of each successive degree of multi-step resistance is 

 distinct and independent — as required by genetical theory — • 

 and leave no room for theories involving the blending inherit- 

 ance that would result from adaptive changes. 



One argument that has been advanced in favour of adaptive 

 change is based on the observation that bacteria exhibiting 

 higher resistance than the original strain can readily be 

 obtained from cultures grown in medium containing a drug 

 in low concentration, where all the bacteria survive. It is 

 reasoned that in such cases the drug has no opportunity 

 to select resistant mutants that might already have been 

 present in the culture, and therefore that the observed 

 increase in resistance results from adaptive changes. How- 

 ever, detailed studies in which Esch. coli was grown in low 

 concentrations of streptomycin have shown that even under 

 these conditions the presence of the drug gives an advantage 

 to resistant variants, which most likely originate as mutants 

 during the previous growth of the bacteria used in the experi- 

 ments (Demerec et al., 1950). In the most critical portion of 

 this study, aliquots containing about one hundred bacteria 

 were plated onto a series of broth agar plates, half containing 

 one (jLg. of streptomycin per ml., and the other half — used as 

 controls — containing no streptomycin. After 24 hours of 

 incubation the numbers of colonies appearing on the experi- 

 mental and on the control plates were about equal, indicating 

 that the presence of streptomycin had not affected survival 



