ANTISEPTICS 149 



with other antiseptics. The table shows the concentra- 

 tions necessary to decrease the growth rate 30% and 85%. 

 The difference betw^een them is significant. It is usually 

 explained by the assum^Dtion that a low concentration of 

 sulfonamide retards growth slightly by attacking only one 

 locus of the cell constituent involved in the reaction. 

 Greater retardation can be brought about by an attack 

 on other loci, or possibly by some secondary reaction be- 

 tween the drug and the cell constituents, which would 

 cause a shift of equilibrium, and require a much higher 

 concentration of the drug. Several authors have re- 

 ported indications that other loci are attacked by larger 

 doses. However, this implies that the first retardation 

 is not increased by higher concentrations, and this impli- 

 cation again would make the action of sulfonamides dif- 

 ferent from that of all other antiseptics. 



The frequent!}^ encountered statement, that retarda- 

 tion of multiplication is caused by a reaction of the sul- 

 fonamides with catabolic enz;ymies of the cell, has very 

 little experimental support. Many investigators have 

 shown that large doses will retard or inhibit enzyme ac- 

 tion, but the same is true with large doses of sodium chlo- 

 ride. The inhibition of enzyme action by large doses of 

 any compound can certainly not be considered proof that 

 growth retardation by small doses is due to decreased 

 enzyme action. In order to prove that retardation of 

 growth is caused by enzyme inactivation, it is necessary 

 to demonstrate that enzymes are affected by doses caus- 

 ing a slight retardation of growth, say 20 to 30%. As 

 early as 1937, Mellon and Bombas measured b}^ the 

 Thunberg technique the effect of sulfanilamide on the 

 dehydrogenase of Pneumococcus Type I, and found that 

 even a concentration as high as 0.17% did not decrease 

 enzyme activity whereas 0.01% decidedly retarded growth. 

 Barron and Jacobs (1937) verified this observation for 

 other species. Chu and Hastings (1938) observed small 

 decreases (occasionally, however, as high as 50%) in the 



