CHEMOTHERAPY 137 



Woods found a similar effect with yeast extracts 

 and brought forward strong evidence that the responsible 



substance was ^^ -amino benzoic acid, NH2<[^ NcoOH, 



which he showed to have a powerful inhibitory effect on 

 sulphanilamide. He suggested that p-amino benzoic 

 acid is essential for the growth of the organism, and is 

 normally synthesised in adequate amounts. Sulphanila- 

 mide, which has a structure very similar to that of 

 2)-aminobenzoic acid, competes with the enzyme involved 

 in its further utilisation and so prevents groA\'th. Addition 

 of p-aminobenzoic acid overcomes the competition for the 

 enzymes and inhibits the action of sulphanilamide. 

 Very small amounts of p-aminobenzoic acid, about one 

 five -thousandth of the inhibitory concentration of 

 sulphanilamide, may suffice to reverse the effect of the 

 latter. He suggested that the varying sensitivit}^ to 

 sulphanilamide of different organisms was due to 

 differences in their power of synthesising 2^-aminobenzoic 

 acid. 



The explanation that sulphanilamide intervenes at 

 the stage of synthesis of ^^-aminobenzoic acid by com- 

 bining with the synthesising enzyme seems to be wrong, 

 because if it were true it would be expected that the 

 amount of 2:>-aminobenzoic necessary to reverse the 

 effect would be independent of the amount of sul- 

 phanilamide present. This is not so, the ratio of 

 2:)-aminobenzoic acid to sulphanilamide being constant. 



Other theories of the action of sulphanilamide have 

 been put forward but have been displaced by the 

 " essential metabolite " theory. It was, for instance, 

 suggested that in presence of sulphanilamide, streptococci 

 lost their power to produce a capsule and that, as a result, 

 they were much more susceptible to phagocytosis. This 

 hypotliesis does not account for the fact that many 

 normally non-capsulated organisms are susceptil)le to 

 sulphanilamide, nor for the in vitro bacteriostatic effect 



