D. W. WOOLLEY 



mins but which were biochemically antagonistic to them. This work 

 was not the first* to demonstrate such antagonism, but it was the first 

 in which the relationship was seen in a light suflficiently bright to cast 

 a shadow ahead. Woods observed that the bacteriostatic action of 

 the sulfonamides was reversed competitively by />-aminobenzoic acid, 

 the structural analogue of sulfanilamide. The chemical relationship 

 here was that sulfanilamide was /)-aminobenzoic acid with a sulfon- 

 amide group instead of a carboxyl group. The hypothesis was ad- 

 vanced that the sulfonamides owed their action in inhibiting growth 

 of bacteria to their competition with /)-aminobenzoic acid in an essen- 

 tial metabolic reaction. This postulate gained some foundation in 

 fact when it was shown that /?-aminobenzoic acid occurred in yeast 

 and other living forms, and, more especially, that it was an essential 

 growth factor for several species of bacteria. 



The discovery of the relationship between /?-aminobenzoic acid 

 and the sulfonamides prompted the application of similar types of 

 structural change to other vitamins in efforts to produce from these 

 vitamins bacteriostatic compounds. It was soon found that 3-pyridine- 

 sulfonic acid and its amide would inhibit the growth of certain bacteria 

 in a manner subject to reversal by nicotinic acid. Likewise, thio- 

 panic acid [pantoyltaurine, jV-(a,7-dihydroxy-/3,/3-dimethylbutyryl)- 

 taurine] acted competitively with pantothenic acid to produce bac- 

 teriostasis, and several a-aminosulfonic acids competed with a-amino- 

 carboxylic acids. (The structural formulas of some of these and suc- 

 ceeding compounds will be found on pages 371-373.) Thus it began 

 to appear that the principle of structural analogy was the basis of a 

 general means of producing bacteriostatic compounds. 



The next advance was made when it was found that some types 

 of structural analogues of various vitamins would cause the appearance 

 of characteristic signs of vitamin deficiency diseases in animals, and 

 that these signs could be cured or prevented by adequate doses of the 

 vitamin involved. There is an excitement and appeal about a spec- 

 tacular experiment with animals which is never quite equaled by simi- 



* The pioneer observation of Quastel and co-workers on the reversible 

 inhibition of the oxidation of succinate by malonate, and the finding of Woolley 

 et al. on the toxic effect of 3-pyridinesulfonic acid in nicotinic-acid-deficient dogs 

 antedated Woods' work; but these two investigations, especially the latter, lacked 

 sufficient appeal and interest to stimulate further searches, 



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