D. E. GREEN 



sullicionlly s(jlul)k\ In othci- words, no new principle emerges. A 

 more effective sulfa drug docs not extend the range of action of sulfa 

 drugs in the sense of inhibiting organisms which are otherwise insensi- 

 tive to the sulfa drugs. From the standpoint of enzyme chemistry, 

 the direction which much of chemotherapy research has taken does 

 not appear to be either profitable or rational. Chemotherapy cannot 

 be attacked intelligently without a detailed knowledge of intermediary 

 metabolism and enzyme chemistry. We may make allowances for 

 the element of urgency in wartime, but after the war, there ought to 

 be a better balance between the sums spent on sheer trial-and-error 

 organic synthesis and the sums spent on fundamental investigations. 



Woolley (7) has pioneered in providing a framework for a 

 rational pharmacology based on the antivitamin concept. He showed 

 that certain antivitamins can produce a state of avitaminosis, in some 

 cases in a matter of hours, merely by displacing the vitamins competi- 

 tively from their catalytic complexes. Since profound pharmaco- 

 logical effects attend the syndrome of avitaminosis, antivitamins have 

 to be regarded as potential pharmacological agents. Thus, pyri- 

 thiamin rapidly induces the disorders of the central nervous system 

 which are characteristic of thiamin deficiency. The lesion is of course 

 righted at once by addition of large enough amounts of thiamin. Since 

 the quantitative importance of the catalytic reaction in which vitamins 

 participate varies depending upon the organ or part of the organ, 

 it does not follow that all antivitamins will exhibit similar pharmaco- 

 logical effects. On the contrary, it would appear that each anti- 

 vitamin would selectively poison only a particular portion of the nervous 

 system as well as only particular organs. A complete series of anti- 

 vitamins should provide a wide range of specific pharmacological 

 agents, all of which are reversible by addition of the vitamins which 

 they imitate. The beginnings in this new field of exploration are still 

 modest but the horizons seem immense. 



The hormones represent a class of substance which, according 

 to the enzyme-trace substance theory, ought unequivocally to qualify 

 as enzymes or essential parts of enzymes. Yet no one has conclusively 

 demonstrated that any one of this large class is either an enzyme or an 

 essential part of an enzyme. Do we have in this class a notable excep- 

 tion to the theory? There is no basis for answering this question defi- 

 nitely one way or the other. There is a possibility that renin, the 



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