D. E. GREEN 



cnzymic effects at tiie jneseiit time, there is n(j alternative explanation 

 that merits serious consideration. Alternative explanations usually 

 amount to substituting an obscure phrase for an obscure phenomenon. 

 Thus, some pharmacologists talk about trace substances upsetting an 

 "active patch" of some important cellular membrane and thereby 

 exerting their action. When interrogated about the properties of the 

 "active patch," the pharmacologist usually admits that he has in mind 

 some specific combining group and in effect admits a somewhat 

 watered-down version of an enzyme reaction. Certainly there is no 

 way of testing the "active patch" hypothesis as commonly stated nor 

 is there any evidence that it has been productive either in explaining 

 or predicting new phenomena. One cannot resist the conclusion that 

 the "active patch" concept is a terminological device for cloaking 

 ignorance. Another variant of the "active patch" concept is the so- 

 called "active surface" which is sensitive to pharmacological agents 

 and which controls certain key biological functions. The effect of 

 agents on these surfaces is said to be exclusively a physical one, /. e., 

 the "active surface" becomes covered by the pharmacological agent 

 and consequently is inactivated. The extraordinary specificity of 

 pharmacological effects and the high dilutions at which these effects 

 occur render this interpretation in purely physical terms unlikely. 



The discovery by Woods (6) that the antibacterial action of the 

 sulfonamides could be explained in terms of the resemblance of the 

 sulfonamides to ^-aminobenzoic acid was an important milestone in 

 our understanding of the mechanism of the action of drugs. It became 

 at once clear that some cnzymic process was at the bottom of the chemo- 

 therapeutic action of the sulfonamides. There is still no clue as to the 

 nature of this enzymic process but there can be little doubt that the 

 process is enzymic. /^-Aminobenzoic acid is a naturally occurring sub- 

 stance in yeast and animal tissues. Many bacteria and molds are 

 unable to grow unless it is present in the medium. The trace con- 

 centrations in which it must be present for optimum growth exclude 

 all but a catalytic role. In fact, /^-aminobenzoic acid has been shown 

 to exist in yeast largely in the form of a polypeptide, which may well 

 be its active catalytic form in the intact cell. One theory of sulfon- 

 amide action assumes that the sulfa drugs displace /^-aminobenzoic 

 acid from its combination with specific proteins and thereby inactivate 

 enzymes important in the growth of certain microorganisms. In 



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