SOME CATALYTIC ASPECTS OF DISEASE AND DRUGS 231 



structure thus characterized. Finally, J. W. Cook, C. L. Hewett 

 and I. Hieger 36 extracted from about two tons of active tar a tiny 

 percentage of 3,4-benzpyrene; it produces epitheliomas in mice 

 after about 5.7 months application of dilute benzene solutions, 

 whereas 1,2,5,6-dibenzanthracene takes about 8 months to produce 

 a like effect. Later it was found that methylcholanthrene, closely 

 related to certain sex hormones and first synthesized by degrading 

 desoxycholic acid (a bile constituent), is still more potent, giving 

 cancers in about 5 months. These carcinogenic agents may cause 

 cancers to develop in various tissues, e.g., epitheliomas when ap- 

 plied to the skin, sarcomas when injected subcutaneously. Prof. 

 Fieser stated: 



"While proof is entirely lacking, it appears possible that many 

 forms of cancer may originate in the metabolic production of 

 methylcholanthrene or related substances from the bile acids, or 

 perhaps from sterols or sex hormones, of the body. . . . Entirely 

 unknown is the mechanism whereby certain hydrocarbons start 

 normal cells on a career of malignancy. If chemical reaction is in- 

 volved, the nature of the change is entirely obscure. . . . Possibly 

 the molecular dimensions and the surface activity of the substances 

 are as important as their chemical characteristics." 



The view here being maintained is that the effects of carcinogens 

 are due to their ability to produce heritable changes in biocatalysts, 

 either by inhibiting or modifying existing catalysts, or by entering 

 into the creation of new ones. 



In some cases viruses are known to produce cancer (e.g., Rous 

 chicken sarcoma), but it is not yet clear whether the self-repro- 

 ducing (autocatalytic) virus acts as a catalyst of itself, whether it 

 induces changes in other biocatalysts, or whether both of these 

 events simultaneously occur. In any event, the virus, whether 

 catalyst or catalyst inhibitor or modifier, is continually supplied 

 by its own autocatalysis. It can catalyze the formation of specific 

 antibodies in the host fowl, and it may compete for, utilize or 

 destroy substances essential to the normal catalysts or metabolism 

 of the cell. 



Since there is not even a suspicion of evidence that the trivial 

 quantities of chemical carcinogens reproduce themselves, it ap- 

 pears that their specificities of chemical structure, reflected in 

 their active surfaces, enter into the formation of new self-dupli- 

 cating catalyst areas. This is the mechanism whereby the cell 

 starts off on a career of malignancy. Where cancer cells reproduce 



