On the Nature of Cancer 127 



The deficiencies of cancer, stressed in this article, contrast strongly 

 with the assumed totipotency of cancer so implicit in the concept of 

 autonomy. Chemotherapy would be a hopeless endeavor indeed if the 

 normal cells were forced to compete with complete autotrophics which 

 could avail themselves not only of simple substrates but also of nu- 

 merous alternate metabolic pathways. The tolerance of adult differ- 

 entiated host cells to most drugs is limited. Although they do not 

 require as much energy as do growing cells they cannot adapt to radical 

 changes in their chemical functional environment. Indeed, it may be 

 just such adversity which produces cancer! Curiously enough it has 

 been suggested and also actually demonstrated that weak or very poor 

 carcinogens are inhibitors of cancer. 



Cancer prevention in man is so far restricted to the elimination of 

 carcinogens from the diet and from the immediate environment. But 

 if it should be found that viruses do in fact play a major role in the 

 dissemination of cancer, then presumably antisera to specific viruses 

 and as yet undeveloped antibiotics would find employment in diagnosis 

 and prophylaxis. It is perhaps fortuitous that some of the experi- 

 mental drugs against cancer, 8-azaguanine, for example, are also anti- 

 viral. The practical aspects of the problem, however, limit therapy 

 to the treatment of cancer after diagnosis has been made, and, indeed, 

 without respect to the precedent chain of events. It must be presumed 

 that diagnosis will not be made until the cancer is well established 

 and even metastatic. Therapy then consists in selective attack on 

 neoplastic tissue. 



Most of the effort in design and synthesis of compounds which will 

 either destroy or modify cancer cells preferentially is devoted to growth 

 antagonism. Preferential, because normal differentiated cells do not 

 have to divide; cancer cells apparently do. Growth antagonism is 

 often thought of as being synonymous with interference with nucleic 

 acid metabolism. This easy assumption is probably an oversimplifica- 

 tion, but it has given rise to many new compounds and a number of 

 interesting biological applications. 



Animal cells make their nucleic acids from amino acid; there is no 

 nutritional requirement for either preformed purines or pyrimidines. 

 Adenine is exceptional among the nucleic acid bases, since it is the only 

 one which is accepted and incorporated by the metazoans. Part of 

 this adenine is converted to polynucleotide guanine. Guanine itself, 

 on the other hand, is not incorporated at all. The protozoan Tetra- 

 hymena geleii, however, has an obligatory requirement for guanine. 

 Kidder, who had interested himself in the dietary requirements of this 



