20 S. S. COHEN 



below, it is scarcely an exaggeration to note that the metabolic apj)roaches 

 to animal virus infection most commonly applied as of this writing are 

 oriented by the biochemistry of the 1930s, Unquestionably, the preoccupa- 

 tion even now with the estimation of oxygen consumption and glycolysis, and 

 the inhibitory effects of cyanide, fluoride, and iodoacetate reflect the classic 

 schooling in biochemistry of our animal virologists. Perhaps the most 

 generally demonstrated and commonly reproduced metabolic studies in this 

 field have shown that (1) the respiration of a host cell is not affected by virus 

 infection, and (2) an inhibitor which interferes with respiration, or alterna- 

 tively with the development of an energy supply, whether generated aerobic- 

 ally or anaerobically, prevents virus synthesis. 



Tlie author does not mean to deprecate the significance of data of this 

 character. However, it seems necessary to stress that, in the last decade, the 

 discipline of biochemistry has proceeded somewhat past this area of investi- 

 gation. The biosynthetic paths leading to the formation of the amino acids 

 and nucleotides have been delineated in such detail that it has been estimated 

 that approximately one-half of the intermediates in these sequences are 

 already known. However, it may quite proj)erly be asked why it might be 

 more illuminating to compare any of these biosynthetic paths in normal and 

 infected cells than it was to study respiration and energy supply. In some 

 virus diseases, such studies might not be useful. However, the following 

 considerations suggest that there might be a point to such exploration: 



(1) The viruses are structurally quite different from their host cells. Their 

 polymers differ from cellular polymers with respect to their specific organiza- 

 tion, as manifested in specific antigenicity and genetic continuity. Such 

 organizational and functional differences often reflect quantitative differences 

 in the amounts of particular amino acids and nucleotides employed. Thus, 

 an infected cell may differ from the normal cell with respect to the amomits 

 required of precursors of these uiiits, or of the units themselves, if supplied 

 exogenously. The infected cell may show a shift in ratio of the nucleic acids 

 or of other units, and thereby may reveal properties of the viruses as yet 

 unrevealed by study of the isolated agent. 



(2) Many paths of metabolism have alternative routes. Virus infection 

 may affect the balance of these, or even eliminate one completely. Our own 

 studies of the effect of virus infection on paths of glucose utilization in 

 Escherichia coli have established the existence of such shifts (Cohen, 1953), 

 and have assisted in the dissection of the controlling mechanisms of meta- 

 bolism in infected bacteria. 



(3) Some viruses have units which are not present in the host, e.g., 

 5-hydroxymethyl cytosine (HMC), which is present in the T-even phage 

 DNA and not in the host nucleic acids (Wyatt and Cohen, 1953). Such units 

 not only provide specific tags and unusual opportunities for the study of 



