18 S. S. COHEN 



Special attention was given to the problem of the size and shape of infectious 

 particles, a problem whose solution was subsequently greatly facilitated by 

 the use of the electron microscope. Chemical effort concentrated on the 

 detection, identification, and estimation of virus nucleic acid, and studies 

 were initiated on the physical characterization of viral fragments, proteins, 

 and nucleic acid. Systematic amino acid analysis was also begun from the 

 point of view of distinguishing genetically different but related viruses. These 

 were the initial steps toward a chemical genetics, operating on the view that 

 proteins were probably the critical elements in determining inheritable 

 specificity.^ Clues to viral parasitism and virus multiplication were sought in 

 the analysis of virus preparations for intermediate metabolites, vitamins, 

 and a few enzymes for which a then primitive biochemistry was capable of 

 testing. 



By the early 1940s the biophysical analysis of the viruses became as 

 sophisticated as the biophysics of the era, and indeed contributed in no small 

 part to its development. On the other hand, biochemical virology was pursued 

 as an exercise in analytical chemistry.^ In addition, having adopted the 

 approach of obtaining maximal analytical information concerning the 

 smallest characteristic particle capable of "self-duplication," chemical 

 virology had become almost divorced from developmental and physiological 

 aspects of biology and from certain major trends then developing in bio- 

 chemistry, particularly enzymology and the study of intermediary meta- 

 bolism. The prevailing orientation was, however, ideally suited to vaccine 

 production, a problem dictated by the exigencies of World War II ; for a 

 number of years in this period, the biochemists working in this field continued 

 to explore the concentration, purification, and characterization of viral 

 antigens, as well as other practical problems. 



B. The Metabolic Machinery and Virus Infection 



1. The Host As a Source of Metabolites Necessary for Virus Multi'plication 



Nevertheless, the biochemical work of the early period established the 

 theoretical basis which called for the shift to the metabohc study of the host 



1 At one time iii this period the autlior was busily engaged in racing preparations of 

 the polymeric ribose nucleic acid (RNA) of tobacco mosaic virus to the analytical ultra- 

 centrifuge rather than to the greenhouse (Cohen and Stanley, 1942), since it was never 

 imagined that isolated RNA might have been infectious. 



2 Biochemistry was quite unprepared at that time to dissect the elephantine polymers 

 presented by virology. However, after almost a decade, some of the same laboratories 

 returned to prod at the structures of tobacco mosaic virus with the new tools of a decade 

 of progress in chemistry and physics, and the virus revealed its innermost secrets at 

 every new, more sophisticated touch; the particle seemed to be only too eager to show 

 how simply it was put together. 



