18 MOLECULES, VIRUSES, AND BACTERL\ 



past few years on virus-controlled synthesis of enzymes and some other 

 proteins in infected E. coli. 



Early data on polymer synthesis in infected cells 



Until 1952 it was thought that the T-even viruses might merely 

 redirect the existing metabolic machinery of the bacterium to the pro- 

 duction of viiTJS by replacing a set of critical bacterial templates with 

 viral templates. Thus infected cells could no longer divide, nor could 

 they be induced to produce ^-galactosidase ( Monod and Wollman, 

 1947). Nevertheless, respiration and assimilation into polymeric sub- 

 stance appeared to continue at the same rate after infection as before 

 infection (Cohen and Anderson, 1946). If one concentrated on the 

 fate of assimilated P, for example, this now was directed almost en- 

 tirely toward the production of viral DNA, while the net synthesis of 

 RNA, the nucleic acid present in largest amount in the bacterium, 

 stopped. The discovery of the new and unique pyrimidine HMC, 5- 

 hydroxymethyl cytosine (Wyatt and Cohen, 1952, 1953), for the first 

 time led to the suspicion that the virus might be contributing another 

 qualitatively new element, i.e., the ability to control a metabolic func- 

 tion which perhaps did not exist at all in the vminfected bacterium.* 

 This function was one essential to viral duplication in providing a new 

 base, a pyrimidine without which viral DNA could not be made. 



Almost from the beginning of chemical study it had been appre- 

 ciated that there was a mystery in protein synthesis in infected cells. 

 As shown in Figure 1, protein synthesis continued from the inception 

 of infection (Cohen, 1947); however, very little of the protein which 

 was formed before viral DNA synthesis began appeared in the virus 

 eventually hberated (Hershey et al., 1954; Watanabe, 1957). Was this 

 bacterial protein which continued to be synthesized? For example, it 

 is known that infection causes a leak in the permeability barrier of the 

 cell and that there is a subsequent repair (Puck and Lee, 1955). It 

 was possible that this repair involved protein synthesis. 



It was demonstrated first by means of the specific analogue, 5- 

 methyl tryptophan (Cohen and Fowler, 1947; Burton, 1955) and sub- 

 sequently with chloramphenicol (Tomizawa and Sunakawa, 1956; 



* Although it had been known that deoxyribonuclease is markedly increased 

 in amount after infection with certain viruses, and that this increase is inhibited by 

 chloramphenicol and thienylalanine (Pardee and Williams, 1952; Kunkee and 

 Pardee, 1956), this effect was most frequently attributed to the activation of pre- 

 existing enzyme rather than to a de novo synthesis of the enzyme ( Kozloff , 1953; 

 Kunkee and Pardee, 1956). This preference probably reflected in large part the 

 intellectual climate at the time of these problems, although evidence for both pos- 

 sibihties had been obtained. \\'hether one or the other or both are correct has not 

 yet been estabhshed. 



