Introduction xiii 



the idea that, prior to its incorporation into intact, infective progeny particles, 

 the phage DNA exists in an intrabacterial phage precursor pool ( 144, 71 ) . 



Further insight into the process of phage multiphcation was gained by the 

 discovery of a variety of "incomplete" phage structures which possess one or 

 another of the properties of the virus without being endowed with the power 

 of self -reproduction, the most complex of all its attributes. Thus, premature 

 lysis of infected bacteria at late stages of the eclipse period liberates newly 

 synthesized proteinaceous material already possessing some of the antigenic 

 properties of the intact bacteriophage (119). The total amount of phage 

 antigen finally liberated upon spontaneous lysis of the cells, furthermore, 

 generally exceeds that incorporated into infective progeny (119, 32, 46). 

 Electron-optical observations of such lysates, furthermore, reveal the presence 

 of structures whose morphology bears some resemblance to the characteristic 

 shape of mature bacterial virus particles (161, 63). Prominent among these 

 structures are the "doughnuts" which Levinthal and Fisher (103) found to 

 appear during the eclipse and then to increase in number at about the same 

 rate as the complete phage particles. Later studies have shown that the dough- 

 nuts are, in fact, empty phage heads, and that the "maturation" of infective 

 progeny at the end of the eclipse seems to represent the stable union of phage 

 precursor DNA with phage precursor protein into structurally intact virus 

 particles (88,89). 



Phage precursor protein and phage precursor DNA are not the only 

 materials whose synthesis within the host cell is induced, or presided over, by 

 the DNA of the infecting parental virus. For, at the outset of intracellular 

 phage growth, the formation of some non-precursor proteins must proceed 

 before replication of the viral DNA can begin. One of these "early" proteins 

 was identified by Flaks and Cohen (53, 54) as the enzyme deoxycytidylate 

 hydroxymethylase, essential for the synthesis of the specific components of the 

 viral DNA, 5-hydroxymethylcytosine (160). Studies by Kornberg, Zimmer- 

 man, Kornberg, and Josse (90), presented in a paper of this collection, 

 revealed the phage-induced formation of four further enzymes, all of which 

 are demonstrably involved in the synthesis and replication of the viral DNA. 

 It is important to realize, therefore, that the phenotypic expression of the 

 genetic substance of the phage is not confined solely to the construction of 

 materials that find incorporation into the mature, infective progeny virus. 



In common with other organisms, bacterial viruses sport occasional 

 hereditary variants, or mutants, in the course of their growth (34, 68, 133). 

 These mutants can diflFer from their parents in a variety of characteristics, 

 such as the type of plaque formed on agar seeded with sensitive indicator 

 bacteria (67), the strains of bacteria which the phage can infect (105), or the 

 physical or chemical properties of the virus particle (2, 43, 26). The mutation 

 of the vegetative phage during its intracellular growth was used by Luria 

 (108) to probe the nature of the self-duplication of the hereditary material of 

 the infecting particle, as shown in a paper of this collection. In his experiment, 



