xii Introduction 



cellular reproductive process after the proteinaceous tail has attached the virus 

 particle to the bacterial surface and the DNA has safely entered the interior 

 of the host cell. This historic discovery showed that it must be the viral DNA 

 that is the carrier of the hereditary continuity, i.e. the germinal substance of 

 the extracellular, resting phage. The release of the DNA from its protein 

 envelope at the very moment of infection also accounts for the existence of the 

 eclipse period at the early stages of intracellular virus development. For 

 having been divested of its attachment and injection organs, the DNA of the 

 infecting phage naturally is unable to gain entrance into any further bacterial 

 cells to which it may be presented in the infectivity test. 



What happens to the viral DNA after its injection into the host cell? In 

 1950 Putnam and Kozloff ( 126 ) devised an experiment directed toward the 

 question of whether any of the atoms of the parental DNA ultimately reappear 

 among the progeny viruses. In this "transfer experiment," bacteria are infected 

 with phage particles whose DNA is isotopically labeled, and the phage yield 

 issuing from such infected cells assayed for its content of parental isotope. The 

 outcome of Putnam and KozlofiF's transfer experiment was that about half of 

 the atoms of the parental DNA were found to be transferred to the progeny. 

 This work was confirmed and extended with improved experimental techniques 

 by Watson and Maal0e (120, 152), one of whose publications is included in this 

 collection. In view of the inference that it is the DNA of the virus which 

 carries the genetic continuity into the host cell, it seemed likely that an under- 

 standing of the mechanism of transfer of DNA atoms from parent to offspring 

 might afford valuable insight into the nature of the reproductive process. 

 Further investigations have revealed that the parental DNA complement of a 

 single parental virus is not transferred intact to a single progeny virus, but that 

 the molecular patrimony is dispersed over several offspring phages (76, 143, 

 101, 145). 



Some theories of the nature of phage multiplication envisaged that there 

 are present, within the normal host bacterium, bacteriophage precursors whose 

 metamorphosis into mature bacteriophages is merely triggered by the infecting 

 phage particle (93). This view was finally dispelled in 1948 by an experiment 

 of Cohen (37), designed to determine the origin of the substance of the 

 progeny phages. This work, reported in a paper of this collection, represents 

 the first use of radioisotopes in the study of bacterial viruses. By exposing 

 bacterial cultures to P*-, either only prior to or only subsequent to their infec- 

 tion with phage, and analyzing the virus progeny for their relative content of 

 radioisotope, Cohen could show that most of the phage DNA is synthesized 

 from materials still in the growth medium at the moment of infection; hence, 

 the phage particles cannot have been derived from pre-existing bacterial pre- 

 cursors. The complete kinetics of assimilation of phage DNA phosphorus were 

 studied subsequently by modifications of Cohen's original method, by either 

 adding to or withdrawing from the growth medium of bacterial cultures P^- 

 at various times before or after their infection. The results of this work led to 



