INTRACELLULAR MULTIPLICATION OF BACTERIAL VIRUSES 269 



phage particles and individual progeny particles are examined for their 

 content of radioactivity by either one of these techniques. Such experiments 

 show that the integrity of the parental DNA is not conserved in the course of 

 the reproduction process and that, instead, the transferred radioactive 

 parental atoms are dispersed over a number of the descendants. The distri- 

 bution of the parental label, however, is far from miiform, in that about half 

 of the transferred atoms wind up in progeny particles which harbor as much as 

 20 % of the DNA of the parent phage, whereas the remaining half of the 

 transferred atoms are dispersed into very much smaller fragments. If the 

 first generation progeny are passed through a second cycle of growth and the 

 distribution of the grandparental DNA atoms among the second generation 

 progeny studied, it is fomid that the second-growth cycle has not produced 

 any serious diminution of the 20 % DNA pieces in either size or frequency 

 relative to the total transferred P^^. Contrary to the high hopes held for them 

 at the outset of these experiments, they do not seem as yet to have brought 

 any decisive revelations concerning the DNA replication mechanism. The 

 reader may, however, find a number of interpretations of their results in the 

 original publications (Levinthal, 1955, 1956; Stent and Jerne, 1955; Stent etal., 

 1958) and in reviews devoted to the subject (Hershey and Burgi, 1956; 

 Delbriick and Stent, 1957). 



C. Superinfection Breakdown 



Shortly after the onset of phage development, some change takes place 

 within the phage-infected bacterium which becomes apparent only upon 

 subsequent infection of the same cell by another homologous phage particle. 

 This change was observed when bacteria already multiply uifected with 

 nonlabeled T-even phages were superinfected with an inoculum of P^^. 

 labeled T-even particles at various later times. For the result of this experi- 

 ment was that if more than 3 or 4 minutes have elapsed between primary and 

 secondary infections, then half of the label of the superinfecting phages is 

 hberated into the medium in a low molecular weight, acid-soluble form. If, 

 however, the secondary infection is made immediately after the primary 

 infection, then most of the P^^ of the labeled phages remains in a high 

 molecular weight, "acid-insoluble" form (Lesley et al., 1950, 1951). This 

 superinfection breakdoum of the DNA of the secondary phages appears to be a 

 way of excluding latecomers from participating in the intracellular reproduc- 

 tive processes, since the formation of acid-soluble label under these conditions 

 is exactly correlated with a decrease in both transfer of DNA and genetic 

 contribution from the superinfecting individuals to the progeny phages 

 (Dulbecco, 1952; Graham, 1953). Superinfection breakdown appears to involve 

 digestion of the superinfecting DNA injected into the host ceU by an intra- 

 bacterial deoxyribonuclease (DNAase), since the breakdown (though not the 



