138 



about the inhibition of nucleic acid synthesis in metabolism and the degradation 

 of large molecules. Apparently radiation can also induce nucleic acid synthe- 

 sis. 



SPIEGELMAN: It, perhaps, might be worthwhile to describe briefly 

 some extremely fascinating series of facts which have recently emerged con- 

 cerning lysogeny. In the first place, it is important to recognize that one can 

 have lysogenic and non-lysogenic varieties of the same strain. The distinction 

 between them can be easily exhibited in many cases by induction with UV. The 

 doses that induce are extremely low and of the order of 5 percent kill for nor- 

 mal cells. Exposing lysogenic cells to this radiation however, leads to virtual- 

 ly a 100 percent kill, as the result of the subsequent development of the virus. 



If one exposes cells of a non-lysogenic strain to what is called temper- 

 ate virus, the cells become infected apparently without any marked effects on 

 their metabolism and without effect on viability. Once the infection with tem- 

 perate viruses has taken place, one can subsequently demonstrate that every 

 cell contains at least 1 virus particle. It is important to note however, that the 

 virus is not present in a recognizable state before induction, since upon break- 

 ing open such cells, one cannot detect the presence of many infective agents. 



These observations raise the question of where the virus is and in 

 what form it exists. This stage of virus existence has been called the prophage 

 stage. I cannot at this time, detail the experimental evidence in support of the 

 conclusions to be mentioned, but I think it worthwhile to simply state them. 

 One can say, with a large amount of certainty, that immediately subsequent to 

 infection the virus does behave like a cytoplasmic particle and is transmitted in 

 a random manner. However, in a few divisions it disappears from the cyto- 

 plasm and takes up a position on the chromosomes. It can be further demon- 

 strated that the position taken up by a particular temperate virus is always the 

 same since it can be localized by means of crossing experiments. Thus, if you 

 cross a lysogenic strain with a non-lysogenic one, you will find in the progeny 

 an association of the transmission of the prophage character with several close- 

 ly linked markers controlling other normal metabolic processes. 



In some instances, it has been possible to demonstrate that 2 alterna- 

 tive positions are possible, and in these it has been demonstrated that 1 cell 

 can be infected simultaneously with 2 viruses in the prophage stage. 



We have here indeed, a most amazing situation. One takes a self- 

 duplicating unit, puts it into a cell where, instead of behaving like an independ- 

 ent entity in the cytoplasm, it incorporates itself into the genetic apparatus of 

 the host. In this manner it is transmitted from 1 cell generation to the next. 

 It will be noted further that this mechanism guarantees that every cell contains 

 the infective agent. 



One other feature of extreme interest is that these viral agents carry 

 in not only the ability to produce more viruses but also other genetic characters. 

 For example, if one has a lysogenic galactose positive cell and induces with UV 

 so that mature virus particles are produced, one can then infect non-lysogenic 

 galactose negative cells with these virus particles. One finds that along with 

 establishing lysogenicity, one also transforms the galactose negative cells into 

 ones capable of fermenting galactose, and the newly acquired character is 

 permanently inherited. 



A most dramatic case of this type of "Transduction phenomenon" has 

 been exhibited in the last few years with respect to toxin-producing diphtheria 



