318 WENDELL M. STANLEY 



resulted from Border's early work on lysogeny and the other which occurred 

 in 1952 and has to do with transduction, have provided experimental evidence 

 for an exceedingly intimate relationship between viruses and genes. In 1928 

 Griffith found that he could transform one specific S type of pneumococcus 

 into another specific S type by injecting mice with non-virulent R forms 

 together with large amounts of heat-killed S pncumococci of a type other than 

 that of the organisms from which the R cells were derived. Living virulent S 

 organisms of the same type as the heat-killed S forms were then recovered from 

 the animals. Later Dawson and Sia as well as Alloway found that the addition 

 of an extract of one type of capsulated pneumococcus to a culture of a non- 

 capsulated rough form would convert the latter into the same type of capsulated 

 pnevmiococcus which provided the extract. It was obvious that something was 

 being transferred and in 1938 I discussed the possibility that this 'something' 

 might be a virus. In 1944 Avery and his colleagues at the Rockefeller Institute 

 proved that this something was a transforming principle consisting of deoxyribo- 

 nucleic acid (DNA). Muller in 1947 discussed the possibihty that the DNA 

 might correspond to still viable parts of bacterial chromosomes loose in solution 

 which, after entering the capsuleless bacteria, undergo a kind of crossing over 

 with the chromosomes of the host, but this suggestion was not widely accepted. 

 That the phenomenon was not an isolated one was demonstrated in 1953 by 

 Leidy and Alexander, who obtained similar results with an influenza-bacteria 

 system. The close relationship to genetics was further emphasized by work of 

 Hotchkiss and by Ephrussi-Taylor who, as well as Leidy and Alexander, showed 

 that drug resistance and other genetic factors could be so transferred. This work 

 provided evidence that genetic factors or genes, if one prefers such a designation, 

 can be represented by DNA and can be obtained in chemically pure solu- 

 tion. 



The persistence of a bacterial virus in an apparently concealed form or pro- 

 phage in lysogenic strains of bacteria, extensively investigated by Lwoif, provides 

 further evidence in this direction. Lysogenic bacteria perpetuate in what may 

 be considered a hereditary maimer the property of being able to produce a 

 bacterial virus. The term prophage is used to describe the form in which the 

 potentiahty to produce a bacterial virus is perpetuated in lysogenic bacteria. 

 Prophage is non-pathogenic and non-infectious in the usual sense, but, since it 

 is multiplied at least once with each cell division, it may be regarded as infectious 

 in the sense that genes or chromosomes are infectious. In other words, the pro- 

 phage might be considered as a temporary part of the genetic apparatus of the 

 cell, the genetic element that differentiates a lysogenic from a sensitive cell, and 

 at the same time as the non-infectious form of a bacterial virus. There are times, 

 therefore, when a virus may not exhibit its normally infectious nature but have 

 its potentially unHmited reproductive capacity under genetic control, so that it 

 repUcates only once with each cell division. There are times when a specific 

 genetic element of a cell can be freed of the normal controUing mechanism of the 

 cell and go forth in viable form in solution or associated with a virus, enter a 

 différent cell, replace a homologous chromosomal segment and resume its original 

 specific function in the new cell. It is obvious that the latter phenomenon could 



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