VIRUSES, CANCER, GENES, AND LIFE — STANLEY 363 



mate of the maximum size of a gene would place it just below tobacco 

 mosaic virus, near the middle of the viruses. Both genes and viruses 

 seem to be nucleoproteins and both reproduce only within specific liv- 

 ing cells. Both possess the ability to mutate. Although viruses gen- 

 erally reproduce many times within a given cell, some situations are 

 known in which they appear to reproduce only once with each cell 

 division. Genes usually reproduce once with each cell division, but 

 here also the rate can be changed, as, for example, in the case of 

 polyploidy resulting from treatment with colchicine. Actually the 

 similarities between genes and viruses are so remarkable that viruses 

 very early were referred to as "naked genes" or "genes on the loose." 

 Two great discoveries, one which began in 1928 and the other which 

 occurred in 1952, have provided experimental evidence for an exceed- 

 ingly intimate relationship between viruses and genes. In 1928 

 Griffith found that he could transform one specific S type of pneu- 

 mococcus into another specific S type by injecting mice with non- 

 virulent R forms together with large amounts of heat-killed S pneu- 

 mococci 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 

 noncapsulated rough form would convert the latter into the same type 

 of capsulated pneumococcus which provided the extract. It was ob- 

 vious 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 some- 

 thing was a transforming principle consisting of deoxyribonucleic 

 acid (DNA). Muller in 1947 discussed the possibility 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 Alexan- 

 der, 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 solution. 



This information, as well as our knowledge of viruses, was soon 

 fortified by the very important discovery by Zinder and Lederberg 

 in 1952 of transduction in Salmonella by means of a bacterial virus. 



