OSWALD T. AVERY, COLIN M. MACLEOD, AND MACLYN MCCARTY 155 



Various hypotheses have been advanced in explanation of the nature of the 

 changes induced. In his original description of the phenomenon Griffith (1) 

 suggested that the dead bacteria in the inoculum might furnish some specific 

 protein that serves as a "pabulum" and enables the R form to manufacture a 

 capsular carbohydrate. 



More recently the phenomenon has been interpreted from a genetic point of 

 view (26, 27). The inducing substance has been likened to a gene, and the 

 capsular antigen which is produced in response to it has been regarded as a gene 

 product. In discussing the phenomenon of transformation Dobzhansky (27) 

 has stated that "If this transformation is described as a genetic mutation — and 

 it is difficult to avoid so describing it — we are dealing with authentic cases of 

 induction of specific mutations by specific treatments. ..." 



Another interpretation of the phenomenon has been suggested by Stanley 

 (28) who has drawn the analogy between the activity of the transforming agent 

 and that of a virus. On the other hand, Murphy (29) has compared the causa- 

 tive agents of fowl tumors with the transforming principle of Pneumococcus. 

 He has suggested that both these groups of agents be termed "transmissible 

 mutagens" in order to differentiate them from the virus group. Whatever 

 may prove to be the correct interpretation, these differences in viewpoint indi- 

 cate the implications of the phenomenon of transformation in relation to similar 

 problems in the fields of genetics, virology, and cancer research. 



It is, of course, possible that the biological activity of the substance described 

 is not an inherent property of the nucleic acid but is due to minute amounts 

 of some other substance adsorbed to it or so intimately associated with it as to 

 escape detection. If, however, the biologically active substance isolated in 

 highly purified form as the sodium salt of desoxyribonucleic acid actually proves 

 to be the transforming principle, as the available evidence strongly suggests, 

 then nucleic acids of this type must be regarded not merely as structurally 

 important but as functionally active in determining the biochemical activities 

 and specific characteristics of pneumococcal cells. Assuming that the sodium 

 desoxyribonucleate and the active principle are one and the same substance, 

 then the transformation described represents a change that is chemically in- 

 duced and specifically directed by a known chemical compound. If the results 

 of the present study on the chemical nature of the transforming principle are 

 confirmed, then nucleic acids must be regarded as possessing biological 

 specificity the chemical basis of which is as yet undetermined. 



SUMMARY 



1. From Type III pneumococci a biologically active fraction has been isolated 

 in highly purified form which in exceedingly minute amounts is capable under 

 appropriate cultural conditions of inducing the transformation of unencapsu- 

 lated R variants of Pneumococcus Type II into fully encapsulated cells of the 



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