The Chemical Basis of Heredity Determinants 325 



structure and the function of heredity determinants. The reasons for 

 this will become clear from the description of the phenomenon and of 

 the agent involved. 



In 1928, Griffith 2 reported that, from mice that had been injected 

 with living non-encapsulated (R) pneumococci mixed with heat-killed 

 encapsulated (S) ones, living S pneumococci were recovered. Of par- 

 ticular interest was the fact that the specific type of S cells was the 

 same as the heat-killed cells rather than the type from which the living 

 R cells were derived. Once the new feature (production of the capsule 

 of a specific type) was established, it was retained and reproduced in 

 subsequent generations as if a new gene had been added to the genetic 

 make-up of the receptor cells; indeed, such transformed cells, when 

 heat-killed, could in turn induce the transformation of R cells exactly 

 in the same way as did the original S cells. 



Alloway was the first to demonstrate that the presence of the whole 

 "donor" (S) cells is not necessary for the phenomenon. This investi- 

 gator prepared cell-free aqueous extracts of the heat-killed S cells, 

 passed the extract through a bacterial filter and demonstrated that the 

 filtrate is still capable of transforming the R cells into S cells. 



In 1944, Avery, MacLeod, and McCarty 3 purified the extract 

 further and found that the responsible agent (the "transforming princi- 

 ple") had all the properties of a highly polymerized deoxypentose 

 nucleic acid. This single finding laid the foundation for the chemical 

 study of the transforming principle. 



Species Susceptible to Transformation 



To date, reproducible transformation phenomena are known only 

 in bacteria. A transformationlike phenomenon in viruses has been 

 reported 12 and confirmed; however, it is difficult to judge whether the 

 nature of this phenomenon is similar to that of bacterial transforma- 

 tion. The transformation of organisms higher than bacteria has not 

 yet been reported. 



Of bacteria, the organism used originally by Griffith, the pneumo- 

 coccus, is still most widely experimented upon, because of the large 

 body of knowledge accumulated, the comparatively low pathogenicity 

 of this organism, and, above all, the reproducibility of results. The 

 disadvantage of this species is the presence in the bacterial cultures 

 of an enzyme, deoxyribonuclease (DNAase), which tends to destroy 

 the transforming principle. 



The transformation in several other bacteria has been reported. 

 These are Escherichia coli, Shigella paradysenteriae, Proteus, Salmo- 



