152 TRANSFORMATION OF PNEUMOCOCCAL TYPES 



DISCUSSION 



The present study deals with the results of an attempt to determine the chem- 

 ical nature of the substance inducing specific transformation of pneumococcal 

 types. A desoxyribonucleic acid fraction has been isolated from Type III 

 pneumococci which is capable of transforming unencapsulated R variants 

 derived from Pneumococcus Type II into fully encapsulated Type III cells. 

 Thompson and Dubos (21) have isolated from pneumococci a nucleic acid of the 

 ribose type. So far as the writers are aware, however, a nucleic acid of the 

 desoxyribose type has not heretofore been recovered from pneumococci nor has 

 specific transformation been experimentally induced in vitro by a chemically 

 defined substance. 



Although the observations are limited to a single example, they acquire 

 broader significance from the work of earlier investigators who demonstrated 

 the interconvertibility of various pneumococcal types and showed that the 

 specificity of the changes induced is in each instance determined by the par- 

 ticular type of encapsulated cells used to evoke the reaction. From the point 

 of view of the phenomenon in general, therefore, it is of special interest that in 

 the example studied, highly purified and protein-free material consisting largely, 

 if not exclusively, of desoxyribonucleic acid is capable of stimulating unencap- 

 sulated R variants of Pneumococcus Type II to produce a capsular polysac- 

 charide identical in type specificity with that of the cells from which the 

 inducing substance was isolated. Equally striking is the fact that the sub- 

 stance evoking the reaction and the capsular substance produced in response 

 to it are chemically distinct, each belonging to a wholly different class of chem- 

 ical compounds. 



The inducing substance, on the basis of its chemical and physical properties, 

 appears to be a highly polymerized and viscous form of sodium desoxyribo- 

 nucleate. On the other hand, the Type III capsular substance, the synthesis 

 of which is evoked by this transforming agent, consists chiefly of a non-nitrog- 

 enous polysaccharide constituted of glucose-glucuronic acid units linked in 

 glycosidic union (22). The presence of the newly formed capsule containing 

 this type-specific polysaccharide confers on the transformed cells all the dis- 

 tinguishing characteristics of Pneumococcus Type III. Thus, it is evident 

 that the inducing substance and the substance produced in turn are chemically 

 distinct and biologically specific in their action and that both are requisite in 

 determining the type specificity of the cell of which they form a part. 



The experimental data presented in this paper strongly suggest that nucleic 

 acids, at least those of the desoxyribose type, possess different specificities as 

 evidenced by the selective action of the transforming principle. Indeed, the 

 possibility of the existence of specific differences in biological behavior of nucleic 

 acids has previously been suggested (23, 24) but has never been experimentally 

 demonstrated owing in part at least to the lack of suitable biological methods. 



