188 



specific transformation been experi- 

 mentally induced hi vitro by a chem- 

 ically defined substance. 



Although the observations are lim- 

 ited to a single example, they acquire 

 broader significance from the work of 

 earlier investigators who demonstrated 

 the interconvertibility of various pneu- 

 mococcal types and showed that the 

 specificity of the changes induced is 

 in each instance determined by the 

 particular type of encapsulated cells 

 used to evoke the reaction. From the 

 point of view of the phenomenon in 

 general, therefore, it is of special in- 

 terest that in the example studied, 

 highly purified and protein-free ma- 

 terial consisting largely, if not exclu- 

 sively, of desoxyribonucleic acid is 

 capable of stimulating unencapsulated 

 R variants of Pneumococcus Type II 

 to produce a capsular polysaccharide 

 identical in type specificity with that 

 of the cells from which the inducing 

 substance was isolated. Equally strik- 

 ing is the fact that the substance 

 evoking the reaction and the capsular 

 substance produced in response to it 

 are chemically distinct, each belonej- 

 ing to a wholly different class of 

 chemical compounds. 



The inducing substance, on the basis 

 of its chemical and physical properties, 

 appears to be a highly polymerized 

 and viscous form of sodium desoxy- 

 ribonucleate. On the other hand, the 

 Type III capsular substance, the syn- 

 thesis of which is evoked by this trans- 

 forming agent, consists chiefly of a 

 non-nitrogenous polysaccharide con- 

 stituted 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 trans- 

 formed cells all the distinguishing 

 characteristics of Pneumococcus Type 

 III. Thus, it is evident that the induc- 

 ing substance and the substance pro- 



AVERY, MACLEOD, MCCARTY 



duced in turn are chemically distinct 

 and biologically specific in their ac- 

 tion 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 nu- 

 cleic acids, at least those of the desoxy- 

 ribose type, possess different specifi- 

 cities as evidenced by the selective ac- 

 tion of the transforming principle. 

 Indeed, the possibility of the existence 

 of specific differences in biological 

 behavior of nucleic acids has pre- 

 viously been suggested (23, 24) but 

 has never been experimentally demon- 

 strated owing in part at least to the 

 lack of suitable biological methods. 

 The techniques used in the study of 

 transformation appear to afford a sen- 

 sitive means of testing the validity of 

 this hypothesis, and the results thus 

 far obtained add supporting evidence 

 in favor of this point of view. 



If it is ultimately proved beyond 

 reasonable doubt that the transforming 

 activity of the material described is 

 actually an inherent property of the 

 nucleic acid, one must still account on 

 a chemical basis for the biological spe- 

 cificity of its action. At first glance, 

 immunological methods would appear 

 to offer the ideal means of determin- 

 ing the differential specificity of this 

 group of biologically important sub- 

 stances. Although the constituent units 

 and general pattern of the nucleic acid 

 molecule have been defined, there is 

 as yet relatively little known of the 

 possible effect that subtle differences 

 in molecular configuration may exert 

 on the biological specificity of these 

 substances. However, since nucleic 

 acids free or combined with histones 

 or protamines are not known to func- 

 tion antigenically, one would not an- 

 ticipate that such differences would be 

 revealed by immunological techniques. 

 Consequenth', it is perhaps not surpris- 



