154 TRANSFORMATION OF PNEUMOCOCCAL TYPES 



glutinated by the antiserum in the medium. Attempts to induce transforma- 

 tion in suspensions of resting cells held under conditions inhibiting growth and 

 multiplication have thus far proved unsuccessful, and it seems probable that 

 transformation occurs only during active reproduction of the cells. Important 

 in this connection is the fact that the R cells, as well as those that have under- 

 gone transformation, presumably also all other variants and types of pneu- 

 mococci, contain an intracellular enzyme which is released during autolysis 

 and in the free state is capable of rapidly and completely destroying the activity 

 of the transforming agent. It would appear, therefore, that during the loga- 

 rithmic phase of growth when cell division is most active and autolysis least 

 apparent, the cultural conditions are optimal for the maintenance of the balance 

 between maximal reactivity of the R cell and minimal destruction of the trans- 

 forming agent through the release of autolytic ferments. 



In the present state of knowledge any interpretation of the mechanism in- 

 volved in transformation must of necessity be purely theoretical. The bio- 

 chemical events underlying the phenomenon suggest that the transforming 

 principle interacts with the R cell giving rise to a coordinated series of enzymatic 

 reactions that culminate in the synthesis of the Type III capsular antigen. 

 The experimental findings have clearly demonstrated that the induced altera- 

 tions are not random changes but are predictable, always corresponding in 

 type specificity to that of the encapsulated cells from which the transforming 

 substance was isolated. Once transformation has occurred, the newly acquired 

 characteristics are thereafter transmitted in series through innumerable trans- 

 fers in artificial media without any further addition of the transforming agent. 

 Moreover, from the transformed cells themselves, a substance of identical 

 activity can again be recovered in amounts far in excess of that originally added 

 to induce the change. It is evident, therefore, that not only is the capsular 

 material reproduced in successive generations but that the primary factor, 

 which controls the occurrence and specificity of capsular development, is also 

 reduplicated in the daughter cells. The induced changes are not temporary 

 modifications but are permanent alterations which persist provided the cul- 

 tural conditions are favorable for the maintenance of capsule formation. The 

 transformed cells can be readily distinguished from the parent R forms not 

 alone by serological reactions but by the presence of a newly formed and visible 

 capsule which is the immunological unit of type specificity and the accessory 

 structure essential in determining the infective capacity of the microorganism 

 in the animal body. 



It is particularly significant in the case of pneumococci that the experi- 

 mentally induced alterations are definitely correlated with the development of a 

 new morphological structure and the consequent acquisition of new antigenic 

 and invasive properties. Equally if not more significant is the fact that these 

 changes are predictable, type-specific, and heritable. 



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