12 



of the pneumococcus which is modified in the change from S 

 to R. After growth in immune serum the virulent pneumococcus 

 colony loses its smooth shiny surface and almost watery con- 

 sistency and becomes dull and finely granular. That is to say, 

 the individual pneumococci tend to adhere and are not separated 

 by some substance which, probably on account of its being 

 soluble in salt solution, permits the formation of a very fine 

 stable emulsion. In addition, the attenuated R form no longer 

 secretes in young broth cultures a soluble substance which reacts 

 with an antiserum from a virulent strain. There is some evidence, 

 therefore, that the R form, which is undoubtedly derived from 

 the S, is differentiated from the latter by the loss of that part 

 of its antigen which is concerned with virulence, capsule formation 

 and secretion of specific soluble substance. The R form may 

 bo considered to be a stage in the degeneration of a pneumococcus 

 from a virulent complex type to an attenuated form with a 

 simpler antigenic structure. 



6. The next observation of interest is that this loss is not 

 necessarily permanent. Though in certain cases, as in old 

 cultures and after repeated serum treatment, the R forms are 

 apparently stable, it has been found, under other circumstances, 

 that this alteration in an important biological function can 

 apparently be reversed, not only by animal passage but also 

 by continued subculture in blood broth. After many generations 

 the R pneumococci assume again their smooth colony formation 

 and at the same time their virulence is restored. Can it be 

 said, in explanation of such results as these, that the original 

 R colony contained a few virulent pneumococci which escaped 

 notice in the earlier subcultures ? This hypothesis, in view of 

 the negative results of the periodical tests for virulence, cannot 

 be regarded as probable. Yet it is difficult to understand how 

 an attenuated organism can recover its virulence simply by 

 repeated subculture without animal passage. A somewhat 

 similar event has been described by Bail in his work on the 

 formation of capsules by B. anthracis. If a culture of anthrax 

 bacilli is exposed to a temperature of 42° C. for a period which 

 falls short of depriving it completely of the power to produce 

 capsules, certain strains are formed which produce a mixture 

 of colonies. Some of these colonies produce cultures all of which 

 invariably fail to form capsules, while others produce in addition 

 a few typical capsule-forming bacilli. This result, he thinks, 

 depends upon a deficient inheritance of the capsule-forming 

 substance, so that an individual bacillus is able to endow only 

 one of its descendants with a sufficient amount to produce a 

 typical capsule -forming strain. 



7. Does this investigation throw any new fight upon the pro- 

 tective action of pneumococcus immune serum ? According to 

 Neufeld's bacteriotropic theory the pneumococci after inoculation 

 into an immunised animal become sensitised and are then des- 



* Centraibl. f. Bakt., Orig., LXXIX., p. 42S, 1017. 



