36 OFFENSIVE FORCES OF INVADING MICROORGANISM 



contrast strongly with the tiny attenuated forms which one is accus- 

 tomed to see in old cultures on the ordinary media. 



The importance of these morphological changes as a defensive 

 mechanism of the bacteria against the opposing forces of the host 

 can hardly be overestimated. It has been conclusively demon- 

 strated, as a matter of fact, that such "animalized" bacteria, as 

 Bail terms them, offer a far greater resistance to the destructive 

 action of bactericidal sera and to phagocytosis than do the corre- 

 sponding forms which have been cultivated on the ordinary media. 

 That such changes must of necessity lead to a marked increase 

 in the virulence of an organism is of course self-evident. This is 

 well illustrated by an experiment of Horiuchi, who relates that he 

 had in his possession a highly virulent, densely capsulated strain 

 of the Micrococcus tetragenus, which resisted phagocytosis almost 

 entirely and killed guinea-pigs in a dose of 100 organisms. When 

 this was grown for a number of days on rather dry agar it lost its 

 capsule-forming power permanently, became readily subject to 

 phagocytosis, and did not affect guinea-pigs even in doses of 

 1,000,000,000 organisms. 



In this connection we may also refer to the observation of Rose- 

 now, that vaccination with pneumococci which have been deprived 

 of their capsules leads to the production of much larger quantities 

 of protective antibodies than are found when capsulated organisms 

 have been introduced (see Antipneumococcus Vaccination). 



In view of our present knowledge of the relation between capsule 

 formation and virulence, we can now readily understand why animal 

 passage of an organism leads to increased virulence. This fact had 

 long been recognized by bacteriologists, but an adequate explana- 

 tion for it had long been wanting. By starting with a laboratory 

 culture that has been grown for many generations on artificial, 

 non-albuminous media, it may be absolutely impossible to produce 

 an infection at all, even though enormous numbers of bacteria be 

 injected. If infection, however, results we may imagine in the 

 case of one of the organisms in which capsule formation occurs 

 that even though the majority of organisms had lost the power 

 of forming capsules, and of thus resisting the offensive forces of the 

 host, a certain number still possessed this property, and that these 

 escaped destruction and multiplied to a greater or less extent. 



If then at the height of the infection the animal is killed, or if it 



