INTRODUCTORY AND GENERAL 17 



which are developed in the body as defensive agents during an 

 attack of disease, and imagine the same process to go on, we 

 shall have an exact reproduction of the rise in virulence occurring 

 during an attack of disease. If we defended ourselves against 

 trypanosomes by the development of fuchsin, Ehrlich's fuchsin- 

 resistant race would be extremely virulent for us. 



The development of epidemics of diseases is probably due in 

 some cases to a spontaneous rise in virulence of the infecting agent, 

 but we have no knowledge of the causes by which this is produced. 



The second method of increasing the virulence of a culture is 

 less general, and of greater theoretical than practical interest. It 

 consists in the cultivation of the organism for several generations 

 in the blood-serum of an animal which has been immuned to the 

 bacterium in question. It was discovered by Walker in the case 

 of B. typhosus, and is found in the case of some other organisms. 

 It is referred to subsequently, and we need only say here that it is 

 allied to passage ; the organism is immunized to the fluids of the 

 resistant animal in vitro instead of in vivo. And the virulence of a 

 culture is in general best sustained by a close approximation to 

 the conditions of the body. Thus it is more rapidly lost at the 

 temperature of the room than at that of the body, and the most 

 suitable culture medium is usually one containing body fluids 

 unaltered by heat. Thus Marmorek cultivates his virulent strepto- 

 cocci in broth to which one-third of its volume of ascitic fluid has 

 been added. In the case of diphtheria bacilli the virulence (as 

 estimated by its power of forming toxin) is best maintained by 

 daily transplantations into broth previously raised to the body 

 temperature, and when treated in this way shows little or no 

 change for years. 



Diminution in virulence occurs, as a rule, when the organism is 

 submitted to conditions quite unlike those of the animal body, and 

 is usually the more rapid the greater the divergence. At the same 

 time, the growth under these conditions gradually becomes (in 

 most cases) more abundant. The organism gradually adapts itself 

 to a saprophytic habitat, losing in so doing its distinctive chemical 

 properties which made it virulent as a parasite. Old laboratory 

 cultures of bacteria which have been grown on artificial media for 

 many generations are usually almost devoid of virulence, though 

 here there are great variations, some species becoming inert far 

 quicker than others. 



The subject is important, since cultures of diminished (" miti- 



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