IMMUNITY 26l 



which are known. Alterations in virulence may be temporary or permanent; 

 both attenuation and exaltation of virulence occurs. 



Pasteur showed that passage of rabies virus (which we assume is bacterial) 

 through successive rabbits produces progressive alteration of its character and 

 virulence up to a certain point, beyond which it remains constant, no matter 

 how many times it is passed from rabbit to rabbit. 



During its transitional stage, modification of the virus is shown by a gradual 

 shortening of the period of incubation following inoculation, and curtailment of 

 the stage of excitement when symptoms develop. When alterations in the 

 character of the virus cease subsequent inoculations of rabbits are followed by 

 a very uniform short period of incubation (5 to 6 days); the clinical signs of 

 disease are those of a rapidly progressive and fatal paralysis without a preceding 

 stage of excitement. Injected into animals other than the rabbit, or into man, 

 fixed virus does not produce rabies it confers immunity to rabies. 



These observations may be summarized as follows: 



First. Passage of rabies virus from rabbit to rabbit produces alterations in 

 it up to a certain point beyond which it remains constant in character and is 

 referred to as "fixed virus." 



Second. Passage of rabies virus from rabbit to rabbit increases its virulence 

 for rabbits and decreases its virulence for other animals. 



If anthrax bacilli, primarily virulent to sheep, are cultivated at a constant 

 temperature of 42C. to 43C., they gradually lose their virulence for animals in 

 general. It is possible to carry this attenuation to any desired degree, and also 

 possible to arrest it and thereafter maintain the strain at any desired virulence 

 as is done in the preparation of anthrax vaccine (page 222). 



In fixed rabies virus and anthrax vaccine we have two examples of perma- 

 nent modification of virulence deliberately effected; the former being intensified 

 for one species and attenuated for other species; the latter being attenuated for 

 animals in general. 



Among the various pathogenic species of bacteria strains are encountered 

 that, from unknown causes, or as a result of prolonged cultivation on artificial 

 media, have partially or entirely, and presumably, permanently lost virulence 

 as in the case of the avirulent tubercle bacillus employed by Von Ruck to 

 produce tuberculin. 



From the evidence we have it seems highly probable that permanent altera- 

 tions in virulence, both exaltation and attenuation, occur, but there is no criter- 

 ion by which one can distinguish permanent from temporary alterations of 

 virulence. Instances of presumably permanently attenuated organisms proving 

 virulent are not lacking. 



FLUCTUATIONS IN VIRULENCE 



Much more commonly met with than permanent alterations of virulence 

 are temporary alterations of brief duration. It is constantly observed in prac- 

 tice that most bacteria manifest their greatest virulence when passed directly 

 from animal to animal, especially when passed from one animal to another of 



