IMMUNITY, IMMUNIZATION, AND CURE. 53 



In place of attenuated causative agents of disease, quan- 

 tities insufficient to cause infection may be introduced. 

 Immunity has been repeatedly induced by marked dilution 

 of unaltered living cultures. The small number of micro- 

 organisms introduced causes only slight local disease, in 

 the sequence of which a certain degree of immunity be- 

 comes manifest. 



An essential difference exists between the methods of 

 immunity hitherto discussed and those in which the im- 

 munizing material no longer contains living bacteria. With 

 the germ-free filtrate of a bacterial culture it is possi- 

 ble, in many cases, in an analogous manner to that with 

 the attenuated living bacteria, to confer immunity, and the 

 attenuated virus (through heat, chemic substances, etc.), as 

 well as the unchanged fully virulent filtrate, may be em- 

 ployed ; the latter, naturally, in a dilution and in amount 

 below the lethal. The amount of toxin is gradually in- 

 creased, a sufficiently long interval being permitted to 

 elapse after the introduction of the next higher dose for 

 the animal to recover completely from the action of the 

 previous inoculation, and to regain its original weight. It 

 may be assumed that here also recovery from the disease 

 coincides with the establishment of immunity, and this 

 seems to point to the fact that not the bacteria themselves, 

 but rather the materials produced by them, contribute to 

 the immunizing effect of the disease. 



Such methods of immunization as seek to confer immu- 

 nity by means of the metabolic products of bacteria, and 

 which succeed in most cases, have been proposed in large 

 number. Besides the germ -free filtrate of bacterial cultures, 

 bacterial poisons of a most varied source have been em- 

 ployed. Immunization to cholera-bacilli and to typhoid- 

 bacilli, for instance, has been attempted by R. Pfeiffer with 

 toxic substances that are contained within the bodies of the 

 bacteria themselves. Similarly, Koch, by mechanical tri- 

 turation and repeated centrifugation, obtained from the 

 bacilli themselves tuberculin R, with which, according to 

 his own statement, he was able to protect guinea-pigs 

 against highly virulent tubercle-bacilli. Immunization with 

 bacterial metabolic products has acquired the greatest im- 

 portance, however, in the cases of diphtheria and tetanus. 

 This fact is not surprising, as both of these diseases 

 belong to the toxic infections in which general symptoms 



