xvi INTRODUCTION 



animals which had been inoculated with this virus, using the second 

 time a culture which was virulent for untreated fowl. He showed 

 that the inoculated fowl were immune to the virulent culture. In 

 1881 he demonstrated with his collaborators, Chamberland and 

 Roux, that this was not an isolated fact, but that essentially the 

 same thing had been accomplished with anthrax. The virus of 

 anthrax could not be attenuated by the same simple method as for 

 fowl cholera, because the bacillus anthracis preserves its virulence 

 by the formation of spores. They showed, however, that they could 

 prevent the formation of spores by growing the bacillus at 42 to 

 43 C. At this temperature growth of six to eight days sufficiently 

 attenuates the organism for protective inoculation. The proof of 

 the vaccination was given publicly before the Society of Agricul- 

 ture at Melun. For this phenomenon Pasteur used the term vac- 

 cination, and in London in 1881 said: " I have lent to the expression 

 vaccination an extension that I hope science will consecrate as a 

 homage to the merit and immense services rendered to humanity 

 by one of the greatest men of England Jenner." In 1882 Pasteur 

 and Loir confirmed Thuillier's observations on the cause of swine 

 fever and then successfully vaccinated pigs against this disease. 

 Then in 1885-1886 came the final brilliant chapter in the work with 

 rabies, in which vaccination was practised without definite knowl- 

 edge of the etiological agent. The work with rabies was of further 

 importance in that it led to the discovery of the fact that a virus 

 may be increased in virulence, a phenomenon quite the reverse of 

 the earlier discovery of the possibility of attenuation. 



In his studies Pasteur had worked almost entirely with the active 

 organisms causing disease, and the next step forward was the dis- 

 covery that the products of bacterial growth and activity can be 

 utilized in the development of immunity. Salmon and Theobald 

 Smith published in 1886 their studies on the immunization of hogs 

 against hog cholera by the use of the products of the specific organ- 

 isms. This idea had been suggested by LoefHer in 1884, but not 

 proven. Before he had made any conclusive experiments the sub- 

 ject had been taken up by numerous other investigators. Behring and 

 Kitasato in 1890 had discovered tetanus toxin and Roux and Yersin in 

 1 888- 1 889- 1 890 had published their discovery of diphtheria toxin. 

 These workers showed that the symptoms of the special diseases 

 studied could be reproduced by the soluble products of the causative 

 organisms and by their later work that one of the important phases of 

 immunity is due to the development of substances capable of neu- 

 tralizing these products. It became evident with further work that 

 this principle does not apply to all pathogenic organisms, and the 

 work of Pfeiffer with cholera in 1891 led to the differentiation of 

 exotoxins and endotoxins. 



The antagonistic action of blood and body fluids on putrefaction 

 had been noted by John Hunter, Traube, and Lister, but Grohman 

 in 1884 was the first to publish well-founded experiments upon the 



