RESEARCH IN MEDICINE 117 



therapy in diphtheria and by vaccine therapy in anthrax. The at- 

 tempts to elucidate the principles underlying these two methods have 

 led to the development of many fruitful hypotheses and theories, and 

 many diagnostic and curative procedures of great value. It was early 

 evident that the explanation of resistance to infection, either natural or 

 acquired, must be sought in the cells or fluids of the body and especially 

 of the blood. Metschnikoff (1884) was the first to show the, importance 

 of the white cells of the blood in combating infection through their 

 power of engulfing and dissolving bacteria, and his pupils have supported 

 his views, both as to the direct and indirect influence of these cells, the 

 leucocytes, in the production of immunity. On the other hand, since 

 Nuttall, in 1888, demonstrated the bactericidal power of the fluids of the 

 body, and particularly of the blood serum, the relation of the body 

 fluids to infection and immunity has been incessantly studied. As a 

 result, schools have arisen, some supporting the cellular theory and 

 others the humoral theory, and still others combining both theories in 

 the attempt to reach an adequate explanation of the process of immu- 

 nity. With these schools are associated most prominently the names of 

 Metschnikoff, Ehrlich and Bordet. 



One of the earliest and most important observations, after the dis- 

 covery of antitoxins, was that of Pfeiffer (1894). This was the demon- 

 stration that a guinea-pig, into which has been injected the spirillum of 

 cholera, develops in its body-fluids a substance capable of dissolving the 

 cholera spirillum. This bacteriolytic substance is specific, that is, it de- 

 stroys only the cholera spirillum; and Pfeiffer and his followers, push- 

 ing their investigations further, found that this principle of a specific 

 lytic body could be applied to other bacteria and to foreign animal cells 

 as well. Its development led to great advances in the theory of im- 

 munity, to the development of the fruitful hypothesis known by Ehr- 

 lich's name, and to the production of antibacterial sera, e. g., anti- 

 streptococcus serum, as contrasted with antitoxic sera. 



Likewise, it was discovered that the serum of animals receiving in- 

 jections of a given bacterium had the power to agglutinate this organ- 

 ism ; and moreover that this principle held good for the blood serum in 

 certain diseases of man. Upon these observations was based (1896) 

 the serum (Widal) reaction for typhoid • fever, a definitely specific and 

 reliable diagnostic method which has been followed by many other val- 

 uable tests based on the same principle and grouped under the general 

 head of serum diagnosis. 



At the same time older procedures were not forgotten, as is shown 

 by Haffkine's extension of Pasteur's principle of vaccination to include 

 protective vaccination against cholera (1893) and plague (1896) and 

 more recently Wright's application of it to typhoid fever. Thus the last 

 decade of the nineteenth century is marked by the birth of both serum- 



