472 INFECTION AND RESISTANCE 



which has prevailed, and, to a great extent, still prevails, regarding 

 the classification of the streptococci and their interrelationship. 

 There are apparently a large number of different strains of strepto- 

 cocci which vary from each other, not only culturally, but also in 

 regard to agglutination and bactericidal reactions. For this reason 

 it is not at all a foregone conclusion that a serum prepared by the 

 immunization of an animal with a streptococcus of one type will 

 have any protective action against other strains. The subject has 

 been still more complicated recently by the discovery of Rosenow 48 

 that the various types of streptococci (viridans, hemolyticus, etc.) 

 are not constant in their properties, but may be artificially trans- 

 formed one into the other, and that even mutation of true pneumo- 

 cocci into true streptococci may take place. Most important in this 

 connection is the observation that a pneumococcus sent to Rosenow 

 was altered by him by special methods of cultivation in such a way 

 that not only its morphological and cultural properties were changed, 

 but also its agglutination reactions. These observations are of the 

 utmost importance in connection with attempts at producing specific 

 sera which can be utilized therapeutically. In all cases, therefore, 

 in which streptococcus immune serum is at all used it must be re- 

 membered that the disease produced in human beings by organisms 

 classified among the streptococci are by no means necessarily closely 

 related in biological reactions, and the same immune serum may be 

 extremely potent in one case and entirely useless in another. 



That animals could be successfully immunized against strepto- 

 cocci was shown early in the history of investigations in immunity 

 by a number of workers, notably Roger, Behring, von Lingelsheim, 

 and Mironoff. The first extensive attempts to produce a curative 

 serum for use in passively immunizing human beings were made by 

 Marmorek 49 at the Pasteur Institute in 1895. The basic idea from 

 which Marmorek worked was the similarity of all the streptococci 

 producing disease in human beings. He also believed that the most 

 powerful serum could be produced with cultures whose virulence 

 had been greatly enhanced by animal passages. When such cultures 

 were grown on mixtures of human serum and broth he asserted 

 furthermore that soluble poisons were produced which could be ob- 

 tained by filtration of the culture fluids. For these reasons he im- 

 munized horses with cultures rendered highly virulent by very 

 gradual injections first of dead then of living organisms, finally 

 injecting also considerable quantities of culture filtrates. 



Testing these sera upon animals, he was successful in protecting 

 against streptococcus infection when the serum was administered 12 

 to 18 hours before the bacteria were injected. He expressed the 

 opinion that the serum was antitoxic as well as antibacterial. In 



48 Rosenow. Journ. A. M. A., Feb., 1914. 

 49 Marmorek. Ann. Past., Vol. 9, 1895. 



