Cytotoxic Serums 103 



All of these reactions are indirect and intermediate, and 

 take place under appropriate conditions both in the bodie's 

 of animals and in the test-tube. 



But the number of reactions that can be brought about by 

 physiologically and chemically active bodies introduced into 

 the bodies of animals seems to be limitless, for Ehrlich and 

 Morgenroth in their studies of hemolysis found that serums 

 rich in "complement" produced reactions productive of 

 anti-complements, and that serums rich in immune bodies, 

 produced similar reactions yielding anti-immune bodies, and 

 that these serums inhibited the activities of the respective 

 factors by whose stimulation they were produced. 



The reactions which when repeated may lead to immunity 

 and to the formation of antibodies seem to be followed by 

 constitutional disturbances much more profound than 

 would be supposed from the apparent freedom from symp- 

 toms manifested by the animal. About 1900 Mattson 

 called the author's attention in private conversation to the 

 fact that when guinea-pigs used for testing antitoxic serums 

 were subsequently injected with another dose of serum, 

 they commonly died. Not being understood, the matter 

 was not thought worthy of publication. Otto* speaks of 

 this fatal action of serums as the " Theobald-Smith phe- 

 nomenon." 



The therapeutic employment of diphtheria antitoxic serum 

 was scarcely popularized before the medical profession was 

 shocked by the immediate death of the healthy child of a 

 noted German professor after a prophylactic injection, and 

 in 1896 Gottsteinf was able to collect eight deaths following 

 the use of the serum, four of them being persons not ill 

 with diphtheria, von Pirquet and SchickJ also pointed out 

 that in a certain proportion of cases the injection of horse 

 serum in man is followed by urticarial eruptions, joint-pains, 

 fever, swelling of the lymph-nodes, edema and albuminuria, 

 these symptoms usually appearing after an incubation 

 period of 8-13 days, and constituting what they call the 

 "Serum disease." Sometimes these reactions are imme- 

 diate; sometimes death appears imminent, and, as has been 

 observed, death sometimes occurs. 



The investigation of the subject was taken up in 1905 



* von Lenthold, " Gedenkschrift," Bd. i, pp. 9, 16, 18. 



f "Therap. Monatschrift," 1896. 



| "Die Serumkrankheit," Liepzig and Wien, 1905. 



