HYPERSUSCEPTIBILITY 355 



observations were made soon after this by Richet with mytilo-congestin, a 

 toxic substance isolated from mussels. In these experiments there remained 

 little doubt as to the fact that the first injection had given rise to a well- 

 marked increased susceptibility of the dogs -for the poison used. 



It was Richet who first applied to this t phenomenon the term "anaphylaxis" 

 ( avd against, </>vAots protection), to distinguish it from immunization or 

 prophylaxis. 



Soon after Richet's earlier experiments, and simultaneously with his later 

 work, Arthus 8 made an observation which plainly confirmed Richet's observa- 

 tions, though in a somewhat different field. The observation of Arthus is 

 universally spoken of as the "phenomenon of Arthus." 



He noticed that the injection of rabbits with horse serum ^a substance 

 in itself without toxic properties for normal rabbits) rendered the rabbits 

 delicately susceptible to a second injection made after an interval of six 

 or seven days. The second injection even of small doses regularly produced 

 severe symptoms and often death in these animals. 



An observation very similar to that of Arthus was made by Theobald 

 Smith 9 in 1904. Smith observed that guinea-pigs injected with diphtheria 

 toxin-antitoxin mixtures in the course of antitoxin standardization, would be 

 killed if after a short interval they were given a subcutaneous injection of 

 normal horse serum. 



The fundamental facts of hypersusceptibility had thus been observed, 

 and Otto, 10 working directly upon the basis of Smith's observation, carried 

 on an elaborate inquiry into the phenomenon. Almost simultaneously with 

 Otto's publication there appeared a thorough study of the condition by 

 Rosenau and Anderson. 11 



The researches of Otto, and Rosenau and Anderson, besides confirming 

 the observations of previous workers, brought out a large number of new 

 facts. They showed conclusively that the action of the horse serum had 

 no relationship to its toxin or to its antitoxin constituents, that the "sensitiza- 

 tion" of the guinea-pigs by the first injection became most marked after a 

 definite incubation time of about ten days. Sensitization was accomplished 

 by extremely small doses (one one-millionth in one case, usual doses 1 / 250 

 to 1 c.c.). Rosenau and Anderson, furthermore, excluded hemolysin or 

 precipitin action as explanations of the phenomena, and proved that hyper- 

 susceptibility was transmissible from mother to offspring, and that it was 

 specific animals sensitized with horse serum not being sensitive to subsequent 



8 Arthus, Compt. rend, de la soc. do biol., 55, 1903. 

 ' Th. Smith, Jour. Med. Bes., 1904. 

 111 Otto, "Leuthold Gedenkschrif t, " 1905. 



11 Roscnaik and Anderson, Hyg. Lab. U. S. Pub. Healt'i and Marine Hosp. Serv. 

 Bull., 29, 36, 1906, 1907. 



