ANAPHYLAXIS OR HYPERSUSCEPTIBILITY 297 



substance in doses of 0.042 grams per kilogram produced vomiting, 

 diarrhea, collapse, and death in dogs. If doses considerably smaller 

 than this were given in quantities sufficient to cause only temporary 

 illness, and several days allowed to elapse, a second injection of a 

 quantity less than one-quarter or one-fifth of the ordinary lethal dose 

 would cause rapid and severe symptoms and often death. Similar 

 observations were made soon after this by Richet with mytilo-conges- 

 tin, 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 phenomenon the term "ana- 

 phylaxis" (fwi against, yuldsts protection), to distinguish it from 

 immunization or prophylaxis. 



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

 later work, Arthus 1 made an observation which plainly confirmed 

 Richet's observations, though in a somewhat different field. The ob- 

 servation of Arthus is universally spoken of as the "phenomenon of 

 Arthus." 



He noticed that the injection of rabbits with horse serum (a sub- 

 stance 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 2 in 1904. Smith ^observed that guinea-pigs injected with diph- 

 theria toxin-antitoxin mixtures in the course of antitoxin standardiza- 

 tion, would be killed if after a short interval they were given a subcu- 

 taneous injection of normal horse serum. 



The fundamental facts of hypersusceptibility had thus been observed, 

 and Otto, 3 working directly upon the basis of Smith's observation, 

 carried on an elaborate inquiry into the phenomenon. Almost simul- 

 taneously with Otto's publication there appeared a thorough study of 

 the condition by Rosenau and Anderson. 4 



The researches of Otto, and Rosenau and Anderson, besides con- 

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



1 Arthus, Compt. rend, de la soc. de biol., 55, 1903. 



2 Th. Smith, Jour. Med. Res., 1904. 



Otto, "Leuthold Gedenkschrift," 1905. 



4 Rosenau and Anderson, Hyg. Lab. U. S. Pub. Health and "Marine Hosp. Serv. 

 Bull., 29, 36, 1906, 1907. 

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