374 INFECTION AND RESISTANCE 



induced and with the smallest quantities by the intravenous method. 

 Besredka and Steinhardt, 49 50 51 52 who began their studies soon after 

 the first publications of Rosenau and Anderson, came to the conclu- 

 sion that the most effectual and rapid method of producing the ana- 

 phylactic shock consisted in direct injection into the brain. Curi- 

 ously enough, while Besredka and Steinhardt obtained the most vio- 

 lent reactions by injection of the second or toxogenic dose into the 

 brain, they were unable to sensitize by this path, at least with doses 

 of 1/4000 c. c., which sufficed to sensitize by the intravenous 

 method. Rosenau and Anderson, in repeating this work, obtained 

 similar results with very minute amounts, but found that intracere- 

 bral sensitization could be accomplished by doses of 0.0001 c. c., or 

 more. According to them, animals intracerebrally sensitized became 

 anaphylactic more rapidly than those in which the injections were 

 subcutaneous. In the former the incubation time was about 7 days, 

 while in the latter it was never less than 9. Lewis, 53 in his thorough 

 study on the same subject, made extensive use of the direct intra- 

 cardial method of injection. In other words, any method of intro- 

 ducing the foreign protein into the blood or tissues seems to lead 

 both to sensitization and to toxic effect, and those methods which 

 introduce the substance, on reinjection, directly into the blood stream 

 or the brain induce the most violent symptoms with the relatively 

 smallest dosage. According to Otto and others, the subcutaneous 

 method, while followed by less violent symptoms, is the method to be 

 preferred when questions of specificity are involved, for, while the 

 reaction is specific in the ordinary sense, yet it is extremely delicate 

 and therefore, as Rosenau and Anderson put it, "quantitatively spe- 

 cific." The less violent subcutaneous method, therefore, might be 

 said to have the same purpose here that dilution of the antigen or 

 immune serum has in safeguarding against error when carrying out 

 specific precipitin or agglutinin reactions. 



y Whether or not sensitization can be accomplished by introduction 

 of the antigen into the intestinal canal, feeding, in other words, is 

 still to some extent an open question and of great importance in 

 view of the many clinical manifestations (urticaria, albuminuria, 

 etc.) which are attributed to possible individual hypersusceptibility 

 to certain proteins taken in the diet (idiosyncrasies). Rosenau and 

 Anderson, in their earliest paper, report success in sensitizing guinea 

 pigs by the feeding of horse meat and horse serum. McClintock and 



49 Besredka and Steinhardt. Ann. de Vlnst. Past., p. 117, 1907; ibid., 

 p. 384. 



50 Besredka. Ibid., pp. 777, 950, 1907; ibid., p. 496, 1908; p. 166, 1909; 

 p. 801, 1909. 



51 Also: Bull, de Vlnst. Past., Nos. 19, 20, 21, 1908; No. 17, 1909. 



52 Also: C. E. de la Soc. Biol, p. 478, 1908, Vol. 65; p. 266, 1909, Vol. 

 67. 



53 Lewis. Jour. Exp. Med., Vol. 10, 1908. 



