CLINICAL SIGNIFICANCE OF ANAPHYLAXIS 441 



The -basic observation leading to the diagnostic use of tuberculin 

 was made by Koch 33 upon guinea pigs. He describes his observa- 

 tion as follows: 



" Tuberculin may be injected into normal guinea pigs in consid- 

 erable quantities without causing noticeable symptoms. Tuberculous 

 guinea pigs, on the other hand, react to comparatively small doses 

 in a very characteristic manner." 



Since, in Koch's experiments upon tuberculin, it was desirable 

 for his particular purposes at the time, to obtain very sharp reac- 

 tions, he did not content himself with the production of moderate 

 symptoms by the injection of slight amounts of tuberculin into in- 

 fected animals, but increased his dosage until the guinea pigs were 

 killed. He showed that guinea pigs having a moderately advanced 

 infection 4 to 5 weeks after inoculation could be killed by doses 

 of 0.2 to 0.3 gram, while animals in very advanced stages would suc- 

 cumb within 6 to 30 hours to quantities as small as 0.1 gram sub- 

 cutaneously. In the animals so studied he determined not only a 

 systemic effect, but a very marked local reaction as well in the skin, 

 areolar tissues, and adjacent lymph nodes. 



Koch's observations upon guinea pigs were applied by him, Gutt- 

 stadt, 84 Beck, 35 and others to man, and the result was the develop- 

 ment of the present important diagnostic test. The fundamental 

 fact in this as well as in other tests of this kind, then, is the 

 appearance of local and systemic reactions in infected subjects to con- 

 tact with specific antigenic material which, at least in the same 

 quantities, produces no effects in normal individuals. The analogy 

 with the phenomena of anaphyJaxis is thus indicated. 



Koch's original interpretation of the phenomenon was of course 

 unaided by any of the later observations on anaphylaxis. According 

 to him the tuberculin contained substances which caused tissue 

 necrosis. The necrotizing action was particularly powerful upon 

 tissues which were tuberculous, and therefore already saturated with 

 the toxic material. The destruction of such tissues resulted in sys- 

 temic symptoms. 



Very similar to this view is the one later expressed by Babes and 

 Broca, 36 who attribute the systemic symptoms to a sudden lighting 

 up of the existing lesions by the small amount of extra tuberculin 

 added to that already present in these foci. 



The first suggestion of the possible association of the tuberculin 

 reaction with the union of an antigen and its antibody was made 

 by Wassermann and Bruck. 37 They accepted Ehrlich's assumption 



33 Koch. Deutsche med. Woch., No. 43, 1891. 



84 Guttstadt. "Klin. Jahrbuch" Erganzung-sband, 1891. 



35 Beck. Deutsche med. Woch., No. 9, 1899. 



36 Babes u. Broca, Zeitschr. f. Hyg., Vol. 23, 1896. 



37 Wassermann and Bruck. Deutsche med. Woch., No. 12, 1906. 



