ESMOND R. LONG 1027 



biological alteration. Extracts of the testis after in vitro and in vivo mixture with 

 tuberculin still failed to cause any reaction in the testis or skin of normal guinea pigs, 

 while causing a typical tuberculin reaction in the tuberculous animal. Identical re- 

 sults were secured when the ground sensitive skin of a tuberculous animal was sub- 

 stituted for the testis. 



The results were so clear cut in every instance, and the recovery of active principle 

 of tuberculin so nearly quantitative, as determined by the most accurate quantitative 

 method available, as to leave me convinced that the active principle was neither ac- 

 tivated nor bound nor neutraUzed by tuberculin-sensitive tissue. Unlike the experi- 

 ments of Bail, Mcjunkin, Lange, and Zinsser, in which the action of truly tuberculous 

 tissue upon tuberculin was concerned, my investigation was confined to the non- 

 tuberculous but highly sensitized tissue of the tuberculous animal. And therein prob- 

 ably lies the explanation for the dilTerence in result. As far as the tuberculin reaction 

 in the latter type of tissue is concerned, i.e., tissue known to be suitable for demon- 

 strating the local reaction, I can only say that the active principle is a specific irritant 

 for sensitized cells, eliciting the reaction in high dilution, without itself being altered. 

 This falls far short, obviously, of an explanation of the phenomenon. 



SPECIFICITY OF THE TUBERCULIN REACTION 



The tuberculin reaction is commonly considered a highly specific reaction, given 

 only by the animal infected with tuberculosis in response to the parenteral introduc- 

 tion of a specific product of the tubercle bacillus (see Krause' on the conditions nec- 

 essary to arouse the state of allergy). It has been proved repeatedly that inoculation 

 with dead tubercle bacilli also produces sensitiveness, and Petroff^ has shown that 

 the allergic state thus produced may be more lasting and of higher degree than has 

 commonly been supposed. In either case, however, as Baldwin and Krause have em- 

 phasized, the sensitiveness is associated with the presence of anatomic tubercle, dead 

 tubercle bacilli producing a lesion less extensive but histologically similar to that 

 caused by the live micro-organisms. Somewhat less constantly, as Krause, Baldwin, 

 Zinsser, WooUey, and Mcjunkin have pointed out (see Baldwin, Petroff, and Gardner, 

 op. cit., p. 136), sensitization has been achieved by the simple injection of tuberculo- 

 protein, but the sensitization is more transient and the reactions ordinarily less in- 

 tense than in tuberculous animals. 



As long ago as 1894 the perfect specificity of the tuberculin reaction was ques- 

 tioned, and beginning with 1925 its specificity has been still more seriously doubted. 

 Matthes,^ Krehl and Matthes,'' and Kircheim and Tuczek (who review the earlier 

 literature)^ all claimed that protein derivatives, particularly the deuteroproteoses, 

 from a variety of sources, elicited skin reactions in tuberculous animals. It is note- 

 worthy, however, that much larger amounts of these products were required than of 

 true tuberculin to elicit the reaction. 



'Krause, A. K.: A>n. Rev. Tithcrc, ii, 343. 1925. 



^Petroff, S. A.: Tr. 20th Ann. Meeting, Nat. Titberc. Assoc, p. 244. 1924. 



sMatthes, M.: Deutsches Arch.f. klin. Med., 54, 39. 1894. 



4 Krehl, L., and Afatthes, M.: Arch, ex per. Path. u. Phariii., 36, 437. 1895. 



5 Kircheim, L., and Tuczek, K.: ibiii., 77, 3S7. 1914. 



