THE SPLIT PRODUCTS OF TUBERCLE BACILLUS 179 



cavity, subcutaneously, subdurally, intracerebrally, by post- 

 orbital injection, and probably by intravenous injection, 

 though the last-mentioned method was not tried. Sensi- 

 tization may be obtained by the injection of only 0.05 mg. 

 of the protein. The best preparations for sensitization 

 are those in which the protein is in solution. The shortest 

 period of incubation found was six days. This was when 

 the sensitizing dose was given postorbitally. Before the 

 twenty-first day sensitization is uneven and inconstant. 

 After this period it proceeds with great regularity, and the 

 longest duration noted was two hundred and eighty-six 

 days. It is likely that it continues in the guinea-pig through- 

 out life. The size of the sensitizing dose bears no relation 

 to the period of incubation. Acute anaphy lactic shock 

 follows when the reinjection is given intravenously or post- 

 orbitally. The minimum toxic dose on reinjection was found 

 to be 0.99 mg. of the dry protein, and the minimum fatal 

 dose on reinjection 1.6 mg. Attempts to establish passive 

 anaphylaxis have been uniformly unsuccessful. Infected 

 animals become autosensitized and are killed by injections 

 of large amounts of the tuberculoprotein. This protein does 

 not act like a toxin, and when injected into animals does 

 not lead to the elaboration of an antitoxin. "If an animal 

 be infected experimentally it begins to react to tuberculin 

 about the fifteenth day; in like manner, the non-tuber- 

 culous but protein-treated animal will react to a second 

 injection about two weeks after the first. Again, both 

 the tuberculous and the sensitized non-tuberculous animals 

 react to exceedingly small doses of the protein; indeed, a 

 certain proportion of the tuberculous will undergo an 

 intoxication that is identical with acute anaphylaxis, 

 provided the toxic dose is applied postorbitally, while if 

 the sensitized animal receives its toxic injection by a route 

 that renders absorption less rapid e. g., an intraperitoneal 

 injection the resulting intoxication will tend to approxi- 

 mate what is generally observed as the tuberculin reaction 

 in the infected guinea-pig (without, of course, any focal 

 reaction). Therefore, while the facts will not at present 



