374 Tuberculosis 



and their relation to the diagnosis and treatment of tubercu- 

 losis, which at once aroused an enormous though transitory 

 enthusiasm. The observations are, however, of great 

 importance. Koch found that when guinea-pigs are 

 inoculated with tubercle bacilli, the wound ordinarily heals 

 readily, and soon all signs of local disturbance other than 

 enlargement of the lymphatic glands of the neighborhood 

 disappear. In about two weeks, however, there appears, 

 at the point of inoculation, a slight induration which develops 

 into a hard nodule, ulcerates, and remains until the death 

 of the animal. If, however, in a short time the animals be 

 reinoculated, the course of the local lesion is changed, and, 

 instead of healing, the wound and the tissue surrounding it 

 assumes a dark color, becomes obviously necrotic, and ulti- 

 mately sloughs away, leaving an ulcer which rapidly and 

 permanently heals without enlargement of the lymph- 

 glands. 



This observation was made by injecting cultures of the 

 living bacillus, but Koch observed that the same changes 

 also occur when the secondary inoculation is made with 

 killed cultures of the bacilli. 



It was also observed that if the material used for the 

 secondary injections was not too concentrated and the 

 injections not too often repeated (only every six to forty- 

 eight hours), the animals treated improved in condition, 

 and, instead of dying of tuberculosis in from six to ten 

 weeks, continued to live, sometimes (Pfuhl) as long as 

 nineteen weeks. 



Tuberculin. Koch also discovered that a 50 per cent, 

 glycerin extract of cultures of the tubercle bacillus tuber- 

 culin produced the same effect as the dead cultures 

 originally used, and announced the discovery of this sub- 

 stance to the scientific world, in the hope that the pro- 

 longation of life observed to follow its use in the guinea-pig 

 might also be true of man. 



The active substance of the "tuberculin" seems to be 

 an albuminous derivative (bacterio-proteid) insoluble in 

 absolute alcohol. It is a proteid substance and gives all 

 the characteristic reactions. It differs from the toxalbumins 

 in being able to resist exposure to 120 C. for hours without 

 change. Tuberculin is almost harmless for healthy animals, 

 but extremely poisonous for tuberculous animals, its injec- 

 tion into them being followed either by a violent febrile 



