Toxic Products 719 



in the tubercle bacillus, making up from 8 to 26 per cent, by weight. 

 The first could be extracted with cold alcohol, the second with hot 

 alcohol, the third with ether. In addition to the fatty substance 

 Ruppel also found what he believed to be a protamin, and called 

 tuberculosamin. It seemed to be combined with nucleinic acid, and, 

 indeed, from it he isolated an acid for which he proposed the name 

 tuberculinic acid. 



Behring* found that this acid contained a histon-like body whose 

 removal left chemically pure tuberculinic acid. One gram of this 

 acid was capable of killing a 600-gram guinea-pig when administered 

 beneath the skin. One gram was fatal to 90,000 grams of guinea- 

 pig when introduced into the brain. If injected into tuberculous 

 guinea-pigs it was much more fatal, i gram destroying 5o,ooo when 

 injected subcutaneously and 40,000,000 when infected into the 

 brain. 



■ Levenef also found free and combined nucleinic acid varying 

 in phosphorus content from 6.58 to 13.19 per cent. He also found 

 a glycogen-Uke substance that reduced Fehling's solution when 

 heated with a mineral acid. 



Toxic Products. — In 1890 Koch J announced some observations 

 upon the toxic products of the tubercle bacillus and their relation 

 to the diagnosis and treatment of tuberculosis, which at once af oused 

 an enormous though transitory enthusiasm. The observations were, 

 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 enlarge- 

 ment of the lymphatic glands of the neighborhood disappear. In 

 about two weeks, however, there appears, at the point of inocula- 

 tion a slight induration, which develops into a hard nodule, ulcer- 

 ates, 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 assume a dark color, become obviously necrotic, and 

 ultimately slough away, leaving an ulcer which rapidly and per- 

 manently 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 occurred 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 continued to live, sometimes (Pfuhl) as 

 long as nineteen weeks. 



Tuberculin. — Koch also discovered that a 50 per cent, glycerin 



* "Berliner klin. Wochenschrift," XXXVI. 

 t "Jour, of Med. Research," i, igoi. 

 % "Deutsche med. Wochenschrift," 1891, No. 343. 



