THE POISON OF THE TUBERCLE BACILLUS. 167 



Here we must first determine whether there is a true tuber- 

 culosis toxine. 



Until quite recently the only preparations actually tested with 

 regard to this point were those of MARAGLiANO. 1 By means of 

 filtration through bacterial filters he obtained from fresh cultures 

 grown at the ordinary temperature a poisonous bouillon, which 

 in large doses caused death, preceded by hypothermia and sweat- 

 ing. The poison was destroyed at 100 C. Similar insignificant 

 results were obtained by BERNHEiM 2 with cultures filtered 

 through a Kitasato filter. 



MARAGLIANO and his pupils also prepared therapeutic sera and 

 antitoxines against tuberculosis, but he himself concluded that 

 the antitoxine did not have a direct neutralising effect upon the 

 "toxine," but only acted as a stimulus to other therapeutic 

 forces ; hence it loses all interest for us. 



These experiments appeared of great importance, and their 

 results were very thoroughly tested as regards their thera- 

 peutical application, though without any material success. But 

 this did not do much to advance the knowledge of the toxine 

 question itself. 



LEDOUX and LEBARD 3 also found in cultivations that had been filtered 

 through a Chamberland filter substances which had, it is true, a pyrogenic 

 and toxic effect on intraperitoneal injection, but their action was so slight 

 that they were inclined to attribute it exclusively to the culture medium 

 itself. 



More recently the results of an investigation into tuberculosis 

 toxine have been published by FRENKEL and BRONSTKIN.* They 

 cultivated tubercle bacilli on a glycerin bouillon of 5 per cent- 

 strength, and thus obtained solutions of poison which, after 

 being freed from the bacilli by filtration, killed a guinea-pig in 

 a few days when injected in a dose of 1-5 to 2 c.c. 



The poison was rapidly weakened by light and air. They 

 prepared it in a concentrated form by means of precipitation 

 with alcohol. 



They claim to have produced immunity by means of inocula- 



1 Maragliano, "Heilungd. Lungentuberkulose durch Heilserumtherapie," 

 BerL klin. Woch., 1895, 689; id., " Ueber das tuberkulose Heilserum u. 

 seine Antitoxine," ibid., 1896, 773; id., " Ueb. d. Tuberkelantitoxin," 

 Mali/s Jb., 1900, 1044. 



2 Bernheim, "Immun. tuberc. et serumtherapie," Soc. BioL, xlviii., 291, 

 1896. 



3 Ledoux and Lebard, " De Faction sur la tempe'r. du bouillon des 

 cultures tuberc.," Arch. d. Med. JExptr., x., 601, 1898. 



4 Frenkel and Bronstein, " Ueber Tuberkulosetoxin und Antitoxine," 

 BerL klin. Woch., 1901, 861. 



