130 CHEMISTRY OF BACTERIA AND THEIR PRODUCTS 



ated in the body either by autolysis, or by heterolysis by the enzymes 

 of the body cells and fluids, and there is some question as to whether 

 they are preformed specific constituents of the bacteria, or merely 

 the poisonous product of enzymatic disintegration of the bacterial 

 proteins, similar to the " anaphylatoxins. " "^'^ 



Endotoxins differ from the true toxins, however, in one important 

 respect: namely, it is difficult or impossible to obtain cm antitoxin 

 for endotoxins by immunization of animals°^ Animals immunized 

 against endotoxins develop in their serum substances that are bacteri- 

 cidal and agglutinative to the bacteria from Avhich the poisons are 

 derived, but the serum will not neutralize the endotoxins. As a re- 

 sult, we are unable to perform experiments indicating whether endo- 

 toxins have the same structure as the true toxins, i. e., a haptophore 

 and a toxophore group, but presumably their nature is different in 

 some essential particular. The chemical nature of the endotoxins is 

 also unknown, for they are always obtained mixed with the other con- 

 stituents of the bacteria.'*'' 



Tuberculin, once supposed to be an albumose, is produced even when 

 the bacilli are grown on a protein-free medium, and in the active solu- 

 tion no albumose or other protein is then found. Hence it seems 

 probable that tuberculin is of the nature of a polypeptid, which gives 

 no biuret reaction but is destroyed by pepsin and trypsin, according 

 to Loevenstein and Pick,^ but not by erepsin (Pfeiffer).- Whether 

 tuberculin should be considered an endotoxin liberated by the disin- 

 tegration of the bacilli in the cultures is unknown ; Pick looks upon it as 

 a secretion of the bacilli, and closely related to the true toxins. 



Since far more bacterial diseases are brought about by endotoxins 

 than by true toxins, the failure to secure antitoxins for these sub- 

 stances has been a great check in the progress of serum therapy, and 

 the problem of the endotoxins is one of the most important in the en- 

 tire field of immunity. 



97a See Dold and Hanau, Zeit. Immunitiit., 1913 (10), 31; Zinsser. "Infection 

 and Resistance," N. Y., 1914, Chap. xvii. 



98 Positive results are claimed by Besredka (Ann. Inst. Pasteur, 1906 (20), 

 304). and some others; see Kraiis, Wien. klin. Wocli.. 1900 (19). 6,5,') : Zeit. 

 Immunitiit., 1909 (3), 646. It is suggested by VVassermann (Kolle and \Yasser- 

 maim's Ilandbuch, 1912 (2), 246) that this dilTiculty in obtaining antiondoloxins 

 depends on the large size of the molecule, — the small diffusible toxin molecule is 

 so altered in its physical condition tlirough union with the antibody that its 

 properties are much altered, whereas the large endotoxin molecule must be di- 

 gested by com])lement before its toxicity is destroyed. 



99 'J'lie Afi(/7-eNsivs of Pail, to which lie ascrilies the pathogenicity of bacteria, 

 are too little esta])lished to permit of a discussion from the chemical standpoint. 

 By many they are Ixdieved to be iiolhing more tluin endotoxins. (Literature 

 given by Miilier, Oppenhcimer'a Ilandb. d. Piochem., 1909 (II (1) ), 6S1 : Dud- 

 geon, Lancet, 1912 (1S2), 1673). According to Ingravelle (Ann. d' ig. sperim., 



1910 (20), 483), typhoid aggressins arc found in the albumins. 



1 Piwhem. Zeit.," 1911 (31), 142. 



2 Wien. klin. Woch., PMl (24), 11 If); see also Lockiiiaiiii. Zeit. pbvsiol. C'liem.. 



1911 (73), 389. 



