62 TOXINES AND ANTITOXINES. 



v. Dungern, "Beitr. z. Kenntn. der Bindungsverh. bei der Verein. v. 



Di.-Gift u. A.," Deutsch. med. Woch., 1904, Nos. 8-9. 

 Wassermann and Brack, " t)b. d. Wirkg. der A.," Deutsch. med. Woch., 



1904, No 21. 



sen, "Constit. der poison dipht.," Centralbl. f. Bakt., xxxiv., 630, 

 ^ 1903. 

 Morgenroth, " t)b. die Bindung von Di.-T. u. A.," Berl. klin. Woch., 



1904, 20; Zeit.fiirHyg., xlviii., 177, 1904. 



H. Sachs, " Konstitution des Tetanusgiftes," Berl. klin. Woch., 1904, 16. 

 Kyes, "Kobragift u. Antitoxin," Berl. klin. Woch., 1904, 19. 

 Nernst, "Ueb. die Anwendbarkeit d. Gesetze d. chem. Gleichgewicht auf 



Gemische von T. u. A.," Z. f. Electrochemie, x., 1904. 

 H. Aron, "Ueb. organische Kolloide, Biochem. Centralbl., iii. [15 and 16], 



1905. 



Endotoxines and Bacterial Proteins. While the production 

 and mode of action of true toxines, such as are formed by the 

 bacilli of diphtheria and tetanus are fairly well known, the case 

 is essentially different and more complicated with a large number 

 of pathogenic organisms, of which we may take the bacteria of 

 cholera and of typhus and B. pyocyaneus as the chief representa- 

 tives. If a cholera cultivation of only a few days' growth be 

 filtered through a bacterial filter, the filtrate is only toxic to 

 a slight extent. Several c.c. are necessary to kill an animal 

 by intraperitoneal injection, and even in these quantities the 

 filtrates are not deadly to all animals. But if we take the 

 residue of the filtration i.e., the filtered-off bacterial cells and 

 destroy these by means of weak disinfecting agents, such as 

 chloroform, it will be found that these dead cells are highly 

 toxic. A few milligrammes of them are sufficient when injected 

 into the peritoneum to kill an animal almost instantaneously 

 with severe symptoms of collapse. In this case, then, the 

 conditions are the reverse of those that obtained with diphtheria 

 bacilli, since at first but little of the poison passes into solution, 

 whereas the dead cells of the bacteria are extremely toxic. If, 

 instead of fresh bouillon cultivations, old ones that have stood 

 for several weeks in an incubating oven are taken, it will be 

 found that there is a considerable increase in the toxicity of the 

 germ-free filtrates. Much smaller doses are sufficient to kill 

 the animals used in the experiment. Yet even under these 

 conditions the toxicity of these filtrates never attains the same 

 degree, as is found with diphtheria and tetanus poison, of which 

 even fractions of a milligramme may cause fatal results. 



The explanation of these experimental results presents no diffi- 

 culty. Obviously cholera bacilli, &c., secrete the greatest part of 

 their poison within their vital substance. This part is only 

 liberated when the bacteria undergo a process of destruction, 



