ON THE NATURE OF TOXINS 59 



to y 1 ^ c.c. to kill in seven days. Macfadyen and Rowland 

 found that they could immunize animals against their toxin, and 

 that its serum was antitoxic. These researches are difficult to 

 harmonize with those of other observers. We must admit, how- 

 ever, that it is possible to prepare an antitoxin to the endotoxins. 

 The failure of other observers to do so may be owing to the fact 

 that their toxins were not prepared in so suitable a manner for 

 this purpose, and may have undergone some unknown secondary 

 alterations. 



But these researches do not clear up the whole of the mystery, 

 for some observations of Metchnikoff and others show that the 

 V. cholera: can produce a soluble toxin whilst in the animal, and 

 apparently without being killed in the process. These observers 

 prepared collodion bags, which they filled with cultures of this 

 organism, hermetically sealed, and inserted into the peritoneal 

 cavities of guinea-pigs. The animals died in a few days with 

 the symptoms of cholera intoxication, although no bacteria had 

 escaped from the sacs ; the organisms in that situation were still 

 alive. Control experiments with dead organisms showed that 

 little toxin was present ; the animals remained alive, though they 

 might show some symptoms of toxic action. It appears, there- 

 fore, that the living bacteria do elaborate an exotoxin whilst 

 within the animal body, and that this exotoxin has the power of 

 diffusing through a collodion membrane. Welch has suggested 

 an explanation which cannot be discussed fully here, but which 

 may be mentioned briefly. He points out that when bacteria 

 are injected in living animals the tissues of the latter react and 

 produce substances bacteriolysins, etc. which are injurious to 

 the bacteria, and which determine in part the resistance of the 

 host, and suggests that the bacteria may also react in a similar 

 way to the cells with which they are brought in contact. Just as 

 the animal host only produces its toxins the bactericidal sub- 

 stances when the bacteria are brought into contact with it, so 

 the bacteria may only produce their protective substances the 

 unidentified true toxins when brought into contact with aggressive 

 animal cells. If this is the case it is obvious that we cannot expect 

 to produce these toxins in vitro, except perhaps by cultivation of 

 the bacteria in question in fresh serum from an immunized animal. 



