ENDOTOXINES AND PROTEINS. 63 



such as occurs when they are dissolved by the fluids in the bodies 

 of animals, or such as take place spontaneously in old cultiva- 

 tions, where part of the cells of the bacteria are brought into 

 solution by the alkaline and other products present in such culti- 

 vations ; and to this extraction process must be attributed the 

 fact that the nitrates from old cultivations are much more toxic 

 than those from fresh cultivations. 



If, now, we ask what position these poisons occupy as regards 

 our definition : whether they are true toxines, against whose 

 action the organism forms antitoxines, we have the following 

 data to go upon : Attempts to prepare a true antitoxine to the 

 poisons contained in the cells of bacteria, the endotoxines, have as 

 yet been unsuccessful. Hence, in the absence of further know- 

 ledge, we must assign an exceptional position to these poisons. 

 Their sole distinguishing characteristic is their extreme toxic 

 nature in experiments on animals. But as yet no convincing 

 proof has been brought that they belong to the true toxines, and 

 possess distinct haptophore and toxophore groups. 



The case is different with the poisons that pass into the filtrate 

 on filtration. A true antitoxine serum for these has been pre- 

 pared e.g., by RANSOM and by Roux and METSCHNIKOFF for 

 cholera, and by A. WASSERMANN for the poison of B. pyocyaneus 

 (q.v.). This was done in the well-known usual manner, by pre- 

 viously treating the animals with increasing doses of the 

 poisonous filtrates. By this means sera were obtained which 

 were capable of neutralising with certainty many times the 

 amount of the lethal dose of the poisonous filtrates. 



Hence, according to the results of all experiments that have 

 been made up to the present, the conditions in the case of these 

 species of bacteria are such that the chief part of the poisonous 

 substance adheres firmly to the cells of the micro-organisms, and 

 does not pass into solution. Such substances are termed the 

 endotoxines, and are comparable with the endoenzymes of yeast 

 and of bacteria themselves. 



Traces of a true toxine which passes into the filtrate also occur. 



The further question now arises, whether we are justified in 

 concluding from these experiments that the production of poison 

 follows the same course under natural conditions i.e., in the 

 organism. 



It seems fairly certain that the answer is in the negative. 



On the contrary, it is extremely probable that the slight traces 

 of poison which we find in these cultivations, and which, as we 

 have seen, increase somewhat in quantity on further extraction 

 of old cultivations, are not those of the primary poison of the 



