38 INFECTION AND RESISTANCE 



tracted or which became free as cell-death occurred and disintegra- 

 tion ensued. 



It was assumed that, when bacteria entered the animal body and 

 were destroyed by the action of the serum or cells, these endotoxins 

 were liberated and poisoning resulted. Thevery protective action 

 of the serum, which prevented the extension of the infectious in- 

 vasion, by limiting bacterial growth, was thus looked upon as the 

 agency by which the endotoxins were set free. Experiments by 

 Radziewsky and others, in which it was shown that large doses of 

 bacteria injected into immunized animals were violently toxic and 

 more rapidly fatal than corresponding amounts injected into normal 

 animals, were taken to mean that in the immune animals a more 

 powerfully cell-destroying property of the serum led to a more rapid 

 liberation of the endotoxins. 



This was the conception of Pfeiffer and, in more recent theoret- 

 ical discussions, that of Wolff-Eisner. Its essential features con- 

 sisted in the assumption that the poisons were preformed and were 

 contained within the cell body as such, and that they were specific for 

 each micro-organism, determining to a certain extent its pathogenic 

 properties. Thus typhoid endotoxin, cholera endotoxin, or dysen- 

 tery endotoxin was supposed each to possess its own particular 

 pharmacological properties by which the clinical manifestations of 

 the respective diseases were partially determined. 



It is chiefly the work of Vaughan 26 which has begun to throw 

 doubt upon Pfeiffer's original views, in that Vaughan has shown 

 that all proteins, bacterial or otherwise, would yield, upon cleavage 

 with alkalinized alcohol, toxic split products which possessed many 

 of the pharmacological properties of the so-called endotoxins. In 

 fact, Vaughan succeeded in producing, in animals, fever and other 

 symptoms which are generally associated with infection, merely by 

 injecting into them graded quantities of his toxic split products. 



Following Vaughan, Friedberger succeeded in showing that 

 toxic substances similar to Vaughan's split products are formed 

 when bacteria of various species are subjected to the action of nor- 

 mal or immune sera, and that such poisons were pharmacologically 

 alike and produced with equal ease from pathogenic and non-patho- 

 genic micro-organisms. These phenomena are discussed in greater 

 detail in our section on bacterial anaphylaxis. It is necessary, how- 

 ever, to point out in this place the uncertainty in which these re- 

 searches have left the conception of endotoxins. They suggest that 

 the toxic effects following upon the introduction of pathogenic bac- 

 teria into the animal body are not due to endotoxins, but are rather 

 the result of the action of toxic cleavage products formed in the re- 

 action between blood plasma and bacterial cell. These split products 



26 For a complete discussion of Vaughan's work see Vaughan, "Protein 

 Split Products," Lea & Febiger, Phila. and N. Y., 1913. 



