TOXINS OF KOCH'S SPIRILLUM 409 



killed by exposure to the vapour of chloroform, when injected 

 intraperitoneally into a guinea-pig, may cause death in from 

 eight to twelve hours. There is extreme collapse, sometimes 

 clonic spasms occur, and the temperature may fall below 30 C. 

 before death. Pfeiffer considers that the toxic substances are 

 contained in the bodies of the organisms that is, they are in- 

 tracellular, and that they are only set free by the disintegration 

 of the latter. This opinion is grounded chiefly on the fact that 

 when bouillon cultures were filtered, he found that the filtrate 

 possessed very feeble toxic properties. He showed also that 

 when an animal is inoculated intraperitoneally with the cholera 

 organism, and then some time later anti-cholera serum which 

 produces bacteriolysis is injected, rapid collapse with a fatal 

 result may ensue, apparently due to the liberation of the intra- 

 cellular toxins. The dead cultures administered by the mouth 

 produce no effect unless the intestinal epithelium is injured, in 

 which case poisoning may result. He considers that the 

 desquamation of the epithelium is an essential factor in the 

 production of the phenomena of the disease in the human 

 subject. Pfeiffer found that the toxic bodies were to a great 

 extent destroyed at 60 C., but even after heating at 100 C. a 

 small proportion of toxin remained, which had the same physio- 

 logical action. Recently A. Macfadyen found that the product 

 obtained by grinding up the spirilla frozen by means of liquid air 

 had a very high degree of toxicity when injected intravenously. 

 Like Pfeiffer he found that the " endotoxin " was in great part 

 destroyed at 60 C. 



On the other hand, other observers (Petri, Ransom, Klein, 

 and others) have obtained toxic bodies from filtered cultures. 

 Metclmikoff, E. Roux, and Taurelli-Salimbeni have demon- 

 strated the formation of such diffusible toxic bodies in fluid 

 media. By means of cultures placed in collodion sacs in the 

 peritoneum of animals, they found that the living organisms 

 produce toxic bodies which diffuse through the wall of the sac 

 and produce toxic symptoms. By greatly increasing the 

 virulence of the organism, then growing it in bouillon and 

 filtering the cultures on the third and fourth day, they obtained 

 a fluid which was highly toxic to guinea-pigs (the fatal dose 

 usually being i c.c. per 100 grm. weight). If the dose of the 

 toxin is very large, death follows in an hour or even less. The 

 symptoms closely resemble those obtained by Pfeiffer, the rapid 

 fall of temperature being a striking feature. They found that 

 the toxicity of the filtrate was not altered by boiling; appar- 

 ently the toxic substance is different from Pfeiffer's endotoxin. 



