470 CHOLERA 



took place in September 1894, at a time when there was no 

 cholera in Germany. On the other hand, in many cases the 

 experimental ingestion of cholera spirilla by the human subject 

 has given negative results. Still, as the result of observation of 

 what takes place in a cholera epidemic 'and of what has been 

 established with regard to cholera carriers, we may consider 

 that only a certain proportion of people are very susceptible to 

 cholera, and the facts just mentioned are, in our opinion, of the 

 greatest importance in establishing the relation of the organism 

 to the disease. 



Toxins. — The general statement may be made that filtered 

 cholera cultures as a rule have little toxic action — that is, com- 

 paratively little extracellular toxin is produced by the organism. 

 It was, however, shown by R. Pfeiffer that th,e dead spirilla were 

 highly toxic, and that, in fact, they produced, on injection into 

 guinea-pigs, the same phenomena as living cultures, profound 

 collapse with subnormal temperature being a prominent feature. 

 Pfeiffer considers that the toxic substances are contained in the 

 bodies of the organisms, — that is, they are endotoxins, — and 

 that they are only set free by the disintegration of the 

 latter. 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, appar- 

 ently due to the liberation of «*the endotoxins. 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 kind of action. Later, 

 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. Metchnikoff, E. Roux, 

 and Taurelli-Salimbeni have demonstrated 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 cause 

 toxic symptoms. By greatly increasing the virulence of the organism, 

 then growing it in bouillon and filtering the cultures on the third and 



