456 CHOLERA 



established with, regard to cholera carriers, we may consider 

 that only a certain proportion of people are 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 the 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, apparently 

 due to the liberation of the intracellular 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 physiological 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 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 cause 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 



