418 CHOLERA. 



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 

 intracellular, and that they are only set free by the disintegra- 

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

 that when bouillon cultures were filtered, he found that the fil- 

 trate possessed very feeble toxic properties. The dead cultures 

 administered by the mouth produce no effect unless the intes- 

 tinal 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. 



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 in the following manner. Small collodion sacs were pre- 

 pared, each containing 2 to 4 c.c. of bouillon. One sac was 

 inoculated with a living virulent culture of the cholera vibrio ; 

 to the second, two entire cultures on agar of the same organism 

 were added, the cultures being first killed by chloroform. Each 

 sac was then closed and placed with aseptic precautions in the 

 peritoneum of a guinea-pig. The animal which received the sac 

 containing the living vibrios soon showed symptoms of choleraic 

 poisoning, and died in a few days, whilst the animal which 

 received the sac containing large quantities of dead organisms 

 showed only transitory symptoms of illness. These observers 

 therefore concluded that toxic substances are formed by the 

 living organisms, which quickly diffuse into the medium (and in 

 the experiments, through the wall of the sac). 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 \ 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, 



