568 THE CHOLERA GROUP 
intoxication in Asiatic cholera is due to the hberation of an endotoxin, 
freed from the organisms by autolysis. Behring and Ransom/ on the 
contrary, claim to have separated a soluble toxin from broth cultures 
of true cholera vibrios which in doses of about 0.5 cc. would kill guinea- 
pigs within twenty-four hours. They have made the additional 
allegation that goats and guinea-pigs may be immunized to the poison 
by the cautious injections of increasing amounts of toxin-containing 
broth cultures of the organism. Antitoxin which forms in response to 
these graded injections is said to protect the treated animal not only 
against the poison, but against infection with the living vibrios as well. 
The toxic substance appears to be unaffected by exposure for moderate 
intervals to temperatures above the thermal death point of the vibrios, 
to chloroform, toluol, or carbolic acid. 
Metchnikoff, Roux and Taurelli-Salimbini- also endeavored to 
demonstrate a soluble toxin among the growth products of the cholera 
vibrio. They enclosed peptone cultures of cholera vibrios in collodion 
sacs, which were placed in the peritoneal cavities of guinea-pigs. i\.s 
controls, killed cultures of the organisms and sterile, uninoculated 
peptone medium respectively, enclosed as before, were introduced into 
the peritoneal cavities of other guinea-pigs. Those animals receiv- 
ing killed cultures of cholera vibrios in capsules become somewhat 
emaciated and exhibited a slight rise in temperature. The guinea-pigs 
that received the collodion capsules containing living cholera vibrios 
died in from three to five days with symptoms of choleraic intoxication. 
These observers concluded from these experiments that the cholera 
organism produced a soluble toxin which was diffusible through col- 
lodion sacs. The toxicity of these cultures was not destroyed by the 
boiling temperature, 100° C. They were able to immunize guinea-pigs, 
rabbits, goats, and horses with this so-called soluble toxin, and found 
the serum of these animals was antitoxic and protective against several 
times the fatal dose of toxin or of the living organisms. Antitoxic sera 
prepared by this method have not been successful in the clinical treat- 
ment of cholera in man. It is not unlikely that the soluble toxic sub- 
stance or substances produced in artificial cultivations of the cholera 
vibrio play a less important part in the disease than the endotoxins, 
which appear to be liberated from the organism with unusual readiness. 
The extremely brief period which elapses between infection and 
death, twelve hours in unusual cases, would suggest that the incubation 
period of the cholera toxin, if such play a part in the disease, is very 
much less than that of any other known soluble bacterial toxin. 
Pathogenesis. — .4rn'???ai^.— Different strains of cholera vibrios vary 
greatly in their virulence for experimental animals; prolonged culti- 
vation on artificial media tends to diminish their pathogenicity as a 
rule. Virulent cultures of cholera vibrios injected intraperitoneally 
into experimental animals, particularly guinea-pigs, frequently incite 
> Deutsch. med. Wchnschr., 1895, 21, 457. 
2 Ann. Inst. Pasteur, 1896, 10, 257. 
