310 PROTECTIVE INOCULATIONS. 



their cultures from the blood and from the various organs gave a 

 negative result. 



Rabbits are not so susceptible, and may recover after the subcu- 

 taneous inoculation of very small doses, but usually die in from four 

 to twenty days when two to four cubic centimetres of a bouillon cul- 

 ture have been introduced beneath the skin. In these animals, also, 

 there is an extensive local oedema, an enlargement of the neighboring 

 lymphatic glands, and a fatty degeneration of the liver. Eoux and 

 Yersiu have shown that in rabbits, when death does not ensue too 

 quickly, paralysis of the posterior extremities frequently occurs, thus 

 completing the experimental proof of the specific pathogenic power 

 of pure cultures of this bacillus. 



Similar symptoms are produced in pigeons by the subcutaneous 

 inoculation of 0.5 cubic centimetre or more, but they commonly re- 

 cover when the quantity is reduced to 0.2 cubic centimetre (Roux and 

 Yersin) . 



The rat and the mouse have a remarkable immunity from the effects 

 of this poison. Thus, according to Roux and Yersin, a dose of two 

 cubic centimetres, which would kill in sixty hours a rabbit weighing 

 three kilogrammes, is without effect upon a mouse which weighs only 

 ten grammes. 



Old cultures are somewhat less virulent than fresh ones, but when 

 replanted in a fresh culture medium they manifest their original viru- 

 lence. Thus a culture upon blood serum which was five months old 

 was found by Roux and Y r ersin to kill a guinea-pig in five days, but 

 when replanted it killed a second animal of the same species in 

 twenty -four hours. 



Evidently a microorganism which destroys the life of a susceptible 

 animal when injected beneath its skin in small quantity, and which 

 nevertheless is only found in the vicinity of the point of inoculation, 

 must owe its pathogenic power to the formation of some potent toxic 

 substance, which, being absorbed, gives rise to toxaemia and death. 

 This inference in the case of the diphtheria bacillus is fully sustained 

 by the results of experimental investigations. Roux and Yersiu 

 (1888) first demonstrated the pathogenic power of cultures which 

 had been filtered through porous porcelain. Old cultures were found 

 by these experimenters to contain more of the toxic substance than 

 recent ones, and to cause the death of a guinea-pig in a dose of two 

 cubic centimetres in less than twenty -four hours. The filtered cul- 

 tures produced in these animals the same effects as those containing 

 the bacilli local oedema, hemorrhagic congestion of the organs, 

 effusion into the pleural cavity. Somewhat larger doses were fatal 



