340 Chapter XI 



toxin of diphtheria. But, as in the tetanus of fowls, it was not long 

 [357] before facts rendered this hypothesis untenable. Kuprianow 1 studied 

 this question under the direction of Loeffler and gave an account 

 of the results of his experiments, which proved that the blood of the 

 sewer rat, which is very refractory against diphtheria, contains no 

 substance that will neutralise the morbific action of diphtheria toxin 

 on susceptible animals, especially the guinea-pig. 



It was necessary to seek some other explanation, and the idea 

 that the immunity of the rat depends on the insusceptibility of its 

 living cells to the diphtheria poison was seized upon. The experi- 

 ments carried out by Roux and Borrel 2 demonstrated the incorrect- 

 ness of this hypothesis. The immunity of rats to subcutaneous or 

 intra-peritoneal injection of diphtheria toxin is very marked. But 

 a very small dose (O'l c.c.) of this poison, introduced directly into 

 the cerebral substance of the rat, produces a complete paralysis, which 

 lasts for several days, and ends in the death of the animal. Roux 

 and Borrel conclude from this " that the brain of the rat is specially 

 sensitive to the action of the diphtheria poison, and that as this 

 animal does not die as the result of the injection of large quantities 

 of toxin into the subcutaneous tissue, it is because the toxin does 

 not reach the brain." These authors have pointed out analogous 

 facts in connection with other examples of natural immunity. The 

 rabbit, which withstands a hypodermic injection of 30 centigrammes 

 of chlorhydrate of morphia, is killed by 1 milligramme only of this 

 salt, introduced directly into the brain. Here, again, neither the 

 cellular insusceptibility nor the antitoxic property of the blood (no 

 " antialkaloidal " power could ever be demonstrated) can explain the 

 immunity, which appears to be due rather to the factor which arrests 

 the poison on its way to the nerve centres. 



In spite of the insufficiency of our knowledge as regards natural 

 immunity against soluble poisons we are quite justified in affirming 

 that this category of phenomena comes mainly into the domain of 

 the cells. The body fluids of animals which exhibit this immunity 

 have been found to be antitoxic in a few species only (scorpion, 

 snake, hedgehog, mongoose). And for the majority of these it is 

 possible to invoke special causes, such as the internal secretion of 

 snake and scorpion venoms by the glands which manufacture them, 

 or the acquisition of an antitoxic power during life resulting from 



1 Centralbl.f. Bakteriol u. Parasitenk., Jena, 1894, Bd. xvi, S. 415. 



2 Ann. de I'Inst. Pasteur, Paris, 1898, t. xu, p. 225. 



