Artificial immunity against toxins 395 



proof of the presence of the tetanus toxin inside the leucocytes [415] 

 charged with spores, with granules of cerebral substance or with 

 grains of carmine, very great difficulties are encountered. How, 

 indeed, is it possible to demonstrate this poison fixed upon these 

 various bodies, a poison, the presence of which cannot be demon- 

 strated except by its injection into the animal ? For this, in the study 

 of the reaction of the organism of the animal against the poisons, it 

 is very important to have recourse to substances, whose presence can 

 be demonstrated more easily than can the microbial toxins. We must 

 first have recourse to the alkaloids, especially atropin, which, in this 

 respect, present numerous advantages. We know that rabbits resist 

 considerable doses of sulphate of atropin, even when this poison is 

 injected directly into the blood. On the other hand, when it is 

 introduced into the brain, according to Roux and Borrel's method, 

 even small quantities are quite sufficient, as demonstrated by Cal- 

 mette^, to produce a fatal poisoning. The intracerebral injection 

 of the one-hundredth part of a dose which, when introduced into the 

 circulation of the rabbit, produces no disturbance, in the same 

 animal at the end of a few minutes sets up an enormous pupillary 

 dilatation with symptoms of very lively excitation, increase of the 

 reflexes, and general anaesthesia. These phenomena are succeeded 

 by paralysis and death, which supervenes three or four hours after 

 the injection. The natural immunity of the rabbit against atropin 

 falls therefore into the same category as that against morphin. It 

 is not due to the innate insusceptibility of the nerve cells, but to 

 something which prevents the alkaloid from reaching these living 

 elements. With the object of ascertaining the mechanism of this 

 immunity, Calmette injected into the veins of rabbits a fairly large 

 quantity of sulphate oi atropin (0*2), he then bled these animals and 

 collected from their blood the plasma and the white corpuscles, 

 separating them by centrifugaUsation. When injected into the brain 

 of other rabbits, these constituents of the blood did not act in the 

 same way. Whilst large doses of plasma set up merely a short period 

 of excitation and a very transitory pupillary dilatation, corresponding 

 quantities of leucocytes caused grave disturbances, sometimes followed 

 by death in from seven to twelve hours. Calmette concludes from his 

 researches that the atropin does not remain in the fluid part of the 

 blood, since mere traces of it are found in the serum, but that it is 



1 " Cinquantenaire de la Societe de Biologie," Volume jubilaire, Paris, 1899, 

 p. 202. 



