346 Chapter XII 



the blood, whilst toxic for mice, might, still, be antitoxic for the frog. 

 The antitoxin of this blood might merely be incapable of neutralising 

 all the abrin present. Fresh investigations, then, are necessary. 



Even in the higher vertebrata, it is often very difficult to obtain 

 a real vaccination against the various toxins. In the small mammals, 

 which exhibit a great susceptibility to these poisons, it is specially 

 difficult to obtain an artificial immunity. As Vaillard and von Behring 

 have demonstrated, it is possible to vaccinate such animals by means 

 of gradually increasing doses of unmodified toxins, but this method 

 demands much time, is often dangerous, and hence is not very 

 practical. Poisons that act through the alimentary canal are the 

 most serviceable for vaccination, as has been demonstrated by 

 Ehrlich. This investigator had to abandon the vaccination of mice 

 by means of subcutaneous injections of ricin on account of the slough- 

 ing set up at the point of inoculation. He then had recourse to 

 vaccination by way of the mouth, which gave very good results, not 

 only with ricin but also with abrin. This mode of vaccination, how- 

 ever, is applicable to a small number of poisons only. 



We can also vaccinate mammals, even laboratory rodents, such as 

 rabbits and guinea-pigs, by means of unmodified snake venom, but 

 this method is a very delicate one and must be carefully watched. 

 It is necessary to begin with very small doses of venom, continue 

 them for some time, and increase the amount of venom injected very 

 slowly. Calmette 1 modified this method by inserting, below the skin 

 and leaving it there, a piece of chalk impregnated with small quantities 

 of venom and surrounded by collodion through which the venom 

 diffuses very slowly and continuously. 



[364] Large mammals, sheep, oxen and horses, can be more easily 

 vaccinated by means of unmodified toxins, but they also require 

 to be treated with very special precaution. Salomonsen and Madsen 2 

 have given the history of their horse, immunised with diphtheria 

 toxin. Into a mare weighing 665 kilos they were able to inject 

 at the commencement only 1 c.c. of this toxin, and the dose had to 

 be increased very carefully. 



In the presence of all these difficulties in the use of unmodified 

 toxins for vaccination, a different method is now generally adopted 

 in the immunisation of animals, small or large, for the purpose of 

 scientific research or for the preparation of toxins on a commercial 



1 "Le venin des serpents," Paris, 1896, p. 54. 



* Ann. de I'lnst. Pasteur, Paris, 1897, t. xi, p. 316. 



