Natural immunity against toxins 331 



frogs kept at a high temperature are innocuous when these animals 

 are living at low temperatures. But we can, by increasing the dose, 

 produce tetanus in frogs even when the temperature is not very high. 

 Thus Marie 1 was able, during the whole of the winter, to tetanise 

 both green and brown frogs living in water the temperature of which 

 oscillated between 13 and 18 C. The incubation period in this case 

 is very much longer (sometimes extending to 25 days) than in frogs 

 kept at higher temperatures. 



Temperature, therefore, is an important factor in the poisoning by 

 the tetanus toxin and in the resistance of the frog, but, in the long 

 run, this poison can exert its specific action even at relatively low 

 temperatures. 



Morgenroth 2 endeavoured to analyse the mechanism of this re- 

 sistance and of the susceptibility of the green frog when maintained 

 at various temperatures. He demonstrated that the tetanus toxin is 

 fixed in the central nervous system, even at low temperatures, near 

 8 C. ; under these conditions, however, it is incapable of causing the 

 slightest tetanic symptom. When placed in an incubator kept at 

 32 C. the frogs contract tetanus after a period of incubation of some 

 (2 to 3) days. During the first 24 hours of this period the frogs 

 manifest no sign of tetanus, and if they are again put in a cool 

 place they continue in good health. If, however, after a not too pro- 

 longed stay in the cold, these animals are subjected a second time to [348] 

 the higher temperature, they become tetanic, after a shortened 

 incubation period. Cold, therefore, may arrest tetanus even at a stage 

 when the toxin has already produced certain latent but permanent 

 modifications of the nervous system. 



Frogs injected with tetanus toxin and kept in a cold place finally 

 get rid of the poison. When transferred to a warm chamber after 

 a certain lapse of time they no longer contract tetanus. We have 

 found that the greater part of the tetanus toxin continues for some 

 time in the blood of frogs injected and kept at a low temperature. A 

 small quantity of this blood withdrawn almost two months after the 

 last injection produced fatal tetanus in a mouse. We do not know 

 how frogs eliminate the toxin, but it has been demonstrated that in 

 this case it causes no production of antitoxin. Morgenroth has con- 

 firmed this result. 



Reptiles must be regarded as vertebrates exhibiting a most 



* Ann. de FInst. Pasteur, Paris, 1897, t xi, p. 697. 



8 Arch, internat. de P/iarmacodyn., Gand et Paris, 1900, VoL vn, p. 265. 



