370 Chapter XII 



feeble resistance of the guinea-pig by frequent injections of very 

 small quantities of toxin. Knorr 1 increased their susceptibility to 

 tetanus toxin by daily injections of one-tenth of a minimal lethal 

 dose. The animals died before they had received the ten tenths of 

 this dose. The hypersusceptibility produced under these conditions 

 might be so great that one-fiftieth of the minimal lethal dose was 

 capable of causing death. From these facts we can understand 

 the great difficulty experienced in the earlier attempts to vaccinate 

 guinea-pigs by means of unmodified toxin. 



Von Behring and Kitashima 2 made analogous researches on the 

 susceptibility of guinea-pigs to diphtheria toxin. By frequent in- 

 jections of very small doses of this poison they succeeded in killing 

 these animals with -^ of the minimal lethal dose distributed over 

 several injections. They never succeeded in vaccinating guinea-pigs 

 with increasing doses of pure diphtheria toxin. Their animals died 

 even when they commenced with one-millionth of the minimal lethal 

 dose. 



[389] Here, then, we have examples of the greatest hypersusceptibility 

 that it is possible to observe. When we compare it with the 

 changes in the antitoxic power of the blood, we find that these are 

 even more marked. Thus, Salomonsen and Madsen's horse, to which 

 we have already referred, presented extraordinary oscillations in this 

 power. After receiving, during the course of immunisation, a fresh 

 dose of diphtheria toxin, the antitoxic value of its blood suddenly fell 

 more than one-third (35 %) In order to neutralise, completely, this 

 dose of toxin, when injected into a normal animal mixed with anti- 

 toxic serum from this same horse, a very small quantity of the blood 

 of the latter would have been sufficient. The injection into the 

 immunised horse should have passed unperceived, as this animal 

 contained in its body more than 50 litres of strongly antitoxic blood. 

 Nevertheless the antitoxic power of this blood fell 12,000 times 

 more than it ought to have fallen according to the calculation made 

 upon the data just indicated. This fall is incomparably greater than 

 the increase of susceptibility to toxin in the most significant examples 

 reproduced above. 



As the fact above cited is not at all unique, it is probable that 

 the phenomena which appear in the animal subjected to vaccination 



1 "Experimentelle Untersuchungen iiber die Grenzen der Heilungsmoglichkeit 

 des Tetanus," Marburg, 1895, SS. 18, 19. 



2 Berl. klin. Wchnschr., 1901, S. 157. 



