354 Chapter XII 



in spite of all their precautions, they were unable to prevent the 

 production of hyperleucocytosis. In all their cases, where they took 

 the precaution to count the leucocytes several times a day, there was 

 an undoubted increase of these cells. We may here recall Salo- 

 monsen and Madsen's account of the immunisation of a horse against 

 diphtheria toxin, in which they point out the frequency of tume- 

 factions and even of abscesses. In most cases the pus was sterile, 

 which renders it probable that the white corpuscles had accumulated 

 at the seat of inoculation as the result of some influence exerted by 

 the diphtheria toxin. 



By far the most important and remarkable change met with in 

 animals vaccinated against toxins and venoms, consists in the appear- 

 ance of antitoxic power in their blood and fluids in general. This 

 [372] fact was, as already mentioned, first demonstrated by von Behring 

 and Kitasato^ in the blood of rabbits immunised against tetanus. 

 The blood itself, or the blood serum, mixed with a quantity of tetanus 

 toxin more than sufiicient to cause fatal poisoning, sets up no disease 

 when injected into animals. In their earliest researches, von Behring 

 and Kitasato kept the mixtures in contact in vitro for 24 hours, 

 before injecting them into test animals. Later, they found that this 

 prolonged contact outside the body was unnecessary and that they 

 could obtain successful results by injecting the serum of vaccinated 

 animals and the toxin simultaneously, even at difierent points of the 

 body. This discovery was immediately afterwards applied by its 

 authors to diphtheria and, in the case of both intoxications, confirmed 

 by numerous observers. 



For some time we were satisfied with vaccinating small laboratory 

 animals and establishing the antitoxic power of their blood serum ; 

 later, the vaccination of large animals, especially horses, was com- 

 menced with the object of obtaining large quantities of antitetanus 

 and antidiphtheria serum for medical use. During the course of 

 these experiments the principal characters of the antitoxic fluids 

 were established. It was deemed desirable to isolate the antitoxic 

 substance from the blood serum in order to get rid of every un- 

 necessary and inactive admixture, so that tlie antitoxin might be 

 used in as pure a form as possible. This idea of isolating the anti- 

 toxic substance had, however, soon to be abandoned as impossible of 

 realisation. Antitoxin is a non-crystallisable substance, of unknown 

 chemical composition, which adheres firmly to the albuminoid 

 ^ Deutsche med. Wchmchr., Leipzig, 1890, S. 1113. 



