120 TOXINES AND ANTITOXINES. 



Now, very important consequences follow from this extraordin- 

 arily great affinity of the toxine for the nervous system. Thus 

 it is easy to render tetanus poison harmless by means of anti- 

 bodies before it enters the nerve tracks, but much more difficult 

 to break up the compound when once formed, to separate the 

 toxine from the receptor, to cure the tetanus. With every hour 

 the combination becomes more stable, and the activity of the 

 serum less. It has been shown by DONITZ l how rapidly this in- 

 jurious result takes place. The same quantity of an ti toxine, 

 which, when simultaneously injected, protected a rabbit from 

 a quadruple lethal dose, was absolutely unavailing when injected 

 four minutes after the toxine (intravenous injection being used 

 in each case). After one hour as much as 40 times the amount 

 of antitoxine was necessary. After five hours even huge doses, 

 such as 600 times the single effective dose, were useless. MOR- 

 GENROTH, to his disappointment, found that the serum failed 

 in its action in an exactly analogous manner in the case of frogs, 

 although more slowly. In the therapeutic treatment of men it 

 has frequently been observed that after the occurrence of the 

 characteristic symptoms of tetanus i.e., after the lapse of the in- 

 cubation period even huge doses of immune serum are usually 

 of no avail. 



I have only dealt with this question to this extent, and the 

 further discussion of it does not concern us here, because, on 

 these facts, taken in conjunction with the occurrence of a longer 

 or shorter incubation period (vide supra), attempts have been 

 made to base conclusions as to the alterations in tetanus poison 

 even in the human system. 



Thus certain authors (e.g., COURMONT and DoYON 2 ) have 

 assumed that the poison that eventually produces the outbreak 

 of tetanus is not the primary toxine of the cultivations. The 

 latter is asserted to act only as a ferment, which, under suitable 

 conditions, decomposes the protoplasm of the attacked cell with 

 the formation of the true tetanus poison, which can then produce 

 its poisonous effects without a period of incubation. In reply to 

 the arguments urged by these authors in support of their view, 

 the following remarks may be made : As regards the period of 



1 Donitz, "Ueber das Tetanusantitoxin," Deutsch. med. Woch., 1897, 

 428. 



2 Courraont and Doyon, inter olios. (a) "Mecanisme de production des 

 contractures du te"tanos," Arch, de Phys., 1893, 64; (b) "La substance 

 toxique qui engendre le te"tanos," Sem. Med., 1893, 122 ; (c) " Du t6t de la 

 grenouille, ibid., 1893, 302; (d) "De la produc. d. t. chez la poule," ibid., 

 1893, 486. See also their papers already quoted, and their work Le 

 Tetanos, Paris, 1899. (For other investigations see Blumenthal, loc. cit.) 



