XLVIII. DISSOCIATION PHENOMENA IN THE TOXIN- 

 ANTITOXIN COMBINATION. 1 



By Doctors R. OTTO and H. SACHS. 



IN recent years a number of investigators have called attention 

 to a curious paradoxical phenomenon, namely, that with suitable 

 mixtures of toxin and antitoxin the toxicity for animals is the greater 

 up to a certain point, the smaller the fractional part injected. It is 

 to the keen observation of Behring 2 that we owe the first data on 

 this subject. Behring found that the injection of 1-50, or even 1-500, 

 part of a mixture of tetanus toxin and tetanus antitoxin was more 

 highly toxic for mice than the injection of the entire amount. It 

 should at once be stated that the fractional parts were diluted with 

 water, so that the volume injected was the same in all cases. Analo- 

 gous observations were recently made by Madsen 3 working with 

 the toxin of botulism. This investigator found that toxin-antitoxin 

 mixtures which exerted only very slight toxic effects might still kill 

 guinea-pigs, if but the fortieth or eightieth part of the mixture were 

 used. Similarly, the slight toxic effects of the full amount could 

 be entirely avoided if ten times this quantity was injected. We, too, 

 encountered the phenomenon some years ago in the course of test 

 tube experiments on the hsemolytic action of garden-spider toxin. 

 After the publication of Madsen's observations, we took up the 

 question anew, and studied the phenomenon in mixtures of botulism 

 toxin and antitoxin. In view of the interest which attaches to the 



1 Reprinted from Zeitschr. f. exp. Pathol. u. Therapie, Vol. Ill, 1906. 



2 E. von Behring, Aetiologie and aetiologische Therapie des Tetanus. Beh- 

 ring's Beitrage zur experimentellen Therapie, Heft 7, 1904, p. 51; also ibid. 

 Heft 3, 1900, p. 1092. 



3 Th. Madsen, Gifte und Gegengifte, Centralblatt f . Bacteriologie, Referate, 

 Vol. 37, 1905; also Proceedings of the Danish Academy of Sciences, Meeting, 

 Dec. 16, 1904. 



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