RELATION OF TOXINES TO ANTITOXINES. 33 



formed into toxoids, whilst, the combination not being broken up, no free 

 antitoxine can be detected. Thus, the negative results of these experi- 

 ments prove nothing, since they might have been predicted beforehand 

 to be theoretically very probable. 



This combination is a chemical reaction, and as such obeys 

 the laws of chemical kinetics. Very considerable differences 

 may be shown as regards firmness of combination and speed of 

 reaction. Thus, diphtheria antitoxine has a far greater affinity 

 for its toxine, and combines with it much more rapidly (five to 

 ten seconds) than is the case with tetanus antitoxine and its 

 toxine (EHRLICH). 



The degree of attraction for reciprocal saturation and the 

 speed of the reaction also depend, to a very considerable extent, 

 upon the temperature (increasing with its rise) as well as upon 

 the concentration (EHRLICH, KNORR 1 ). Combination takes place 

 much more rapidly in concentrated solutions. 



We must defer consideration of the question of the condition 

 of equilibrium between toxine and antitoxine. 



The view that antitoxines do not combine with toxines in 

 fixed numerical proportions, but that their action depends upon 

 a protective influence upon the cells, has not yet been entirely 

 abandoned, notwithstanding all proofs to the contrary. In 

 particular, attempts have been made to base this conclusion on 

 the alleged facts that when the dose of toxine is multiplied the 

 same multiple of antitoxine is insufficient i.e., that its "pro- 

 tective " power fails with large doses of poison. This view has 

 recently been advanced again e.g., by BOMSTEIN. 



But EHRLICH'S experiments on ricine, and the absolutely ana- 

 logous results of CALMETTE with snake poison^ of CAMUS, KOSSEL, 

 &c., with eeVs Hood poison, and of many others with erythrocytes, 

 lead us to exclude any intervention on the part of the organism, 

 and are only to be explained on the assumption of a direct 

 fixation of the poison by the antitoxine. And apart from this, 

 the assertion that there is a discrepancy in the numerical pro- 

 portions rests upon very insufficient data. 



COBBETT and KANTHACK 2 were able to demonstrate that the 

 multiples exactly corresponded with theory, provided a large 

 multiple of the lethal dose was used at the very beginning of 

 the experiment. They give a simple reason for concluding that 

 when a quantity of poison approximating a single lethal dose is 



1 Knorr, * ' Die Entstehung des Tetanusantitoxins, " Fortschr. d. Med., 

 1897, 657. 



2 Cobbett and Kanthack, "Ueber das Schicksal d. Diphtherietoxins im 

 Tierorganismus," Centralbl.f. Bakt., xxiv., 129, 1898. 



3 



