TETANOLYSINE. 135 



It is particularly interesting to note that MADSEN was able to 

 show that this weakening was due to the formation of toxoids. 



In his experiments he followed exactly the same methods as 

 were used by EHRLICH in elucidating the constitution of diph- 

 theria poison i.e., he determined the conditions of combination 

 with the specific anti-body of tetanolysine. This antilysine is 

 present in the preparations of antitoxine against tetanus. In 

 the first place, MADSEN established a unit of toxic activity and 

 a unit of the antilytic power of the anti-body, in accordance 

 with Ehrlich's methods, though here obviously the experiment 

 on an animal had to be replaced by a determination of the 

 blood-solvent power in a test tube. Then, on investigating the 

 conditions of the partial neutralisation of the poison with anti- 

 toxine, he found that they were quite analogous to those in 

 the case of diphtheria poison, for the neutralisation did not 

 take place regularly throughout the whole quantity of poison, 

 but zones of different combining power with regard to the anti- 

 lysine could be detected. 



An addition of only one-thirteenth of the total amount of 

 antitoxine required to neutralise the toxic unit was sufficient 

 to reduce the hsemolytic power by a half ; an addition of a fifth 

 neutralised as much as nine-tenths of the poison ; whilst one-half 

 neutralised ninety-nine hundredths. 



From this it follows that that part of the poison which has 

 the greatest affinity for the antilysine is also endowed with the 

 main proportion of the activity, that then come a second and 

 third zone with less affinity and also smaller solvent capacities, 

 and finally the " spectrum " is completed by a zone with slight 

 affinity and little toxic activity. 



We have here, then (to employ the terminology adopted in 

 the case of diphtheria poison), a zone of highly active prototoxine, 

 with then a broad zone of less active deuterotoxine (hemitoxine *?), 

 followed by the zone of tritotoxine, and, lastly, the toxones, which 

 only act upon certain particularly susceptible erythrocytes, and 

 also enter much more slowly and feebly into combination. 



In general, only prototoxine and deuterotoxine act in the cold 

 (MADSKN'). " If a poison is so far neutralised with antilysine that 

 these two groups remain inactive, the still remaining tritotoxine 

 has absolutely no solvent action at 8 C., even when present in 

 the largest quantities. 



This, as MADSEN has shown, is due to the fact that at that 

 temperature the toxophore group of the tritotoxine is inactive, 

 for it combines with the erythrocytes even at that temperature, 

 1 Madsen, quoted by Dreyer, Zeit. /. Hyg., xxxvii., 274, 1901. 



