108 TOXINES AND ANTITOXINES. 



non-poisonous haptines has as yet hardly been systematically 

 investigated. The haptophore group appears to undergo a 

 simultaneous change during the extraordinarily rapid decrease 

 in strength that occurs in fresh poisons ; but at the same time it 

 has not yet been proved beyond doubt that there can be a diminu- 

 tion in the toxic activity while the neutralisation value remains 

 constant. All observers, however, have recorded differences 

 between the direct and the indirect toxic value (i.e., that required 

 to neutralise a corresponding quantity of antitoxine), which point 

 to the existence of non-poisonous haptines. 



BEHRING, 1 in particular, has called attention to this fact. He 

 found that in the case of fresh poisons the direct toxic value was 

 the same as the indirect value (expressed in terms of T ^Vo of an 

 antitoxine unit). Hence he named these "equivalent poisons." 

 On the other hand, in older cultivations he invariably found the 

 direct toxic value was smaller i.e., toxoids had obviously been 

 formed, and had neutralised part of the antitoxine, so that it was 

 necessary to add fewer toxic units to reach L than in the case of 

 fresh poisons containing only toxine. Such poisons containing 

 toxoids are well adapted for immunising purposes, as has been 

 stated by BRIEGER, and is easily explicable. The toxoids appear 

 to have different toxic effects upon different animals ; at all 

 events, the poison scale approximates very closely to that of the 

 equivalent poisons (vide supra) in the case of certain species. 



The existence of toxones appears probable in the light of the 

 experiments of KNORR, 2 who found, for example, that on ap- 

 proximate neutralisation with antitoxine (and therefore in the 

 " differential zones ") an added quantity of poison had a consider- 

 ably smaller toxic value than its corresponding direct toxic value, 

 just as in the case of diphtheria poison far more than a lethal 

 dose is required to convert the value L into L + . He himself, 

 however, appears to reject this conclusion, and to account for the 

 fact in a different way. 



Physiological Action of Tetanus Toxine. Tetanospasmine 

 varies very greatly in its action upon different species of 

 animals, especially with subcutaneous injection. 



In the case of very susceptible animals, its toxic effect is 

 astonishingly great when it is introduced subcutaneously in the 

 usual way. VAILLARD prepared a solution, O'OOl c.c. of which 

 killed a guinea-pig. This dose contained about 0*000025 grin, of 



1 Behring, " Ueber Tetanusgiftmodifikationen," Fortschr. d. Med., xvii., 

 501,1899. 



2 Knorr, " Die Entstehung des Tetanus- Antitoxins," Fortschr. d. Med., 

 1897, 657. 



