DIPHTHERIA TOXINE. 89 



stance was also found in abundance by WASSERMANN and PBOSKAUER (loc. 

 cit. ) in weakened cultivations. It must be left an open question whether 

 it has anything to do with the toxoids. 



On the other hand, we know that free toxones, which form a 

 second primary decomposition group of products, and can be 

 studied beyond doubt in the transitional stage, do exert quite dis- 

 tinct toxic effects. EHRLicn 1 has observed oedema, and secondary 

 paralytic affections. MADSEN S found that they produced cedema, 

 but not necroses or alopecice. The secondary paralysis occurred 

 in thirteen to thirty-three days, and, in the case of large doses, 

 invariably ended in death. He also observed differences in the 

 behaviour of different cultures. With very much weakened 

 poisons, in particular (i.e., those in which a large amount of 

 toxones was present in the transition from L to L + ), there was 

 a more frequent occurrence of cases in which death was delayed. 

 On the other hand, it is very remarkable that rabbits are killed 

 with very acute symptoms by toxones (EHRLICH). 



But the question of toxones is also of great theoretical interest. 

 If toxones are really true haptines i.e., substances which possess 

 haptophore groups identical with, or closely allied to, those of the 

 true toxines they must also be able to throw off receptors i.e., 

 to produce immunity, if EHRLICH'S side-chain is correct. 



This very interesting question has been experimentally investi- 

 gated by MADSEN and DREYER, 3 and answered in the affirmative. 

 In the case of many poisons which were so far neutralised by 

 antitoxine (vide supra) as to contain only toxones still in the 

 free state, they succeeded in producing a fairly high degree of 

 immunity in guinea-pigs, rabbits, goats, and horses. The serum 

 of the animals thus treated contained fairly considerable, though 

 very fluctuating, quantities of antitoxine, reaching nearly as much 

 as 400 I.E. per c.c. in the case of a horse. They were then also 

 immune against the action of large doses of the fully poisonous 

 toxine, from which the conclusion may be drawn that there is a 

 close relation between the haptophore groups of the toxones and 

 those of the true toxine. 



The rabbit occupied an exceptional position. At first the 

 animal proved extremely susceptible. Mixtures which only 

 produced the effect of toxones upon guinea-pigs still produced 



1 Ehrlich, " Zur Wertbemessung des Diphtherieheilserums," Klin. 

 Jahrb., vi. 



2 Madsen, "Constit. du Poison diphthe"rique," Ann. Past., xiii., 568, 

 1899. 



3 Madsen and Dreyer, " Ueb. Immunisierung mit d. Toxonen d. Diph- 

 theriegiftes," Zeit. f. Hyg., xxxvii., 249, 1901. 



