44 TOXINES AND ANTITOXINES. 



The conversion of toxine into toxoids usually takes place by merely 

 keeping the poisons. The L value then generally becomes constant after 

 some time, and new toxoids are no longer produced. 1 This rule, however, 

 does not appear to be without exceptions ; at least MADSEN, S whose work 

 has completely confirmed EHKLICH'S results, has described a poison which 

 appears to decrease continuously in its toxic activity. He found in the 

 last determination that L had already sunk to 10 and L+ to 15, and hence 

 considers it possible that the bouillon might eventually become completely 

 non-toxic and contain nothing but toxoids. 



A further interesting point is that the toxones, too, do not remain un- 

 changed, as has been proved by EHRLICH and also by MADSEN. In their 

 case it is the haptophore group that suffers, with the result that toxonoids 

 are formed. This is made manifest by the increase in the value L , for 

 when in a mixture consisting of 100 parts of toxine : 100 parts of toxone, 

 part of the toxone that combines with the antitoxone changes as regards 

 its haptophore group, so that it can no longer be identified by reason of 

 its combining, it obviously follows that the proportion of toxine to the 

 200 saturation units is greater than 100. MADSEN regards the fact that 

 L values of, e.g., 133 (which he found in one case) can occur even with 

 fresh poisons, as evidence that the formation of toxonoids may probably 

 be going on spontaneously the whole time during the production of the 

 toxine. 



Light, according to MADSEN, has an injurious effect upon both the 

 haptophore and the toxophore groups. He found, on exposing a poison 

 mixture to sunlight, that, although the toxicity diminished greatly, yet 

 the values L and L + showed a simultaneous increase. Eventually the 

 specific character of the toxine completely disappeared, but the mixture 

 still remained poisonous. It caused animals to die of cachexy, but none 

 of the characteristic effects of diphtheria poison were found on section. 

 Thus toxic toxoids, if the term be permissible, are formed under the influence 

 of light. 



Not content with all these tedious experiments to determine 

 the constitution of diphtheria virus by repeated determinations 

 of the L and L + values, EHRLICH has obtained a further insight 

 into their nature by the aid of a second and still more ingenious 

 method. 



If we grant the hypothesis that toxoids, toxines, and toxones 

 have a different degree of affinity for the antitoxine, the postulate 

 follows that they do not combine in equal proportions with a 

 given quantity of antitoxine. This is already shown to be 

 probable by a determination of the L + value, but it can only 

 be proved by a direct quantitative estimation of the different 



1 This condition appears usually to be reached in a year. Hence, in 

 testing sera, only such poisons are used as have been kept for a year, in 

 considerable quantities (4 to 5 litres of bouillon), under a thick layer of 

 toluene (Donitz, "Ber. iib. die Thatigkeit des kgl. Instituts f. serum- 

 forschung, &c.," reprint. Klin. Jahrb., vii., 1899). 



2 Madsen, " Constitution du poison diphtherique, Ami. Past., xiii., 568, 

 1899. 



