THE CONSTITUENTS OF DIPHTHERIA TOXIN. 507 



Another fundamental difference, one which in my opinion argues 

 in favor of the individuality of toxin and toxon, consists in the differ- 

 ent action of the two constituents. The action of diphtheria toxin, 

 as is well known, is such that the animals die with symptoms of 

 hydrothorax, ascites, congestion of thesuprarenals, necrosis of the skin. 

 Somewhat smaller doses kill guinea-pigs in from six to seven days, 

 the animals showing ulceration and extensive necrosis. Still smaller 

 doses, \, \, , % L. D., no longer produce death, but regularly cause 

 necroses which are surrounded by an extensive area of total loss of 

 hair. Small fractions of the fatal dose always produce emaciation 

 of the animals. In contrast to this, the toxon, i.e. a serum-poison 

 mixture in which only the toxin fraction is completely neutralized, 

 never kills animals acutely, even in high doses. The inflammatory 

 properties may be entirely absent in small doses, while in large doses 

 they are present to only a slight degree. The oedema disappears 

 completely in the course of a few days, there are no necroses, and 

 the loss of hair, if it occurs at all, is only partial. On the other hand 

 the paralyses are very characteristic, and these appear at any time 

 between the fourteenth and twentieth day, depending upon the dose, 

 usually in the third week. Frequently the animals do not show even 

 a trace of local reaction and maintain their weight ; then suddenly they 

 are attacked with the paralyses and may die from these within a few 

 days. I have never seen such a result in animals inoculated with a 

 pure diphtheria poison. Now and then a guinea-pig was observed 

 which showed these paralytic phenomena. It was usually one that 

 had received a considerable fraction of the L. D. Invariably it 

 showed extensive necroses, was generally very sick from the beginning, 

 and had suffered considerable loss of weight. In view of the slight 

 amount of toxon which I found in these poisons, such animals were 

 evidently supersensitive to the toxon. 



Dreyer and Madsen have succeeded in differentiating toxin and 

 toxon qualitatively, as follows : They found that mixtures of a diph- 

 theria poison and antitoxin in which the limit of complete toxin 

 neutralization was nearly approached, exerted only toxon effects 

 when given in small doses. If, however, the mixture was increased 

 tenfold, death was brought about by the toxin. This is readily 

 explained. The determination of toxon by means of 1 I. E. natu- 

 rally cannot be absolutely exact, for a small residue of toxin, e.g. 

 Vio L. D., can readily escape observation. If, however, a sufficiently 

 large multiple of this mixture, e.g. ten times the original quantity, is 



