10 
Another fundamental difference — one which in Ehrlich’s opinion argues in favor of 
the individuality of toxin and toxon — consists in the different action of the two con- 
stituents. The action of diphtheria toxin, as is well known, is such that the animals 
die with lesions of hydrothorax, ascites, congestion of the suprarenals, 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 days, 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. Ehrlich has 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 was found in these poisons, such animals were evi- 
dently supersensitive to the toxon. 
Ehrlich believes that the diphtheria poison contains at least three different varie- 
ties of poison and that these possess different affinities and different actions. These 
poisons are : 
1. Toxin, possessing the highest affinity, kills rabl)its and guinea pigs acutely, but 
is more toxic for the former. 
2. Toxon, killing rabbits acutely and guinea pigs with symptoms of paralysis. 
3. Toxonoid, producing paralyses in rabbits; nontoxic for guinea pigs. 
The fact that all three poisons act more strongly on rabbits than on guinea pigs 
is explained by the absolute higher susceptibility of the former. 
Upon the constituents of diphtheria toxin Ehrlich sums up his views as follows; 
1. The diphtheria ijacillus produces several kinds of poison, especially toxins and 
toxons. 
2. The affinity of diphtheria toxin to the antitoxin is very great. 
3. The deviations from a straight line as they manifest themselves in the graphic 
representation of the neutralization of the poison can not be explained by the 
assumption of a single poison possessing a weak affinity. They are rather the expres- ' 
sion of the fact that the poison bouillon contains admixtures of various kinds of sub- 
stances of a toxoid character. 
4. The Awarded affinity of the toxoids can not be explained by the assumption that 
a simple toxin when transformed into toxoid suffers a change in affinity either posi- 
twely or negatively. Rather does this indicate that the toxic bouillon contains, 
preformed, various toxins of different affinities. 
5. There is no change in the haptophore group in the formation of toxoid. 
6. The absolute number of combining units contained in the immune unit or in 
the L° dose of poison is 200. 
