IMMUNITY AND SUSCEPTIBILITY. 79

When this point is, however, safely passed, the Increase
in dosage can be very rapid, yet without signs of poison-
ing, seemingly because the drug is no longer simply tol-
erated, but tolerated and simultaneously neutralized. By
experimentation Khrlich has shown that during" the
period of simple tolerance the blood of the animal is
unaltered, but that as soon as the tolerance becomes
unlimited the blood contains a new substance, capable
not only of protecting the animal by which it is pro-
duced, but also other animals into whose blood it is in-
troduced. In the ricin experiments this substance was
described as autiricin ; in the experiments with abrin, as
antia.br in.

These investigations of Khrlich with the poisons of
higher plants succeeded, but threw much light upon, the
extraordinary work of Behring, Wernicke, and Kitasato,
who experimented with the toxins of diphtheria and
tetanus, and showed that in the blood of animals accus-
tomed to these poisons, new substances—antitoxins, found
by Brieger to be proteid in nature—were produced.

The antitoxic theory of immunity, being, in the cases
cited at least, a fact capable of demonstration, has estab-
lished itself at present as the most important hypothesis.
According to it, acquired immunity, at least, depends upon
the development in the 1)1 ood of a neutralizing' substance
probably related to the nuclei us.

It is of prime importance to remember that the anti-
toxin is an entirely new substance which does not occur
in the blood of normal animals, even when they possess
a high degree of natural immunity, except in rare in-
stances, and then only in minute amounts not propor-
tional to the degree of immunity. Culmette has called
special attention to this fact, and points out that while
fowls and tortoises resist abrin, their blood contains no
anti-abrin; Vaillard has shown that, although the fowl
resists tetanus, its blood contains no protective substance
destructive to tetanus-toxin. Calmette finds that the
blood of the ichneumon and hedgehog, which are im-