The period of incubation, however, may be shortened if an animal is rendered passively anaphylactic. This process depends upon the fundamental observation of Gay and Southard that a normal guinea-pig may be sensitized by injecting it with the serum of another guinea-pig which is already sensitized. If a normal guinea-pig is thus injected with the serum of an animal (guinea-pig, or rabbit more usually) which was sensitized some weeks previously, this normal guinea-pig becomes fully sensitized within twenty-four hours and will respond with typical symptoms when injected with the same proteid which was used to sensitize the donor of the serum (Otto). The serum of an actively sensitized animal, that is, one sensitized by the injection of a foreign proteid, therefore contains some substance, termed a serum-rest or anaphylactin by Gay and Southard, which upon injection fully sensitizes a normal animal within a few hours.
Intoxication.—In this stage we observe how a sensitized animal responds with violent symptoms to an injection of the same proteid which it formerly tolerated with no apparent ill effect; we see the remarkable transformation of what formerly was an apparently harmless substance into a violent poison. The symptoms and signs noticeable in an animal during this stage vary with the species and with the site of injection of the toxic dose. If the injection is given subcutaneously in rabbits, an area of edema develops in the place injected; this edema may gradually lead to a circumscribed necrosis of the skin (phenomenon of Arthus). The same change may also occur in guineapigs, as Lewis has shown. If the second injection is given intravenously in rabbits, a more or less marked respiratory disturbance associated with muscular weakness and increased peristalsis develops (Arthus); if the rabbits are highly sensitized, convulsions followed by death occur in a few minutes (Arthus). In the dog, the respiratory symptoms are not prominent, but the animal shows nausea and vomiting, profound muscular weakness and often discharge of urine and feces. The animals, however, usually recover. In the guinea-pig, the stage of intoxication is dominated by respiratory symptoms. The animal makes such powerful respiratory attempts that the costal arch is drawn inwards with each inspiration; these efforts swiftly become convulsive and the animal dies a few minutes after the intravenous injection of an adequate dose (Auer and Lewis).
Anatomical and Functional Changes Found in the Stage of Intoxication.—The study of anaphylaxis from the clinical symptoms alone is unsatisfactory. The symptoms offer nothing which could not be produced by numerous drugs available to the investigator; they do not indicate why the animal shows these disturbances. For an adequate picture of the process the seat of these reactions and a finer analysis of the functional disturbances is necessary. Moreover, no rational thera-
