normal guinea-pig will easily tolerate five, a rabbit twenty and a dog one hundred cubic centimeters intravenously, without showing any obvious effect on blood-pressure or respiration. Harmlessness on first injection is, however, not an absolute essential, and animals may easily be sensitized by primarily toxic sera or poisonous animal extracts, for the amount needed to sensitize is very slight, and is only a small fraction of the lethal dose.
The amount necessary to sensitize is almost unbelievably minute; according to Rosenau and Anderson, 0.000,001 cubic centimeters of horse serum may suffice for a guinea-pig, and Wells has succeeded in sensitizing the same animal species with a still smaller quantity of pure egg albumen, 0.000,000,05 gram. These quantities are beyond the capacity of any balance or test tube to detect, and the biological reaction, as usual, is shown to be the most delicate.
The substance used for sensitization may be incorporated in a variety of ways: by subcutaneous, peritoneal or intravenous injection. Even by feeding the proteid, sensitization may be produced in the guinea-pig according to Rosenau and Anderson. The usual method employed, however, is either subcutaneous or intraperitoneal injection; both these procedures are swiftly and easily carried out, and give but slight or no discomfort to the animal.
Although not every species of animal has been tested, it seems probable that all may be sensitized. The only difference noted is that some species are more difficult to sensitize than others; the guinea-pig is most easily sensitized of all animals tested so far, and for this reason has been the classical animal for investigation. The dog and the rabbit are also rendered hypersusceptible with comparative ease. Fowl are more refractory; man also can be sensitized.
The length of time that sensitization lasts varies in the different animal species. In the guinea-pig that state persists for life, which is about three years (Rosenau and Anderson). In the rabbit the degree of sensitization diminishes after three or four weeks, but persists to a greater or less extent for many months, and in man symptoms have been noted seven years after the first injection.
The degree of sensitization varies also in the different animals and will be considered more fully later.
Incubation.—After the animal has received an unaltered foreign proteid into its circulating juices, this foreign material causes a profound change in the reactions of the host to this proteid. This change occurs gradually and reaches its maximum only after some weeks. If the animal is tested after a few days no reaction will be obtained. In guinea-pigs, for example, ten to fourteen days must elapse before an anaphylactic response can be expected with some certainty, and even with these animals it is best to allow three weeks to pass before testing.
