total loss of direct irritability to mechanical and electrical stimuli; the lungs show areas of emphysema, but collapse more or less completely when the thorax is opened; the blood shows delayed coagulability, but by no means as great as that observed in a dog. The fall in blood pressure is probably secondary to the failure of the heart. In the guinea-pig, the lungs are the chief organs affected and their function is abolished by a stenosis of the finer air passages preventing in the final stage both the entrance and exit of air, so that death results from asphyxia. The anatomical sign of this condition is furnished by the large inflated lungs which do not collapse on excision from the chest cavity (Fig. 1). The heart keeps on beating after final respiratory stoppage, with no obvious loss of irritability; the blood shows only a slight delay in coagulation and the fall in blood pressure is probably due to the fatal asphyxia. These differences between the three species of animals show clearly the necessity of judging each species by the anaphylactic signs characteristic for it and not by manifestations only found in another species. This important point, that each animal species must be measured by its own yard-stick when examined in anaphylaxis, has not been realized, unfortunately, by some investigators.
Causation of Anaphylaxis.—The remarkable phenomena which characterize anaphylaxis early led investigators to search for the causative agent. Numerous theories, more or less supported by experimental facts, were advanced to explain how, for example, the originally harmless horse serum becomes toxic when injected into an animal sensitized by this substance. The pioneer work of Vaughan, Friedemann and Friedberger deals particularly with this aspect of anaphylaxis. A discussion of all the theories here, however, would lead too far and would only befog the reader. It will suffice to state that the basic idea of the chief theory is that the sensitized organism has acquired the power to split the alien serum very rapidly into its components when injected for the second time, and that these components then act as a poison. There can be no theoretical objection to this conception; it is a legitimate working hypothesis. But there are weighty objections just as soon as one substance or mixture of substance is produced from proteids in the test tube by chemical or biological processes and considered as the causative agents of anaphylaxis because when injected into normal animals they produce more or less completely the signs and symptoms which are characteristic of true anaphylaxis. The assumption may be true, but no rigid proof has so far been advanced that these substances really are produced in the animal body during anaphylaxis. The mere fact that these toxic substances produce a lesion which also occurs in true anaphylaxis, by no means justifies the conclusion that the causative agents were the same in the two processes. Take, for example, the pale, rigid, distended lungs produced in a sensitized guinea--
