we are justified in speaking of the response as an undoubted reaction of anaphylaxis. The three conditions necessary for the employment of this word are fulfilled, and we are dealing with the same phenomena or group of phenomena which the older observers noted and which they called hypersensitiveness, Theobald Smith's phenomenon or anaphylaxis. If these considerations are followed a field of investigation with sharply defined borders is opened up, and every observer is enabled to judge whether or not his particular patch lies within this territory.
These criteria yield a sharply circumscribed mass of phenomena which are undoubtedly caused by the same general process, and which may now be further analyzed without any doubt, whether or not they are of anaphylactic origin. The more obvious signs and symptoms have already been established in dog, guinea-pig and rabbit, which are the animals usually employed in laboratory investigation. But it must be continually borne in mind that the characteristic anaphylactic responses of these three species are characteristic only when they are obtained after the second injection of a soluble proteid; the profound drop in blood pressure in the dog, the large immobilized pale lungs in the guinea-pig and the loss of irritability and contractility of the heart muscle in the rabbit, do not occur when a harmless soluble proteid like horse serum is injected for the first time; they only appear when the injection is repeated after the period of incubation, and this peculiarity characterizes them as anaphylactic and differentiates them at the same time from similar reactions which occur on first injection of a large number of substances.
These considerations render clear, perhaps, why it is not justified at present to admit that those cleavage products of proteids which cause a similar disturbance on first injection really produce true anaphylaxis, for as soon as this assumption is granted the three characteristic conditions of anaphylaxis which give this symptom complex an independent existence by delimiting it from similar complexes, is obliterated. Moreover, the clean and outspoken functional responses found in the three animal species in anaphylaxis lose their diagnostic character and independence, and fall back into the ruck, indistinguishable from a mass of similar reactions. This is surely a heavy price to pay for an extension of the meaning of anaphylaxis, especially as this extension is not necessary. Even when true anaphylatoxins are isolated, no such broadening of the term will be necessary, for only those substances can be considered true anaphylatoxins which are isolated biologically from the tissues and circulatory juices of a case of true anaphylaxis; and these substances must practically not be present in normal animals, but when injected into these normal animals the anaphylactic symptoms and signs characteristic for the species employed must be obtained. Such substances may be the product of proteid cleavage, but they will bear
