Decembee 31, 1920] 



SCIENCE 



623 



Pasteur's phrase, the sharply contrasted hyper- 

 sensitiye state. 



. But the time for the systematic investiga- 

 tion of the phenomenon was approaching, for 

 between 1902 and 1904, Eichet and his pupils 

 had their attention arrested by an extraordi- 

 nary incident, as it then seemed. In under- 

 taking to effect immunization with certain 

 poisonous proteins of animals, they found that 

 instead of inducing resistance, they induced 

 hypersensibility. To this latter condition they 

 applied the name anaphylaxis. Although as it 

 subsequently turned out, the idea involved mis- 

 conception of the nature of the process, yet 

 these studies stand forth illuminatingly as 

 recognizing for the first time the dependence 

 of the hypersensitive state upon a preceding 

 ;injection of a given protein substance and 

 the necessity of an incubation period covering 

 a number of days between the injections, in 

 order that the sensitive condition mig'ht be 

 ushered in. That the sensitizing effect was of 

 the nature of a general biological reaction of 

 ■the animal body to the parenteral introduction 

 of natural proteins into the body, without ref- 

 erence to their primarily poisonous character, 

 came to be appreciated a little later as the re- 

 sult of observations made on rabbits and 

 guinea pigs injected and then reinjected with 

 horse serum, as well as with other innocuous 

 proteins. In order to arouse the reaction of 

 immunity in the animal body, some degree of 

 primary poisoning of the cells, as with bac- 

 teria, their metabolic products and similar 

 substances originating in other varieties of 

 living beings, must be accomplished; while the 

 sensitive state arises from the interaction of 

 the animal body with any native protein sub- 

 stance whatever which finds its way directly 

 or indirectly into the blood. 

 - From the many investigations which now 

 ensued, it appeared that while many kinds of 

 warm blooded animals are subject to the con- 

 dition, yet the most striking, because most uni- 

 ;form and dramatic effects are yielded by the 

 ^guinea pig, which has since become, as it were, 

 ,the "classical" animal for observing and 

 ;Studying anaphylaxis. The reason for this 

 phoice arises from lihe circum.stance that in 



the guinea pig a sensitization of the smooth 

 muscle fibers occurs, so that on reinjection of 

 the original protein, among other effects, a 

 'Contraction of the lining membrane of the 

 bronchi takes place, which by closing their 

 lumina and excluding air, quickly causes death 

 from asphyxiation. Moreover, the guinea pig 

 has proved exquisitely responsive to sensitiza- 

 ,tion, so that minute quantities, measured even 

 ;in fractions of milligrams, of pure native pro- 

 teins suffice to induce a specific hypersensitive 

 condition, whence it has followed that the pre- 

 pared guinea pig has been found suitable for 

 the investigation of the ultimate chemical re- 

 lationships, not otherwise observable, which 

 subsist between native proteins. 



Profoundly different as are the obvious fea- 

 tures of the anaphylactic and immune reac- 

 tions, yet certain of the fundamental condi- 

 tions governing both coincide. It will be 

 recalled that in arousiing immunity in animals 

 by artificial means, certain new substances of 

 jthe general nature of antipodes, or as tech- 

 juically named, antibodies, are made to arise 

 in the blood of the treated animal ; and it now 

 appears that in the course of sensitization of 

 animals, antibodies to the proteins injected 

 also develop. In both instances the material 

 originally injected, whether primarily poison- 

 ous or not, if active, belongs to a class now 

 called antigens, that is generators of antibodies. 

 The expression of the immunity reaction, in 

 its simplest terms, consists of a chemical or 

 physico-dhemical union between the original 

 Antigen and the manufactured antibody, taking 

 place in the body or in a test tube, through 

 which the primarily poisonous antigen is 

 rendered innocuous. In other words, the im- 

 mune antigen-antibody complex is a harmless 

 |Compound. 



I In a similar manner the sensitizing antigen 

 and induced antibody unite in anaphylaxis, but 

 the product of the union is essentially differ- 

 ent from the one just considered, in that it is 

 highly injurious, and the effect of the antigen- 

 antibody complex is not to protect, but to 

 poison the animal. The basic distinction be- 

 tween the immune and the anaphylactic con- 

 dition, as described, is further enforced when 



