400 INFECTION AND RESISTANCE 



of blood, it would react more energetically and to small amounts of 

 the homologous serum. There are many interesting by-products of 

 Schultz's work, such as the differences between fresh arterial blood 

 and blood serum in their abilities to stimulate contraction, but this 

 and other points will not be discussed at present. The important and 

 incontrovertible fact established by Schultz is the changed reaction- 

 energy or, in truth, "allergie" of the smooth muscle of anaphylactic 

 animals to the stimulus of the sensitizing antigen. Dale 47 has con- 

 firmed and extended these observations of Schultz. He removed the 

 uteri from guinea pigs after thoroughly perfusing them with Ringer's 

 solution to remove all blood. He then suspended them in baths of 

 Rimer's solution and by the customary physiological methods meas- 

 ured the contractions following the addition of various amounts of 

 foreign protein in the form of among other things horse serum 

 and beef serum. He found that the uterus of an animal sensitized 

 to horse serum would react to this substance in dilutions of 1 :2,000 

 or 1 : 10,000, while the organ taken from a normal guinea pig reached 

 its limit of reactionability at dilutions often less than 1 :200. A 

 uterus that had reacted strongly was found to be subsequently desen- 

 sitized. A normal uterus could not strangely be passively sen- 

 sitized by immersion into a solution containing serum antibodies. 

 This method of investigation has recently, also, been taken up by 

 Richard Weil 48 who has fully confirmed the principles laid down 

 by Schultz and Dale. He has incidentally also answered an objec- 

 tion to the conclusions of Dale and Schultz (never indeed a very 

 valid objection), namely, that the reaction of the muscle tissue of a 

 sensitized animal might be in part due to the fact that the blood, 

 i.e., the antibodies, had not been entirely washed out of the tissue 

 spaces by perfusion. Weil performed the very simple and ingenious 

 experiment of injecting a normal guinea pig with large amounts of 

 immune serum (anti-horse serum) and, after a few minutes, killing 

 the animal. He then suspended the uterus in Ringer's solution in 

 the usual manner without washing it completely free of blood. Con- 

 tact with the homologous antigen produced no response. We may 

 accept as definitely established by these researches of Schultz, Dale, 

 and Weil that the fixed cells of anaphylactic animals possess an in- 

 creased reaction-ability toward the antigen which is in no sense sec- 

 ondary to processes involving the circulating antibodies. Moreover, 

 the work of We 1 "! seems to indicate that desensitization of a pas- 

 sively prepared guinea pig deprives the uterus of its power to re- 

 spond and that the gradual spontaneous diminution of hypersuscep- 

 tibility on the part of the guinea pig is accompanied by an entirely 

 parallel loss of reaction-capacity on the part of the isolated uterus. 



47 Dale. Jour. Pharmacol. and Exper. Therap., 1913, iv. 



48 Weil, R. Jour. Med. Research, 27, 1913; 30, 1914; Proc. Soc. Exper. 

 Biol. and Med., 1914, xi, 86. 



