VON PIRQUET'S EARLY STUDIES 533 



by protein substances in the toxin nitrate; others regard von Behring's 

 explanation as satisfactory. Further reference to this subject will be 

 made later on in this chapter. 



^/iRichet's Studies. The fundamental observations upon which our 

 present knowledge "of anaphylaxis is based were made in 1898 by 

 Hericourt and Richet. 1 These observers found that repeated injections 

 of eel serum into dogs gave rise to an increased susceptibility to this 

 substance, instead of immunizing the dogs against the serum. These 

 studies were continued by Richet 2 and his assistants with extracts of the 

 tentacles of certain sea anemones. These studies showed that a second 

 injection of the poison into dogs, given after an interval of several days, 

 is followed by greater and more intense activity than marked the first 

 injection. If the animal survives, however, the disease is conquered 

 more readily after the second than after the first injection. As pre- 

 viously stated, Richet coined the word " anaphylaxis/' meaning " with- 

 out protection," and indicating that the first injection destroyed any 

 natural resistance that the animal might possess against the poison 

 (actionocongestin) . From these studies he concluded that two dif- 

 ferent substances are contained in eel serum and in the tentacles of 

 actiniens, one concerned in establishing an immunity, and the other in 

 calling forth a hypersensitiveness; thus far, however, the separate 

 existence of these two hypothetic substances has not been proved. 



Arthus Phenomenon. In 1903 Arthus, 3 at the instigation of Richet, 

 showed that similar results may be obtained with non-toxic substances, 

 like serum and milk. On injecting rabbits at definite intervals with 

 normal horse serum, he found that the first two or three doses were 

 absorbed, whereas subsequent injections, given subcutaneously, led to 

 increasingly severe local reactions (Arthus phenomenon) . If the animals, 

 however, were first injected subcutaneously and later intravenously, 

 or intraperitoneally, serious symptoms of dyspnea, convulsions, and 

 diarrhea, and even death resulted. 



Von Pirquet's Early Studies. For a long time urticarial eruptions 

 were occasionally observed to follow transfusion of blood from lambs 

 and other lower animals to persons suffering from anemia and similar 

 conditions. Soon after diphtheria antitoxin was discovered the medical 



1 Compt. rend. Soc. de Biol., 1898, 53. 



2 Compt. rend. Soc. de Biol., 1902, liv, 170; 1903, Iv, 246; 1904, Ivi, 302; 1905, 

 Iviii, 112; 1907, Ixii, 358, 643; 1909, Ixvi, 763; 1909, Ixvi, 810; 1909, Ixvi, 1005. 

 Ann. de Hnst. Pasteur, 1907, xxi, 497, 1908, xxii, 465. 



3 Compt. rend. Soc. de Biol. 1903, Iv, 817; 1906, Ix, 1143. Archiv. internat. de 

 Physiol., 1908-09, vii, 472. 



