82 
sheep, hog, and rabbit serums caused infiltration, and of large quan- 
tities (15 to 20 c. c.) necrosis. On the other hand, cattle serum 
caused death in doses of 10 to 15 c. c., while horse serum in doses 
of 20 c. c. caused no infiltration and in larger doses a very slight 
infiltration which entirely disappeared within fort}^-eight hours. 
Pfeiffer a confirmed Uhlenhuth’s findings and believed that the 
necrotic action was due to a “haptin” substance identical with the 
hemolytic action of blood serum. 
Yon Pirquet and Schick, in their work on “ Die Serumkrankheit,” 
have developed the clinical manifestations following the injection 
of horse serum in man into a syndrome which they call “the serum 
disease.” The principal manifestations of this disease are a period 
of incubation varying from eight to thirteen days, fever, skin erup- 
tions, swelling of the lymph glands, leukonemia, joint symptoms, 
edema and albuminuria. 
The following historical development of this phase of the subject, 
which bears such a close relation to our work, is largely a free trans- 
lation of von Pirquet and Schick’s monograph. 
As a result of their studies von Pirquet and Schick consider their 
most important conclusions to be the fact that the power of reaction 
in serum disease may show itself either immediately or after a short- 
ened period of incubation. 
Arthus b described hypersensitiveness and explained its signifi- 
cance with special reference to the serum disease. He based his 
work upon that of Richet, c who showed in his experiments upon 
actinia poison (the actinia is a sea anemone) that the first injection 
causes death in dogs in doses between 0.2 and 0.18 gram per kilogram 
of body weight. In no case does death occur before ten hours. 
Upon subsequent injection the animal died from smaller doses 
-<£(0.15 gm.) and much more quickly. These injections were all intra- 
venous. The following is a characteristic example: A dog receives 
the first time 0.1 gm. of the actinia poison per kilogram of his body 
weight, from which it shows scarcely perceptible symptoms. After 
twenty- two days the dog was again injected with 0.1 gm. per kilogram 
of weight in the saphenous vein. Several seconds later the dog 
developed coughing respiration and could hardly drag itself along, 
lay upon its side, bowels evacuated, bloody vomiting, and died in 
twenty-five minutes. Richet extracted two different bodies from the 
a Pfeiffer, Hermann : Ueber die nekrotisirende Wirkung normaler Seren. Zeit.f. Hyg., 
Bd. 51, 1905, p. 183. 
b Arthus: Injections repetees de serum de cheval chez le lapin. Compt. rend., 1903. 
cRichet: De l’anaphylaxie, ou sensibilite croissante des organismes a des doses suc- 
cessives de poison. Arch, di fisiol., 1904, p. 129. De Faction de la congestine sur 
les lapins et de ses effets anaphylactique. Compt. rend. Soc. biol., Jan. 21, 1905. 
De l’anaphylaxie apres injections de congestine chez le chien. Compt. rend. Soc. biol., 
1905. 
