Effects of Gastro-Intestinal Resections in Swine on the Anti-Anemia Potency of the Liver

Shortly after Minot and Murphy37 announced the successful treatment of Addison's pernicious anemia with liver, Castle and his associates3 6,8,9 clearly established a fundamental relationship between a defect in gastric secretion and the occurrence of pernicious anemia. Evidence was presented that gastric juice from normal individuals contained in abundance an unidentified thermolabile substance ("intrinsic factor") that interacted with another unidentified thermostable article of diet ("extrinsic factor") to form a thermostable product ("anti-anemia principle") which was capable of inducing a remission of the disease. The gastric juice of patients with pernicious anemia was found deficent, although not wholly lacking,4' 30 in the intrinsic factor, and the stomach was therefore considered incapable of adequate production of the anti-anemia principle that protected against the disease. It was further postulated that the anti-anemia principle, after absorption, served to promote normal maturation of the red blood cells in the bone-marrow, and that it was also stored in the body, especially in the liver, to serve as a continuous source of supply for the needs of the bone-marrow. Some evidence had accumulated which suggested that the effect3veness of liver and certain other organs33'46 in pernicious anemia was due not to an inherent property of these tissues but was a result of storage therein, or of final synthesis and storage, of the anti-anemia principle. Thus, Richter, Ivy, and Kim,40 in inconclusive experiments, found that the liver of an adequately treated case of pernicious anemia contained the anti-anemia principle in one of three assays, while the liver of a tardily treated fatal case was lacking in potency. Later, Goldhamer, Isaacs, and Sturgis2" and Wilkinson