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It has been shown (1, 2) that the oral administration of normal human gastric juice (intrinsic factor) together with beef muscle (extrinsic factor) causes increased blood production and clinical improvement in patients with addisonian pernicious anemia. Positive effects appear if a mixture of beef muscle and gastric juice, with or without preliminary incubation, is administered to the patient at pH 5 or 7 (2). Since neither beef muscle (1) nor gastric juice (2, 3, 4, 5, 6, 7) when administered alone has a positive effect on blood production, it has been inferred that an interaction between these substances is essential for hematopoiesis (2, 3, 7). Such clinical evidence, however, does not serve to indicate whether this interaction occurs in titro, witlhin the alimentary tract, or parenterally. Until very recently, no evidence has been obtained of any chemical activity in sitro in neutral mixtures of beef muscle and gastric juice. Unpublished experiments made in 1930, in collaboration with Dr. C. W. Heath, on mixtures of beef muscle and gastric juice incubated in vitro at pH 7.4 resulted in no detectable increases in the amino nitrogen content of the mixture. Klein and Wilkinson's (8) claim that they have demonstrated the synthesis of the thermostable principle of liver by in vitro interaction of beef muscle and intrinsic factor from hog's gastric mucosa has not been sustained in our hands when

the journal of clinical investigation/the journal of clinical investigation

OBSERVATIONS ON THE ETIOLOGIC RELATIONSHIP OF ACHYLIA GASTRICA TO PERNICIOUS ANEMIA. VII. RESEMBLANCES BETWEEN THE PROTEOLYTIC ACTIVITY OF NORMAL HUMAN GASTRIC JUICE ON CASEIN IN NEUTRAL SOLUTION AND THE ACTIVITY OF THE INTRINSIC FACTOR 1