The action of gastric juice on beef muscle-globulin, with reference to anaemia.

PERNICIOUs anaemia results from a failure of the supply of healthy red cells to the circulating blood. No way was known of restoring this lost power of regeneration of healthy red cells until Minot and Murphy [1926] observed that by feeding liver to persons suffering from this type of anaemia increased numbers of reticulocytes, or young red blood cells, appeared in the circulation, with the result that the blood was gradually restored to its normal condition. Following on this discovery, Castle [1929; Castle and Townsend, 1929] announced that changes in the blood, similar to those produced by liver feeding, could be caused by daily administration of raw beef which had previously been digested by normal gastric juice, either in the stomach of a normal person or in vitro. Neither beef nor gastric juice was effective alone or when fed successively. Castle suggested that pernicious anaemia is a deficiency disease of a new type; that it is due to a lack of some unknown substance or principle produced from protein during normal digestion; and that the gastric secretion in pernicious anaemia is deficient in a factor necessary for the production of this principle. According to this work there are, therefore, two factors involved in the maintenance of the proper supply of red blood cells: (1) an intrinsic factor in the gastric juice, and (2) an extrinsic factor contained in protein. By the interaction of these factors the haematopoietic principle is produced. Normally this principle is concentrated in the liver, hence the efficacy of this organ in the treatment of anaemia. In his later work Castle et al. [1930] demonstrated that the protein of beef muscle, precipitated at pH 6 and washed with saline of the same reaction, could act as the extrinsic factor: washed caseinogen and wheat gluten were unsuitable. The principle could be obtained by digesting this precipitated beef protein with normal gastric juice at a neutral reaction. The intrinsic factor appears to be neither HCI, nor pepsin, nor trypsin; it is confined to the gastric juice and is destroyed by boiling and behaves like an enzyme [Castle et al., 1931]. In view of what is known of the intrinsic factor, its resemblance to an enzyme, etc., we felt that it would be of value to study more closely the interaction of gastric juice and muscle-protein with the object of obtaining chemical evidence of the production of the active principle. Up to this time the test for the presence of the haematopoietic principle in digests, and incidentally, for the presence or absence of the intrinsic factor in a given sample of gastric juice, has been a reticulocyte response after feeding the products of digestion to cases of pernicious anaemia.