Discovery of vitamin B12 in the liver and its absorption factor in the stomach: a historical review.

This review describes the early chronological events in the pursuit of a treatment for pernicious anaemia, and the subsequent discovery of vitamin B12 and the intrinsic factor. It details Castle's experiments which established the theory of extrinsic and intrinsic factors as hemopoietic principles, and describes the studies on purification of the anti-pernicious anaemia principle from liver tissue that terminated in the crystallization of vitamin B12 and identification of its coenzyme forms. Biochemical purification and characterization of the intrinsic factor secreted by the gastric parietal cells, and two other vitamin B12 proteins, R-binder (transcobalamin I, haptocorrin), and transcobalamin II, are discussed in detail. The biochemical reactions in micro-organisms and humans in which vitamin B12 is involved are then briefly reviewed, and finally and briefly the immunological basis of pernicious anaemia is discussed.