William B. Castle first hypothesized that an 'intrinsic factor' was necessary to work with Vitamin B12 (known as Extrinsic Factor - ie from the diet) to cure Pernicious Anemia. It took over 2 decades for scientists (Glass, 1952 and Latner, 1953) to begin to identify proteins extracted from stomach juice that were shown to bind to Vitamin B12. Even before they knew how this newly isolated stomach extract worked, they showed that if vitamin B12 was given alone, it did not improve the anemia of Pernicious Anemia, but when the stomach extract (Intrinsic Factor) was added, the anemia was corrected, thereby confirming the vital role of Intrinsic Factor in the vitamin B12 absorption.