The effectiveness of an incubated mixture of meat and normal human gastric juice against anemia was first described by Castle1 in 1929.
In the original hypothesis it was assumed that a protein-like substance in the meat was split up by a proteolytic ferment of the normal gastric juice, either in vivo in the normal stomach or in vitro by incubation at 37 C., with formation of the effective antianemic substance. It was assumed by most authors that this newly formed substance was identical with the antianemic factor in liver, although this identity was not expressly stated by Castle.
The active factor in normal human gastric juice (called the intrinsic factor) was found to be thermolabile (it was destroyed by a temperature of 60 C. in one-half hour). This intrinsic factor was not identical with either of the known ferments pepsin and rennin.
The active factor in the meat (called
FORMIJNE P. EXPERIMENTS ON THE PROPERTIES OF THE EXTRINSIC FACTOR AND ON THE REACTION OF CASTLE. Arch Intern Med (Chic). 1940;66(6):1191-1214. doi:10.1001/archinte.1940.00190180003001