Pernicious Anemia - History

History

The British physician Thomas Addison first described the disease in 1849, from which it acquired the common name of Addison's anemia. In 1907, Richard Clarke Cabot reported on a series of 1200 patients with PA. Their average survival was between one and three years. Dr. William Bosworth Castle performed an experiment whereby he ingested raw hamburger meat and regurgitated it after an hour, and subsequently fed it to a group of ten patients. Untreated raw hamburger meat was fed to the control group. The former group showed a disease response, whereas the latter group did not. This was not a sustainable practice, but it demonstrated the existence of an 'intrinsic factor' from gastric juice.

Pernicious anemia was a fatal disease before about the year 1920, when George Whipple suggested raw liver as a treatment. The first workable treatment for pernicious anemia began when Whipple made a discovery in the course of experiments in which he bled dogs to make them anemic, then fed them various foods to see which would make them recover most rapidly (he was looking for treatments for anemia from bleeding, not pernicious anemia). Whipple discovered ingesting large amounts of liver seemed to cure anemia from blood loss, and tried liver ingestion as a treatment for pernicious anemia, reporting improvement there, also, in a paper in 1920. George Minot and William Murphy then set about to partly isolate the curative property in liver, and in 1926 showed it was contained in raw liver juice (in the process also showing it was the iron in liver tissue, not the soluble factor in liver juice, which cured the anemia from bleeding in dogs; thus, the discovery of the liver juice factor as a treatment for pernicious anemia had been by coincidence). For the discovery of the cure of a previously fatal disease of unknown etiology, the three men shared the 1934 Nobel Prize in Medicine.

After Minot and Murphy's verification of Whipple's results in 1926, pernicious anemia victims ate or drank at least one-half pound of raw liver, or drank raw liver juice, every day. This continued for several years, until a concentrate of liver juice became available. In 1928, chemist Edwin Cohn prepared a liver extract that was 50 to 100 times more potent than the natural food (liver). The extract could even be injected into muscle, which meant patients no longer needed to eat large amounts of liver or juice. This also reduced the cost of treatment considerably.

The active ingredient in liver remained unknown until 1948, when it was isolated by two chemists, Karl A. Folkers of the United States and Alexander R. Todd of Great Britain. The substance was a cobalamin, which the discoverers named vitamin B₁₂. The new vitamin in liver juice was eventually completely purified and characterized in the 1950s, and other methods of producing it from bacteria were developed. It could be injected into muscle with even less irritation, making it possible to treat PA with even more ease. Pernicious anemia was eventually treated with either injections or large oral doses of B₁₂, typically between 1 and 4 mg (1000 to 4000 mcg) daily.