Liver therapy for pernicious anemia

George Minot had watched patients with pernicious anemia since his student days at the Massachusetts General Hospital. They passed through relapses and remissions despite arsenic, blood transfusions and removal of the spleen, and all of them eventually died. Because the disease waxed and waned on its own, a few cases could not show whether any treatment worked.

The lead came from dogs. From 1920 George Whipple, who moved from the University of California to Rochester, New York, in 1921, bled dogs to make them anemic and compared how fast different foods rebuilt their blood. Liver worked best, then kidney and meat, and some plant foods such as apricots. Pernicious anemia was thought to be a different disease, caused by a poison acting on the bone marrow, but Minot had come to believe that the immature red cells crowding the marrow lacked something they needed to mature. He and William Murphy decided to try a Whipple-style diet on patients.

After feeding small amounts of liver to a few patients in 1924 and early 1925, they fed it intensively every day, and by May 1926 they had treated 45 patients. Many felt better within about a week. Their main evidence was objective: counts of reticulocytes, the young red cells released from the marrow. Their JAMA paper that August spoke of a special diet, not a liver diet, but the regimen shifted steadily toward liver, and patients had to eat several hundred grams a day, raw or cooked.

Hospitals across the United States and then abroad confirmed the results, and patients whose blood returned to normal stayed well instead of relapsing. The poison theory gave way to the idea that something needed to make red cells was missing and that liver supplied it. Edwin Cohn at Harvard soon made a potent extract to be taken by mouth, and in 1929 Minot's group showed that the active material worked intravenously in tiny amounts. Injectable extracts replaced about 1,500 to 3,000 grams of liver a week with a few cubic centimeters of fluid. In 1928 Castle had shown the part the stomach played in causing the disease.

Minot, Murphy and Whipple shared the 1934 Nobel Prize in Physiology or Medicine for their discoveries concerning liver therapy in anemias.