Pernicious anemia—a condition in which the body no longer produces enough red blood cells—was a fatal disease until 1926, when two-Boston based doctors, George Minot, MD, and William Murphy, MD, published a landmark paper detailing the success of a raw liver diet in treating 45 patients with the disease.
This cure—the result of three decades of research—would not have happened without the contributions of many physicians and scientists—most significantly George Whipple, MD, who first identified raw liver as a treatment for anemia in dogs in 1918.
Whipple, Murphy and Minot, who trained at Mass General and started his research into dietary treatments for blood disorders here at the hospital, shared the 1934 Nobel Prize for Physiology and Medicine—becoming the first Americans to win the prize.
The Path to Discovery
Pernicious anemia results from a decrease in the production of red blood cells that occurs when the intestines cannot properly absorb vitamin B12, a vitamin that is crucial to the production of blood cells.
Symptoms include pain, difficulty walking, uncontrollable muscle movements, trouble with thinking and memory loss, mood changes, problems with smell, taste and vision and digestive disorders.
The treatment of pernicious anemia had been unsuccessful and arbitrary until the early 1900s, when the liver was recognized as an important player in the process of creating blood and bone marrow cells.
Whipple, a New Hampshire native, made the first big breakthrough by publishing a series of landmark studies demonstrating that raw liver fed to anemic dogs was the most effective diet additive for reversing the anemia by boosting the production of red blood cells.
In a first example of serendipity, a lab technician in Whipple’s lab accidentally fed the dogs raw liver instead of cooked liver as the experiment’s protocols called for. The dogs who consumed raw liver improved so significantly that the results could not be ignored.
Minot and Whipple Take the Reins
The son of a Mass General physician, George Minot, MD, first became interested in blood diseases as an intern at Mass General in 1913, when he was called into consultation by his father for a case that was later diagnosed as pernicious anemia.
Minot began studying dietary therapy after his diagnosis with type 1 diabetes in 1922—a disease that nearly proved fatal prior to the discovery of insulin in 1922.
Fortunately, Minot’s doctor was able to secure some insulin for him in 1923, which set him back on the path to discovery.
This was a second instance of serendipity—if not for the discovery of insulin, Minot may not have been healthy enough to continue in his research.
Minot met George Murphy, MD, while recovering and the two men discovered a shared interest in testing dietary treatments in anemia patients.
After some promising initial results, Murphy and Minot conducted a more detailed, rigorous trial in hospitalized anemia patients, using a diet “rich in iron and purine derivatives.” That diet included 120 grams of “muscle meat,” leafy vegetables, fruit, eggs and milk.
The two doctors eventually found that the consumption of lightly cooked liver meat was most effective in treating pernicious anemia in humans.
They announced their findings in the Journal of American Medical Association in 1926, detailing the treatment of 45 patients who successfully recovered on a liver-based diet.
“Following the diet, all patients showed a prompt, rapid and distinct remission of their anemia with at least marked symptomatic improvement,” Minot and Murphy wrote.
While the diet was effective, it was difficult for many patients to follow due to the need to consume large quantities of lightly cooked liver.
By 1928, further development of the treatment reduced the daily requirement from 300 grams of liver to 12.5 grams of a yellow powder.
Two years later, scientists developed a method for isolating an extract from liver that could be injected as a daily treatment for anemia patients.
Pernicious Anemia Cure Earns Nobel Recognition
In 1934, the Nobel Prize committee recognized Whipple, Murphy and Minot as the first American recipients of the Nobel Prize for Physiology and Medicine.
“I am very happy,” Minot told the Boston Globe upon receiving news of the recognition. “Not so much for myself, but because of the recognition American medicine has received”.
Minot said he hoped the award would inspire other Americans to become “able physicians and investigators and to seek the betterment of their fellow human beings.”
In a 1934 newspaper column, Logan Clendening, MD, described Minot, Murphy and Whipple’s findings as “the most romantic discovery in medical science since the X-ray.”
While diabetes could be treated somewhat successfully prior to the discovery of insulin, treatment prior to the discovery of the liver-based diet had no effect on the life expectancy of pernicious anemia patients, Clendening wrote.
“Then came the announcement of this absurdly simple treatment just to eat liver. I suppose few doctors really believed it at first, except the source of the announcement, the Massachusetts General Hospital in Boston, was so authoritative as to compel attention.”
In 1948, the anti-pernicious anemia factor was named vitamin B12, and it was shown that the administration of a few micrograms of B12 could prevent relapse in the disease.
This lifesaving treatment would not have happened without collaboration, persistence, and serendipity.
About the Mass General Research Institute
Research at Massachusetts General Hospital is interwoven through more than 30 different departments, centers and institutes. Our research includes fundamental, lab-based science; clinical trials to test new drugs, devices and diagnostic tools; and community and population-based research to improve health outcomes across populations and eliminate disparities in care.
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