Liver Therapy, 1926 – Understanding Anaemia and B12

Anaemia means having fewer red blood cells than normal. Pernicious anaemia is an autoimmune form in which gastric parietal cells and intrinsic factor (vitamin B12  absorption requires this glycoprotein) are destroyed. 

In the 1920s, pernicious anaemia (PA) killed about 6,000 Americans annually. Symptoms included personality changes and clumsy movements, and the condition often ended in death. 

Anaemia occurs in various forms but generally involves reduced red blood cell (RBC) numbers and the amount of haemoglobin they contain. Haemoglobin is an iron-containing molecule that carries oxygen for tissues to use.

In 1925, American physician George Whipple showed that iron played a central role in canine anaemia through studies in which he drained dogs’ blood. Feeding anaemic dogs liver relieved their symptoms, and he observed the important role of liver iron in their recovery. 

In 1926, American physicians George Minot and William Murphy showed that eating large quantities of raw liver reduced symptoms in PA patients, leading to frequent prescription of “liver therapy”. Some patients were so weakened by PA that they had to receive liquefied raw liver through stomach tubes inserted through their nostrils.

American physician William Castle wondered why so much liver was needed to trigger a response in PA patients. It emerged that these patients also lacked stomach acid. After he regurgitated meat (undigested food coming back up the oesophagus into the mouth) and gave patients raw hamburger, he observed reduced PA symptoms. He thought that “something” in liver or gastric fluids must be responsible.

Today, we know that the required factor is vitamin B12. Vitamin B12 is needed to produce haemoglobin. Normal gastric parietal cells secrete both acid and intrinsic factor (IF), which is necessary for vitamin B12 absorption in the small intestine. In pernicious anaemia, insufficient vitamin B12 prevents the body from making enough healthy red blood cells. Without enough vitamin B12, these cells do not divide normally and become excessively large. Enlarged cells may have difficulty passing from the bone marrow (the spongy tissue inside bones where blood cells are made) into the bloodstream. 

Severe, long-lasting pernicious anaemia can damage the heart, brain and other organs. It may also cause nerve damage, neurological problems (such as memory loss) and digestive complications. People with pernicious anaemia may also face a higher gastric cancer risk. In a sense, Whipple’s liver therapy, used to supplement iron in iron-deficiency anaemia, also paved the way for treating PA associated with vitamin B12 deficiency.

Historical figures mentioned: George Richards Minot (1885–1950), George Hoyt Whipple (1878–1976), William Parry Murphy (1892–1987), William Bosworth Castle (1897–1990)

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