Dam and the discovery of vitamin K

Henrik Dam was studying cholesterol, not bleeding. At the Biochemical Institute of the University of Copenhagen he reared newly hatched chicks on artificial diets with the sterols extracted, adding vitamins A and D, to learn whether birds could make their own cholesterol. They could. But some chicks kept on the diet for more than two or three weeks developed hemorrhages under the skin and in muscles and other organs, and their blood was slow to clot.

Extra cholesterol and lemon juice did not stop it. A Canadian group at the Ontario Agricultural College described it in 1931 and went no further, and Holst and Halbrook in California, finding that fresh cabbage prevented it, blamed a lack of vitamin C. Once pure vitamin C was available, Dam showed that injections of it failed. In 1934 he announced that the disease came from a missing, unrecognized dietary factor. Testing then showed green leaves and hog liver to be among the richest sources. In 1935 he called it vitamin K: K was the first unused letter of the alphabet and the first letter of koagulation in Scandinavian and German spelling. Almquist and Stokstad at Berkeley soon confirmed it.

The missing clotting protein in deficient chicks turned out to be prothrombin. In 1939 Edward Doisy's group in St. Louis isolated two pure forms, K1 from lucerne seed and K2 from fish meal, showed that vitamin K was a naphthoquinone, and synthesized it.

The first human disease traced to a lack of vitamin K was the bleeding of obstructive jaundice. Without bile the vitamin is poorly absorbed, and the bleeding had made operations for gallstones or tumors dangerous. Three groups, including Dam's, reached this independently early in 1938, and a dose before surgery removed the risk unless the liver itself was badly damaged. Waddell and co-workers at the University of Virginia hospital found that newborns regularly have low prothrombin in the first week of life, correctable with vitamin K. Dam put visible bleeding at about 1 percent of newborns, from the umbilicus, gut, skin or brain.

Dam and Doisy shared the 1943 Nobel Prize in Physiology or Medicine; Dam was then at the University of Rochester, after a 1940 to 1941 lecture tour of Canada and the United States planned before Germany occupied Denmark in April 1940. Since 1961 the American Academy of Pediatrics has recommended one vitamin K injection at birth. Infants who do not receive it are estimated to be 81 times more likely to develop late vitamin K deficiency bleeding.