Wednesday, March 28, 2007

Nobel Laureates: Dam and Doisy


The Nobel Prize in Physiology or Medicine 1943.

Henrik Carl Peter Dam (1895-1976): "for his discovery of vitamin K"

Edward Adelbert Doisy (1893-1986): "for his discovery of the chemical nature of vitamin K"

Henrik Dam and Edward Doisy won the Nobel Prize in 1943 for their contributions to the understanding of blood clotting, especially the role of vitamin K.

Dam was working at the Biochemical Institute in Copenhagen during the 1930's. He was studying diet in chickens and noticed that his flock was suffering from frequent hemorrhages. After eliminating the most obvious causes, including lack of vitamin C, Dam proceeded to isolate the missing factor that caused the deficiency in blood clotting. The effort is described in the presentation speech.
In cooperation with F. Schønheyder, it was found by Dam in 1934 that an addition of hempseed to the food prevented the bleedings. This forced him to the conclusion that hempseed must contain a still unknown substance which has a protective effect against certain hemorrhages. This substance, which was found to be necessary for the coagulation of the blood, is termed by Dam the coagulation vitamin or vitamin K. Dam moreover found that this vitamin occurs not only in the vegetable kingdom, for example in the seeds of cabbage, tomatoes, soya beans and lucerne, but also in certain animal organs, especially in the liver. Dam and the American investigator Almquist showed almost simultaneously that activity follows the non-saponifiable lipoid fraction. Vitamin K is formed also by bacteria in the intestinal canal, as was shown in 1938 by Almquist and his co-workers. The organism's need of this vitamin may thus be satisfied either by supply with the food, or by its formation in the intestinal canal.
Dam was able to show that a lack of vitamin K led to a deficiency in prothrombin, the precursor of thrombin. Thrombin is the enzyme that cleaves fibrinogen to create fibrin and it is fibrin molecules that interact to form a blood clot.

The nature of vitamin K remained a mystery until 1939 when Edward A. Doisy, Professor of Biochemistry at St. Louis University School of Medicine, determined its structure and synthesized it in the laboratory.

By 1943 it was apparant that vitamin K could relieve the symptoms of inappropriate hemorraging in humans and treatment with vitamin K became routine as described in the Nobel Prize presentation speech.
It was in fact soon found that this vitamin was to assume great importance in the treatment of hemorrhagic diseases in man. Certain diseases of the liver and gall ducts with jaundice are characterized by a marked tendency to hemorrhage, and it was found that this tendency, being due to a lack of prothrombin, could be remedied with vitamin K. In this way operative treatment in such cases has become much less risky than before. Also in certain protracted intestinal diseases there is a hemorrhagic tendency, due to insufficient absorption of vitamin K through the intestine. These cases too have been successfully treated with vitamin K.

It is, however, in the checking of hemorrhages in newborn babies that this vitamin has assumed its greatest practical importance. At this early age, hemorrhages - sometimes involving menace to life - occur far oftener than in more advanced stages. A great many of these cases have proved to be due to deficiency of vitamin K and can be cured by the supply of that vitamin. What is more, by treating the mother shortly before delivery, or the newborn child immediately afterwards, it is possible also to prevent the occurrence of such hemorrhages. Even if there are also neonatal hemorrhages which are not due to a lack of vitamin K and therefore cannot be cured by the supply thereof, the number of cases of such deficiency in the neonatal stage is rather large, and then vitamin K often conduces to save life. Indeed, it may be said that the discovery of vitamin K has revolutionized the treatment of these not uncommon cases.
Nowadays the role of vitamin K is so well understood, and the compound is so easily available, that it's rare to encounter deficiencies.

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