Identification of vitamin C as the antiscorbutic factor

Scurvy had been recognized as a disease of dietary deprivation for centuries before its specific cause was known. The Royal Navy had issued lemon juice to all its sailors since 1795 on purely empirical grounds, and the connection between fresh citrus and prevention of scurvy was well established in clinical observation. What remained unknown through the nineteenth century and into the twentieth was the identity of the chemical responsible: which compound in citrus or fresh vegetables was doing the preventive work, and whether it was a single substance or a mixture.

Albert Szent-Gyorgyi, a Hungarian physiologist, had isolated a reducing substance from adrenal glands while working in Cambridge under Frederick Gowland Hopkins and at the Mayo Foundation in Minnesota. He called it hexuronic acid, published its chemical characterization in 1928, and after taking a chair at the University of Szeged in 1930 suspected it was the antiscorbutic factor. Confirmation required showing the isolated compound could prevent or cure scurvy. At the University of Pittsburgh, Charles Glen King and his collaborator W. A. Waugh were pursuing the same compound from lemon juice by a different route. King and Waugh published in April 1932 in Science, identifying their crystalline isolate as the antiscorbutic agent. In Szeged, Szent-Gyorgyi and Joseph Svirbely tested hexuronic acid on guinea pigs and reported the same conclusion in Nature in 1932, and hexuronic acid was renamed ascorbic acid. A priority dispute that both men prosecuted actively for years followed.

Neither the dispute nor its resolution changed what was known about the compound itself. King and Waugh published first by a matter of weeks, and both groups had reached the same molecule by different routes. Its structure was then worked out by Norman Haworth's group in Birmingham: a six-carbon lactone with a reducing enediol group, stable in acid and unstable in alkaline or oxidizing conditions. In 1933 Haworth's group and Tadeus Reichstein in Zurich each synthesized the compound independently, so supply no longer depended on extracting it from food.

Biochemical characterization of ascorbic acid's roles has continued since 1932. It is a cofactor for prolyl hydroxylase and lysyl hydroxylase, the enzymes needed to make stable collagen; deficiency interrupts collagen synthesis and produces the connective tissue breakdown characteristic of scurvy. Ascorbic acid also acts as a water-soluble antioxidant and takes part in carnitine biosynthesis and in making noradrenaline. Recommended daily allowances have been revised multiple times as these roles have been worked out.

Szent-Gyorgyi received the 1937 Nobel Prize in Physiology or Medicine for discoveries on biological combustion, with special reference to vitamin C; Haworth shared that year's chemistry prize for his work on carbohydrates and vitamin C. King received no Nobel. Szent-Gyorgyi also found that Hungarian paprika contained large amounts of the vitamin. Reichstein's production process, one fermentation step followed by several chemical steps, remained the main industrial method until the late 1990s.