Albert Szent-Györgyi isolated “hexuronic acid” in England, and four years later, in Hungary, he and Joseph L. Svirbely proved that this substance was vitamin C.

Vitamin C is both a complex chemical substance and the physiological linchpin in the deficiency disease scurvy. Scurvy Physicians in the Middle Ages had recognized some aspects of this disease, which was characterized by weakness, swollen joints, a tendency to bruise easily, bleeding from the gums, and the loss of teeth. It was not until the eighteenth century, however, that the Scottish physician James Lind recognized that these symptoms constitute a disorder caused by defective nutrition. His experiments on sailors during long ocean voyages showed that the ingestion of certain fruits and vegetables could cure the disease. [kw]Szent-Györgyi Discovers Vitamin C (1928-1932)[Szent Györgyi Discovers Vitamin C (1928 1932)]
[kw]Vitamin C, Szent-Györgyi Discovers (1928-1932)
[kw]C, Szent-Györgyi Discovers Vitamin (1928-1932)[C, Szent Györgyi Discovers Vitamin (1928 1932)]
Vitamins;vitamin C
Nutrition;vitamins
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[g]England;1928-1932: Szent-Györgyi Discovers Vitamin C[06980]
[g]Hungary;1928-1932: Szent-Györgyi Discovers Vitamin C[06980]
[g]United States;1928-1932: Szent-Györgyi Discovers Vitamin C[06980]
[c]Science and technology;1928-1932: Szent-Györgyi Discovers Vitamin C[06980]
[c]Biology;1928-1932: Szent-Györgyi Discovers Vitamin C[06980]
[c]Chemistry;1928-1932: Szent-Györgyi Discovers Vitamin C[06980]
[c]Health and medicine;1928-1932: Szent-Györgyi Discovers Vitamin C[06980]
Szent-Györgyi, Albert
King, Charles Glen
Svirbely, Joseph L.

Albert Szent-Györgyi.

(The Nobel Foundation)

The most significant step toward the discovery of vitamin C was made in 1907, when Axel Holst, Holst, Axel a bacteriologist, and Theodor Frölich, Frölich, Theodor a pediatrician, published their discovery that, through dietary manipulations, a disease analogous to human scurvy could be generated in guinea pigs. (Like humans and unlike most animals, guinea pigs do not manufacture their own vitamin C.) When Holst and Frölich fed hay and oats (foods deficient in vitamin C) to guinea pigs, the animals developed scurvy, but when they were fed fresh fruits and vegetables, they remained healthy. In this way, Holst and Frölich were able to measure a food’s ability to prevent scurvy.

While other scientists were trying to isolate vitamin C directly, Albert Szent-Györgyi actually found the substance in the course of searching for something else. In the 1920’s, his research centered on biological oxidation, that is, on how cells oxidize various foodstuffs. He was particularly entranced by the observation that some plants (apples and potatoes) turn brown after being cut and exposed to air, whereas others (oranges and lemons) experience no color change.

Szent-Györgyi suspected that a certain substance was controlling these color-change reactions, and he looked for it not only in fruits and vegetables but also in the adrenal cortex of mammals. He believed that the color change to a bronzelike skin in patients with Addison’s disease (a disorder of the adrenal gland) was associated somehow with the color changes in plants. He hoped to isolate this substance, a powerful reducing agent, from the adrenal glands.

Unfortunately, his research was plagued with problems until he met the English biochemist Frederick Hopkins Hopkins, Frederick at a conference in Sweden in 1926. Hopkins was interested in vitamins and biological oxidation, and he invited Szent-Györgyi to the University of Cambridge to continue his research. Using many glands from oxen, Szent-Györgyi was able to separate a reducing agent from all other substances present. He also was able to obtain the same substance from orange juice and cabbage extracts, a result that his colleagues found most surprising.

Through chemical analysis, Szent-Györgyi determined that the substance contained six carbon atoms and eight hydrogen atoms and that it was a carbohydrate related to the sugars. He initially wanted to name the substance “Ignose” (from the Latin ignosco, meaning “I don’t know,” and ose, the designating suffix for sugars). The editor of the Biochemical Journal thought that the name was too flippant, however, whereupon Szent-Györgyi suggested “Godnose,” which was similarly rejected. Because the substance contained six carbon atoms and was acidic, he and his editor agreed on the name “hexuronic acid.” Hexuronic acid News of the discovery of this acid was published in 1928.

At the time, scientists recognized five distinct vitamins. They had failed, however, to isolate any of them successfully. For this reason, it was not clear that Szent-Györgyi’s hexuronic acid and vitamin C were the same substance.

In the fall of 1931, Joseph L. Svirbely, a postdoctoral student, arrived at Szeged, Hungary, where Szent-Györgyi had gone to continue his studies of vitamin C. Svirbely had done his doctoral studies on vitamin C under Charles Glen King at the University of Pennsylvania. King was trying, with limited success, to isolate vitamin C from lemon juice. He was testing his results with time-consuming experiments using animals.

Svirbely provided a bridge between King’s work and Szent-Györgyi’s. Szent-Györgyi had not previously tried to prove that hexuronic acid was identical to vitamin C because he did not enjoy working with animals. Furthermore, he was against vitamin research (he once said that vitamins were problems for the chef, not the scientist).

Nevertheless, when Svirbely mentioned that he could tell if something contained vitamin C or not, Szent-Györgyi gave him some of his hexuronic acid for experimentation. In a fifty-six-day test using guinea pigs, Svirbely established, in the fall of 1931, that the animals without hexuronic acid in their diets died with symptoms of scurvy, whereas the animals receiving hexuronic acid were healthy and free from scurvy. Further experiments in 1931-1932 proved once and for all that hexuronic acid and vitamin C are identical.

The isolation of vitamin C generated widespread comment and convinced most scientists that the long-sought vitamin had been found. Vitamin C’s impact was deepened and extended by Szent-Györgyi’s discovery in 1933 that Hungarian red peppers contained large amounts of the vitamin. Whereas previously biochemists could make only minuscule amounts of the material with great difficulty, Szent-Györgyi now could produce the substance in great quantities. In his lectures about his work, he liked to hold up a bottle containing several kilograms of the vitamin. To scientists accustomed to thinking of vitamins solely in extremely minute amounts, this was a surprising and enlightening experience.

In the 1930’s, the League of Nations set up a committee to establish international standards for the vitamin, and the committee recommended that individuals ingest at least 30 milligrams each day to prevent scurvy. The vitamin came to be known as “ascorbic acid” Ascorbic acid for its property of combating scurvy. In the period during and after World War II, some scientists suggested that dosages larger than the recommended 30 milligrams would help keep humans in the best possible health. Many people, convinced that modern food processing was destroying vitamins, began to supplement their diets with vitamin pills, and some industries began to fortify their products with vitamins.

Beginning in 1965, Nobel Prize-winning chemist Linus Pauling Pauling, Linus became interested in the megavitamin theory popularized by industrial chemist Irwin Stone in 1960. Pauling suggested that many maladies, from schizophrenia to cancer to the common cold, could be treated and prevented by large doses of vitamins. Pauling’s books and articles created an ongoing controversy, guaranteeing that this fascinating substance, discovered through the efforts of Szent-Györgyi and others, will continue to provide subjects for rewarding scientific research well into the future. Vitamins;vitamin C
Nutrition;vitamins
Medicine;vitamins

• Carpenter, Kenneth J. The History of Scurvy and Vitamin C. Cambridge, England: Cambridge University Press, 1986. The story of scurvy told by a professor of nutrition at the University of California, Berkeley. Makes occasional use of chemical formulas, but most of the discussions are accessible to the general reader. Illustrated with many photographs and line drawings. Includes tables, extensive references, and detailed index.
• _______. “A Short History of Nutritional Science: Part 3 (1912-1944).” Journal of Nutrition 133 (October, 2003): 3023-3032. Third part of a four-part series includes brief discussion of the discovery of vitamin C. Places Szent-Györgyi’s work in the context of the history of nutritional science in general.
• Friedrich, Wilhelm. Vitamins. New York: Walter de Gruyter, 1988. A systematic presentation of the historical, chemical, biological, and medical aspects of the most important vitamins. Valuable research tool for scientists as well as for students synthesizes a massive amount of material, as is particularly evident in the chapter on vitamin C. Concludes with literature supplement and extensive index.
• Goldblith, Samuel A., and Maynard A. Joslyn, eds. Milestones in Nutrition. Westport, Conn.: AVI, 1964. Anthology of important papers in nutrition (part of a series), intended to “inspire and encourage” students to learn the chief ideas of food science through the foundational classics of the discipline. Ample section on vitamin C includes the principal papers of Szent-Györgyi, King, and others.
• Leicester, Henry M. Development of Biochemical Concepts from Ancient to Modern Times. Cambridge, Mass.: Harvard University Press, 1974. History of biochemistry written by a biochemist with a strong interest in the history of science. Chapter on vitamins discusses the history of ascorbic acid. Includes endnotes and indexes.
• Moss, Ralph W. Free Radical: Albert Szent-Györgyi and the Battle over Vitamin C. New York: Paragon House, 1988. Depicts Szent-Györgyi as a romantic scientist, ruled by intuition in his personal, political, and scientific lives. Takes Szent-Györgyi’s side in the controversy with King over the discovery of vitamin C, and presents new information to bolster Szent-Györgyi’s claim. Includes endnotes and index.
• Packer, Lester, and Jürgen Fuchs, eds. Vitamin C in Health and Disease. New York: Marcel Dekker, 1997. Collection of scholarly papers begins with a chapter on the history of vitamin C. Includes index.
• Pauling, Linus. Vitamin C, the Common Cold, and the Flu. San Francisco: W. H. Freeman, 1976. Updated version of Vitamin C and the Common Cold (1970), which was dedicated to Szent-Györgyi for his discovery of the vitamin. Argues that a proper understanding of previous research leads to the conclusion that most people would benefit from larger amounts of vitamin C in their diets. Award-winning book, aimed at a general audience; initiated a controversy about the effectiveness of megadoses of vitamin C in preventing colds and alleviating their symptoms. Includes references and index.
• Waugh, William A. “Unlocking Another Door to Nature’s Secrets: Vitamin C.” Journal of Chemical Education 11 (February, 1934): 69-72. A review of studies on the isolation and characterization of vitamin C written by one of King’s principal associates. Presents the story from King’s point of view, but is objective in tone. Includes references.

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