Albert Szent-Györgyi's Discovery of Vitamin C
Dedicated May 11, 2002, at the University of Szeged Albert Szent-Györgyi Medical Faculty in Szeged, Hungary.
Humankind has long suffered from a lack of understanding of basic nutrition. Scurvy was among many diseases suffered due to malnutrition. It wasn’t until the 1930’s that Albert Szent-Györgyi discovered the chemical ascorbic acid—also known as vitamin C—that enables the body to efficiently use carbohydrates, fats, and protein. His discovery was among the foundations of modern nutrition.
Those sitting down to nutritious meals usually do not consider what would happen if fresh vegetables and fruit or vitamin-supplemented juices and cereals were not routinely available. Centuries ago, sailors experienced such a lack first-hand: swollen and bleeding gums, loose teeth, hemorrhaging under the skin, and slowed healing of wounds. What we now know as vitamin C was in short supply on most ships, and human bodies reacted by developing the condition known as scurvy. Death could, and often did, quickly follow, thousands of miles away from otherwise life-sustaining provisions.
Scurvy had long been the scourge of those who sailed for extended distances without fresh food and supplies, with the first clear-cut descriptions of the malady appearing in the medieval records of the European Crusades. Toward the end of the 15th century, scurvy was cited as the major cause of disability and mortality among sailors on long sea voyages. Although Danish mariners were long acquainted with the condition, and included lemons and oranges in their marine stores, it was not until 1753 that scurvy was recognized in the British medical community at large as directly related to dietary deficiency.
In 1769, William Stark, a young British physician, began a series of experiments on diet and nutrition, using himself as the experimental subject. After consuming only bread and water for 31 days, Stark added other foods to his diet one by one, including olive oil, figs, goose meat, and milk. In two months, Stark recorded that his gums were red and swollen, bleeding easily to the touch. Seven months later he died, possibly from scurvy, and likely from the cumulative effects of malnutrition. Stark’s diet was heavy on meat and starch, but devoid of fresh vegetables and citrus fruits.
Twelve years before Stark’s ill-fated experiments, Scottish physician James Lind, having observed the preventive and curative powers of citrus fruits and lemon juice during his years as a naval surgeon, wrote a treatise recommending their mandatory consumption by British sailors. By 1795, Lind’s advocacy had resulted in the issuance of lime juice to all naval vessels and the gradual elimination of scurvy within the entire British fleet. At the time, no one, including Lind, knew of the existence of ascorbic acid, which would eventually become commonly known as vitamin C.
It would take more years to pinpoint the scurvy-prevention substance responsible for maintaining the body’s connective tissues. That would take the meticulous work of a brilliant Hungarian-born researcher named Albert Szent-Györgyi, whose isolation and identification of vitamin C and discovery of the metabolic mechanism that enables its use within cells would be recognized with a Nobel Prize in Physiology or Medicine.
Vitamin C enables the body to efficiently use carbohydrates, fats, and protein. Because vitamin C acts as an antioxidant — a nutrient that chemically binds and neutralizes the tissue-damaging effects of substances known as free radicals — it is vital to the growth and health of bones, teeth, gums, ligaments, and blood vessels. Vitamin C also plays a key role in the formation of collagen, the body’s major building protein, and is therefore essential to the proper functioning of all internal organs.
Vitamin C is found in various foods, including citrus fruits such as oranges, lemons, and grapefruit; in green vegetables such as spinach, broccoli, and cabbage; and in tomatoes and potatoes. Food processing may degrade or destroy vitamin C, as can exposure to air, drying, salting, cooking (especially in copper pots), or processing. (Freezing does not usually cause loss of vitamin C unless foods are stored for a very long time.)
In modern times, access to fresh fruits and vegetables is common, rendering full-blown cases of vitamin C deficiency relatively rare. Cases are normally limited to isolated elderly adults, usually men whose diet is limited to foods lacking in vitamin C, as well as to infants fed reconstituted milk or milk substitutes without a vitamin C or orange juice supplement. Those with certain illnesses, such as AIDS, cancer or tuberculosis, surgical patients, and those exposed to long periods of cold temperatures can also suffer from vitamin C insufficiency.
The existence of vitamin C was long suspected. Researchers Axel Holst and Alfred Frohlich had proposed its existence as early as 1907, but no definitive agent emerged as the likely candidate. As researchers struggled to identify the unique substance, one, Albert Szent-Györgyi, in the 1920s, was making experimental connections others did not.
Born to a family that already included three generations of scientists, Szent-Györgyi was interested in science from an early age. He enrolled at the University of Budapest, but his studies were interrupted by the outbreak of World War I. Fervently anti-war throughout his life, Szent-Györgyi wounded himself to escape combat and returned to the university to finish his studies in 1917. He was reputed to have said that he was “overcome with such a mad desire to return to science that one day I grabbed my revolver and in my despair put a shot through my upper arm.”
Szent-Györgyi received a medical degree upon graduation, thereafter studying at various European universities. He began his scientific career by studying the chemical changes that occur when cells utilize foodstuffs, such as carbohydrates, fats, and protein, a process sometimes known as biological combustion. In the course of his studies Szent-Györgyi isolated a molecule from adrenal glands that lost and regained hydrogen atoms. This “hydrogen carrier,” containing six carbon atoms, had the properties of a sugar and an acid. Szent-Györgyi christened it “hexuronic acid.”
In the 1920s, he became interested in cell respiration and energy production in plants, closely investigating the “browning” processes that interrupted or impeded growth and normal functioning. Szent-Györgyi discovered that as plants brown, they do so as a result of damage at the cellular level: a breakdown in the mechanism that supplies enough hydrogen to prevent excessive oxidation.
While conducting a series of experiments on citrus plants, he found that browning could be induced with peroxidase, a plant enzyme active in oxidation. Szent-Györgyi was then able to delay the browning with the addition of citrus juice to the peroxidase. Further experiments allowed Szent-Györgyi to isolate the protective hexuronic-acid agent he believed was active in citrus juice.
Life is a wondrous phenomenon. I can only hope that some day man will achieve a deeper insight into its nature and its guiding principles and will be able to express them in more exact terms…To express the marvels of nature in the language of science is one of man’s noblest endeavors.”
— Albert Szent-Györgyi
In 1930, Szent-Györgyi returned to Hungary, accepting a post as professor of medicinal chemistry at the University of Szeged. There he showed his sample of hexuronic acid to J. L. Svirbely, an American-born chemist of Hungarian descent, who had previously worked with Charles King, a vitamin researcher at the University of Pittsburgh. Svirbely, working with Szent-Györgyi, conducted a landmark experiment on guinea pigs, which, like humans, must ingest vitamin C to maintain health since it cannot be produced within their bodies.
Svirbely divided the animals into two groups: one that received boiled food (boiling destroys vitamin C) and the other that was fed food enriched with hexuronic acid. The latter group flourished, while the first aggregation of guinea pigs developed scurvy-like symptoms and died. Svirbely and Szent-Györgyi decided hexuronic acid — renamed ascorbic acid to reflect its anti-scurvy properties — was indeed the long sought vitamin C. In 1933, Szent-Györgyi set about to find additional, natural sources of ascorbic acid for further study.
Although orange juice and lemon juice have high levels of ascorbic acid, they contain sugars that make purification extremely difficult. Szent-Györgyi solved the problem by making imaginative use of the local specialty, paprika. Szeged is the paprika capital of the world, where matching salt and paprika shakers are found on every restaurant table. One night, Szent-Györgyi recalled, his wife served him fresh red paprika for supper. As he wrote in his autobiography, “I did not feel like eating it so I thought of a way out. Suddenly it occurred to me that this is the one plant I had never tested. I took it to the laboratory ... [and by] about midnight I knew that it was a treasure chest full of vitamin C.”
Within several weeks Szent-Györgyi had produced three pounds of pure crystalline ascorbic acid, enough to show — when fed to the vitamin C-deficient guinea pigs — that the acid was equivalent to vitamin C.
Just four years after the ascorbic acid discovery, Szent-Györgyi received the Nobel Prize for his seminal work. That year, in 1937, the deliberations in the Nobel Committee centered on whether the Prize should go to Szent-Györgyi alone or be shared with several other scientists who had conducted similar work. In the end, the Prize was given to Szent-Györgyi alone, but the deliberations were reportedly long and acrimonious.
Szent-Györgyi went on to identify and study actin and myosin, proteins responsible for muscle contraction, and demonstrated that the compound adenosine triphosphate (ATP) is the immediate source of energy necessary for muscle contraction. He later carried out additional studies of citrus fruits, identifying flavonoids and postulating its function as strengthening capillary blood vessels.
Szent-Györgyi then turned to the study of organic compounds known to play a part in the breakdown of carbohydrates to carbon dioxide, water, and other substances necessary for the production of usable energy by the cell. His work laid the foundation for Sir Hans Krebs' explanation of what later would be known as the Krebs cycle: the three-stage process by which living cells break down organic molecules in the presence of oxygen to harvest the energy required for growth and division.
In 1947, Szent-Györgyi immigrated to the United States, where he assumed the directorship of the Institute for Muscle Research in Woods Hole, Massachusetts. There he investigated the causes of cell division and the root causes of cancer. He was an accomplished and prolific author, producing among other works “The Crazy Ape” (1970), a passionate commentary on science and the prospects for human survival on Earth. Albert Szent-Györgyi died on October 22, 1986.
The American Chemical Society and the Hungarian Chemical Society designated Albert Szent-Györgyi’s work in biological combustion and the identifying of vitamin C as an International Historic Chemical Landmark with a ceremony in Szeged, Hungary, on May 11, 2002. The English text of the plaque commemorating the event reads:
Albert Szent-Györgyi (1893- 1986), biochemist, pioneered the study of biological oxidation mechanisms during the 1920s. Between 1930 and 1936, while a Professor at Szeged University, he proved that hexuronic acid, which he had previously isolated, is identical with vitamin C and that it could be extracted in kilogram quantities from paprika. In 1937, he was awarded the Nobel Prize in Physiology or Medicine “for his discoveries in connection with the biological combustion processes, with special reference to vitamin C and the catalysis of fumari.” In later years he and his collaborators achieved world renown in the field of the biochemical mechanism of muscular contraction. From 1948 until his death, he worked in the United States where he was also involved in cancer research.
The Hungarian text of the plaque reads:
Szent-Györgyi Albert (1893-1986), biokémikus, a 20-as években úttöro munkát végzett a biológiai oxidáció mechanizmusának felderítésében. 1930 és 1936 között, a Szegedi Egyetem professzoraként, sikerült bebizonyítania, hogy a korábban általa izolált hexuronsav a C-vitaminnal azonos, és kilogrammos mennyiségben paprikából kivonható. 1937-ben kapott fiziológiai-orvostudományi Nobel-díjat a “biológiai égésfolyamatok, különösen a C-vitamin, valamint a fumársav-katalízis terén tett felfedezéseiért”. Késöbb, munkatársaival együtt, világszínvonalú eredményeket ért el az izomösszehúzódás biokémiai mechanizmusának vizgálatában. 1948-tól haláláig az Amerikai Egyesült Államokban dolgozott, ahol rákkutatással is foglalkozott.
Written by James Schultz.
Produced by the National Historic Chemical Landmarks program of the American Chemical Society in 2002.
American Chemical Society National Historic Chemical Landmarks. The Discovery of Vitamin C by Albert Szent-Györgyi http://www.acs.org/content/acs/en/education/whatischemistry/landmarks/szentgyorgyi.html (accessed Month Day, Year).
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