Vitamin C - History - Discovery

Discovery

In 1907, the needed biological-assay model to isolate and identify the antiscorbutic factor was discovered. Axel Holst and Theodor Frølich, two Norwegian physicians studying shipboard beriberi in the Norwegian fishing fleet, wanted a small test mammal to substitute for the pigeons then used in beriberi research. They fed guinea pigs their test diet of grains and flour, which had earlier produced beriberi in their pigeons, and were surprised when classic scurvy resulted instead. This was a serendipitous choice of model. Until that time, scurvy had not been observed in any organism apart from humans, and had been considered an exclusively human disease. (Pigeons, as seed-eating birds, were also later found to make their own vitamin C.) Holst and Frølich found they could cure the disease in guinea pigs with the addition of various fresh foods and extracts. This discovery of a clean animal experimental model for scurvy, made even before the essential idea of vitamins in foods had even been put forward, has been called the single most important piece of vitamin C research.

In 1912, the Polish American biochemist Casimir Funk, while researching beriberi in pigeons, developed the concept of vitamins to refer to the non-mineral micronutrients that are essential to health. The name is a blend of "vital", due to the vital biochemical role they play, and "amines" because Funk thought that all these materials were chemical amines. Although the "e" was dropped after skepticism that all these compounds were amines, the word vitamin remained as a generic name for them. One of the vitamins was thought to be the anti-scorbutic factor in foods discovered by Holst and Frølich. In 1928, this vitamin was referred to as "water-soluble C," although its chemical structure had still not been determined.

From 1928 to 1932, the Hungarian research team of Albert Szent-Györgyi and Joseph L. Svirbely, as well as the American team led by Charles Glen King in Pittsburgh, first identified the anti-scorbutic factor. Szent-Györgyi had isolated the chemical hexuronic acid (actually, -hexuronic acid) from animal adrenal glands at the Mayo clinic, and suspected it to be the antiscorbutic factor, but could not prove it, without a biological assay. At the same time, for five years, King's laboratory at the University of Pittsburgh had been trying to isolate the antiscorbutic factor in lemon juice, using the original 1907 model of scorbutic guinea pigs, which developed scurvy when not fed fresh foods, but were cured by lemon juice. They had also considered hexuronic acid, but had been put off the trail when a coworker made the explicit (and mistaken) experimental claim that this substance was not the antiscorbutic substance.

Finally, in late 1931, Szent-Györgyi gave Svirbely, formerly of King's lab, the last of his hexuronic acid, with the suggestion that it might be the anti-scorbutic factor. By the spring of 1932, King's laboratory had proven this, but published the result without giving Szent-Györgyi credit for it, leading to a bitter dispute over priority claims (in reality it had taken a team effort by both groups, since Szent-Györgyi was unwilling to do the difficult and messy animal studies).

Meanwhile, by 1932, Szent-Györgyi had moved to Hungary and his group had discovered that paprika peppers, a common spice in the Hungarian diet, was a rich source of hexuronic acid, the antiscorbutic factor. With a new and plentiful source of the vitamin, Szent-Györgyi sent a sample to noted British sugar chemist Walter Norman Haworth, who chemically identified it and proved the identification by synthesis in 1933. Haworth and Szent-Györgyi now proposed that the substance L-hexuronic acid be called a-scorbic acid, and chemically -ascorbic acid, in honor of its activity against scurvy. Ascorbic acid turned out not to be an amine, nor even to contain any nitrogen.

In part, in recognition of his accomplishment with vitamin C, Szent-Györgyi was awarded the unshared 1937 Nobel Prize in Medicine. Haworth also shared that year's Nobel Prize in Chemistry, in part for his vitamin C synthetic work.

Between 1933 and 1934, not only Haworth and fellow British chemist (later Sir) Edmund Hirst had synthesized vitamin C, but also, independently, the Polish chemist Tadeus Reichstein, succeeded in synthesizing the vitamin in bulk, making it the first vitamin to be artificially produced. The latter process made possible the cheap mass-production of semi-synthetic vitamin C, which was quickly marketed. Only Haworth was awarded the 1937 Nobel Prize in Chemistry in part for this work, but the Reichstein process, a combined chemical and bacterial fermentation sequence still used today to produce vitamin C, retained Reichstein's name. In 1934 Hoffmann–La Roche, which bought the Reichstein process patent, became the first pharmaceutical company to mass produce and market synthetic vitamin C, under the brand name of Redoxon.

In 1957, the American J.J. Burns showed that the reason some mammals are susceptible to scurvy is the inability of their liver to produce the active enzyme -gulonolactone oxidase, which is the last of the chain of four enzymes that synthesize vitamin C. American biochemist Irwin Stone was the first to exploit vitamin C for its food preservative properties. He later developed the theory that humans possess a mutated form of the -gulonolactone oxidase coding gene.

In 2008, researchers at the University of Montpellier discovered that, in humans and other primates, the red blood cells have evolved a mechanism to more efficiently utilize the vitamin C present in the body by recycling oxidized L-dehydroascorbic acid (DHA) back into ascorbic acid, which can be reused by the body. The mechanism was not found to be present in mammals that synthesize their own vitamin C.