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The history of vitamin C research in India 185 Perspectives The history of vitamin C research in India I B CHATTERJEE Dr B C Guha Centre for Genetic Engineering and Biotechnology, Calcutta University College of Science, Kolkata 700 019, India (Email, [email protected]) 1. Prelude of seamen. In 1753, in his book A treatise of scurvy, Lind pointed out the importance of lemons, oranges and fresh Vitamin C is perhaps the most controversial, highly green vegetables for the prevention and cure of scurvy. publicised yet least understood of all vitamins. Eighty years It took another 175 years to discover the antiscorbutic have passed since its discovery, but till now its precise factor vitamin C. The discovery was accidental. In 1927, biological function has remained an enigma. It is perceived Albert Szent-Györgyi (fi gure 2a), a young Hungarian by the general public as a panacea, a miracle pill that is scientist, came to work for one year in the laboratory of F capable of curing myriad diseases. Humans, in contrast to G Hopkins at Cambridge, England, with a fellowship from many animals, are incapable of synthesising this vitamin and are totally dependent on its dietary intake for their survival. The biosynthetic pathway of vitamin C in animals and its defective counterpart in humans have been completely elucidated, mainly by the pioneering work done in the USA and India. In this essay, besides the discovery of vitamin C by Szent-Györgyi (1928) as well as King and Waugh (1932), I shall elaborate on vitamin C research done exclusively in India. 2. Discovery of vitamin C The distinctive features of scurvy resulting from vitamin C defi ciency were described in the Ebers Papyrus around 1700 BC. They are also found in the texts of Susruta, the great Indian surgeon, around 400 BC; the writings of Hippocrates; and the works of Chang Chi of China ça 200 AD. The knowledge that humans cannot synthesise vitamin C was gained by experience. Between 1500 and 1800 AD, scurvy took a toll of at least two million sailors (McCord 1959). In that period, more seamen died of scurvy than of all other causes combined, including other diseases, shipwrecks, accidents and battle wounds. Scurvy also ravaged whole armies and inhabitants of besieged cities. It was perhaps the main disease resulting from an occupational hazard and, as a Figure 1. The Scottish doctor James Lind with “A Treatise of nutritional defi ciency disease, has caused the most suffering the Scurvy” (published in 1753) in his hand. Lind discovered the in recorded history (McCord 1959). It was the genius of importance of lemons, oranges and fresh green vegetables for the James Lind (fi gure 1) that banished this merciless killer prevention and cure for scurvy. Keywords. Biological function; biosynthesis; emphysema; genetic defects in human; vitamin C http://www.ias.ac.in/jbiosci J. Biosci. 34(2), June 2009, 185–194, © Indian AcademyJ. Biosci. of 34 Sciences(2), June 2009 185 186 I B Chatterjee the Rockefeller Foundation. Szent-Györgyi’s fi eld of interest hexuronic acid he had isolated at the Mayo Clinic and asked was oxidation reactions of compounds present in both plant him to test it on guinea pigs with induced scurvy. Repeated and animal tissues. trials proved that hexuronic acid was, in fact, vitamin C. In Hopkins’s laboratory, his objective was to isolate Szent-Györgyi had suspected this, but had put the project aside some redox substances present in ox adrenal glands. He rather than take up the messy, expensive and labour-intensive measured the amount of reducing factor in samples by animal studies required. King, meanwhile, had also been their power to decolourise iodine. While extracting and close to reaching a similar conclusion. Svirbely wrote to his concentrating redox compounds from ox adrenal gland, he former mentor in March 1932, telling King what he had found isolated some sugar-like crystals that he knew nothing about. at the Szeged laboratory, adding that he and Szent-Györgyi This ignorance was apparent from the title of the paper he were submitting a report to Nature. On 1 April 1932, Science submitted to Biochemical Journal: “Observation on the published King’s paper entitled “The chemical nature of function of peroxidase systems and the chemistry of the vitamin C” claiming that he had discovered vitamin C, which adrenal cortex: description of a new carbohydrate derivative” was identical to hexuronic acid. King cited Szent-Györgyi’s (Szent-Györgyi 1928). He was so ignorant of the nature of earlier work on hexuronic acid but gave him no credit for the the carbohydrate derivative that he fi rst named it ignose (ign discovery of vitamin C. The story of the discovery was quickly for ignorance and ose for sugar). However, the Editor of picked up by the American press. Two weeks later, astonished Biochemical Journal did not accept the name. Later, Szent- and dismayed, Szent-Györgyi and Svirbely sent off their own Györgyi named it godnose (God only knows). However, the Editor objected to this name as well. Finally, the structure report to Nature entitled “Hexuronic acid as the antiscorbutic of the carbohydrate was elucidated by the famous English factor” (Svirbely and Szent-Györgyi 1932), challenging chemist W M Haworth at the University of Birmingham and King’s claim to the discovery. A bitter controversy ensued. was named hexuronic acid (hex = six carbon uronic acid) King, as was well-known, had been working on the problem (fi gure 3). During the same period, King and Waugh (1932) for over fi ve years; he had many supporters who were ready to of Columbia University isolated the antiscorbutic factor vilify Szent-Györgyi as a plagiarist. Yet European and British from lemon juice and named it vitamin C. It had all the scientists also knew of Szent-Györgyi’s long research on this characteristics of Szent-Györgyi’s hexuronic acid. antioxidant substance and accepted his claim. Ultimately, In January 1931, Szent-Györgyi left Cambridge and Szent-Györgyi’s claim prevailed. In October 1937, he was returned to Hungary to chair the medical chemistry awarded the Nobel Prize for Physiology or Medicine “for department at the University of Szeged. In the fall of 1931, an his discoveries in connection with the biological combustion American post-doctoral fellow, Joseph Svirbely, joined Szent- processes, with especial reference to vitamin C and the Györgyi’s research team. Svirbely had been working with C catalysis of fumaric acid”. G King (fi gure 2b) at the University of Pittsburgh, trying to In fact, Szent-Györgyi was surprised when informed isolate vitamin C. Szent-Györgyi gave him the remains of the of the Nobel Prize. Here was a scientist who worked only (a) (b) for a year on a problem with quite a different objective and without doing a single animal experiment but got full credit for discovering vitamin C (Carpenter 1988). C G King, who Figure 2. (a) Albert Szent-Györgyi (1893–1986). Photo by J W McGuire. Szent-Györgyi discovered hexuronic acid from the adrenal gland in 1928. (b) Charles Glen King (1896–1988). King discovered vitamin C from lemon juice in 1932 and showed that it had all the characteristics of hexuronic acid. Figure 3. Structure of hexuronic acid (vitamin C). J. Biosci. 34(2), June 2009 The history of vitamin C research in India 187 had published fi ve papers and isolated vitamin C, did not. In and started work immediately. Guha believed that research the words of Szent-Györgyi himself: “I was not acquainted should be carried out to alleviate human suffering and not a with animal tests in this fi eld and the whole problem was, single day should be lost. During his short stay in BCPW for me too glamorous, and vitamins were, to my mind, (1932–1935), Guha published 38 papers, most of which theoretically uninteresting. Vitamin means that one has to were on nutritional science with special reference to vitamin eat it. What one has to eat is the fi rst concern of the chef, not C. None of the above-mentioned questions were addressed the scientist” (Szent-Györgyi 1963). at that time. In 1936, at the age of 32, Guha joined the Department of Applied Chemistry of Calcutta University as the Rashbehari Ghosh Professor and Head of the Department. 3. Initiation of vitamin C research in India He started a full-fl edged school of nutrition, but in course of time he became involved with various administrative jobs. B C Guha (fi gure 4), one of the founders of modern Although Guha continued research on vitamin C through biochemistry in India (Chatterjee and Burma 2004), his students, the important questions in the fi eld remained pioneered vitamin C research in India. Between 1927 unaddressed. and 1928, while Guha did research in the laboratory of F G Hopkins at Cambridge, he was in close association with Szent-Györgyi. In fact, Guha’s interest in vitamin C 4. How I came to vitamin C research originated at Cambridge during his stay in 1928. After the discovery of vitamin C, the knowledge of the cause of and After an MSc in Applied Chemistry at Calcutta University in cure of scurvy was clear. However, the following questions 1952 with a specialisation in oil technology, I started research remained unsolved: (i) How is vitamin C synthesised by for a PhD in the same department on the reclamation of rancid most animals? (ii) Why are humans incapable of producing fat. Guha rejoined the Department of Applied Chemistry in the vitamin? (iii) What is the precise biological function November 1953. By that time, although a signifi cant portion of vitamin C? After his return from Cambridge, Guha of my PhD research had already been done, I approached joined the Bengal Chemical and Pharmaceutical Works Guha, whom I considered an ideal mentor, and was inducted (BCPW) at Calcutta (now Kolkata).