Earning the Nobel Prize

To date, physician and biochemist Albert Szent-Györgyi (b. Budapest, 1893; d. Woods Hole, 1986) remains the only Hungarian scientist to have received the Nobel Prize for research conducted while living in Hungary. In 1937, he was awarded the prize "for his discoveries in connection with biological combustion processes, with special reference to vitamin C and the catalysis of fumaric acid" in recognition of his work in Szeged.

In 1928, Szent-Györgyi was appointed to head the Institute of Medical Chemistry at the Royal Hungarian Franz Joseph University in Szeged. In actual fact, he only assumed his position in 1930, upon the completion of research work he had started four years earlier at the University of Cambridge, where he served as a Rockefeller Fellow. Before moving to Szeged, he spent twelve years working at various research institutes around the world, including Bratislava (1918), Prague (1919), Berlin (1919–20), Hamburg (1920–21), Leiden (1921–22), the Institute of Physiology in Groningen (1922–26; with additional work in the United Kingdom in 1925), and the Institute of Biochemistry in Cambridge (1927–30; with a brief period at the Mayo Clinic in Rochester, Minnesota, in 1929).

Around 1922, still at the University of Groningen, Szent-Györgyi conducted a series of studies on biological oxidation and became aware of a potent reducing agent. He established that the compound in question was present both in the cell sap of plants that did not exhibit peroxidative browning upon lesioning and in the adrenal cortex of animals. The photo on the right was taken in December 1926 as Szent-Györgyi was saying goodbye to his colleagues at the Institute of Physiology in Groningen. By January of the following year, he was already working in the United Kingdom. While in Cambridge, he successfully isolated the substance in crystalline form from bovine adrenal glands, obtaining a very limited amount of about 5 grams. This quantity was sufficient for Szent-Györgyi to describe quite a few characteristics of the substance. However, due to residual contamination in even the purest batches of the preparation, he was only able to take preliminary steps toward determining the structural formula of the substance, despite having already established its molecular formula (C6H8O6). At the time, Szent-Györgyi still used the term “hexuronic acid” when referring to the compound. In 1929, he was invited to work at the Mayo Clinic in Rochester, Minnesota, US. There, he managed to extract 25 grams of “hexuronic acid” from approximately 85 kg (!) of bovine adrenal glands. Yet, even this amount was only enough to verify that, contrary to his initial assumptions, the substance was not, in fact, a hormone.

In 1930, Szent-Györgyi continued his work in Szeged. By the end of 1931, the experiments he conducted jointly with American researcher Louis Svirbely revealed that “hexuronic acid” exhibited vitamin C activity. The two researchers published their findings in the April 1932 issue of Nature under the title “Hexuronic acid as the antiscorbutic factor” (Nature, April 16, 1932; last accessed: September 10, 2021). However, due to the lack of a sufficiently pure batch of the substance, they could not exclude the possibility that vitamin C was present in “hexuronic acid” merely as a contaminant.

Later that year, Szent-Györgyi’s research efforts faced significant difficulties, as global stockpiles of “hexuronic acid” were depleted in 1932. This was due to the fact that research on the substance was being conducted not only by Szent-Györgyi but also by several research laboratories around the world, all fiercely competing to be the first to publish their results. The primary source of “hexuronic acid” was bovine adrenal glands, though attempts were made to extract the substance from alternative sources, such as lemon or rose hip. However, none of these sources yielded adequate quantities to determine the structural formula of the substance successfully.

It was at this point, in October 1932, that Szent-Györgyi made his groundbreaking discovery. Struck by a sudden idea while having dinner, he decided to put some red peppers to the test, and they turned out to be an excellent source of vitamin C (ascorbic acid). Serendipitously, the idea of subjecting red peppers to analysis came to him in the fall; in any other season – such as early summer – red pepper fruits would not have been ripe and would have contained no more vitamin C than a green leaf of the plant. Led by Szent-Györgyi, a team processed 500 kg of tomato peppers that fall and extracted nearly 500 grams of crystalline vitamin C. This amount was enough to establish some of the fundamental information that had been missing and to confirm that what researchers had previously called “hexuronic acid” was, in fact, identical to ascorbic acid (vitamin C). The team’s far-reaching single-sentence announcement was published in Nature in January 1933, as part of their paper titled “Hexuronic Acid (Ascorbic Acid) as the Antiscorbutic Factor” (Nature, January 7, 1933; last accessed: September 10, 2021).

The first batch of vitamin C crystallized by Szent-Györgyi is still preserved in a small glass vial. The label above the vial reads: “C. vitamin / fűszerpaprikából előállította: Dr. Szent Györgyi Albert egyet. ny. r. tanár” [Vitamin C / Extracted from red peppers by Public Ordinary Professor Dr. Albert Szent-Györgyi].

However, the structural formula of the substance still hadn’t been determined. This feat was achieved by Norman Haworth (UK), who built on research conducted by Paul Karrer (Switzerland). Haworth analyzed pure ascorbic acid supplied by Szent-Györgyi. In 1937, both Haworth and Karrer were also among the Nobel laureates of the year, sharing the Nobel Prize in Chemistry. It is interesting to note that ascorbic acid may be quite unique as far as chemical substances go – in that it was successfully synthetized even before its precise structural formula was determined. In the fall of 1933, the production of vitamin C continued, and the Institute of Medical Chemistry at the university in Szeged was converted into a processing plant. Women known as “paprika splitters”, along with institute staff and their family members, all contributed to the processing effort. Following Szent-Györgyi’s instructions, a centrifuge was constructed to extract the juice from red peppers. As a result, in a relatively short time, the team processed 3.3 tons of tomato peppers and obtained over 3 kilograms of pure vitamin C. This batch, however, was no longer intended for chemists but for researchers investigating the physiological effects of the substance.

In 1933, Szent-Györgyi stopped working in the field of vitamin C research and returned to his original focus: studying cellular respiration and the combustion processes (biological oxidation mechanisms) that operate within living organisms – an academic pursuit that ultimately secured him the Nobel Prize. This significant step was also highlighted by Professor Einar Hammarsten, member of the Nobel Committee for Physiology or Medicine, when he addressed Szent-Györgyi in his speech at the award ceremony on December 10, 1937: “You never swerved from your unyielding purpose to study the primary and fundamental processes of biological oxidation. […] Not even your important discoveries regarding vitamin C could deter you from following a certain strain of thought. I am deducing now from a close observation of your work that you were drawing distinctions in your mind at this occasion between your interesting discovery of ascorbic acid and the bare possibility of some other audacious plans of yours coming true.”

Between 1934 and 1937, Szent-Györgyi received a total of 23 nominations for the Nobel Prize. Eventually, on October 28, 1937, the Karolinska Institutet of Stockholm awarded him the Nobel Prize in Physiology or Medicine. (In his will, Alfred Nobel specified, among other things, the bodies responsible for awarding the various Nobel prizes. The decision to award the Nobel Prize in Physiology or Medicine is therefore always made by the Karolinska Institutet of Stockholm, Sweden’s most prestigious medical university.) The next morning, leading Swedish dailies such as the Dagens Nyheter and the Stockholms-Tidningen ran the story on their front pages, as did the Svenska Dagbladet, which featured a lengthy editorial detailing Szent-Györgyi’s career and work. The cover photo (pictured here) shows members of the Karolinska Institutet making their decision. Seated in the forefront is renowned brain surgeon Herbert Olivecrona, who, interestingly, operated on Hungarian author, playwright, poet, journalist, and translator Frigyes Karinthy. Next to him are Professors Lichtenstein, Antoni, and Söderlund, with Rector Gunnar Holmgren seated at the head of the table. It is important to note that the prize awarded to Szent-Györgyi was not shared with anyone, indicating that no other researchers had achieved comparable results in his field. However, the decision-making process was far from smooth.