AN INTERVIEW WITH ANN AND MANUEL VARELA: WHO WAS ALBERT SZENT GYÖRGYI? And what did he discover about fruit?

Jun 26, 2020 by


ALBERT SZENT GYÖRGYI

Michael F. Shaughnessy –

1) One of the furthermost beautiful cities in Europe is Budapest. It is divided by the Danube River—and it is two parts—Buda—on one side of the river—and Pest on the other. I mention this because it is close to the birthplace of someone who is a precursor to Linus Pauling—Albert Szent-Györgyi. So, when, and exactly where was Albert born, and what do we know about his parents?

Albert Szent-Györgyi was a Nobel Laureate and well known as the discoverer of vitamin C. He is also famous for his studies of Krebs cycle substrates. Szent-Györgyi was born on September 16, 1893, in Budapest, the Kingdom of Hungary, the Austro-Hungarian Empire. Szent-Györgyi had many relatives on his mother’s side who had scientific careers.

One of his uncles was a renowned physician, neuroanatomist, physiologist, and professor. The young Szent-Györgyi was quite influenced by this uncle, in particular, who took an interest in his academic performance. Albert’s father, Miklós Szent-Györgyi, was a landowner of a large estate from a noble family, and his mother, Jozefa, was a homemaker with enthusiasm for music. However, she did not pursue a career in opera due to her singing abilities.

2) What were his early experiences and education like in Hungary and abroad?

Szent-Györgyi began his college education at Semmelweis University in 1911. His collegial training was interrupted because of World War I and his summons to duty, where he served as an army physician in northern Italy until 1916 when he admittedly shot himself in the arm. Szent-Györgyi knew enough about human anatomy to inflict a wound that would not do irreparable damage to his limb. Szent-Györgyi met his first wife, Kornélia “Nelly” Demény, when he returned to the university and obtained his M.D. degree in 1917. They married and then headed back to the war effort. Fortunately, for Szent-Györgyi and his wife, the assignment was located at a military hospital in northern Italy.

He started research in pharmacology in the Hungarian province of Pozsony but soon fled in 1919 when Pozsony became a part of the newly established Czechoslovakia. With most of his research work secretly in tow, Szent-Györgyi headed back to Hungary.SoonSzent-Györgyi was on the move from 1920-1922, performing research experiments in various laboratories located in such cities as Prague and Berlin.

During the next several years, 1922-1926, Szent-Györgyi continued his education at numerous universities in Germany and the Netherlands, including the University of Groningen. Szent-Györgyi worked at the University of Cambridge in 1927, 1929, and at the Mayo Foundation, Rochester, New York (1928).By the time Szent-Györgyi had become proficient as an assistant to the pharmacologist, Storm Van Leeuwen, Van Leeuwen, had become too attentive to Szent-Györgyi’s wife.

His work on the chemistry of cellular reparation enabled him to secure him a position as a Rockefeller Foundation fellow from 1926-1930 at the University of Cambridge, where he took his Ph.D. in 1929 from Fitzwilliam College, Cambridge. From 1931-1945, Szent-Györgyi accepted a position at the University of Szeged. In 1947, Szent-Györgyi emigrated to the United States, and he founded at the Marine Biological Laboratory in Woods Hole, Massachusetts, the new Institute for Muscle Research. In 1948, Szent-Györgyi received a research position with the National Institutes of Health (NIH) in Bethesda, Maryland.

3) He came from a family of scientists—what do we know about this?

Szent-Györgyi was a member of four generations of scientists, all on his mother’s side, the Lenhosséks. His grandfather and great-grandfather were believed to be professors of anatomy. His uncle, Michael Lenhossek (Mihály Lenhossék), Jozefa’s brother, was a noted professor of physiology at the University of Budapest, and he was a significant influence on the career aspirations of young Szent-Györgyi. When Albert was a teenager, he announced that he wished to become a scientist. His uncle Mihály was vigorously opposed to this career-choice. Instead, the good professor suggested Albert become a dentist or a pharmacist, or even pursue a career in cosmetics.

However, when his uncle became aware of Szent-Györgyi’s academic brilliance, graduating with honors from high school, Professor Lenhossék suggested medical school to be a proctologist—his uncle had hemorrhoids—the dutiful Szent-Györgyi did, at first.

While a medical student, Szent-Györgyi, grew bored with his medical studies and entered his uncle’s laboratory, where he published his first scientific paper in 1913 on the histology and anatomy of the anal and rectal tegument. In later years Szent-Györgyi would report that because of his uncle Lenhossék, he (Szent-Györgyi) started the study of “science at the wrong end.”

4) In 1937, he took the Nobel Prize in the realms of Physiology or Medicine. For what exactly did he receive this award?

Szent-Györgyi was awarded the Nobel for his contributions toward the biological combustion process involving oxidation of several Krebs cycle intermediates, with particular reference to his discovery of vitamin C—one of history’s most significant scientific discoveries ever made. He had entered the biological oxidation field to help solve a controversy between two giants of biochemistry, Drs. Heinrich Wieland, and Otto Warburg, and each of their dedicated followers.

On the one hand, Wieland, and collaborator Torsten Thunberg, proposed in 1922 that when food is combusted during its breakdown, hydrogen atoms are activated, resulting in the loosening of the hydrogens that were stuck to the foodstuffs. Activation of hydrogen was thought to weaken their bonds. Thus, the hydrogens would come off the catabolized food. Based on this hypothesis, Wieland had further reasoned that the enzymes involved consisted of so-called dehydrogenases, which removed the loose hydrogens from degraded food.

On the other hand, Warburg in 1925 had proposed that during food breakdown, it was the oxygen that was activated during this catabolic respiration, instead of hydrogen. Otto Meyerhof had been firmly in the Warburg camp. Warburg had proposed that the responsible oxygen-activating enzymes be referred to as respiratory enzymes. In today’s parlance, one of these enzymes is called cytochrome oxidase.

The conflict centered around these two seemingly disparate explanations for food breakdown. The essence of the dispute was whether hydrogen activation (Wieland) versus oxygen activation (Warburg & Meyerhof) occurred during metabolic catabolism of food. The two camps and their notions vehemently opposed each other.

To address the disagreement, Szent-Györgyi spent his time at Groningen attempting to integrate the concepts from both camps and to show that hydrogen activation and oxygen activation complemented one another. Thus, Szent-Györgyi, hypothesized that in cells of the muscle, which readily undergo food combustion, activated oxygen oxidized the activated hydrogen. If true, the idea would become a unified theory of sorts that converted Wieland-Warburg warfare into the Wieland-Warburg merger.

Szent-Györgyi tested his merger hypothesis in the laboratory by combining elements of the biological machinery thought to play roles in each of the two activation systems. He had hoped that by putting the two activation pieces together, he could reconstitute food breakdown artificially. He added, for instance, the respiratory enzyme cytochrome (Warburg hypothesis) to dehydrogenase (Wieland hypothesis), together with food. The experiment failed—no food combustion was observed.

Not to be easily deterred, Szent-Györgyi reasoned that in the failed experiment, perhaps other elements were missing from the artificial mixture. If he could supply these putative components into his artificial mixture, he might then reconstitute food breakdown in the lab. His search for the missing components would lead to the Nobel.

Unfortunately, at first, none of the initial candidates arising from the two camps of Wieland and Warburg seemed to suffice in producing the required food combustion when combined in the lab.

First, Szent-Györgyi focused on the hydrogen donors, which he traced from sugar. He found that the hydrogens moved to oxaloacetate. The hydrogen movement involved an enzyme called malate dehydrogenase. This enzyme, in turn, would pass the hydrogens onto malate. The result now permitted dehydrogenated oxaloacetate to receive additional hydrogens. Malate passed along its hydrogens to fumarate and then to succinate dehydrogenase, to produce succinate. This hydrogen movement from molecule to molecule meant its activation, supporting the Wieland half of Szent-Györgyi’s merger concept.

Second, in Szent-Györgyi’s unifying scheme, he showed that the hydrogens from succinate went to cytochrome, thus oxidizing it using the oxygen of the respiratory enzymes. These results had now supported the Warburg half of the Szent-Györgyi merger hypothesis!

https://upload.wikimedia.org/wikipedia/commons/thumb/6/61/2507_The_Krebs_Cycle.jpg/800px-2507_The_Krebs_Cycle.jpg

https://upload.wikimedia.org/wikipedia/commons/thumb/6/61/2507_The_Krebs_Cycle.jpg/800px-2507_The_Krebs_Cycle.jpg

Figure The Krebs cycle

Szent-Györgyi demonstrated that food combustion involved C4 dicarboxylic acids. Today, they are known as intermediates in the famous Krebs cycle, and they include oxaloacetate, malate, fumarate, and succinate. Szent-Györgyi had provided definitive experimental evidence that during the breakdown of food oxidation (oxygen activation), dehydrogenation (hydrogen activation) was involved. That is to say, Szent-Györgyi had shown the cellular respiration involved oxidation and reduction.

Just as importantly, Szent-Györgyi’s work now permitted Krebs to expand upon the role of the C4 dicarboxylic acids and to make his intellectual leap of the metabolic cycle notion, to get the Nobel. The breakthrough by Szent-Györgyi’s would also result in his nomination for the Nobel, but it was only part of the overall reason.

There was a second reason Szent-Györgyi was considered for the Nobel. It was his discovery of vitamin C. The story represents an exceptional case of insight in connecting two seemingly different scientific territories to solve a mystery and make one of history’s most important discoveries, vitamin C.

Between 1922 and 1926, Szent-Györgyi was an assistant at Groningen under the famed physiologist Prof. Hartog Jacob Hamburger. The story of vitamin C begins with Szent-Györgyi and his curiosity about a fatal disease called Addison’s. The illness is characterized failure of the adrenal glands, perhaps from damage to the adrenal cortex. When the adrenal glands cease to function, one of the distinctive characteristic symptoms of Addison’s is that the skin turns brown. Szent-Györgyi astutely made a brilliant connection between the pigmentation of Addison’s and of leaves turning brown in the sun or the discoloration of bruised fruit, such as bananas, apples, or pears.

Szent-Györgyi turned to the oxidation of potatoes, which discolor when damaged, to shed light on the function of adrenals. He found that potatoes harbor an enzyme called polyphenol oxidase that converts polyphenol to quinone and oxygen. When the potato is damaged, phenol is oxidized, leaving quinone unreduced and available for turning into a brown pigment. Szent-Györgyi had made a breakthrough with potato discoloration, but unfortunately, the data did not inform him at all regarding adrenal function.

At about this time, Szent-Györgyi was keenly aware of the fact that in plants that do not discolor when they die, they have an active enzyme called peroxidase. The enzyme activates peroxide that, in turn, oxidizes aromatic compounds into pigmented products.

Then, Szent-Györgyi deduced that in fruits which do not discolor, such as that seen in citrus varieties, there must be a yet unknown substance that naturally prevents such a pigmentation reaction. Szent-Györgyi set out to purify this putative substance. He tried to examine the adrenals to find it.

Unfortunately, before he could progress further, his mentor Prof. Hamburger in 1926 died suddenly, and the professor’s successor was not receptive to the idea of overseeing Szent-Györgyi’s adrenal work. Hamburger’s replacement was a psychologist who liked neither chemistry nor Szent-Györgyi. Without a degree, a supervisor, and monetary support, Szent-Györgyi had no choice but to stop work on the project and sent his wife and child back home to Hungary. Soon, while at a scientific conference, Szent-Györgyi met the distinguished Frederick Gowland Hopkins (see the Hopkins chapter in this book), who knew of his work and who offered Szent-Györgyi the opportunity to continue his studies at Cambridge while sponsored by a fellowship from the Rockefeller Foundation.

At Cambridge, Szent-Györgyi purified his reductive agent from adrenals and plants, showing that the substance was hydrocarbon in nature with a chemical formula of C6 H8 O6 and seemingly resembling a sugar.

https://upload.wikimedia.org/wikipedia/commons/8/81/Ascorbic_acid_structure.png

https://upload.wikimedia.org/wikipedia/commons/8/81/Ascorbic_acid_structure.png

Figure Vitamin C (ascorbate) structure, previously called hexuronic acid

For generations, the famous story has been told amongst biochemists about Szent-Györgyi’s attempts to publish his new reducing substance. Being uncertain of the precise nature of his phenolic oxidation inhibitor sugar-like substance, he humorously named it “ignose” because he was “ignorant” of its true nature. Still, it might have been sugar, hence, the suffix “-ose.” The term was derived from “ignosco,” meaning “I don’t know.”

Shockingly, Szent-Györgyi kept the “ignose” term in the manuscript! He then sent it to the eminent professor and editor of the Biochemical Journal Arthur Harden! The good professor was not amused and immediately rejected the paper for publication. The story goes on that Szent-Györgyi changed the offending term to “godnose” and resubmitted the new version back to Harden, who immediately rejected the revised manuscript a second time! At this point, Dr. Harden proposed a counteroffer, suggesting Szent-Györgyi use “hexuronic acid” because the substance had six carbons. Hence, the prefix “hex,” and it was acidic. The project constituted his Ph.D. thesis, passing his defense in 1927. The accepted manuscript was published in Harden’s Biochemical Journal in 1928.

Trouble soon followed, however, when Szent-Györgyi ran out of adrenal glands—the only good source of the hexuronic acid—plants were unfortunately not good sources for lab purification. He needed a substantial amount of fresh adrenal glands. Adrenal tissues were shipped from Copenhagen, but the samples arrived in a decomposed state and could not be used.

So, in 1929 Szent-Györgyi moved to Rochester, MN, in the U.S., where he worked at the Mayo Clinic with Professor N. Kendall. Using plenty of adrenal glands from a nearby cattle slaughterhouse, Szent-Györgyi spent a year preparing 25 grams of a crystalline form of hexuronic acid. He returned to Cambridge with the new substance in his pocket and gave half of it to Walter Norman Haworth to study its structure and composition. Unfortunately, the 12-13 grams of hexuronic acid were not enough to elucidate its structural nature, and Haworth got nowhere with Szent-Györgyi’s sample.

Szent-Györgyi used his half of the purified hexuronic acid to determine whether it alleviated clinical symptoms of Addison’s disease—it did not. Thus, the hexuronic acid treatment was not a suitable replacement for lost adrenal function. The hexuronic acid did, however, cause the pigmentation in the patients to clear up. At this point, Szent-Györgyi was under the correct impression that the hexuronic acid and vitamin C were the same molecules. Then, with Szent-Györgyi almost out of his hexuronic acid sample, with barely one gram left, and without funds or means to attain more hexuronic acid, he was back to ground zero.

Then, after giving up, Szent-Györgyi returned to the University of Szeged as a member of their chemistry department. There, Dr. Joseph L. Svirbely arrived in Szent-Györgyi’s laboratory. They tested the remaining sample of Szent-Györgyi’s hexuronic acid for vitamin C-like properties in guinea pigs. They had definitively demonstrated that the hexuronic acid was virtually identical in its chemical behavior as an anti-scurvy agent! The reducing agent, hexuronic acid, later became known as ascorbic acid, because it prevented the onset of scurvy, the scientific name was scorbutus, hence the name “a-scorbic acid.” Later, the ascorbic acid molecule (ascorbate) would become more popularly known as vitamin C.

Regarding the Nobel, Szent-Györgyi was considered along with Norman Haworth and Paul Karrer, both of whom had studied vitamin C. The Nobel commission debate within the halls of the famed Karolinska Institute had been enormously contentious. When committee chair Dr. Hans Christian Jacobaeus emerged from the meeting to make a statement about their long-awaited decision, he instead suffered a heart attack and dropped dead at the press conference!

The final decision had been that Haworth and Karrer would share the 1937 Nobel in chemistry, whereas Szent-Györgyi would be the sole recipient of the 1937 Nobel in medicine or physiology.

5) Fascinating side note—After he received the Nobel Prize—what did he do with the prize money?

One source relates the story that in 1940 Szent-Györgyi allocated most, if not all, of the funds from his Nobel Prize money to aid the Finland resistance against the invasion by the Russians. He recounted later in an article published by the Annual Review of Biochemistry how he had even given up the gold contained within the Nobel medal itself over to the Finnish resistance cause. The Nobel gift to Finland got Szent-Györgyi in serious trouble, however, after the Soviet Union had occupied Hungary during World War II. Soon after the Russian occupation of Budapest, the Soviet authorities went searching for him.

When the Soviet patrol caught up with Szent-Györgyi face-to-face, he immediately surrendered, but he was not arrested. They had conveyed to him that they were under orders to bring him directly to Vyacheslav Molotov, for Szent-Györgyi’s “own safety.” Szent-Györgyi refused to go along with the patrol, and the officials left. Next, Szent-Györgyi immediately sent his family to actual safety.

Shortly after that, Szent-Györgyi traveled directly to Moscow to plead with Stalin to call off his Hungary occupation forces who were housing the captured Hungarian citizens under starvation and unsanitary prison conditions. Many of the captured had succumbed to infections or simply “disappeared.” Instead of meeting with Stalin, Szent-Györgyi was met by an underling, the director of the Foreign Office, Vladimir Dekanozov, whose purpose was to ascertain what Szent-Györgyi wanted of Stalin. After explaining the dire Hungarian situation at the hands of the Russian forces to Dekanozov and hoping to come to a positive solution, Szent-Györgyi reported that Dekanozov instead angrily shouted at him.

Feeling betrayed, Szent-Györgyi returned to Hungary and took steps to rescue educated Hungarians from demise by establishing membership for many in a “Scientific Academy,” which was a ruse; it was a grocery store, where the starving could acquire food for free. The food Academy enterprise was funded by donations from a wealthy friend, István Ráth, who also funded Szent-Györgyi’s research laboratory. With another friend and writer, Lajos Zilahy, they arranged for funding of the Academy by providing transportation for wealthy patrons who wished to leave the country.

Then, in 1947 while Szent-Györgyi was on a skiing vacation in the Swiss Alps, he learned that the Soviet authorities had taken advantage of his absence and arrested his friend and benefactor István Ráth. He was falsely accused of stealing and tortured. The kidnapping of Ráth while Szent-Györgyi was abroad turned out to be a blunder on the part of the Soviet authorities. With Szent-Györgyi still in Switzerland, he was able to call worldwide interest in the plight of Ráth, who was then released from captivity and permitted to leave Communist Hungary. As a result of the incident, Szent-Györgyi decided not to return to Hungary and instead left Switzerland for Woods Hole, Massachusetts, in the U.S.

Ironically, because Hungary was under Communist control when he emigrated to the U.S., he was now in trouble with U.S. officials. After his visa expired, he was, thus, forced to return to Hungary for several months before the emigration could become official. He would not return to Hungary again for 26 years when, in 1973, he received an honorary doctorate. For the remainder of Szent-Györgyi’s life, he would be consistently surveilled by the FBI.

6) Now, some people credit the British for making the connection between eating fruit, for example, limes, (resulting in the British being called ” limeys”) on long ocean voyages and the prevention of scurvy. But we now know that it was the ascorbic acid or vitamin C—in the fruit that prevented scurvy. But what occurs in the human body when one does not get enough vitamin C?

Indeed, vitamin C is widely known to reside in large concentrated in citrus fruits, like oranges, lemons, limes, plus vegetables and in foods, like sauerkraut. Scurvy is due to a shortage or absence of vitamin C in the diet of the affected patient. According to oceanic lore, British sailors and pirates were thought to bring along limes or sauerkraut during their voyages.

This sort of behavior was practiced long before the anti-scurvy benefit of vitamin C was known. Humanity had long been aware of scurvy, however, as the condition was recorded by ancient Egyptians around 1500 B.C. and noted by Hippocrates during the fifth century, B.C. When Ferdinand Magellan circumnavigated the planet of Earth by sailing, between 1519 and 1522, he lost the vast majority of his crew from scurvy.

Then, in 1535, explorer Jacques Cartier learned from Native Americans along the St. Lawrence River that cedar tea stopped the scurvy, and it saved the expedition from disaster. We know today that cedar tea contains vitamin C.

Dr. James Lind of the Royal Navy conducted a study in 1747 aboard the warship HMS Salisbury. Lind found that sailors who were provided with oranges and lemons cured their scurvy, and he published the discovery in 1753. Unfortunately, no changes in behavior policies were made until 1795, when the British Admiralty ordered that during their voyages, the sailors should be given concentrated lime juice; hence, the moniker “Limeys.”

As mentioned above, Drs. Albert Szent Györgyi and Joseph Svirbely had elegantly demonstrated the scurvy-preventing nature of vitamin C. Their hexuronic acid was vitamin C. The biochemical roles of vitamin C in the body are manifold. For example, the vitamin is necessary for the biochemistry of proline and lysine in the collagen of connective tissue. Without vitamin C, connective tissue tends to degrade, resulting in weakened blood vessels, weak teeth, bone pain, and slow wound healing. Humans lack a crucial enzyme in the biosynthetic pathway of vitamin C production. Thus, ascorbic acid must be included in the diet in the form of fresh vegetables and fruits.

The medical term for scurvy is scorbutus, and patients with the condition can suffer terribly. Because vitamin C plays a role in so many biochemical systems, its scarcity or absence can result in a wide-ranging constellation of medical signs and symptoms. In general, the signs and symptoms of scurvy can be divided into two phases, early and late.

The early signs and symptoms of scurvy can be non-specific. They may include fatigue, malaise (uneasiness or discomfort), appetite loss, nausea, fever, diarrhea, pain in the joints or muscles, and petechia, which is tiny, pinpoint-like bleeding from hair follicles in the skin.

The late signs and symptoms of scurvy may be more specific in scope, as well as more severe. These later warning signs include new conditions. Patients can have swollen, purple, sponge-like and bleeding gums, loosened teeth, proptosis (eyes that bulge), skin that’s dry, scaly and brownish, dry curly hair that breaks off easily, bleeding into the skin (bruising easily or severely), bleeding joints, and bleeding muscles, and slow or incomplete wound healing. In patients who are infants and children, the growth of bones may be prematurely stopped.

In most cases, diagnosis is often through laboratory confirmation of abnormally low levels of vitamin C in the blood as a definitive clinical sign. Other tests may include X-rays of joint and ribs and measurement of blood iron levels. Treatment, of course, is indicated with vitamin C supplemental intake. Dietary sources of vitamin C include fruits and vegetables. Fruits with proper levels of vitamin C include lemons, limes, oranges, tomatoes, strawberries, mangos, and grapefruits. Vegetables with vitamin C consist of cabbage, broccoli, peppers, and spinach. Organ meats liver and kidney contain vitamin C.

In modern times, thanks to the work of Szent-Györgyi, scurvy is a rare ailment. Unfortunately, because of its rarity and its non-specific nature of the early scurvy signs and symptoms, its presence can be missed in an individual or even misdiagnosed as a completely unrelated disease. Thus, physicians must continue in their awareness of biomedical history.

7) He used the electron microscope to study muscles—what was he interested in exactly?

Before his work on muscle using the electron microscope, Szent-Györgyi and Ilona Banga had, in the late 1930s and early 1940s, helped to establish the functional roles of ATP and myosin chains A and B during muscle contraction. Thus, he had held an interest in muscle physiology for many years before his groundbreaking work at Woods Hole, MA.

Szent-Györgyi spent a great deal of his time at the Marine Biology Laboratory, visualizing muscle structure using the electron microscope. One source even attributes Szent-Györgyi as being one of the first investigators to do so. His work on the biology of muscle was valuable also to the study of cardiovascular disease. He began the new work in the early 1950s. At the same time, he was the director of the famed Marine Biological Laboratory, in the tiny town of Woods Hole, MA, in the U.S. He had focused his attention to the contractile elements of muscle. One important finding revealed that when muscle tissue was kept in a concentrated solution of glycerin, the tissue retained its contractile properties. Thus, the finding permitted muscle physiologists to store excised muscle tissue for long periods without having to use freshly harvested muscle for every new experiment.

https://live.staticflickr.com/5767/20549429828_c2e4a9fc02_b.jpg

https://live.staticflickr.com/5767/20549429828_c2e4a9fc02_b.jpg

Figure Electron micrograph of muscle

Another important discovery by Szent-Györgyi involved his analysis of muscle fibrils. He found that a typical muscle fibril was composed of a bundle of actin filaments that transmitted muscle tension induced by myosin rodlets that were inserted between the actin threads. At the time, it was appreciated that actin and myosin could be disassociated from one another when in the relaxed state but acutely associated with each other during muscle contraction.

Szent-Györgyi further reasoned that actin and myosin were bundled together in so-called hexagonal lattice networks. He further speculated that myosin packed hexagonally around each of the individual actin filaments.

As he had predicted, such muscular threads appeared to contract, producing alterations in the muscle banding characteristics. If the actin and myosin overlapped during contraction, it would show alterations in banding patterns (see figure). Such was the case in studies of muscle structure, made possible with the electron microscope. In short, the pioneering work of Szent-Györgyi led to new advances in the field of muscle contraction, especially in the mechanism for actin-myosin (actinomycin) mechanics.

8) Vitamin P and flavonoids—what did he learn about these things?

Albert Szent-Györgyi’s involvement with vitamin P stems from attempts to prepare large-scale amounts of vitamin C. Adrenal glands were in short supply again, and vitamin C isolation in sufficient quantities from vegetables was impractical. The story starts with the inspiration of Albert’s wife, Kornelia Nellie (Nelly) Szent-Györgyi, who prepared a stuffed-pepper dish one evening, using Hungarian red peppers, also known as paprika. The University of Szeged is situated in the center of an agricultural industry devoted to paprika derived from red peppers.

Szent-Györgyi related the following story. During the dinner, he did not feel like eating the red pepper dish and was trying to formulate an excuse not to eat it, recalling that a market vendor had once warned him that “paprika was poisonous.” Just as he was getting his excuse to refuse the dish correct in his mind, he suddenly realized that he had never used red pepper as a source for extracting vitamin C.

Szent-Györgyi elaborated that he went straight to the laboratory that night with the pepper. At about midnight, he knew that paprika was laden with large concentrations of extractable vitamin C! The yield was enormous, with every gram of pepper harboring at least 2 milligrams—it was a tremendous concentration, “bucket loads” in biochemical parlance—of vitamin C.

Then, Szent-Györgyi used his new preparation of vitamin C extract to determine whether it provided relief in the case of Henoch’s Purpura, a condition characterized by subcutaneous bleeding, a known symptom of scurvy. The new extract, but not highly pure ascorbic acid, alleviated the purpura! The results were completely the opposite of what was expected—Szent-Györgyi and his colleagues thought pure (and not impure) vitamin C would work—the exact opposite was the case. The impure vitamin C extract worked to reverse the subcutaneous bleeding.

This result meant that there was something else in the extract preparation—something else besides vitamin C, that produced the desired remedying effect of purpura. Szent-Györgyi speculated, therefore, that the vitamin C extract contained another vitamin. He was not entirely sure, however, that the therapeutic substance was a bona fide vitamin in the strictest sense of the word, i.e., a substance not synthesized in the body and thus needing dietary sources. Therefore, Szent-Györgyi named his new vitamin “P,” using a letter further down the line in the alphabet, in case it would later be deemed incorrect. Further, he reasoned that the vitamin P was a member of the so-called flavones. Thus, he tested whether pure flavonoid compounds extracted from paprika mimicked the effects of his vitamin P on the purpura—it did! Szent-Györgyi published the new findings in 1936. In modern times, the vitamin P, also known as rutin, is a member of the so-called flavonoids or bioflavonoids.

9) Later in life—what did he research or investigate?

In addition to his early studies on muscle tissue, physiology, energetics, Krebs cycle metabolism, and vitamin C, he was involved in studies of other scientific fields. One field, in particular, was cancer. The new interest was likely because of the untimely deaths of his daughter, Kornelia, and his second wife, Márta Borbíró Szent-Györgyi (1941–1963), from cancer in the early 1960s. His investigations of cancer dealt primarily with the progression of tumors by chemical adducts called free radicals, which harbor free electrons and are, thus, highly oxidative agents. Free radicals can damage DNA and proteins of healthy cells, possibly transforming them into tumors.

From Szent-Györgyi’s work on free radicals in the early 1970s would emerge the elucidation of a biochemical mechanism for which vitamin C neutralized the unpaired electron nature of these highly oxidative free radical chemical structures. Thus, the positive health effects of vitamin C likely stems from its biochemical role as an antioxidant. From this, Szent-Györgyi discovered that individual flavonoids, such as rutin (vitamin P), could work in concert with vitamin C in mediating anti-inflammatory changes within the skin.

The work in dealing with electrons would take Szent-Györgyi to the sub-atomic levels, such as quantum mechanics and sub-molecular biology. Another controversial area is called the bioelectronic theory of cancer. The theory emerged from his studies of methylglyoxal, glyoxalase enzymes, and cancer. Szent-Györgyi proposed that vitamin C was acutely associated with their biochemistry and in trapping a carcinogenic cell within a so-called alpha state. In the process, proteins that formed complexes with methylglyoxal produced increased low-frequency dielectric dispersion levels. In modern times, this field is less frequently investigated.

10) Albert left us with a vast number of quotes—some of which are below for your thoughtful reflection:

Here we stand in the middle of this new world with our primitive brain, attuned to the simple cave life, with terrific forces at our disposal, which we are clever enough to release, but whose consequences we cannot comprehend.”

I am the son of a small and far-away nation and the other laureates have all come from different countries from all over the world and we all were equally received here with signs of sympathy.”

Investigations during the last few decades have brought hydrogen instead of carbon, and instead of CO2, water, the mother of all life, into the foreground.

Research is to see what everybody else has seen, and to think what nobody else has thought.”

Research is four things: brains with which to think, eyes with which to see, machines with which to measure and, fourth, money.”

So I set out to study the oxidation system in the potato, which, if damaged, causes the plant to turn brown. I did this in the hope of discovering, through these studies, the key to the understanding of adrenal function.”

The foodstuff, carbohydrate, is essentially a packet of hydrogen, a hydrogen supplier, a hydrogen donor, and the main event during its combustion is the splitting off of hydrogen.”

The real scientist is ready to bear privation and, if need be, starvation rather than let anyone dictate to him which direction his work must take.”

Whatever man does, he must do first in his mind.”

The source of this energy is the sun’s radiation.”

A discovery is said to be an accident meeting a prepared mind.”

A vitamin is a substance that makes you ill if you don’t eat it.”

A living cell requires energy not only for all its functions but also for the maintenance of its structure.”

This celebration here tells me that this work is not hopeless. I thank you for this teaching with all my heart and lift my glass to human solidarity, to the ultimate victory of knowledge, peace, good-will, and understanding.”

Discovery consists of seeing what everybody has seen and thinking what nobody has thought.”

This oxidation of hydrogen in stages seems to be one of the basic principles of biological oxidation.”

Without energy, life would be extinguished instantaneously, and the cellular fabric would collapse.”

Water is life’s matter and matrix, mother and medium. There is no life without water.”

Dr. Albert Szent-Györgyi was a prolific author, publishing over 300 scientific articles in peer-reviewed journals and 11 books, leaving behind a tremendous legacy for future generations of scientists and philosophers alike. These quotations above, all attributable to a great scientist and used by many other authors as introductory statements in pre-chapters headings, are a true testament to the veritable intellect of Szent-Györgyi. There can be no doubt whatsoever that Szent-Györgyi was a true genius.

For instance, one insight that arises immediately out of the first quote above is his realization that humankind has not been able to overcome its inability to anticipate the consequences of our cleverness in developing new technologies. An avid anti-nuclear arms race advocate, Szent-Györgyi, was speaking to the problem of humanity’s incomprehension of the consequences of our advances in the arms race. In his book called “The Crazy Ape,” he conceded our cleverness with enhancing the speeds of communication, travel, energy resources, and population growth. He stated that we are, nevertheless, still stuck with a caveman-like brain, unable to alter the speed of our brains to accommodate the changes and to adapt.

Many of the quotes above are relevant to his scientific research areas. For instance, his statement about potato oxidation and discoloration refers to his keen insight into the function of the adrenal deficiency diseases. His quote about “seeing what every one has seen but thinking what no one else has thought” is reminiscent of his intelligent, intellectual connections. He made these disparate connections repeatedly in his scientific investigations, and they constituted evidence of his genius.

Szent-Györgyi made a linkage between two seemingly different biological observations (potato bruising and a human disease symptom). He turned the relationship into a world-changing discovery of vitamin C.

In Szent-Györgyi’s quote, he related food, packets of hydrogen, and chemical activation. From their relationship, he deduced functional roles in food combustion. Then, Szent-Györgyi explored two conflicting explanations, i.e., hydrogen versus oxygen activation, and he united them! Furthermore, he provided fresh, experimental evidence to do so.

Particularly fascinating are the statements about water, carbon, biological energy, the radiation of the sun, cell structure, and vitamins. Szent-Györgyi thought genuinely about each of these disparate fields of study, and he made tremendous strides in gathering experimental evidence in each of these areas. For a typical scientist, making a long-lasting contribution to even one of them, or any scientific area, may be considered a significant life accomplishment. Szent-Györgyi made enduring significant contributions to all of them!

Szent-Györgyi’s comment about privation and starvation of scientists likely refers to his World War II and post-war experiences in which he dealt with Nazi and Communist occupations of Hungary. He was likely speaking to outside political and funding sources attempting to influence the direction of research studies in his and others’ laboratories. It seemed he got into trouble with Nazis and Communists. The quotations are the result of lessons learned during the Second World War.

In Germany, and later in German-occupied Hungary, he referred to enduring “slight hunger edema.” With a Nobel Prize already in hand, he held a certain degree of prestige. He was, therefore, recruited by the Hungarian government to undertake a secret mission of a delicate nature to Istanbul, under the guise of a giving a speech, to initiate a collaboration with American and British allies. The Hungarian officials were hoping to avoid an iron-fisted grip on their country by Nazi Germany. Unfortunately, after meeting with the British Secret Service, the secrecy of the diplomatic Istanbul mission had somehow been compromised, and Szent-Györgyi was placed under house arrest. When Germany did occupy Hungary, arrest warrants were issued by Hitler’s Gestapo against Szent-Györgyi and his family! The Szent-Györgyi family dispersed and went into hiding.

Szent-Györgyi hid at the Swedish Legation in Budapest, where he began a secret correspondence with his friend and editor, Hugo Theorell, for his muscle work to be published in the journal Acta Scandinavica. A telegram of the manuscript’s acceptance from Theorell arrived at the Legation, which compromised the secrecy of his hideout. Word soon arrived that arrest was imminent. He was smuggled out of the Legation that night in the back seat of a car. The next night German Nazis invaded the Swedish Legation and trashed the place while searching for Szent-Györgyi. Meanwhile, Szent-Györgyi moved from location to location, one step ahead of Hitler’s Gestapo. He escaped Nazi Germany but soon was under the auspices of the Communist Soviet Union.

11) Here in the U.S., we typically associate vitamin C and ascorbic acid with Linus Pauling—how did Pauling build on the work of Albert?

Biochemist and two-time Nobel Laureate Dr. Linus Pauling strongly advocated daily consumption of vitamin C mega doses. For many years, he advocated high doses of vitamin C for maintaining good health and for disease prevention. He endorsed its use for protection against the common cold, the flu, bacterial infection, cardiovascular disease, and controversially, cancer.

Pauling commenced his foray into vitamin C because of brewing biochemist, Dr. Irwin Stone, who contacted Pauling in 1965. Stone told Pauling that with mega-doses of vitamin C, he could live longer, perhaps another 50 years.

Pauling wrote to Szent-Györgyi sometime during the late 1960s. He asked whether Szent-Györgyi might advocate vitamin C. He replied to Pauling that taking merely the recommended daily allowance (RDA) amount, which prevented scurvy, was not enough to maintain full health in humans. The RDA of vitamin C was between 75 and 90 mg. Szent-Györgyi conveyed, furthermore, that he took one gram of vitamin C daily. Such advocacy for mega-doses of vitamin C by its discoverer, the distinguished Szent-Györgyi, was all that Pauling needed. Pauling relayed Szent-Györgyi’s advocacy in his speeches and writings on the topic.

Pauling was also suitably encouraged about vitamin C and cancer by a physician. Dr. Ewan Cameron reported that the statuses of his cancer patients were improved by vitamin C. The issue of cancer and whether vitamin C is efficacious remains controversial to this day. The term cancer refers to a constellation of hundreds of distinctive diseases, depending on the affected cell type, tissue, organ, the individual patient, and the particular immune status. Perhaps vitamin C is preventative or curative in certain cancer cases but not others. Whatever the case, however, much scientific work will need to be completed before the full story about vitamin C and cancers is resolved.

12) What still needs to be said about this famous Hungarian Scientist?

Albert Szent-Györgyi was genuinely active in politics, especially throughout the 1960s. He was against nuclear arms buildup, the war in Vietnam, and the Cold War. Szent-Györgyi supported the student protests on these issues and which were held in front of his Marine Biological Laboratory. He took part in public debates on these issues, as well. Much of his political views were articulated in his book titled Crazy Ape, from which some quotations above originated.

Szent-Györgyi had a cousin, Andrew Szent-Györgyi, who was often mistaken for Albert and who also spent a few years as a scientist at Woods Hole.

Szent-Györgyi was married four times. He married his first wife, Kornélia “Nelly” Demény, in 1917, and they had a daughter Kornélia. The couple divorced in 1938 (though some sources say 1941). Szent-Györgyi married his second wife, Marta Miskolczy, in 1941, and they were married unit her death from cancer in 1963. In 1965, he married 25-year old June Susan Wichterman, and the couple had a daughter. They divorced in 1968. In 1975, he married his fourth wife, Marcia Houston, and they adopted a daughter, Lola Von Szent-Györgyi. The marriage lasted until his death at the age of 93 on the 22nd of October, in 1986, in Woods Hole, Massachusetts.

For more information about Dr. Albert Szent-Györgyi, go to:


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1 Comment

  1. Avatar
    Butterly

    The author of this writes, misleadingly, that Pauling’s advocacy of vitamin C therapy for cancer is and remains “controversial.”

    The facts show it’s a manufactured “controversy.”

    Everyone should keep the following in mind: there are many bogus voices around who strive to distract the public from (1) the value of vitamin C therapy and (2) the fact that Pauling’s VALID work with vitamin C supplementation for cancer has been “falsified” by data distortions and lies, and he as a person (a double Nobel laureate) has been slandered as some deluded idiot by the criminal medical establishment and its countless quackwatch shills, lackeys, ignoramuses, and trolls for decades and it continues today — search for the scholarly report “2 Big Lies: No Vitamin Benefits & Supplements Are Very Dangerous” by Rolf Hefti (a published author of the Orthomolecular Medicine News organization).

    But you can’t discredit the facts with lies. That only exposes and discredits the liars (see citations above).

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