Kazimierz Funk (1884 - 1967)

Funk was the first to use the word "vitamin" and, based on existing knowledge and his own research and observations, he hypothesized that these were simple chemical compounds found in food, essential for the proper functioning of animal and human bodies. The Polish biochemist demonstrated that diseases such as beri-beri, scurvy, and pellagra were caused by deficiencies of specific vitamins in the diet. This was a groundbreaking discovery. Today, over a century later, diseases like rickets or scurvy are largely confined to historical medical literature, while vitamins remain a cornerstone of interest for biologists, biochemists, and medical professionals alike.

The term "vitamin," as proposed by Funk, has been universally adopted, with similar pronunciation in almost every language: vitamina, vitamin, vitamino, vitamene, vitaminum, vitaminas. Kazimierz Funk was nominated for the Nobel Prize in Physiology or Medicine in 1914 and 1925 and for the Nobel Prize in Chemistry in 1926 and 1946.

The discovery of the vitamin was prompted by studies on the disease beriberi, caused by a prolonged deficiency of vitamin B1 in the diet. This condition had been known since ancient times, but its most severe manifestations emerged at the end of the 19th century in Asia, where rice formed the basis of human and animal diets. This coincided with the widespread adoption of rice polishing for consumption. Shiny white rice was tastier and more desirable than unpolished brown rice. Additionally, in Asia's tropical climate, brown rice would quickly spoil and become inedible, whereas white rice, even after prolonged storage, remained usable.

The main symptoms of beriberi, caused by vitamin B1 deficiency, include cardiovascular disorders, limb paralysis, muscle tissue atrophy, and dramatic weight loss. Patients may also experience memory loss, disorientation, and depression. Prolonged thiamine deficiency can lead to permanent brain damage. The name of the disease comes from the word beri, which in Sinhalese (one of the national languages of Sri Lanka) means I cannot or weak. The term is repeated twice (beri-beri, I cannot-I cannot, weak-weak) to emphasize the extreme fatigue and slowness exhibited by patients affected by the deficiency. Medical literature of the time described the condition vividly, stating, for instance: "patients lie like logs in their beds, unable to move a limb or even a finger" (Manson, P.: Tropical diseases: a manual of the diseases of warm climates. Cassell, 1909).

White rice nearly defeated the Imperial Japanese Navy as well. On December 19, 1882, the Navy's most powerful ironclad warship at the time, the Ryūjō, embarked on a training voyage with 376 crew members aboard. The journey began at Shinagawa port in Japan and included stops in Honolulu, Hawaii, as well as ports in New Zealand, Chile, and Peru, before returning to Shinagawa on October 15, 1883. During this nine-month voyage, symptoms of beriberi appeared in 169 sailors, 25 of whom died. The crew's primary food source was white rice.

Kanehiro Takaki, the chief medical officer of the Japanese Navy, persuaded the naval command to fund an experiment to demonstrate that the cause of beriberi in the Japanese fleet was a diet consisting exclusively of white rice. Thus, on February 3, 1884—with the emperor's approval—the warship Tsukuba embarked on an "experimental" voyage. The ship carried 333 crew members and followed the same route as the Ryūjō, departing from Shinagawa Port in Japan to Honolulu, Hawaii, with stops in New Zealand, Chile, and Peru, before returning to Shinagawa Port on November 16, 1884.

The Tsukuba followed the exact same path as the Ryūjō and, like the earlier voyage, lasted nine months. This time, however, the crew of the Tsukuba was fed a diet that included not only white rice but also meat, bread, milk, fish, barley, and beans. Among the 333 crew members, only 14 sailors developed beriberi, and none of them died. Further investigation revealed that those 14 sailors who exhibited symptoms of beriberi had not strictly adhered to the new diet and primarily consumed white rice. Thus, the crew members who deviated from the new dietary regimen were the only ones to develop beriberi.

Takaki was convinced that rice as a food was too low in protein and that a diet richer in milk, meat, fish, bread, and vegetables prevented beriberi due to its high protein content. Takaki, of course, did not know that beriberi was caused by a deficiency of vitamin B1. However, an increase in protein intake does indeed prevent beriberi because the amount of protein in the diet correlates with the amount of vitamin B1. Nevertheless, Kanehiro Takaki achieved a significant breakthrough: he was the first to identify the therapeutic role of food and the first to uncover the deadly secret of white rice.

Despite Takaki's success, his experiment did not convince everyone. At the time, the prevailing belief in medical circles worldwide was that beriberi was an infectious disease. This was also the opinion of scientists and physicians from the Tokyo Imperial University, many of whom served as doctors in the Japanese Imperial Army. As a result, the primary food for soldiers in the Japanese Army remained white rice, and the findings of Kanehiro Takaki's experiment remained largely unknown. The mysterious disease continued to claim lives.

By the end of the 19th century, Europe began investigating the causes of beriberi. It became apparent that the disease also afflicted soldiers in the Dutch Colonial Army in Indonesia, which at the time was the largest and wealthiest Dutch colony, known as the Dutch East Indies. The myth that beriberi was exclusively a disease of the native Asian population was debunked. The Dutch government was compelled to address the issue actively when it became clear that the disease was wreaking havoc among Dutch soldiers fighting against the Sultanate of Aceh in northern Sumatra.

In 1873, the Netherlands declared war in an attempt to take control of the entire island. This effort at annexation by the Kingdom of the Netherlands marked the beginning of long and bloody battles, officially ending in 1903 with a Dutch victory. However, military operations continued, carried out by the Sultanate's guerrilla troops hiding in Aceh’s jungles and mountains (rising over 2,600 m above sea level). Marian Raciborski, a distinguished Polish botanist who conducted research on the island of Java from 1896 to 1900, wrote in 1897 in the journal Wszechświat that two reasons why the Dutch army had been unable to defeat the Acehnese for nearly 30 years were bambu duri (thorny bamboo) hedges and the disease beri-beri (Raciborski, M.: Patma. Wszechświat, 1897, 16, 433–438). The main food of the soldiers in the Dutch Colonial Army was, of course, white rice.

In 1886, at the initiative of the Dutch government, two scientists from Utrecht University, physiologist Cornelius Pekelharing and psychiatrist and neurologist Cornelius Winkler, were sent to Java. The Pekelharing-Winkler mission also included a young Dutch doctor, Christiaan Eijkman, a graduate of the Military Medical School at the University of Amsterdam. After completing his studies in 1883, Eijkman left the Netherlands for the Dutch East Indies, where he became a medical officer, first on Java’s southern coast and later on Sumatra.

During their stay in the Dutch East Indies, the scientists determined that the cause of the disease was an unknown bacterium. From late 1886 to September 1887, research aimed at identifying the microorganism causing beri-beri was conducted in a laboratory established at the Military Hospital in Batavia (present-day Jakarta, the capital of Indonesia). In late 1887, Pekelharing and Winkler were recalled to the Netherlands. As a result, Eijkman became the laboratory director in Batavia and also took on the role of director of the Javanese Medical School, STOVIA, where he lectured on physiology and organic chemistry.

In the Batavia laboratory, Christiaan Eijkman attempted to infect rabbits and monkeys by injecting them with microorganisms isolated from individuals who had died of beri-beri. These experiments failed, as the infected animals showed no symptoms of the disease. Undeterred, Eijkman continued to believe that beri-beri was an infectious disease. By the end of 1889, he began conducting similar experiments on chickens, likely because they were cheaper and easier to maintain than monkeys and rabbits. In hindsight, this decision proved fortuitous.

While monkeys and rabbits did not develop beri-beri symptoms regardless of whether they were injected with microorganisms from deceased individuals or served as controls and remained uninfected, the opposite was true for chickens. All the chickens, both infected and control groups, developed beri-beri symptoms. Eijkman believed that the healthy chickens had contracted the disease from the sick ones. To test this hypothesis, he purchased another batch of chickens and kept them in separate cages. Yet, the chickens still became ill.

This led Eijkman to conclude that the entire laboratory was contaminated. He relocated the chickens to a new facility, but unfortunately, the birds continued to fall ill, become paralyzed, and die. Eijkman was bewildered (Eijkman was bewildered. Pietrzak, K.: Christiaan Eijkman (1856–1930). J. Neurol., 2019, 266, 2893–2895).

Fate smiled on the Dutch doctor for a second time. A new cook was employed in the hospital kitchen, who decided that, according to military regulations, rice purchased for the soldiers could not be used to feed "civilian chickens" that were not, after all, soldiers. The chickens were thus given cheaper, unpolished brown rice. They stopped getting sick, and those that had already been ill recovered. It was this accidental change in diet—replacing white rice with brown rice—that finally set the research on the right path.

Had it not been for the rule-abiding cook... Based on this experience, Eijkman proposed the hypothesis that the cause of beri-beri was a toxic substance present in polished rice, which was neutralized by another compound found in the rice husk. He was mistaken, as Kazimierz Funk's research later demonstrated the opposite: it is the rice husk that contains a substance whose absence in husked rice leads to beri-beri. Nevertheless, Christiaan Eijkman had, for the second time, "discovered the deadly secret of white rice." The first, as we recall, was the Japanese doctor Kanehiro Takaki. However, this knowledge had previously been known only to a select few. This time, news of the "deadly secret of white rice" quickly spread among colonial army soldiers not only in the Netherlands but also in Britain. As a result, this information soon reached the Lister Institute of Preventive Medicine in London, where Kazimierz Funk was working.

In 1911, Kazimierz Funk and Evelyn Ashley Cooper conducted a series of experiments on pigeons and demonstrated that the symptoms of beri-beri in birds were not caused by a toxic substance in polished rice. They also determined that the unknown substance preventing the disease did not belong to any of the known essential nutrient classes at the time: carbohydrates, fats, phosphorus compounds, or mineral salts. Nor was it an amino acid, as Dr. Charles Martin, director of the Lister Institute, had speculated. The results of these experiments were published by Cooper and Funk in The Lancet in November 1911. Subsequently, Funk conducted a series of complex chemical procedures on an acidified alcoholic extract of rice bran, which led to the isolation of active crystals of an organic compound. As little as 50 mg of this preparation was sufficient to reverse the disease symptoms in pigeons.

Kazimierz Funk HAD DISCOVERED A VITAMIN

Biography

Kazimierz Funk was born on February 23, 1884, in Warsaw. His father, Jakub Funk, was a practicing physician specializing in dermatology. He also conducted clinical research, the results of which were published in sixty scientific articles. His mother, Gustawa née Zysan, was also a physician by training but devoted her career to managing the household. At a Warsaw gymnasium, young Kazimierz studied, among other subjects, foreign languages: German, Russian, French, and English. In 1900, at the age of just 16, he passed his final exams and left for university studies in Switzerland. He initially studied biology at the University of Geneva and later transferred to Bern, where he studied chemistry under the guidance of the Polish chemist Professor Stanisław Kostanecki.

Stanisław Kostanecki was a pioneer in research on the chemistry of plant dyes. Among other achievements, he (together with Janina Miłobędzka and Wiktor Lampe) identified the structure of curcumin, which is widely used today. In 1899, Stanisław Kostanecki began research on dyes derived from wood: the blue dye isolated from the logwood tree (Haematoxylum campechianum), called hematoxylin, and the red dye extracted from Brazilwood (Caesalpinia brasiliensis), called brazilin.

These dyes, known since the 16th century, were used for coloring fabrics. The trees from which they were obtained were thus of significant economic importance. The value of these resources is indirectly reflected in the fact that the country encompassing the region where Caesalpinia brasiliensis grows is named Brazil (Brasil). While synthetic dyes are primarily used for fabric coloring today, natural dyes are still applied in specific areas. For example, hematoxylin is used in modern diagnostic laboratories as a cytological and histological stain.

It was these two dyes, brazilin and hematoxylin, that Kazimierz Funk focused on in his doctoral dissertation, prepared under Stanisław Kostanecki's supervision, which he defended in 1904. At that time, he was just 20 years old. In the subsequent years, he worked at the Pasteur Institute in Paris (1904–1906), the Department of Organic Chemistry at the University of Berlin (1906–1910), and the Lister Institute of Preventive Medicine in London (1910–1913), where he discovered a vitamin.

In recognition of his contributions, Kazimierz Funk received the prestigious Alfred Beit Fellowship and a Doctor of Science degree from the University of Cambridge. From 1913 to 1915, Funk worked at the Research Institute of the London Cancer Hospital, where he conducted studies on the role of vitamin B1 in carbohydrate metabolism and investigated the causes of cancer. He hypothesized a close connection between dietary components and tumor growth.

During the summer of 1913, while vacationing with his parents in Belgium, Kazimierz Funk met Alice Denise Schneidesch, 11 years his junior, whom he married a year later.

The outbreak of World War I (1914) and the deteriorating research conditions prompted him to leave for New York with his wife in February 1915. In June 1915, their son, Ian Casimir (Jan Kazimierz), was born. Kazimierz Funk remained in the United States until 1923, holding various research positions, including at the Harriman Research Laboratory in New York, the Calco Chemical Company in New Jersey, the Metz and Company pharmaceutical firm in New York, and the Department of Biochemistry at Columbia University in New York.

During this eight-year stay in the United States, Kazimierz Funk contributed to improving the treatment of syphilis with salvarsan. The modified salvarsan caused fewer side effects because, as a water-soluble compound, it was more easily eliminated from the body. Kazimierz Funk also played a role in developing technological solutions for the industrial production of synthetic adrenaline and was a co-creator of the world's first vitamin preparation.

This preparation was launched in 1922 under the name OSCODAL. It consisted of tablets containing vitamins A and D derived from cod liver and was marketed as a product to prevent rickets in infants and young children. According to the literature, the name OSCODAL is an acronym formed as follows: OS – bone, CO – co-occurrence of vitamins D and A, L – lozenge (tablet). As a side note, for readers who enjoy word games, it could also be formed as follows: OS – bone, COD – codfish, D and A – vitamins, L – liver.

In the United States, Kazimierz Funk also conducted research in which he demonstrated that certain vitamins are essential for the proper growth and reproduction of microorganisms and yeast. In 1920, he received American citizenship. However, he always emphasized that he was Polish. In 1923, under the patronage of the Rockefeller Foundation, he returned to independent Poland with his wife and son. In 1924, as the head of the Department of Biochemistry at the newly established State Institute of Hygiene in Warsaw, he purchased the necessary equipment with his own money and began the production of insulin from bovine pancreases, personally engaging in laboratory work.

It should be recalled that insulin was discovered by Canadian scientists in 1921. The first injection of insulin was given to a human in January 1922 in Toronto. The patient was 14-year-old Leonard Thompson. At that time, he weighed 29 kg, was in a comatose state, and was dying. Thanks to insulin treatment, Leonard Thompson lived for another 13 years, dying of pneumonia at the age of 27.

Diabetes ceased to be a fatal disease. The American pharmaceutical industry became interested in the new discovery almost immediately – Eli Lilly company in Indianapolis established contact with the University of Toronto to develop a method for mass production of insulin. The first insulins, named "Iletin," were available on the market by 1923. Soon after, insulin production began in Europe as well: in Denmark, Spain, and England. In the spring of 1923, insulin produced by a Danish company, which today is known as Novo Nordisk, was administered to the first patients in Copenhagen. In the fall of 1923, insulin production began in the Netherlands. Meanwhile, in Poland, insulin was still difficult to access. This situation soon changed.

Kazimierz Funk, who had come to Warsaw from the United States, was fully aware of the significance of the discovery by the Toronto scientists. By the end of 1924, the State Institute of Hygiene had produced over 300,000 units of this hormone. Poland thus joined just a few European countries – England, Denmark, Spain, and the Netherlands – that were among the first to launch insulin production in Europe. In a relatively short time, insulin production at the State Institute of Hygiene in Warsaw increased to nearly 1,400,000 units per year. As written by Kazimierz Funk's biographer and friend, Benjamin Harrow: Funk processed 40 kg of pancreases per day. Insulin reached Polish clinics and hospitals. It should be noted that Kazimierz Funk was not only involved in insulin production; the hormone was also the subject of his scientific research. The results of these studies were published by Kazimierz Funk in several international journals. These were the first research papers on insulin in Poland. Funk was also one of the first people in the world to be interested in the oral administration of insulin.

During his time in Poland, Kazimierz Funk actively participated in numerous scientific congresses organized in various European centers, including Sweden, Denmark, Romania, and the former Soviet Union (now Russia). These conferences were an opportunity to exchange opinions and experiences, acquire new knowledge, and meet many prominent scientists. In Lviv, Kazimierz Funk met Jakub Karol Parnas, one of the most outstanding Polish biochemists of the first half of the 20th century, and the creator of the Polish school of biochemistry. In Leningrad (now St. Petersburg), he met Ivan Pavlov, the Russian physiologist and discoverer of the laws of conditioned reflexes, who was awarded the Nobel Prize in Physiology or Medicine in 1904. It is also worth mentioning that in Warsaw, the third edition of the classic monograph Die Vitamine by Kazimierz Funk was prepared and published in 1924 (the book was first published by J. F. Bergmann Publishing House in Wiesbaden in 1914). In Poland, on July 7, 1924, Kazimierz Funk and his wife had their second child, a daughter, Doriane Jacqueline.

Unfortunately, in the autumn of 1927, Kazimierz Funk, along with his wife and children, left Poland. His decision was strongly influenced by the country's unstable political situation. During the military coup led by Marshal Józef Piłsudski in Warsaw in May 1926, the Funk family's apartment was shot at multiple times. “...The hall of his apartment riddled with bullets...” – this is how Paul Griminger describes the situation in his biographical sketch of Kazimierz Funk (Griminger P.: (1972). Casimir Funk: A Biographical Sketch (1884–1967). The Journal of Nutrition, 102(9), 1105-1113).

Initially, the Funk family stayed in Brussels, at Alice's parents' house. However, the professional prospects did not satisfy Kazimierz, and after a five-month stay in Belgium, the Funk family moved to Paris. Here, Kazimierz Funk made contact with the Grémy company, which produced serums and vaccines.

The cooperation with Grémy was short-lived. Kazimierz Funk, utilizing grants from various sources, built a private research center called Casa Biochemica (The House of Biochemistry) in Rueil-Malmaison, a town near Paris. The center housed both laboratories and the Funk family's apartment. Additionally, from 1929 to 1939, Kazimierz Funk also worked at the pharmaceutical company Roussel Company.

In the research work conducted at Casa Biochemica, Kazimierz Funk's son, Ian, then a medical student, also participated. Their first joint publication, published in 1934, dealt with sex hormones. Noteworthy are also the experiments conducted by Kazimierz Funk together with Artur Lejwa, a biochemist of Polish descent. Funk and Lejwa were the first to demonstrate that the "factors" effective in treating anemia are present not only in the liver but also in yeast. Today, we know that this referred to vitamin B12. Based on these studies, Kazimierz Funk assisted the Roussel Company in developing a therapeutic preparation that did not contain iron but was effective in treating anemia caused by vitamin B12 deficiency.

While still in France, Kazimierz Funk signed a contract with the American company U.S. Vitamin Corporation, where he worked as a consultant. As a result of this collaboration, the American pharmaceutical corporation expanded the production of nicotinic acid and nicotinamide on a large scale. Today, we know that these two compounds (nicotinic acid and nicotinamide) are collectively referred to as vitamin B3, also known as niacin or vitamin PP.

This is the vitamin whose deficiency in food leads to the disease known as pellagra. On September 1, 1939, German forces invaded Poland. On September 8, the Battle of Warsaw began, culminating in the surrender of the capital on September 28. The news of these events led the Funk family to decide to leave for the United States. At the end of September 1939, they boarded a small ocean liner in the port of Bordeaux and arrived in New York on October 5. They left France with only small luggage containing the most essential items. Their entire property remained in France: Casa Biochemica, the Funk family home with its garden, Kazimierz's laboratories, his library, chemicals, and equipment, as well as the family pets—a German shepherd, three black cats—and laboratory animals, including rats, mice, guinea pigs, rabbits, turkeys, and pigeons.

In the USA, Kazimierz Funk collaborated with several pharmaceutical companies, sharing his knowledge and experience in the production of medicines and vitamins. From 1947, he served as the director of the "The Funk Foundation for Medical Research," which was specifically established for him. In the last years of his life, he focused on researching cancer. He passed away on January 19, 1967, in Albany. For Kazimierz Funk, the United States became his second homeland. His first, as he always emphasized, was Poland.