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CASIMIR FUNK (1884-1967) by guest on June 28, 2014

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CASIMIRFUNK Casimir Funk

— A Biographical Sketch (i884-1967)

". . . the deficient substances, which are Polish, was also fluent in Russian and of the nature of organic bases we will call German. Soon he was also to acquire "vitamines"; and we will speak of a beri fluency in French: feeling that there was beri or scurvy vitamine, which means a no future for Casimir in Poland, his par substance preventing the special disease." ents sent him to Geneva, Switzerland, to The paper containing this sentence was study biology. He later moved to Berne, published by Casimir Funk in 1912. In this where he specialized in organic chemistry; so-called résuméhetried to show that at the age of 20, Casimir passed his oral

various diseases listed in the subtitle, such exams and defended his doctoral thesis on Downloaded from as scurvy and beriberi, were due to nutri the chemistry of two organic dyes of the tional deficiencies, and not to food intoxica stilbene family (1904). tions or infectious diseases, as was widely A fair number of Polish and Russian believed at that time; they could all be teachers and students could be found in prevented by a complete diet. Swiss universities at that time; these in The man who wrote this historic paper cluded some men of great promise. It is was born on February 23, 1884, in War not surprising that this caused resentment, jn.nutrition.org saw, Poland, the son of Jacques and and perhaps jealousy, in some circles of Gustawa Funk. Jacques Funk was a physi the native-born population. While this did cian who had specialized in dermatology, not in any way interfere with Casimir's and a scientist in his own right: his clini studies and progress, the sensitive young cal research resulted in sixty publications, man was keenly aware of it. Even in later by guest on June 28, 2014 and his reputation had spread beyond the years, in the , he never borders of his native Poland, most of seemed to lose entirely the feeling of being which was, at that point in history, under somewhat different, and, therefore, not the heel of the Russian Empire. wholly wanted. If Casimir's home environment pro Having finished his graduate work, vided an excellent background for a scien Casimir went home to discuss his future tific career, the socio-political conditions with his parents, who discouraged him did not. After some years of home tutor from following in his father's footsteps and ing, which included extensive reading, studying medicine. He decided to enter the Casimir, despite excellent marks, failed to newly blossoming field of biochemistry. At gain entrance into the Russian Govern the Pasteur Institute in Paris a chair in ment school for ethnic reasons. In fact, biochemistry was already in existence. It there existed a "black market" in secondary was occupied by Gabriel Bertrand, a soli school acceptance. Later, entrance was tary worker with limited interest in stu arranged for him, but the timid boy's four dents. There Casimir became involved, years in the dull and anti-Polish Govern among other things, in chemical work with ment school were not a complete success. amino acids and organic bases, which was He finished his secondary education as the probably the reason for his next move, two best student in his class in a better, private, years later, to Emu Fischer's laboratory in school. A congenital dislocation of the hip Berlin. In Paris he also befriended von had previously brought him for prolonged, Euler, who in later years was to receive though unsuccessful, treatments to Ger a Nobel prize in chemistry, and became many and to Austria. The latter was also acquainted with Arrhenius and Metchni- the family's favorite destination during koff. He also seemed to have thoroughly vacation time. Thus it happened that at enjoyed the artistic and intellectual life of age 16 Casimir, whose native tongue was the French metropolis. While the following

J. NUTRITION,102: 1105-1114. 1107 1108 CASIMIR FUNK year in Berlin may have been culturally polishings, thus causing a protein defi less stimulating, it was of great scientific ciency. Funk, given the job of finding the value to the young scientist. At that time, missing substance, discarded the "protein Berlin was a world center of scientific deficiency" theory on the basis of his pre progress, especially in chemistry and allied liminary experiments, and started to look sciences. Casimir worked under Emu Abderhalden, who was Fischer's private for some undefined material present in rice polishings, but absent in the polished medical assistant, and their cooperation rice. In 1912 he succeeded in preparing resulted in several publications. His inter thiamin-containing extracts, first from rice ests covered various aspects of physiologi polishings, and later from yeast, milk, and cal chemistry, with emphasis on amino ox-brain. According to Williams (1961) acids and protein. these extracts were relatively low in beri In 1907 08 Funk, who up to this time beri-preventing activity. Williams quotes had been supported by his parents, earned Barger as having suggested in 1914 that his first money as a biochemist at the mu the original substance isolated by Funk nicipal hospital in Wiesbaden, Germany. There he adapted Bertrand's assay for may have been impure nicotinic acid, the

antineuritic properties being due to the Downloaded from sugar to the determination of blood sugar, impurities. On the other hand, Funk was worked on peptide separation, and famil able, in the same year, to state that "the iarized himself with the characteristics curative substance is a pyrimidine base, of malignant tumors. Still in cooperation analogous to uracil and thymine . . .", with Abderhalden, he undertook research indicating that he must have had a product on uric acid metabolism. This finally led him back to Berlin in 1908. Abderhalden's on hand that contained appreciable jn.nutrition.org position having changed, relations between amounts of the . In the following the two men became strained, and Funk year, he actually isolated and identified transferred to the Charité,the University nicotinic acid from one of the fractions of Hospital in Berlin. During his eight months his extract, without, however, recognizing at the hospital, he undertook some respira its vitamin nature. by guest on June 28, 2014 tion studies on babies. Not seeing much To Funk must go not only the honor of hope for a rewarding future at the preparing the first useful concentrate, however impure, of the antineuritic fac Charité,he moved to the Lister Institute in tor. More important, in this writer's London in 1910 on the recommendation of the Englishman Dean, whom he had opinion, was his scientific intuition, ex befriended in Fischer's laboratory. emplified in the well-known résumémen The Lister Institute, under the leader tioned earlier, in which he listed a number ship of Charles James Martin, was devoted of deficiency diseases, coined the term mainly to preventive medicine. In 1911 "vitamine" deficiencies for these diseases, Funk published his first paper in English and even predicted, from the apparent —the language of the majority of his later minuteness of the requirements for the publications —on the synthesis of dihy- proposed micronutrients, that they may be droxyphenylalanine ("DOPA"). His suc used as, or transformed into, ferments cess in this field was probably instru (enzymes). F. G. Hopkins as well as other mental in his subsequent appointment as a scientists of that time also believed in the Scholar of Lister, with an annual salary existence of substances, other than the of 150 pounds. known major nutrients, that were required The head of the Institute (he became in small amounts. The boldness of Funk's Sir Charles Martin in 1927) was in com predictions, however, in this paper as well munication with an English doctor in as in his later book on (1914) Malaya, W. L. Braddon, who was inter had a profound influence on subsequent ested in beriberi and had published a book work. Scientists began to take an active about the disease in 1907. Braddon be interest in the new field, which resulted, lieved that beriberi was caused by a toxin, within 35 years, in the discovery of all while Martin thought that an essential vitamins known today, and, incidentally, amino acid was discarded with the rice in the creation of a billion-dollar industry. A BIOGRAPHICAL SKETCH 1109

At the Lister Institute, Funk worked for chemicals of all types greater than under rather primitive conditions, either ever, this was a time of opportunity for alone or with the aid of a servant not the growth of the American chemical in trained in the sciences. While his vitamin dustry. Funk, with imagination and skill, theory did not create many converts in the became one of the pioneers in the develop medical profession, he made an excellent ment of this industry. impression on Hopkins at Cambridge: His first position was not a success; the Casimir received a Beit Fellowship and the second position was a great improvement, degree of Doctor of Science of the Uni but required an amount of travel that versity of London for his efforts. In the would make even a hardy commuter shud spring of 1913 he had also been joined by der. Funk had to get up at five in the morn his parents; Funk senior helped with the ing, take an elevated train to the ferry to collection and evaluation of data and New Jersey, then take another train, fol abstracted the literature for his son. The lowed by a trolley, and finally walk in younger Funk, however, was not entirely order to reach the Calco Company in satisfied, and eventually accepted a posi Bound Brook, New Jersey. There he pre

tion at the Cancer Hospital. There he had pared cinchophen, benzoic acid, and Downloaded from at his disposal a micro-analytical labora benzonaphthol, which were all in great tory equipped according to the suggestions demand. While he was apparently happy of the Austrian analytical chemist, Fritz with the job, a better and geographically Pregi, and was able to concentrate on vita more convenient opportunity soon offered min problems and the study of tumors. He itself: a responsible position in the re was also given an assistant, who later search department of H. A. Metz and Com became professor of biochemistry at the pany, with a promise for time to work on jn.nutrition.org University of London, and, for his valuable vitamins. This position ended his finan work as chief of nutrition of the British cial worries. Government during World War II, was At first, there was little time to continue knighted Sir . in his primary field of interest, the vita While vacationing with his parents in mins. He had to solve, among other things, by guest on June 28, 2014 Ostend, Belgium, Funk met Alice Denise Metz's problems in the preparation of Schneidesch, and was married to her in salvarsan and neo-salvarsan, which here the following year. During their honey tofore had been imported from Germany, moon, World War I broke out. and organize the industrial synthesis of England at war offered a less favorable adrenaline. He worked very hard and, in climate for research, and had less sym the words of one of his co-workers, he was pathy for foreigners, than the England that a genius at thinking out future research. had greeted Funk in 1910. He accepted a The success of Funk's activity for the com position at the Harriman Research Labora pany finally led to greater freedom for tory in New York, and arrived there early himself. Transferred to the Hudson Street in 1915. Later in the same year, a son, Ian, Branch in the city, he had the valuable was born to the Funks. cooperation of H. E. Dubin and Louis At first, Funk was intrigued by the New Freedman. An early product of the new World. He was especially impressed by the effort was "Oscodal," a vitamin A and D lack of need for registration and identifi concentrate, which was the first vitamin cation cards, something that had been de preparation accepted by the American veloped to a science in the Old World. The Medical Association as an ethical product. first shock came when he saw his new The group was less successful, for unex laboratory —a dark room without equip plained reasons, with a B-vitamin product ment. While the laboratory problem was from yeast. From 1920 to 1923 Funk also eventually solved, the need for research held the position of Associate in Biochem funds forced him to look for industrial istry at Columbia University. There he met connections. After a health breakdown, Benjamin Harrow, who was to become possibly from overwork, he accepted a Funk's biographer (1955). This period full-time industrial position. With deliv saw a number of publications with Dubin eries from Germany halted, and the need and Freedman on factors influencing the ino CASIMIR FUNK vitamin requirements of rats, and on the ful, and certainly stimulating to the local vitamins in yeast. Freedman, whose doc scientific effort. Funk also visited many toral research at Columbia was supervised European laboratories and attended various by Funk, investigated nutritional require meetings. Sweden, Rumania and Russia ments of yeast and bacteria, methods for were among his destinations. In Sweden measuring bacterial growth, and the use he heard that he was under consideration of yeast growth for the assay of B-factors. for the Nobel Prize for his vitamin work. Despite progress, Funk was not entirely Eventually the Prize went to two other par happy, and a change in scenery seemed in ticipants in the search for the first acces order. The medical director of the League sory food factors: Eijkman and Hopkins. of Nations was then, with the help of the In Russia he lectured on hormones —he Rockefeller Institute, trying to provide bet still had a fair command of Russian —to ter health services for various countries, a most attentive audience. He visited with and engaged Funk to work for 2 years for Pavlov, and was offered the directorship of the Health Institute in , Poland. a nutrition and hormone institute in Mos In 1923, at the age of 39, Funk left New cow, an offer which he declined.

York, making several professional visits Their life in Warsaw was not unpleas Downloaded from on the way, including one to Pregi in Graz, ant, and Mrs. Funk had made many Austria, where he tried to perfect his friends. The political situation in Poland, analytical techniques. however, was still unsettled. Inflation and In Warsaw, the family settled in a starvation were bywords of the scene. The modest apartment, and Funk faced the uprising in 1926 under Pilsudski once problem of setting up a laboratory without again brought home the basic instability sufficient funds for either equipment or of the situation. During the uprising, jn.nutrition.org chemicals. In order to create an income for Funk's Institute was hit with shrapnel, and his institute, he initiated a small-scale the hall of his apartment riddled with bul manufacture of insulin, using his own lets. It was only natural that he decided funds as seed money. A severe case of to look westward again. In the fall of pneumonia, perhaps contracted on one of 1927, at the end of his Rockefeller appoint by guest on June 28, 2014 his cross-country trips in an open Ford to ment, he left for Brussels, the home of his obtain materials, interrupted his efforts. in-laws. There were frequent contacts with Recovery was slow. His serious illness the medical school faculty during his five probably caused concern to the Polish au months' stay, but the relationship did not thorities : the family was moved to a small bloom into a position at the University. In house in the suburbs, and he obtained 1928 he moved to Paris to accept a part- newer and better laboratories. Money, how time position with the pharmaceutical ever, was still in short supply. In 1924, a house of Grémy,which left him time for second child, a daughter, was born to the the effort needed to locate a laboratory Funks in Danzig: they felt that in Danzig suitable for the advancement of his own better medical care would be available research interests. than in Warsaw, and had gone there to Grémymanufactured sera and vaccines, await the birth of the child. and needed a research and development The Rockefeller Institute was satisfied with Funk's insulin work, extended his stay center for new products not heretofore pro duced in France. Funk had been interested for another two years, and assigned him for some time in sex hormones, and now $3,000 for equipment, which he pur submerged himself into a study of the chased in Berlin. Funk and his cooperators identification of the male hormone in —including S. K. Kon, whom he recom urine. Conditions at Grémydeteriorated, mended for a Rockefeller Fellowship, and however, and Funk decided to branch out who later became well known for his nutri for himself. With the help of grants from tion work at Reading, England —pub various sources he built the "Casa Bio- lished widely on insulin, on vitamin prob chemica," which contained laboratories as lems, and on methods in nutritional well as his home. Various circumstances, biochemistry, and developed an interest in including the financial disaster of 1929, hormones. The years in Warsaw were fruit brought about a much more modest build- A BIOGRAPHICAL SKETCH 1111 ing than originally planned, but Funk, sessions included all his chemicals, his with the help of his children and a handy library, apparatus and valuables, a garden man, was already hard at work in the ani that the family had planted, a Great Dane, mal laboratory while workmen were still three black cats, and hundreds of pigeons, hammering away in other parts of the rats, mice, guinea pigs, rabbits, and building. Harrow, who worked with Funk, turkeys. After waiting for a week in vividly described the cluttered laboratory Bordeaux, the family was finally able to in his biography, but noted that Funk board a small ocean liner and proceed to always knew how and where everything New York. was, a lack of identification marks not When the Funks arrived in New York, withstanding. The years in Paris resulted daughter Doriane was 15, and son Ian in work on the chemical differentiation 24. Ian had studied medicine in Paris, between male and female hormones, a while working at the same time in his series of papers on the male hormone and father's laboratory, and received the M.D. the preparation of active hormone extracts degree from the Albany Medical College from urine, and similar preparations of in 1942. Volunteering for service with the

pituitary gonadotrophic hormone. Another United States Army, he was severely Downloaded from urine fraction yielded an active material wounded in 1944 when his jeep was blown that caused hyperglycemia and an increase up by a land mine in France. Recovery was in acetone bodies in rats. At the same time, very slow. Later, Dr. Ian Funk became the "Casa" turned out an insulin product head of the Psychiatric Division of the that was as good as anything imported into Veterans Administration Hospital in Al France at that time. In the area of nutri bany, New York. Doriane, now Mrs. Henry tion, Funk, in cooperation with Lejwa, Coenen, followed a college career in pure jn.nutrition.org found that not only liver, but also yeast and applied art, and later also made her contained an antianemic factor for new home in Albany. born rats, and concentrated the active frac Funk senior worked with the U.S. Vita tion in both materials. In this connection min Corporation, for which he had previ he helped the Roussel concern, then the ously consulted, but had time left for by guest on June 28, 2014 second largest pharmaceutical house in independent research. He worked with France, to prepare an iron-free liver extract B. Harrow at the City College of New York, that was effective in pernicious anemia. and with I. M. Chamelin at the Welfare In 1934 Funk junior first appeared as a Hospital. His interests ranged from trace coauthor on one of his father's papers, elements to ulcers, diabetes and cancer, and he continued to cooperate in his with the latter emerging as his main con father's hormone work until joining the cern. In 1944, he joined forces with Dr. army during World War II. Edward Jacobs, and once again the scarcity During this time, Funk also served as a of funds made it necessary for the junior consultant for the U. S. Vitamin Corpora members of the family to help in the tion, and in collaboration with American laboratory. firms developed the production of nicotinic In 1945, a patron appeared on the scene acid and nicotinamide. Even though the in the person of Mr. Spanci, President of investigation of the chemistry of hormones the International Latex Corporation. The seemed to have been his major interest at Funk-Jacobs-Spanel Foundation was set up that time, he was never far away from in 1945 with headquarters and laboratories nutrition, and, especially, from the area in Manhattan. In 1946, however, Funk of vitamins. withdrew and returned to full-time em On September 1, 1939, World War II ployment with the U. S. Vitamin Corpora started with the invasion of Poland by tion, which incorporated the Funk Founda Nazi-Germany. By the time Poland's fate tion for Medical Research in 1947. Funk had been sealed with the fall of Warsaw, was now 63, and this was his last move; Funk and his family had already arrived he remained with the Foundation until his at the port of Bordeaux, leaving their ma retirement in 1963 at the age of 79. Much terial possessions behind in Paris. Accord of his work at the Foundation centered ing to his biographer, Harrow, these pos around the chemistry of carcinomas, and 1112 CASIMIR FUNK

on factors influencing the production of ulcers. Funk's interest in oncology had and biographer, Harrow, his imagination was sometimes more that of a poet than developed early in his career. In 1915, of a scientist, and often his ideas were while attempting to diagnose sarcoma by ahead of what was warranted by estab chemical means, he had noted a disturb lished scientific work. While some may ance of carbohydrate metabolism in the only remember him as the coiner of the affected birds. In the same year he also term "vitamines," and the creator of a new published a novel method of an inter- era in this field of endeavor, he contributed species transfer of a tumor, and again to many facets of biochemical-medical showed some interest in oncology while in research and to methodology in the phar Warsaw. After 1951, however, the nature maceutical industry. His legacy to the of the development of malignant tumors scientific world includes over 140 tech and their chemistry became his overriding nical papers, about 30 reviews and non interest. He succeeded in demonstrating technical articles, and numerous abstracts hormonal influences on cancer growth, and of oral presentations, the last one dated worked on the concentration of cancer- 1963. stimulating and cancer-reducing sub Funk was of small stature, with a gentle Downloaded from stances from beef spleen. Of interest to Funk and co-workers in face and blue eyes. A connoisseur of the arts, especially music, he was shy with the early forties was also the action of strangers, but charming with friends. He liver extracts in counteracting the toxic effects of diethylstilbestrol and of sulfanila- was a man of strong opinions and definite mide. In the fifties he published several convictions. His restlessness, in combina studies on the ulcer problem. He attempted tion with the vagaries of the political jn.nutrition.org unsuccessfully to isolate enterogastrone, a destinies of the countries in which he re substance claimed by Ivy to inhibit gastric sided, forced him to start many times from secretion, and was experimenting with ma scratch. One may speculate how much terials showing antiulcer as well as anti- more he might have accomplished had he acid secretion activity. Even in retirement, been able to concentrate on his interests by guest on June 28, 2014 he continued to keep himself informed on without pressures of economics and geog developments in his field of endeavor. He raphy. Notwithstanding these obstacles, he died from cancer in the home of his son has left an indelible mark on many areas on November 19, 1967, at the age of 83 of biological research, and enriched sci and, in accordance with his wishes, was ence by his work and his vision. cremated. ACKNOWLEDGMENTS The life of some scientists can be par titioned by a biographer into neat little I am grateful to Dr. Louis Freedman for packages marked "private" and "profes sharing with me his personal recollections sional." Not so the life of Casimir Funk. of Casimir Funk, and to Mrs. Olga Grim- Having left his home as a youth, and inger for her help in gathering informa buffeted by the upheavals of two World tion and the preparation of this sketch. Wars, his private life was always closely Thanks are due to Dr. E. Neige Todhunter intertwined with his professional activities. who provided the photograph. A list of It is also difficult to use a simple label for almost all publications by Funk can be his scientific career. His strength was in found in the biography by Benjamin Har organic and biochemistry, but his work row, which also provided an appreciable spanned nutrition and medicine, analytical part of the information used in these pages. biochemistry and chemical synthesis, PAUL GRIMINGER oncology and endocrinology. Nutrition Department of Nutrition must have had a special fascination for Rutgers University Funk, since he frequently searched for New Brunswick, New Jersey 08903 implications of nutritional factors within REFERENCES the areas of his respective research inter 1. Funk, C. 1904 Zur Kenntnis des Brasilins ests. He was a hard worker, with a keen und Hämatoxylins. Dissertation, University mind. According to his co-worker, friend, of Berne, Switzerland. A BIOGRAPHICAL SKETCH 1113

2. Funk, C. 1912 The etiology of the défi- 4. Harrow, B. 1955 Casimir Funk —Pioneer ciency diseases. Beri-beri, polyneuritis in in Vitamins and Hormones. Dodd, Mead & birds, epidemic dropsy, scurvy, experimental Company, New York. scurvy in animals, infantile scurvy, ship 5. Williams, R. R. 1961 Toward the Con beri-beri, . J. State Med. 20: 341. quest of Beriberi. Harvard University Press, 3. Funk, C. 1914 Die Vitamine. J. P. Berg- Cambridge, mann, Wiesbaden. Downloaded from jn.nutrition.org by guest on June 28, 2014