Vigno, Vincent du

Vincent du Vigno was born in Chicago . By origin, he was a Frenchman, the son of Alfred du Vigneau, inventor and designer of machines, and Maria Theresa du Vigno. He studied at Karl Schulz High School in Chicago, from which he graduated in 1918 . When he was in the first grade of school, two of his friends invited Vincent to conduct chemical experiments in their home lab. They received chemical reagents from a pharmacist and conducted experiments related to the preparation of sulfur-containing explosives. This was his first acquaintance with science. At that time, the First World War was going on , and young people were needed for farms. High school graduates were offered the opportunity to work in the spring on farms, and get diplomas in June. Young Vincent worked all spring and summer on a farm near Caledonia , Illinois . He was very proud that he could manually milk twenty cows. Vincent decided to become a farmer, but his older sister, Beatrice, helped him change his mind and offered to enter the University of Illinois at Urbana-Champaign to study chemistry . He followed her advice and received a degree in chemical engineering in 1923 . Young du Vigno had no money, but he had to finish university and magistracy . He went through vegetables, picked apples, worked in the library, poured carbonated soda water — this is an incomplete list of his studies at that time. However, the most paid job for him was a head waiter . One day, while working as a waiter, Vincent saw a pretty red-haired girl and told one of his colleagues: “This is the woman I'm going to marry,” and they really got married. The young girl's name was Zella Zon Ford. Her specialty was English , but when he and Vincent got to know each other better, he learned that she was taking lessons in mathematics and chemistry. Although she graduated from university with a degree in English, she knew chemistry fairly well, so after their wedding in June 1924, she was able to teach chemistry in high school. One of the professors who had a significant influence on the young du Vigno was Karl Shipp Marvel. Du Vigno was shocked by his lectures and research program and decided to write a master's thesis under his leadership. As a student, Vincent du Vigno was increasingly interested in the interaction of organic chemistry and biochemistry . He listened to the in-depth biochemistry courses of G. B. Lewis and nutritionist V. S. Rose, whose work on the study of the digestion of white rats later influenced some of the metabolism studies of du Vigno himself. He received his master's degree in 1924, and later worked for some time with Dr. Walter Carr at the Central Military Hospital in Philadelphia . In the spring of 1925, du Vigno received an invitation from Professor John R. Murlin to attend medical school at the University of Rochester to work on insulin chemistry, and he accepted this offer. In 1927, du Vigneau defended his thesis on the topic of "sulfur in insulin", receiving a Ph.D. In the last year of his stay in Rochester, he received an award from the National Research Council, which, after defending his thesis, allowed him to continue his studies with John Jacob Abel, professor of pharmacology at the medical school at J. Hopkins University . Here, in collaboration with Oscar Wintersteiner and Hans Jensen, he continued the study of insulin. Getting a second prize allowed du Vigno to go abroad. He became acquainted with peptide synthesis in the Max Bergman laboratory at the Kaiser Wilhelm Society Institute ( Dresden , Germany ), and spent some time with Professor George Barger at the University of Edinburgh ( United Kingdom ).

Having enough equipment to begin independent research, du Vigno in 1929 took up a position at the Department of Physiological Chemistry in his alma mater in Illinois. Biochemistry has become his chosen field, and he has the opportunity to have his own graduate students. In 1932, at the age of 31, du Vigneau became a professor and head of the department of biochemistry at the medical school at the University of Washington in Washington . He was sorry to leave the distinguished department in Urbana , where he spent three happy years, and such great professors like Adams, Marvel, Shnerner and Fuson — organic chemists, and Professor Roza — a biochemist, but the possibility of greater independence was decisive. Vincent du Vigno remained at George Washington University until 1938 , when he was invited to head the Department of Biochemistry at the Cornell University College of Medicine in New York , previously held by Stanley R. Benedict. In 1967, Vincent du Vigno was given an honorary status and he headed the department of chemistry at Cornell University in Ithaca .

Insulin Studies

Abel crystallized insulin in 1926 , and then Jensen, Wintersteiner and du Vigno studied the composition of crystalline hormone acid hydrolysates. Despite the rather primitive methods available at the time, the presence of cystine and other various amino acids in the hydrolyzate was established. On this basis, it was concluded that insulin is a protein . ^[4] Later du Vigno spoke on this subject: “It may now seem strange to talk about work proving the protein nature of insulin, because nowadays the fact that a hormone can be a protein, or that a protein can be a hormone, is a well-known fact however, at that time (1928) this view was reluctantly accepted. ” ^[5] The idea of ​​the time was strongly influenced by the concept of the chemical nature of the R.Villestätter enzymes ; it was believed that the enzymes consist of a small functional part - coenzyme , and protein carrier.

Studies of sulfur-containing amino acids

Many of Du Vigneau’s work on intermediate metabolism concerned the formation of cysteine ​​in animals and the metabolic relationship between methionine , cysteine, homocysteine , cystathionine and choline . He called the reactions underlying metabolic processes by transsulfurization and transmethylation . It was known that the inclusion of methionine in the diet of the cysteine-free diet of rats supported their development . Roze showed that methionine is an independent amino acid in the diet of rats. In short, the rat's organism is able to synthesize cysteine, but methionine is incapable. In 1931, processing methionine with concentrated sulfuric acid , du Vigno discovered a new sulfur-containing acid ^[6] . This compound was the senior symmetric homolog of cystine, and he called it homocystine. He later discovered that the reduced form of this amino acid, homocysteine, is an important metabolic compound. According to the observations of du Vigneau, homocysteine ​​also supports the growth of rats on a diet with a shortage of cystine ^[7] . These observations pointed to the metabolic interaction of methionine and homocysteine, a hypothesis was proposed that methionine demethylation could be the stage of cysteine ​​biosynthesis. Du Vigno synthesized L-cystathionine, in which the carbon chains of cysteine ​​and homocysteine ​​are joined by one atom of sulfur , and found that this compound also supported the growth of rats on a diet poor in cysteine. This observation suggested that the rat was able to break the thioester bond to form cysteine. Further observations, based on the study of hepatic sections in vitro , showed that cystathionine does not turn into homocysteine. Adding to the liver sections a mixture of homocysteine ​​and serine led to a 60% conversion of homocysteine ​​sulfur to cysteine, which served as serious evidence that homocysteine ​​is an intermediate in the formation of cystathionine. Du Vigno applied the new technology of introducing radioactive labels to study the conversion of methionine to cysteine. He synthesized racemic methionine, labeled in beta and gamma positions with the ¹³ C isotope and containing the ³⁴ S isotope, and fed this compound to rats. The rats were shaved before the start of the experiment, and the wool was cut after 38 days after the start of the experiment. Cystine isolated from wool contained ³⁴ S, but did not contain ¹³ C. Based on the results of this experiment, it was concluded that only sulfur, but not the carbon chain of methionine, was used in the process of cysteine biosynthesis . Therefore, the final conclusion was made that in the rat organism, the synthesis of cysteine ​​from methionine involves the stage of demethylation with the formation of homocysteine, which is further condensed with serine to form cystathionine. The latter is cut to form cysteine ​​and alfaketobutyrate (2-oxobutanoic) acid. The bottom line is that the conversion of methionine to cysteine ​​involves the transfer of methionine sulfur to serine. Thanks to du Vigno, this process is called trans-sulfurization. The scientist made the observation that choline, a compound rich in methyl groups, can act as a donor of the latter in the process of converting homocysteine ​​to methionine ^[8] . This led to the emergence of the concept of transmethylation and the concept of mobile methyl groups.

Biotin Research

Paul György asked du Vigno to help establish the chemical nature of liver biotin , which György called vitamin H. In rats fed a diet containing a large amount of raw egg proteins as a source of protein, severe dermatitis and nervous disorders developed, and they died if the conditions did not change . Certain foods , such as liver and yeast , contain a substance that can prevent and heal these disorders. Healing factor György called vitamin H (from the German word haut, meaning skin). Biotin, a yeast growth factor , was isolated from egg yolks by Kögl and Ténis. Du Vigno, György and co-workers were able to cure egg white syndrome (vitamin H deficiency) with pure Kyogl biotin, demonstrating that vitamin H and biotin are the same compound ^{[9] [10]} . Biotin was isolated from extracts of the liver and milk in the Cornell laboratories , and its chemical structure was established ^[11] . The structure established by du Vigno and the staff was confirmed by chemical synthesis in the Merck laboratories. Biotin, first discovered as a yeast growth factor, turned out to be an important vitamin in mammals .

Penicillin Research

The Second World War interrupted the work of the laboratory, and du Vigno was invited to the Military Medical Research Committee to join the scientists of the United States and England to work together on penicillin chemistry. Cornell Laboratory has made a significant contribution to the study of penicillin chemistry. Perhaps the most important result was the synthesis of micro-quantities of the antibiotic , and evidence of its identity with the natural compound ^[12] .

Hormone studies of the posterior pituitary gland

Du Vigno's work on the hormones of the posterior lobe of the pituitary gland with oxytocin and vasopressin began in 1932 and continued until 1940 , when they were interrupted by World War II, but at that time the laboratory focused on the metabolic aspects of transsulfurization and transmethylation, and du Vigno considered work on hormones the posterior lobe of the pituitary gland is their hobby . Certain results were achieved in methods of purification of hormones, mainly using methods of precipitation and electrophoresis , but some preliminary observations were most important, which suggested that oxytocin and vasopressin are cystine derivatives. During the war, new methods became available, which greatly influenced the project on the study of hormones of the posterior lobe of the pituitary. Of immediate importance was the Craig’s countercurrent distribution method, published in 1944 , and Moore’s and Stein’s column chromatography techniques for quantitative separation of amino acid mixtures of acidic protein hydrolyzate on microscales. Du Vigno returned to the study of hormones in the posterior lobe of the pituitary gland in 1947 . The qualitative composition of oxytocin was established by analysis of acid hydrolyzate by the method of Moore-Stein. The cyclical nature of the hormone was proven by oxidation with peroxomolux acid and subsequent analysis of the hydrolyzate, which showed the presence of cystine acid. The cycle was closed by the formation of a disulfide bond between two cysteine ​​residues ^[13] . The structure of oxytocin was established by the Singer method of dinitrofluorobenzene and the combination of the Edman method with the analysis of partial acid hydrolysates ^[14] . After establishing the structure, the scientist confirmed its synthesis ^[15] . Subjected to sodium reduction in liquid [ammonia] e, oxytocin was converted to an open-chain substance, oxytocein. During work on oxytocin, the structure of vasopressin was also determined in a similar way ^[16] . The structure of arginine vasopressin was very similar to oxytocin. This hormone has the same ring structure as oxytocin, but contains two amino acid substitutions. Isoleucine is replaced by phenylalanine , and leucine is replaced by arginine . Lysine vasopressin contains lysine instead of arginine. The discoveries of du Vigno associated with oxytocin and vasopressin were of fundamental importance. For the first time, it has been demonstrated that the replacement of certain amino acid residues in the sequence of a physiologically active peptide can cause significant changes in biological behavior.

Obtaining the Nobel Prize in Chemistry in 1955 "for the isolation, structural identification, and general synthesis of the cyclic peptide, oxytocin," was an absolute triumph for du Vigno. In response to a congratulatory letter, he replied that the real joy of receiving the award was the sharing of happiness with friends , especially with those with whom he traveled the research path.

Professor du Vigno's scientific career was suddenly interrupted when he suffered a stroke in 1974 . He died on December 11 , 1978 . His wife Zella passed away a year earlier. Vincent du Vigno left behind a son and a daughter , they became doctors .

In addition to his outstanding scientific achievements, Vincent du Vigno was an excellent teacher and lecturer. One of his employees , Klaus Hofmann, later recalled that the lectures of du Vigno to students were interesting and well prepared. He emphasized the importance of teaching and said that teaching is more important than research. It was a real pleasure to listen to his presentations, which were also carefully prepared and rehearsed as his scientific articles. His lab was surprisingly well organized. Since he was a very busy man, and not always available for consultation, he invented a system of colored stripes to communicate with him. The pink bar - to offer new ideas and new research approaches, the green bar - to report on the results of research, and, finally, a white bar signified a request for microanalysis. Most of all du Vigno loved the green stripes. He wanted every researcher in the group to give them to him every week. And he read them with great attention. Du Vigno said that when he was presented with a set of research results, he was aware of all the experiments , as he himself would take part in these studies every day. Many employees were amazed at his memory for details in every research report, even after months and years, he could recall details pertaining to the problem at hand. Now it becomes clear the role of green stripes! In the laboratory, no one was doing nothing, and hard work was the daily norm. Graduate students were supposed to spend several evenings a week in the lab, also part Sunday , and written work was often done until late at night. Professor du Vigno lived in a suburb of New York , but he rented a beautifully furnished room in the pulpit, where he spent many nights a week. There were evenings when he invited his employees to visit. Grinding a cigar , which he gracefully held between his strong fingers, du Vignot spilled soft drinks and discussed the latest research results. For du Vigno was characterized by a critical approach to laboratory results. Each possible side of the project was discussed for a long time, and new approaches and ideas that could clarify the problem were studied in depth. Articles were written along with the staff doing the work. The secretary was present during the discussion, who collected the latest version during the discussion. Before the chef was satisfied, a lot of versions were recorded. Of course, du Vigneau worked in a team and the staff highly respected him. He communicated easily with people. Every year, Vincent du Vigno invited his entire team to his home in Scarsdale for a picnic with softball and other activities. " ^[3]

Scientific degrees

• Bachelor's Degree, University of Illinois, 1923
• Masters Degree, University of Illinois, 1924
• Ph.D. (biochemistry), University of Rochester, 1927

Honorary Degrees

• PhD, New York University, 1955
• PhD, Yale University, 1955
• PhD, University of Illinois, 1960
• Doctor of Science, University of Rochester and St. Louis, 1965

Memberships

• National Academy of Sciences of the USA , 1944 ^[17]
• American Philosophical Society, 1944
• Royal Society of Upsalls, 1950
• Honorary membership in the Royal Society of Edinburgh, 1954
• Honorary membership at the Royal Institute of London, 1959

Awards and prizes

Among the awards and prizes of Vincent du Vigno:

• Hillebrand Prize, Washington Chemical Society, 1936
• Nichols Medal, New York Section, American Chemical Society, 1945
• Borden Award, Association of American Medical Colleges, 1947
• Merita Prize for Military Studies, US Government, 1948
• Lasker Prize , American Public Health Association, 1948
• Messenger lectures , 1949
• Osborne and Mendel Prize, 1954
• John Scott Prize , Philadelphia, 1954
• Chandler Prize, Columbia University, 1955
• Nobel Prize in Chemistry , 1955
• Passano Prize, Passano Foundation, 1955
• Willard Gibbs Award , Chicago Section, American Chemical Society, 1956
• Award of American College of Medicine, 1965

• The labile sulfur of insulin. Proc. Soc. Exp. Biol. Med., 24: 547-48, 1927
• Studies on crystalline insulin. Iii. Sulfur linkage. The isolation of cystine and tyrosine from hydrolyzed crystalline insulin. J. Pharmacol. Exp. Then, 32: 367-85, 1928
• Studies on crystalline insulin. Iv. The isolation of arginine, histidine and leucine. J. Pharmacol. Exp. Then, 32: 387-95, 1928
• Of dextrorotatory cystine. J. Biol. Chem., 94: 243-52, 1931
• Isolation of methionine by enzymatic hydrolysis.J. Biol. Chem., 94: 641-45, 1932
• The formation of a homologue of cystine by the decomposition of methionine with sulfuric acid. J. Biol. Chem., 99: 135-42, 1932
• It has been shown that the growth rate of homocystine is increased. J. Biol. Chem., 101: 719-26, 1933
• The synthesis of homocystine. J. Biol. Chem., 111: 393-98, 1935
• The chemistry and compounds of sulfur. Annu. Rev. Biochem., 5: 159-80, 1936
• It is a synthesis of di-N-methylhomocystine and N-methylmethionine. J. Biol. Chem., 116: 277-84, 1936
• Sulfur chemistry. Annu. Rev. Biochem., 6: 193-210, 1937
• It is a study of the hormones in the electrophoretic study of the pituitary gland. J. Biol. Chem. 123: 485-89
• Methionine-free diet. J. Biol. Chem., 28: cviii, 1939
• The effect of choline on the ability to replace methionine in the diet. J. Biol. Chem., 131: 57-76, 1939
• The biotin and coenzyme R. Science, 91: 243-45, 1940
• A further note on biotin. Science, 92: 609,1940
• Isolation of biotin (vitamin H) from liver. J. Biol. Chem., 140: 643-51, 1941
• On the structure of biotin. J. Am. Chem. Soc, 64: 188-89, 1940
• The structure of biotin. Science 96: 455-61, 1943
• Synthetic penicillin. Science 104: 431-33 1946
• Degradative studies on vasopressin and performic acid-oxidized vasopressin. J. Biol. Chem., 205: 133-43, 1953
• Natural and synthetic oxytocin. Obstet. Gynecol. 6: 254-57, 1955
• The synthesis of lysine vasopressin. J. Am. Chem. Soc, 79: 5572-75, 1957
• Experiences in the polypeptide field: Insulin to oxytocin. Ann. NY Acad. Sci., 88: 537-48, 1960
• The concept of transmethylation in mammalian metabolism and isotopic labeling through in vivo experimentation. In: Transmethylation and Methwnine Biosynthesis, ed. Shapiro and Schlenk, pp. 1–20. Chicago: University of Chicago Press, 1965
• Hormones of the mammalian posterior pituitary gland and their naturally occurring. Johns Hopkins Med. J., 124: 53-65, 1968