The word sulphur may give rise to rather disparate sensations; to most people it has not a very pleasing ring. Also many chemists are inclined to keep their distance; they know that organic sulphur compounds may infect the atmosphere around wood pulp mills and that they form part of the chemical weapon of the common skunk. In spite of that, the element sulphur is of vital importance, and it has many functions in the living organism.
Professor du Vigneaud once defined true exploratory research as "the working out of a winding trail into the unknown". He himself has followed the trail of sulphur in metabolism.
The story starts in the nineteen-twenties with insulin, a substance whose importance is now well-known. As to its chemical nature, it is a protein with a remarkably high percentage of sulphur. The proteins are built up from so-called amino acids, and their sulphur is due to the presence of one or two sulphur-containing amino acids: cystine and methionine. Considering the special properties of insulin, one could perhaps expect to find its sulphur in quite a new combination, but it turned out that it was present in cystine. The result may seem to be of little significance, but the trail pointed in a definite direction; the sulphur-containing amino acids must be more closely investigated.
It would lead too far to give an account of Professor du Vigneaud's numerous works on cystine, methionine, and related compounds. They led, inter alia, to the discovery of the biological importance of the methyl group and of its migrations in the organism. I must also leave aside the distinguished works on biotin, also known as vitamin H, and coenzyme R, and the important contributions to the chemistry of penicillin.
Underneath the brain, there is a small, well-protected gland, the pituitary gland. In man it is about as big as a bean. There are secreted several hormones, that is, substances which regulate important physiological functions. spite of its small size, the pituitary gland is made up of several distinct parts with different functions. We are interested here in the posterior lobe, which contains two substances called oxytocin and vasopressin. The former stimulates the contractions of the uterus and also the lactation, the latter raises the blood pressure and regulates the function of the kidneys. As early as in 1933, when rather impure preparations from the posterior lobe were used in experiments, du Vigneaud found a high percentage of sulphur, which seemed to be correlated to the physiological activity.
Using the experimental methods, which the development of science has put at his disposal and making the best of his own intimate knowledge of the organic chemistry of sulphur, du Vigneaud has step by step forced his way. Both hormones were isolated in a state of purity, and it was found that they are built up from amino acids in the same way as proteins, but with a far lower molecular weight. Such compounds are, as distinguished from real proteins, called polypeptides. The nature of the amino acids and their positions in the molecule could be determined. The sulphur is present in cystine. The two hormones have a very similar structure; both contain eight amino acids, connected to a chain, which at one point is closed to a ring. The molecule has some resemblance to a figure six or nine, where the loop contains five amino acids and the "tail" three. Two sulphur atoms, linked to each other, form a part of the ring.
The design of the molecule was thus known. It remained to build it up by synthesis and check the correctness of the design. That was perhaps the most difficult part of the work. The interest was first concentrated on the synthesis of oxytocin. Step by step the amino-acid chain was built up with the two sulphur atoms in the proper positions, one at the end of the chain and the other near the middle. At last the ring was closed by formation of a bond between the sulphur atoms. Now followed the most thrilling moment, the testing of the chemical properties and the physiological activity; perhaps there had been some mistake after all. It turned out, however, that the synthetic polypeptide was identical with the natural product.
A biologically important substance of complicated structure had been investigated and synthesized with eminent skill. However, more important still are the far-reaching consequences of this achievement. It is the first synthesis of a polypeptide hormone. It also shows, that such substances with very important physiological properties may be built up from well-known amino acids according to well-known principles. The eight amino acids must, however, be combined in a special sequence; it may not be out of place to draw attention to the principle of the combination lock. The result may also be of importance for revealing the secrets of the real proteins.
Vincent du Vigneaud's speech at the Nobel Banquet in Stockholm, December 10, 1955
Your Majesties, Your Royal Highnesses, Your Excellencies, Ladies and Gentlemen:
I wish to express to you my deep appreciation for the honor that you have bestowed upon me by the Nobel Award. This honor is without question the most signal honor that could come to a chemist. I am deeply grateful to the Nobel Foundation and the Royal Swedish Academy of Science for the recognition, as expressed in the terms of the citation, of the "work on biochemically important sulfur compounds, especially the first synthesis of a polypeptide hormone". This hormone, oxytocin, the principal uterine-contracting and milk-ejecting hormone of the posterior pituitary gland, is a sulfur-containing compound, and its synthesis was the culmination of many experiences along a trail of research stemming from my original interest in sulfur and in insulin. It was truly a trail of "sulfur research".
I have had the privilege and the thrill of following this trail of research in the company of a group of graduate students and postdoctoral associates, without whose loyal and effective collaboration the advances along this trail could not have come to pass, and in the acceptance of this high honor, I wish to make due acknowledgment to this splendid collaboration.
Finally, allow me again to thank you, not only for the award, but for your gracious hospitality to both Mrs. Du Vigneaud and myself. We are very happy to be here.
Vincent du Vigneaud was born in Chicago, Illinois, on 18th May, 1901, the son of the late inventor and machine designer Alfred J. du Vigneaud and his wife, Mary Theresa. He studied under Professor C.S. Marvel at The University of Illinois and took his B.Sc. degree in 1923 and M.Sc. in 1924.
During the year 1924-1925 he was assistant biochemist to Dr. W.G. Farr at the Philadelphia General Hospital and served on the Staff of the Graduate School of Medicine of Pennsylvania University. In 1927 he worked with Professor J.R. Murlin and submitted a thesis to the School of Medicine of Rochester University which earned him the Ph.D. As a Fellow of the National Research Council he worked with Professor J.J. Abel at Johns Hopkins University Medical School, with Professor George Barger at Edinburgh University Medical School and with Professor Charles R. Harington at London University College Hospital.
On his return to America, du Vigneaud joined the Physiological Chemical Staff at The University of Illinois under Professor W.C. Rose and in 1932 he became Head of the Biochemistry Department at the George Washington University School of Medicine. The Cornell University Medical College offered him a Professorship as Head of the Biochemistry Department in 1938.
Du Vigneaud has held many lectureships in universities in the United States and England, among the latter the Liversidge Lectureship at Cambridge, and in the summer of 1947 he was Visiting Lecturer of the American Swiss Foundation for Scientific Exchange in Switzerland. His Messenger Lectures at Cornell University in 1950 were published in 1952 as A Trail of Research in Sulphur Chemistry and Metaholism and Related Fields. Many learned chemical societies in America have conferred awards on du Vigneaud and he received the Chandler Medal of Columbia University in 1955 and the Willard Gibbs Medal of the American Chemical Society a year later. Honorary science doctorates were bestowed on him by New York and Yale Universities in 1955, and by The University of Illinois at Urbana-Champaign in 1960.
Honorary fellowships have been conferred on du Vigneaud by the Royal Society of Edinburgh, the Chemical Society and the Royal Institute of Chemistry, London. He has been elected to membership of many scientific academies among the most noteworthy being the Board of Trustees of the Rockefeller Institute and the National Institute of Arthritis and Metabolic Diseases.
His researches have centred mainly about sulphur-containing compounds of biochemical importance, being concerned originally with the sulphur of insulin and more recently with two hormones of the posterior pituitary gland-oxytocin and vasopressin. He has also studied intermediary metabolism, amino acids and peptides, transmethylation and metabolism of onecarbon compounds, transsulphuration, biotin and penicillin.
Du Vigneaud married Zella Zon Ford in 1924; they have a son, Vincent, Jr. (b. 1933) and a daughter, Marilyn Ren?e (b. 1935).
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