Interview with Vincent du Vigneaud - ACS Publications

Interview with. Vincent du Vigneaud by Robert A. Plane terested in those aspects of organic chemistry that had to do with medicinal substances and beg...
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VINCENT DU VIGNEAL Cornell University hhaca. New York 14850

Interview with Vincent du Vigneaud by Robert A. Plane

ROBERT A. PLANE Cornell University Ithaca. New York 14850

Plane:

Professor du Vigneaud, what do you recail as your first exposure to science? do Vigneaud: It so happened that when i was a freshman at Carl Schurz High School in Chicago I had two friends who had a smail chemical laboratory. They invited me to join them. There was a pharmacist who suppfled us with chemicals and we did all kinds of experiments together, much of it on explosives involving sulfur. This actively took place even before I had anv chemistrv in hioh schooi. We were also interested in the collection of insects and taxidermy. i'm sure that aii this influenced my choice of career it was our interest in taxidermy that put an end to this laboratory when we tackled the mountin0 of a oreat bin black cat. The mother of one of my "coworkers", closed the operation when she 'bot wind of it". The laboratory was in her basementi Plane: Were there family associations that proved important in your choice of career? du Vigneaud: My eider sister Beatrice always encouraged me through schooi and urged me to go-on to coiieie after graduation in 19 18. Worid War I was underway andpeopie were needed to work on farms. Seniors in high schooi were offered the opportunity of going out and working on farms in Aprii and then getting their diplomas in June. i went to a farm near Caiedonia, Ilflnois, near the Wisconsin border, and worked through the spring and summer it was while I was there that my sister Beatrice came up to see me, and we discussed what i was going to do after this farm experience. You know. i almost decided to go into farming! I even learned to milk 20 cows by hand. Actuaily it was my sister who suggested the possibility of going to the University of iilinois at Urbana-Champaign to study chemistry. Plane: Professor du Vigneaud, what are your recollections concerning your undergraduate days at the University of I/#nois? du Vigneaud: When I first went down there I registered in Chemical Engineering, but i found during the first year that it was chemistry rather than engineering that appealed to me most. I switched to a major in chemistry since I was deepiy impressed by the upper division students' work, especially in organic chemistry. iaiso found that i was most in-

terested in those aspects of organic chemistry that had to do with medicinal substances and began to develop an interest in biochemistry. At my first opportunity i took a b b chemistry course. One of the most important things that happened to me at the University of iliinois was meeting a certain young lady, Zelia Zon Ford, who had come to Urbana from Southern iilinois Normal at Carbondale in her third year. She was an Engiish major, but as we became further acquainted, and with an eye to the future, I saw to it that she took courses in mathematics and chemistry. Aithough she graduated as an Engiish major she had sufficient chemistry so that later, after we were married, she taught chemistry.

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Plane:

You did your senior and master theses both with Professor C. S. Marvel What influenced this choice? du Vigneaud. Carl Shipp Marvel was known as "Speed around the Department. He gave tremendous lectures. i was verv much impressed byhim. i decided I wouid iike to do m i senior thesis with him. ii so happened that Marvel was interested, among many other problems, in the relationship of structure to biologicalactivity. The problem i worked on with him was to synthesize a compound combining in the same molecule the pressor activity of epinephrine along with the local anesthetic activity of procaine, thus affording a possible substitute for cocaine for medicinal purposes. in going on for my M.S. degree. I decided to continue with him. I thoroughly enjoyed working under his direction. Tell us about your course in biochemistrv. .. since it seems to figure with great importance in your later career. du Vigneaud: i had become interested in the relation of organic chemistry to biochemistry. i took my first course in b b chemistry as an undergraduate under Professor H B. Lewis in 1921. Later i had an advanced course in intermediary Metabolism and one in Ciinical Chemistry with Professor W C. Rose, who succeeded Lewis when the latter went to the University of Michigan. Both were very inspiring teachers. Professor Lewis was particularly interested Piane:

in sulfur-containing compounds, particularly cystine and cysteine. Undoubtedly, this influenced my interests through the years in sulfur biochemistry. 1recail the thriil of listening to Professor Rose in 1923 talk on the subject of insulin-the work of Banting and Best-nd the curiosity that was aroused in me as to the chemical nature of this compound that could bring about the miracuious results he descrlbed At that time, it was not known that insulin was a sulfur-containingcompound. Plane: How did you finance your undergraduate days, as well as your Master's work at the University of Illinois, Professor du Vigneaud? du Vigneaud: Well. Iwas really on my own except for some help from Beatrice my sister whom Imentioned earlier. Iarrived at Urbana with money ihad saved from five months work on the farm and a loan of $100. From then on, Ihad to earn the entire amounts needed for tuition. fiving expenses, etc., and Idld ail kinds of jobs. Iworked tearing down boilers, pickedapples, mrked at the library, jerked sodas. But the job that helped me most financially through most of the years, including the MS year was as a head waiter. The other most remunerativep b turned out to be teaching cavalry tactics and equitation as a Reserve 2nd Lieutenant in the Cavalry. Plane: Was the teachingyou did of equitation your first teaching? du Vigneaud: Yes, it was. h the cavalry tactics courses, Ihad to lecture and conduct quizzes, and so forth, and learned much about dealing with students. Also. the experience of directing a group of some 15 waiters and dishwashers later was valuable in dealing with groups. There were occasional violent disagreements between the miters and dishwashers. i decided-/ don't know how Ilearned this at this early stage-that If they knew one another better, and could talk to one another calmly, that they would get on better. Ihaw used this same technique of bringing together people that were battling each other so that they could just talk calmly to one another in a variety of situations since, such as school boards as well as facu8y meetings. Plane: Where did your career lead you next, following the completion of your M.S. degree at the Universityof iliinois h February 19247 duVigneaud: After first trying to locate something in the pharmaceutical industry, iaccepted a position with DuPont and work& inan anawicai laboratmy at the Deep Water Point Laboratories across the river from Wiimingfon. lt was in Wilmingfon that Zelia and I were married on June 12, 1924, thus celebrating our 50th anniversary in 1974. Plane: At that time, did you have any thoughts of returning to the university for a doctorate degree, either a PhD or an MD? du Vigneaudr Yes, indeed! From the very start. iplanned to go on with graduate work towards a PhD afler working for a while, and, in fact, discussed this with Professor Marvel before Ileft {enjoyed the work at the DuPont Laboratories, but through the help of Dr. Marvel Iaccepted a position with the Philadelphia General Hospital under Dr. Walter G. Kan in the Fall of 1924. There was an opportunity to do research as weli as gain experience in ciinical chemistry. ialso had the opportunity of teaching In the Graduate School of Medicine at the University of PennsyL vania under Dr. Stoner. There was also the possibility of doing graduate work while at the Phiiadelphla General Hospital with Professor Wilson in the Department of Biochemistry of the Medical School. h the Spring of 1925. 1 received a letter from Professor Murlin inviting me to visit the School of Medicine of the Universityof Rochester. He was interestedin havinga c h e h t @inhim as a graduate student and research assistant to work on the chemistry of insulin in his Department of Vital Economics. Professor Lewis at the University of Michigan and Professors Marvel and Rose at Illinois were hstrumental in this change since they knew of my desire to continue with graduate work. I

accepted MurNn's invitation and was deeply Impressed by the tvDe .. of man Professor Murlin was, and the ODDOrtunhv .. of doing graduate work under his direction in his Department of Vital Economics. The chance to work on the chemistry of insulin transcended ali other interests and I accepted Professor Murh's invitation. FTcfessor Mwlin had had an intensive program underway on this pancreatic hormone for several years on the University campus before the Vital Economics Department was moved to the Medical School. He had independentlypreparedactive extracts at the time of the more wldely publicized announcement of Pantingand Best. Plane: Imust plead Ignorance, perhaps you had better tell us what is "vital economics" and how did it fit into the medical program? du Vigneaud: In 1925. Rochester was just opening its new medical school. The funds for estabfishing the new school were made available by the General Education Board of The Rockefeller Foundationand bv G w r m Eastman The new students took their first courses in biochemistry andphysioioav -. in their first vear. Thev were scheduled to take the course in "&I economics" the second year under Professor John R. Murlin. This was a muniouroose course in. . cludng nutrition, intermediary metabolism. energy metaboiism. physiology and biochemistry of the gastrointestinal tract and endocrinology. ihope it is now obvious what the term "vital economics" meant. The term realiy is an excellent choice to indicate the "economy of thebody': Unfortunately, many people thought of it as "economics". Plane: This might be a gwd time to discuss the development of biochemistry during this critical period in its history. 1take il that at the University of Ubnois, biochemistry was an integrai part of the Chemistry Department. h Rochester, it was part of the Medical College. Were there any other methods of organization of biochemistry and which was most prevalent during the twenties. du Vigneaud: At that time it was very rare for departments of chemistry to actually have divisions of biochemistry or physiological chemistry, as it was often called back then. The development of biochemistry in the U.S. occurred mainly in medicai schools and in schools of aqvicuitwe. ~ h e were i a few other places that had biochemistry in chemistry departments. At lliinois it receivedpartioular attention. Imight say that in my estimation no chemist is really completely trained unless he has had some biochemistry. Planer On the other slde of that coin, do you feel it was important to your career and your later successes that you were trained in molecular structure and its application to biological problems, rather than the inverse which probably would have been the case had vou come through . a medical phys!ologrcal chemistry department9 du Vroneaud Idon't thmk mere 1s any doubf but what thm background that Ihad, particular;; in organic chemistry at Uiinois, Playeda role in all of my subsequent work-and still does. On the other hand. the experiences that ihadat The University of Rochester School of Medicine, teaching medical students how to cannulate blood vessels and doing other physiologicalexperiments, has also played a role as well. The experiences Ilater had at The Johns Hopkins University Medical School with Professor Abel in pharmcoiogy were iikewise important to my later work. I can't shess too strongly the importance of my research with Dr. Marvel on the relationship of structure to biological activity. Plane: In the Medical School environment at Rochester, did you miss contacts with chemical coileagues? du Vigneaud: Professor Morlin, although keenly interested in the chemical attacks on bloiogica&oble&, was a physiologist, not a chemist. h view of this, he saw to it that Iwas provided with ample opportunity of talking over the more chemical aspects of my researches with two outstanding

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organic chemists. He arranged to have me mest his friends. Or. h'ans Clarke, then wtYh Eastman Kodak and later Professor of Biochemistry at the College of Physicians and Surgeons of Columbia University, and Dr. Ralph Helmcamp, Professor of Organic Chemistry at the University of Rochester. We had many wonderful sessions together on insuiin and various aspects of sulfur chemistry. lt was the beginning of lifelong friendships with these men. How did your interests in insulin develop during your period as a graduate student at Rochester? du Vigreaud: There was no insulin available at the beginning of my work. I had to prepare tha insulin myself from pancreases obtained from a slaughterhouse, no mean undertaking. Later I was abla to obtain extracts from Eli Lilly and Compew. There had been some suspicions by various workers that insulin might possibly be a sulfurcontaining c o m pound. All of my preparations that I made always contained sulfur, and they also contained protein. I became more and more interested in the nature of the sulfur and really, the question of the &ntity of the sulfur moiety, if it were in the insulin molecula, became one of para&unt importance to me. The interest that had been aroused in me in sulfur chemistry back in 1921 by Pmfessor Lewis at Illinois made this logical and intriguing. This then became my main research interest at Rochester. The title of my thesis was "The Sulfur of Insulin". The suspicion that ins* lin might be a sulfur-containing compoundgrew into a defk nite possibility as a result of the work of Professor Abel and Dr. Oeifino in 1925 at The Johns Houkins Universitv ~ c aSchGl. l They found that the am& of sulfur easi Iv split out by weak alkafi ~aralleledthe activity of certain .&norphous >reparations and that when the~sulfurwas split out, the activity was destroyed. These findings led them to raise a question concerning the etiology of diabetes mellitus: to quote. "To what extent, if any, the Islets of Langerhans are dependent upon the presence in our food of a special labile sulfur compound, a precursor indispensable for the elaboration of the hormone, in the absence of an adequate supply of which, pathological alterations in the cells of the Islets of Langerhans would take place." In our own work, we were able to obtain evidence that ins* lin contained cystine, and that the labile sulfur of insulin could be accounted for on the basis of the presence of cystine and not a shange sulfur compound. Although the sulfur of cystine was stable to weak alkali, the sulfur of cystine peptldes, such as dialanylcystine as Pointed out bv . . Brand Sandburg, was quite labile to weak alkali. Thi high degree of lability of insulin sulfur did not necessarily indicati that the sulfor was not cystine sulfur. 1found that when the labile sulfur was spUt out of the insulin by treatment with dilute alkali, the colormetric test for cystine in insulin hydroiysates by the highly specific Sullivan method was greatly reduced in intensity and furthermore, the sulfur in the acid-hydrolysatesof insulin became stable to dlute alkali, fike that of free cystine. This change in lability upon hydrolysis was idsntical with what would be expected of peptides of cystine. Thus, we came to the conclusion that the sulfur present was present as the disulfide linkage, and that insulin was most likely a derivative of cystine. We suggested that the cystine in insulin was linked wlth the rest of the molecules by pept& finkages. In this work at Rochester, we were also able to confirm Dr. Abel's crystallkation of insulin that he announced in 1926, and found that the crystalline insulin possessed the behavior just discussed. This thesis work was pubfished in the ~ovemberissue of the Journal of Biological Chemistry in 1927.

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Plane:

Next. you worked with Professor A M . What is your assessment of or. Abel's impact on biochemistry? . . . and on Pharmacology?

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du Vigneaud: hrring my last year at Rochester, I applled for a Mational Research Council Fellowship. This I was fortunate h receiving and it enabled me to work with Professor John Jacob Abel, Professor of Pharmacology at The Johns Hopkins University Medical School. Professor Abel was one of the leaders in the field of pharmacobgy and in particular, in the field of the endocrines. One may recall that at the beginning of the century, Dr. Abel worked on epk nephrine and later on various other hormones, including the Posterior ~ltuitaryhormones. I've alreadv mentioned his iontributio" to the labile sulfur of insufin and also that he crystallired insulin in 1926. When I came to his laboratory h the Fall of 1927, Professor Abel had turned away from the study of insulin, and had gone back to his earlier stmlbs on the posterior pituitary h m n e s . He was delighted to have me carry on the work on the chemistry of insulin in his laboratory. He gave me every encouragement and help that he could. We succeeded h crystallizing insulin on quite a large scale by various procedures. One of the first things I wanted to do was to isolate crystalline cystine from cfystalline insulin. This, we accom plished. Then, in other work, in collaboration with Oscar Wintersteiner and Hans Jensen, we tackled other aspects of the chemistry of insulin. lt was ourpint work that led to the establishment of insulin as a wotein. lt is almost unbelievable lwking back how d i f f i i h it was to convince the field as a whole that insulin was a Wotein or. to .out it the other way around, that a protein could be a hormone. This was also the period when J. B. Sumner was finding it so difficult to get chemists and biologists to accept the fact that en enzyme could be a protein. It is of historical interest that Professor Abel isolated crystalline insulin in November. 1925, end submined his manuscript to the Procsedings of the National Academy of Sciences in February, 1926. This was really the first isolation of a protein of biological or pharmacologicalactivity in crystalline form. Professor Sumner isolated crystalfine urease in April, 1926 and submitted his manuscript to the Journal of Biological Chemistry in June, 1926. lt took quite a while for Sumner to convince the field that his crvstalline protein uresse was the enzyme. Of course, Professor Sumner's work was recognized with a Nobal Prize. Was Pmfessor Abel's work so rewarded? du Vigneaud: You may recall that lt was not until 1946 that Professor James B. Sumner received the Nobel Prize. This was awam'ed jointly to him, to Or. John H. Northrop and to Or. Wendeli M. Stanlay for their isolation in crystalline form of biologically active proteins. Unforlunately. Professor Abel had passed on by that time. If he had been living, 1don't think there's any doubt that he would have shared in this prim for the isolation of the first crystalfine protein hormone, insulin. It is a pfiy that this isolation of crystalfine insulin was not recognized by the Nobel Prize to Professor Abel while he was still living. In fact, I recall an episode in the Fall of 1927 when Professor Abel invned all of our group in the Department of Pharmacology to his home for an affernoon. During the course of this gathering, Mr... Abel took us up to the second floor to show us the array of medals that Pmfessor Abel had received. Then, some youngster asked Mrs. Abel, "Where is the Nobel Medal?" I could tell that she was verysurprisedand, as both Mrs. du Vigneaud and I recall. showed great disappointment in that he did not have that medal. This impressed us and I can recall driving back to Baltimore from the suburbs where they were livhq and taikinq with my wife that this orobablv . ran. resentedi reflection-of Profissor Abel's own disappointment. This made a very strong on both of us .imDression . and I remember (Mrs. du Vigneaud could verify this) that I said, "Zella, I am expecting to stay in the research field in the academic worM. but I want to tell you I wiX never work Plane:

towards any prlze." And then I recall saying, "I refuse to let my reward rest in the hands of any committee." The reward is in the accomplishment and I am sure that this was Professor A b e h reai philosophy, alfhough everyone enjoys receiving recognition for his work. Plane: After your Johns Hopkins experience, you want abroad, did you not? du Vigneaud: Yes, indsed. lapplied for an extension of the Fellowship--for another year and to go with Professor Max Bergmann at the Kaiser Wilhalm institute in Dresden, Gsrmany. Out of my insulin interest, I wanted to work on the synthesis of peptides and so I chose io go with Max Bergmann. I was the first American student to work with him. In the following Spring, that wouid be in 1929, 1went from Dresden to Edinburgh to work for a short time with Professor George Barger who was Professor of Medicnal Cham istry at the University of Edinbw&. i a h spent a while with his student, Charles Harrington (later Sir Charles). Plane: From Britain, how did you find a permanent position back in this country? du Vigneaud: Weli. at Enburgh, I must say 1became very anxious as to what the future might hoM. Here i was w,Yh a wife and no job, and as many postdoctorals find, it's not too easy to arrange for a position back home. However, within a two-week periw: I'd had fa) an offer from Professor Murlin at Rochester. (b) one from Professor Abel at Johns Hopkins in the Department of Pharmacology, (c) a position at the University of Pennsylvania, and (d) one in New York in clinical chemistry. In addition, there came a cable from Professor Rose and Roger A d a m offering me a position at the University of llllnois in the Department of Physioiogicai Chemistry with Professor Rose. By that time. I knew that I wanted to be a biochemist, and i fen that the opportunity of doing teaching in biochemistry and research with the o p p m u n v of having graduate studsnts was what i really wanted. I was delighted to accept the illinois offer. alfhough this OfFer was one-half the salary of the highest paying position. Plane: How long were you at the University of lilinois, and what lnduced you to leave? du Vigneaud: I was three years at the University of Illinois, and indeed was very, very happy there, but I was offered a Professorship in Biochemistry in the Medical School of The George Washington University, Waslington, D.C. This appeared to me to be very attractive, to have my own department, to be a Professor, and in 1932 1 accepted the offer. it was with some reluctance that I left Urbana for this was a wonderful department with Roger Adams. Marvel, Shriner, and Fuson in organic chemistry, and Professor Rose in biochemistiy i was able to take along with mr, three of my graduate students at Iliinois, Hubert Loring, Robert Seaiock, and Robert Sifferd, and Jessie Harman who had just received his Ph.D. with Roger Adams, to help get underway our researches and institute a new teaching program in biochemistry at The George Washington Universiiy School of Medicine. At Illinois, I had continued my work on the chemistry of insulin; and particularly, on the cystine of insulin. 1 had aiso become interested in the metabolic aspects of amino acids and worked on glutathione. on the isomers of cystine, on carnoshe and a variety of other biochemical compounds. h fact, it was there thet we made the discovery that homocystine, which we had isolated through the chemical decomposition of methionine by sulfuric acid, couid replace cystine in the dbt. it was aiso there in coliaboration with L. F. Audrieth and Hubert Loring that we found that we couM reduce cystine to cysteine with sw'ium in //quid ammonia and aiso that the sulfhydryl group in liquid ammonia could be benzylated with benryichloride. All of these probims were continued in Washington and il was there we iniliafed our studies on the hormones of the posterior pituitary gland in 1932. Our interest in this Droblem arose from our studies on insulin.

While at The George Washington University, your work re. ceived its first official recognition, in terms of an award from the Chemlcal Society Washlngton, did it not? du Vignead: Yes. this was the first award that i received. it was made in 1937 for our work on "The chemistry of biologically significant sulfur compounds, and especially for the synthesis of glutathione." Plane: How long were you at George Washington? du Vigneaud: i was there From 1932 to 1938, and was invited to come to Cornell University Medical College h New York City as Professor of Biochemistry, and Head of the Da partment of Biochemistry, succeeding Professor Stanley R. Benedict. When I came to Cornell Medical College. I brought along five members of my research group, Mitdred Cohn, George Irving, Theodore Loring. Gail Miller, and John L. Wood. As in the transfer from Illinois to George WaMngton. I thus had continuity, p o p k with whom I had already been working. This I regard as very important when moving from one pla.ce to another. Just as in transplanting a tree with some of the soil around 8, if possible it is well to move a man with some of his envimnment. At Comeil, we continued our studies on insulin, the work on the posterior pituitary hormones, work on vitamin f f (which we later identified as biotin and established b structure). We also continued our work on the mechanism of the conversion of methionine to cystine (transuifuration) in tha animal body. n was while working on that problem that we encountered the metabolk relations hi^ of choline and honwcystine in replacing methionine, which in turn led to our concept of transmethylation, that is, the transfer in the body of a methyl group in toto by direct transfer and not by oxidation reduction, or so forth. hrring WorM War I we worked on antAvesicants in 1941 and 1942, and had an extensive program on the chemistry of penicillin during 1944 and 1945. Plane: At Corneil Medical, your work continued to receive various awards, including the Nichols Medal in 1945, the Oibbs Medal which was announced in 1955 and awarded in 1956, and the Nobel Prize in 1955. WouM you quote the citation for the Impact readers? du Vigneaud: The citation of the Nobel A ward reads. "For his work on biochemically important sulhxcontaining compounds, especially for the first synthesis of a polypeptide hormone." You will notice that the wording of the Nobel A ward is awfully close to that of the woding of the A ward from The Chemical Society of Washington almost twenty years earlier. In fact, the methods that we used for the synthesis of glutathione, particularly with the protection of sulfur with a benzyl group and its removal at the end of a .. series of reactions with scdium and liquid ammonia were the very basis of our strategic approach to the synthesis of this first polypeptide hormone mentioned in the Nobel Award, and that of course was oxytocin. Plane: Professor du Vigneaud, you toid us earlier of your feefings towards workin0 for awards, but in your vkw how imDortant is the exisfence of awards and irlzes to the progress of science? du Vigneaud: i do believe that it really is important not to work towards a prize, but to do the things that you really get a kick out of and do what you'd like to do. But there is no denying that a wards and prizes play a role in the develop ment of any discipline by the recognifion of contributions that have been made. There is no getting away from it, that it is a real thrill to have your work recognized by your peers and you're lucky if it can happen in your lifetime. Plane: What factors were most important in aiding your research career? du Vigmud: I have had the privilege and the t M of following those researches that I've wanted to do. I've always had the p M g e of working on wimt I've wanted to work on. i have been accompanied in the various stages of these exploratory researches by a group of fine and loyal assoPlane:

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ciates. I've also been fottunate through the years in the generous research support I've received from h e Rocke. feiier Foundation end also, on an academic basis, from VarSws companies, particularly from Eb Liily and Company, the migy Chemical Corporation, the Lederle Laboratories Division of the American Cyanamid Company, and Parke Davis and Company. i have also received generous suppMt from the Heart and Lung institute of the National institutes of Heath since 1954. The Universities where i have been also contributed to my researches in no smali way. For aii of this support lam truly grateful. Plane: What are you doing now? do N4neaM: On November 11. 1964. I acceoted an invitation from Professor ~ a r o t d ~cheiaga(the" Chairman of the Department of Chemistry at Corneii Universw in itheca) to continue my research program as Professor of Chemistry in the Department of Chemistry. Come11 University after achieving emeritus status which wouM occur in 1967 at Corneil University Medical College. Here at lthaca we have continued our interests in the relationship of chemical structure to the pharmacological activities of oxyiocin and vasopressin, the hormones of the posterior pituitary gland. ihave also had the use o f a laboratory for the study of the pharmacological activities of our analogs of the hormones.

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In your present position in the Corneil Chemistry Department.. v w are full time at research end not doino - anv , teaching. Throughouf your career you have been active in teaching4id you enjoy the teaching?

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du VigneaM: Yes, ihave always gotten a thrill out of teaching. The fact of the matter is i can say that as a professor ialways regarded teaching as my first responsibility. i have often said I looked upon my research as a hobby. There is much advantage in this viewpoint. Some people raise their eyebrows at this statement. But then I tell them the story of the visiting psychiatrist who was visiting a mental hospital and the resident psychiatrist was showing him around the institution. They stopped in front of a room and looked through the door. There was a chap riding around and around the room on a broomstick. The visiting psychiatrist, in trying to bring about some rapport with the patient said. "My, that's a wonderful horse you have there." The chap continued around the room and as he came by the door, he kwked at the psychiatrist and said, "Horse, hell, this is a hobby horse! Ifit wasn't, i couldget off it." Plane: Your hobby horse, which served as the "Trail of Research" for your whole career should serve as a modei for others in its carefuiplanning, in ifs motion between chemistrydepartments. medical colleges, phamcology, analytical chemistry iabs; wherever your interests took you, you were there. Were there any points during the career when you were tempted to take anotherpath? du Vignead: Wet of course, there were temptations from time to time. There were certain industrial offers which really were very attractive. There were other Professorships that I was offered, but when it came down to it, i ahvays made the decision with my wife as to where we thought we wouid be the happiest.