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Comptes RendusBiologiesChristiane Mougin, Jean Rossier and Bertrand BlochTribute to Roger Guillemin, a pioneer in neuroendocrinology (1924–2024), NobelPrize in Physiology or MedicineVolume 347 (2024), p. 53-58Online since: 27 August 2024https://doi.org/10.5802/crbiol.156This article is licensed under theCreative Commons Attribution 4.0 International License.http://creativecommons.org/licenses/by/4.0/C EN T R EMER S ENN EThe Comptes Rendus. Biologies are a member of theMersenne Center for open scientific publishingwww.centre-mersenne.org — e-ISSN : 1768-3238Comptes Rendus. Biologies2024, Vol. 347, p. 53-58https://doi.org/10.5802/crbiol.156Biographical noteTribute to Roger Guillemin, a pioneer inneuroendocrinology (1924–2024), Nobel Prize inPhysiology or MedicineChristianeMougin a, Jean Rossier ,b,c and Bertrand Bloch ,∗,da Department of Cellular Biology, University of Franche-Comté, Franceb Academy of Sciences, Institut de France, Francec Royal Academy of Medicine, Belgiumd University of Bordeaux, FranceE-mail: bertrand.bloch@u-bordeaux.fr (B. Bloch)Abstract. Roger Guillemin discovered and characterized the hypothalamic factors that control ante-rior pituitary functions. He consequently demonstrated that these brain peptides regulate a largenumber of major body activities through neuroendocrine mechanisms. This especially includegrowth, fertility and reproduction, endocrine gland functions and stress. These seminal workspaved the way to major applications in many fields of physiology and medicine for diagnosis,pharmacology and therapy, far beyond the initial discovery and properties of these molecules, includ-ing in cancerology, immunology, inflammation, drug addiction and behavior.Keywords. Neuroendocrinology, Releasing factors, Hypothalamus, Anterior pituitary, Endorphins.Manuscript received 15 May 2024, revised 5 June 2024, accepted 17 June 2024.Roger Guillemin, Nobel Prize in Physiology andMedicine in 1977, died at the age of 100 on Febru-ary 21, 2024, in San Diego (California) where he wasliving.Roger Guillemin was born in Dijon on January 11,1924. He was a student at the Carnot High School,and then began his medical studies in 1943. Hisyouth was nourished by the “Franche-Comté” rootsof his father’s family. A great-grandfather was an iron-master in Vuillafans; his father was born in Dole, andit was through this family that, as a child, teenagerand later medical student, he became very close tothe Duvernoy family in Besançon. He strongly con-tributed to the French resistance during World War II,∗Corresponding authorduring the German occupation of Besançon, withina group of smugglers founded by Doctor MauriceDuvernoy. It was from Maurice Duvernoy, director ofthe Besançon School of Medicine, that he later gothis first anatomy lessons. By a fair turn of events,Roger Guillemin’s first works inspired some of theneuroanatomical work of his son, Henri Duvernoy,on the vascularization of the hypothalamic-pituitaryarterial system.Very early on his career, Roger Guillemin becamepassionate about endocrinology. At the end of hismedical course, he met Hans Selye in Paris, a pio-neer in stress studies. Fascinated by his lecture deal-ing with the adaptation of the body to stress, RogerGuillemin left France to work with him at the Univer-sity of Montreal. His research work allowed him tofirst defend his medical thesis in Lyon, then subse-quently his PhD in 1953 in Montreal. He then startedISSN (electronic): 1768-3238 https://comptes-rendus.academie-sciences.fr/biologies/54 Christiane Mougin et al.Figure 1. Roger Guillemin at the Salk Institutein 2017 (Personal collection, Bertrand Bloch).to work for several years at Baylor University Collegeof Medicine (BUCM) in Houston (Texas).At the end of the 1940s, Geoffrey Harris, one ofthe pioneers in neuroendocrinology at Oxford Uni-versity, proposed that substances present in the hy-pothalamus could reach the pituitary gland throughthe portal vascular system, and control the releaseof pituitary hormones and consequently many bodyfunctions, including stress. From this concept, RogerGuillemin decided to isolate and characterize thesefactors and synthesize them. This work will lead himto the Nobel Prize. Between 1960 and 1963, he cameback to the Collège de France in Paris where he devel-oped his very first experiments devoted to hypothala-mic factors through innovative bioassays [1]. But ac-cording to his words, the working conditions and ad-ministrative obstacles encountered in France at thatmoment were at odds with his vision of the ambi-tious and innovative research he wanted to develop.Roger Guillemin then returned to BUCM in Hous-ton in 1963. In his laboratory, he created the mate-rial, technical, and organizational conditions neces-sary for the isolation of these molecules.He hypothesized that these factors were smallproteins (“peptides”) produced by neurons in thehypothalamus. Even though his concepts and hisfirst results were strongly criticized by part of thescientific community, he relentlessly developedinnovative strategies to isolate these substancespresent in minute quantities inside the brain. Hecollected several tons of hypothalamic fragmentsfrom millions of sheep in slaughterhouses. At theend of 1968, Roger Guillemin and his team, includ-ing his students Roger Burgus, Wylie Vale, Catherineand Jean Rivier, and Nicholas Ling, obtained 1 mg ofthe first hypothalamic peptide from 300,000 sheephypothalamus [2]. This peptide, called TRF, stimu-lates the production of thyroid hormones throughaction on the pituitary gland. Thanks to this firstpioneering discovery, neuroendocrinology became amajor field in biology and medicine. The structureof this peptide was established in 1969. Simulta-neously, his competitor Andrew Schally identifiedwith his team the same TRF from pig hypothalamicfragments.In 1970, Roger Guillemin founded and directedthe Laboratories for Neuroendocrinology at the SalkInstitute in San Diego (California), and focused hisresearch on the purification, isolation and charac-terization of the hypothalamic peptide which stim-ulates the release of hormones acting on the go-nads (Gonadotropin-releasing hormone or GnRH).He also tried to isolate the peptide that stimulatesthe production of growth hormone. It took manyyears of sometimes unexpected research results, be-cause the first peptide he discovered was an inhibit-ing substance, somatostatin. And it was a few yearslater that GRF, the peptide activating the productionof growth hormone, was unexpectedly isolated froma pancreatic tumor responsible for acromegaly [3].This last discovery had direct consequences for clin-ical medicine. The search for hypothalamic releas-ing hormone ended in early eighties with the identi-fication, by his former student Wylie Vale, of CRF, thepeptide that controls ACTH release [4].Following the discovery of enkephalins, these en-dogenous morphines, by John Hughes and HansKosterlitz in 1975, Roger Guillemin also discoveredseveral other opioid peptides, work to which one ofus (JR) contributed [5].Roger Guillemin therefore made a decisive con-tribution to the understanding of the mechanismsChristiane Mougin et al. 55Figure 2. Henri Duvernoy (left) next to the future Nobel Prize in Medicine Roger Guillemin, himself nextto his mentor Maurice Duvernoy (Personal collection, C. Mougin; gift of H. Duvernoy).Figure 3. Roger Guillemin and his team at the Salk Institute in 1983 (Personal collection, Bertrand Bloch).56 Christiane Mougin et al.Figure 4. The Salk Institute for Biological Stud-ies (Personal collection, C. Mougin).by which the brain controls the secretions of the pi-tuitary gland and the endocrine system. The con-sequences of his discoveries went quickly beyondthe scope of neuroendocrinology and are of partic-ular interest for endocrine physiology and pathology,control of fertility (contraception, medically assistedreproduction, sterility . . . ), tumor and inflammatorypathologies, regulation of mood disorders and psy-chiatry and, of course, pharmacology [6]. Theseachievements also found numerous applications inthe veterinary field, something Roger Guillemin likedto point out.His work therefore led him to the Nobel Prize inPhysiology or Medicine in 1977, that he shared withAndrew Schally and Rosalyn Yalow. Roger Guilleminalso received the highest international honors. Hewas elected as a member of the American Academyof Sciences in 1974 and as a member of the Acad-emy of Arts and Sciences in 1976; in France, he wasappointed foreign associate member of the Acad-emy of Sciences in 1984. His work has been rec-ognized by numerous other prizes and honors. Hewas “commandeur de la Légion d’honneur”. Sev-eral universities have conferred on Professor RogerGuillemin the title of Doctor Honoris Causa, in-cluding the University of Burgundy (November 4,1978) and the University of Franche-Comté (Novem-ber 20, 1998).Roger Guillemin has indeed trained and inspireddozens of students and researchers around the world.Those who knew him have been impressed by his in-genious mind combined with a sound science andwillingness, and a serenity associated with constantauthority. Each of us had the privilege to be part of histeam in the late 1970s and early 1980s, like several re-searchers from France, in this science paradise that isthe Salk Institute. His laboratory was a hive of worldcitizens, where young researchers and skilled scien-tists of all origins were interacting. Roger Guillemin’sscientific demands went together with a generosityand benevolence that permanently stimulated cre-ativity. Roger Guillemin was fully committed to pro-moting a science without ideological or geographi-cal borders; he has been involved on numerous occa-sions with many other researchers in promoting thishumanist vision of science, open to the world andanchored in the needs of our societies. This is evi-denced by the numerous personal relationships es-tablished with colleagues from all over the world, in-cluding in France, throughout his life. Among manyexamples, let’s remind his deep ties of friendship andscience with Professor Etienne Emile Baulieu, inven-tor and promoter of RU486, the molecule for safe ter-mination of early pregnancy. Well beyond scientificdiscoveries and borders, his personal influence al-lowed each of his students and collaborators to cre-ate unwavering friendships and to promote his spiritand his values.Roger Guillemin was also an elegant esthete, avery distinguished oenologist, an artist and a loverof innovative art. He painted on screen using hiscomputer and basic softwares. No one knows whatpainter he would have become if he had not decidedto devote himself completely to science.He explained that the process leading to the cre-ation of each of his “computer paintings”, as hecalled them, was not very different from the intel-lectual process of research carried out in the labo-ratory about a scientific fact or a concept. How-ever, according to him, there is a major difference be-tween the approach of a scientist and that of an artist:Christiane Mougin et al. 57Figure 5. Hypothalamic neurons producing peptides (Immunohistochemical detection) (DocumentsBertrand Bloch).Figure 6. Roger Guillemin during the “Hon-oris causa” ceremony at the University ofFranche-Comté with Henry Duvernoy (on hisleft), Bertrand Bloch and Christiane Mougin(on his right) (Personal collection, ChristianeMougin).“There are rules and laws from which the scientistcannot escape: the laws of gravity, the fact that sucha DNA sequence encodes such a protein and not an-other, that gold melts at such and such a tempera-ture and not another, etc., while the rule for the con-temporary artist is precisely that there are no rules. Itis probably a higher level of what neuroscience andcognitive sciences call qualia.” His sculptures andpottery of pre-Columbian origin from Mexico, Van-uatu and New Guinea, his relationships with numer-ous artists, including Nikki de Saint Phalle, illustratehis refined interest for art. His six children reflect thispassion for art: a son who is a sculptor in Prince-ton, a daughter who is a gallery owner, another adancer . . . and his late wife Lucienne Guillemin, a tal-ented pianist, and accomplished painter, deceasedin 2021 at the age of 100. With his family, RogerGuillemin always enjoyed being on his farm in anoutstanding natural site, in Truchas, New Mexico,far from any urbanization; this haven of peace hasconstantly been a specific location for him to thinkand work.58 Christiane Mougin et al.Figure 7. Computer painting exhibit fromRoger Guillemin in Milano (1991) (Personal col-lection, Bertrand Bloch).Declaration of interestsThe authors do not work for, advise, own shares in, orreceive funds from any organization that could bene-fit from this article, and have declared no affiliationsother than their research organizations.References[1] R. Courrier, A. Colonge, E. Sakiz, R. Guillemin, M. Jutisz, “Pres-ence in a saline extract of hypothalamus of an rsh type follicle-stimulating activity”, C. R. Hebd. Seances Acad. Sci. 257 (1963),p. 1206-1210, [Article in French].[2] R. Burgus, T. F. Dunn, D. Desiderio, R. Guillemin, “Molecularstructure of the hypothalamic hypophysiotropic TRF factor ofovine origin: mass spectrometry demonstration of the PCA-His-Pro-NH2 sequence”, C. R. Acad. Hebd. Seances Acad. Sci.D 269 (1969), p. 1870-1873, [Article in French].[3] R. Guillemin, P. Brazeau, P. Böhlen, F. Esch, N. Ling, W. B.Wehrenberg, B. Bloch, C. Mougin, F. Zeytin, A. Baird, “Soma-tocrinin, the growth hormone releasing factor”, Recent Prog.Horm. Res. 40 (1984), p. 233-299.[4] R. Guillemin, “Neuroendocrinology: a short historical review”,Ann. N. Y. Acad. Sci. 1220 (2011), p. 1-5.[5] J. Rossier, Q. Pittman, F. Bloom, R. Guillemin, “Distribution ofopioid peptides in the pituitary: a new hypothalamic-pars ner-vosa enkephalinergic pathway”, Fed. Proc. 39 (1980), p. 2555-2560.[6] R. Guillemin, “Neuroendocrine basis of human disease”, Ann.N. Y. Acad. Sci. 1038 (2004), p. 131-137.

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