CR Biologies

Christiane Mougin

Jean Rossier

Bertrand Bloch

Comptes Rendus
Biologies
Christiane Mougin, Jean Rossier and Bertrand Bloch
Tribute to Roger Guillemin, a pioneer in neuroendocrinology (1924–2024), Nobel
Prize in Physiology or Medicine
Volume 347 (2024), p. 53-58
Online since: 27 August 2024
https://doi.org/10.5802/crbiol.156
This article is licensed under the
Creative Commons Attribution 4.0 International License.
http://creativecommons.org/licenses/by/4.0/
C EN T R E
MER S ENN E
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Comptes Rendus. Biologies
2024, Vol. 347, p. 53-58
https://doi.org/10.5802/crbiol.156
Biographical note
Tribute to Roger Guillemin, a pioneer in
neuroendocrinology (1924–2024), Nobel Prize in
Physiology or Medicine
ChristianeMougin a, Jean Rossier ,b,c and Bertrand Bloch ,∗,d
a Department of Cellular Biology, University of Franche-Comté, France
b Academy of Sciences, Institut de France, France
c Royal Academy of Medicine, Belgium
d University of Bordeaux, France
E-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 large
number of major body activities through neuroendocrine mechanisms. This especially include
growth, fertility and reproduction, endocrine gland functions and stress. These seminal works
paved 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 and
Medicine in 1977, died at the age of 100 on Febru-
ary 21, 2024, in San Diego (California) where he was
living.
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. His
youth was nourished by the “Franche-Comté” roots
of his father’s family. A great-grandfather was an iron-
master in Vuillafans; his father was born in Dole, and
it was through this family that, as a child, teenager
and later medical student, he became very close to
the Duvernoy family in Besançon. He strongly con-
tributed to the French resistance during World War II,
∗Corresponding author
during the German occupation of Besançon, within
a group of smugglers founded by Doctor Maurice
Duvernoy. It was from Maurice Duvernoy, director of
the Besançon School of Medicine, that he later got
his first anatomy lessons. By a fair turn of events,
Roger Guillemin’s first works inspired some of the
neuroanatomical work of his son, Henri Duvernoy,
on the vascularization of the hypothalamic-pituitary
arterial system.
Very early on his career, Roger Guillemin became
passionate about endocrinology. At the end of his
medical 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, Roger
Guillemin left France to work with him at the Univer-
sity of Montreal. His research work allowed him to
first defend his medical thesis in Lyon, then subse-
quently his PhD in 1953 in Montreal. He then started
ISSN (electronic): 1768-3238 https://comptes-rendus.academie-sciences.fr/biologies/
54 Christiane Mougin et al.
Figure 1. Roger Guillemin at the Salk Institute
in 2017 (Personal collection, Bertrand Bloch).
to work for several years at Baylor University College
of Medicine (BUCM) in Houston (Texas).
At the end of the 1940s, Geoffrey Harris, one of
the pioneers in neuroendocrinology at Oxford Uni-
versity, proposed that substances present in the hy-
pothalamus could reach the pituitary gland through
the portal vascular system, and control the release
of pituitary hormones and consequently many body
functions, including stress. From this concept, Roger
Guillemin decided to isolate and characterize these
factors and synthesize them. This work will lead him
to the Nobel Prize. Between 1960 and 1963, he came
back 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 that
moment 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 small
proteins (“peptides”) produced by neurons in the
hypothalamus. Even though his concepts and his
first results were strongly criticized by part of the
scientific community, he relentlessly developed
innovative strategies to isolate these substances
present in minute quantities inside the brain. He
collected several tons of hypothalamic fragments
from millions of sheep in slaughterhouses. At the
end of 1968, Roger Guillemin and his team, includ-
ing his students Roger Burgus, Wylie Vale, Catherine
and Jean Rivier, and Nicholas Ling, obtained 1 mg of
the first hypothalamic peptide from 300,000 sheep
hypothalamus [2]. This peptide, called TRF, stimu-
lates the production of thyroid hormones through
action on the pituitary gland. Thanks to this first
pioneering discovery, neuroendocrinology became a
major field in biology and medicine. The structure
of this peptide was established in 1969. Simulta-
neously, his competitor Andrew Schally identified
with his team the same TRF from pig hypothalamic
fragments.
In 1970, Roger Guillemin founded and directed
the Laboratories for Neuroendocrinology at the Salk
Institute in San Diego (California), and focused his
research 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 stimulates
the production of growth hormone. It took many
years of sometimes unexpected research results, be-
cause the first peptide he discovered was an inhibit-
ing substance, somatostatin. And it was a few years
later that GRF, the peptide activating the production
of growth hormone, was unexpectedly isolated from
a 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, the
peptide that controls ACTH release [4].
Following the discovery of enkephalins, these en-
dogenous morphines, by John Hughes and Hans
Kosterlitz in 1975, Roger Guillemin also discovered
several other opioid peptides, work to which one of
us (JR) contributed [5].
Roger Guillemin therefore made a decisive con-
tribution to the understanding of the mechanisms
Christiane Mougin et al. 55
Figure 2. Henri Duvernoy (left) next to the future Nobel Prize in Medicine Roger Guillemin, himself next
to 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 beyond
the scope of neuroendocrinology and are of partic-
ular interest for endocrine physiology and pathology,
control of fertility (contraception, medically assisted
reproduction, sterility . . . ), tumor and inflammatory
pathologies, regulation of mood disorders and psy-
chiatry and, of course, pharmacology [6]. These
achievements also found numerous applications in
the veterinary field, something Roger Guillemin liked
to point out.
His work therefore led him to the Nobel Prize in
Physiology or Medicine in 1977, that he shared with
Andrew Schally and Rosalyn Yalow. Roger Guillemin
also received the highest international honors. He
was elected as a member of the American Academy
of Sciences in 1974 and as a member of the Acad-
emy of Arts and Sciences in 1976; in France, he was
appointed foreign associate member of the Acad-
emy of Sciences in 1984. His work has been rec-
ognized by numerous other prizes and honors. He
was “commandeur de la Légion d’honneur”. Sev-
eral universities have conferred on Professor Roger
Guillemin 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 inspired
dozens of students and researchers around the world.
Those who knew him have been impressed by his in-
genious mind combined with a sound science and
willingness, and a serenity associated with constant
authority. Each of us had the privilege to be part of his
team in the late 1970s and early 1980s, like several re-
searchers from France, in this science paradise that is
the Salk Institute. His laboratory was a hive of world
citizens, where young researchers and skilled scien-
tists of all origins were interacting. Roger Guillemin’s
scientific demands went together with a generosity
and 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 this
humanist vision of science, open to the world and
anchored 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 many
examples, let’s remind his deep ties of friendship and
science with Professor Etienne Emile Baulieu, inven-
tor and promoter of RU486, the molecule for safe ter-
mination of early pregnancy. Well beyond scientific
discoveries and borders, his personal influence al-
lowed each of his students and collaborators to cre-
ate unwavering friendships and to promote his spirit
and his values.
Roger Guillemin was also an elegant esthete, a
very distinguished oenologist, an artist and a lover
of innovative art. He painted on screen using his
computer and basic softwares. No one knows what
painter he would have become if he had not decided
to devote himself completely to science.
He explained that the process leading to the cre-
ation of each of his “computer paintings”, as he
called 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. 57
Figure 5. Hypothalamic neurons producing peptides (Immunohistochemical detection) (Documents
Bertrand Bloch).
Figure 6. Roger Guillemin during the “Hon-
oris causa” ceremony at the University of
Franche-Comté with Henry Duvernoy (on his
left), Bertrand Bloch and Christiane Mougin
(on his right) (Personal collection, Christiane
Mougin).
“There are rules and laws from which the scientist
cannot escape: the laws of gravity, the fact that such
a 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. It
is probably a higher level of what neuroscience and
cognitive sciences call qualia.” His sculptures and
pottery of pre-Columbian origin from Mexico, Van-
uatu and New Guinea, his relationships with numer-
ous artists, including Nikki de Saint Phalle, illustrate
his refined interest for art. His six children reflect this
passion for art: a son who is a sculptor in Prince-
ton, a daughter who is a gallery owner, another a
dancer . . . and his late wife Lucienne Guillemin, a tal-
ented pianist, and accomplished painter, deceased
in 2021 at the age of 100. With his family, Roger
Guillemin always enjoyed being on his farm in an
outstanding natural site, in Truchas, New Mexico,
far from any urbanization; this haven of peace has
constantly been a specific location for him to think
and work.
58 Christiane Mougin et al.
Figure 7. Computer painting exhibit from
Roger Guillemin in Milano (1991) (Personal col-
lection, Bertrand Bloch).
Declaration of interests
The authors do not work for, advise, own shares in, or
receive funds from any organization that could bene-
fit from this article, and have declared no affiliations
other 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, “Molecular
structure of the hypothalamic hypophysiotropic TRF factor of
ovine 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 of
opioid 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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