Roger Guillemin, a neuroscientist who was a co-discoverer of the unexpected hormones with which the brain controls many bodily functions, died on Wednesday at a senior living facility in San Diego. He was 100.
His death was confirmed by his daughter Chantal.
Dr. Guillemin’s career was marked by two spectacular competitions that ruffled the staid world of endocrinological research. The first was a 10-year tussle with his former partner, Andrew V. Schally, which ended in a draw when the two shared half of the Nobel Prize in Physiology or Medicine in 1977. (The other half went to the American medical physicist Rosalyn Yalow for unrelated research.)
The second competition began shortly afterward when Wylie Vale Jr., Dr. Guillemin’s longtime collaborator and protégé, set up a rival laboratory on the same campus at the Salk Institute for Biological Studies in San Diego, where both men worked, plunging Dr. Guillemin yet another period of intense scientific struggle.
Roger Charles Louis Guillemin (pronounced, with a hard g, GEE-eh-mah) might have pursued a quiet career as a family doctor in the French city of Dijon, the Burgundy region’s capital, where he was born on Jan. 11, 1924, and where he went to public schools and then medical school. But a chance meeting with Hans Selye, an expert on the body’s reaction to stress, took him to Montreal, where he was introduced to medical research at Dr. Selye’s newly created Institute of Experimental Medicine and Surgery at the University of Montreal.
There he became interested in a leading problem of the day — that of how the brain controls the pituitary gland, the maestro organ that cues production of the body’s other major glands.
The pituitary sits in a small pocket of bone just under a central brain region called the hypothalamus. No one could find any nerves linking the hypothalamus to the pituitary, so a fallback conjecture was that the hypothalamus might control the pituitary with hormones. But many biologists refused to believe that the brain might produce hormones like a mere gland.
The postulated hormones were called releasing factors, because they arguably made the pituitary release its own hormones.
In 1954, Dr. Guillemin made a critical observation: Pituitary cells cultured in glassware would not produce any hormones unless cells of the hypothalamus were cultured with them. The finding supported the idea of releasing factors, and Dr. Guillemin was determined to prove it. He moved to Baylor College of Medicine in Houston, where he tried to isolate the postulated releasing factors from the hypothalami of cattle killed in a kosher slaughterhouse.
Success eluded him, and in 1957 he teamed up with another young researcher, Andrzej V. Schally, known as Andrew. The two worked together for five years, but the mysterious releasing factors foiled their best efforts. The partnership broke up. Dr. Schally moved to the Veterans Affairs Hospital in New Orleans. Dr. Guillemin eventually hired two key researchers at Baylor — Dr. Vale as a physiologist and Roger Burgus as a chemist — who were to be the mainstays of his efforts for the next 10 years.
Working independently, Dr. Guillemin and Dr. Schally both decided that they needed much larger numbers of hypothalami in order to extract sufficient amounts of releasing factor. Each turned his laboratory into a semi-industrial processing plant, aided by liberal government research funds that were made available after the Soviet Union launched the Sputnik, the first artificial space satellite, in 1957. Dr. Guillemin eventually processed more than two million sheep hypothalami, and Dr. Schally worked on the same scale with pig brains.
The rivalry between the two teams was intense, especially in matters of scientific credit. “Let me also remind you,” Dr. Schally wrote to Dr. Guillemin in a letter in 1969, “of your deliberate, repeated and personal scientific attacks against me as well as your constant failure to recognize our contributions.”
Dr. Schally later told an interviewer, “An equal partner I could be with him, but he wanted me to be his slave.”
The releasing factors exist in such minute amounts in the brain that they were barely detectable by the techniques of the day. A single fingerprint left on glassware contained enough amino acids — the components of releasing factors — to ruin a whole experiment. After a further seven years of effort, neither Dr. Guillemin nor Dr. Schally had isolated a releasing factor. Other researchers said that the government, which had been funding the two men’s work for years, should cease wasting its money. There was more evidence for the Loch Ness monster, they said.
In 1969, the committee of scientists that advised the National Institutes of Health on endocrinology research convened a meeting to prepare for cutting off support to the two laboratories. But a few days before the meeting, Dr. Burgus made a significant advance toward identifying the chemical structure of the releasing factor that controls the thyroid gland via the pituitary. Within a few months, the Schally and the Guillemin teams had fully identified the releasing factor, known as TRF, and the funding cutoff was averted.
A race now began to find a second releasing factor, FRF, which controlled the body’s reproductive systems. Dr. Schally’s team was narrowly first, but Dr. Guillemin then recouped by discovering a releasing factor involved in control of the body’s growth.
Dr. Guillemin succeeded because he had identified a critical problem that he and Dr. Schally had pursued against daunting odds while better known researchers had failed. Identification of the releasing factors was a major event in medicine, and the Nobel committee in Stockholm duly awarded its prize for the achievement.
Dr. Guillemin had little time to rest on his laurels. His research team had become disenchanted with his relentless search for scientific glory. Dr. Vale later complained of “what hell it can sometimes be for people who get caught up in the meat grinder, churning out more and more gloire for Guillemin, especially if you are the meat.”
Dr. Vale set up his own laboratory at the Salk Institute in 1977 (Dr. Guillemin had established one there in 1970), and endocrinologists were treated to the spectacle of yet another furious rivalry, this time between Dr. Guillemin and his protégé. They competed to find the releasing factors known as CRF, which is involved in stress, and GRF, which spurs growth. Both succeeded, though Dr. Vale’s lab was first in each case.
Dr. Guillemin in 1951 married Lucienne Jeanne Billard, who had been his nurse during an almost fatal attack of tubercular meningitis in Montreal. In addition to his daughter Chantal, he is survived by four other daughters, Claire, Hélène, Elisabeth and Cece; a son, François; and four grandchildren. His wife died in 2021, also at 100.
Dr. Guillemin and Dr. Vale later reconciled and became close friends. In a tribute at Dr. Vale’s 65th birthday, Dr. Guillemin, well aware of the irony of competing with his “scientific son,” quoted Freud’s analysis of the Oedipus myth: “Part of any son worth his salt is planning the killing of the father he loves and taking his kingdom.”
Kellina Moore contributed reporting.
