Roger Guillemin, a Nobel Prize-winning physician whose work on hormones produced by the brain helped lead to the development of the birth control pill and treatments for prostate and other cancers, and who engaged for decades in a famously scathing but productive scientific rivalry, died Feb. 21 at a senior-living facility in Del Mar, Calif. He was 100.
His daughter Chantal Guillemin confirmed the death but did not know the specific cause.
Dr. Guillemin, a founder of the field of research known as neuroendocrinology, was born in France and settled in the United States after World War II. He spent his formative professional years conducting painstaking experiments in search of minute quantities of brain secretions, “neurohormones” so elusive many scientists doubted they existed.
Dr. Guillemin was affiliated with the Salk Institute in San Diego when he shared the 1977 Nobel Prize in physiology or medicine with Rosalyn Sussman Yalow and Andrew V. Schally — the latter a onetime collaborator turned scientific arch-adversary.
A 1981 book by New York Times science journalist Nicholas Wade detailed their 21-year battle, which the polished Dr. Guillemin described as “competition in a good sense” and the rougher-edged Schally called “many years of vicious attacks and bitter retaliation.”
In violation of scientific practice, the men concealed data from each other and refused to share samples. They mocked each other’s errors onstage at conventions. Both were reluctant to share credit for their discoveries — with each other, as well as with laboratory co-workers.
At the Nobel ceremony, Wade recounted in his book, the tuxedoed Dr. Guillemin and Schally “looked like men going to their execution.” In winning the prize together, he observed, “they were denied the victory that each also craved, the final triumph over the other.”
In fact, all three laureates were pivotal to the development of neuroendocrinology, which developed in the mid-20th century from a hypothesis that the brain releases chemical signals — hormones — into the bloodstream to control the pituitary gland, the master regulator that controls the various endocrine organs of the body. Usually, the brain sends signals through the electrical impulses and the release of neurotransmitters between cells.
This revolutionary idea challenged the prevailing scientific view of the brain as the seat of higher thought and emotion, and not as a run-of-the-mill endocrine gland.
“It is justifiable to say that they have uncovered a substantial part of the link between body and soul,” the eminent endocrinologist Rolf Luft said of Dr. Guillemin and Schally, citing their work on protein hormones during the Nobel presentation. (Luft also credited Yalow for vital groundwork in a related but different area of research.)
Proving that neurohormones existed was a difficult technical challenge. The substances were produced in the brain structure known as the hypothalamus, tucked away near the base of the skull. The brain made them in such small quantities that they couldn’t be measured in the blood circulating through the body.
The hormones could be detected only within the tiny net of capillaries surrounding the hypothalamus, itself “incredibly small,” said Gary Hammer, director of the endocrine oncology program at the University of Michigan’s Comprehensive Cancer Center.
“It was a herculean task,” Hammer said.
Dr. Guillemin belonged to a small group of researchers who devoted themselves fanatically to the pursuit. After seven years of grueling and sometimes gruesome work with animal brains, Dr. Guillemin failed to discover the first target of his search, a hormone known as corticotropin-releasing factor that was involved in the body’s reaction to stress. Schally, incidentally, also couldn’t find the substance.
It took another seven years, and 270,000 sheep hypothalami, for Dr. Guillemin in 1969 to isolate one milligram of thyrotropin-releasing hormone, which directs the pituitary gland to control the thyroid gland. He would go on to find other hormones, including gonadotropin-releasing hormone, which tells the pituitary to send commands to the ovaries and testes.
His discoveries had an impact on many fields of medicine, Hammer said, because understanding how the endocrine system worked helped researchers develop treatments for a number of endocrine-related disorders.
Isolating and analyzing gonadotropin-releasing hormone, for instance, sped along scientists’ understanding of the hormonal control of the menstrual cycle, and ultimately the development of birth control pills and of hormonal therapies for prostate cancer.
Somatostatin, another hormone found by Dr. Guillemin, is the basis for the nausea drug Zofran, and has also been instrumental in the development of therapies that inhibit the growth of neuroendocrine pancreatic and other hormone-responsive tumors.
Roger Charles Louis Guillemin was born in Dijon, France, on Jan. 11, 1924. His father was a toolmaker. After graduating from the University of Dijon in 1942, he started medical school at the University of Lyon, interrupting his studies to join the French underground’s efforts to move refugees to Switzerland during World War II.
He received a medical degree in 1949 and then pursued a PhD at the University of Montreal. In 1950, he almost died after a bout with tubercular meningitis; the following year, he married his nurse, Lucienne Billard. His wife died in 2021, also at 100. In addition to Chantal, survivors include five other children, François, Claire, Hélène, Elisabeth and Cece; four grandchildren; and two great-grandsons.
After completing his PhD in 1953, Dr. Guillemin joined the faculty at the Baylor University College of Medicine in Houston, where he taught physiology and searched for the neurohormones, for a time working alongside Schally, who departed the institution in 1962. In 1970, Dr. Guillemin moved to the Salk Institute — lured by a phone call from virologist Jonas Salk and the glorious ocean views, he said.
He remained there for the majority of his career, discovering the hormone somatostatin, which acts on the pituitary gland to suppress growth hormones, and also investigating endorphins, chemicals in the brain that act as natural opiates.
He retired from active research in 1989 but served as interim president of the Salk Institute from 2007 to 2009.
Dr. Guillemin and Schally shared half of the Nobel Prize. The remaining half was awarded to Yalow for the development of radioimmunoassays, which detect substances in the body that exist in very small quantities.
While perhaps unseemly, Dr. Guillemin’s conflict with Schally might have been key to their success, Wade suggested, because it motivated the scientists to persist through a long and difficult — and ultimately very important — search.
“Science is best done in teams where different expertise is coming to the table,” Hammer said. Dr. Guillemin “was a master of that. He brought physiologists and chemists and molecular biologists and later cell biologists all together to crack the nut.”
