Roger Guillemin (1924 to 2024): Discoverer of brain hormones that control physiology

Roger Guillemin, widely recognized as the father of Neu roendocrinology, passed away on February 21, 2024, in La Jolla, California.He had still been able to celebrate his 100th birthday a few weeks earlier in the joyous presence of his family, friends, and many ex-colleagues.His copious scientific contributions, which led to numerous prizes and awards, culminating in the Nobel Prize for Physiology or Medicine in 1977, had opened the way, not only to a new understanding of the mechanisms that control the function of the anterior pituitary gland but also to the development of novel treatments for sex-steroiddependent cancers, endometriosis, precocious puberty, and pancreatic tumors.Born in Dijon (France) on January 11, 1924, Guillemin had developed a keen interest in biology and physiology early on, but at the time, the only way to study these fields was to go to medical school.He therefore obtained his medical degree in 1949 from the University of Lyon, but quickly found the practice of medicine too restrictive.While in Paris, Guillemin attended a seminar given by Hans Selye, the physician who had observed that regardless of their specific illness, hospitalized patients all displayed the same set of "nonspecific" symptoms.Guillemin became fasci nated by this concept of "stress" and followed Selye to the University of Montreal in Canada, where he obtained a PhD in experimental endocrinology in 1953.Corticosteroids had just been discovered as a major player in our body's response to stress, but for Guillemin, it was their antiinflammatory properties that turned out to be literally life saving.He had contracted tubercular meningitis at a time when few treatments were available, so Selye decided to try an untested experimental approach to save his stu dent's life: injection of these steroids into the spinal fluid.This worked so well, that having recovered, Guillemin was able to marry his nurse!A marriage that lasted 67 years and produced six children.While in Canada, Guillemin had encountered the British scientist Geoffrey Harris who promoted the then-revolutionary hypothesis that the anterior pituitary was regulated by "humoral" signals transported from the hypothalamus through blood vessels-one of the two portal systems of the human body.This went against the more generally accepted concept that this control was neuronal, and at that time, passionate battles raged between the two camps.However, experimental demonstration that hormonal compounds manufactured by the hypothalamus could reach the anterior pituitary through the portal vessel system as hypothesized by Harris, remained extraordinarily difficult.After leaving Selye's laboratory, Guillemin was recruited to Baylor College of Medicine in Houston, Texas, where he remained until 1970.Once at Baylor, Guillemin decided to join the "humoral" vs. "neural" battle and, in order to provide support for Harris's hypothesis, he tried another approach.In the mid-1950s, he designed a highly original experiment, that while simple in concept, represented a very difficult and novel strategy: He cocultured hypothalamic and pituitary cells and noticed that when the two types of tissues remained in close contact, hypo thalamic cells produced a substance which stimulated adren ocorticotropic hormone (ACTH) release by the pituitary cells.However, when the two cell populations were subsequently separated, ACTH release stopped.Guillemin concluded, cor rectly, that the hypothalamus produced signals that were humoral, and not neuronal, as they could act on pituitary cells

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