Étienne-Émile Baulieu (1929–2025): Scientist of steroids and champion of women’s reproductive rights

Abstract

Having trained as a physician, Étienne-Émile Baulieu soon turned his focus to research, as early as his medical internship. He went on to make major contributions on ketosteroids and other steroids, such as estrogen, and how they act on target organs through receptors to which the hormones bind and activate physiological responses. Later, he consulted with a French pharmaceutical company, encouraging them to pursue his concept for an antigestational agent, which became the iconic RU-486 (Mifepristone). For this, he was applauded by many and criticized by others. He died at his home in a suburb of Paris on May 30, 2025, at the age of 98. To his last days, he vigorously maintained his support for women’s reproductive rights.

Baulieu was born Étienne Baum on December 12, 1926, to Jewish parents in Strasbourg, France. His mother was an attorney and pianist, and his father was a nephrologist. Later, his mother moved the family to Paris and then Grenoble as the war loomed. Étienne took the name Étienne-Émile Baulieu when he joined the Communist Party before college. He received a medical degree from the Faculté de Médicine, Paris, followed by an internship during which he undertook his first research project (the identification of a steroid). He then obtained a Ph.D. in 1963 at the Faculté des Sciences, Paris, and was appointed immediately thereafter as director of the INSERM. In 1970, he joined the Faculté de Médicine de Bicêtre in Kremlin, outside of Paris, where he spent his entire research career.

Étienne-Émile Baulieu. Image credit: Collège de France/Jean-Pierre Martin (photographer).

The field of steroid hormone biology, like any scientific discipline, had many tributaries. There were those who achieved isolation and chemical definition, of whom Tadeus Reichstein in Basel and Edward Kendall at the Mayo Clinic were important figures in the modern era. As to steroid action and clinical applications, there is Phillip Hench, also at Mayo, as a vivid example. Reichstein, Kendall, and Hench shared the 1950 Nobel Prize in Physiology or Medicine, the latter two suiting up for Stockholm only 18 months after their breakthrough discovery that Kendall’s “compound E” (i.e., cortisone) effected a clinically significant alleviation of rheumatoid arthritis.

Étienne-Émile Baulieu stands with these giants and many others in the pantheon, but in a somewhat different way. He had medical training yet did not pursue a clinical career as a diagnosing/treating endocrinologist. Nor was he a chemist. Rather, he was best defined as a biochemist and physiologist of steroid hormones. His initial independent work (1950s) was on adrenocorticotropic hormone and others in an array of physiological processes and pathological situations, with a comparable number in both categories, his previous clinical orientation clearly evident. In the 1960s and 1970s, his laboratory transitioned to the interactions of steroid hormones with cells and tissues, a more molecular focus, as this topic was sweeping across the field in many quarters. His most important contributions at this time were studies of the binding of estrogen to uterine proteins and the identification of testosterone-binding proteins in plasma. From this work, he was among the first to deploy the term “hormone receptor.” A point of historical interest is that Baulieu had, for a short time, entertained the idea that steroids exert their effects by binding to DNA (an idea to which others in the field also transiently succumbed). But once he had envisioned (and demonstrated) receptors for steroids, he focused on how these complexes, not the free steroids, are the agents. During a sabbatical at the Salk Institute, he collaborated with Suzanne Bourgeois to define a new dimension of this, namely that a glucocorticoid antagonist influences the binding of the hormone and its receptor to DNA (1).

In 1962, Baulieu experienced what he would later describe as the most transformative event of his career. At this time, he had become keenly interested in the steroid dehydroepiandrosterone (DHEA) and contacted Seymour Leiberman at Columbia University’s College of Physicians and Surgeons. Leiberman was then a world master of this and related steroids (2). Years later, Baulieu told me that when he was visiting Leiberman’s lab, he had been contacted by Gregory Pincus, at the Worcester Foundation for Experimental Biology, in Shrewsbury, Massachusetts. Earlier, Pincus and Min-Chueh Chang at the Foundation discovered the first female oral contraceptive (“the Pill”). This epochal phone call does not rest solely on my recollection of the conversation with Baulieu. Leon Speroff, Pincus’ biographer (3), conducted an interview with Baulieu about this, and it is worth repeating here as it conveys Baulieu’s demeanor.

• Speroff: When did you first meet Pincus?

• Baulieu: It was 1962. Seymour Lieberman was interested in DHEA- had me to come (sic). In one day there, Pincus called, and I remember vividly that Lieberman came to me. He said something like, “The great Pincus wants to speak to you. He wants you to come.”

• He was so famous that I was afraid of him. He invited me to go to the Worcester Foundation, and I brought my family there.

• He asked me: when I returned to France, instead of going straight to France, to pass along to Puerto Rico and see the clinic. So I did that, two or three days. So it went very well (4). (The “clinic” refers to the one Pincus et al. had set up, after the initial field trials there and the Pill’s approval by the US Food and Drug Administration, to continue studying the Pill’s use, efficacy, and side effects.)

This encounter with Pincus likely accelerated Baulieu’s interest in hormone-mediated female contraception, though it was more likely a case of “a prepared mind.” Ironically, Baulieu’s subsequent work and publications do not have a theme or even a thread of contraception. Even a decade later, he had published only two articles in which this idea was floated, and these were not in a prominent journal.

As his research on hormone receptors moved forward into the 1980s, he acquired a compound from the French pharmaceutical company Roussel-Uclaf and used it, simply as a reagent, in several studies that revealed its agonistic action on glucocorticoid and progesterone/progestin receptors; these studies involved cultured fibroblasts, rat ovary tissue, and nonhuman primates (5–8). This research and his idea that the compound, named RU-486, might have a use in the control of conception led the company to bring it out, as Mifepristone. It became a way for women who so choose to interrupt a conception and brought both accolades and criticism to Baulieu. He coined the term “antigestational” to describe its action, preventing the fertilized ovum from attaching to the uterine wall, the event that triggers the physiological condition of pregnancy. Detractors claimed he was playing with words, even as some of these same opponents also opposed barrier contraception. The question of when life begins was not something on which Baulieu focused. He, of course, knew the Judaic doctrine, viz. that life begins at “quickening” (16 to 20 weeks). But in his writings, lectures, and our conversations, he was not religiously centered on this issue. His constant theme was simple and deeply held, the reproductive rights of women.

Baulieu was honored by many awards and elections, including election to the US National Academy of Sciences, receipt of the Gregory Pincus Memorial Medal of the Worcester Foundation for Experimental Biology, and induction into the Collège de France in 1974. In his induction lecture, he recounted having walked by this august citadel when he was a medical student nearby and also mentioned “sneaking in” to hear some lectures.

Étienne-Émile Baulieu created a way for women to control gestation and later became an ardent spokesperson for women’s reproductive choice overall, as well as a champion for engaging the public on the importance of science, not just endocrinology and reproductive biology but science qua science. I had the privilege of knowing him for the last quarter of his life and witnessed how engaged he remained in his final decade. We shall not see his likes anytime soon.