Historical profile. In the late 1960s, a physiologist at Brandeis University named Susan Leeman was hunting for a hormone she never managed to isolate. She was trying to purify corticotropin-releasing factor, the brain signal involved in initiating the body’s hormonal stress response, from bovine hypothalamus. What she found instead made the test rats salivate. That accident led her and her colleagues to isolate substance P, an eleven-amino-acid peptide whose biological activity had been known since the 1930s but whose chemical identity remained unresolved.
Substance P would become one of the most studied signaling molecules in neuroscience, with roles in pain transmission, inflammation and nausea. Decades later, blocking one of its receptors became a way to prevent chemotherapy-induced nausea and vomiting. Leeman also helped discover neurotensin, another important signaling peptide. She died on January 20, 2026, at 95, leaving a career that changed neuroendocrinology even as she spent much of it fighting for a secure place in science.
A Career Built Against the Grain
Leeman was born in Chicago on May 9, 1930, and grew up in Bethlehem, Pennsylvania, the daughter of Jewish immigrants from Russia. According to a 2016 profile in Goucher College’s magazine, she graduated from Goucher in 1951 with a degree in physiology, then earned a master’s degree in 1954 and a doctorate in physiology in 1958 from Radcliffe College, through a graduate program taught at Harvard.
She was one of four women among thirteen students in her graduate program and, according to the Goucher account, the only woman in that group who continued into scientific research. Before her qualifying examinations, two physiology professors told her that educating women in science was largely pointless because they would probably leave the field. It was the sort of advice that could close a career before it started.
Leeman continued anyway. She joined Brandeis University in 1959 and built a research program around the body’s hormonal control systems. She was particularly interested in corticotropin-releasing factor, or CRF, a signal from the hypothalamus that stimulates a hormonal cascade involving the pituitary and adrenal glands.
In an autobiographical chapter published by the Society for Neuroscience, Leeman described years of professional uncertainty. At Brandeis, she recalled being told that she could remain if she secured her own research funding, but that the department chair would oppose her tenure. Later, at Harvard Medical School, she continued to face difficulty obtaining a secure academic appointment.
She returned to Harvard Medical School in 1972. In 1980, the University of Massachusetts Medical School offered her a full professorship. Boston University appointed her professor in 1992, and she became director of its neuropeptide laboratory.
The unusual part of her scientific story is that her most important work began when the experiment did something she had not planned.
The Fraction That Made Rats Drool
At Brandeis, Leeman and graduate student Richard Hammerschlag were studying extracts of bovine hypothalamus. They separated the material by chromatography, collecting fractions that could then be tested for biological activity. Their original goal was to find CRF by measuring changes in adrenal steroid levels in rats after exposure to the extracts.
Leeman made an experimental choice that proved important. Rather than testing only the prominent protein peaks emerging from the chromatography column, she insisted on examining material across the entire separation. That included fractions which might otherwise have been overlooked.
One pooled fraction produced an unexpected reaction. After it was injected into the test animals, Leeman noticed that fluid appeared in their mouths. In her autobiography, she remembered that “fluid welled up in the mouths of the test animals.”
She suspected it was saliva. If so, the extract contained something capable of stimulating salivary secretion, a property that was not the response she had been looking for in her stress-hormone experiments.
She went looking for a stress hormone. The unexpected salivation response pointed her toward a different peptide entirely.
Leeman changed the direction of the project. Working with graduate student Michael Chang, she pursued the saliva-inducing activity through further purification. Their work eventually led them to substance P, a biological activity first described by Ulf von Euler and John Gaddum in 1931. The name had survived for decades, even though the active molecule had proved difficult to isolate and chemically define.
On September 25, 1970, Chang and Leeman published their isolation of a sialogogic peptide from bovine hypothalamic tissue in the Journal of Biological Chemistry, identifying the purified material as substance P.
The decisive chemical description followed on July 21, 1971. Chang, Leeman and Hugh Niall published the amino-acid sequence of substance P in Nature New Biology. A companion paper described its chemical synthesis. The peptide was now known to contain eleven amino acids, with a defined molecular structure that other laboratories could reproduce.
That changed what researchers could do with it. A chemically identified peptide could be synthesized, tested at controlled doses, used to produce antibodies and tracked in tissue. Scientists could move beyond detecting an unidentified biological activity and start investigating the molecule responsible.
A Second Peptide Hiding in the Same Extract
The salivation response was not the only interesting activity in Leeman’s hypothalamic extracts. During the purification work, she also observed a separate activity affecting blood vessels. It could be distinguished from the substance P fraction, suggesting another biologically active molecule was present.
Her graduate student Robert Carraway took on the task of isolating it. On October 10, 1973, Carraway and Leeman published the isolation of a new hypotensive peptide from bovine hypothalamus in the Journal of Biological Chemistry. They called it neurotensin, a name referring to its nervous-system origin and its blood-pressure-lowering activity.
Its chemical characterization continued beyond that first report. In March 1975, Carraway and Leeman published neurotensin’s complete amino-acid sequence, establishing it as a thirteen-residue peptide. A companion paper described its synthesis.
The distinction between the two discoveries matters. Substance P was already known as a biological activity before Leeman’s laboratory purified and chemically defined it. Neurotensin was a newly identified peptide. Both came from the same broader investigation of hypothalamic extracts, and both helped establish peptides as important chemical messengers in the nervous system.
One research program turned a decades-old mystery into a defined molecule and revealed another peptide that science had not previously recognized.
Leeman’s discoveries belonged to a wider transformation in neuroscience. The brain was increasingly understood not only through electrical activity and conventional neurotransmitters, but through chemically diverse messengers that could act within and beyond the nervous system.
Other laboratories were helping reshape that picture. Grey Pepper has covered how John Hughes and his colleagues identified the enkephalins, endogenous peptides with opioid-like activity, and how Candace Pert’s receptor research helped establish measurable targets for opioid signaling.
Leeman’s work became an important part of the same scientific shift. In 1991 she was elected to the U.S. National Academy of Sciences, becoming the first woman elected in its physiology and pharmacology section.
From Substance P to a Chemotherapy Nausea Drug
Substance P is involved in more than one physiological process. Research has linked it to the transmission and modulation of pain signals, inflammatory responses and the neural pathways involved in nausea and vomiting. One of its principal molecular targets is the neurokinin 1 receptor, usually abbreviated NK1.
That receptor eventually became a drug target. In 2003, the FDA approved Merck’s aprepitant, marketed as Emend. It is a selective antagonist of the substance P/NK1 receptor, meaning it blocks the receptor’s activation by substance P.
Unlike substance P itself, which activates NK1 signaling, aprepitant works by preventing that signaling. Used alongside other anti-nausea medicines, it helps prevent acute and delayed nausea and vomiting associated with certain cancer chemotherapy regimens, including highly emetogenic treatments such as high-dose cisplatin.
The connection is important, but it should not be overstated. Leeman did not invent aprepitant, and the compound was developed by Merck after decades of subsequent research into substance P biology, receptor pharmacology and drug chemistry. It was one of the clinical outcomes made possible by a field that her laboratory helped establish.
Nor did the development of an NK1 antagonist mean that substance P had become a straightforward treatment target for every condition associated with it. The story of pain research is more complicated. Although substance P participates in pain-related signaling and inflammation, aprepitant’s established therapeutic role is in preventing nausea and vomiting, not treating chronic pain.
The scientific journey ran from an unexplained biological response in rats to a purified peptide, then to receptor biology, drug design and an approved treatment. No single laboratory accomplished all of it. Leeman’s contribution was foundational because it helped turn an elusive biological activity into a molecule that could be studied precisely.
What the Discovery Did Not Settle
Substance P is often described as a pain-signaling peptide, but that shorthand can be misleading. Its biological activity extends across nervous, inflammatory and other physiological systems. The fact that a molecule participates in a disease-related pathway does not establish that blocking it will produce a useful treatment in every setting.
Its relationship to chronic pain, migraine and inflammatory disorders remains an active field of investigation. Neurotensin likewise has been studied in numerous physiological and disease contexts, but the existence of an association does not mean that a proven neurotensin-targeted therapy follows from it.
The historical record deserves care as well. Leeman’s discovery story is supported by the published experiments and by her detailed first-person account, but autobiographical recollections are still one person’s perspective. Her descriptions of institutional discrimination should be attributed to her account rather than presented as independent findings about every event.
The chronology, however, is firm. Substance P was purified in 1970, its sequence was published in 1971, neurotensin was isolated in 1973, and its sequence was reported in 1975. Those papers establish the central scientific achievements without requiring any retrospective embellishment.
A Long Working Life
Leeman continued working long after many scientists would have retired. According to her February 2026 obituary in The New York Times, her daughter Jennifer said she retired at nearly 90. Through decades of laboratory work, she remained involved in the study of neuropeptides, their receptors and their physiological functions.
Her institutional recognition eventually included membership in the American Academy of Arts and Sciences, election to the National Academy of Sciences, the FASEB Excellence in Science Award and the Mika Salpeter Lifetime Achievement Award, which recognizes achievement in neuroscience and contributions to women in the field.
Yet professional recognition did not erase the insecurity she described experiencing throughout her career. In her autobiography, she wrote, “I never felt safe to fully commit myself to a career in science.”
That line sits uneasily beside a scientific record that helped redefine how researchers understand chemical communication in the brain. She had isolated one peptide whose identity had resisted scientists for decades, helped discover another and continued investigating their biology long after the original experiments.
Her story is also a lesson in experimental attention. The crucial finding did not emerge from the protein peak that looked most promising on the chromatography chart. It emerged because Leeman was willing to test material outside the expected signal and investigate a result that initially seemed irrelevant.
The rats were supposed to reveal a stress hormone. Instead, they salivated. Leeman noticed, changed the direction of her research, and helped open an entire field of peptide neuroscience.
That is the discovery worth remembering: not simply that an experiment went wrong, but that a scientist recognized when the unexpected result mattered more than the question she had started with.
Sources
- Chang MM, Leeman SE. Isolation of a sialogogic peptide from bovine hypothalamic tissue and its characterization as substance P. Journal of Biological Chemistry, September 25, 1970.
- Chang MM, Leeman SE, Niall HD. Amino-acid sequence of substance P. Nature New Biology, July 21, 1971.
- Tregear GW et al. Synthesis of substance P. Nature New Biology, July 21, 1971.
- Carraway R, Leeman SE. The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami. Journal of Biological Chemistry, October 10, 1973.
- Carraway R, Leeman SE. The amino acid sequence of a hypothalamic peptide, neurotensin. Journal of Biological Chemistry, March 10, 1975.
- Susan E. Leeman. Autobiographical chapter in The History of Neuroscience in Autobiography, Volume 6, Society for Neuroscience.
- Goucher Magazine. Susan Epstein Leeman ’51, February 16, 2016. Used for biographical details; the article’s erroneous substance P length and discovery chronology have not been reproduced.
- National Academy of Sciences. Susan E. Leeman, membership and research profile.
- The Boston Globe. Susan Epstein Leeman obituary, January 26, 2026.
- The New York Times. Susan Leeman, 95, Dies; Explored How the Brain Influences the Body, February 24, 2026.
- U.S. National Library of Medicine, DailyMed. EMEND (aprepitant), prescribing information and approved indications. Initial U.S. approval 2003.
