Ferid Murad

Ferid Murad
Murad at a lecture in 2008
Ferid Murad
Born	14 9, 1936
Birthplace	Whiting, Indiana, U.S.
Died	Template:Death date and age Menlo Park, California, U.S.
Nationality	American
Occupation	Physician, pharmacologist
Known for	Discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system
Education	DePauw University (BS, 1958) Case Western Reserve University (MD, PhD)
Spouse(s)	Carol A. Leopold
Children	5
Awards	Nobel Prize in Physiology or Medicine (1998) Albert Lasker Award for Basic Medical Research (1996)

Ferid Murad (September 14, 1936 – September 4, 2023) was an American physician and pharmacologist whose research fundamentally transformed the scientific understanding of how cells communicate in the cardiovascular system. Born in the industrial town of Whiting, Indiana, to an Albanian immigrant father and an American mother, Murad pursued a combined MD-PhD program at Case Western Reserve University, where he trained under Nobel laureate Earl Sutherland Jr. His career-defining research demonstrated that nitroglycerin and related vasodilating compounds relax smooth muscle by releasing nitric oxide, which in turn activates the enzyme guanylate cyclase and increases levels of the signaling molecule cyclic guanosine monophosphate (cyclic GMP). This discovery, which revealed that a simple gas could function as a biological signaling molecule, opened vast new avenues in cardiovascular medicine, neuroscience, and immunology. For this work, Murad shared the 1998 Nobel Prize in Physiology or Medicine with pharmacologists Robert F. Furchgott and Louis J. Ignarro. Over the course of a career spanning more than five decades, Murad held positions at the National Institutes of Health, the University of Virginia, Stanford University, Abbott Laboratories, the University of Texas at Houston, and George Washington University, contributing to both academic science and the pharmaceutical industry.

Early Life

Ferid Murad was born on September 14, 1936, in Whiting, Indiana, a small city adjacent to Chicago known for its oil refinery and working-class immigrant communities. His father, Jabir Murat Ejupi, was an Albanian immigrant who had come to the United States as a teenager, and his mother, Henrietta Josephine Bowman, was of mixed European ancestry. The family eventually settled in the suburbs south of Chicago, where Murad grew up alongside his siblings.

According to his Nobel autobiography, Murad's parents operated a restaurant during part of his childhood, and the family faced the economic challenges common to immigrant households during and after the Great Depression and World War II. Despite these difficulties, Murad showed early aptitude in science and mathematics. His interest in medicine and research was kindled during his secondary school years, and he became determined to pursue a career that combined clinical practice with scientific investigation.

Murad's Albanian heritage remained an important part of his identity throughout his life. In Albania and among Albanian diaspora communities, he was celebrated as a figure of national pride, representing the achievements possible through education and determination. His background as the son of an immigrant who rose to the highest levels of scientific achievement was frequently noted in biographical accounts.

Education

Murad enrolled at DePauw University in Greencastle, Indiana, where he earned a Bachelor of Science degree in 1958. His undergraduate experience at DePauw proved formative; the liberal arts environment and the mentorship he received there encouraged his commitment to a research-oriented career in medicine. He would maintain a lifelong relationship with the institution, returning to campus on multiple occasions and being honored by the university in subsequent decades.

After completing his undergraduate degree, Murad entered Case Western Reserve University (then Western Reserve University) in Cleveland, Ohio, where he enrolled in a combined MD-PhD program. This was a relatively uncommon path at the time, but it suited Murad's ambition to integrate laboratory research with clinical training. At Case Western Reserve, Murad came under the mentorship of Earl Sutherland Jr., who would himself be awarded the Nobel Prize in Physiology or Medicine in 1971 for his discoveries concerning the mechanisms of action of hormones, particularly the role of cyclic adenosine monophosphate (cyclic AMP) as a second messenger. Murad also studied under Theodore Rall, another leading figure in cyclic nucleotide research. This training in cyclic nucleotide biochemistry laid the intellectual groundwork for Murad's later discoveries concerning cyclic GMP and nitric oxide signaling. He completed both his MD and PhD degrees at Case Western Reserve, making him a triple alumnus of the institution when considered alongside his later professional affiliations.

Career

Early Research and the National Institutes of Health

Following completion of his medical and doctoral training, Murad undertook clinical internship and residency work before transitioning into full-time research. He joined the National Institutes of Health (NIH) in Bethesda, Maryland, where he continued and expanded the research on cyclic nucleotides that he had begun under Sutherland. At the NIH, Murad began investigating the enzyme guanylate cyclase and its product, cyclic GMP. While cyclic AMP had received substantial attention as a second messenger molecule, the role of cyclic GMP in cellular signaling was far less understood. Murad's early work at the NIH helped establish that cyclic GMP served important signaling functions distinct from those of cyclic AMP, particularly in smooth muscle cells and the cardiovascular system.

University of Virginia

Murad subsequently moved to the University of Virginia, where he held academic and research appointments. During this period, his laboratory made a series of observations that would prove to be among the most consequential in modern pharmacology. Murad and his team investigated how nitroglycerin and related nitrovasodilator drugs caused blood vessels to relax. Nitroglycerin had been used in clinical medicine since the late nineteenth century for the relief of angina pectoris—chest pain caused by insufficient blood flow to the heart—but the molecular mechanism by which it worked remained a mystery.

Through a series of experiments conducted in the late 1970s and early 1980s, Murad demonstrated that nitroglycerin and other nitrovasodilators release nitric oxide (NO), and that this gas activates the enzyme guanylate cyclase in smooth muscle cells, leading to an increase in cyclic GMP levels. The elevated cyclic GMP then causes the smooth muscle to relax, resulting in dilation of blood vessels and reduced blood pressure. This finding was remarkable in multiple respects. First, it identified a specific biochemical pathway for a widely used but poorly understood class of drugs. Second, and more fundamentally, it suggested that a simple, short-lived gas—nitric oxide—could serve as a biological signaling molecule, a concept that was initially met with skepticism by many in the scientific community.

Murad's hypothesis that nitric oxide was the active mediator was part of a broader tapestry of research that was being developed independently by other scientists. Robert F. Furchgott at the State University of New York had identified what he called "endothelium-derived relaxing factor" (EDRF), a substance produced by the inner lining of blood vessels that caused relaxation of the surrounding smooth muscle. Louis J. Ignarro, working at the University of California, Los Angeles, subsequently provided evidence that EDRF was in fact nitric oxide. Together, the work of Murad, Furchgott, and Ignarro established nitric oxide as a fundamental signaling molecule in the cardiovascular system.

Stanford University

Murad joined the faculty of Stanford University in California, where he continued his research on nitric oxide and cyclic GMP signaling. At Stanford, he further characterized the enzymatic pathways involved in nitric oxide synthesis and explored the broader physiological roles of this molecule beyond the cardiovascular system. Research in his laboratory and others revealed that nitric oxide played important roles in neurotransmission, immune defense, and inflammation, among other biological processes.

Abbott Laboratories

In a career move that reflected his interest in translating basic research into therapeutic applications, Murad joined Abbott Laboratories, one of the major American pharmaceutical and health care companies, as vice president of pharmaceutical research and development. During his time in the pharmaceutical industry, he oversaw research programs and gained experience in drug development and corporate science management. This period gave Murad a perspective on the practical challenges of moving discoveries from the laboratory bench to the clinic, an experience that informed his later academic work and public commentary on the state of biomedical research.

University of Texas at Houston

Murad subsequently returned to academic life as a faculty member at the University of Texas Health Science Center at Houston (now UTHealth Houston), where he served in several leadership roles, including as chair of the Department of Integrative Biology and Pharmacology and as director of the Institute of Molecular Medicine. The Houston years were highly productive, and Murad continued to publish extensively on nitric oxide biology, cyclic nucleotide signaling, and related areas of cardiovascular pharmacology. His research group at the University of Texas explored the roles of nitric oxide in a wide range of pathological conditions, including hypertension, atherosclerosis, and septic shock.

George Washington University

Later in his career, Murad joined George Washington University in Washington, D.C., where he served as a professor and continued his research and mentoring activities. His appointment at George Washington University reflected his continued engagement with academic science well into the later decades of his career.

Contributions to Pharmacology and Medicine

The implications of Murad's research on nitric oxide extended far beyond the initial context of nitroglycerin and angina treatment. The recognition that nitric oxide served as a signaling molecule opened up entirely new fields of biomedical research. One of the most prominent practical outcomes was the development of sildenafil (marketed as Viagra) for the treatment of erectile dysfunction, which works by modulating the nitric oxide–cyclic GMP pathway. While Murad was not directly involved in the development of sildenafil, the drug's mechanism of action was directly built upon the fundamental science that he and his colleagues had established.

The nitric oxide research also had implications for the understanding and treatment of pulmonary hypertension, septic shock, and neurodegenerative diseases. Inhaled nitric oxide itself became an approved therapy for newborns with persistent pulmonary hypertension. The broader field of nitric oxide biology grew rapidly after the foundational discoveries, and by the time of the Nobel Prize announcement in 1998, thousands of research papers had been published on the molecule's roles in physiology and pathology.

Personal Life

Ferid Murad married Carol A. Leopold, and the couple had five children together. Murad was known to colleagues and friends by the nickname "Fred." He maintained close ties to his alma maters, particularly DePauw University and Case Western Reserve University, throughout his life. He was a resident of the San Francisco Bay Area in his later years.

Murad died on September 4, 2023, in Menlo Park, California, ten days before what would have been his eighty-seventh birthday. His death was reported by major scientific and news outlets, including The New York Times, Science, and The Lancet, all of which published obituaries or remembrances honoring his contributions to science and medicine.

Recognition

Murad received numerous awards and honors over the course of his career, reflecting the significance of his contributions to biomedical science. His most prominent recognition was the 1998 Nobel Prize in Physiology or Medicine, which he shared with Robert F. Furchgott and Louis J. Ignarro "for their discoveries concerning nitric oxide as a signalling molecule in the cardiovascular system." The Nobel Committee's citation highlighted the paradigm-shifting nature of the discovery that a gas could serve as a signal molecule in the body, with widespread applications in medicine.

Two years before the Nobel Prize, Murad was awarded the Albert Lasker Award for Basic Medical Research in 1996, often considered the most prestigious biomedical science prize in the United States and a frequent precursor to the Nobel Prize.

Murad was also a recipient of the Golden Plate Award from the American Academy of Achievement.

At DePauw University, his undergraduate alma mater, the Ferid Murad Medal was established in his honor. The medal is presented annually to the graduating senior who has demonstrated the most significant scholarly or artistic achievements during their time at the university. Murad also delivered an Ubben Lecture at DePauw in April 1999, shortly after receiving the Nobel Prize, in which he discussed the trajectory of his research and the field of nitric oxide biology.

Case Western Reserve University, where Murad earned both his MD and PhD, also honored him and remembered him prominently after his death as one of the institution's most distinguished alumni.

Murad was a signatory of the Mainau Declaration, a statement by Nobel laureates on issues of global concern.

Legacy

Ferid Murad's scientific legacy rests primarily on his role in establishing nitric oxide as a signaling molecule in biological systems, a discovery that fundamentally altered the understanding of cell communication in the cardiovascular system and beyond. Before Murad's work, the idea that a simple, toxic gas could function as a precise and essential messenger within the body was outside the mainstream of biochemical thinking. His research on the mechanisms by which nitroglycerin and related drugs relax smooth muscle provided not only an explanation for a century-old therapeutic practice but also opened an entirely new chapter in molecular biology and pharmacology.

The field of nitric oxide biology that emerged from the foundational work of Murad, Furchgott, and Ignarro grew into one of the most active areas of biomedical research in the 1990s and 2000s. Nitric oxide research has had direct clinical applications in cardiology, pulmonology, urology, and neuroscience. The development of drugs targeting the nitric oxide–cyclic GMP pathway, including phosphodiesterase type 5 inhibitors such as sildenafil, represented a direct translational outcome of the basic science discoveries that Murad helped to pioneer.

As a mentor and educator, Murad trained numerous graduate students and postdoctoral fellows who went on to contribute to pharmacology and biomedical research in their own right. His career, which spanned positions at the NIH, multiple universities, and the pharmaceutical industry, illustrated the potential for productive exchange between academia and industry in the life sciences.

Science magazine, in its obituary for Murad, described his discoveries as "paradigm-shifting," noting that they had changed the way scientists and physicians understood the molecular underpinnings of cardiovascular function. The Lancet similarly emphasized the transformative nature of his work, placing it in the historical context of more than a century of nitroglycerin use in medicine and noting that Murad's research had provided the mechanistic explanation that had eluded researchers for generations.

Murad's story—from the son of an Albanian immigrant growing up in industrial Indiana to a Nobel laureate whose research transformed modern medicine—has been cited as an example of the contributions of immigrant families to American science and culture.