A Charleston boyhood
Robert Francis Furchgott was born in Charleston, South Carolina, on June 4, 1916, to Arthur Furchgott and Pena Sorentrue Furchgott. His grandfather Max Furchgott and Max’s brothers had come to America from Nitra, in present-day Slovakia, in the early 1860s and settled in Charleston as the Civil War ended, founding a dry-goods business on King Street in 1866. Max later ran M. Furchgott and Sons with his sons Arthur, Melvin and Oscar.
In Charleston the boy fell in love with natural history. He took nature-study classes and field trips to beaches, marshes and woods run by the Charleston Museum, collected shells and watched birds, hobbies he kept for life. In 1929, as the Depression set in, the family store failed, and his father moved the family to Orangeburg, a rural town of about 8,000 people where Robert’s mother had grown up, and opened a women’s clothing store. In high school Robert competed with his cousin Edwin Moseley for the top grades (Edwin won) and decided he wanted to be a scientist. His parents gave him chemistry sets and a small microscope, and he read the science column in his father’s Sunday New York Times.
Chemistry in hard times
Out-of-state tuition at the University of North Carolina was more than his father could afford, so Furchgott spent his first college year at the University of South Carolina. When his father moved the business to Goldsboro, North Carolina, in 1934, Robert became a state resident and transferred to Chapel Hill, where he majored in chemistry and worked as a lab assistant through a New Deal student job programme. He graduated in 1937.
Dozens of applications for graduate positions brought nothing until, in mid-June, an unexpected offer of a teaching assistantship arrived from the physiological chemistry department of Northwestern University Medical School in Chicago. He earned his PhD in biochemistry there in 1940. In the summer of 1938 he attended the Cold Spring Harbor Symposium on protein structure, earning his keep by running the lantern-slide projector, and met many of the leading biologists of the day.
A pharmacologist’s career
From 1940 Furchgott worked at Cornell University Medical College in New York, studying circulatory shock, partly under wartime government funding. In 1941 he married Lenore Mandelbaum, a native New Yorker. In 1949 they drove west to St. Louis, where he joined the pharmacology department of Washington University School of Medicine; Lenore said it felt like going west in a covered wagon. They had three daughters, all of whom became artists rather than scientists.
In 1956 he became chairman of pharmacology at the State University of New York’s Downstate Medical Center in Brooklyn, where he stayed for the rest of his working life. He built a reputation for careful, classical pharmacology: how drugs act on receptors, how blood vessels and heart muscle contract. He developed a widely used mathematical method for measuring the strength of drug binding to receptors, and he noticed that strips of rabbit aorta relax when exposed to light, a curiosity he first spotted because two strips near a window fluctuated with the clouds.
The accident of 1978
For decades pharmacologists had been puzzled by a contradiction. Acetylcholine, a nerve messenger, was known to widen blood vessels in living animals, yet when researchers tested it on strips of artery in the laboratory it usually made them contract. In May 1978, in the very first experiment of a new study, a technician’s error produced a preparation of rabbit aorta that relaxed in response to acetylcholine instead of contracting. Furchgott was intrigued and set out to discover why.
The answer lay in the endothelium, the single layer of cells lining the inside of every blood vessel. The usual laboratory method of preparing artery strips rubbed off this delicate lining. When it was intact, acetylcholine relaxed the vessel; when it was removed, the relaxation vanished. In 1980 he showed in an ingenious experiment that the endothelial cells, stimulated by acetylcholine, release a substance that diffuses to the muscle of the vessel wall and makes it relax. He called the unknown messenger endothelium-derived relaxing factor, or EDRF.
A gas as a messenger
The search for EDRF’s identity became one of the great hunts of 1980s biology. The factor was extraordinarily short-lived, vanishing in seconds. Ferid Murad had shown in 1977 that nitroglycerin and related heart drugs act by releasing nitric oxide, a simple gas better known as an air pollutant from car exhausts. In 1986 Furchgott and Louis Ignarro, independently and at the same time, concluded that EDRF was nitric oxide. When they presented their findings at a conference in July 1986, the Nobel Assembly later wrote, it set off an avalanche of research around the world.
It was the first discovery that a gas can act as a signalling molecule in the body. Nitric oxide turned out to regulate blood pressure and blood flow to organs, prevent blood clots, carry signals between nerve cells and help white blood cells kill bacteria and tumour cells.
The finding surprised biologists for several reasons. Nitric oxide is utterly unlike any other known signalling molecule: it is a tiny, unstable gas that is converted to nitrate and nitrite within about ten seconds, and it passes straight through cell membranes rather than binding to a receptor on the surface. It was known to be made by bacteria, but nobody expected such a simple molecule, a common pollutant formed when nitrogen burns, to carry messages in mammals. Furchgott’s once-overlooked laboratory curiosity turned out to be a molecule present in most living creatures and made by many kinds of cells.
How it changed medicine
The discovery solved a century-old mystery. Nitroglycerin, the explosive in Alfred Nobel’s dynamite, had been used since the 19th century to relieve angina, the chest pain of heart disease, but no one knew why. Now it was clear: the body converts nitroglycerin into nitric oxide, which relaxes and widens the coronary arteries. In atherosclerosis the endothelium produces less nitric oxide, and nitrate drugs make up for the shortfall.
The Nobel Assembly enjoyed the irony. When Alfred Nobel, who had made his fortune by taming nitroglycerin in dynamite, developed heart disease late in life, his doctor prescribed nitroglycerin. Nobel refused it, knowing that it caused headaches and doubting that it could ease chest pain; he wrote that it was ironical to be ordered to eat nitroglycerin. It took a hundred years, and Furchgott’s accident, to explain why it worked.
New treatments followed. Inhaled nitric oxide gas is used in intensive care to lower dangerously high blood pressure in the lungs, including in newborn babies. Sildenafil, developed as a possible heart drug, was found to act on the nitric oxide pathway and became a treatment for erectile dysfunction and pulmonary arterial hypertension. Measuring nitric oxide in exhaled breath helps doctors diagnose and monitor asthma. And the health of the endothelium, and its ability to make nitric oxide, became a central concept in understanding heart disease, diabetes and high blood pressure.
Nobel Prize
In October 1998 Furchgott, Ignarro and Murad shared the Nobel Prize in Physiology or Medicine for their discoveries concerning nitric oxide as a signalling molecule in the cardiovascular system. Furchgott was 82. He had already received the Gairdner Foundation International Award in 1991 and the Albert Lasker Award for Basic Medical Research in 1996. He travelled to Stockholm with family and friends to receive the prize.
In his Nobel autobiography he was strikingly modest. He described his research as rather old-fashioned pharmacology, said he still enjoyed doing bench work with his co-workers, and admitted that without the lucky accident of 1978 he would probably have been left far behind by scientists using newer molecular methods.
A Jewish family of the South
Furchgott was Jewish, and his family belonged to the long-established Jewish community of Charleston. The Furchgotts had been members of the Reform congregation Kahal Kadosh Beth Elohim since their first generation in the city, and the family’s story of immigrant merchants from Central Europe is preserved by the Jewish Historical Society of South Carolina. In 2001 Robert recorded oral history interviews about his family and career for the Jewish Heritage Collection at the College of Charleston.
His wife Lenore died in 1983. He later married a family friend, Margaret (Maggie) Gallagher Roth, who died in 2006. For most of his married life he lived in Woodmere, on Long Island.
Later years and legacy
Furchgott stepped down as department chairman in 1982 and retired from his professorship in 1989, becoming professor emeritus so that he could keep doing research without teaching duties. For years afterward he spent about three and a half months each winter at the University of Miami School of Medicine, writing up papers and trying, as he put it, to keep up with the impossible flood of nitric oxide research. In 2008 he moved to Seattle, and he died there on May 19, 2009, at the age of 92, survived by his three daughters, four grandchildren and three great-grandchildren.
His career is a lesson in curiosity. A career pharmacologist in his sixties paid attention to a result that seemed to be a mistake, and in doing so revealed a signalling system no one had imagined. Today nitric oxide is one of the most studied molecules in biology, and the treatments that grew from his work help patients in heart wards, newborn intensive care units and clinics around the world.
Sources & further reading
Robert F. Furchgott, Biographical, NobelPrize.org · Press release: The Nobel Prize in Physiology or Medicine 1998, NobelPrize.org · The Furchgott Stores, since 1866, Jewish Merchant Project, Jewish Historical Society of South Carolina · Robert Furchgott oral history interviews, Jewish Heritage Collection, College of Charleston (LCDL catalogue) · Robert F. Furchgott, Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.
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