A Nobel prizewinner, he showed how nitric oxide affects blood flow
Nitric oxide, one of the simplest molecules on the planet, was once known simply as a pollutant from cigarettes and car exhausts. But in 1992 the journal Science nominated it as molecule of the year, following the discovery that it plays a vital role in the human cardiovascular system. For years scientists had tried to identify a substance that made smooth muscle in the blood vessels relax, and Robert Furchgott, who has died aged 92, announced in 1986 at a conference in Rochester, Minnesota, that it was probably nitric oxide. Another team later demonstrated that this was true.
Scientists had been used to the idea that biochemical processes in the body were produced by complex molecules that lock on to specific docking sites, called receptors; nitric oxide, therefore, could not have been a more unexpected candidate. NO, to give it its chemical formula, usually dissipates before it can be detected, yet it plays a key role as a signalling molecule and also has numerous other functions in the body, from brain function to penile erection. Without the discovery of NO, there would be no Viagra. Furchgott won the 1998 Nobel prize in physiology or medicine for his research, sharing it with fellow pharmacologists Ferid Murad and Louis Ignarro, all three working independently.
Furchgott was born in Charleston, South Carolina. His family owned a department store that closed in the depression, and when he was 13 they moved to nearby Orangeburg and opened a dress shop. Robert’s parents encouraged him in his ambition to be a scientist, giving him chemistry sets and a microscope.
As a penniless chemistry undergraduate at the University of North Carolina at Chapel Hill, he supplemented his income by working as a lab assistant – an arrangement funded by Franklin Roosevelt’s New Deal. A holiday job at Philadelphia airport after he graduated in 1937 gave him a free flight to Chicago, where he studied for a PhD in physiological chemistry at Northwestern University’s medical school. He lived on $50 a month, earned as a demonstrator. In 1940, during a summer visit to Cold Spring Harbor laboratory in Long Island, he was offered a postdoctoral job at Cornell University.
He spent nine years at Cornell, learning methods for tissue metabolism. As part of the war effort, the lab had to change direction and study physiological shock. By 1944 this produced evidence that surgical shock involved unidentified substances affecting blood vessel walls. This triggered Furchgott’s interest in the pharmacology of smooth muscle. From 1949 he was at Washington University in St Louis, Missouri, before moving in 1956 to the State University of New York (SUNY), where he remained for the rest of his career.
He continued his work on blood vessel walls, using isolated vessels from animal cadavers. In 1978, one such experiment, on a rabbit aorta, gave an unexpected result, with the vessel dilating instead of constricting. He discovered that the vessel’s lining cells – the endothelium – had been accidentally scraped off. He inferred that something released from the lining cells was acting on the muscle. Publishing his findings in 1980, he called this EDRF – endothelium-derived relaxing factor – and the race was on to identify it.
In 1978, Murad, working at the University of Virginia, had shown that glyceryl trinitrate, used against angina, dilated blood vessel walls and was broken down to nitric oxide. Ignarro, a pharmacologist at the University of California, Los Angeles, became involved in the quest. In 1986, Furchgott’s team and Ignarro’s group independently proposed that EDRF was nitric oxide. A year later, a team led by Salvador Moncada at the Wellcome laboratories, in Kent, produced results that supported the proposal. These discoveries have opened up many new areas of research in medicine.
After more than 30 years at SUNY, Furchgott became emeritus professor in 1988 and retired from teaching. He then spent three months each winter as adjunct professor in the pharmacology department of Miami University, a position that allowed him to take up golf. He published his last original research in 1997 and his last review paper in 2004.
Modest and sweet-natured, Furchgott said the greatest pleasure he obtained from his work was when he had set up an experiment to test a paradoxical hypothesis and obtained supporting results. He wrote: “It is not just the obvious pleasure of obtaining such results but also the anticipated pleasure of discussing the results with others doing research in the same area.”
His recreations were birdwatching, sailing, golf and travel. In old age he enjoyed visiting museums and galleries, and walking on the beach.
He married Lenore Mandelbaum in 1941; they had three daughters. After her death in 1983 he married Margaret Roth, who died in 2004.
He is survived by his daughters.