Robert Furchgott

In 1980, Furchgott discovered that blood vessels only dilate in response to certain drugs if the endothelial cell layer lining the vessel is intact, meaning the endothelium produces a diffusible relaxing factor he called EDRF. He later proposed, along with Louis Ignarro, that EDRF is in fact nitric oxide (NO), a gas. This was a radical idea because no one had expected a toxic gas to serve as a signaling molecule in the cardiovascular system.

Furchgott shared the 1998 Nobel Prize in Physiology or Medicine with Louis Ignarro of UCLA and Ferid Murad of the University of Texas Medical School in Houston. Ignarro independently confirmed that EDRF was nitric oxide, while Murad had earlier discovered that nitroglycerin and similar vasodilators work by releasing nitric oxide. All three were recognized for revealing nitric oxide as a fundamental signaling molecule.

The discovery that nitric oxide is a key signaling molecule in blood vessel dilation inspired research into the NO-cGMP pathway throughout the body, including penile erectile tissue. Pfizer scientists developing a heart drug called sildenafil found it enhanced this pathway, producing erections as a side effect, and repurposed it as Viagra, approved by the FDA in 1998. Sildenafil inhibits the enzyme PDE5, which degrades cGMP, the second messenger produced when nitric oxide activates guanylate cyclase.

Furchgott carried out his EDRF research at the State University of New York (SUNY) Downstate Medical Center in Brooklyn, where he was a department chair for many years. His classic 1980 experiments used rabbit aorta strips mounted in organ baths to demonstrate that removing the endothelial layer abolished acetylcholine-induced relaxation. He remained at SUNY Downstate for essentially his entire independent career.