Hot—and cool—research wins Nobel Prize in Physiology or Medicine | Science

The discoveries that explain why chili peppers taste hot and mint tastes cool—and the molecules that help us sense a gentle breeze or a sharp poke—have been awarded the 2021 Nobel Prize in Physiology or Medicine. David Julius and Ardem Patapoutian share the award for their discoveries of key molecules that tell us how hot or cold something is, and whether the skin is experiencing mechanical pressure.

The sense of touch “has fascinated humankind for thousands of years,” Patrik Ernfors, a member of the Nobel Committee, said this morning at the announcement in Stockholm. René Descartes, for example, envisioned a cord that connected different parts of the body with the brain to transmit pain signals. The 1944 medicine prize was awarded for the discovery of nerve fibers that sense painful and nonpainful touch sensations.

This year’s laureates’ research “has unlocked one of the secrets of nature, by explaining the molecular basis for sensing temperature and mechanical force,” said Ernfors, who studies somatic sensation himself at the Karolinska Institute.

Julius, who works at the University of California, San Francisco, discovered the sensor in the skin’s nerve endings that detects heat. Researchers knew that capsaicin, the compound that makes chili peppers “hot,” could activate nerves and cause pain. In the 1990s, Julius and his colleagues used DNA fragments isolated from nerves sensitive to heat, pain, and touch. They expressed each of these gene fragments in cells that usually do not react to capsaicin, exposed the cells to the compound, and watched for cells that had become sensitive to the pepper’s heat.

This helped them identify a gene that codes for a so-called ion channel, now called TRPV1, which reacts to capsaicin or heat by letting ions flow into the nerve cell. They later showed that mice lacking the gene for TRPV1 were impervious to both hot peppers and heat.

A few years later, Julius and Ardem Patapoutian, who works at Scripps Research and the Howard Hughes Medical Institute, found a related channel, called TRPM8, that reacts to cold—and also to menthol, which makes mint taste minty cool. TRPV1 and TRPM8 work together with a range of other receptors to sense temperature and trigger the pain induced by heat or cold.

Patapoutian also discovered the gene that enables nerve cells to sense pressure, whether from a gentle hug or a painful rock underfoot. He and his colleagues found a cell line that, in a petri dish, reacted to being poked by a micropipette with an electrical signal. They then sifted through 72 candidate genes, looking for one that would render the cells impervious to the pipette’s touch. They finally found a gene that codes for an ion channel, which they named Piezo1, after the Greek word for pressure.

The team soon found a closely related channel—Piezo2—which has a similar role. Both channels are activated in response to pressure on cell membranes. Later work has shown that the same molecules also help us sense the position our body is in and whether we are moving. And they help control blood pressure, breathing, and the bladder.

“If we didn’t have these proteins we couldn’t sense the world, at least the world close to our skin,” says Félix Viana de la Iglesia, a neuroscientist at the Institute of Neuroscience, Alicante,. The laureates’ work led to the discovery of a range of additional molecules that allow nerves to perceive a range of touch sensations, he notes.

“These novel receptors will for sure be targets for drug development in the future,” Nils-Göran Larsson, the chair of the Nobel Committee, said this morning. But so far, developing drugs that target the ion channels has been more complicated than initially hoped, because the channels are so fundamental that blocking them causes a range of side effects. The work is continuing, and researchers remain hopeful that they will be able to find ways to more specifically target the receptors that lead to pain.

This story will be updated.

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