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How hot peppers helped scientists win the 2021 Nobel prize in medicine

David Julius and Ardem Patapoutian, winners of the 2021 Nobel Prize in Medicine
Niklas Elmehed / Nobel Prize Outreach
David Julius and Ardem Patapoutian, winners of the 2021 Nobel Prize in Medicine
  • Samanth Subramanian
By Samanth Subramanian

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There’s never such thing as a shoo-in at the Nobel Prizes. The scientists who developed the various Covid-19 vaccines saving lives around the world may have been thought to be the frontrunners for this year’s Nobel in physiology and medicine.

Instead, the prize went to a pair of scientists who discovered something even more fundamental: why we feel the light prick of the vaccine needle and other kinds of touch, and why we feel painful heat and cold.

The Nobel Committee today (Oct. 4) named the US scientists David Julius and Ardem Patapoutian as the joint winners of this year’s prize. In 1997, Julius, a physiologist at the University of California San Francisco, tweaked cells to be responsive to capsaicin, the active chemical in chili peppers. By watching how these cells reacted to capsaicin, Julius found a sensor in nerves that signaled sensations of “pain” and “heat” when the skin encounters high temperatures.

Julius and Patapoutian, a Beirut-born scientist working at Scripps Research in California, independently discovered another sensor that responds similarly to painfully cold temperatures. Patapoutian also identified “mechanically activated” sensors that allow us to feel external, physical forces like touch: the sensation of the grass below our bare feet, or of holding a baby’s hand, or of how we move when we dance.

Together, Julius and Patapoutian helped reveal how the human body experiences the world it lives in.

The 2021 medicine Nobel rewarded science that can alleviate pain

When Julius became interested in the subject of pain, the nerve receptor triggered by capsaicin hadn’t yet been identified. There had been plenty of false candidates, he told an interviewer in 2015, but he set his mind to it only after a grocery run with his wife, the physiologist Holly Ingraham.

“I remember standing in the supermarket looking at all these rows of spices,” Julius said. “Holly was off somewhere, and she came around and I said, ‘This is such an interesting problem.’ And she said, ‘So quit f**king around and do it!'”

Finding that receptor—one of several responding to heat, it turned out—was merely the first accomplishment. (Another, similar sensor is popularly known as the “wasabi receptor.”) Julius then showed that the capsaicin receptor was activated whenever it sensed temperatures above 40° Celsius (104° Fahrenheit)—a threshold for thermal pain. In 2002, researchers led by Julius and Patapoutian independently discovered a receptor for cold sensations using menthol.

Julius and Patapoutian’s research, the Nobel committee said, “is being used to develop treatments for a wide range of disease conditions, including chronic pain.”

Sunburned or otherwise injured skin, for instance, feels acute heat even upon encountering mild temperatures. One condition called cold allodynia induces a hypersensitivity to temperatures that would normally be considered innocuous. Triggered by nerve injury or among cancer patients undergoing chemotherapy, cold allodynia can feel like a stabbing, burning pain.

A new class of drugs that can selectively target the nerve sensors feeling painful sensations might be able to block out the pain without the side effects of opioid painkillers, scientists hope.

“We’re as impatient as anybody,” Julius said, in a joint interview with Patapoutian last year, after they won the Kavli prize in neuroscience. “Wouldn’t it be great if a drug came out against one of the targets that the field had worked on—a new analgesic? That would be fantastic, and I’d love to see that happen.”

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