Mechanisms of Chili’s Heat, Menthol’s Cool Garner Nobel
Mechanisms of Chili’s Heat, Menthol’s Cool Garner Nobel

Mechanisms of Chili’s Heat, Menthol’s Cool Garner Nobel

David Julius and Ardem Patapoutian won this year’s Nobel Prize in Physiology or Medicine for their research on the ion channels involved in perceiving heat, cold, pain, and touch.

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Chloe Tenn

Chloe Tenn is a graduate of North Carolina State University, where she studied neurobiology, English, and forensic science. Fascinated by the intersection of science and society, she has written for...

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Oct 4, 2021

ABOVE: David Julius and Ardem Patapoutian
© NIKLAS ELMEHED © NOBEL PRIZE OUTREACH

This year’s Nobel Prize in Physiology or Medicine goes to David Julius of the University of California, San Francisco, and Ardem Patapoutian of Scripps Research Institute, the Nobel Assembly announced today. The prize recognizes discoveries by the winners of receptors that allow perception of temperature, pressure, and pain. 

“Their collective discoveries explain how we feel the warm sun, a cool breeze and [a] loved ones touch,” writes Alexander Chesler, an NIH investigator who completed his postdoc with Julius, in a Twitter message to The Scientist. “They provide us with the details about how we detect dangerous stimuli. These discoveries completely changed the fields of somatosensation and pain.” 

“These are fundamental discoveries in the field of physiology and it will be the beginning of a new era where we can identify drugs active in those channels,” says Eric Honore, a researcher at the Institut de Pharmacologie Moléculaire et Cellulaire in France who studies one of the channels discovered by the pair. “This is still at an early stage, and I think it’s the beginning of a new field.”  

According to an autobiography of Julius, he was born in Brighton Beach, Brooklyn, and attended MIT for his undergraduate degree. There, “I learned that curiosity, persistence, hard work, luck, humor, and vigorous discussion are essential elements of the scientific process. . . . I realized that I was driven to solve problems, and that I derived great satisfaction from bench work,” he writes. He went on to earn his PhD at the University of California, Berkeley, with Jeremy Thorner and Randy Schekman as his thesis advisors. He then did a postdoc in Richard Axel’s laboratory at Columbia University before joining the faculty at UCSF in 1989. 

At the time, it wasn’t yet known how capsaicin, the active ingredient in hot chilies, interacts with cells to induce a burning sensation. He and members of his lab set out to find the receptor capsaicin works by screening candidate genes in cultured cells, and ultimately identified an ion channel, later dubbed TRPV1, which they reported in Nature in 1997. In addition to sensing capsaicin, “We started throwing nonchemical stimuli at the receptor and found, to our surprise, that heat could activate the channel,” Julius told The Scientist in 2018. 

“Working with David changed my life. He has this uncanny insight into how biology works at its deepest level,” Chesler writes. 

Michael Caterina, a neuroscientist at Johns Hopkins University School of Medicine who was the first author of the 1997 Nature paper while a postdoc in Julius’s lab, calls him a terrific and optimistic mentor. “There was a moment where Dr. Julius went to wash the food processor out in the sink, and got a waft of hot pepper steam and had to step back away from the sink for a couple of moments,” he remembers. “It was illustrative of the fact that he genuinely enjoys doing science. He runs a relatively little lab, but one that packs a lot of punch. He’s intimately involved in the experiments in the lab and is really there to troubleshoot and lend support and to come up with brilliant ideas.” 

See “David Julius Probes the Molecular Mechanics of Pain” 

According to his CV, Patapoutian was born in Beirut, Lebanon in 1967. Growing up during the civil war in Lebanon, “As Armenians, we were usually treated as quasi-neutral parties to the Christian-Muslim strife, and I attended small Armenian schools which continued shrinking in class size as more families escaped the war,” he wrote in an autobiography. “By my freshman high school year, we were down to five students, all dear pals, where I was perhaps middle of the pack in my subjects but definitely the shortest in stature.”  

Later, as a student at the American University in Beirut, Patapoutian was “captured and held by armed militants,” he wrote. “A few months later, I moved to Los Angeles.” He graduated from the University of California, Los Angeles, in 1990, and went on to earn a PhD at Caltech with thesis advisor Barbara Wold. He then did a postdoc with Louis Reichardt at UCSF, where he studied neurons that sense touch and pain. “During this period of studying the development of these sensory neurons, it gradually became more urgent to me that the defining proteins that underlie the function of these cells, the molecules that allow them to detect physical stimuli such as temperature and mechanical force, were largely a mystery,” he wrote in his autobiography. “On the temperature front, David Julius across campus had recently cloned TRPV1 as an ion channel activated by heat. Following the visionary Peter Schultz to San Diego, I established my new lab at Scripps Research and set out to test whether other TRP channels were temperature channels.” 

That was in 2000. In 2002, Patapoutian’s and Julius’s groups separately reported that they’d each discovered another ion channel, TRPM8, that senses cold and menthol. Patapoutian and his colleagues went on to find two ion channels, PIEZO1 and PIEZO2, that enable cells to respond to mechanical pressure, which they reported in Science in 2010. 

The Weizmann Institute of Science’s Fabian-Simone Passini, who has collaborated with Patapoutian, says it was a pleasure to work with him. He writes in an email to The Scientist that “His contribution to our collaboration was key to discovering how tendons sense mechanical forces and adapt to physical demands. . . . His passion for basic science and his brilliant thinking clearly stood out.”

See “When Normal Touch Becomes Painful, the Same Neurons Are Involved” 

In addition to the Nobel, the pair also share the 2019 Rosenstiel Award for Distinguished Work in Basic Medical Research and the 2020 Kavli Prize in Neuroscience. 

Patapoutian and Julius will each receive a gold medal and will share 10 million Swedish kronor, which is equivalent to just over $1 million.  

“I realized that sensory systems are beautiful things to work on because it is basically how we view the world,” Julius told The Scientist in his 2018 interview. “The colors we can see and the things we can smell are just a product of the molecular detectors that we have.”