Nobel Prize Awarded for Research About Temperature and Touch

David Julius and Ardem Patapoutian were honored for their discoveries about how heat, cold and touch can initiate signals in the nervous system.

Patrik Ernfors, right, of the Nobel Committee for Physiology or Medicine, announced the winners of the 2021 prize, David Julius and Ardem Patapoutian, during a news conference in Stockholm on Monday.
Patrik Ernfors, right, of the Nobel Committee for Physiology or Medicine, announced the winners of the 2021 prize, David Julius and Ardem Patapoutian, during a news conference in Stockholm on Monday.Credit...Jonathan Nackstrand/Agence France-Presse — Getty Images

By Benjamin Mueller, Marc Santora and Cora Engelbrecht

Published Oct. 4, 2021Updated Oct. 5, 2021

The Nobel Prize in Physiology or Medicine was awarded jointly on Monday to David Julius and Ardem Patapoutian, two scientists who independently discovered key mechanisms of how people sense heat, cold, touch and their own bodily movements.

Dr. Julius, a professor of physiology at the University of California, San Francisco, used a key ingredient in hot chili peppers to identify a protein in nerve cells that responds to uncomfortably hot temperatures.

Dr. Patapoutian, a molecular biologist at Scripps Research in La Jolla, Calif., led a team that, by poking individual cells with a tiny pipette, hit upon a receptor that responds to pressure, touch and the positioning of body parts.

After Dr. Julius’s pivotal discovery of a heat-sensing protein in 1997, pharmaceutical companies poured billions of dollars into looking for nonopioid drugs that could dull pain by targeting the receptors. But while research is ongoing, the related treatments have so far run into huge obstacles, scientists said, and interest from drug makers has largely dried up.

Neither winner was easy for the Nobel committee to reach before it announced the prize around 2:30 a.m. California time. Dr. Julius said in an interview that his phone pinged with a text message from his sister-in-law, who told him that she had gotten a call from the Nobel Assembly’s secretary-general but had not wanted to give the man Dr. Julius’s phone number.

Dr. Patapoutian said that the committee eventually reached his 94-year-old father on a landline, who in turn called Dr. Patapoutian to tell him, “I think you won the Nobel Prize.”

“I’m a bit overwhelmed,” Dr. Patapoutian said a few hours later, “but pretty happy.”

Why did they win?

Pain and pressure were among the last frontiers of scientists’ efforts to describe the molecular basis for sensations. The 2004 Nobel Prize in Medicine was given to work clarifying how smell worked. As far back as 1967, the prize was awarded to scientists studying vision.

But unlike smell and sight, the perceptions of pain or touch are not located in an isolated part of the body, and scientists did not even know what molecules to look for. “It’s been the last main sensory system to fall to molecular analysis,” Dr. Julius said at an online briefing on Monday.

The biggest hurdle in Dr. Julius’s work was how to comb through a library of millions of DNA fragments encoding different proteins in the sensory neurons to find the one that reacts to capsaicin, the key component in chili peppers. The solution was to introduce those genes into cells that do not normally respond to capsaicin until one was discovered that made the cells capable of reacting.

At that point, scientists in Dr. Julius’s lab knew that the receptor they had identified — TRPV1, a channel on the surface of cells activated by capsaicin — had to have evolved primarily for a more common stimulus, beyond the rare instances when someone might encounter hot peppers. That other stimulus turned out to be heat, said Dr. Michael Caterina, a professor of neurosurgery at the Johns Hopkins University School of Medicine who helped run a critical 1997 study on the topic in Dr. Julius’s lab. Acid activated the channel, too.
The 2021 Nobel Prizes

• Prize for Physics: Syukuro Manabe, Klaus Hasselmann and Giorgio Parisi were honored for their work, which “laid the foundation of our knowledge of the Earth’s climate and how humanity influences it.”
• Prize for Medicine: David Julius and Ardem Patapoutian were honored for their discoveries about how heat, cold and touch can initiate signals in the nervous system.
• What to Know: Here’s a quick guide to this year’s prizes.
• How Do the Nominations Work?: Thousands of people, including university professors, can submit nominations. Hundreds are submitted per year.
• A Nobel Prize That Might Have Been: A recent study of black holes has confirmed a fundamental prediction made by Stephen Hawking nearly five decades ago. But the ultimate award is out of his reach.
• A Life-Changing Call: Here’s how eight scientists learned about their Nobel Prizes.
• A Growing List of Questionable Choices: The Nobel Peace Prize has been awarded at least six times in the past three decades to recipients whose recognition is being second-guessed.

Tobias Rosen, an undergraduate in the lab, “came up with the clever recognition that essentially what we had cloned was a hot and sour soup receptor,” Dr. Caterina said. “It has acid, it has hot temperature, and it’s spicy.”

In search of the molecular basis for touch, Dr. Patapoutian, too, had to sift through a number of possible genes. One by one, he and his collaborators inactivated genes until they identified the single one that, when disabled, made the cells insensitive to the poke of a tiny pipette.

The channel integral to the sense of touch became known as Piezo1, after the Greek word for pressure. That channel and a similar one, both described in a 2010 paper, are now known to regulate a number of bodily functions that involve stretching, said Dr. Walter Koroshetz, the director of the N.I.H. National Institute on Neurological Disorders and Stroke, which provided funding to Dr. Julius’s and Dr. Patapoutian’s labs.

Those functions include the working of blood vessels, breathing and sensitivity to a full bladder.

Why is the work important?

The identification of pain receptors prompted a flurry of interest from pharmaceutical companies: If you could block the channel identified by Dr. Julius, they reasoned, you could address chronic pain.

But there were several major problems. One is that some sensitivity to pain is useful; without it, people risk running a scalding hot bath or burning their hands on a stovetop. “Pain serves a purpose,” Dr. Caterina said.

Another is that the same channels responsive to heat also turned out to contribute to the control of body temperature. Blocking them was found to cause a slight fever — a potentially major liability.

As a result, some scientists — including Peter McNaughton, a professor of pharmacology at King’s College London — have focused on the channels’ tendency to become hypersensitive when inflammation occurs. Instead of trying to stop the channels’ normal activity, the scientists studied ways to safely block them from revving up even further in response to inflammation.

Another approach is to take advantage of the fact that repeated exposure to capsaicin makes sensory neurons less sensitive — the same reason that people who eat spicy foods develop a certain tolerance, Dr. Caterina said. Apply a prescription-strength patch with a lot of capsaicin, Dr. Caterina said, and it should deaden the pain response.

Still, difficulties remain. For example, it turned out that there were multiple heat-sensing channels. Block some, and others would compensate. “If you whack one of them, the other ones can still respond to noxious heat,” said Professor John Wood of University College London, who studies pain and touch.

The channels identified in Dr. Patapoutian’s work, Dr. Wood said, were involved in so many processes that they made for difficult drug targets.

“It’s fascinating mechanistically,” Dr. Wood said, “but I don’t think it has much clinical relevance to treating pain.

Who are the winners?

Ardem Patapoutian of the Howard Hughes Medical Institute at Scripps Research in La Jolla, Calif.
Ardem Patapoutian of the Howard Hughes Medical Institute at Scripps Research in La Jolla, Calif.Credit...Sandy Huffak/Howard Hughes Medical Institute/Scripps Research/EPA-EFE, via Shutterstock

Dr. Patapoutian, who is of Armenian origin, grew up in Lebanon during the country’s long and calamitous civil war before fleeing to the United States with his brother in 1986 at age 18. Needing to establish residency in California so that he could afford college, Dr. Patapoutian worked eclectic jobs for a year, delivering pizzas and writing the weekly horoscopes for an Armenian newspaper.

At U.C.L.A., in the course of preparing to apply to medical school, he joined a research laboratory so that the professor would write him a good recommendation.

“I fell in love with doing basic research,” Dr. Patapoutian said in an interview. “That changed the trajectory of my career.”

He added: “In Lebanon, I didn’t even know about scientists as a career.”

Dr. Patapoutian said that he gravitated to studying the sense of touch and pain because those systems remained so mysterious. “When you find a field that’s not well understood,” he said, “it’s a great opportunity to dig in.”

David Julius in his office in San Francisco, Calif.
David Julius in his office in San Francisco, Calif. Credit...University of California, San Francisco/EPA, via Shutterstock

Dr. Julius, too, became fixated on the question of how the body’s sensory receptors worked. Growing up in Brighton Beach, Brooklyn, he said that he began considering a career in science while at nearby Abraham Lincoln High School, where a former minor league baseball player turned physics teacher spoke to students about calculating the trajectory of a baseball.

“He was the person who made me think, ‘Maybe I should do science,’” Dr. Julius said.

As a graduate student at the University of California, Berkeley, and later a postdoctoral scholar at Columbia University, he said he became interested in how magic mushrooms and LSD worked, and more broadly in how things from nature interact with human receptors.

No sensory system matters more to survival than pain, he said. And hardly any was as poorly understood. So his lab began investigating the workings of a wide range of unpleasant natural substances: toxins from tarantulas and coral snakes, capsaicin from chili peppers and the chemicals that make horseradish and wasabi so pungent.

Who won the 2020 Nobel Prize in medicine?

Dr. Harvey J. Alter, Michael Houghton and Charles M. Rice received the prize for their discovery of the hepatitis C virus. The Nobel committee said the three scientists had “made possible blood tests and new medicines that have saved millions of lives.”
Who else won a Nobel Prize in the sciences in 2021?

The Nobel Prize in Physics on Tuesday was awarded to Syukuro Manabe of Princeton University, Klaus Hasselmann of the Max Planck Institute for Meteorology in Hamburg, Germany, and Giorgio Parisi of the Sapienza University of Rome. The committee said their work has been essential to understanding how Earth’s climate is changing and how human behavior is influencing those changes.
Who else won Nobel Prizes in science in 2020?

• The physics prize went to Roger Penrose, Reinhard Genzel and Andrea Ghez for their discoveries — including work on black holes — that have improved the understanding of the universe.
• The chemistry prize was jointly awarded to Emmanuelle Charpentier and Jennifer A. Doudna for their work on the development of Crispr-Cas9, a method for genome editing.
• When will the other Nobel Prizes be announced?
• There are two more science prizes. Physics will be announced on Tuesday, and Chemistry on Wednesday, both in Stockholm.
• The prize in Literature will be announced in Stockholm on Thursday. Read about last year’s winner, Louise Glück.
• The Nobel Peace Prize will be announced on Friday in Oslo. Read about last year’s winner, the World Food Program.
• The Nobel in economic science will be announced in Stockholm on Oct. 11. Last year’s prize was shared by Paul R. Milgrom and Robert B. Wilson.

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