By Benjamin Mueller, Marc Santora and Cora Engelbrecht

CALIFORNIA – The Nobel Prize in physiology or medicine was awarded jointly Monday (4) to David Julius and Ardem Patapoutian, two scientists whose work identifying how people sense heat, cold, touch and their own bodily movements have opened the door to the development of non-opioid painkillers.

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

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

“This knowledge is being used to develop treatments for a wide range of disease conditions, including chronic pain,” the Nobel committee said in a news release.

Neither winner was easy for the Nobel committee to reach before it announced the prize around 2:30 a.m. California time. Julius said 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 Julius’ phone number.

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

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

Why did they win?

The pair made breakthrough discoveries that began intense research activities that in turn led to a rapid increase in understanding how our nervous system senses heat, cold and mechanical stimuli. The laureates identified critical missing links in our understanding of the complex interplay between our senses and the environment.

Julius used capsaicin, a pungent compound from chilli peppers that induces a burning sensation, to identify a sensor in the nerve endings of the skin that responds to heat.

Patapoutian used pressure-sensitive cells to discover a novel class of sensors that respond to mechanical stimuli in the skin and internal organs.

Why is the work important?

The Nobel committee said the two scientists helped answer one of the most profound questions about the human condition: How do we sense our environment?

“The mechanisms underlying our senses have triggered our curiosity for thousands of years, for example, how light is detected by the eyes, how sound waves affect our inner ears, and how different chemical compounds interact with receptors in our nose and mouth generating smell and taste,” the committee wrote.

In the 17th century, philosopher René Descartes envisioned threads connecting different parts of the skin with the brain. In that way, when a flame touches the foot, a signal is sent to the brain. Subsequent research found that sensory neurons register changes in our environment.

In 1944, Joseph Erlanger and Herbert Gasser received the Nobel Prize in physiology or medicine for their discovery of different types of sensory nerve fibers that react to distinct stimuli, for example, in the responses to painful and non-painful touch.

But a fundamental question has remained. How are temperature and mechanical stimuli converted into electrical impulses in the nervous system?

The work by Julius and Patapoutian, for the first time, allows us to understand how heat, cold and mechanical force can initiate the nerve impulses that allow us to perceive and adapt to the world around us.

Their work, the committee said, has already spurred intensive research into the development of treatments for a wide range of disease conditions, including chronic pain.

Who are the winners?

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, Patapoutian worked eclectic jobs for a year, delivering pizzas and writing the weekly horoscopes for an Armenian newspaper.

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

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

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

Patapoutian said he became interested in the nervous system but gravitated to studying the sense of touch and pain sensation because he said it seemed like an easier target than the brain itself. The question of how sensory neurons pick up on physical forces like pressure and temperature, he said, was not well understood.

“When you find a field that’s not well understood,” he said, “it’s a great opportunity to dig in.”

Julius, too, became fixated on the question of how the body’s sensory receptors worked. A native of Brooklyn’s Brighton Beach neighbourhood, 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,’” 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.

Not that Julius himself was a glutton for heat.

“I’m one of those people who enjoys eating habaneros out of a jar,” he said, “but everything in moderation.”

In 2020, Julius and Patapoutian received The Kavli Prize in Neuroscience, which is presided over by the Norwegian government, for their groundbreaking discovery of proteins that help bodies sense pressure.

-New York Times