Some touching research took the 2021 Nobel Prize in physiology or medicine. David Julius and Ardem Patapoutian were awarded the prize October 4 for their research identifying the sensors on nerve cells that detect heat, cold and pressure.
Julius works at the University of California, San Francisco. Patapoutian, a native of Lebanon, works at the Scripps Research Institute in La Jolla, Calif. The men discovered proteins called receptors that relay sensory signals to the brain from the skin and other organs. Those signals could communicate the burning heat from chili peppers or a hot stove. They can detect menthol’s cooling sensation. They can even help you feel a hug.
The award for basic research is important. After all, touch is “such an elemental function of the nervous system, which is how we react with our environment,” says Walter Koroshetz. He directs the U.S. National Institute of Neurological Diseases and Stroke. It’s in Bethesda, Md.
The skin’s temperature sensors warn of danger from fire or extreme cold, notes Abdel El Manira. He’s a neuroscientist and a member of the Nobel Assembly of the Karolinska Institute in Stockholm, Sweden (which awards the prize for physiology or medicine).
Touch receptors are important for feeling where our body parts are in space. “Without them, we would not be able to stand. We would not be able to touch or feel our surroundings,” El Manira said. “Over the last year, we’ve been social distancing from one another. We have missed the sense of touch, the sense of the warmth we get from one another like during a hug.”
Scientists had been searching for touch and temperature receptors long before Julius and Patapoutian began their work, Koroshetz points out. “Everybody knew [the receptors] were there,” he says. It’s just that “nobody could find them.” Then the two laureates came up with some clever ways to look for the proteins.
The hunt for sensory receptors
Julius is a biochemist and molecular physiologist. To find receptors through which people feel a chili’s burn, he turned to capsaicin. It’s the compound that gives chili peppers their bite. He then found that same receptor, TRPV1, also responds to heat. The protein is an ion channel. That’s a type of molecular gate. It’s nestled in a cell’s outer membrane. And it opens or closes to control the flow of ions — charged atoms or molecules — into or out of a cell.
In this case, when TRPV1 encounters capsaicin or heat, it opens. This lets charged calcium ions into the cell. That flood of calcium triggers electrical signals that warn the brain the skin has touched something hot.
Julius used another natural compound, the winter-fresh menthol, to tease out a cold-sensing receptor. It’s known as TRPM8. Working independently and using a different method, Patapoutian, a neuroscientist, simultaneously discovered that same receptor. His work was funded in part by the Howard Hughes Medical Institute.
After spending about a year poking nerve cells in lab dishes, Patapoutian discovered a receptor that opens in response to mechanical pressure. Called PIEZO1, it’s named after the Greek word for pressure. A second receptor, called PIEZO2, also allows people to feel touch.
PIEZO2 is the receptor on nerve cells in the skin called Merkel cells. They sense light touches and caresses. This receptor also helps nerves in the lungs keep the organs from overinflating. It even plays a role in bladder and bowel functions. And children born without PIEZO2 receptors have balance problems; they can’t tell where their limbs are, Koroshetz explains. “They have to look to see where their fingers are when they reach out to grab something.” Abnormal responses by this receptor may play a role in glaucoma, an eye disease, and high blood pressure, too.
Touch and temperature receptors may help us sense pain, too. Some companies are trying to block these heat receptors. Doing so may relieve pain. But drug companies have struggled to find new medicines that would work through these receptors, says Gary Lewin. His lab at the Max Delbrück Center for Molecular Medicine in Berlin studies the molecular action of how the body responds to sensory stimulations.
A major stumbling block in new medicines, here, comes from the fact that drugs shutting down TRPV1 tend to induce a fever. Other closely related receptors may be more promising, says Lewin. Treatments based on these receptors, however, might one day offer an alternative to pain medications that can be addictive, such as opioids.
For their work, Julius and Patapoutian will split the Nobel Prize of 10 million Swedish kronor. That amounts to a little more than $1.1 million.