Two neuroscientists, David Julius, PhD, and Ardem Patapoutian, PhD, have been awarded the 2021 Nobel Prize in Physiology or Medicine for their work surrounding the discovery of receptors for temperature and touch. Both West Coast researchers, Julius is a professor and chair of the department of physiology at the University of California, San Francisco, and Patapoutian, professor of molecular and cellular neuroscience at Scripps Research and a Howard Hughes Medical Institute investigator.
Did they expect to win? According to Thomas Perlman, secretary of the Nobel assembly, not really. Perlman, who has the task of making the early morning call, reported that both men were “very surprised,” and even “a little bit shocked.”
This is not the first time that work in the sensory system has garnered the award. In 2004, Richard Axel, MD, at Columbia University, and Linda Buck, PhD, at the Fred Hutch, were awarded the Nobel Prize for their discoveries in the olfactory system. Buck is one of only 12 women (out of 111 total prizes) to have won the Nobel Prize in Physiology or Medicine.
This year, the sense in the spotlight is somatosensation—the sense at the center of the ability to feel our body surface and internal organs—monitoring temperature, pain, touch, and the location and movement of our body.
The questions surrounding somatosensation have been the focus of great thinkers for thousands of years—documented by philosopher René Descartes in the 17th century.
Both Julius’ and Patapoutian’s work tried to understand how nerves convert the physical stimuli of heat and touch into a biological signal. To do that, they showed that receptors are able to detect and convert heat and touch into impulses, and identified which receptors are the main players. According to Perlman, explaining how, at a molecular level, stimuli can be converted into nerve signals has unlocked “one of the secrets of nature.”
Hot and cold
Anyone who has eaten a hot chili pepper knows that the minutes that follow can be uncomfortable—even painful. The body’s response to the hot pepper is triggered by the presence of capsaicin, the active compound in chili peppers responsible for inducing the burning sensation.
When someone eats the hot chili peppers, they start sweating, indicating that capsaicin tricks the brain into thinking that there is a temperature change.
Julius used this system to identify a sensor in the nerve endings of the skin that responds to heat. More specifically, his team identified the receptor for capsaicin—which turned out to be a temperature-sensitive ion channel named TRPV1. This discovery led to many more, opening up a series of findings of multiple TRP channels that are activated at different temperatures, leading to cold sensitivity and heat-induced pain.
Don’t touch
Patapoutian didn’t need capsaicin to investigate touch—the area of the sensory nervous system he was interested in. He identified a cell line that gave off a measurable electric signal when individual cells were poked using a direct, mechanical force. He used pressure-sensitive cells to identify 72 candidate genes that could include the novel class of sensors that respond to mechanical stimuli (or mechanosensors). Then, through a laborious search, his lab identified one of the 72 genes responsible for the signal. They identified an ion channel activated by mechanical force—PIEZ01.
These breakthrough discoveries launched intense research activities leading to a rapid increase in our understanding of how the nervous system senses heat, cold, and mechanical stimuli. The laureates identified critical pieces in the understanding of the complex interplay between our senses and the environment. In addition, their work lays the foundation for the development of translational applications and treatments for a wide range of disease conditions, including chronic pain.
COVID-19
In the early morning press conference, Perlman was asked by a reporter if the committee had seen, in the past year and a half, research on COVID-19 that could warrant a future Nobel Prize? For example, the two scientists who pioneered the mRNA technology that sits at the center of two successful COVID-19 vaccines.
Perlman’s answer was that seeking out new research is, “not really how we work.” Rather, their process originates from nominations. So, he said, they have to wait for the work to be nominated. But, he said reassuringly, “big breakthroughs in medicine usually reach us.”
