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Joint Nobel Prize for Temperature, Touch Receptor Discovery

The 2021 Nobel Prize in Physiology or Medicine has been awarded jointly to David Julius and Ardem Patapoutian for the discovery of temperature and touch receptors, it was announced at a press conference.

The award was revealed by Thomas Perlmann, PhD, secretary of the nobel assembly at Karolinska Institutet, Stockholm, Sweden, on 4 October, and was live streamed over the internet.

The first to be announced in a week of Nobel Prizes, it was given for discoveries that, together, “unlocked one of the secrets of nature”, said Patrik Ernfors, PhD, professor of tissue biology at Karolinska Institutet.

Narrow Criteria

The Nobel Prize in Physiology or Medicine is awarded for discovery of major importance in life science or medicine.

Alfred Nobel was “very clear in his will when he listed the criteria” for the physiology or medicine prize, explained Juleen Zierath, professor of physiology at Karolinska Institutet, and a member of the Nobel Assembly.

“He specifically stated he was looking for a discovery that would have a benefit to humankind, so our criteria is very narrow.”

In practice, that means a discovery that is “paradigm shifting”; one that has “opened doors” or changed “the way we think about a problem”. That has also been interpreted to include “basic discoveries that extend the horizon of human knowledge in profound ways”.

“Very often those basic discoveries become useful to humankind in more direct ways many years after the award, but at the time we make decisions, the immediate practical benefit is sometimes obscure.”

Candidates for the Nobel Prize cannot nominate themselves, but must be nominated by, among others, members of the Nobel Assembly and Royal Swedish Academy of Sciences, and Nobel Prize laureates in physiology or medicine and chemistry.

Proprioception

Prof Ernfors said that the 2021 prize is about somatosensation. He gave the example of a morning walk, in which one feels “the warmth of sun, the coolness of the morning dew, the caressing of morning breeze,” and the “blades of grass” beneath ones feet.

Moreover, the sensation of temperature and touch allow the detection of pain and the location and movement of our body through space and time. It is this proprioception that connects the “internal and external world”.

While the discovery of the nervous system allowed basic understanding of those systems, it was the work of David Julius, PhD, professor and chair of physiology at University of California, San Francisco, CA, with capsaicin, an active component of chili peppers, that showed how heat can be registered by the nervous system.

Prof Ernfors said that the chemical can “trick the brain into thinking there is an actual change in body temperature”, and it was Prof Julius’s assumption that this was underpinned by a single gene.

He made millions of DNA fragments, hoping one would contain the gene for the receptor. He introduced them to capsaicin-insensitive cells, finally succeeding with TRPV1. This is a heat-sensitive ion that allows scalding heat to be perceived as pain.

Prof Julius and Ardem Patapoutian, PhD, a professor in the Department of Molecular and Cellular Neuroscience at The Scripps Research Institute, La Jolla, CA, then independently searched for a cold sensitive channel, finding TRPM8.

This led on to the discovery of a number of different channels activated at different temperatures to send information to the brain.

However, touch “remained an enigma”, said Prof Ernfors.

As mechanical force can be mimicked on a cellular level, Prof Patapoutian identified 72 candidate genes for touch sensation. He silenced them one-by-one and then tested mechanistic sensitivity.

It was only when he silenced the last one, named PIEZ01, that he was able to stop cellular sensitivity. This led to the discovery of the PIEZ02, both of which encode for mechanosensitive ion channel protein that, when activated, underly proprioception.

Previous Awards

Between 1901 and 2020, the physiology or medicine prize was awarded 111 times to 222 laureates, including 12 women. The youngest laureate was Frederick G. Banting, who, at 32 years of age, was awarded the 1923 medicine prize for the discovery of insulin.

In 2020, the prize went jointly to Harvey J. Alter, from the National Institutes of Health, Bethesda, MD, Michael Houghton, from the University of Alberta, ON, Canada, and Charles M. Rice, Rockefeller University, New York, NY, for the discovery of the hepatitis C virus.

In their announcement, the Nobel Assembly said at the time that the three scientists had made a “decisive contribution to the fight against blood-borne hepatitis”.

“Prior to their work…the majority of blood-borne hepatitis cases remained unexplained,” they continued.

“The discovery of Hepatitis C virus revealed the cause of the remaining cases of chronic hepatitis and made possible blood tests and new medicines that have saved millions of lives.”

No funding declared.

No relevant financial relationships declared.

The 2021 Nobel Prize in Physiology or Medicine.

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