Nobel Prize in Physiology or Medicine 2021: Receptors for Temperature and Touch

This note covers the Nobel Prize in Physiology or Medicine 2021: who won it, how David Julius and Ardem Patapoutian discovered the receptors that let our nerves sense temperature and touch, how each discovery unfolded, why these findings matter for medicine, and quick facts for exams.

What was the Nobel Prize in Physiology or Medicine 2021 awarded for?

The official citation reads: "for their discoveries of receptors for temperature and touch". This recognised two scientists who independently solved a puzzle that had troubled biologists for a very long time: how does a nerve cell know that something is hot, cold or being pressed?

In plain words, our skin and internal organs are full of sensory nerve endings. These nerves must somehow convert a physical event, such as heat from a flame or pressure from a touch, into an electrical signal that travels to the brain.

Before this work, nobody knew which exact molecules in the nerve cell membrane did this conversion. David Julius found the molecule that senses heat, and Ardem Patapoutian found the molecules that sense mechanical pressure.

The award is formally called the Nobel Prize in Physiology or Medicine, and it was announced on 4 October 2021 by the Nobel Assembly at Karolinska Institutet. The two laureates shared the prize equally, each receiving one half.

Who are the laureates?

David Julius

David Julius was born on 4 November 1955 in New York, NY, USA. At the time of the award he was affiliated with the University of California, San Francisco, CA, USA, where he had worked since 1989. He received one half of the prize.

Julius used capsaicin, the pungent compound in chili peppers that causes a burning sensation, as a chemical tool.

He searched for the gene whose protein reacts to capsaicin, and in doing so discovered an ion channel that also responds to painful heat, later named TRPV1.

This was the first molecular identification of a temperature-sensing receptor in the nervous system.

Ardem Patapoutian

Ardem Patapoutian was born in 1967 in Beirut, Lebanon. At the time of the award he was affiliated with Scripps Research, La Jolla, CA, USA, and with the Howard Hughes Medical Institute, USA, where he had been an investigator since 2014. He received the other half of the prize.

Patapoutian searched for the receptor that converts mechanical pressure into an electrical signal. Working with cells that produced a measurable current when poked, he and his team found a previously unknown ion channel family, which they named Piezo1 and Piezo2, after the Greek word for pressure.

What question were scientists trying to answer?

Humans sense the world in many ways. We already understood, at least broadly, how the eye detects light, how the ear detects sound and how the nose and tongue detect chemicals.

But a less obvious sense, the ability to feel heat, cold, touch and the position of our own limbs, remained mysterious at the molecular level.

As early as the 17th century, the philosopher René Descartes imagined a thread running from the skin to the brain, so that a foot touching a flame would mechanically pull a signal through to the brain.

This idea was later replaced by the discovery of specialised sensory neurons. Three earlier Nobel Prizes in Physiology or Medicine (1906, 1932 and 1944) had already described the structure and electrical behaviour of these nerve fibres, including the finding that different fibres react to different kinds of stimuli, such as painful versus non-painful touch.

What remained unknown until the discoveries honoured in 2021 was the identity of the actual molecular sensors sitting in the nerve cell membrane: the proteins that physically detect heat, cold or pressure and open to let an electrical current flow, starting the nerve impulse.

This was the fundamental unsolved question that both laureates addressed, each from a different angle.

How did David Julius find the heat receptor?

In the late 1990s, Julius and his co-workers at the University of California, San Francisco wanted to find the molecule that reacts to capsaicin, since this was known to cause a burning, pain-like sensation.

They reasoned that a single gene, expressed in the sensory neurons that respond to pain and heat, must be responsible.

The method followed a logical sequence of steps:

1. The team built a library of millions of DNA fragments copied from genes active in sensory neurons that can react to pain, heat and touch.
2. They inserted individual genes from this library into cultured cells that normally did not respond to capsaicin at all.
3. They tested each batch of transfected cells to see whether any of them became sensitive to capsaicin.
4. After a long search, they found a single gene that, when inserted, made the cells respond to capsaicin.
5. Further experiments on this gene's protein showed it was a novel ion channel, which was later named TRPV1.

When Julius tested whether this same channel responded to heat, he found that it activated at temperatures that humans perceive as painfully hot, around and above 40°C.

This showed that TRPV1 is a genuine heat-sensing receptor, not just a receptor for the chili compound. Independently, both Julius and Patapoutian later used the cooling compound menthol to identify a related channel, TRPM8, which responds to cold.

Other related channels were later found to respond to warmth and other temperature ranges, together forming a family of thermal sensors.

Draw a row of culture dishes, each containing cells with a different batch of inserted DNA fragments from the sensory-neuron gene library.

Add a drop of capsaicin to each dish and mark with an arrow the one dish where cells show a reaction, leading to the single gene that was later named TRPV1.

How did Ardem Patapoutian find the touch receptors?

While Julius was unravelling temperature sensing, the mechanism for sensing mechanical pressure, such as touch, remained unknown in vertebrates. Mechanosensitive channels had already been found in bacteria, but nobody had identified the equivalent receptor in animals with a nervous system.

Patapoutian, working at Scripps Research, developed a new screening strategy, following these steps:

1. His team found a line of cells that produced a measurable electric current when individual cells were poked with a fine micropipette.
2. They assumed the current was caused by an ion channel in the cell membrane that opens under mechanical force.
3. They identified 72 candidate genes that could plausibly encode such a channel.
4. Each candidate gene was silenced, one at a time, and the cells were poked again to see whether the current disappeared.
5. Silencing a single gene eliminated the mechanically activated current, revealing the receptor, which was named Piezo1 after the Greek word for pressure.
6. A second, related gene was then found through its similarity to Piezo1, and named Piezo2.

Sensory neurons were found to express high levels of Piezo2, and further studies showed that Piezo1 and Piezo2 are ion channels directly opened by pressure on the cell membrane.

Later work by Patapoutian's group showed that Piezo2 is essential not only for the sense of touch, but also for proprioception, the sense of where our own body parts are in space.

Draw a single mechanosensitive cell line being poked with a micropipette while a wire records an electrical current on a screen. Beside it, draw a checklist of 72 candidate genes being crossed out one by one until only one gene remains, labelled Piezo1.

How do these sensing channels work in the body?

Both discoveries describe the same basic principle: a protein sitting across the nerve cell membrane changes shape in response to a physical stimulus, opening a channel that lets electrically charged ions flow into the cell. This flow of ions is what starts the nerve impulse that travels to the brain.

TRPV1 and TRPM8 belong to a wider family of ion channels called TRP channels, each tuned to a different range of temperature. Research that followed the original discoveries found several more members of this family. TRPA1, found independently by the Julius and Patapoutian laboratories, reacts to pungent substances in mustard oil, garlic and similar plants, and in some species also to cold or heat. Two further channels, TRPM3 and TRPM2, were later shown to help detect painful heat and ordinary warmth respectively, working alongside TRPV1 and TRPA1.

Piezo1 and Piezo2 belong to an entirely separate family discovered specifically by Patapoutian's team, with Piezo2 concentrated in the sensory neurons responsible for touch and body position, while Piezo1 is found much more broadly across many other cell types in the body.

Beyond skin sensation, Piezo1 and Piezo2 were later shown to play roles in other organs. Patapoutian's group and collaborators reported that Piezo1 and Piezo2 together help regulate blood pressure through the baroreflex, while Piezo2 alone controls breathing by sensing the stretch of the lungs and manages urinary bladder control by detecting the filling of the bladder wall, because mechanical sensing is useful wherever pressure changes carry useful information inside the body.

How did the discovery unfold?

Note on the row for 2000: Patapoutian, who had been a postdoctoral fellow at the University of California, San Francisco, became a scientist at Scripps Research in La Jolla, California, where he was later made Professor.

Why does it matter?

These discoveries answered one of the oldest open questions in physiology: how a physical stimulus such as heat or pressure becomes an electrical nerve signal.

This is not a narrow technical detail, it underlies every moment of our interaction with the physical world, from feeling the warmth of sunlight to coordinating a step while walking or gripping a glass of water without crushing or dropping it.

The press release for the prize noted that 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.

Since the original discoveries, researchers have found that TRP and Piezo channels are involved in many additional processes, including the regulation of blood pressure through the baroreflex, breathing reflexes that stop the lungs over-inflating, and bladder control through sensors in the bladder wall.

The scientific background material noted that intensive ongoing research building on these discoveries is focused on understanding the role of these channels in a wide variety of physiological processes, and on developing treatments for disease conditions, including chronic pain.

The committee and subsequent research have pointed to possible uses in medicine, particularly in the search for new treatments for chronic pain, since TRPV1 is closely tied to how the body senses painful stimuli, and drugs that block TRPV1 have already been tested in early human trials.

Ongoing research continues to investigate exactly how these channels contribute to different physiological processes and diseases, including rare inherited conditions caused by mutations in the very genes that Julius and Patapoutian discovered.

How does this connect to what you study?

This discovery connects directly to the chapters on the nervous system studied in school biology. Students learn that sensory neurons carry information from receptors to the brain as electrical impulses, but textbooks often do not explain what the receptor molecule actually is at the start of that chain.

The work of Julius and Patapoutian fills exactly that gap: it shows that specific proteins called ion channels, sitting in the membrane of a sensory nerve cell, are the actual physical sensors.

When heat, cold or pressure causes the channel to open, charged ions flow in, and this is the very first electrical event in what becomes a nerve impulse travelling towards the spinal cord and brain.

Understanding this helps make the abstract idea of "sensation" into something concrete and molecular, bridging biology and basic chemistry of ion movement across membranes.

What happens when these receptors are faulty in humans?

Because mice cannot describe what they feel, researchers also studied people who carry natural mutations in these genes, to confirm how the channels work in humans.

In the case of TRP channels, one family was found to carry a mutation in the TRPA1 gene that causes a rare inherited condition in which cold, fasting or physical stress trigger episodes of severe upper-body pain, a disorder named Familial Episodic Pain Syndrome. Other small genetic differences in TRPA1 and TRPV1 have been linked to altered sensitivity to pain, cold or the burning effect of capsaicin in different people.

The clearest human evidence, however, comes from Piezo2. People who inherit two faulty copies of the PIEZO2 gene survive, unlike mice lacking the gene, but they show a condition marked by joint contractures in the fingers, feet and toes along with a severely reduced sense of touch, vibration and proprioception. These patients also have difficulty controlling the bladder and can suffer breathing problems around birth, matching the organ roles identified for Piezo2 in animal studies. Different mutations in PIEZO2 instead overactivate the channel and cause other inherited joint disorders.

Piezo1 mutations have their own distinct effects. Loss-of-function mutations in both copies of the gene cause a rare disorder of the lymphatic system marked by swelling of the face and limbs. Mutations that instead overactivate Piezo1 cause an inherited form of anaemia in which red blood cells lose water and become misshapen. Separately, one particular Piezo1 variant that dehydrates red blood cells is notably common in African populations and has been linked to a lower risk of severe infection by the malaria parasite Plasmodium falciparum, suggesting it may have been favoured by evolution in regions where malaria is widespread.

Together, these human genetic findings supported the animal experiments and showed that TRP and Piezo channels are not just laboratory curiosities but genuinely responsible for how real people sense temperature, touch, pain and internal body signals.

Quick facts for exams

The Nobel Prize in Physiology or Medicine 2021 was awarded jointly to David Julius and Ardem Patapoutian for their discoveries of receptors for temperature and touch.

The prize was announced on 4 October 2021 by the Nobel Assembly at Karolinska Institutet, with each laureate receiving one half of the prize.

Julius, working at the University of California, San Francisco, discovered the heat receptor TRPV1 using capsaicin from chili peppers. Patapoutian, working at Scripps Research and the Howard Hughes Medical Institute, discovered the pressure receptors Piezo1 and Piezo2.

Together, these findings explained how temperature and mechanical stimuli are converted into nerve impulses, a question that had remained unsolved for decades.

Note: Source. The prize facts in this note are from the Nobel Prize's official site, nobelprize.org.

Glossary

• Receptor — a protein that detects a specific stimulus, such as heat, pressure or a chemical, and triggers a response in the cell.
• Ion channel — a protein that forms a pore in a cell membrane, letting charged particles called ions flow across when it opens.
• Nerve impulse — an electrical signal that travels along a nerve cell, carrying information towards the spinal cord and brain.
• Capsaicin — the pungent compound in chili peppers that causes a burning sensation by activating heat-sensing nerve receptors.
• TRPV1 — the ion channel discovered by David Julius that is activated by capsaicin and by painful heat.
• TRPM8 — an ion channel activated by cold temperatures and by menthol, found independently by Julius and Patapoutian.
• Piezo1 — a mechanically activated ion channel discovered by Patapoutian's team, found in many cell types throughout the body.
• Piezo2 — a mechanically activated ion channel concentrated in sensory neurons, essential for touch and proprioception.
• Proprioception — the sense of where one's own body parts are positioned and how they are moving, without looking at them.
• Mechanosensation — the ability of a cell or organism to detect and respond to mechanical force, such as pressure or stretch.
• Sensory neuron — a nerve cell specialised to detect a stimulus from the environment and convert it into an electrical signal.
• cDNA library — a collection of DNA fragments copied from the active genes of a particular tissue, used to search for a specific gene.

Common errors and misconceptions

• Misconception: David Julius and Ardem Patapoutian worked together as a team on one project. Correct: They worked independently at different institutions, and were jointly awarded the prize for separate discoveries on temperature and touch.
• Misconception: TRPV1 only senses the chemical capsaicin. Correct: TRPV1 is primarily a heat receptor; it is also activated by capsaicin, which is how Julius first identified it.
• Misconception: Piezo1 and Piezo2 do exactly the same job. Correct: Piezo2 is concentrated in sensory neurons and is essential for touch and proprioception, while Piezo1 acts more broadly in many other cell types in the body.
• Misconception: The receptor for touch had already been known before Patapoutian's work. Correct: Mechanosensitive channels were previously found only in bacteria; the vertebrate touch receptor was unknown until Patapoutian's discovery.
• Misconception: The prize was given for inventing a medical treatment. Correct: The prize recognised a basic scientific discovery about how nerve cells sense temperature and touch, not a finished treatment.
• Misconception: Only one gene was tested to find each receptor. Correct: Both discoveries required screening large numbers of candidate genes, such as the 72 candidates tested in Patapoutian's search.

Exam-style questions with model answers

Q1. For what discovery was the Nobel Prize in Physiology or Medicine 2021 awarded? [2 marks]

1. It was awarded for the discoveries of receptors for temperature and touch, made by David Julius and Ardem Patapoutian.

Q2. Name the two laureates and state one discovery made by each. [2 marks]

1. David Julius discovered TRPV1, the heat-sensing receptor, and Ardem Patapoutian discovered Piezo1 and Piezo2, the pressure-sensing receptors.

Q3. Explain how David Julius identified the gene for the heat-sensing receptor. [4 marks]

1. Julius and his co-workers built a library of DNA fragments from genes active in sensory neurons that respond to pain and heat. They inserted individual genes from this library into cultured cells that did not normally react to capsaicin. After testing many batches, they found a single gene that, once inserted, made the cells sensitive to capsaicin. Further study showed this gene encoded a novel ion channel, later named TRPV1, which was also activated by painful heat, confirming it as a genuine heat sensor.

Q4. Describe the method Ardem Patapoutian used to discover Piezo1. [4 marks]

1. Patapoutian's team first found a cell line that produced a measurable electric current when individual cells were poked with a micropipette. Assuming this current came from a pressure-activated ion channel, they identified 72 candidate genes that might encode it. Each gene was silenced one at a time, and the cells were tested again by poking. Silencing a single gene eliminated the current completely, revealing the mechanosensitive channel, which was named Piezo1 after the Greek word for pressure.

Q5. Discuss why the discoveries of TRPV1, Piezo1 and Piezo2 matter beyond basic science. [5 marks]

1. These discoveries solved the long-standing question of how heat and pressure are converted into nerve impulses, filling a gap left by earlier Nobel-winning work on nerve fibre types. Beyond this basic understanding, the identified channels have since been linked to many other body functions: Piezo channels help regulate blood pressure, breathing reflexes and bladder control, while TRP channels are central to how we feel and respond to painful heat and cold. Because these channels are closely tied to pain pathways, they are of particular interest for developing new treatments for chronic pain, and ongoing research continues to explore their roles in a wide range of physiological processes and diseases.

Q6. What is proprioception, and which receptor is essential for it? [2 marks]

1. Proprioception is the sense of the position and movement of one's own body parts, and the Piezo2 channel discovered by Patapoutian's team is essential for it.

Q7. Compare the temperature ranges sensed by TRPV1 and TRPM8. [3 marks]

1. TRPV1, discovered by Julius, is activated by temperatures perceived as painfully hot, around and above 40°C, and also by capsaicin. TRPM8, discovered independently by Julius and Patapoutian, is activated instead by cold temperatures and by the cooling compound menthol. Together they show that different TRP channels are tuned to different ends of the temperature range, allowing the nervous system to distinguish heat from cold.

Key takeaways

• David Julius and Ardem Patapoutian shared the Nobel Prize in Physiology or Medicine 2021 for discovering receptors for temperature and touch.
• Julius found TRPV1, a heat- and capsaicin-activated ion channel, by screening DNA from sensory neurons in the late 1990s.
• Julius and Patapoutian independently found TRPM8, a cold- and menthol-activated ion channel, in 2002.
• Patapoutian discovered Piezo1 and Piezo2 by silencing 72 candidate genes one by one in a pressure-sensitive cell line.
• Piezo2 is essential for touch sensation and for proprioception, the sense of body position and movement.
• These discoveries answered a long-unsolved question about how physical stimuli become electrical nerve impulses.
• Piezo and TRP channels also contribute to blood pressure control, breathing reflexes and bladder function.
• The findings have opened research directions towards new treatments for chronic pain.

Test yourself

Where was David Julius affiliated at the time of the award?

David Julius was affiliated with the University of California, San Francisco, CA, USA, at the time of the award.

Where was Ardem Patapoutian affiliated at the time of the award?

Ardem Patapoutian was affiliated with Scripps Research and the Howard Hughes Medical Institute, both in the USA.

What compound did Julius use to find the heat receptor?

David Julius used capsaicin, the pungent compound in chili peppers, to identify the heat-sensing receptor TRPV1.

What is the name given to the pressure-sensing ion channels discovered by Patapoutian?

Patapoutian named them Piezo1 and Piezo2, after the Greek word for pressure.

How many candidate genes did Patapoutian's team test to find Piezo1?

Patapoutian's team identified and tested 72 candidate genes, silencing each one in turn until Piezo1 was found.

Which cold-sensing channel did both laureates find independently?

Both David Julius and Ardem Patapoutian independently identified TRPM8, a channel activated by cold and by menthol.

What body function, besides touch, depends on Piezo2?

Piezo2 is also essential for proprioception, the sense of the position and movement of one's own body parts.

When was the Nobel Prize in Physiology or Medicine 2021 announced?

The prize was announced on 4 October 2021 by the Nobel Assembly at Karolinska Institutet.