Discovery of temperature and touch wins the 2021 Nobel Prize in Physiology

On the afternoon of October 4, the Nobel Committee announced the 2021 Nobel Prize in Physiology, which belonged to two American scientists, David Julius and Ardem Patapoutian, for their discoveries of temperature and touch.

The announcement was made by the expert panel of the Nobel Prize at the Karolinska Institutet in Stockholm. The two scientists won the prize for "important discoveries related to the mechanism of temperature and touch receptors". Their work sheds light on how chronic and acute pain relief is associated with a number of diseases, injuries, and treatments.

"Our ability to feel heat, cold, and touch are all essential to life, and underpin our interactions with the world. In everyday life, we take feeling for granted, but how to know how nerve impulses respond to temperature and pressure , " the Nobel committee said in a press release.

Scientists Julius and Patapoutian helped answer this question. They made groundbreaking findings and began many in-depth studies, thereby learning about how the nervous system perceives hot, cold and mechanical stimuli.

Julius and Patapoutian complement humanity's lack of understanding of the complex interplay between the senses and the environment. Specifically, Julius used capsaicin, a hot compound from chili peppers, to determine how the skin's nerve endings respond to heat. His collaborator Patapoutian used pressure-sensitive cells to discover a different response to mechanical stimulation in the skin and internal organs.

The Nobel committee said the two scientists helped answer one of the most profound questions about the human body: "How do we perceive our surroundings?". "The mechanisms within the senses have intrigued us for thousands of years, such as how the eye detects light, how sound waves affect the ear, various compounds that interact with receptors (distribution of protein molecules) in the nose and mouth produce taste," the Nobel committee wrote.

In the 17th century, philosopher René Descartes used the image of a thread to describe the connection of parts to the brain. In this way, when the human foot is exposed to fire, a signal is sent to the brain. Later research showed that sensory neurons record changes in the living environment. In 1944, two scientists Joseph Erlanger and Herbert Gasser received the Nobel Prize in Biomedical Sciences for discovering different types of sensory nerve fibers, which respond to different stimuli. But one question remains open, which is "how temperature and mechanical stimulation are converted into nerve impulses?".

In the late 1990s, David Julius was working on capsaicin, the compound that gives chili peppers their spiciness, causing your tongue to burn every time you touch it. Capsaicin has been known to activate the neurons that cause pain, but how this chemical actually triggers pain remains an unsolved question.

In their original study, Julius and colleagues observed sensory neurons when they were activated by our sensations of pain, heat, or touch. He filtered out the genes that were expressed for them, and then built a library of millions of these DNA.

Julius' hypothesis was that if there was a protein-coding DNA capable of reacting with capsaicin, it would have to be in this vast collection. And to find it, he would implant each of these pieces of DNA into cells that had not previously responded to capsaicin. If a gene triggers the response, that's the target to look for.

After this meticulous process of testing, Julius finally identified a single gene that gives us the sensation of spiciness when exposed to capsaicin. Further experiments showed that this gene encodes a new ion channel protein, it was named TRPV1 , henceforth known as the capsaicin receptor .

The discovery of TRPV1 became a major breakthrough, leading Julius to later discover temperature and pain receptors. Working independently, David Julius and Ardem Patapoutian later further identified TRPM8 , a receptor that is activated when we feel cold.

With two receptors TRPV1 and TRPM8, scientists have explained why humans and other organisms perceive a range of temperatures from cold to hot and generate survival responses afterwards. For example, when TRPV1 is more strongly expressed than TRPM8, we will see heat and vice versa.

Many laboratories have pursued studies on these two receptors, for example, they have genetically engineered mice so that they have no sense of temperature. As a result, these mice lost an important viability.

Where is the origin of all our bodily sensations?

While the mechanisms that produce the sensation of heat have been explained, an important question remains about how our touch works? For example, when a needle is pricked into the skin, or when you simply make a fist, we can all feel a mechanical pressure on our skin.

Researchers have previously found bacteria to be also capable of mechanoduction, but the underlying mechanism of induction in vertebrates remains unexplored. Ardem Patapoutian, while working at Scripps Research in La Jolla, California, set out to identify this elusive mechanism.

In a breakthrough, he and his colleagues found a line of cells that emit electrical signals whenever pressure is applied to them. They assumed that the receptor activated by mechanical force was an ion channel. So in the next step, Patapoutian counted all 72 genes that could encode those receptors.

Contrary to Julius' approach of inserting genes into new cells, Patapoutian chose to inactivate them one by one to see which genes were actually responsible for the cell's ability to sense mechanical stress.

Equally hard work, but eventually Patapoutian and colleagues successfully identified a single gene that does just that, activating a new and completely unknown mechanistically induced ion channel. Scientists named it Piezo1, after the Greek word for pressure (í; píesi).

Not stopping there, a second gene has been discovered , Piezo2 , which is also strongly expressed when our sensory neurons are activated. Further studies have firmly established that Piezo1 and Piezo2 are ion channels that are directly activated when pressure is applied to the cell membrane.

Ultimately, Patapoutian's breakthrough led to a series of papers by him and other scientists demonstrating that the Piezo2 ion channel is the key receptor contributing to the human ability to perceive touch.

Furthermore, Piezo2 also plays an important role in sensing our body's position and movements, known as proprioception, or our sixth sense. Further studies on Piezo1 and Piezo2 also show that they are involved in the regulation of important physiological mechanisms in the body including blood pressure, respiration and urinary control in the bladder.

The groundbreaking discovery of TRPV1, TRPM8 and Piezo channels by this year's two Nobel laureates has allowed us to understand how temperature and mechanical force trigger nerve impulses, which in turn allows us perceive and adapt to the outside world.

This knowledge is being widely applied to the medical field, allowing doctors to treat a wide range of conditions, including chronic pain.

Taking place in the midst of the Covid-19 epidemic, the Nobel Prize 2021 was adjusted to fit the actual situation. Last year, several events were cancelled, the ceremony was held online. This year's awards ceremony combines both online and in-person formats.

The brightest candidates for this year's Nobel Prize in Biomedical Sciences are in many fields, notably research on messenger RNA (mRNA) - the premise for a Covid-19 vaccine; B and T lymphocyte white blood cells, necessary for the human immune system; and work to identify cancer risk genes, paving the way for potential treatments.

Winners are awarded the Nobel certificate, Nobel medal and prize money, next December. Total prize money last year amounted to 10 million Swedish krona, or about $1.1 million.

In 2020, the Nobel Committee named three American and British scientists, Harvey Alter, Michael Houghton, and Charles Rice, for their achievements in discovering the hepatitis C virus, contributing to saving millions of lives.

All three were honored for their "decisive contribution in the fight against blood-borne disease, a global health problem that causes cirrhosis and end-stage liver cancer , " according to the Nobel Committee.

Two scientists won the 2021 Nobel Prize in Physiology.

From 1901 to the present, the Committee has awarded a total of 111 Nobel Prizes in Physiology or Medicine. The youngest person ever to win the prize was scientist Frederick G. Banting. He was honored in 1923, at the age of 32, for discovering insulin. The oldest person is Peyton Rous for the work on detecting the tumor virus. He was named in 1966, at the age of 87.

In 2019, the Nobel Committee asked to diversify candidates by gender, geographical location and field. Of the more than 100 Nobel Prizes in Physiology or Medicine, 12 are female scientists.

Last year, two female scientists Emmanuelle Charpentier and Jennifer A. Doudna won the Nobel Prize in Chemistry for developing the CRISPR method to edit the genome. Scientist Andrea Ghez won the Nobel Prize in Physics for her work.

There is no shortage of female scientists with potential awards. However, geographical diversity remains unclear. Most of the Nobel laureates come from institutions in the US and Europe, although according to David Pendlebury, an expert at Clarivate Analytics , Asia has more studies cited.