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EXPLAINED: How 2021 Medicine Nobel Winners Made 'Sense' Of How We Feel What We Feel

David Julius (L) and Ardem Patapoutian are both based in California, US. (Image: Nobel Foundation)

David Julius (L) and Ardem Patapoutian are both based in California, US. (Image: Nobel Foundation)

The American duo that has won this year's medicine Nobel is behind ground-breaking work on how we sense temperature and touch

Even before we develop the ability to think, we become aware of different sensations, of heat, cold, etc. But how our senses really work has been one of the mysteries of modern science. David Julius, 66, and Ardem Patapoutian, 54, the American duo that has won this year’s medicine Nobel, have solved the question of how nerve impulses are initiated so that temperature and pressure can be perceived. Here’s the lowdown.

Why Is The Work Of The Duo Important?

That our body uses specialised mechanisms to convey different sensations to our mind and enable us to react to changes in the environment has been known for centuries. The 17th century French philosopher Rene Descartes, known for his legendary maxim, “I think, therefore, I am" (“cogito, ergo sum", in Latin), had interestingly, also investigated how sense perception works. He came to the conclusion that different parts of the skin were connected via thread-like structures with the brain and worked by carrying mechanical signals to the brain from the part of the body that was exposed to a particular sensation.

With the growth of modern medicine, it became clear that our body has specialised sensory neurons that register changes in our environment. It has also been known for some time now that nerve cells are highly specialised for detecting and translating differen sensations, “allowing a nuanced perception of our surroundings", like the ability to feel different textures or distinguish between pleasant and extreme sensations.

Where the work of Julius and Patapoutian is important is that they demonstrated how “temperature and mechanical stimuli [are] converted into electrical impulses in the nervous system", a question that had remain unsolved until they made their discoveries. The Nobel Foundation said that this year’s laureates “identified critical missing links in our understanding of the complex interplay between our senses and the environment".

How Did They Make Their Breakthroughs?

Julius has chilies to thank for his discovery of “a heat-sensing receptor that is activated at temperatures

perceived as painful". Or, more specifically, capsaicin, which is a pungent compound from chili peppers that induces a burning sensation.

Doing research in late 90s at the University of California at San Francisco, Julius homed in on capsaicin to ascertain how it causes the burning sensation when we come into contact with chili peppers. Putting in painstaking work, Julius and his collaborators “created a library of millions of DNA fragments" that are present in sensory neurons which can react to pain, heat, and touch.

Acting on the hunch that their “library" would include a DNA fragment encoding the protein capable of reacting to capsaicin and adopting a strategy of elimination that involved “laborious search", they identified a “single gene… that was able to make cells capsaicin sensitive". The newly discovered capsaicin receptor was later named TRPV1.

“When Julius investigated the protein’s ability to respond to heat, he realised that he had discovered a heat-sensing receptor that is activated at temperatures perceived as painful," the Nobel Foundation said, adding that “Julius’ discovery of TRPV1 was the breakthrough that allowed us

to understand how differences in temperature can induce electrical signals in the nervous system".

While the means of how our body perceived temperature was being unravelled, it was not entirely clear how mechanical input was converted into the senses of touch and pressure.

At Scripps research in California, Patapoutian set about to “identify the elusive receptors that are activated by

mechanical stimuli".

To do this, he first worked with his team to identify cells that gave off a measurable electric signal when they were individually prodded in a laboratory. They then zeroed in on 72 candidate genes that carried possible receptors that allowed them to respond to the mechanical prodding. After “an arduous search" that involved inactivating these genes one by one “Patapoutian and his co-workers succeeded in

identifying a single gene whose silencing rendered the cells insensitive to poking with the micropipette".

Thus, “a new and entirely unknown mechanosensitive ion channel had been discovered and was given the name Piezo1, after the Greek word for pressure," the Nobel Foundation says, adding that a second such gene was subsequently discovered and named Piezo2. This work soon became the basis of further research that showed how Piezo2 was essential for the sense of touch and played a “key role in the critically important sensing of body position and

motion". The Piezo1 and Piezo2 ion channels are also responsible for regulating processes like blood pressure,

respiration and urinary bladder control.

Why Is Their Work Helpful?

The Nobel Foundation said that the “groundbreaking discoveries… by this year’s Nobel Laureates have allowed us to understand how heat, cold and mechanical force can

initiate the nerve impulses that allow us to perceive and adapt to the world around us".

The discoveries of Julius and Patapoutian lie at the heart of research on treatments for a wide range of disease conditions, including chronic pain, it added. For their

“discoveries of receptors for temperature and touch", Julius and Patapoutian will be equally sharing this year’s Nobel for medicine.

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first published:October 04, 2021, 16:52 IST