Interview med nobelpristager i biologi om smerte
More than three decades ago, an 18-year-old boy served sandwiches at a fast food joint in Los Angeles, wearing his uniform beanie. He was a refugee of Armenian descent who had just arrived in the United States fleeing the civil war in his native Lebanon. Desperate, he started working on anything, even writing horoscopes. This Monday, that young man, called Ardem Patapoutian , has won the Nobel Prize in Medicine , endowed with almost one million euros. Patapoutian, today a 54-year-old biologist, has revealed what was one of the great secrets of human life: the proteins that perceive pressure on the skin and in other parts of the body. Caresses are felt thanks to these molecules, called Piezos.
The researcher, grandson of orphans from the Armenian genocide , has opened a new door to science. Life is not a simple dialogue between chemical substances, as was thought. Mechanical forces also play an essential role. The scientist’s laboratory – at the Scripps Institute, in San Diego (USA) – has discovered that these proteins are also involved in pain, blood pressure and even the sensation of having a full bladder with urine. Two weeks ago, Patapoutian visited Bilbao to collect the BBVA Foundation’s Frontiers of Knowledge Award, endowed with 400,000 euros , which he shares, like the Nobel Prize, with his colleague David Julius .
Question. When you were 18 years old, you wrote horoscopes in a newspaper.
Answer. Yes, I was working in an Armenian newspaper and the editor-in-chief asked me if I wanted to write some. It was weird, but I got really involved, writing messages on my friends’ zodiac signs. If someone believes in these things, let them know that there are people like me behind them, writing random sentences.
Q. You also worked at the time as a pizza delivery man and serving sandwiches. It’s a huge leap from there to winning the Kavli Prize [one million dollars] and the Fronteras. [The interview was done two weeks before he also won the Nobel Prize].
A. Yes, right? Life has wonderful surprises sometimes. I couldn’t have imagined it.
Pain is an emotion that your body creates to avoid things that are harmful to you
Q. What is pain?
R. There is discussion about what pain is. It is, above all, an emotion that your body creates to avoid things that are harmful to you. Pain is initiated by sensory processes: if I put my hand on something hot, the sensation of burning your fingers initiates the pain signal. But, in our field of research, we differentiate between nociception, which is the act of feeling something harmful, and pain, which is feeling an emotion in the brain. Pain is very helpful. There are human diseases that prevent pain and most of these people die because they take too many risks and hurt themselves. On the opposite side is chronic pain. That pain is not helpful. That is the pain that we want to suppress, for example, in people who suffer from neuropathic pain.
Q. Is pain essential to survival?
A. Yes, we need pain to survive. There are people in the Middle East who feel no pain and stick knives in shows to make money. A boy who felt no pain thought he was invulnerable and jumped from a four-story building. He died, of course. It is very important to have an internal signal that tells you: “Don’t do this.”
Q. Sometimes you can feel pain in dreams.
A. Yes, that is interesting. If you think of pain as an emotion, it is similar to other emotions, such as anger, sadness, love. It is a sensation in the brain, separate from the stimulus. So you can feel pain without any stimulation, of course, because the brain is so complex.
P. Then you can feel pain without any stimulus and vice versa: not feel pain despite the existence of a painful stimulus.
A. Exactly. A great example is pain in a phantom limb . There are people who, for example, lose an arm in the war and continue to feel pain in the fingers that they no longer have. It is very difficult to imagine, but if they put anesthesia on your stump, you stop feeling that pain in your fingers. The pain is in the brain: you can feel pain in a part of the body that you no longer have.
Q. You explain in your talks that a neuron in a basketball player can measure more than two meters. Single cell.
A. Yes, they are the longest cells in the body. If you feel a stimulus in the foot it has to quickly reach the brain to tell what is happening. Not only with pain, but also with touch, temperature and all the information from the outside that is translated through these fascinating neurons.
Q. Your team discovered Piezos proteins in these neurons in the spinal ganglia.
Proprioception is the sense by which you can close your eyes and touch your nose
Q. You know people who have these dysfunctional proteins.
A. It is fascinating. It was not known what happened to these people. The most obvious thing is that they do not walk properly. They have no coordination. Doctors often think they have a muscle problem or motor neuron disease. Nobody thinks about sensory neurons, not even in hospitals. They sequenced the genome of a family with this mysterious disease and found mutations in Piezo2 [one of the proteins in the Piezos family]. We already knew that if you inactivate this protein in mice, they don’t feel touch and they don’t have proprioception either. Proprioception is one of the most important senses we have. Most people don’t know they have it.
Q. It is a sixth sense.
A. Sometimes they call it the sixth sense. It is the sense by which you can close your eyes and touch your nose. You can do it because you know how much your muscles stretch, without seeing where your fingers are in space. So we can play the piano with our eyes closed, but you can also stand up and walk, because you receive information from your body without looking. People take this sense for granted, but there are people who do not have Piezo2 and do not know where their body is, so they walk with difficulty. They need to look at their legs to walk. And they don’t have a sense of touch either. Our most recent research shows that these people do not feel a full bladder, so they have trouble controlling their urine.
Q. Touch can become painful.
A. When touch becomes pain it is called allodynia . It is something like when you burn your skin when you sunbathe and then they touch you and it hurts. Many people with neuropathic pain cannot even put on their clothes without pain. This is totally dependent on Piezo2 proteins. People with Piezo2 deficiency do not feel pain to the touch. We are excited about the possibility that by blocking these proteins, a relevant form of pain can be inhibited. The problem is that Piezo2 has too many functions and if you completely block it with a pill, you would not feel that pain, but you would also lose touch, proprioception, the ability to feel your bladder. It is not viable. The most logical possibility would be to achieve local inhibition, by injection or administration to the skin. There are still many challenges ahead: going from basic biology to finding a drug usually takes 10 to 20 years.
Your brain tricks you into thinking you need to do something
Q. In one of your most recent research, you included a phrase by the American writer Henry Miller: “Emptying a full bladder is one of the greatest pleasures of human beings.” Is Piezo2 to thank for that feeling of happiness when going to the bathroom?
A. Absolutely. That feeling of a full bladder is due to Piezo2. One of the most fascinating aspects is that link between a mechanical sensation in the bladder and these complex emotions.
Q. You often say in your talks that the burning sensation when rinsing your mouth with Listerine is not caused by killing bacteria, but by Wintergreen oil , which acts on a temperature sensor in neurons. Is that feeling just a gimmick?
A. Totally. All those burning sensations with mouthwashes are absolutely bogus. It’s like hot peppers, which burn your mouth, but there is nothing burning, it is just a chemical that activates one of these sensors.
Q. Is pain also a chemical mirage in the brain?
A. Yes. It is like when you feel hungry: nothing is happening, except that your body decides that you need nutrients and makes you feel that way so that you act. You could say that your brain tricks you into thinking you need to do something. And usually it is right.