How Humans Sense / Davos 2025

Summary

This discussion features Nobel laureate Ardem Patapoutian explaining his groundbreaking research on the sense of touch and proprioception. Patapoutian introduces the concept of somatosensation, which encompasses touch, temperature sensing, pain, and proprioception. He focuses on proprioception, describing it as the ability to sense the position of one’s body parts without visual input.

Patapoutian details his discovery of piezo proteins, which are responsible for sensing pressure in various bodily functions. He explains how these proteins work at a molecular level, even demonstrating their mechanism using a tattoo on his arm. The discussion highlights the importance of piezo proteins in touch, pain, and internal organ sensing, as well as their presence across different species, including plants.

The conversation then shifts to the challenges in discovering these proteins and the potential medical applications of this research. Patapoutian discusses ongoing work to develop treatments for conditions related to piezo protein deficiencies or malfunctions. He also shares insights on the scientific process and career advice for aspiring researchers.

The Q&A session explores topics such as the variations in piezo proteins, their role in space travel and bone density, and the development of targeted therapies. The discussion concludes with questions about individual differences in pain perception and the complexities of how the body interprets sensory information.

Overall, this discussion provides a comprehensive overview of cutting-edge research in touch and proprioception, emphasizing its wide-ranging implications for human health and biology.

Keypoints

Major discussion points:

– The sense of touch and proprioception, including their importance and how they work

– Discovery of piezo proteins as mechanosensors responsible for touch, proprioception, and other pressure-sensing functions in the body

– Wide-ranging roles of piezo proteins in human physiology, plants, and even single-celled organisms

– Challenges in studying mechanosensation and lessons learned from a career in scientific research

– Potential therapeutic applications targeting piezo proteins

Overall purpose:

The goal of this discussion was to explain the groundbreaking discovery of piezo proteins and their critical role in touch, proprioception, and other pressure-sensing functions across biology. It aimed to convey the importance and wide-ranging impacts of this research to a general audience.

Tone:

The overall tone was enthusiastic and engaging, with the speaker using humor, personal anecdotes, and even a tattoo demonstration to make complex scientific concepts accessible. The tone remained consistently passionate and informative throughout, with an emphasis on conveying the excitement of scientific discovery. The Q&A portion maintained this tone while delving into some more technical aspects of the research and its implications.

Speakers

– Ardem Patapoutian: Nobel Prize winner, scientist studying touch and pressure sensing

– Irene Tracey: Pain scientist, session moderator

– Audience: Attendees asking questions

Additional speakers:

– Yuki: Musician mentioned, performed earlier

– President Obama: Mentioned in an anecdote

– Alex Chesler: Colleague at NIH, mentioned for work on piezo protein mutations

– Christoph Neumann: Artist, created drawing mentioned in presentation

Expanded Summary of Discussion on Touch and Proprioception Research

This discussion featured Nobel laureate Ardem Patapoutian, moderated by pain scientist Irene Tracey, exploring groundbreaking research on the sense of touch and proprioception. The session began with a musical performance by Yuki, setting a unique tone for the scientific presentation that followed.

Introduction to Somatosensation and Proprioception

Ardem Patapoutian introduced the concept of somatosensation, encompassing touch, temperature sensing, pain, and proprioception. He emphasized the unique and profound nature of touch, highlighting its diversity and complexity. Patapoutian described proprioception as “the most important sense that you have that probably many of you didn’t even know that you had,” crucial for everyday movement and coordination.

To illustrate the sensitivity of touch, Patapoutian mentioned that humans can feel a deflection on their skin as small as 10 nanometers, equivalent to the diameter of a small virus. He also touched on the importance of affective touch in emotional health and social interactions, sharing an anecdote about President Obama to exemplify the power of touch in human communication.

Discovery and Function of Piezo Proteins

Patapoutian’s groundbreaking discovery of piezo proteins, responsible for sensing pressure in various bodily functions, was a central focus. He creatively demonstrated their mechanism using a tattoo on his arm, making complex scientific concepts more accessible to the audience.

Piezo proteins were described as pressure-sensitive ion channels that change shape when stretched. Their role extends beyond touch, encompassing:

1. Pain and itch sensation

2. Internal organ sensing

3. Breathing regulation

4. Blood pressure control

5. Bladder function

Importantly, Patapoutian highlighted that piezo proteins are present across many species, including unicellular organisms and plants. In plants, these proteins play a role in root growth and mechanosensing. The speaker detailed how individuals with piezo mutations have severe deficits in touch sensation and proprioception, emphasizing their critical nature in human physiology.

Challenges in Research and Scientific Process

Patapoutian shared insights on the challenges faced in discovering these proteins, noting their widespread distribution in the body made isolation difficult. He emphasized the importance of changing fields and bringing new perspectives to scientific discovery, particularly highlighting the value of immigrants in bringing fresh ideas to research.

Advice for Scientists and Professionals

Patapoutian stressed the value of creating time to think and not being too busy, viewing this as crucial for creativity in science. He advised:

1. Changing fields to bring new perspectives

2. Creating unstructured time for creative thinking

3. Embracing failure as part of the scientific process

4. Collaborating with others to broaden one’s scientific approach

Potential Medical Applications

The discussion explored potential medical applications of this research, including:

1. Developing treatments for conditions related to piezo protein deficiencies or malfunctions

2. Possibility of piezo-blocking drugs for certain pain conditions

3. Using genetic databases linked to health records to connect conditions with specific genes

4. Exploring the role of pressure sensing in immune cell functions

Patapoutian and Tracey acknowledged the complexity and time-consuming nature of translating scientific findings into practical applications, noting it often takes 10-15 years for discoveries to reach clinical trials.

Q&A Session and Further Explorations

The Q&A session covered various topics:

1. Variations in piezo proteins across individuals

2. Their role in space travel and potential link to bone density in astronauts

3. Development of targeted therapies

4. Individual differences in pain perception, noting that pain experiences vary between individuals and are influenced by internal states

An audience member, identified as a physician, inquired about genetic variations in Piezo channels associated with pain syndromes, prompting a discussion on the potential for discovering Piezo-related genetic variations linked to pain conditions.

Conclusion and Future Directions

The discussion concluded by emphasizing the crucial role of piezo proteins in various bodily functions, their presence across species, and the potential for new therapeutic applications. It highlighted the importance of interdisciplinary approaches and creative thinking in scientific discovery.

Unresolved issues and areas for future research were identified, including the full extent of piezo protein functions, potential systemic treatments, mechanisms of individual pain experiences, and long-term effects of piezo protein mutations on human health and development.

Overall, the discussion provided a comprehensive exploration of touch and proprioception research, effectively bridging highly technical content with accessible explanations, while offering valuable insights into the scientific process and career development in research.

Ardem Patapoutian: I will explain what that’s all about within a minute, so just be patient with me. I think the sense of touch is one of the most amazing senses. It is very diverse, it’s very unique, and it’s very profound. Compared to other senses, vision, smell, taste, hearing, which are easily defined, the sense of touch is a bit more different. What I mean by that is, so for example, if you think of the fifth sense, of course touch is normal, but it also includes, if you define it more generally, sense of temperature, sense of pain, sense of your internal organs, we call it interoception. In scientific terms, we sometimes call this somatosensation. And what keeps them all together is that they sense physical stimuli, like temperature, and translate it into chemical signals that the neurons can understand. But my favorite sense within this whole idea of somatosensation is actually proprioception. So what is this? I call it the most important sense that you have that probably many of you didn’t even know that you had it. What it really is, is that as you move around, your muscles get stretched, and from how much your muscles are stretched, you have a very clear idea of where your limbs are in space. I can, for example, close my eyes and know exactly where my fingertips are and touch my nose. I can walk, coordination without looking. You can do tightrope walking, like this image shows, or perhaps most impressively, play an amazing piece of music, like Yuki just did, blindfolded. So why do we not know about this, and why do we take it for granted? I think mainly because you can’t turn it off. You can close your eyes and imagine a world without sight, but you can’t turn proprioception off, and so it’s always there. So we’re going to talk about this, but coming back to the tactile skin touch sensation, it’s really amazing, the sensitivity. So you can sense indentations in your skin that is 1 500th diameter, 1 500 diameters of the human hair. So take the human hair, divide it into 500 times, that little of indentation in your skin, and you can feel it. But literally, it’s not just about sensitivity, there’s quality too. And, of course, touch is very pleasant, and we call this affective touch, and we know that without it, your emotional health is really relying on this sense of touch. But, you know, I think this picture, to me, shows the power of touch more than any other. So this little guy is visiting the White House, and he’s very shy, and he tells the president that, I heard that other kids tell me that my hair looks like yours. And President Obama just bends down and says, Touch it, dude. And so we often say seeing is believing, but clearly touching is believing as well. And I’m not just talking about the texture of his hair. Once again, that affective touch, the pleasantness of touch, for this boy to feel like someone that looks like him, that his hair feels like his, is the President of the United States, is a very powerful message. So the flip side of touch is, of course, pain. And this is a beautiful painting by Frida Kahlo. She suffered through chronic back pain, and this is her imagination or telling you how pain feels to her. So pain, acute pain itself, is absolutely essential for life. But chronic pain, we usually define chronic pain as pain that lasts after the stimulus that caused it is gone away. And that’s a major unmet medical need. People suffering from neuropathic pain, we don’t have great medications for it, and so it’s a very important medical field as well. And pain is complicated. It’s a sensation as well as an emotion. So all of these, touch, proprioception, temperature sensation, pain, how do you sense this? You have neurons on two sides of your backbone, next to the spinal cord, and these little balls that you see, I think this works. I went backwards instead of using the lighter. These balls that you see are groups of about 8,000 neurons that send these tiny little processes. We call them neurites. They look like little antenna, and they innervate every part of your body. They get information from there, take it to the spinal cord and the brain, and it’s through these neurons. This is a zebrafish embryo, a video of it developing. This network of sensors tell you all this information that we talked about. So if we now think more from a molecular point of view, you know, genes and proteins, how do you do this? How do you sense protein? The thing that was in common to everything I said, sensing touch, proprioception, pain, is all about sensing pressure. So we knew for a long, long time that there are these specialized molecules called ion channels that sit outside the cell. The cell is surrounded by lipid bilayer, this fatty thing that protects the cell. But to communicate with the outside, there’s this protein that sits there and does different things. The ones that we care about is there should be pressure sensing, in the sense that if that membrane is stretched, you want them to open and let ions in. And this is the language of neurons. If there’s ions coming in, it’s like little electricity going into the neuron, and that’s enough to start the whole signal to tell the brain what’s going on. But what is the identity of this protein was unknown for the longest time, and that’s what my lab was studying. So how do we find this? Initially, we tried to find it directly from neurons, but that proved to be very difficult. So in science, sometimes we say, we take a reductionist point of view. So we found a cell that we can grow in a dish in a culture in the lab that was mechanosensitive. And we found the protein within this. So what you’re looking at is actually the assay that we used to measure this. There are two glasses involved. What you’re seeing here is the cell. With this glass probe, we’re actually poking the cell, giving it some little pressure. And on this glass, we’re actually recording the electric current that this pushing would cause if it had this ion channel. I’m not going to go through how we did and what we found. But we did find the gene or the protein that is responsible for pressure sensing. And this is what it looks like. This is the structure of the protein that we have resolved. And it’s a thing of beauty. So it has three identical members here drawn in three different colors that come together. In the center is that when schematically I showed is the pore where the ions would go through. But the characteristic feature of this protein is all these little ribbons. We call them helices that actually are used to extend into the plasma membrane. And this is how they sense it. And you can see it has this bizarre puckered dimension. The cell is supposed to look like this. And this protein is looking like this. It’s very unusual for a protein to be that way. But we figured out that that’s actually how it’s pressure sensitive. And I’ll show you in the next slide. So what we in the field, us and others, have found out that when you stretch the cell, this shape that’s closed up actually opens. It stretches. It’s like a little molecular machine that can change shape. And when it opens, you get these ion channels coming through. OK. So now I have slides. I can easily show you this mechanism. But a few months ago, I thought, what if I was in a bar talking to someone? And I love talking about my science. And I wanted to show how this works. What would I do? So this is like a little bit of performance art in the middle of science. I’m going to ask Yuki to hold my jacket for a second. And so I thought the best way to do this was to get a tattoo of this protein so that I can demonstrate it without slides. So here it is. Woo! Woo! Woo! Woo! Thank you. Thank you. And it’s instructional, although my institute has not reimbursed me for the cost of this. And if you look at it, I’ll try to do it. So this is open. And here’s closed. So I can really show the biology of it right here on my arm. A parlor trick, if you will. Thank you. OK, where were we? Tattoo. Tattoo. OK, so I mean, we found the thing. What does it do? So we’ve used both animal models to see what they do. And indeed, without this protein, animals do not sense touch. They do not have proprioception. It means they’re uncoordinated. And then our colleagues, Alex Chesler and others at the NIH, actually identified individuals who have mutations in the piezo protein. And very interestingly, these individuals, just like what we’ve shown in the mice, they have severe deficit in touch sensation and proprioception. So this is one such individual. She’s blindfolded, just like Yuki. But she doesn’t have piezo, too. And she’s simply asked to walk in a straight line. As you can see, she has major issues doing this because of this lack of proprioception. Happy to talk about it later. Clinically, this is so interesting because doctors are not used to sensory deficits. And when this individual, for example, went to see doctors, they just told her that she must have muscle problems, motor neuron problems. It’s not just you. Even doctors don’t know about proprioception. But there’s now about 100 individuals who have been identified worldwide that have this deficit. And so it’s becoming a new syndrome. And we’re learning so much more about the importance of proprioception and, hopefully, how we can treat it better. So piezos, over the last 10, 14 years we’re studying, they’re doing so many things. But everything has to do with pressure sensing. All those things in your body that happens because of pressure or tension seems to be mainly through these ion channels. So I talked about touch and proprioception. We’ve shown that some form of pain is through piezo, too. And this is called tactile aladynia. Two complex words. All it means is that when touch becomes painful. So you experience this, for example, after sunburn or injury. But this is something that folks suffering from neuropathic pain experience all the time. So very important clinical manifestation. Mechanical itch. If you have blood crawling on your skin or wear a sweater that’s very itchy, that’s through piezos. Every time you experience these things, please think of piezo. Another thing I quickly mentioned in the beginning is this idea of interoception, which is sensing of internal organ, your internal self. And these are also piezo dependent. We found, for example, that every breath you take, you’re sensing how much your lung stretches. And with this information, you’re controlling your breathing rate. Baroreception is control of blood pressure. Now, you’re completely not conscious of this. But with every heartbeat, your aortas have sensors that are measuring your blood pressure and changing it to make sure you have constant blood pressure all the time. You’re not even aware that your body is doing this. Now, this one you’re very conscious of. Again, every time you have to go to the restroom, think of me. Think of piezo. As your bladder stretches, it’s telling you it’s time to go. And individuals who have mutation in piezo2 that I mentioned actually have this problem. They don’t sense the bladder filling at all. So they go to the restroom three, four times a day to avoid accidents. Also for gut motility, and there’s lots of new research that we haven’t even started yet. I love this drawing by Christoph Neumann. And it’s telling you that he’s very full. Now, if you eat a lot, you feel full. It sounds very mechanical. But most of research on this is based on nutrient sensing. Nobody really has studied how much this stomach stretch contributes to how much you eat, when you eat, diabetes, obesity, et cetera. And me and our colleagues are now studying this to understand and have a new way of understanding and treating diseases associated with this. So everything I told you till now is about humans and animals. But remarkably, piezos are actually present in almost every species we know. They’re present in even unicellular organisms. They’re present in plants. In one of the studies that we did, actually, we found that piezos are expressed at the tips of plants’ roots. And then they are actually required there to sense how rough the soil is and to navigate the soil through that. So just imagine evolution, once it has found this sensor of pressure, it uses it for you to sense touch and for plants to sense the dirt, the soil that they have to penetrate. I find that quite an amazing example of evolution. So that’s all the science I was going to tell you today. Also, I feel it’s a bit presumptuous to say I feel it’s a bit presumptuous that I am giving you some lessons I’ve learned across the 25 years of research that I’ve done. And some of these, I think, mainly apply to scientists. But I actually think that anyone can potentially benefit from this. And all of you at Davos are people who have lots to do all the time. And this is my favorite concept that I adhere to very strongly. And that is, don’t be too busy. I feel like I’m not creative when I’m busy. And so I create the time for myself to be able to think, read, and not just do busy work. I have meeting-free Tuesdays, for example. No meetings on Tuesday. I love it. Change fields. I’ve changed fields a lot during my career. And I think it’s such a, to do something else is so important, because it brings a new experience. You bring your experience, new perspective to new problems. And you can look at this concept in as wide of an angle as you want. I’m also an immigrant, Armenian, born in Lebanon, came to US. And I think immigrants bring so much new perspective with them. And so big fan of that. It’s kind of funny in a list of advice to tell you don’t listen to advice. But I also find this very useful, because in the beginning of my career, you get so much advice. And sometimes when you hear it from distinguished people, like all of you here at Davos, you feel like you have to listen to them, but you don’t. It has to make sense to you. Surround yourself with critics. This is so important, especially if you’re in a place where people are always praising you and saying nice things about you. It’s very important. And I don’t seem to have a problem with this, because all my family and friends are very eager to criticize me. And I think the last one is, for me, I could say that I got into science to cure diseases. But the reality is I did it because I love it. It’s fun. And I think for many of you, probably, you do what you do because you think it’s fun. But I also realize that sometimes the little details take over. And oh, my grant was not funded. My paper is not accepted. It kind of gets to you, and you stop. You pay more attention to those or not. So I like to remind myself once in a while that I do this because it’s super fun, and just kind of ignore the annoying details. Anyway, thank you very much for coming to this session. And I think now we have time for some Q&A with Irene.

Irene Tracey: All right. Well, hello, everybody, and welcome to this session. We definitely will have time for some of your questions, but before that, let me just first of all on your behalf and once again from me as a fellow pain scientist congratulate Adam not just on winning the Nobel Prize, deservedly so, but just on a fantastic presentation there. This is a really tough subject and your skill at presenting it in such an accessible way is absolutely awesome, so thank you so much for that, and also to you, Keith, for that stellar performance. Absolutely wonderful, so thank you. Thank you. Thanks for sending it. I didn’t know you had a tattoo, so the burning question literally I have is how painful was it to get that done? Because that’s a huge, huge tattoo. I’m just wondering.

Ardem Patapoutian: It took six hours. It was painful, and you know, different parts of your body are more painful than others, and this, where the cap of the protein is, is quite painful, but as I was getting it, I was totally amused by the fact that what I’m sensing is partly because of what’s being tattooed, so there are a lot of interesting parallels.

Irene Tracey: A lot of symbolism in having it done. It’s a very cool thing, and it works really well. I think it’s a demo. It’s a fantastic thing. Ardem, considering how important proprioception is, as you very clearly detailed, it strikes me as odd that it’s taken this long for us to discover it. Why do you think it has been such a challenge? I mean, it goes back to sort of that need to persist in science and having the fun with it and keeping going, but it is, you know, striking that it’s, you know, this is a recent discovery, and so what were some of the hurdles, and why did you particularly want to go into that space? I mean, I think about this a lot.

Ardem Patapoutian: I think the other senses, vision, taste, and smell, I don’t want to get into much technical detail, but because they’re in one place, there’s a lot of material for neuroscientists to take and tease apart. They also were in a group of proteins, GPCRs, that are very homologous, so you can, if you find one, you find ones that look like this. This, as I said, you saw those neurons extending. They’re all over the place. You don’t have easy access to it, and we didn’t know what this was going to look like. So in the genome, you have 20,000 proteins, and we had no idea which one it is. One in 10 are membrane proteins, but that’s 200, so that’s very, very difficult, 2,000, so that’s very difficult to kind of parse it out. In science, a lot of times, discoveries happen when the unknown question starts overlapping with technology that’s available, and in this case, you know, molecular biology has come a long way, and there was this technology called RNAi, where you can knock down one gene at a time and see what happens, and we didn’t have this technology before, so you couldn’t do this cellular experiment that we did. But yeah, the general idea is that for any young scientist listening to this and picking a question, pick the biggest unanswered question, but with the practical idea that it should also, you should have the tools to address this in the next 5, 10 years.

Irene Tracey: Yeah, it’s a really key point, particularly those maybe listening online as well. You’ve presented the one structure, and you’ve obviously got it forever emblazoned on your arm. That’s a vulnerability, though, in biology, so presumably there must be some what we call redundancy or variations of a theme. I’m just interested for the audience and listeners online to learn how many different types of that are available so that if you sort of had a genetic mutation and one was knocked down, you could see from that video just how devastating that would be for humans, really worried about what would happen in plants, considering food security issues. So could you bring to life a little bit the work you’re doing to understand maybe the question about how resilient are we with maybe a few variations of those receptors?

Ardem Patapoutian: So we have two PSOs, and it seems like PSO2 is mainly in neurons, but we’re finding that PSO1, the sister molecule, is expressed in many different cells, in immune cells, and one of the very exciting directions we’re going is the way I introduced it, we knew there was all this pressure sensing in the body, and then kind of what I call the first stage of our discovery was to say, ah, yes, PSO2 is responsible for touch, for this type of pain, et cetera. Now we’re finding completely new areas of biology that are dependent on pressure sensing, immune cells, macrophages, eating up red blood cells, for example. Nobody really thought about that being a mechanosensitive, very important immune function, but we showed that that’s indeed the case. This and many other cases, I think in 10 years, we’re going to look back and say, we had underestimated how important physical sensing is to our physiology, and usually diseases.

Irene Tracey: Yeah, I can see another Nobel Prize coming, because there’s a lot more discoveries yet to be had, and it’s sort of on a systems level, which is sort of where I work at the sort of brain end of things, you know, that importance of touch, as you say, the communications between the immune cells, different cells, different roles for it that we wouldn’t understand. It sort of emphasizes the community sense, and why do people turn up in freezing cold Davos and slip around on the ice? It’s because we want to be together, so whether at a molecular level all the way through to a sort of a community level, I think there’s some really interesting points there about the importance for biology and life to have touch and to communicate.

Ardem Patapoutian: I totally agree, and I find fascinating is how you can start with the molecule, it kind of opens the door to understand bigger questions of biology and physiology, and we’re having a great fun doing it.

Irene Tracey: And just, you know, slightly left field question, what happens in space when there’s no gravity? What’s the sort of cost? Because often they say when they come back, if they’ve been out on the space station, they have some trouble walking, they talk about proprioception being gone. Are they right?

Ardem Patapoutian: It’s actually, this is not our work, but this is actually also PSO dependent. So astronauts who go into outer space, and if they stay there without gravity for a while, they come back with reduced bone density, which is of course not good. And in mice, at least it’s shown that if you don’t have PSO1 in the bones, you have the same thing without having to go into outer space, that bone density is controlled by, so the constant tension in the bones is really required for this. And this bone density and pressure works both ways. For example, professional tennis players who use one arm much more than the other have higher bone density in their dominant arm compared to the other. So just again, another example of, you don’t think about it all the time, but pressure and biology, there’s lots

Irene Tracey: of links there. Yeah, really interesting. And before I open up for questions from the audience for the last couple of minutes, you know, what are the therapies that can come for those sort of rare conditions that are lacking the PSO? Are you working in that space about sort of genetic engineering?

Ardem Patapoutian: Absolutely. So one of the trouble with, you know, it’s so hard to make drugs for various diseases, and as I said, there’s a need for pain medication. And there’s been many, for example, that they are developed in animal models and then don’t translate to humans. What’s good about this, what we call Target, is that I showed you we have human validation, proof of concept that it will work. The concern here is that although tactile aladinia we know will be in a way ameliorated by blocking PSO2, obviously it’s not a drug that you would want to take orally and get rid of all your touch and proprioception and pain. Nobody wants to do that. And so we’re trying to develop small molecules that would block PSO2, but it has to be in indications where it could be used topically, like only on your knee, on your elbow, for example, so it doesn’t interfere with your normal body functions. It’s early stage. It really takes another channel, TRPA1, that my lab cloned up. There’s phase two clinical trials on it. We found it 20 plus years ago. So it’s just, there’s so much work to be done from the basic biology to translation.

Irene Tracey: Yeah, that’s just a long journey. Well, it’s time for you to have the opportunity to ask Ardo any questions. So we have a roving mic, if you could just put your hand up. Please, the gentleman at the back.

Audience: Thank you. That was amazing in so many levels. I’m a physician and I was wondering, outside of patients who have an obvious neuropathy from nerve damage, there’s patients who have actually hyperpatic syndrome and pain and all that. Is that a hyper excitability of those receptors or it’s a decrease in a threshold? What is the mechanism?

Ardem Patapoutian: There are other genes, including TRPA1, that we’ve talked about where it’s hyper excitability causes pain syndromes. We haven’t found any that’s associated with PSOs yet, but that doesn’t mean it doesn’t exist. There’s very exciting databases now of genetic data associated with your health record, UK Biobank, US is starting one called All of Us. And these kind of databases really help us connect what conditions are associated with what genes. So work in progress.

Irene Tracey: Fantastic. I’m just going to ask the organizers, can I take another two questions? Is that okay? I know online have gone off, but it’d be great to have one more question. One more, one more question. I think there was somebody on this side. Hands up again, those who’d like to… Okay, gentleman in the front.

Audience: And that was great. Thank you. Do different people feel pain differently? So if I put my finger in hot boiling water and you put your finger in boiling water, is it different?

Ardem Patapoutian: Absolutely. I think there’s what we call neuroscientists as internal state, which really dictates. So you’re not automatic electrical wires. I gave the thing, but it’s not quite like that. I’ll give you the easiest explanation. You’re outside in Davos, you’re super cold. You go take a warm shower, it feels so nice. But if you went on running on a hot day and you come and take a shower at the same temperature, you’d find it painfully hot. And so within your individual, the same stimulus is different all the time. So there’s no question that we all experience things slightly differently.

Irene Tracey: I’m so sorry we’ve run out of time, but Ardem, I’m sure you’re willing to stay for a few moments either here or outside the room if there’s somebody else coming in to take a few more questions, because I can sense the hands up. Thank you all for coming. Adam, thank you so much for giving a brilliant presentation. Congratulations once again, and to Yuki as well.

Agreement Points

Importance of proprioception

speakers

– Ardem Patapoutian
– Irene Tracey

arguments

Proprioception allows awareness of limb position and coordination without visual input

Individuals with piezo mutations have severe deficits in touch sensation and proprioception

summary

Both speakers emphasize the critical role of proprioception in human movement and coordination, highlighting its often overlooked importance in daily life.

Piezo proteins’ diverse functions

speakers

– Ardem Patapoutian
– Irene Tracey

arguments

Piezos are involved in many pressure-related functions beyond touch, including pain, itch, and internal organ sensing

Piezo proteins are pressure-sensitive ion channels that change shape when stretched

summary

The speakers agree on the wide-ranging functions of piezo proteins in various biological processes, from touch sensation to internal organ function.

Similar Viewpoints

Both speakers acknowledge the complexity and time-consuming nature of translating scientific discoveries into practical applications, emphasizing the importance of persistence and diverse perspectives in scientific research.

speakers

– Ardem Patapoutian
– Irene Tracey

arguments

The journey from basic science discovery to clinical applications is long

Changing fields and bringing new perspectives is important for scientific discovery

Unexpected Consensus

Importance of touch in social and emotional contexts

speakers

– Ardem Patapoutian
– Irene Tracey

arguments

Touch is a diverse and profound sense that includes temperature, pain, and proprioception

The journey from basic science discovery to clinical applications is long

explanation

While the main focus was on the scientific aspects of touch and proprioception, both speakers unexpectedly touched upon the social and emotional importance of touch, highlighting its role in human interaction and emotional well-being.

Overall Assessment

Summary

The speakers demonstrated strong agreement on the importance of piezo proteins in various biological functions, the significance of proprioception, and the challenges in translating scientific discoveries to clinical applications.

Consensus level

High level of consensus, with both speakers complementing each other’s points and building upon shared understanding. This consensus strengthens the validity of the research findings and emphasizes the potential impact of this field on future medical applications and our understanding of human physiology.

Different Viewpoints

Unexpected Differences

Overall Assessment

summary

The discussion was primarily informative and collaborative, with no significant disagreements observed.

difference_level

Minimal to none. The speakers demonstrated alignment in their understanding and appreciation of the research on piezo proteins and their implications for touch, proprioception, and related biological functions.

Partial Agreements

Similar Viewpoints

Both speakers acknowledge the complexity and time-consuming nature of translating scientific discoveries into practical applications, emphasizing the importance of persistence and diverse perspectives in scientific research.

speakers

– Ardem Patapoutian
– Irene Tracey

arguments

The journey from basic science discovery to clinical applications is long

Changing fields and bringing new perspectives is important for scientific discovery

Key Takeaways

Piezo proteins are crucial for sensing touch, proprioception, and other pressure-related functions in the body

Individuals with piezo mutations have severe deficits in touch sensation and proprioception

Piezo proteins are present across many species and have diverse functions beyond touch sensing

The discovery of piezo proteins opens up new areas of biology and potential therapeutic applications

Pain perception varies between individuals and is influenced by internal state

Changing fields and bringing new perspectives is important for scientific discovery

Creating time to think and not being too busy is crucial for creativity in science

Resolutions and Action Items

Continue research on piezo proteins to uncover new areas of biology dependent on pressure sensing

Develop small molecules that could block Piezo2 for potential topical pain treatments

Utilize genetic databases linked to health records to connect conditions with specific genes

Unresolved Issues

The full extent of piezo protein functions in the body

The potential for developing systemic treatments using piezo-blocking drugs without interfering with normal body functions

The exact mechanisms of how different individuals experience pain differently

The long-term effects of piezo protein mutations on human health and development

Suggested Compromises

Develop topical applications of piezo-blocking drugs for localized treatment to avoid systemic effects on touch and proprioception

I think the sense of touch is one of the most amazing senses. It is very diverse, it’s very unique, and it’s very profound. Compared to other senses, vision, smell, taste, hearing, which are easily defined, the sense of touch is a bit more different.

speaker

Ardem Patapoutian

reason

This comment sets the stage for the entire discussion by highlighting the uniqueness and complexity of touch compared to other senses. It challenges the audience to think about touch in a new way.

impact

This framing guided the rest of the presentation, allowing Ardem to explore the multifaceted nature of touch and related senses like proprioception.

My favorite sense within this whole idea of somatosensation is actually proprioception. So what is this? I call it the most important sense that you have that probably many of you didn’t even know that you had it.

speaker

Ardem Patapoutian

reason

This introduces the concept of proprioception, a crucial but often overlooked sense. It’s thought-provoking because it reveals something fundamental about how we perceive our bodies that many people are unaware of.

impact

This comment shifted the focus to proprioception, leading to a deeper exploration of this sense and its importance in daily life and medical contexts.

So I thought the best way to do this was to get a tattoo of this protein so that I can demonstrate it without slides.

speaker

Ardem Patapoutian

reason

This unexpected demonstration shows Ardem’s dedication to communicating science in innovative ways. It’s a striking visual aid that makes complex molecular concepts more accessible.

impact

This moment added a memorable and engaging element to the presentation, likely increasing audience interest and retention of the information about the piezo protein.

Everything I told you till now is about humans and animals. But remarkably, piezos are actually present in almost every species we know. They’re present in even unicellular organisms. They’re present in plants.

speaker

Ardem Patapoutian

reason

This comment broadens the scope of the discussion, showing how a single molecular mechanism is conserved across diverse forms of life. It provides a powerful example of evolutionary continuity.

impact

This insight expanded the conversation beyond human biology to touch on broader concepts in evolution and the unity of life.

Don’t be too busy. I feel like I’m not creative when I’m busy. And so I create the time for myself to be able to think, read, and not just do busy work.

speaker

Ardem Patapoutian

reason

This advice challenges common assumptions about productivity and success, especially in high-pressure environments like scientific research or business leadership.

impact

This comment shifted the discussion from scientific content to career and life advice, offering valuable insights for both scientists and non-scientists in the audience.

Overall Assessment

These key comments shaped the discussion by guiding it from an introduction to the complexity of touch, through detailed explanations of proprioception and the piezo protein, to broader implications in evolution and even career advice. The combination of scientific depth, unexpected demonstrations, and personal insights created a multifaceted and engaging presentation that likely resonated with a diverse audience. The discussion effectively bridged highly technical content with accessible explanations and relatable concepts, making complex scientific ideas approachable and relevant to a general audience.

How can proprioception deficits be better diagnosed and treated?

speaker

Ardem Patapoutian

explanation

Ardem mentioned that doctors are not used to sensory deficits and often misdiagnose proprioception issues. Better understanding and treatment of proprioception deficits is an important area for further research.

How does stomach stretch contribute to eating behavior, diabetes, and obesity?

speaker

Ardem Patapoutian

explanation

Ardem highlighted this as an understudied area that could lead to new ways of understanding and treating diseases associated with eating and metabolism.

What are the new areas of biology dependent on pressure sensing, particularly in immune cells?

speaker

Ardem Patapoutian

explanation

Ardem mentioned discovering new roles for pressure sensing in immune cell function, suggesting this as an important area for further research.

How can small molecules be developed to block Piezo2 for localized pain treatment without interfering with normal body functions?

speaker

Ardem Patapoutian

explanation

Ardem discussed the challenge of developing targeted treatments that don’t interfere with essential touch and proprioception functions, indicating an important area for further drug development research.

Are there genetic variations in Piezo channels associated with pain syndromes?

speaker

Audience member (physician)

explanation

An audience member asked about the mechanism behind hyperpathic syndrome, prompting Ardem to discuss the potential for discovering Piezo-related genetic variations associated with pain conditions.