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Huberman Lab Essentials, where we look back at past episodes to find the most effective and practical science-based tools for mental, physical health, and productivity. I'm Andrew Huberman, a professor of neurobiology and ophthalmology at Stanford School of Medicine. And now to my conversation with Dr. Noam Sobel. Dr. Sobel, Noam, congratulations. Thank you. I must say, I am extremely happy about this conversation. I'm a big fan of your work, and today I'd like you to tell us about the amazing world of chemosensory, specifically olfaction-our sense of smell-and the perceptual or
subconscious abilities associated with it, including pheromones and so on. To get us all on the same page, I'd like to start by asking: What are the main components of our ability to smell? Obviously, or at least I like to think it has something to do with the nose. That's right. Could you give us a general overview, or even a detailed analysis, of the parts of the system and their roles? Primary smell is called orthonasal smell, meaning through our nose. We breathe air, and breathing is very important. I think we'll talk about this a lot today in different contexts. So we breathe in through our nose, and to answer your general question about
the organization of the system: the molecules, the molecules in the air, pass through a person's nose for about 6 to 7 centimeters, here's where they interact with -- I'll use the word "layer" of receptors, although "layer " is a bit misleading here. This is not a layer, it is very winding. We have about 7 million of these receptors lining a structure known as the olfactory epithelium. This is the sensory surface of the olfactory system, the olfactory epithelium. Again, a person probably has about 6 or 7 million of them. Humans probably have about 350 different types. This is simply incredible. This means that a significant percentage of your genome is dedicated to exactly this, to the specific types of olfactory receptor subtypes
that you have in your nose. So odorants interact with these receptors here in our epithelium, where they go through a process called transduction. That is, odor molecules attach to the receptor and are converted into a nerve signal. And this nerve signal, actually action potentials, not any gradient potentials, propagates through the olfactory nerve through the thinnest part of our skull, which is perforated. It has many holes. The nerve passes through these openings and forms a synapse in the brain's first target, the olfactory bulb. The pattern of this synapse corresponds to what is called the most extreme case of convergence in the, all receptors of the same subtype converge at one location in the bulb. This place is called a glomerulus, or, in
the plural, glomeruli. And this may be a somewhat simplistic view. It's actually two glomeruli. According to textbooks, each such receptor subtype responds to a small group of different molecular shapes, sometimes called odorotopes-the molecular aspects of smell. And each odorite will activate a separate set of receptors. Then, through this convergence, a kind of map emerges on the bulb, reflecting the identity of the receptors. So, let's assume that this coffee activates receptors types 1, 3, and 7 . Then the glomeruli of receptors 1, 3, and 7 will " light up," so to speak, when I smell coffee. If you could take a picture of this, you would theoretically get a coffee map. This is, so to speak, a classic idea of how the system works.
The information then travels from the bulb to several targets in the brain. I mean what's called the primary olfactory cortex-it's the piriform cortex and the entorhinal cortex. It's on the ventral surface of the brain, at the bottom of the temporal lobe, and the information goes there directly, but it also goes directly to the amygdala. It probably also goes straight to the hypothalamus. Perhaps it goes directly to the cerebellum. It spreads throughout the brain. So information is projected widely from there, and as far as we know, the map that might exist in the bulb doesn't exist in other parts of the brain, and understanding how
encoding occurs in the rest of the brain is hazy. Again, in our lab we already said, "Well, yes, we know that. "This is old news." But. Sometimes when I give public lectures to non-olfactory audiences, I emphasize this. Humans have an extremely amazing sense of smell. We observe people's behavior a lot. We try to look at it through the prism of our nose and how we evaluate people's actions. We try to think: " If I were a dog, what would I think about this?" And you know, if you look at dogs, right? You know, when they interact, they noticeably sniff each other. This is very obvious. They approach each other and sniff. But people don't usually approach a stranger to sniff them closely, right? I mean, we're kind of
obligated to sniff our babies. This is considered something you almost have to do. And it's not a cultural taboo to sniff your loved ones. This does n't seem like such a strange thing. But we don't sniff strangers, do we? Although, do n't we do that? So we are finding more and more mechanisms by which we do this. And the one I'm talking about now, as an example-we started to explore handshakes. We actually have a very poor understanding of how this behavior evolved. Like, where, where did this even come from? You know, if you look at the Wikipedia version, right? Then they will tell you that it is to show that you do not have a weapon in your hand. But there is actually no solid evidence for this. And we started watching people shake hands, and we noticed, or we
thought we noticed, that people would shake hands and then do this and that For those listening and not watching: Noam takes his hand and wipes it on his face Yes, they touch themselves. Yes, these are things we do all the time. After the handshake. Well, first of all, we do it all the time, just in general, right? The baseline here is very high, and we'll get to that in a second, but these are the kinds of actions you could easily overlook, right? So we asked ourselves if this was really the case . This was a study that was led by Don Frumkin in our lab at the time. So, we invited the participants to our lab, sat them in an experimental room, and told them that the experiment would start soon and that they should wait for us there. They didn't know
why they had come. Without their knowledge, they were already being videotaped, and they sat there for 3 minutes. And during those 3 minutes, we could later quantify how much, just as a baseline, they touch their nose, their forehead, or their chin, or how many times their hand touches their face. And, by the way, this basic level is not low. And then, after 3 minutes, the experimenter entered the room and spoke the memorized text: they said, we are still setting up the equipment in another room, so just wait here, we will be back soon, but for now, wait here. And in half of the cases, it was accompanied by a handshake. This was a new experimenter, not the one who had brought them into the room. So, they met for the first time. It was like, "Hi
, I'm so-and-so," they would extend their hand and shake it or not. Thus, we had conditions with and without a handshake, which allowed us to quantify the behavior of raising the hand to the nose after a handshake. And a significant increase in cases of raising the hand to the nose after a handshake was observed. This is incredible. Very interesting. The hand reaches for the nose. We conducted several control measurements to confirm that this is an olfactory behavior. First, the participants did not know that we were measuring nasal airflow. And people don't just put their hand to their nose, they smell it. And this happens with perfect synchronicity. They do it like this, you know? So, they sniff their hands. This
was truly olfactory behavior. Without a doubt. We are absolutely sure of this. And here's another interesting point, because people did n't just smell the hand they were shaking. They also sniffed the other hand. We believe that this is where we compare ourselves to others. And we think that many cases of this " self-sniffing" may reflect this. I would like to take a short break and thank one of our sponsors-Element. Element is an electrolyte drink that has everything you need and nothing you don't . This means electrolytes: sodium, magnesium, and potassium in the right proportions, but without sugar. Proper hydration is critical for optimal brain and body function.
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raspberry. I really like the citrus flavor. Element now has a limited edition lemonade flavor that is simply delicious. I don't like to say that I like one flavor more than another, but this lemonade one is on par with my favorites: raspberry or watermelon. Again, I can't choose just one flavor. I love them all. If you want to try Element, go to drinkelement.com/huberman, spelled drinklmnt.com/huberman, to get a free sample kit with the purchase of any Element blend. Once again, this is drinkelement.com/huberman to get a free trial set. There is a study that we published with Inbal Raviv in our lab. Where Inbal came from with this basic interest in the phenomenon conventionally called "instant friendship." These are people
you meet and immediately find common ground with. Everyone has experienced this in their life, you know, to some extent. And the question is, what exactly was there, right? What was that? Is it because you look alike? Maybe. Is it because you supported the same sports team? Or is there something deeper here? And Inbal's theory was that the similarity of body odor might contribute to this. That people who smell the same somehow find common ground more quickly. So to explore this, she actually recruited friends who felt this "click" from all over Israel. She wrote on all social networks to find a couple of friends. These were same-sex, non-romantic couples. So, these are friends, men and women,
whose friendships began with the same "clique." And then she took samples of their body odor. We have a special protocol for this. They are given unscented shampoo and soap to use for three weeks or so. And then they sleep in T -shirts for two nights, where they must sleep alone. And then we get the body odor out of the t-shirt. We have a method and technique for removing body odor. Then she first asked whether friends who felt a "click" actually had more similar body odor than would be expected by chance. She tested this using a device we call an electronic nose. An electronic nose is essentially a very unsuccessful attempt to mimic what a mammalian nose does. At its core, it is a set of sensors that
respond to molecules in the air. In this case, these are sensors called MOX sensors, i.e. sensors with a metal oxide coating. So, she used an electronic nose to analyze these body odors. And she discovered that friends who instantly understood And that was a significant difference. After she figured out that the device could do this, she recruited other participants. She had people smell the scents of friends and non- friends, and they rated them as more similar to each other. Now, again, you might ask, is this a cause- and-effect relationship or not? Because maybe friends go to the same restaurant all the time or live in the same neighborhood, and that's why they smell the same. So, to figure out causality, she recruited complete
strangers, first analyzed them with an electronic nose, and then engaged them in a social interaction -a game of mirroring. So, in the mirror game, one person moves their hands, and the other, being very close so that they can smell each other, must repeat these movements. One of the predictions came true, the other did not. What didn't work: She predicted that people who smelled more similar would play the game better, meaning they would follow each other better. This did not come true. However, the interaction was completely nonverbal. They weren't allowed to talk, and she set up a full round-robin tournament where everyone played everyone else.
It was a crazy experiment. At the end, each person rated the other on a scale of desire to be friends, as well as a number of other characteristics: how nice they seemed, how friendly they seemed, and so on. All of this was predicted using an electronic nose. So, people whose smells are similar believe that the other person is more likely to be their friend, is a good person, etc. So we could actually predict friendship using an electronic nose. So, this is not a consequence of friendship. This plays a role in the causal elements of friendship building. People are constantly aware of their own smell and constantly sniffing others. I want to touch on some more so-called pheromone effects.
Whether it's the classic pheromone effect, or olfaction, or something else, it's chemosensory signaling between individuals. It all becomes semantics, right? Like some boring subtleties. Yes, it's all semantics. So I.in our publications we don't use the term "pheromone," you know, because it would n't help me, it would probably only hurt me. And so we talk about chemosignals, and people definitely emit chemosignals from their bodies, and those chemosignals affect other people and their behavior. The hit of the last 10 years in this industry is something called the "smell of fear." People emit a particular body odor
when they are in a state of fear, and this odor affects other people, actually increasing their autonomic arousal, their sympathetic state. So, in essence, you could say that fear is a bit contagious. So, the smell of fear is contagious. By the way, culturally we have long known that dogs can smell fear in humans, but this was actually only proven about a year and a half ago in one study. So it was always said, but it wasn't effectively proven. About a year and a half ago, a study showed that dogs can indeed sense human fear. And people can feel human fear. So, several labs, starting with Denise Chen and Haviland Jones, and then in our lab and others, if you collect body odor from people in a state of fear and body odor from the same people when
they're not in a state of fear, other people can tell which one is in a state of fear and which one is not, and that affects their behavior. And this once again highlights, you know, that we are incredibly olfactory creatures. We had a guest on this podcast who I'm sure you're familiar with, Charles Zucker, a professor at Columbia University who has done incredible work in vision, smell, and thirst, and I talked a little bit about how there's something about the breath of romantic partners that hopefully is attractive, not repulsive. Just like in children; He talked about the smell of his grandson, the back of his head, the back of his neck, and how he missed that smell,
because when he thinks about missing his grandson or his children, that's the smell he associates with that feeling. Hexadecanal. Hexadecanal? Yes. This is a study conducted by Eva Mishor, who was a graduate student in our lab. Eva was interested in aggression. So when she started, we said, "Okay, let's do chemosignals of aggression." She actually went to MMA clubs and collected body odors. We had all sorts of ideas and she worked on it for quite a while. Nothing really came of it. At the same time, Heinz Breer was investigating in his lab the molecule hexadecanal, which was a chemosignal in mice that promotes social
buffering. So when there are a lot of mice together, they feel good in a group, and this is called social buffering. And this is facilitated by hexadecanal, which they secrete with their excrement. So Breer and his colleague Stormmann discovered the receptor for this. And then they found that this receptor is very highly conserved throughout mammalian evolution, and so they suggested that perhaps this is a universal mammalian signal. This is unusual because in chemosignaling it is generally assumed that everything is very specific to each species. So he came to us and said, "Listen, you should study this in humans, right?" Because he knows us as a " human group," right? I mean, we go to these olfaction conferences where a lot of
people are studying mice, zebrafish, etc., and we're a group that works with humans. And in the end, he just sent us the hexadecanal by courier. And Eve had no luck with studying aggression using sweat from human participants. And yet she built an entire paradigm for studying human aggression. These are standard paradigms. This is a paradigm known as TAR, Taylor Aggression Paradigm. And what's good about this is that it allows you to quantify aggression. So, you have a measure of aggression. Again, the Taylor Aggression Paradigm, obviously invented by Taylor, very well validated, studied everywhere, you know, very standard protocol. So, we invited participants and had them play TAR either under the influence of hexadecanol or a control group. And
first, I'll tell you the result with men: hexadecanal consistently reduced aggression. People were less aggressive under the influence of hexadecanal. The effect size was quite significant compared to effects observed in the world of aggression research. Really, really strong effects. So, unusually strong. So hexadecanal reduced aggression in males, and we thought, "Cool, this is exactly what we were hoping to see, it's consistent with the hypothesis and how it works in mice." But then we looked at the data for women, and hexadecanal increased aggression just as significantly. Is this considered something related to a maternal protective instinct?
We are getting closer to this. So she went and did the whole experiment again, and this time inside an fMRI magnet so that we could also track brain activity during this process. And above all, the results were confirmed again. So, once again, hexadecanal made men less aggressive, and women more aggressive. And yet I told everyone, "But you know, it doesn't make any sense to me." And then her epiphany, which, of course, later looked like "but it's obvious." It's: "No, there's a situation where it makes perfect sense, and that's if you're a baby mammal." Because parental aggression is often directed at you. Infanticide occurs everywhere, and unfortunately, male aggression towards children is also present in humans. And maternal aggression is often protective.
So if you're a baby, and you have a molecule that makes your mother more aggressive and your father less aggressive-both options are to your advantage. So, you win. So the main takeaway from all of this is that hexadecanal is the most common semi-volatile substance on babies' heads. A huge amount of it is released from the heads of babies Well, babies are waging chemical warfare, right? They reduce aggression in their fathers or the men around them and increase aggression in their mothers or the women around them, and both of these phenomena are beneficial to them. I would like to take a short break and thank our sponsor, AG1. I am happy to announce that AG1 has just released their newest formula-AG1 Pro. AG1 Pro takes the clinically proven AG1 formula
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this day in the study of emotions is Darwin's book "On the Expression of the Emotions in Man and Animals," I think that's the full title of the book. The sixth chapter is devoted to tears. So, Darwin systematically went through the expression of emotions and found a functional predecessor for each one and explained everything very well. And then he got stuck on tears, right? Because tears are an obvious emotional expression. And he couldn't find a functional predecessor. So eventually he said, "Yes, it's an epiphenomenon." So we thought, "Maybe the function is a chemical signal." With that in mind, we gathered emotional tears. We collected
tears and exposed participants to these tears. First of all, tears are completely odorless. You can't feel them at all. Completely odorless. And yet, when you inhale them, you have a pronounced decrease in testosterone levels after about 20 minutes, half an hour. These are men and women who smell women's tears. Men smell women's tears, but they don't Nothing. They just inhale them. And you have about a 14% drop in free testosterone levels. People who study testosterone, and that's not me , tell me that it's a very strong effect. Even pharmacologically, it is difficult to achieve such a rapid effect. That is, no one in pharmacology.
Yes, years ago I spent time studying endocrine effects of this kind, and it's an extremely precise effect. And so I'll just mention here in passing that one of our concerns in the effort to do this research was that no one would ever try to replicate it. And to our delight, about 2 years later, an independent group from South Korea, Oh et al., whom I do n't know at all, have reproduced the effect of testosterone down to the smallest detail. I mean, the same numbers. So, it lowers testosterone. And we also investigated, uh, using MRI, uh, the effect on brain activity and saw a pronounced effect: inhibition, decreased activity during, during the state of arousal, decreased activity in both the hypothalamus and the fusiform gyrus
. For what reason, I don't know. area. Uh, among other things, yes. Uh, and we don't know why. Uh, but pronounced. Typically in our work on chemosignaling, we look at what happens in rodents and see if the same thing happens in humans. This was a rare case where more or less identical effects were found in rodents after our work. So, uh, a paper published in Nature two years later found that tears from mice, uh, tears from baby mice reduce aggression in, uh, adult male mice toward them. Depending on the smell. Yes, yes, yes. And they also actually found a component in tears, which is a tear pheromone, that reduces aggression. Isn't that right? So, you know, it makes us think of tears as a kind of chemical blanket that you
cover yourself with again, you know, to protect yourself from aggression, right? Since smell is such a rich source of behavioral, hormonal, and other deep information, what experience do you have with generating odors in silico, in computers? And here, friends, for those of you who don't get the point, and I don't expect everyone to, because what we're really hinting at is the idea that you'll type into a search engine, for example, " blueberry pancake recipe," and you'll get not only pictures of these pancakes and the recipe, but also, hopefully, the verified smell of these pancakes, coming to you in real time via your computer. So, Google had an April Fool's joke.
Yes. And they released this video about Google Smell. Of course? And there were all these classic advertising images: you hold your phone up to a rose, and it generates the scent of a rose, and so on, right? So Google is now trying to do this, well, digitize smell. And there are other companies that are trying to do this too. And recently in our lab we had, and I hope this doesn't sound too presumptuous, but we made a kind of mini-breakthrough on this front. Calling something a mini-breakthrough is not at all presumptuous. This is a paper led by Aaron Ravia from our lab, with significant contributions from Kobi Snitz as well Article published in Nature. In this work, we have developed an
algorithmic framework with which we can predict the perceptual similarity of any two molecular mixtures with very high accuracy. So, if you give me two molecular mixtures, I can predict how similar you will find them to smell. Of course? We could not only predict this, but also design it. So we can create mixtures with given levels of similarity. The result that was highlighted-and you, as vision experts, will appreciate this-is that with our algorithmic solution, we created olfactory metamers. We measured mixtures that have no overlap in their molecular structure, but smell exactly the same. Of course? If you go to a classic perfumer or most perfumers and tell them that it is possible to create two blends that have no molecules in common but smell
identical, they will tell you that it is impossible. And yet we did it, and anyone can recreate them. It's actually simple. In the article, we do several things, for example, we create a metamer for Chanel No. 5 without having a single component from the original. I would like to take a quick break and thank our sponsor, Eight Sleep. Eight Sleep makes smart mattress pads with cooling, heating, and sleep tracking features. Eight Sleep has just released the Pod 6-their most advanced sleep system yet. The Pod 6 is half the size of their previous models. It cools and heats up 20% faster, and has nine times more sensors to track your sleep. The reason Eight Sleep is so effective in improving sleep quality and duration is because it helps
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many countries around the world, including Mexico and the UAE. Once again, eightsleep.com/huberman to save up to $200. In a way, we've created an infrastructure for digitizing smells because our algorithm, our system, assumes similarity. But in a way, that's enough for you. Why is this enough? We have a map of 4,000 molecules. For each of them, we know how it is perceived by smell. Now you can create any mix you want for me. I can project it onto this map and measure the pairwise distance to all the points on it. If it lands on a lemon, then what you created smells like a lemon. And if it gets on, you know, a tomato, then what you created smells like a tomato. So, we solved this problem.
We can predict the smell of any molecular mixture. We say what it will smell like. What we can do is find a set of components, which we call olfactory primaries, that can be used to create any odor. And that's exactly what we're working on now. This is happening in collaboration with Jonathan Williams' laboratory at the Max Planck Institute in Munich. atmospheric chemist, but he's very skilled at using GC-MS, instruments that measure molecules. So Jonathan Williams measured odorants in Germany and transmitted the information to us via IP. We entered it into our algorithmic system and reproduced it using a device that mixes primary elements. We tried to reproduce four different odorants in our test sample. One of them
was a rose, and we were unable to recreate it. We essentially recreated something that had a smell, but most people perceived it as chewing gum. The second one we tried to recreate was anise, and we couldn't recreate it. Most people said it was cherry, which isn't too far from the truth, but it was a failure. The third was gasoline, and we did a little better than a random guess, but it was significant. And the fourth was violets. And 15 out of 16 people said it was violets. So, the first scent transmitted over IP is violets. Don't expect it to appear on your table tomorrow. All we have now is an initial concept, but we are on the right track. We're talking about trying to achieve the olfactory equivalent of 1956 black-and-
white television, you know? In general, right? And, you know, I wouldn't dream of, say, telling you the difference between Cabernet and Merlot, right? But if I can recreate something that even remotely resembles wine, that would be an incredible success, from my perspective, right? But imagine taking a step towards transmitting smells in 4K- then we'll be talking about medical diagnostics, because although it's a bit of an exaggeration, you could almost say that every disease has its own smell. That is, each disease is a specific metabolic process. Metabolic processes have metabolites, and metabolites have odors. When the sense of smell is digitized in high resolution, although, again, that's not in our hands-I mean, we're talking about my retirement, maybe
I'll read about it someday, if I still have my sight. That is, it is not yet too soon. But when the digitization of smell reaches the equivalent of the 4K video and audio that you have now, then it will appear in medical diagnostics. Sorry for the insult, but you will have an electronic nose in your bathroom. Each of us will have it in the toilet. And he will constantly conduct diagnostics. And that's exactly where everything is heading. But, again, not in the near future. And now I want to thank you for your time today. First of all, it was an extremely interesting conversation. We touched on so many things: hormones, smells, the architecture of the olfactory system. I know the audience understands this, but I'll say it anyway: what an
incredible gift you've given us as an expert in this field, giving us a tour of the work that you and others to whom you so generously give credit have done, and the spirit that you put into it. Whatever fuels that spirit, as the great late Ben Barres said, keep going, because we all benefit immensely from it. And I also want to tell the audience that the spirit of science, as you mentioned, is complicated politics and a lot of other things, but it's absolutely clear that you enjoy your work. And I also get pleasure from it. I am grateful for that. I appreciate your time today. So from myself personally and from the many people listening to this, I want to express my immense gratitude. Thank you very much for such warm words.
