How Smells Influence Our Hormones, Health & Behavior | Dr. Noam Sobel

1. 0:00 – 3:46

   Dr. Noam Sobel

   1. AHAndrew Huberman0:00

      Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today my guest is Dr. Noam Sobel. Dr. Noam Sobel is a professor of neurobiology in the Department of Brain Sciences at the Weizmann Institute of Science. His laboratory studies olfaction and chemosensation. Olfaction is, of course, our sense of smell. Chemosensation is our ability to respond to chemicals in our environment. Today you are going to learn some absolutely incredible facts about how you interact with the world and other people around you. For instance, you will learn that humans can smell things around them as well as dogs can. In fact, humans are incredibly good at sensing the chemical world around them. You will also learn, for instance, that every time you meet somebody, you are taking chemicals from that person, either from the chemical cloud that surrounds them or directly from the surface of their body, and you are actually applying it to your own body, and you are processing information about that person's chemicals to determine many things about them, including how stressed they are, their hormone levels, things that operate at a subconscious level on your brain and nervous system, and that impact your emotions, your decision-making, and who you choose to relate to or not to relate to. You will also learn that tears, yes, the tears of others, are impacting your hormone levels in powerful ways. You will also learn that every so often, actually on a regular schedule, there is an alternation of ease through which you can breathe through one nostril or the other, and that alternation reflects an underlying dynamic of your nervous system and has a lot to do with how alert or sleepy you happen to be. The list of things that Dr. Noam Sobel's laboratory has discovered that relate to everyday life and that are going to make you say, "Wow, I can't believe that happens," but then go out into the real world and actually observe that that happens in ways that are incredibly interesting just goes on and on. In fact, his laboratory discovered that we are always sensing our own odors. That's right. Even though you might not notice your own smell, you are always sensing your own odor cloud, and throughout the day you periodically smell yourself deliberately, even though you might not realize it, in order to change your cognition and behavior. I first learned of Dr. Sobel's laboratory through a rather odd observance. That observance took place when I was a graduate student many years ago at UC Berkeley. At the time, Noam Sobel was a professor at UC Berkeley. As I mentioned before, he has since moved to the Weizmann. Well, I was walking through the Berkeley campus and I saw people on their hands and knees, but with their head very close to the ground, and their eyes were covered, their hands were covered, their mouths were covered, and only their nose was exposed. And what I was observing was an experiment being conducted by the Sobel Laboratory in which humans were following a scent trail. That scent trail was actually buried some depth underneath the earth, and yet they could follow that scent trail with a high degree of fidelity. It was from that experiment and other experiments done in Dr. Sobel's laboratory at Berkeley and at the Weizmann involving neuroimaging and a number of other tools and techniques that revealed the incredible power of human olfaction and humans' ability to follow scent trails if they need to. And that, of course, led to many other important discoveries, some of which I alluded to a few moments ago, but you are going to learn about many, many other important discoveries in the realm of olfaction and chemosensation that have been carried out by Dr. Sobel's laboratory through the course of today's episode. And by the end of today's episode, I assure you that you will never look at or smell the world around you the same way again.

2. 3:46 – 6:46

   Sponsors: ROKA, Thesis, Helix Sleep

   1. AHAndrew Huberman3:46

      Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero-cost-to-consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is ROKA. ROKA makes eyeglasses and sunglasses that are of the absolute highest quality. I've spent a lifetime working on the biology of the visual system, and I can tell you that your visual system has to contend with an enormous number of challenges in order for you to be able to see clearly. ROKA eyeglasses and sunglasses were designed with the biology of the visual system in mind, so no matter whether or not you're wearing them for sport, whether or not you're wearing them for work or for socializing, you can always see with crystal clarity. Their glasses are extremely lightweight, so most of the time you don't even realize that you're wearing them. I wear ROKA Readers at night and sometimes when I drive at night, and I wear ROKA sunglasses throughout the day, except, of course, I do not wear them for my morning sunlight viewing. If you'd like to try ROKA eyeglasses or sunglasses, go to ROKA, that's R-O-K-A, .com and enter the code Huberman to save 20% off your first order. Again, that's R-O-K-A .com and enter the code Huberman at checkout. Today's episode is also brought to us by Thesis. Thesis makes custom nootropics, and nootropics is a word that I do not like because it means smart drugs. As a neurobiologist, I can tell you that there is no neural circuit in your brain for being smart. There are neural circuits for focus, there are neural circuits for memory, there are neural circuits for creativity, and there are neural circuits for task switching. Thesis understands that there's a diversity of neural circuits that support different brain body states and therefore have designed nootropics that are customized to achieve specific brain body states. If you go to the Thesis website and take a brief quiz, they will design a nootropic starter kit. Some of those nootropics that they'll send you are designed to enhance your focus, others for clarity, others for creativity, and so on. To get your own personalized nootropic starter kit, you can go to takethesis.com/huberman and take a three-minute quiz, and Thesis will send you four different formulas to try in your first month. That's takethesis.com/huberman and use the code Huberman at checkout to get 10% off your first order.Today's episode is also brought to us by Helix Sleep. Helix Sleep makes customized mattresses and pillows that allow you to get the best possible night's sleep. So if you go to the Helix website, you can take a very brief quiz, it only takes about two minutes, and answer questions such as, do you tend to sleep on your back or your side or your stomach? Do you tend to run hot or cold throughout the night? Maybe you don't know the answers to those questions. But they'll match you to a mattress that's ideal for your sleep needs. For me, that was the Dusk, D-U-S-K, mattress, which is not too firm and not too soft, and I've been sleeping on it for more than two years and it's the best sleep that I've ever had. If you'd like to try a Helix mattress, go to helixsleep.com/huberman. Take that two-minute quiz and they'll match you to a customized mattress and you'll get up to $350 off any mattress order and two free pillows. Again, if you're interested, you can go to helixsleep.com/huberman for up to $350 off and two free pillows. And now for my discussion with Dr. Noam

3. 6:46 – 14:49

   Olfaction Circuits (Smell)

   1. AHAndrew Huberman6:46

      Sobel. Dr. Sobel-

   2. NSNoam Sobel6:47

      Uh.

   3. AHAndrew Huberman6:47

      ... Noam, welcome.

   4. NSNoam Sobel6:48

      Thank you.

   5. AHAndrew Huberman6:49

      I must say, I am extremely excited for this conversation. I've been a huge fan of your work for more than a decade or two, uh, yes?

   6. NSNoam Sobel6:58

      Kind of frightening-

   7. AHAndrew Huberman6:59

      Yeah.

   8. NSNoam Sobel6:59

      ... but yeah (laughs) .

   9. AHAndrew Huberman6:59

      We overlapped at UC Berkeley some time ago, although we did not meet, and we-

   10. NSNoam Sobel7:05

       (laughs) Although we lived in the same apartment (laughs) .

   11. AHAndrew Huberman7:07

       And we just learned that the amazing apartment that you moved out of was the apartment that my girlfriend and I at the time moved into in 2006-

   12. NSNoam Sobel7:17

       Yup.

   13. AHAndrew Huberman7:17

       ... I believe. So, uh, we've shared quite a few things.

   14. NSNoam Sobel7:22

       Certainly.

   15. AHAndrew Huberman7:22

       Um, and today I'd love for you to share with us, um, all about the amazing landscape of chemosensation, in particular olfaction, our sense of smell, and some related perceptual abilities or subconscious abilities, including pheromones, et cetera. To get everybody on the same page, I'd like to just start off by asking, what are the major components of our ability to smell? Obviously, or I like to think it involves the nose at some level.

   16. NSNoam Sobel7:50

       It does.

   17. AHAndrew Huberman7:51

       To what extent is that mixed in with other senses, like taste, and perhaps more importantly, what about the chemicals that we are sensing through this thing, and for those of you listening, um, and not watching, I'm tapping my nose, that we are not aware of? You know, the- the chemicals that are, that we're inhaling and, um, making sense of without our awareness. Um, if you could just, um, give us the top contour or even deep contour, if you like, of the, uh, the parts list and the, uh, various roles they play.

   18. NSNoam Sobel8:24

       So you, you've asked a lot of questions at once. Um, you know, I'll start with a little comment on the way you, you said smelling through our nose, which we indeed do, but we also smell through our mouth actually. There's a process referred to as retronasal olfaction where, um, odorants come up through our, the back of our throat and out of our nose the reverse way, and we smell things that way as well. And in fact, a big part of the contribution of olfaction to food and taste comes from that, from retronasal olfaction. But, uh, uh, primary olfaction is referred to as orthonasal olfaction, that is through our nose. We sniff, and sniffing is a big thing. Well, I have a sense we might talk about that a lot today in all sorts of contexts. So we sniff in through our nose and to answer your general question of the organization of the system, um, so molecules, airborne molecules travel up our nose, a distance in the human of about six or seven centimeters to about here where they interact with, I will u- use the word sheet of receptors, but sheet is a bit misleading here. It's not a sheet. It's very convoluted. We have about 7 million such receptors, uh, lining a structure known as the olfactory epithelium. This is the sensory surface of the olfactory system, the olfactory epithelium. Again, about, probably about six or seven million receptors in the human. In the human, probably of about 350 different kinds, so that's amazing. That means a- a meaningful percentage of your genome is devoted just to this, just to the kinds of olfactory receptor subtypes you have in your nose. By the way, I can share an amusing story. I would imagine amusing stories are good for podcasts. So that number of six or seven million receptors i- is probably not very well grounded, uh, it's hard to count, uh, but it's reasonably grounded, and there was this thing roaming around in the literature about bloodhounds having a billion receptors in their nose, which is why they're so amazing. And this number was, you know, it sort of propagated through the literature and, and our lab, um, has written over the years a few review chapters and, and we were repeatedly writing the olfaction chapter for a very large, one of these large textbooks, the Gazzaniga Handbook of Cognitive Neuroscience I think it's called, um, and- and we had that in there as well somewhere and- and one time when we were renewing the chapter for a new version of the book, I told the graduate student who was leading that at the time, Araya Sharoon, she's now a- a professor at Tel Aviv University, I told her, "Check that, check that reference out. Where in the world did that come from?" And we started going back and back and back, and it turns out it comes from a textbook, an Australian textbook, and we found the author of the textbook and- and we wrote her and I said, "Look, there's this thing in- in the literature of a billion receptors in- in the bloodhound. Where did that come from?" And- and surprisingly she answered me, and you know, I was hoping to get a reference, right? But it wasn't a reference and- and this is where it really becomes funny for us because she said, "I- I- I was once, um, at a lecture of, uh, an olfaction geneticists, geneticist by the name of Doron Lanset and he said that in the lecture." Now this is really funny because she's in Australia, this is all over the world, this number, and I'm writing home to her from Israel.... and Doron Lancet is in the building next to me, okay? He's in, a- and Weizmann Institute Genetics. I mean, he used to be. He's, he's retired now. Uh, and, and he, he had meaningful contributions in the history of olfaction. Um, so I picked up the internal phone and, and I said, "Hey, Doron, you know, did you say that there's a billion receptors in the bloodhound nose?" And he said, "What's a bloodhound?" (laughs) And so this is totally made up, right? It totally made up and it propagated. I mean, you can, you can probably go into Google and type like a billion receptors in the bloodhound and, and you'll get a lot of hits. But there was absolutely no evidence for that. (laughs)

   19. AHAndrew Huberman12:32

       Amazing. And not just amazing in light of what it, it tells us about olfaction in bloodhounds or otherwise, but amazing because it sheds light on just how much of what is in textbooks, scientific and medical, is absolutely wrong.

   20. NSNoam Sobel12:46

       Things, things propagate and, and, you know, you cite yourself and ... Right? So we fix that in, in that version of the-

   21. AHAndrew Huberman12:51

       Right.

   22. NSNoam Sobel12:51

       ... of the ... And, and so to finish the line, so that, so, so odorants interact with these receptors, um, here in our epithelium, uh, where they undergo what is referred to as transduction. That is, the odorants are docked at a receptor and turn into a neural signal or, or en- force the receptor to respond in a neural signal and, uh, this neural signal, in fact, action potentials, not gradient potentials of any kind, uh, propagates, uh, via the olfactory nerve. Now, this is a nerve that goes from our epithelium, uh, right here.

   23. AHAndrew Huberman13:23

       Behind the forehead?

   24. NSNoam Sobel13:25

       No, it ... Well, yeah.

   25. AHAndrew Huberman13:26

       Yeah.

   26. NSNoam Sobel13:26

       Here. Uh, through, uh, the thinnest part of our skull, uh, an area referred to as the cribriform plate, which is perforated. It has a lot of holes. The nerve goes through those holes and synapses at the first target in the brain, uh, which is the olfactory bulb. In humans, uh, that forms an interesting, uh, uh, point of sensitivity, um, because a lot of people lose their sense of smell due to trauma, uh, because of that structure. Uh-

   27. AHAndrew Huberman13:58

       Yeah, a head hit type trauma.

   28. NSNoam Sobel13:59

       Well, yes, although, uh, you denoted hitting on the front of the head, which is where all this real estate is, but actually, uh, the more common cause for losing your sense of smell for trauma is the back of the head-

   29. AHAndrew Huberman14:10

       Mm-hmm.

   30. NSNoam Sobel14:10

       ... because of what's referred to as a contrecoup injury. So as your listeners probably know, our brain is floating in liquid, in CSF, in cerebrospinal fluid inside our skull, and when we get hit in the back of the head, the brain has this forward and backward movement, uh, in the liquid, in, in the skull. It sort of crashes. It can crash against the front of the skull, which is why you also have, in a contrecoup injury, you also often have frontal damage. But what happens is that this generates a shearing motion on the cribriform plate and the olfactory nerve is severed, and if it's completely severed, it's, it's lost.

4. 14:49 – 21:39

   Loss & Regeneration of Smell, Illness

   1. NSNoam Sobel14:49

      Um-

   2. AHAndrew Huberman14:49

      For- Forever? Because my, my understanding is that the olfactory sensory neurons can ... Are among the few central nervous system neurons in adult humans that can regenerate.

   3. NSNoam Sobel14:58

      So-

   4. AHAndrew Huberman14:59

      Or replenish themselves.

   5. NSNoam Sobel15:01

      Right. So, so I'll, I'll ... Again, there are a few questions in one.

   6. AHAndrew Huberman15:03

      Yeah, that's okay. We will-

   7. NSNoam Sobel15:04

      So first of all-

   8. AHAndrew Huberman15:05

      We will spin many plates simultaneously.

   9. NSNoam Sobel15:06

      If, if it's completely severed, completely, then yes, you're lost.

   10. AHAndrew Huberman15:11

       Forever?

   11. NSNoam Sobel15:11

       Yeah. If it's completely severed, because even if you'll have regeneration at the basal cell level at the epithelium, they won't manage to find their way back, uh, to the bulb. If, if you have partial or something left or something shows up in a short while after the injury, then you have a good chance of recovery. Um-

   12. AHAndrew Huberman15:33

       Ah, because they grow along the trajectory of the other accents-

   13. NSNoam Sobel15:35

       Yeah. Yeah.

   14. AHAndrew Huberman15:35

       ... or pioneering the way for them.

   15. NSNoam Sobel15:37

       Assumingly. Yeah.

   16. AHAndrew Huberman15:38

       Interesting.

   17. NSNoam Sobel15:39

       And, and so, so basically, and, and basically the timeframe, and you know, it's funny, I get a lot of emails on this, although I'm not a medical doctor, but, but I get a lot of emails from people who have lost their sense of smell because it's very distressing. And now more people know this because of COVID, that it's very distressing and, and basically the rule of thumb is that if you don't get it back within a year to a year and a half, you'll never, uh, get it back.

   18. AHAndrew Huberman16:03

       My, my understanding of the statistics on olfactory loss in COVID and, and, and other viral type infections is that, um ... First of all, I had, I experienced that when I got COVID. Um-

   19. NSNoam Sobel16:13

       Including total anosmia?

   20. AHAndrew Huberman16:15

       For one day, and not total. It was just, there was a remnant of an ability to s- to smell or s- or perceive the smell of a lemon and I was huffing as hard as I possibly could.

   21. NSNoam Sobel16:25

       So-

   22. AHAndrew Huberman16:26

       I actually ... Uh, there's an over-the-counter remedy, and this is not, uh, pseudoscience because there's a number of p- papers published about this on PubMed, that alpha-lipoic acid can accelerate the recovery of, of, of smell.

   23. NSNoam Sobel16:38

       Yeah.

   24. AHAndrew Huberman16:38

       And I ... And so that's something that, um, it worked successfully for me. I'm not saying that-

   25. NSNoam Sobel16:42

       Wow.

   26. AHAndrew Huberman16:42

       ... that's the only, uh, route.

   27. NSNoam Sobel16:44

       You don't know if it worked successfully for you or if you would have recovered anyway. I mean, you didn't do a controlled study. (laughs)

   28. AHAndrew Huberman16:47

       True, but I was not willing to do the controlled experiment.

   29. NSNoam Sobel16:50

       (laughs)

   30. AHAndrew Huberman16:50

       Uh, exactly.
5. 21:39 – 24:40

   Brain Processing of Smell

   1. AHAndrew Huberman21:39

      m- I-

   2. NSNoam Sobel21:40

      Should I finish the, the path just so we have the-

   3. AHAndrew Huberman21:42

      Please. Please.

   4. NSNoam Sobel21:43

      So, so we said, so, so information then synapses at the olfactory bulb from, from, uh, uh, uh, the, the olfactory epithelium, and the pattern of that synapsing follows what's referred to as the most extreme case of convergence in the mammalian, uh, nervous system. More specifically, what happens is that all the receptors of a given subtype, and remember in humans we said we have about 350, in the mouse we have about 1,200 probably. Um, so all the receptors of one subtype converge to one location in the bulb, and, uh, this location is referred to as a glomerulus or in plural glomeruli, and, and that may be a slight oversimplification. It's in fact two glomeruli. There's a mirror, sort of a mirror cut line, and so all the receptors of one subtype will converge to two mirrored glomeruli on the olfactory bulb. So you end up having, uh, two glomeruli that reflect that one receptor subtype. And so if, and this is as far as th- I'm giving you now the textbook view of, of how the system works, but then I can, I'll happily share with you things that pose a problem for the textbook view of how things work. But the textbook view of how things work is that every such receptor subtype is responsive to a small subset of different molecular shapes, what's sometimes referred to as ototopes, the molecular aspects of deodorant. So each receptor is, is responsive to a different subset of ototopes, let's say 10, and each ototope will activate a different subset of receptors. So potentially you have this insane combinatorics of this potentially 350 dimensional space in the human, potentially, but then because of this convergence you end up having on the bulb in a way a map reflecting o- receptor identity. So, so let's say this coffee, uh, activates receptors of type one, three, and seven, so the glomeruli of receptors one, three, and seven will "light up," quote unquote, when I smell the coffee. And if you could take a snapshot of that, theoretically you would have the map of, of coffee and, and so on and so forth. This, this is sort of the textbook view of how the system works, and, and then information goes from the bulb to several targets in the brain. I mean, what is referred to as primary olfactory cortex is piriform cortex and, and entorhinal cortex. This is on the ventral surface of the brain, the lower portion of our temporal lobe, um, and information goes there directly but it also goes directly to the amygdala. It probably goes directly to the hypothalamus. It may go directly to the cerebellum. Uh, it goes all over the brain.... so, so information projects widely from there, and as far as people understand, the map that may exist on the bulb, uh, doesn't exist in the rest of the brain. And the understanding of, of how coding occurs in the rest of the brain is, is murky.

6. 24:40 – 27:52

   Smell & Memories

   1. NSNoam Sobel24:40

   2. AHAndrew Huberman24:40

      Commonly one hears that the memories that we have of odors are somehow more robust, um, than the memories of other perceptual events in our life. I, I don't know if this is true or not, but, um, people will say, for instance, "I can still remember the smell of my grandmother's hands, or the smell of cookies in her kitchen." At a minimum, it points to the fact that smell and memory are closely linked, and you just mentioned a direct, um, you know, multi-station, but nonetheless somewhat direct path from the nostrils to the hippocampus, uh, one of the primary encoding centers of, of memories in the brain.

   3. NSNoam Sobel25:17

      Two, two synapses away, yeah.

   4. AHAndrew Huberman25:19

      Yeah, which is, which is a remarkably short pathway considering that, for instance, uh, just by example, 'cause, uh, some of our listeners won't be familiar with this, but some will, that sound waves that, uh, you know, are transduced into neural signals at the level of the inner ear go through many stations before they arrive at the location in the brain where we make sense of those sound waves as voices or music, et cetera, whereas olfaction is more of a direct route, um, to the, to the, uh, memory centers. Um, is there any, uh, just so story or real, uh, objective truth to the idea that olfactory memories are formed more easily or maintained longer or more robustly than other sorts of memories?

   5. NSNoam Sobel25:58

      So, so yes (laughs) . Uh, but first I, I should, I should say that I'm not an authority on olfactory memory. It's sort of an, it, olfactory memory's a huge field of research, and somehow our lab has never really, um, gone much into that. Although, uh, again, the same student I happened to talk about before, Yarai Sharoon, who's again now a, a faculty at Tel Aviv, uh, um, ran a study, a paper we, I think we published in Current Biol- Biology called The Privileged Representation of Early Olfactory, uh, Associations. Basically, there's something about the first time you experience a smell that generates a particularly robust representation, more than other sensory stimuli, and, and that's what she in fact compared. So there's something about the first exposure to a smell, um, in terms of the brain encoding, that, that etches it into our, uh, being. And, and this is an effect that has, you know, it has echoes of course in literature. I mean, you know, the, the, the biggest cliché in this is to bring up the Proust effect, right? So, the Proust effect is when he ate the madeleine and it immediately, the taste and smell immediately reminded him, uh, of, of an event in his childhood where, where, uh, where the same m- madeleine, uh, appeared. Uh, um, b- but s- so that's something very real. There, there's a lot of research on it, uh, not coming from our work, so I'm, I'm not an authority.

   6. AHAndrew Huberman27:25

      But it does sound like there's something special about olfaction, um, and that doesn't mean that there isn't something special about vision or audition.

   7. NSNoam Sobel27:33

      Uh, no. I- I'm-

   8. AHAndrew Huberman27:33

      E- each one has its own, uh, unique, uh, tone.

   9. NSNoam Sobel27:36

      I'm the last to argue that there's something special about olfaction.

   10. AHAndrew Huberman27:38

       (laughs)

   11. NSNoam Sobel27:39

       I- it's, uh, my, my, my students make fun of me, because they say, and there's some truth to that, that I try to explain everything through the olfactory system. I mean, for me, everything is olfactory. So, so yes.

   12. AHAndrew Huberman27:51

       Through the lens of the

7. 27:52 – 29:07

   Sponsor: AG1 (Athletic Greens)

   1. AHAndrew Huberman27:52

      nose. I'd like to take a quick break and acknowledge one of our sponsors, Athletic Greens. Athletic Greens, now called AG1, is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs. I've been taking Athletic Greens since 2012, so I'm delighted that they're sponsoring the podcast. The reason I started taking Athletic Greens and the reason I still take Athletic Greens once or usually twice a day is that it gets me the probiotics that I need for gut health. Our gut is very important. It's populated by, uh, gut microbiota that communicate with the brain, the immune system, and basically all the biological systems of our body to strongly impact our immediate and long-term health. And those probiotics in Athletic Greens are optimal and vital for microbiotic health. In addition, Athletic Greens contains a number of adaptogens, vitamins, and minerals that make sure that all of my foundational nutritional needs are met, and it tastes great. If you'd like to try Athletic Greens, you can go to athleticgreens.com/huberman and they'll give you five free travel packs that make it really easy to mix up Athletic Greens while you're on the road, in the car, on the plane, et cetera. And they'll give you a year's supply of vitamin D3K2. Again, that's athleticgreens.com/huberman to get the five free travel packs and the year's supply of vitamin D3K2.

8. 29:07 – 39:25

   Humans & Odor Tracking

   1. AHAndrew Huberman29:07

      When I was at Berkeley, um, I was walking across campus one day, and I saw, I think students, but I saw people on their hands and knees with goggles on, gloves on-

   2. NSNoam Sobel29:21

      Yeah.

   3. AHAndrew Huberman29:21

      ... and, um, I think their mouths were covered too, um-

   4. NSNoam Sobel29:24

      Everything was covered.

   5. AHAndrew Huberman29:25

      ... was covered, and they were walking, well, they were crawling along the ground, um, and I thought this was peculiar, but then again, uh, it's UC Berkeley, and the joke is if it, to get noticed on the UC Berkeley campus, you have to be naked and on fire, right?

   6. NSNoam Sobel29:39

      (laughs)

   7. AHAndrew Huberman29:39

      One or the other would not be sufficient. Please don't run this experiment anybody.

   8. NSNoam Sobel29:43

      Yeah. (laughs)

   9. AHAndrew Huberman29:43

      Um, it's that kind of place. Um-

   10. NSNoam Sobel29:45

       Yeah.

   11. AHAndrew Huberman29:45

       ... but nonetheless, um, a, a paper came out, uh, a few years later describing the results of what turned out to be your experiment that your laboratory was running, which was having people follow an odor trail with their nose, and, um, and my understanding is that people can improve their ability to track scents quite robustly, especially if we deprive them of vision and somatosensation, that is touch and some other, um, sensations. Maybe you could just tell us a little bit about that study, and-

   12. NSNoam Sobel30:18

       Sure.

   13. AHAndrew Huberman30:19

       ... um, and for, I think in our audience I'm suspecting that many people have a keen, keen sense of smell. Very, I have a family member who just, like, could detect any negative o- you know, putrid odor in the environment, and, uh, but also-... good odors, um, exquisitely well. And I have, I have other family members whose sense of smell is quite poor. Um, I'd love for all of those people to learn a bit about what is possible in terms of training up or-

   14. NSNoam Sobel30:46

       Right.

   15. AHAndrew Huberman30:46

       ... improving our ability to smell, and, um, perhaps in the context of that study, if you will.

   16. NSNoam Sobel30:51

       Yeah. So, so first, before even talking about improving, just off the bat, humans have a remarkable sense of smell. And this is something, again, in our lab we already said, you know, yeah, we know this. This is old news. But, but to people who, who come from different worlds, we have to reiterate this. Sometimes when I give, uh, you know, public lectures to, to non-olfaction audiences, I reiterate this. Humans have an utterly remarkable sense of smell. To, to put that a bit into sort of, you know, things that you could, that are tangible. So, so for example, um, mercaptans, which are added to cooking gas so that we smell it because otherwise it wouldn't have a smell, so that the smell of gas is not the smell of gas, of propane. It's an additive.

   17. AHAndrew Huberman31:35

       Mercaptan?

   18. NSNoam Sobel31:36

       Yeah, it's mercaptan.

   19. AHAndrew Huberman31:37

       The sulfur, like, smell?

   20. NSNoam Sobel31:39

       Yeah. So, so, uh, our detection threshold, that is the level at which we can detect it, is 0.2 parts per billion. Okay? There's no machine that can really do that that effectively, no gas chromatograph, nothing. Now, to give you another sense of, of, of making this, again, really tangible, we're working with a deodorant in our lab called ester tetraenol, that our participants can detect when we have it mixed at 10 to the negative 12 molar in the liquid phase. To give you a real sense of that, we did the math. If you would take two Olympic-sized swimming pools and you would pipette 1 mL, one drop into one pool versus the other, you could smell the difference between the pools.

   21. AHAndrew Huberman32:27

       Incredible.

   22. NSNoam Sobel32:28

       That's the detection threshold that you have with your nose. People have an utterly amazing nose, okay? So, so that's just in terms of its detection abilities, which are, are just, you know, remarkable, really up there in the mammalian world. We're not a bad mammal at olfaction. Um, and, and beyond that, we can, we can improve, okay? And, and the example you're talking about actually started off, uh, as a lab bet. (laughs) Okay? We, we were having a lab picnic. So I guess I should here fill in because I, I'm, I'm your guest from the Weizmann Institute of Science in Israel, but before going back to my home in Israel, I was a, uh, um, faculty at UC Berkeley in the Helen Wills Neuroscience Institute, and this study was done during that time. And we were on a lab picnic, and we were having indeed one of these sort of lab discussions, arguments on what humans can and can't do with their sense of smell, and, and I said that humans could truly even track odor like a dog, and people there said, "No way." And we ran this quick experiment, uh, which I have video of, but I don't think we'll show it here, uh, but I actually have original ... Uh, the picnic video, we have it, and, uh, a graduate student by the name of Christina Solano, a brilliant graduate student at that time who's now, she's now a professor at Northwestern, uh, and she's really leading the field of, of olfaction imaging today, but she was the volunteer, and we dragged a chocolate bar across the grass and blindfolded her and checked if she could track the track we made with the chocolate, which she did very effectively, right? And as far as-

   23. AHAndrew Huberman34:06

       Did you place her at the starting point of the line, or-

   24. NSNoam Sobel34:08

       I think we did. I don't exactly remember what we did on that sort of picnic, uh, uh, tryout, but, you know, I, I assume she never practiced that in her life before, right? And yet, you know, she, she did it really, really well. And, and then this went on as a lab bet in a way that, that I, I said to my, my students, "Okay, we, we have to make this into a- an experiment, put it in an experimental setting and, and, and quantify what's going on." Uh, and they all said that it would be uninteresting, and that was the bet, and, and I told them it would be in Nature, which is a bet I won in this case. (laughs)

   25. AHAndrew Huberman34:42

       Nature, of course, being one of the-

   26. NSNoam Sobel34:44

       (laughs)

   27. AHAndrew Huberman34:44

       ... the ape- three apex journals, Science, Cell, and Nature.

   28. NSNoam Sobel34:46

       Mm-hmm. It was, it was Nature Neuroscience to be fair.

   29. AHAndrew Huberman34:48

       Yep.

   30. NSNoam Sobel34:48

       But, but, uh, so, so then we, we turned it into an experiment, and, and what the experiment was is that we brought in participants, naive participants, not, not graduate students from our lab, uh, completely deprived them of any other sensory input. So we blocked their eyes, we blocked their ears, we blocked everything. We blocked, they were wearing heavy gloves. Uh, you know, they, they couldn't sense anything, and we generated, uh, uh, uh, a consistent odor path in the grass, which is what you saw. Uh, we did that by burying twine under the grass, an- an odor-impregnated twine, so that way we could generate a consistent, uh, odor trail every time. And-
9. 39:25 – 48:18

   The Alternating Nasal Cycle & Autonomic Nervous System

   1. NSNoam Sobel39:25

      Um, uh, you know, I, I can share with you something that, that I think will interest your, your, uh, listeners and viewers as well, and, and, and we think is, is really, uh, uh, one of the most overlooked things in, in neuroscience. Uh, I'll-

   2. AHAndrew Huberman39:41

      Please do.

   3. NSNoam Sobel39:41

      ... I'll invite you, I'll invite you to do the following experiment.

   4. AHAndrew Huberman39:43

      Okay.

   5. NSNoam Sobel39:43

      So occlude one nostril by pressing on it from the side and sniff in, (sniffs) and then occlude the other and sniff in. (sniffs) Do you sense a difference in flow?

   6. AHAndrew Huberman39:51

      Yes.

   7. NSNoam Sobel39:51

      Okay, do you know why that is?

   8. AHAndrew Huberman39:53

      No, and it was the next-

   9. NSNoam Sobel39:54

      Okay.

   10. AHAndrew Huberman39:54

       ... question on my list, so yeah.

   11. NSNoam Sobel39:55

       Then don't feel badly about not knowing why that is.

   12. AHAndrew Huberman39:57

       Mm-hmm.

   13. NSNoam Sobel39:57

       Um, most people don't. Uh, but that is a reflection of something referred to as the nasal cycle. So in fact, if you were to do that repeatedly, you would find that your high flow nostril and low flow nostril alternate every two and a half hours on average.

   14. AHAndrew Huberman40:15

       In an absolute way, or is it kind of like a sine wave, like gradual shift to the one and then gradual shift back?

   15. NSNoam Sobel40:20

       It can vary. (laughs)

   16. AHAndrew Huberman40:21

       Mm-hmm.

   17. NSNoam Sobel40:22

       It can vary, and we don't yet know the rules, uh, all the rules. But, but you have this constant shift from side to side. The shift becomes incredibly pronounced in sleep, so we can measure the power of the difference and, and in sleep you have this phase shift of power, you have a huge, like one closes and one opens totally. And it turns out that this is linked to, uh, balance in the autonomic nervous system. So as you and your listeners know, we have an autonomic nervous system that has a sympathetic and parasympathetic component to it, and, and they're in balance or imbalance in many diseases, for example. And this interplay between the, uh, auto- in, between the, the sympathetic and parasympathetic nervous system drives the switch from left to right nostril. Uh-

   18. AHAndrew Huberman41:10

       Just to remind people-

   19. NSNoam Sobel41:11

       Yeah.

   20. AHAndrew Huberman41:11

       ... um, sympathetic nervous system has nothing to do with sympathy.

   21. NSNoam Sobel41:15

       (laughs)

   22. AHAndrew Huberman41:15

       Um, has everything to do with generating patterns of alertness, it's sometimes called the fight or flight system, but any pattern of arousal, positive or negative, and then it's balanced in a coordinated way, or at least in parallel with the parasympathetic nervous system, which is sometimes called the rest and digest system, but is, uh, uh, associated with all sorts of things, the sexual arousal response, um, and a number of other aspects of our physiology, so think of it like a seesaw of alertness and calm, yeah?

   23. NSNoam Sobel41:39

       Perfect. So now imagine, right, imagine, imagine you would walk around living your life, right, half of the time with one eye closed like this, and the other half with one eye closed like this, and you had this eye cycle, right? And that was linked to autonomic arousal. I assure you, you would go to PubMed, there would be five million papers on the eye cycle, right? And the eye cycle in every disease you can name, and what it denotes, and what it tells us, and what we can do with it. You have exactly this marker. You're walking around with a marker on balance in your autonomic nervous system, and we do nothing with it. So w- we're in fact now doing a lot with it, okay? So we built, we built a wearable device that, uh, is pasted to your body and measures airflow in each nostril separately, and logs it for 24 hours, and we're collecting these 24-hour recordings, we're calling it the nasal halter. So we measure with the nasal halter, and, and we're finding it is a disease marker. Um, I can, I can give you a nasal halter measurement as an adult and I can say, this is work by Tim Nasteroca, a graduate student in our lab now, uh, I can s- so we, we can tell the difference between, uh, ADHD and non-ADHD adults.... and we can tell just from the recording, we can tell if the adults are on Ritalin or not. So, I can, I can measure your nasal airflow and say if you are or are not with ADHD, and if you are or are not on Ritalin.

   24. AHAndrew Huberman43:07

       Incredible.

   25. NSNoam Sobel43:08

       (laughs)

   26. AHAndrew Huberman43:09

       I, I have a, a couple of questions about this. Is it the case that airflow through one nostril is reflective of a sympathetic nervous system dominance versus parasympathetic?

   27. NSNoam Sobel43:20

       (laughs) Yes.

   28. AHAndrew Huberman43:20

       Um, or is it simply the case that this alternating left-right nostril, um, periodicity, um, which you said I think is on the order of about every two hours-

   29. NSNoam Sobel43:29

       Two-and-a-half.

   30. AHAndrew Huberman43:29

       Two-and-a-half, it switches to, uh, maximal on one side versus the other. Is that simply reflective of an overall balancing? Let, let's, maybe is it the hinge in the seesaw or is it the tilt of the seesaw?
10. 48:18 – 54:47

    Cognitive Processing & Breathing

    1. AHAndrew Huberman48:18

       earlier you were describing the architecture of these, um, smelling systems, and you mentioned these glomeruli where the olfactory receptors converge-

    2. NSNoam Sobel48:28

       Right.

    3. AHAndrew Huberman48:28

       ... in the bulb, and then later you mentioned that the system is unilateral, but with a mirror representation on both sides of the brain. So, for those who don't think in terms of neuroanatomy, um, what Noam was describing is the fact that of, of course there are two nostrils, and then a bunch of receptors, they converge in these glomeruli, but you have a mirror representation of that on both sides of the brain, and that most of that information is kept on one side of the brain or the other. There isn't a lot of extensive intermixing at the first order of processing.

    4. NSNoam Sobel48:54

       Right.

    5. AHAndrew Huberman48:54

       So, the question I have is whether or not you believe, I'm not asking for data, first I just want to know what you believe, that this alternating nostril airflow phenomenon-... has anything to do with preferential processing of olfactory information in terms of right brain, left brain, with the caveat that anytime we hear right brain, left brain, um, we've covered this in a previous episode. Most of what people hear out there about right brain, left brain, emotionality, logical stuff, is completely wrong. Completely wrong. Doesn't exist. It's a total fabrication, um, and we'd like to abolish that myth. But with that aside, or set aside rather, what are your thoughts on why the information would switch from one side of the brain to the other at all?

    6. NSNoam Sobel49:39

       Yeah. I don't think, I don't think that, that the nasal cycle is an olfaction story. Um, so, so I, I don't think that, um, that this was shaped by the olfactory system, nor do I think this has major impact on olfaction. I think the nasal cycle story is a different story about brain function. Um, so, so you know, we have, we have this sort of pet theory we're calling now the sniffing brain approach, where we're basically... We think that, that nasal inhalation is timing and driving a lot of aspects and patterns of, of neural activity and cognitive processing, and, and this theory is, is olfaction-inspired in its beginning. That is, I mean, if, if you think of the mammalian brain, right, it's... Which, which evolved from olfaction. It's sitting there and, and in olfaction, because olfaction depends on sniffing, you have this situation where you have a (sniffs) you have a sniff, you have information, and then flat. Nothing. Right? And then (sniffs) you have information, and then nothing. So, information processing is, is one-to-one linked to nasal inhalation, and, and we think that, that this property evolved to, to be meaningful in brain processing in general. Not only of, of olfactory information, but of any type of information, because the brain evolved in this way, in this way that it processes information on inhalation onset. So, a study led by Ofer Pe'er from our, our lab, uh, two, three years ago, um, we looked at, at something completely non-olfactory. We looked at, at visuospatial processing, and we compared visuospatial processing on inhalation versus exhalation, and the brain does this completely different on inhalation versus exhalation. You, you are... In, in that particular task, people performed significantly better on inhalation versus exhalation.

    7. AHAndrew Huberman51:52

       What was the task? Was it an olfactory test?

    8. NSNoam Sobel51:54

       No, no. It's a visuospatial task.

    9. AHAndrew Huberman51:56

       Oh, excuse me, yeah.

    10. NSNoam Sobel51:56

        So, this is a task where, where, uh, the, the, the specifics of the task were, um, that you see a, a shape and you have to determine if it's a shape that can or cannot exist in the real world. So, some of them are these, like, Usher shapes, like, you know, where, where one facet doesn't reach the other facet.

    11. AHAndrew Huberman52:15

        The impossible figure type stuff.

    12. NSNoam Sobel52:16

        It's... Yeah.

    13. AHAndrew Huberman52:17

        Yeah.

    14. NSNoam Sobel52:17

        But, but, but structural shapes. Not-

    15. AHAndrew Huberman52:20

        Mm-hmm.

    16. NSNoam Sobel52:20

        Not... And, and so, so a pure visuospatial task. We, we intentionally went for a task that is not considered a ventral temporal task, an olfactory cortex task in any way, and, and people performed much better on inhalation versus exhalation at doing this task.

    17. AHAndrew Huberman52:39

        Was there a both nostrils occluded, um, version where people were forced to mouth breathe?

    18. NSNoam Sobel52:44

        Yes, and in this particular task, they also did better on mouth inhalation versus mouth exhalation, but the difference wasn't as pronounced as it was with nasal inhalation versus exhalation.

    19. AHAndrew Huberman52:58

        So bet... Uh, I'm, I'm a big proponent of nasal, not mouth breathing whenever possible-

    20. NSNoam Sobel53:03

        For sure.

    21. AHAndrew Huberman53:04

        ... for, um, many health-related reasons. I'm a big fan of the book, Jaws: A Hidden Epidemic, uh, written by colleagues of mine at Stanford.

    22. NSNoam Sobel53:11

        Familiar with it.

    23. AHAndrew Huberman53:11

        Yep, and this idea that people who mouth breathe, um, experience more colds, more infections of various kinds. It's not good aesthetically or for the dentist- dentature. I never know... The teeth, gums, and stuff.

    24. NSNoam Sobel53:25

        Yeah.

    25. AHAndrew Huberman53:25

        Folks, sorry.

    26. NSNoam Sobel53:25

        Stuff.

    27. AHAndrew Huberman53:25

        My, uh, my dentist is going to come after me. Um, need to go to the dentist anyway. The, um, that nose breathing is great for your health relative to mouth breathing.

    28. NSNoam Sobel53:34

        So, so I think it's also good for your cognition, not only for your, your dental health. Uh, I think that, that nose breathing shapes cognition, and, and there, there are other labs, uh, who, who are, uh, are finding the same. Uh, again, uh, Cristina D'Alessandro is doing work on this line. She, she had major contributions here, and, and Johan Lundström is doing work on this line. There, there's lots of studies suggesting that, um, nasal inhalation is timing cognitive processing, and, and modulating it.

    29. AHAndrew Huberman54:09

        Incredible. Um, perhaps not surprising given what you've taught us about the olfactory system. I mean, th- these two holes in the front of our face, these nostrils, I mean, are a pathway to the brain, right? I, I love to tell people 'cause I work on the visual system in my lab that, you know, your eyes are two pieces of brain extruded from the cranial vault.

    30. NSNoam Sobel54:29

        Right.
11. 54:47 – 1:00:12

    Neurodegenerative Diseases & Olfaction

    1. NSNoam Sobel54:47

       it's the only place where your brain meets the outside world, because in your retina they're protected by, by a lens.

    2. AHAndrew Huberman54:52

       Mm.

    3. NSNoam Sobel54:53

       And here, here you have neurons in contact with, with the world. This, this actually has been the source for some theories on a potential, uh, route for, for neurodegenerative, um, um, mechanisms. So, as, as you may know-... um, loss of the sense of smell is one of the, if not the earliest sign of neurodegenerative disease. So for example, in Parkinson's disease, there's, uh, a loss in the sense of smell, probably 10 years before any other symptom. Um, but people have failed to make this a diagnostic tool because it's non-specific. So it's not as if you could come to your doctor and say, "I'm losing my sense of smell." And they'll say, "Oh, early sign of Parkinson's." Because you can have many reasons to lose your sense of smell and, and, and so on. Um, but, but olfactory loss, again, is, is an early sign of, of neurodegeneration. And there's at least one theory, particularly about Alzheimer's disease, suggesting that, that Alzheimer's may be the result of, of a, a pathogen that enters the brain through the olfactory system.

    4. AHAndrew Huberman56:04

       Mm.

    5. NSNoam Sobel56:05

       Um-

    6. AHAndrew Huberman56:05

       How interesting.

    7. NSNoam Sobel56:06

       It's, it's not of course a, a, a mainstream or widely accepted theory of any type, but, but it's just, it just highlights this notion that, that the nose is a path to our brain.

    8. AHAndrew Huberman56:18

       I think these non-invasive, um, readouts of potential neurodegeneration, um, such as, uh, visual tests, because of the fact that the retinas are part of the brain and loss of neurons in the retina is often associated with other forms of central degeneration, Alzheimer's, um, Parkinson's, et cetera. As it's a little more invasive than what you're describing, I'm beginning to wonder why we don't, um, get, have a, uh, olfactory task every time we go to the doctor, um, that would allow tracking over time. Because of course, so, as you mentioned, someone can lose their sense of smell, does that mean they're getting Alzheimer's? Not necessarily. But if their sense of smell was terrific the year before and it's 50% worse the next year-

    9. NSNoam Sobel56:58

       That's a really bad sign.

    10. AHAndrew Huberman56:59

        Yeah, that's a bad sign, and so what we were talking about is something completely non-invasive, um, and could be relatively pleasant to innocuous-

    11. NSNoam Sobel57:06

        Right, so-

    12. AHAndrew Huberman57:06

        ... depending on the odors used.

    13. NSNoam Sobel57:07

        So yeah, so, so first, I can answer that, right? And the reason that that's not happened, and that might, that, that may be changing right now, but the reason that has not happened is because olfaction has not been effectively digitized, right? So if, if you need to generate, you know, really precise visual information, you can buy a monitor for, you know, 100 bucks that is at the resolution of the visual system basically. And if you want to generate auditory stimuli really precisely, then you can buy an amplifier for, you know, maybe a bit more than 100 bucks, but not that much more. And you'll be at the resolution of the auditory system. In our lab, we build devices that generate odors. Uh, we call them olfactometers, which is a misnomer because they don't measure anything, but that's what they've always been called, so we call them olfactometers as well. And we've already built at least one olfactometer that cost a quarter of a million euro, and it's pathetic, right? So it just, it's pathetic. It's, it's slow, it's contaminated. It's nowhere near the resolution of your system. So one of the reasons that's not happened is just the utterly poor control of the stimulus. Mind you, to some extent it has happened in that there, there are, uh, uh, standard clinical tests of olfaction, basically two that sort of control, uh, the world in this respect. The older one is, is a test called the UPSIT, which stands for the University of Pennsylvania Smell Identification Test. It was developed by Richard Doty in Penn, and it's a test where you scratch and sniff and, and it's a four alternative forced choice test with 40 odorants. So you have these 40 pages that you page through and you sniff and smell, and, and, um, you know, it's been normed on gazillions of tests. Um, I, I'm always amused by it because ... So, so Richard Doty made a ton of money, uh, on the UPSIT, but he needed it because he has a habit. He has a NASCAR thing that he ... (laughs) So this, every time we buy UPSITs in the lab, I say there's another gallon of gas into Richard Doty's-

    14. AHAndrew Huberman59:12

        He races NASCAR?

    15. NSNoam Sobel59:14

        It's not, not like NASCAR but like, one lower than that, like I don't know, like some, some sort of Formula A or Formula Ford or something. He races a car, and so that's where all the UPSITs went, so I always feel good about buying UPSITs because I know they're going to that good cause. But, bu-

    16. AHAndrew Huberman59:29

        Keeping him in, in, in, in the fast lane.

    17. NSNoam Sobel59:31

        (laughs) Yeah, but, but so, so that's one test that's out there and, and indeed, you know, has been shown as a, a, you know, so, so there's reduced UPSIT in Alzheimer's and Parkinson's and, and in a host of other diseases.

    18. AHAndrew Huberman59:43

        Mm-hmm.

    19. NSNoam Sobel59:43

        And there's a European version called sniffing sticks, uh, that Thomas Hummel, uh, has developed, and, and it's, it's, mm, basically the same sort of concept of ... That one isn't scratch and sniff. It's like these pens that you open up and, and sniff. But, but those exist, but they're not as, as convenient as, as, uh, as d- delivering stimuli in vision and audition, and that's why, uh, you don't have what you've just suggested.

    20. AHAndrew Huberman1:00:10

        Interesting.

    21. NSNoam Sobel1:00:11

        You know, another thing, another

12. 1:00:12 – 1:05:01

    Congenital Anosmia

    1. NSNoam Sobel1:00:12

       place where you don't have it which, which I think is even more, would have been even more meaningful is, is you don't ... Olfaction's not tested in, in newborns, right? Where vision and audition is. You know, there's this thing called congenital anosmia, right, which is being without the sense of smell from birth supposedly, congenital. Uh, which is half a percent of the population.

    2. AHAndrew Huberman1:00:34

       It's not a trivial number.

    3. NSNoam Sobel1:00:36

       N- not totally, yeah. But nobody knows if that really is true because h- here's an amazing factoid. Guess the average age at which congenital anosmia is diagnosed, and this is, this is a horrible statistic for me, for the way I see the world. But what do you think the average age of diagnosis is for congenital anosmia?

    4. AHAndrew Huberman1:00:59

       Five years of age?

    5. NSNoam Sobel1:01:00

       14.

    6. AHAndrew Huberman1:01:01

       Incredible.

    7. NSNoam Sobel1:01:02

       14.

    8. AHAndrew Huberman1:01:02

       So most people who are one half of 1% of the human population presumably-

    9. NSNoam Sobel1:01:08

       Yeah.

    10. AHAndrew Huberman1:01:08

        ... is, uh, without the sense of smell and doesn't realize that until they're 14 years old?

    11. NSNoam Sobel1:01:13

        Well, I don't know when they realized it first, but, but it's formally diagnosed at 14 on average.... which means, some of them even later, right? (laughs) After.

    12. AHAndrew Huberman1:01:21

        And, um, and, uh, right, it's a distribution. W- what, um ... Do they suffer?

    13. NSNoam Sobel1:01:27

        Yes. So, so first of all, they, they suffer socially. Um, and there's a host of, of deleterious life events associated with congenital anosmia. Um, the, i- they die younger. Um, the, the, so it's, it's, it's a, it's ... This is work out of, uh, Ilona Kroih in Germany. Um, and, you know, amongst the various things that are predicted by, uh, anosmia is shorter lifespan. Uh, but things like, you know, reduced, uh, social contacts, uh, reduced, um, uh, romantic/social contacts, um, it's not a good thing. Um, and-

    14. AHAndrew Huberman1:02:12

        And, and, and do they lack olfactory bulbs? Uh, I'm presuming they have noses and nostrils.

    15. NSNoam Sobel1:02:16

        They have noses-

    16. AHAndrew Huberman1:02:16

        There is a condition I'm aware of where, where, uh, children are born without noses or nost-

    17. NSNoam Sobel1:02:20

        The, the, they have a rare-

    18. AHAndrew Huberman1:02:21

        Very rare.

    19. NSNoam Sobel1:02:22

        Yeah.

    20. AHAndrew Huberman1:02:22

        Very rare.

    21. NSNoam Sobel1:02:22

        It's a rare thing.

    22. AHAndrew Huberman1:02:22

        We won't focus on that because it's, it's exceedingly rare.

    23. NSNoam Sobel1:02:24

        Yeah.

    24. AHAndrew Huberman1:02:24

        Um, so-

    25. NSNoam Sobel1:02:25

        But they're born with noses and nostrils. Um, and here's the thing, right? We don't know if they're born with olfactory bulbs. Um, most of them, although not all of them, but most of them don't have olfactory bulbs in adulthood or, or I should rephrase that, have remnant olfactory bulbs, really shriveled olfactory bulbs. But, you know, nobody can say the cause and effect here.

    26. AHAndrew Huberman1:02:48

        Before we talk about the role of the, the, uh, requirement for olfactory bulbs for olfaction, a very interesting topic in its own right, I, I'm curious as to whether or not their endocrine system is altered. Because as we'll soon talk about, there's a lot of signaling through the nose from-

    27. NSNoam Sobel1:03:06

        Right.

    28. AHAndrew Huberman1:03:06

        ... between individuals that, (sniffing) uh, triggers things, everything from the onset of puberty to feelings of romantic attraction, attachment-

    29. NSNoam Sobel1:03:13

        Right.

    30. AHAndrew Huberman1:03:13

        ... these sorts of things. Um, is it known whether or not ... A- and I should say, excuse me for interrupting myself, but as long as I'm interrupting you every five minutes, I might as well interrupt myself too, that, um, we are well aware of the proximity of the olfactory system to some of the hypothalamic systems that regulate the release of gonadotropins-
13. 1:05:01 – 1:06:19

    Sponsor: InsideTracker

    1. AHAndrew Huberman1:05:01

       that. I'd like to just take a brief moment and thank one of our podcast sponsors, which is InsideTracker. InsideTracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals. I've long been a believer in getting regular blood work done for the simple reason that blood work is the only way that you can monitor the markers such as hormone markers, lipids, metabolic factors, et cetera, that impact your immediate and long-term health. One major challenge with blood work, however, is that most of the time it does not come back with any information about what to do in order to move the values for hormones, metabolic factors, lipids, et cetera, into the ranges that you want. With InsideTracker, changing those values becomes very straightforward because it has a personalized dashboard that you can use to address the nutrition-based, behavior-based, supplement-based approaches that you can use in order to move those values into the ranges that are optimal for you, your vitality, and your longevity. InsideTracker now includes a measurement of apolipoprotein B, so-called apo b, in their Ultimate plan. Apo b is a key marker of cardiovascular health, and therefore there's extreme value to knowing your apo b levels. If you'd like to try InsideTracker, you can go to insidetracker.com/huberman to get 20% off any of InsideTracker's plans. Again, that's insidetracker.com/huberman to get 20% off.

14. 1:06:19 – 1:15:07

    Handshaking, Sharing Chemicals & Social Sensing

    1. AHAndrew Huberman1:06:19

       I have a, a story/question that I'd like to, um, tell you, ask you as a segue to that, um, noting of course that we'll get back to the, the requirement for olfactory bulbs, yes or no, for olfaction.

    2. NSNoam Sobel1:06:33

       (laughs)

    3. AHAndrew Huberman1:06:33

       Uh, and, um, this relates to when I was growing up, I grew up at the, uh, end of a street with a l- a lot of boys of my age who, just by coincidence had a lot of older sisters that were my sister, my older sisters' age. I was fortunate, so I had a lot of kids to play with. We would hang out at each other's houses, bike, build jumps, and do all this things, like kid stuff, fort stuff, get into trouble or whatnot, and oftentimes we would end up leaving our articles of clothing at each other's houses all the time, like T-shirts and jackets. And so my mom was constantly coming in and saying, "There's all, there's his clothes." Like, "Someone left this here. I don't know who it was." We were all more or less the same size, and from the, as far back as I could remember...... six, seven years old and onward. I could pick up a shirt or a jacket, smell it, and say, "Oh, well, that's Eric Eisenhart's shirt." A friend of mine there, I just gave his name. Or, (sniffs) "Oh, that's Scott Madsen's shirt." I, I could just smell the shirt and in a conscious way know who it belonged to, having never, I promise, not that I would pretend if I ha- if I had, um, pretend that I hadn't if I had, but having never actually done the exercise of going and taking, uh, and smelling my friend intentionally.

    4. NSNoam Sobel1:07:49

       Right.

    5. AHAndrew Huberman1:07:49

       Okay? In fact, if anything, I had all the reasons in the world to avoid smelling-

    6. NSNoam Sobel1:07:53

       (clears throat)

    7. AHAndrew Huberman1:07:53

       ... uh, the other young boys in my neighborhood.

    8. NSNoam Sobel1:07:54

       Yeah.

    9. AHAndrew Huberman1:07:55

       Okay. So-

    10. NSNoam Sobel1:07:55

        Yeah.

    11. AHAndrew Huberman1:07:57

        ... um, that raises the question of whether or not we are consciously and/or subconsciously coding identification of people that we interact with frequently or infrequently in terms of their smell, eh, or some other aspect of their, um, chemistry.

    12. NSNoam Sobel1:08:15

        Yeah. So, yes. (laughs) Um, w- we're doing that all the time, in my view, and a lot of this processing, almost all of it, uh, is subconscious, and I don't know why. Already, already s- put that out there, right? I have no idea why, why, uh, human nature has, has, uh, or, or nature, or culture, or whatnot, has, has, has pushed this into the realm of, of subconscious and, and something we're unaware of. Um, but we do it all the time, and, and, um, and our lab has lots of studies on this front. Um, one of them you may be familiar with that, that had gained some notoriety because it's amusing. Um, so, so we, we look at human behavior a lot. We try to look at it through our nose in, in the way we look at what people are doing. You know, we try to think, you know, if I was a dog, what, what would I think of this? And, and, you know, if you look at dogs, right, they, they ve... You know, when they interact, they visibly sniff each other. It's very obvious. They walk up to each other and they sniff each other. Um, and yet humans don't typically walk up to a stranger and carefully sniff them, right? I mean, it's... W- we're, we're sort of obliged to sniff our, our babies. That's considered almost something you're supposed to do.

    13. AHAndrew Huberman1:09:42

        Mm-hmm.

    14. NSNoam Sobel1:09:42

        Um, and it's not culturally taboo to sniff our loved ones. It sort of doesn't seem like an odd thing to do. But we don't sniff strangers, all right? Well, or do we? So w- we're finding more and more mechanisms where we do this, and, and the one I'm referring to now f- for one example is we started looking at handshaking. Handshaking is this really odd behavior, and it's not only in the West, by the way. Some people think it's only a Western thing. It's not. It's almost everywhere.

    15. AHAndrew Huberman1:10:12

        (sniffs)

    16. NSNoam Sobel1:10:12

        And, and there's really poor understanding of how this behavior evolved, like where did, where did this c- thing come from? So if, if you, you know, if you look for the Wikipedia version, right, then they'll tell you that it's to show that you're not holding a weapon in your hand. But there's really no good evidence for that. It's a bit like the trillion blood hound receptor story, right? I mean, we tried to find it. You know, why do people say that? Mm, they just do. And we started looking at people handshaking, and, and we noticed, or it seemed to us that we're noticing that, you know, people will shake hands and then go like this and like this and-

    17. AHAndrew Huberman1:10:48

        For those of you listening, not watching-

    18. NSNoam Sobel1:10:50

        Um, yeah.

    19. AHAndrew Huberman1:10:50

        ... Noam, um, is taking his hand and, and wiping it on his face.

    20. NSNoam Sobel1:10:54

        Yeah, or-

    21. AHAndrew Huberman1:10:55

        Grabbing his nose or, or-

    22. NSNoam Sobel1:10:56

        ... yeah, or touching myself.

    23. AHAndrew Huberman1:10:57

        ... touching the side of his cheek.

    24. NSNoam Sobel1:10:57

        Yeah, these things, these things that we do all the time.

    25. AHAndrew Huberman1:11:00

        After a handshake.

    26. NSNoam Sobel1:11:01

        Well, so, so first of all, we do them all the time just period, right? The baseline here is really high, and we'll get to that in a second, but, but, but these behaviors that, you know, you, you could easily not notice, right? And, and so we, we asked whether that's a real thing. Um, and this was a study led by Idan Frumin in our lab at the time, um, and what we did first, and, and if you want, we, we can link so... So this was published in eLife, and one of the nice things about eLife is that it has a very effective way to, uh, embed videos in the publication. So if you want, we can link this to your system later on, the, the eLife-

    27. AHAndrew Huberman1:11:36

        Yeah, we'll put it in the show note captions as a link o- on YouTube and the other four, uh, platforms, Spotify, Apple.

    28. NSNoam Sobel1:11:42

        So, so what we did is, is, um, we, we brought in participants to our lab, and we sat them in the room, uh, experiment room, and, and told them the experiment would start soon and they should wait for us there. They didn't know what they were coming from. Unbeknownst to them, they were already being videoed. Uh, of course, later on, they, they had the opportunity to, to not agree to us saving the video, in which case we would delete it immediately or, or letting us use it for science or some letting us use it for more than science for, for the video that's now on eLife. And, and we would walk into the room and say, "Okay, just wait here. Uh, we'll be right back with you, uh, to set up our experiment." And they would sit there for three minutes, and during those three minutes, we could later quantify how much indeed they, just by baseline, how much they touch their nose, or their forehead, or their chin, or how many times their hand, uh, uh, reaches their face. And by the way, that baseline is not low, okay? Um, and then three minutes later, an experimenter would walk into the room and, uh, would share a, a consistent text. It would be, "You know, we're still setting up our equipment in the other room. Uh, our... And, and so just wait here and we'll be right back with you, but in the meantime, just wait here." And the experimenter went through this like 20-second fixed text, and in half of the cases, it included a handshake. This was a new experimenter, not the one who put them in the room. So that's the first time they met. So it'd be a little, "I'm, you know, so and so." They would put out their hand and shake their hand or not. Okay? And we did all possible interactions in terms of gender, so we matched, uh, male participants with male and female experimenters, and female participants with female and male experimenters. And so you had handshake and no handshake conditions, and then you can quantify that behavior of the hand going to the nose after handshake. And there was a remarkable increase in the hand going to the nose after handshake. And-This is one of the nice cases we... The paper includes statistics but you don't need statistics here, just look at the video. It's un- it's unreal. The video is unreal.

    29. AHAndrew Huberman1:13:42

        So interesting.

    30. NSNoam Sobel1:13:42

        So the hand goes to the nose. Now, we did a few controls here to verify that this is an olfactory behavior. One is, unbeknownst again to participants, we measured nasal airflow, and, and people not only bring their hand to their nose, they sniff it. So, and this is perfectly timed, they go (sniffs) like this, okay? So they're sniffing their hands. And in an additional control study, we manipulated it, so we built this little James Bond thing of a watch on the experimenter's hand that could emit an odor. And the experimenter didn't know what odor they were emitting, and they could emit either a pleasant or an unpleasant odor, and we could drive the self-sampling afterwards up or down. So this was an olfactory behavior, no doubt about it. I mean, we're, we're quite confident that-
15. 1:15:07 – 1:22:02

    Smelling Ourselves & Smelling Others

    1. NSNoam Sobel1:15:07

       There's, uh, on, on the same line, and again, to, to link to your childhood story of, of, of, uh, identifying your friends by, by smell, um, a study we published just last year by, uh, Inbal Rav-Rebbi in our lab, um, where Inbal came with this, uh, uh, basic interest in this phenomenon that's loosely referred to as click friendships. So people you meet and you click right away, right? You immediately become close friends. And this is a phenomenon that, uh, that, you know, is poorly described or is poorly described in liter- literature as, as, as an entity, and yet anybody will tell you they know what you're talking about, right? I mean, if you tell, you know, if somebody you click with right away, you, you become intimate within five minutes, right? Everybody experienced this in their life, you know, to some extent. And the question is how... What, what was there, right? What was it? Was it because you looked the same? It could be. Was it because, you know, you had the same sports team that you liked or is there something, uh, uh, deeper here? And, and Inbal's theory was that, that, um, that a similarity in body odor may contribute to this. That people who smell the same will click in some way. And so to address that, she, she actually recruited, uh, um, click friends from all over Israel, she posted all over social media, uh, to identify, uh, pairs of friends, so these are, are same sex, non-romantic dyads. So these are friends, men and women, uh, whose friendship started as a click, where here this becomes sensitive because it has to be a mutual click, right? Later on, we discovered there could be one-sided clicks (laughs) so if somebody's sure they clicked with somebody else but the other person...

    2. AHAndrew Huberman1:16:55

       There's a name for that in neurology that our, uh, common friend, the late Ben Barres taught me which is, there's a phrase that neurologists use-

    3. NSNoam Sobel1:17:02

       Okay.

    4. AHAndrew Huberman1:17:02

       ... called sticky. These are people that come up to you and-

    5. NSNoam Sobel1:17:05

       (laughs)

    6. AHAndrew Huberman1:17:05

       ... and start asking you questions and then won't leave you alone. They're, they're so-called sticky people-

    7. NSNoam Sobel1:17:10

       Okay.

    8. AHAndrew Huberman1:17:10

       ... that are... And if you ask these sticky people, um, "sticky" in air quotes 'cause they're not physically sticky, um-

    9. NSNoam Sobel1:17:17

       They may be.

    10. AHAndrew Huberman1:17:17

        ... what (laughs) ... They could be. Um, you know, what do you think of the per- this person? They'll say, "Oh, they're great. We're really good friends," and so they've made a unilateral, um, click friendship, um-

    11. NSNoam Sobel1:17:29

        Yeah, yeah, yeah.

    12. AHAndrew Huberman1:17:29

        ... and, uh, yes, neurologists are talking about you. If you're, if you're-

    13. NSNoam Sobel1:17:32

        (laughs)

    14. AHAndrew Huberman1:17:32

        ... one of these people neurologists are talking about you, there's a, an, an informal diagnostic code, uh, sticky.

    15. NSNoam Sobel1:17:38

        (laughs) So, so, so, uh, she, she recruited, um, um, click friends, and then she, um, sampled their body odor. And, and we have a protocol for this so they're given, you know, uh, uh, odorless shampoo and soap to use for three weeks or something, and then they sleep two nights in this T-shirt, uh, where they have to sleep alone and then we extract the body odor from the T-shirt, and so we have a way to extract, uh, a method to extract body odor. And then she, she first asked, um, whether indeed click friends are more similar in their body odor than you would expect by chance. And she first tested this with a, with a device, a machine we call an electronic nose. So an electronic nose is sort of a very poor effort to mimic what the mammalian nose does. Basically, it's a bunch of sensors that respond to airborne molecules. In this case, sensors referred to as MOXors, those are metal oxide covered sensors. Um, and so she used an electronic nose to sample these body odors and she found that click friends are indeed more similar to each other, uh, than you would expect, uh, by chance, by random dyads, and- and this was a significant difference. And after she found that a device could do this, she had other participants do this. So, so she had people smelling the click friends versus non-click friends and, and they judged them as being more similar to each other, uh, than not. Now again, you, you might wonder, is this causal or not, right? Because maybe click friends go to the same restaurant together or all the time or whatever, live in the same neighborhood and, and that's why they, they, they smell the same. So to address causality, she recruited total strangers and first smelled them with the electronic nose and then engaged them in a social interaction, something called the mirror game. So in the mirror game, one person moves their hands and the other person is really close to them, like, right here, so they can smell each other, and has to move their hands with the other person.... and one, one prediction there panned out, uh, but another didn't. The one that didn't, so she predicted that people would smell more, uh, similar to each other, would be better at the mirror game. That is, they would follow each other better. That did not pan out. However, she then also had, the, the interaction was completely non-verbal. They were not allowed to speak with each other, and she did an entire round robin, so everybody played with everybody else. This was an insane experiment to run. And she then, at the end of the experiment, each person rated each other person as to how much they think they would want to be their friends, and also on a bunch of ratings, how nice they think they are, or how affectionate they think, a bunch of ratings, okay? All of this was predicted by the electronic nose. So people who smell more similar to each other think that the other person is more likely to be their friend, is more likely to be a nice person, et cetera, et cetera. So we could actually predict friendship using the electronic nose. So this is not a result of friendship. It's, it, it plays into the causal elements of, of building friendship. So this is to relate to your childhood story. Uh, there's something going on here. We're, we're constantly smelling ourselves. Constantly. This constantly s- uh, I mean, if you want to link, um, and I'll, uh, the reason I'm smiling, I mean, and, and your viewers or listeners will understand (laughs) why I'm smiling, I'll send you a video to link, uh, uh, in, in the, in, into your podcast here. Uh, we thought of calling, the, the, the fact that people constantly sniff themselves, we thought of calling this the Loh effect. And Loh, uh, so, so in, in America, this won't pass that effectively, but in, in, in the rest of the normal world, uh, Joachim Loh is the soccer, the national soccer coach of the German soccer team, so yeah, I mean, I don't know who would be a very famous coach here, but Steve Kerr, or, uh, I mean, this is the, you know-

Episode duration: 3:13:15