Huberman Lab - Dr. Noam Sobel: How Smells Influence Our Hormones, Health & Behavior

Episode Date: May 1, 2023

In this episode, my guest is Noam Sobel, PhD, professor of neurobiology in the department of brain sciences at the Weizmann Institute of Science. Dr. Sobel explains his lab’s research on the biological mechanisms of smell (“olfaction”) and how sensing odorants and chemicals in our environment impacts human behavior, cognition, social connections, and hormones. He explains how smell is a crucial component of “social sensing” and how we use olfaction when meeting new people to determine things about their physiology and psychology, and he explains how this impacts friendships and romantic partners. He explains how smell influences emotions, hormone levels, memories and the relationship between breathing and autonomic homeostasis. He describes how smell-based screening tests can aid disease diagnosis and explains his lab’s work on digitization of smell — which may soon allow online communication to include “sending of odors” via the internet. Dr. Sobel’s work illustrates how sensitive human olfaction is and how it drives much of our biology and behavior. For the full show notes, visit hubermanlab.com. Thank you to our sponsors AG1 (Athletic Greens): https://athleticgreens.com/huberman ROKA: https://roka.com/huberman Thesis: https://takethesis.com/huberman Helix Sleep: https://helixsleep.com/huberman InsideTracker: https://insidetracker.com/huberman Supplements from Momentous https://www.livemomentous.com/huberman Timestamps (00:00:00) Dr. Noam Sobel (00:03:46) Sponsors: ROKA, Thesis, Helix Sleep (00:06:46) Olfaction Circuits (Smell) (00:14:49) Loss & Regeneration of Smell, Illness (00:21:39) Brain Processing of Smell (00:24:40) Smell & Memories (00:27:52) Sponsor: AG1 (00:29:07) Humans & Odor Tracking (00:39:25) The Alternating Nasal Cycle & Autonomic Nervous System (00:48:18) Cognitive Processing & Breathing (00:54:47) Neurodegenerative Diseases & Olfaction (01:00:12) Congenital Anosmia (01:05:01) Sponsor: InsideTracker (01:06:19) Handshaking, Sharing Chemicals & Social Sensing (01:15:07) Smelling Ourselves & Smelling Others (01:22:02) Odors & Romantic Attraction (01:24:58) Vomeronasal Organ, “Bruce Effect” & Miscarriage (01:40:20) Social Chemo-Signals, Fear (01:50:26) Chemo-Signaling, Aggression & Offspring (02:03:57) Menstrual Cycle Synchronization (02:12:11) Sweat, Tears, Emotions & Testosterone (02:27:46) Science Politics (02:37:54) Food Odors & Nutritional Value (02:45:34) Human Perception & Odorant Similarity (02:52:12) Digitizing Smell, COVID-19 & Smell (03:05:50) Medical Diagnostic Future & Olfaction Digitization (03:10:55) Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Momentous, Social Media, Neural Network Newsletter Title Card Photo Credit: Mike Blabac Disclaimer

Welcome to the Uberman Lab podcast where we discuss science and science-based tools for everyday life. I'm Andrew Uberman 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 Weisman 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 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 also learned that tiers, yes, the tiers 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. Nome 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, Noem Sobel was a professor at UC Berkeley, as I mentioned before, he has since moved to the Weissman. 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. 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 centrail 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 Weisman involving neuroimaging and a number of other tools and techniques that revealed the incredible power of human olfaction and human's ability to follow centrails if they need to. And that of, 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. Solvul'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. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research rules 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.

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go to roka. That's roka.com and enter the code huberman to say 20% off your first order. Again, that's roka.com and enter the code huberman at checkout. Today's episode is also brought to us by thesis. Thesis makes custom neutropics. And neutropics 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

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Check out 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 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, 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 at the USK 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 Helix mattress, go to helixleap.com slash 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 helixleap.com slash huberman for up to $350 off and two free pillows. And now for my discussion with Dr. Nome Sobel. Dr. Sobel, known.

Welcome. Thank you. 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. Yes. Kind of frightening. Yeah. We overlapped at UC Berkeley some time ago,

although we did not meet. And we lived in the same apartment. 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, I believe. So we've shared quite a few things. And today I'd love for you to share with us all about the amazing landscape of chemosensation in particular, olfaction or 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 where I like to think it involves the nose at some level. It does. 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 and not watching? I'm tapping my nose that we are sensing through this thing and for those of you listening and not watching, I'm tapping my nose, that we are not aware of, you know, the chemicals that are that we're inhaling and making sense of without our awareness. If you could just give us the top contour or even deep contour of you like of the parts list and the various roles they play. So you've asked a lot of questions at once.

You know, I'll start with a little comment on the way you said smelling through our news, which we indeed do, but we also smell through our mouth, actually. There's a process referred to as retro nasal infection where odorants come up through 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 all faction to food and taste comes from that, from retro nasal all faction. But primary all faction is referred to as ortho nasal all faction that is through our nose. We sniff and sniffing is a big thing. 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.

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 do you 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 seven million such receptors lining a structure known as the olfactory epithelium. This is the sensory surface of the olfactory system, the olfactory epithelium. This is the sensory surface of the olfactory system, the olfactory epithelium. Again, probably about six or seven million receptors

in the human. In the human, probably about 350 different kinds. So that's amazing. That means 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 is probably not very well grounded. It's hard to count, 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 our lab has written over the years a few review chapters and we were repeatedly writing the all-faction chapter for a very large, one of these large textbooks, the Gezzanaga, handbook of cognitive neuroscience, I think it's called. And we had that in there as well somewhere. And one time when we were renewing the chapter

for a new version of the book, I told the graduates, soon, who is leading that at the time, Aray Shurun, she's now 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 we wrote her and as it looked, there's this thing in the literature of a billion receptors in the bloodhound.

Where did that come from? And surprisingly, she answered me. And I was hoping to get a reference, right? But it wasn't a reference. And this is where it really becomes funny for us because she said, I was once at a lecture of an olfaction geneticists by geneticist by the name of Doron Lancet. 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 her from Israel and Doron Lancet is in the building next to me. Okay, he's in white-smann incident to genetics. I mean, he used to be, he's retired now. And he had meaningful contributions in the history of all faction. So I picked up the internal phone and I said,

hey, DeRan, did you say that there's a billion receptors in the Bloodhound nurse? And he said, what's a bloodhound? So this was totally made up, right? It totally made up and it propagated. I mean, you can probably go into Google and type like a billion receptors into the blood town and you'll get a lot of hits.

But there was absolutely no evidence for that. Amazing. And not just amazing in light of what it tells us about it all faction and bloodhounds or otherwise, but amazing because it sheds light on just how much of what is in textbooks. Scientific and medical is absolutely wrong. Things propagate and you know you cite yourself and right so we fix that in that version of the right of the and so to finish the line so that so so odorants interact with these receptors here in arachythelium where they undergo what is referred to as transduction that is the odorants

what is referred to as transduction, that is the odorants are docket or receptor and turn into a neural signal or enforce the receptor to respond in a neural signal. And this neural signal, in fact, action potentials, not gradient potentials of any kind, propagates via the olfactory nerve. Now, this is a nerve that goes from our epithelium right here behind the forehead. No, it's, well, yeah, yeah, here, through the thinnest part of our skull, an area where it refers to as the crib reform plate, which is preferated, it has a lot of holes. The nerve goes through those holes and synapses at the first target in the brain, which is the olfactory bulb. And humans, that forms an interesting point of sensitivity because a lot of people lose their sense of smell due to trauma because of that structure. Yeah, head-hit type trauma.

Well, yes, although you denoted hitting on the front of the head, which is where all this real estate is, but actually the more common cause for losing your sense of smell for trauma is the back of the head. Because of what's referred to as a country quenjury. So as your listener has probably known, our brain is floating in liquid and CSF and cerebral spinal fluid inside our skull. And when we get hit in the back of the head, the brain has this forward and backward movement in the liquid, in the skull. It sort of crashes. It can crash against

the front of the skull, which is why you also have, in a contract winder, you also often have frontal damage. But what happens is that this generates a shearing motion on the crib form plate. And the olfactory nerve is severed, and if it's completely severed, it's lost. Forever because my understanding is that the olfactory sensory neurons are among the few central nervous system neurons in adult humans that can regenerate. So we replenish themselves. Right.

So I'll, again, there are a few questions in the line. That's okay. So, first of all, we will spend many plates simultaneously. If it's completely severed, completely, then yes, you're lost. Forever. Yeah. If it's completely severed, because even if you'll have regeneration at the basal level at the pithelium, they won't manage to find their way back to the bulb. 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. Because they grow along the trajectory of the other axles or pioneering the way for them. Assumingly, yeah. And so basically, the timeframe, and you know, it's funny, I get a lot of emails on this, although I'm not a medical doctor funny, I get a lot of emails on this,

although I'm not a medical doctor, 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 basically the rule of thumb is that if you don't get it back within a year to year and a half, you'll never get it back. My understanding of the statistics on olfactory loss

in COVID and other viral type infections is that, first of all, I had experienced that when I got COVID, including total and loss for one day. And not total, it was just, there was a remnant of an ability to smell or perceive the smell of a lemon and I was huffing as hard as I possibly could. I actually, there's an over-the-counter remedy and this is not pseudoscience

because there's a number of papers published about this on PubMed that alpha-lipobic acid can accelerate the recovery of smell. Yeah. And so that's something that it worked successfully for me. I'm not saying that that's the only or round. You don't know if it worked successfully for you or if you would have recovered anyway. I mean, you didn't do a control.

Sure. But I wasn't out wanting to do the control experiment. Exactly. Let me say two things on this front. First, the dean on the alpha of pocacid is. Oh, yeah. It's not overwhelming. Yeah. But losing your sense of smell is overwhelming.

Yeah, you know, I know. I know. And so I think people will be desperate. One word about the smelling the lemon. And this is, I'll take that opportunity to share more information. When we smell things, it's the result of more sensory subsystems than the olfactory system along. So you have several chemocensory sensitive nerves in your nose. A primary one beyond the olfactory nerve is the trigeminal nerve, the fifth cranial nerve. So the trigeminal nerve has sensory endings

in your nose and your throat and in your eye. It has three branches. That's why an onion has a smell and burns your eyes and burns in your throat. Is that what? It's trigeminal, yeah. The tearing of cutting an onion is trigeminal reflex. Amazing. We talked about trigeminal in the context of headache

during a headache episode. It's a trigeminal reflex. So the lemon you were smelling may have been a trigeminal sensation. So smelling the lemon with my eyes is what you're saying. No, with your nose, but with your trigeminal receptors and not your olfactory receptors. So within, you know, all faction researcher jargon, there's what we refer to as pure

olfactants. These are orders that will stimulate ural factory nerve alone. They won't influence your trigeminal nerve at all. And an example, just to get a sense of what that might be would be the coffee right here, is a pure olfactant of vanilla is a known pure olfactant. These things have no trigeminal activation. As long as we're on this topic and we'll weave back and forth, but I'm glad we are on this topic because a tremendous number of people wrote to me during the pandemic and continue to

about olfactory loss. Is the I've heard of this olfactory training, whereby if you have a partial or even a complete loss of a primary olfaction, that one is encouraged to smell a number of different smells, I grew up studying activity dependent wiring of the nervous system, it makes total sense to me why keeping neurons active keeps them alive.

So this is not fire together, wire together type thing. By the way, that's a quote from Carla Shatz, not Donald head folks or me. But this is about keeping neurons electrically active. In this case, both factory neurons in order to maintain their connections, because otherwise they will die. All faction is a definite use it or lose it system. And so that makes total sense. And indeed, there's very strong evidence for success of the training programs, more than the Alpha-A-Poic acid. Right.

And so that's a real thing. And what's cool about that is that you don't need to go out and buy expensive things. Although you can, of course, there are people who are capitalizing on this commercially already. But you can just take things from your refrigerator or your makeup cabinet or whatever and smell them, you know, attentively and constantly and sniff them.

And that exposure will help you recover. There is good data on that by now. You made that point in passing about regeneration in the olfactory system. And neither one of the cool things, so in olfaction, you can study many things through olfaction. And indeed, one of them is newer regeneration because the olfactory neurons are really the only neurons that do that systematically in the adult mammalian brain.

And whether the human olfactory system shows the same level of regeneration as it does in other mammals, is and was somewhat questionable. And I'm just bringing that up to share a really cool study that was published in neuron, I think somewhere around 2014, where to address this question, I just really liked the idea of doing that. What the authors did was look at, in post-mortem, they looked at levels of C14 in adults who were exposed to atomic bomb experiments. So you can actually look at these neurons and time them based on exposure to radiation. And that paper suggested that there's not as much tremor in the human olfactory

bulb as there is in other mammals. Other lines of data suggest otherwise. So this is kind of a debated question as to what extent of neurodegeneration you have in the human olfactory system as opposed to other mammals. But that was just a really cool paper, I think, of doing that. Fascinating. Should I finish the path? So we said. So we said, so information, then synapses at the olfactory bulb from the olfactory epithelium. And the pattern of that synapsing follows what's referred to as the most extreme case of convergence in the mammalian 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. So all the receptors of one subtype converge to one location in the bulb. And this location is referred to as a glomerulus or an implorical ameryly.

And that may be a slight oversimplification. It's in fact, two glomeruli. There is a mirror, sort of a mirror cut line. And so all the receptors of one subtype will converge to two meriglomeruli on the olfactory bulb. So you end up having two glomeruli that reflect that one receptor subtype. And so if, and this is as far as,

I'm giving you now the textbook view 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 text we view of how things work is that every such receptor subtype is responsive to a small subset of different molecular shapes, what sometimes refer to as autotopes, the molecular aspects of the odorant. So each receptor is

responsive to a different subset of autotopes, let's say 10, and each autotope will activate a different subset of receptors. So potentially you have this insane common entoricsks 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 or receptor identity. So let's say this coffee 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 a coffee. And if glomeruli of receptor is one, three and seven will light up, quote unquote, when I smell a coffee and if you could take a snapshot of that, theoretically you would have the map of coffee

and so on and so forth. This is sort of the textbook view of how the system works. And then information goes from the bulb to several targets in the brain. I mean, what is referred to as primary olfactory cortex is peripheral cortex and enthyrinol cortex. This is on the ventral surface of the brain, the lower portion of our temporal lobe. 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.

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 doesn't exist in the rest of the brain. And the understanding of how coding occurs in the rest of the brain is murky. Commonly one hears that the memories that we have of odors are somehow more robust than the memories of other perceptual events in our life. I don't know if this is true or not, but 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 multi-station, but nonetheless, somewhat direct path from the nostrils to the hippocampus. One of the primary encoding centers of memory in the present. To synapses away. Yeah, which is a remarkably short pathway,

considering that, for instance, just by example, because some of our listeners are won't be familiar with this, but some will, that sound waves that, you know, are translucent to 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, etc. Whereas, olfaction is more of a direct route to the memory centers. Is there any just so story or real objective truth to the idea that Ulfactory memories are formed more easily or maintained longer or more robustly than other sorts of memories?

So yes. But first I should say that I'm not an authority and all factory memory. It's sort of, it, all factory memory is a huge field of research and somehow our lab has never really gone much into that. Although, again, the same student I happened to talk about

before your I. Sheroon, who's again now a faculty at Tel Aviv, ran a study paper, we we I think we published in current biology, biology called the privilege representation of early olfactory 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 that's whatact compare it. So there's something about the first exposure to a smell in terms of the brain encoding that etches it into our being. And this is an effect that has, you know,

it has echoes, of course, in literature. I mean, you know, the biggest cliche and this is to bring up the proust effect, right? So the proust effect is when you eat the Madeleine and immediately the taste and smell immediately reminded him of an event in his childhood where where the same Madeline appeared. But so that's something very real. There's a lot of research on it not coming from our work. So I'm not an authority. But it does sound like there's a lot of research on it not coming from our work. So I'm not an authority. But it does sound like there's something special about all faction. And that doesn't mean that there isn't something special about vision or audition.

I'm not sure. Each one has its own unique. I'm the last to argue that there's something special about all faction. And it's 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 yes, through the lens of the nose, I'd like to take a quick break and acknowledge one

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And I thought this was peculiar, but then again, 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. One or the other would not be sufficient. Please don't run this experiment. That kind of place. But nonetheless, a paper came out 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 odored trail with their nose. And my understanding is that people can improve their ability to track sense quite robustly, especially if we deprive them of vision and some add a sensation that is touching some other sensations. So maybe you could just tell us a little bit about that study. And for, I think in our audience, I'm suspecting that many people have a keen, keen sense

of smell. Various, I have a family member who just like detect any negative, you know, putrid odor in the environment, but also good odors. Exquisitely well, and I have other family members whose sense of smell is quite poor. I'd love for all of those people to learn a bit about what is possible in terms of training up or improving our ability to smell and perhaps in the context of that study if you will. So first before we've been 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, yeah, we know this, this is all news. But to people who come from different worlds, we have to reiterate this sometimes when I give, public lectures to non-alfection audiences, I reiterate this, humans have an utterly remarkable

sense of smell, to put that a bit into sort of, things that are tangible. So for example, 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, it's not the smell of gas of propane. It's an additive.

Mercaptan? Yeah, it's Mercaptan. This is all for like smell. So 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 making this again really tangible, we're working with a no-dirt in our lab called estrateratraenol, that our participants can detect when we

haven't 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-size swimming pools and you would pipe it one ML, one drop into one pool versus the other, you could smell the difference between the pools. Incredible. That's the detection threshold that you have with your nose. People have an utterly amazing nose, okay? So that's just in terms of its detection abilities, which are just remarkable, really up

there in the mammalian world, we're not a bad mammal at all faction. And beyond that we can improve. Okay, and the example you're talking about actually started off as a lab bet. Okay, we were having a lab picnic. So I guess I should hear Philin because I'm your guest from the White Smen Institute of Science in Israel, but before going back to my home in Israel, I was a 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 do with their sense of smell. 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, which I have video of,

but I don't think we'll show it here. But I actually have a original, the picnic video we have it. And a graduate student by the name of Christina Zalano, a brilliant graduate student at that time, who's now, she's now a professor at Northwestern. And she's really leading the field of all faction 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 laser at the starting point of the line. Or I think we did. I don't exactly remember what we did on that sort of picnic tryout. But, you know, I assume she never practiced that in her life before, right? And yet, you know, she did it really, really well. And, and then this went on as a lab bed in a way that I said to my students,

okay, we have to make this into an experiment, put in an experimental setting and quantify what's going on. And they all said that it would be uninteresting. That was the bet. And I told them it would be in nature, which is a bet I won in this case. Nature of question being one of the APEC journal science. So it was nature neuroscience to prepare. But so then we turned it into an experiment.

And what the experiment was is that we brought in participants, naive participants, not graduates from our lab, 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, they couldn't sense anything. And we generated a consistent odor path in the grass, which is what you saw. We did that by burying twine under the grass, an odor-impragnated twine. So that way, we could generate a consistent odor trail every time. Was it at the base of the grass or in the dirt itself?

It was buried. It was buried under the grass. Really? Yeah. Yeah. Wow. And I did not know that. It was buried under the grass.

And we conducted aerial photography. And participants also had this sensor pack that they were wearing where we measured nasal airflow in each nostril in real time. And they all we also use something called RTK GPS, which is a way to lay radio frequency grid over the GPS grid so that you have millimeter resolution and space basically. It's used by surveyors mostly so that we have millimeter resolution and space, basically. It's used by surveyors mostly, so that we could track behavior. And we found a few things doing this.

One is that people could just do this right off the bat. The second thing we found that is when we trained them up, then within average of four days, the rate limiting factor became the speed at which they could crawl. So as fast as you could crawl, you could centrack. Of course, you can't crawl as fast as a dog can run, but as fast as you can crawl, you can centrack.

And then to sort of add what made it really interesting from a system as neuroscience perspective, is that we asked whether having two nostrils contributes to this. So we built, we constructed a nasal prosthesis, if you will, that had two versions. One is that it combined both nostrils into one big nostril centered and the other is that it maintained two separated nostrils. And we compare it performance under these two conditions. And people perform better with two nostrils over one centralized nostril, although the flow remain the same. So you're taking advantage of the information that comes from remain the same. So you're taking advantage of the information that comes from your two separate, totally separate nostrils. By the way, the system I described before of your

epithelium in bulb and connection to cortex, you have two of those, right? It's completely unilateral. Well, almost completely unilateral system. There are some very small exceptions to that. But so a representation on both sides of the brain. Much in the same way we have two eyes, we're not a cyclops. We can gain depth perception information. We can perceive motion better as a consequence and a number of depth, especially stereopsis. And we can locate sound because of the difference between our ears and how it blocks them between.

Amazing. Another question about the mechanics and strategies that you observed, because I think there's information about the system, the brain, as a consequence. Were you in a position to measure sniffing frequency? And the specific question I have is, were people doing something along the lines of a quick sniffing or a, like a, you know, long withdrawal. So, you know, we did, so we, yes, we were measuring sniffing and recording it and we have all the data.

There was nothing very remarkable in that data in that study, although it may reflect that we didn't analyze it carefully enough as well. I mean, it was, it wasn't a major component of our analysis. Although we did look at it to some extent, again, you're asking me about a paper from quite a few years ago, so I may be forgetting parts of it as well. But I'm sure if it was a major component of it, it would have risen to the top. No, it definitely wasn't a major finding of the sniffing behavior in the paper.

Although, again, sniffing behavior is a huge portion of our life and lab. And it's taking us to places. And it's re-emerging now in our work. We're doing tons of sniffing work. places and it's re-emerging now in our work. We're doing tons of sniffing work. I can share with you something that I think will interest your listeners and viewers as well.

And we think is really one of the most overlooked things in neuroscience. I invite you to do the following experiment. So, we'll include one nostril by pressing on it from the side and sniffing, and then include the other and sniffing. Do you sense a difference in flow? Yes. Okay.

Do you know why that is? No, and it was the next question on my list. Don't feel badly about not knowing why that is. Most people don't. 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. In an absolute way, is it kind of like a sine wave, like gradual shift to the one and then

gradual shift back? It can vary. It can vary and we don't yet know the rules, all the rules. 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 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 balance in the autonomic nervous system. So as you're in your list, there's no,

we have an autonomic nervous system that has a sympathetic and parasympathetic component to it and they're in balance or imbalance in many diseases, for example. And this interplay between the sympathetic and parasympathetic nervous system drives the switch from left to right nostril. Just to remind people, sympathetic nervous system has nothing to do with sympathy. 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 associated with all sorts of things, the sexual arousal response,

and a number of other aspects of our physiology. So think of it like a seesaw of alertness and calm. Perfect. So now imagine, right? 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 autonomous nervous system and we

do nothing with it. So we're in fact now doing a lot with it. So we built a wearable device that is pasted to your body and measures airflow in each hospital 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 we're finding it as a disease marker. I can give you a nasal halter measurement as an adult. And I can say, this is worked by Tim Nasiroka, a graduate student in our lab now. We can tell the difference between ADHD and non-ADHD adults.

And we can tell just from the recording, we can tell if the adults are in riddle or not. So I can measure your nasal airflow and say, if you are or are not with ADHD and if you are or are not unredoeling. Incredible. I have 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? Or is it simply the case that this alternating left, right, nostril periodicity, which you said I think is on the order of about every two hours, two and a half, two and a half? It switches to a maximal on one side versus the other. Is that simply reflective of an overall balancing? Let's maybe is it the hinge in the seesaw, or is it the tilt of the seesaw? So I don't have a good answer.

I don't have a good answer. I mean, I could give you sort of a, you know, I could say that to some extent, right nostril more open is more sympathetic and left nostril more open is more parasympathetic, but that wouldn't be very correct. I mean, you know, it is, you know, the yogis are gonna be all over this.

So wait, because I get to start, my lab does do some stuff on breathing and the yogis are always saying, okay, you know, because there's this thing, I don't do yoga anymore, but not for any particular reason. I am, but where they'll have you breath through one nostril or the other. And I've probably been asked this question on social media 10,000 times. Oh, wait, I'm going to become public enemy number one of the yogis right now. So let's say we, they'll come at you with yoga mats,

which are not very dangerous. We really, so since we're so interested in this mechanism, one of the things we'd really like to know how to do is to gain control of it somehow. And there's this world out there of yoga who claims to have control over this. So we said, okay, let's bring really serious yoga practitioners and see if they can shift their nasal cycle

from left to right by will alone, right? Not by manipulating themselves somehow. And if yes, we'll learn from them how they do this and then we might use this to cure ADHD or whatnot, right? So we posted on all the lists of the yoga teachers and had this parade of yoga teachers walking into our lab. This was one of the strangest. A lot of our molded odors and bare feet.

Right, right, clueless and so on. And so we studied, I actually know, we studied 14 yoga teachers, all 14 by, you know, by the conditions of enlistment for this, came in saying that they can control shifting from left to right nostril without plugging in. Yeah, yeah, by the power of thought, and you know how many of 14 succeeded? Zero, including, including one, you know, there was extreme one, it was we had this guy who, you know,

and we're recording, and we know how to record this really well, right? And he's sitting there saying, yeah, I'm switching now and it's switching. And you know, you're looking at the monitor and no, it's not switching. And so no yoga teacher that we found could willfully switch between left and right nostril flow.

And yet they are convinced that they are, and I have to imagine they're not trying to, you know, there's no incentive for them to lie, right? Yeah, no. Even the opposite. I mean, you know, this puts them in an awkward position once. Yeah, I don't know what the deal is, but none of them can do it. Given that the alternating flow through one or the other nostrils reflect over the autonomic nervous system has this two and a half hour periodicity,

if I suddenly enter a bout of stress, for instance, does it switch because that's reflective of the autonomic nervous system? Yes. The reason I'm asking this question is not because I think that's necessarily important as it relates to stress, but I'm trying to understand the direction of causality. In other words, is the as our unilateral smelling through or unilateral nostril smelling

periodicity that when we named it something I could think of the wrong thing, I'm sure is that driving the shift in the autonomic nervous system or is it merely reflective of the shift? So you've very concisely now worded aim two of a grants that was probably just rejected, but basically we're trying to answer exactly that question and we're currently running experiments on that line.

So we have one experiment where we're looking, so we're exposing participants to pain. We're using cold water hand exposure. It's a really cool paradigm because there's huge individual differences. We just started this. We built the setup just now. And you have a lot of meat to work with there because there's a lot of individual differences. It's capped at three minutes, so for safety reasons, because you have participants putting their hand in two degrees Celsius water, but there'll be participants who will pull

it out at like 10 seconds, 9 seconds, and then you'll have three minutes as well. So there's lots of, lots of, and already, and so now I'm sharing pilot data with the USU, you know, to, to, this might, you know, when it, when this ends up being published, it might be the opposite, but so far it seems that, that the exposure to cold generates a shift in the nasal, in nasal balance. So autonomic arousal can drive the shift potentially. Earlier you were describing the architecture of these smelling systems. And you mentioned these glomerular eye

where the olfactory receptors converge 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, what no one was describing is the fact that, of course, there are two nostrils, and then a bunch of receptors, they converge in these glomerular eye,

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. 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,

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 is a total fabrication 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? think, I don't think that the nasal cycle is an all-faction story. So I do think that this

was shaped by the olfactory system, nor do I think this has major impact on all-faction. I think the nasal cycle story is a different story about brain function. So we have this sort of pet theory where calling out the sniffing brain approach, where we think that nasal inhalation is timing and driving a lot of aspects and patterns of neural activity and cognitive processing. This theory is all-faction inspired in its beginning. If you think of the mammalian brain, which evolved from all-faction, it's sitting there and in all faction,

because all faction depends on sniffing. You have this situation where you have a sniff, you have information, and then flat, nothing, right? And then you have information and then nothing. So information processing is one to one linked to nasal inhalation. is one to one linked to nasal inhalation. And we think that this property

evolved to be meaningful in brain processing in general, not only of all factory 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 Peril from our lab two, three years ago, we looked at something completely not all factory. We looked at visual spatial processing. And we compared visual spatial processing on inhalation versus exhalation.

And the brain does this completely different on inhalation versus exhalation. And the brain does this completely different on inhalation versus exhalation. You're in that particular task, people performed significantly better on inhalation versus exhalation. What was the task? Was it an olfactory task? No, no, it's a visual spatial task. So this is a task where the specifics of the task

were that you see 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 like, these like usher shapes, like, you know, where one facet doesn't reach the other facet. The impossible figure. Yeah, but structural shapes, not. And so a pure visual spatial task, we intentionally went for a task that is not considered a ventral temporal task, an olfactory cortex task in any way.

And people performed much better on inhalation versus exhalation at doing this task. Was there a both nostrils occluded version where people were forced to mouth breath? 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. So I'm a big proponent of nasal not mouth breathing whenever possible. Sure. For many health related reasons, I'm a big fan of the book, not mouth breathing, whenever possible. For many health-related reasons,

I'm a big fan of the book, JAWS, a hidden epidemic written by colleagues of mine, at Stanford. You're familiar with it. And this idea that people who mouth breathe experience more colds, more infections, of various kinds, it's not good aesthetically or for the denture, I never know.

The teeth, the gums, it's stuff. Oops. Sorry, my dentist is gonna come after me. Need to go to the dentist's dentature, I never know it. The teeth, the gums, it's stuff. Yeah, sorry, my dentist is gonna come after me. Needs other dentist anyway. The, that nose breathing is great for your health relative to mouth. So I think it's also good for your cognition. Not only for your dental health, I think that nose breathing shapes cognition.

And there are other labs who are finding the same. Again, Christina Zalano is doing work on this line. She had major contributions here. And Yohan Lunstrom is doing work on this line. There's lots of studies suggesting that nasal inhalation is timing cognitive processing and modulating it. Incredible. Perhaps not surprising, given what you've taught us about the olfactory system, I mean,

these two holes in the front of our face, these nostrils, I mean, are pathway to the brain. I love to tell people, because I work on the visual system in my lab that, you know, your eyes are two pieces of brain extruded from the cranial vault, which they are, the retinus anyhow. And then you never look at anyone the same way again, it's okay. But the olfactory sensory neurons are right there at the top, so those caverns that we call nostrils, and they are brain. Yeah, definitely. It's the only place where your brain meets the outside world, because

in your retina, they're protected by alens. And here, here you have neurons in contact with the world. This actually has been the source for some theories on a potential route for neurodegenerative mechanisms. So as you may know, 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 loss in the sense of smell, probably 10 years before any other symptom. 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 so on. But, but olfactory loss, again, is an early sign of neurodegeneration, and there's at least one theory, particularly about Alzheimer's disease, suggesting that that Alzheimer's may be the result of a pathogen that enters the brain through the olfactory system. It's not, of course, a mainstream or widely accepted theory of any type, but it just highlights this notion that the nose is a path to our brain. I think these non-invasive readouts of potential neurodegeneration, such as visual tests, because of the fact that the retinas are part of the brain and loss of neurons in the retinas, often associated

with other forms of central degeneration, Alzheimer's, Parkinson's, etc. It's a little more invasive than what you're describing. I'm beginning to wonder why we don't have an olfactory task every time we go to the doctor that would allow tracking over time. Of course, 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.

That's a really bad sign. Yeah, that's a bad sign. And so what we're talking about is something completely non-invasive and could be relatively pleasant to innocuous depending on the order is used. So yeah, so first I can answer that, right? And the reason that that's not happened, and that might, that may be changing right now, but the reason that has not happened is because all faction has not been effectively digitized. So if you need to generate really precise visual information,

you can buy a monitor for 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 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 orders. We call them all factometers, which is a misnomer, because they don't measure anything, but that's what they've always been called. So we call them all factometers as well. And we've already

built at least one all factometer that cost a quarter of a million euro. And it's pathetic, right? So it just, it's pathetic. It's, it's pathetic, 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 are a standard clinical tests of all-faction, basically two that sort of control the world in this

respect. The older one is a test called the UPS IT, which stands for the University of Pennsylvania smell identification test. It was developed by Richard Dodie and Penn, and it's a test where you scratch and sniff, and it's a four alternative force choice test with 40 order. And so you have these 40 pages that you page through and you sniff and smell and, and, you know, it's been normed on gazillions of tests. I'm always amused by it because so Richard Dodie made a ton of money on the UPS IT, but

he needed it because he has a habit. He has a NASCAR. And so this, every time we buy UPS IT's in the live, I say there's another gallon of gas into Richard Dominguez. He raises NASCAR. It's not like NASCAR, but like when lower than that, like I didn't know, like some sort of formula A

or form the Ford or some, he raises a car. And so that's where all the UPS IT's went. So I always feel good about buying UPSITs because I know they're going to that good cause, but keeping him in the fast lane. Yeah. But so that's one test that's out there. And indeed, you know, has been shown as a, you know,

so there's reduced UPSIT and Alzheimer's and Parkinson's and in a host of other diseases. And there's a European version called sniffing sticks that Thomas Hume has developed. And it's basically the same sort of concept of that one isn't scratch and sniff. It's like these pens that you open up and sniff. But there's exist, but they're not as convenient

as delivering stimuli and vision and audition. And that's why you don't have what you've just suggested. Interesting. You know, another place where you don't have it, which I think is even more, would have been even more meaningful, is you don't, of actions not tested in newborns, right? Where vision and audition is. You know, there's this thing called congenital and osmere, right? Where vision and audition is. You know, there's this thing called congenital and osmia, right? Which is being without the sense of smell from birth, supposedly, contend role, which is half a percent of the population. It's not a trivial number, not totally. Yeah.

But nobody knows if that really is true. Because here's an amazing factoid. Guess the average age at which congenital anosmia is diagnosed, and 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? Five years of age. Fourteen.

Incredible. Fourteen. So most people who are one half of a one percent of the human population, presumably, is without the sense of smell and doesn't realize that until they're 14 years old. Well, I don't know when they realized it first, but it's formally diagnosed at 14 on average, which means some of them even later, right? Half of them. And, right, it's a distribution.

What do they suffer? Yes. So first of all, they suffer socially. And there's a this is work out of Ilona Kroy in Germany. And amongst the various things that are predicted by an Osmeah is shorter lifespan. But things like, you know, reduced social contacts reduced Romantic social contacts It's not a good thing um And and and do they lack olfactory bulbs? I'm presenting they have noses and nostrils

There is a condition. I'm aware of where where our children are born without noses They're very rare. Yeah, very rare. We'll focus on that because it's exceedingly rare But they're born with nos noses and nostrils. And here's the thing, we don't know if they're born with olfactory bulbs. Most of them, although not all of them, but most of them don't have olfactory bulbs in adulthood. Or I should rephrase that, have remnants of olfactory bulbs really shriveled olfactory bulbs.

But, you know, nobody can say the cause and effect here. should rephrase that, have remnants of factory bulbs really shriveled off factory bulbs. But nobody can say the cause and effect here. Before we talk about the requirement for all factory bulbs for all faction, a very interesting topic in its own right, 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 between individuals that triggers things, everything from the onset of puberty to feelings of romantic attraction, attachment, these sorts of things. Is it known whether or not, 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 we are well aware of the proximity

of the olfactory system to some of the hypothalamic systems that regulate the release of gonadotropins, which control testosterone, an estrogen production, et cetera. So are they hormonally normal? So some are and some aren't, and I'll be specific. So there is a condition known as calm and syndrome, which is hypogonetic development in men. And in calm and syndrome, they're practically all anosmic. So to answer a question, yes, there's a direct link and it materializes in Kalman syndrome. That said, not all congenitally, anosmic individuals have Kalman syndrome, and not all, but almost all people who have Kalman syndrome are anosmic.

So Kalman syndrome goes with an osmia. I think, so there's a female equivalent of Kalmans, or I don't remember its name. It's not a, it's not a, in the Turner syndrome family, it's not true. Okay. And I think it's also associated with anosmia, but I'm not confident of that. But calmons is associated with anosmia.

So the answer is yes. And, and you know, we can maybe, you know, all-faction and reproduction are tightly linked, and they're tightly linked in all mammals, and we are big terrestrial mammals, and all-faction reproduction are linked in humans as well. We will definitely get into that. I'd like to just take a brief moment and thank one of our podcast sponsors, which is Inside Tracker. Inside Tracker is a personalized nutrition platform. They analyze this data from your blood and DNA to help you better understand your body

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olfaction. And this is really so when I was growing up, I grew up at the end of a street with a lot of boys of my age, who just by coincidence, had a lot of older sisters, they were my older sisters age. It 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 those things, like kids 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 this clothes, like someone left this here, I don't know who it was, we were all more or less the same size.

And from 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, oh, that's Scott Madson shirt. 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 had, pretend I hadn't if I had, but having never actually done the exercise of going and smelling my friend intentionally, okay? In fact, if anything, I had all the reasons in the world to avoid smelling the other young boys in my neighborhood. Okay, so that raises a 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 or some other aspect of their chemistry. Yeah. So yes, we're doing that all the time in my view and a lot of this processing, almost all of it, is subconscious. And I don't know why already. Already put that out there, right? I have no idea why human nature has, or nature, or culture, or whatnot has pushed this into the realm of subconscious and something

we're unaware of. But we do it all the time and our lab has lots of studies on this front. One of them, you may be familiar with it that had gained some notoriety because it's amusing. So we look at human behavior a lot. We try to look at it through our nose and the way we look at what people are doing. We try to think, if I was a dog, what would I think of this?

And if you look at dogs, when they interact, they visibly sniff each other. It's very obvious. They walk up interact, they visibly sniff each other. It's very obvious. They walk up to each other and they sniff each other. Yet humans don't typically walk up to a stranger and carefully sniff them. We're sort of obliged to sniff our babies. That's considered almost something you're supposed to do. 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, right? Well, or do we? So we're finding more and more mechanisms where we do this. And the one I'm referring to now for one example, is we started looking at hand-shaking. Hand-shaking 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 almost everywhere. And there's really poor understanding of how this behavior evolved, like where did this thing come from? So if you look for the Wikipedia version, 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 Bloodhound receptor story, right? I mean, we tried to find it. You know, why do people say that?

They just do. And we started looking at people hand-shaking, and we noticed, or it seemed to us, that we're noticing that people will shake hands, then we'll go like this and like, those of you listening on watching, it was taking his hand and wiping it on his face. Yeah, rolling his nose or touching my inside of your feet. Yeah, these things that we'd wall the time after a handshake. Well, so first of all, we'd 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 could easily not notice, right? And and so we we asked whether that's a real thing. And this was a study led by done Frooming in our lab at the time. And what we did first, and if you want, we can link. So this was published in E-Life, and one of the nice things about E-Life is that it has a very effective way to embed videos in the publication. So if you want, we can link this to your system later on. The E-Life and the Show Note captions as a link on YouTube and the other for platforms Spotify Apple. So what we did is we brought in participants to our lab

and we sat them in the room, experiment room 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. Of course, later on, they had the opportunity to not agree to saving the video in which case we would delete it immediately or letting us use it for science

or some letting us use it for more than science for the video that's now on E-Life. And we walk into the room and say, okay, just wait here. I will be right back with you 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 far head

or their chin or how many times their hand reaches their face. And by the way, that baseline is not low. And then three minutes later, an experiment would walk into the room and would share a consistent text. We're still setting up our equipment in the other room. And so just wait here and we'll be right back with you, but in the meantime, just wait here. And the experiment went through this like 20 second fixed text. And in half of the cases 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 would be a low- 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 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 unreal. The video is unreal. So interesting. So the hand goes to the nose. Now we did a few controls here to verify that this is an all factory behavior. One is unbeknownst to participants. We measured nasal air flow and And people not only bring their hands to their nose. They sniff it. So in this is perfectly time they go 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 hands. They 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 all factory behavior, no doubt about it. I mean, we're quite confident.

So people, in that case, people must have been sensing the odor on their own hand because they'd shook the hand of the of the experimenter, Pleasant odor, and they're more frequently bringing that hand to their nose versus unpleasant odor that had been introduced to their own hand by the experimenter. Yeah, but I, but no, I think I think they were sensing the ambient odor that came in with the hand that thatook and then that either drove them to snip their hands more or less. The odor cloud of the experiment.

Yeah. And there's an interesting thing going on here too because people didn't only smell the hand that chook, they also smell the other hand. And we think that there's something going on here comparing self to other. And we think a lot of self sampling might reflect that. There's on the same line and again to link to your childhood story of identifying your friends by smell. Study we published just last year by Inbader of Rebbe in our lab, where Inbal came with this 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 is poorly described or is poorly described in literature as an entity. And yet, anybody will tell you they know what you're talking about. I mean, if you tell somebody who clicked with it right away, you become intimate within five minutes.

Everybody experienced this in their life, to some extent. And the question is, what was there? What was it? Was it because you looked the same? Could it be? Was it because you had the same, could be? Was it because you have the same sports team that you liked or is there something deeper here? And in Buzz3 was that a similarity in body order

may contribute to this, that people who smell the same will click in some way. And so to address that, she actually recruited click friends from all over Israel. She posted all over social media to identify pairs of friends. So these are same sex, non-romantic diets. So these are friends, men and women,

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. So somebody's sure they clicked with somebody else, but the other person. There's a name for that in neurology that our common friend, the late Ben Barris, taught me,

which is there's a phrase that neurologists use. Okay, called sticky. These are people that come up to you and start asking you questions and then won't leave you alone. They're so called sticky people. That if you ask these sticky people, sticky and air quotes,

because they're not physically sticky. They may be. What they could be. What do you think of this person? They'll say, oh, they're great. We're really good friends. And so they've made a unilateral click friendship. And yes, neurologists are talking about you.

If you're one of these people, neurologists are talking about you, there's an informal diagnostic code, sticky. So she recruited click friends. So she recruited click friends and then she sampled their body order and we have a protocol for this. So they're given, you know, a Otolis shampoo and soap to use for three weeks

or something and then they sleep two nights in this t-shirt where they have to sleep alone and then we extract the body order from the t-shirt and we have a way to extract a method to extract body order. And then she first asked whether indeed click friends are more similar in their body order than you would expect by chance. And she first tested this with the device. A machine we call in the 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 refer to as moxers, as a metal oxide covered sensors. And so she used an electronic nose to sample these body orders. And she found that click friends are indeed more similar to each other than you would expect by chance, by random diets. This was a significant difference. After she found that a device could do this, she had other participants do this. She had people smelling the click friends versus non-click friends, and they judged them as being more similar to each other than not. Now, again, 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 that's why they smell the same. So to address causality, she recruited total strangers and first smelled them with the electronic nose and then engage 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 hand out but another didn't the that didn't. So she predicted that people would smell more

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 interaction was completely nonverbal. 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,

how affectionate they think, a bunch of ratings, okay. All of this was predicted by the electronic news. 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 an ICE person, et cetera, et cetera. So we could actually predict friendship using the electronic news.

So this is not a result of friendship. It plays into the causal elements of building friendship. So this is to relate to your childhood story. There's something going on here where we're constantly smelling ourselves constantly. This constantly, I mean, if you want to leak, I'm not, the reason I'm smiling, I mean, and your viewers are listening, those will understand why I was following. I'll send you a video to link in the, in, into your podcast here. We thought of calling the fact that people constantly sniff themselves. We thought of calling this the low effect and low.

So in America, this won't pass that effectively, but in the rest of the normal world, Yochim Low is the soccer, the national soccer coach of the German soccer team. So I mean, I don't know who would be a very famous coach here, but Steve Kerr, right? I mean, this is the, you know, this is a super, super famous name all around the world, where soccer is the primary sport that people watch. And once people will see this video, they'll understand why we thought of calling this the low effect. It's a very graphic. But, but people are constantly smelling themselves.

They're smelling themselves with their hands. They're smelling themselves explicitly. People are constantly smelling themselves, constantly smelling others. I find this topic so interesting. And first of all, confession, I definitely smell myself multiple times per day. And everybody does. Okay, good. Yeah. And I would do it anyway. I think I like most people. I either find my own smell to be neutral to pleasant. Right? I occasionally, I'll be like, whoa, I need to take a shower. As long as we're talking about smelling oneself and friendship, kinship, and its relationship to smell, we have to talk about the relationship between smell and romantic attraction and bond. So my understanding is that if, for instance, a mouse is given the option to mate with any number of other different mice.

They will bias their choice toward the mouse that has the immune composition, the so-called MHC, major histocomatability complex, which reflects immune diversity, the immune system that is most distant from theirs at the evolutionary argument being that they to produce offspring that the array of immune genes would be much broader than if they were to select an animal very close to them. And in addition to that, that one of the most strongly selected against behaviors, not just culturally, but at the level of eliciting a sense of disgust, maybe even from the activity of the hypothalamus, is mating with very close

kin, aka incest, because that can potentially, we know, produce as a higher rate of mutations. In other words, whereas you described the relationship between smell and choice of friends as you choose people who smell more like you, my understanding is that in the context of choosing romantic partners or sexual partners or both, that you choose the person whose odor and therefore immune composition is most different. Right. So, the way you describe the animal literature is correct, and there's evidence to similar mechanisms in humans. Our lab has not worked directly on this issue

of romantic selection based on odor. There's a bunch of papers, wedkined at Alan and the wedkin lab, and also Porter, I'll email these you later on, that have done a lot of this work and find exactly, as you say, that romantic odor preferences in humans are influenced by body order and that this is linked to MHC, histocomatobillility complex makeup of the portion of our genome that shapes our immune system

portion of our genome that shapes our immune system to some extent. So this effect has been studied and reported on, again, extensively in mice and also in humans, not work that we've done. The one sort of tangent work we've done and I'd like to maybe tell you about it relates to an effect that is one of the most remarkable effects in mammalian social chemo signaling. And also related to romanticism in any way, but it's related to reproduction. And indeed, in our lab, we've not looked at romanticism, we have looked at, or are looking at reproduction.

They're not always the same. Certainly. Oh, they can. Animal mammalian or terrestrial mammalian reproductive behavior is dominated by the sense of smell in mammals. And here, remember, initially when you started off, I noted that there are several subsystems in our nose that transducerodorins, and so primarily the main olfactory

system, which is cranial nerve number one, and the trigeminal nerve, which is cranial number five. Most terrestrial mammals have another subsystem referred to as the secondary olfactory system that has a separate sense organ in the nose. This organ is known as the vulmaronazel organ. It's a small pit in the nasal passage of most terrestrial mammals. Sometimes it's described as a communicating pit

because sometimes it connects the nasal passage to the roof of the mouth. Sometimes it connects both. And so there's this sense organ with its specific receptor subtypes, VNRs, Vermonayasal receptors, and this is linked to a This is linked to a sort of separate portion of the olfactory bulb, not really the main olfactory bulb, but it's referred to as the accessory olfactory bulb. And from there directly to the limbic system, to the portions of the brain that control reproductive behavior and aggressive behavior. And in most terrestrial mammals, this subsystem processes odorants that are sometimes referred to as pheromones,

although that's in many ways a problematic term, but odorants that are referred to as pheromones, namely odorants that are emitted by another member of the species to influence that member of the species and alter behavior or hormonal state. And some of these hormonal effects are utterly remarkable. And in my view, the most remarkable of all is an effect known as the Bruce Effect.

This was an effect discovered by Margaret Bruce in 1959. She was a British scientist. And in the Bruce effect, when you expose a pregnant mouse at an early critical stage of the pregnancy, I think up to about day three, if you expose the pregnant mouse to the order of what is referred to in technical terms is the non-stud male, That is a male who did not

father the pregnancy. She will miscarry the pregnancy. She will abort it. Now, that's an insane decision made by the female here, right? Because she's invested quite a lot in this, right? In biological terms and forming this pregnancy and maintaining it, and yet she drops it on the basis of an odor. And this effect is remarkably robust. And what do I mean by a remarkably robust? So this will occur on about 80% of exposures. Now as you know, 80% is 100% in biology, right? I mean, there's nothing that happens

at more than 80%. So it's a remarkably robust effect, this dropping of the pregnancy. And we know it's mediated by chemosensation through the nose. For sure, and we know in the following way. So first, it's enough to just bring the order of the non-stud male. You don't have to bring the male himself, right?

So you just can bring bedding from a non-sun male and that will induce the bruce effect. But of course, the most telling set of experiments is that if in the female mouse you ablate the vomeronazel organ, you just burn this tiny structure in the nose, then the effect disappears. So the effect is completely dependent

on the vomeronazel organ. And I find the subtleria remarkable effect, right? I mean, because, again, because of the extent of cost that the female takes on here, based on this information and smell. Now, humans, the sort of the going notion in all factions is that humans don't have a functional of umarune's organ. So we don't have that functional organ in our nose. Now I'll point out we actually do have the pit.

So the structure or the outlining structure is there. But the pit that we have is considered vestigial and non-functional. And what about this thing I learned about at Berkeley, in integrative biology class, that we have something called Jacobson's organ. This is the same organ. So Jacobson's organ is the vomeronais organ. It's also called Jacobson because I think Jacobson was a military physician in like the 1800s in Holland or something and he founded in the soldier who was

operating on or something like that. But the story comes from something like that. But Jacobson in the organ is another name for the vom of these organs. These are one in the same, the sensory organ of the accessory olfactory system. And again, the going notion is that the human Jacob's in organ or woman's organ is vestigial. It's non functional. Does that necessarily mean that we don't have these fair amount of effects? No, it does not. So first of all, we know that lots of what are considered for our monol effects, namely social chemo, so going in rodents are mediated by the main olfactory all, we know that lots of what are considered for hormonal effects, namely social chemo-sigolian

rodents are mediated by the main olfactory system. We know that for sure. There are several examples for this in mice and rats and rabbits and so on and so forth. So, A, these can be mediated by the main olfactory system. And I'll come back to that in a second. But first, to finish the Bruce effect. And I'll come back to that in a second. But first to finish the Bruce effect. And second, and I'm going out on a limb here, but I'm willing to take that risk. I'm, for me, the jury is still out

on human vomeronasal organ. The decision or the notion that it's non-functional relies on about one and a half papers, postmortem, looking for the nerve that connects this thing to the brain and failing to find it, using staining and so on and so forth. But staining postmortem studies in humans are notoriously complicated. Basically, you know, for many reasons, one of them is that the material is just always has gone through, you know, it's not ideally set

as it is when you sacrifice an animal and study its tissue. So based on really, really a positive studies that fail to find this nerve, the notion is that the structure is vestigial in humans. I don't have any evidence that it's functional, mind you, but I'm just not sure that it's not. But what we do have a suspicion is that humans may experience something similar to Bruce Effect. So first of all, humans have an enormous number or ratio of spontaneous miscarriage.

Are they occurring more often in the first trimester? Because you mentioned that in the Bruce Effect and the Mises in the first three days are so fall in pregnancy, which in the mouse gestation as I recalls about 21 days in the mouse, you're talking about 1 7th of total gestation. So I'm not quick enough to nor is it important to translate, but this would be first trimester

in the comments, which is indeed first trimester. When most miscarriage occurs. Now, humans have again a. When most miscarriage occurs. Now, humans have again a huge number of miscarriages and the numbers I'll assume share them with you, they sound odd. And the reason they sound odd is because if you have what's sometimes simply referred to as failed implantation, right, this can occur, you know, in days one, to nobody ever knows. So some papers talk about 90% of all human pregnancies and in miscarriage. This is counting a failed implementation in day one, two, et cetera.

More conservative studies talk about 50%. Nobody will argue 30%. Okay, so a huge number, a huge number of human pregnancies and then miscarriage. Now out of these, there's a portion that are unexplained, right? So nobody knows why. I mean, there are portions that are explained, but all sorts of genetic factors, developmental factors, and so on and so forth. But there's also a portion that are unexplained. And, and so all I'm saying is that there's a statistical backdrop or setting, if you will, for something like a remnant

Bruce effect in humans. Now, with that in mind, we approach the group of, we enlisted a group of, of, they're not really patients and participants in a study of people who or couples who are experiencing what is referred to as is unexplained repeated pregnancy loss. So formally, if you have two consecutive unexplained miscarriages, then that is sufficient for the diagnosis of unexplained repeated pregnancy loss. However, in our cohort of 30, we had couples who experienced 12 consecutive unexplained repeated pregnancy losses. So the two is just the formal. All of our cohort was like 12, 5. So this is an emotional difficult place to be.

And these are couples who are losing their pregnancy for no apparent reason. So they've gone through all the tests that you can imagine of genetic incompatibilities and all sorts of issues clotting, all the known suspects for pregnancy loss. And the medical establishment remains totally at a loss as to why these pregnancies aren't holding. And so we hypothesized that perhaps here there's something akin to a Bruce type effect. Obviously, it's not going to be the same as in mice, but something

like a Bruce effect. Now, of course, at that stage, we could not do anything causal to test this, right? But what we could do is to seek circumstantial evidence to see if where there's fire, maybe there's smoke. And what we did was we tested all faction and more specifically the response to male to mail body order in the couples experiencing repeated pregnancy loss. And we found a few things. First of all, if you think of the mechanism as behind the Bruce Effect, the Bruce Effect implies that the female has to have a very clear memory of the fathering male, because if she's going to miscarry in response to the non-father, she has to know father and non-father.

I mean, that means that there is a pronounced olfactory memory at the moment of mating, okay? And in mice, this has been very well characterized and attributed to the anterior olfactory nucleus, a structure in the brain. But you'd have to have this memory in order to make that decision. Now, so to address that, and here you're going to see that you and your childhood story from before stand out a bit as skillful, is that the first thing we did was just behaviorally test whether these women and control women could identify the smell of their spouse. And you might be disappointed or we would know, we would all probably have been disappointed

to learn that control women are very poor at this. So you would think that women would be good at identifying the body order of their spouse, they're not. They're not far from chance. However, the women who experience repeated pregnancy loss are more than their double at their performance level. So this is not a nuance effect. Women who experience repeated pregnancy loss can identify their husbands or their spouses by their body order. With much greater acuity than the typical person. Double.

A bit more than double. And way above tense. Yeah, no, sorry, I posted as a question, but I meant yes, with much greater acuity and double is a significant improvement. Are they much better at detecting any odor? No, they're not. We did the controls and they're not. And then we also measured using FMRI,

we measured their brain response to a stranger male body odor. And this was quite remarkable because we approached, so this was a full brain analysis so without a region of interest analysis, so it's not as if you're tweaking your statistics to look at one part of the brain. You're just looking at the entire brain in the response to male body order and asking,

they know, is there a difference between these two groups of participants? And there was one huge difference and it was in the hypothalamus. And so there was a difference in response and it was in the hypothalamus. And so there was a difference in response to strange or male body order between the two groups. So, so all faction is altered in spontaneous repeated spontaneous pregnancy loss. We don't know this is causal, right? But that was enough for us to approach the ethics committee To run a causal experiment And we're at the beginning of that now

Incredible. I can't wait to hear the results of the it's gonna take it. It'll probably take years a few because These are slow experiments to run. Recruitment is complicated. But basically we're blocking smell in couples who are trying to maintain a pregnancy. I want to touch on some other so-called pheromone effects. And one thing I heard you say during a talk, which I think really captures this whole issue of are there Pharma-on-Effects in humans?

Very nicely, as you said, whether or not it's a classic Pharma-on-Effect or whether or not it's olfaction or something else, this is chemo-sensory signaling between individuals. The reason this is important to me is a few years ago, I did a social media post about Pharma-on-Effects and animals and some potential Pharma-one effects in humans and a couple of the human o-factionistas, more from the actually who work on animal models, really came after me with

intense sniffing, saying, you know, there is no evidence for human pharomone effects, human pharomone organs. And I think today you've beautifully illustrated how regardless of the answer to that, humans are contained and are emitting chemical signals that influence each other's physiology and behavior. For sure. For sure.

And the term Pharmaone is a problematic term in any case. I mean, the term was put forth to describe insect behavior, right? So, you know, if you were given a hard time by the mouse people, you could have given them an equally hard time if you were an insect person, right? Because really, the place that term is accurate is, you know, so the first firm on that was discovered was Bambechal, which is the firm one that has the male mothoth follow the scent trail of the female moth. Bambecal is a fernmone. Insect fernmone people will argue that this stuff that people talk

about in mice and rats is not fernmones. Nice to. And it all becomes semantics. Yeah, sort of like nerdy inside ball. It's all semantics. So I don't I'd in our publications, we don't, in our publications, we don't use the term pheromone, you know, because it would not help me and it would probably only hurt us.

And so, you know, we talk about chemosignals and humans definitely emit chemosignals from their body. And these chemosignals influence other humans and influence their behavior, you know, and there are several examples of this. One of them, I'll point out first, which is sort of the most widely studied and not mostly from our lab actually.

I mean, the flavor of the month for the past 10 years in this field is what's referred to as the smell of fear, right? So this is probably true of many mammals and humans. It's true of we emit a specific body odor when we're in the state of fear. This was first discovered in humans by Denise Chen out of, I think, brown, not true. I think that's right.

Humans emit a particular body order when they're in a state of fear. And this body order influences other humans in effect, increasing their autonomic arousal, their sympathetic state. So in effect, you could say that fear is contagious a bit. So the smell of fear is contagious. By the way, culturally, we know for ages that dogs can smell

fear in humans, but actually that was only really shown about a year and a half ago in the study. So it was always said, but it wasn't really shown effectively. It was shown about a year and a half ago in the study. The dogs indeed can smell human fear. And humans can smell human fear. So several labs starting from Denise Chen and Havelin Jones and then in our lab and in other labs, if you collect body order from people

in the state of fear and collect body order from the same people when they're not in the state of fear, other people can determine which is the state of fear or not and this influences their behavior. What about the smell of safety or is that simply the absence of fear and not, and this influences their behavior. What about the smell of safety, or is that simply the absence of the odor corresponding to fear? And the reason I ask this is somewhat woven into our prior discussion about mate choice. Again, I'll ask the question in a form of brief anecdotes. I'll use that I had a friend who approached here.

But one phenomenon that has nothing to do with me in particular, I think this is a common phenomenon is romantic partners, leaving articles of clothing at each other's homes. Now, this could have other purposes to mark territory, but visually marking territory, but also I'm sent marking territory, is very common in the animal kingdom. It's not uncommon for romantic partners when one is traveling or away for the other partner to smell their article of clothing in order to bring about positive connotations to the other partner, very common behavior.

If you're doing this, folks, other people are doing this too. It raises questions, for instance, about whether or not the morning period post post break up, whether by decision by death or by some other phenomenon that's forced the breakup, um, whether or not that morning period has something to do with an olfactory unlearning of, um, and mates like, and on and on and on. With all these insights, I would offer you to be a postdoc. Well, I was, listen, I have a sabbatical coming up. So I would love to do what's about it.

But it's going to kill me. Exactly. You don't want me to work for you. We talked about this earlier. That's what I'm saying. That's the reason. There's a story that what NOMA is referring to, I was just tell people could get inside jokes on a podcast.

Didn't don't really work. Earlier I was a free, in fact, that I've had three incredible scientific mentors undergraduate, graduate in postdoc, but for reasons that are unclear to me, the first one died of suicide, the second one cancer at 50 and the third one, pancreatic cancer in early 60s.

And the last one before he died was an MD in a common friend of gnomes and I turned to me and said, you know, you enter, you're the common denominator. So, you know, the joke that- I prefer joke to my businesses, you don't want me and said, you know, you enter, you're the common denominator. So, you know, the joke that- I prefer joke to my businesses, you don't want me to work for you. So, nonetheless, I would love to do a sabbatical in your life.

No, so when I was trying to say in that round about ways that those are all really keen observations and good ideas for fur. And they just highlight again, you know, that we're incredibly olfactory animals. You know, and you're even talking about the nuance. We're very olfactory, even not in the nuance. I mean, I have this, when people tell me

that we don't use our sense of smell, we don't need it in all that. And I have to deal with this a lot, right? I have to deal a lot. You study vision, nobody will tell you that vision is unimportant, right? I have to visually dependant. I don't need a dog to take over my olfactory system if I lose olfaction, but I'll tell you from having lost my sense of smell for one

day, right? I was in intense fear. I bid into a blue I love blueberries. I'm like a dry by blueberry either. If they're there, I just kind of pick them up like a gursley bear in the fram of them in my mouth. So keep them away from me if you don't want them eating. But I can't I almost can't help myself. I bid into a blueberry or a handful of blueberries and they just, it was the sensation of little bags of water and I immediately felt like tremendous, tremendous grief. I'll tell you a sort of a throw away line that I use in this one when I talk with people. You know, I mean, you know, take the two most basic behaviors that sustain us, right?

Let's say I give you a choice between a beautiful looking layer cake with strawberries and blueberries and whipped cream, but that smells of sewage versus some gray brown mix that smells of cinnamon. Which do you eat? Simple. The latter. You eat the latter. Now, imagine I offer you a mate, choose the gender of your liking, right? It looks like a Greek god or goddess, right?

But smells of sewage. Or an ordinary looking individual that smells of sewage. Or an ordinary looking individual that smells of sin itself. Who do you choose? The latter. So in the two most basic behaviors we have, we follow our nose, not our eyes, right? Definitely not always in predictable ways

because you offered an extreme example, which is the best example. But I, for instance, for reasons I don't know, I've never liked the smell of perfume ever. In fact, I find it aversive, but I do, I confess, I do like the smell of certain body odors very much. And I'm very particular about that. And I know within an instant. And so this is a problem for any romantic partner who likes perfume for me,

but I know many people like perfumes and colognes and things that are sort of. I like perfume. And in fairness, I've also been told that by someone that they couldn't spend time with me because they do not like my smell. In fact, they dislike it. And fortunately for me, there's at least one person on the planet who said, yeah, so the, so I completely agree

with what you're saying. I can also say that I imprinted on the smell of, I had a bulldog mastiff when I raised from the time he was a puppy. And I imprinted on, I imprinted on his smell immediately. And even though to other people, it was a bulldog mastiff after all, his smell was rather aversive. To me, he smelled delicious, right? And it made me smell like home. And he was my best animal friend for a long time. So, and on and on and on, right? The smell of children, as you said, the backs up, we had a guest on this podcast who I'm sure you're from the Charles Zucker. Yeah.

A professor at Columbia has done incredible work in vision and all the fact that they're sensing it. And he, and I talked a little bit about this that there's something in the breath of romantic partners that's hopefully a petitive, not aversive, as well as in children, he was talking about the smell of his grandchild, the nape of their neck, and the back of their neck, and how he misses that smell because when he thinks about missing his grandchild or children,

it's that smell that's associated with that feeling. Hexadecanael. Hexadecanael? Yes. Charles, your grandchild and smell like Hexadec. Yes, he's going to grow after me now. And so this is a study ran by Iva Mishor, who was a graduate student in our lab. And Iva was interested in aggression. She was really into aggression. And actually, when she started, and so when she started off, we said, okay, let's do chemo signaling of aggression,

she actually was going to MMA clubs and collecting body odors. We had all sorts of ideas going and she worked on that quite a bit. It never went anywhere really. Then at the same time, we had a colleague of ours from Germany. I mean, when I say colleague, primarily a friend or acquaintance, I met at conferences, Heinz Breer. And he was studying in his lab, a molecule, hexadecaneal, that was a chemosigil in mice. Where in mice, it was described as a chemosigil that promotes social buffering. Where social buffering, as far as I understand, it's not my field, but as far as I understand,

it's basically a feel-good together thing. So when lots of mice start together, they feel good about it being in a group, and that's social buffering, and it's promoted by hexadecanal, which they emit in their feces, mice. And in his work on hexadecanal, and so Breer and his colleague, Sourceman, they discovered the receptor for this and then they went and discovered that the receptor is very highly conserved throughout mammalian evolution.

And therefore, they hypothesized that maybe this is a universal mammalian signal, which is unusual because in chemo signaling, typically you tend to think of things as being very species-specific. But here they hypothesize that maybe hexadecaneal, which promotes social buffering in mice, may do something in all mammals. Again, because this receptor is very highly conserved, or 37B, I think. So he approached us and said, look, you've got to study this stuff in humans, right? Because he knows us as the human people, right? I mean, we go to these all-faction conferences where lots of people study mice and zebrafish and whatnot, and we're the human group.

So, and eventually he just FedEx does, hexadec and L. And so we had this thing sitting around and Eva was not going anywhere with her aggression studies with sweat from human participants. And yet she built the entire paradigm to study human aggression. So they're standard paradigms. This is a paradigm, knowing as the tap, the Tyler aggression paradigm. I'll soon describe it. And so we said, okay, we have this hexadecanal stuff here, and it promotes social buffering, social buffering sounds like it would make you less aggressive. Why don't you run your tap experiment using hexadecanal? What's the tap experiment? So basically, what you do is you bring in a participant to lab, you do is you bring in a participant to lab and you have them thinking that they're going to be playing against another person in this game. And you can do something like have another person walk

into the other room playing online so connected. So you can fool them into being quite convinced that this is what's happening. And they go into their own room. And in the initial game, they play on each round, they're provided with a sum of money. And this is real money that they'll receive at the end of the experiment. And by turn, each one of them decides how to divide the money up between the two. Right. So they're playing against another person, they think, but that's actually a computer algorithm that they're playing against. And the computer algorithm is programmed to be an inside-to- if it's terminology a jerk. So, like, let's say they have to divvy up 100 check-all, which is the Israeli currency. So the other player would say, okay, I'll keep 96 and you get four.

Then you can either accept it or not accept it and then neither of you get anything. So basically, you're being shafted by the other side all the time. And this is called the provocation phase. You're really getting angry at this person because they're really not nice. They're shafting you on every trial or almost. they're really not nice, right? They're shafting you on every trial or almost. And you play this game and it goes to its end. And then you play a second game

as far as you know against the same participant. And the second game is a reaction time game. So a target shows up and the first to press it wins. And on every trial where you win, if you want, you can blast the other participant with a loud noise. And it's a really loud noise. So you're also wearing earphones, it's 90 dB, and it's a screeching, horrible sound. It's the most punishment that an IRB committee will let you endure on a participant's experiment. Unless you're in stand for 70 years ago or whatever that was.

No, it's referring to the classic prisoner experiment, which took place in the building next door to where I went. So you can blast the other participant with varying levels of sound and you have a selection box from something very low to something very high. And what's nice about this is that it then allows you to quantify aggression because the more volume you're blasting the opponent with the more aggressive you are towards your opponent. And so you have a measure of aggression. Again, the Tyler aggression paradigm, obviously, invented by Tyler, very well validated, studied all over, you know, a very standard protocol.

So we brought in participants and had them play the Tyler of the tap, either under exposure to hexadecanal or control. Now, hexadecanal doesn't, it's incredibly difficult even to detect hexadecanal, but just in case, because it's not very, it's considered a semi-volatile, it doesn't have a strong smell, but we buried both the control and the hexadecanal in a control order that hit them in a mask. And she ran lots and lots and lots and lots of participants, men and women. And I'll first tell you the result with men, which is that hexadecanal consistently reduced aggression. People were less aggressive under heck's said heck and L.

The effect size was quite meaningful. And later on, we learned because I'm no specialist in the world of aggression, but compared to the effects seen in the aggression world in research, really, really strong effects. So unusually strong. So heck's said heck and L lowered aggression in men. And we were like, cool, this is sort of what we were hoping to see,

consistent with hypothesis, and consistent with it seems to do in mice. But then we looked at the data from women, and hexadecanal increased aggression, equally significantly. Is this thought to be something related to maternal protective? We're getting there. So you got there really fast fast it took me a year But and and and I've got to it really I'll tell you because remember we're reaching the back of the head of your of

Who's was it? grandchildren The kingpins of the New York neuroscience mafia. Yes, so one of the kingpins of the New York neuroscience mafia. Yes. So this was really odd to me at that time. So I didn't have the intuition you just had. And I was like, there was some bug here. I mean, this, it makes no sense to me.

You know, why would something increase aggression in women and decrease aggression in men? This is really, really strange. And I said, okay, I want to see this happen again before we go ahead with this. So she went and did the entire experiment again, and this time she did it within the Ephraim or I magnet so that we can also track brain activity

while this was happening. And first of all, it replicated again. So once again, Hexadec and element made men less aggressive and women more aggressive. And the extent of more than the effect alone, the dissociation was remarkable. This has, it's almost like a chromosomal test. I mean, you look at the data on the unit slope line

and all the men are below and all the women are above. There's this figure in the paper. Then she also looked at the brain data, and this is, although our lab does a ton of fMRI, it's one of the major tools we use to measure brain activity. I'm quite cognizant of the limitations of fMRI, and this is, I think, sadly, I think the only study in my career at least where

I actually managed to also get a mechanism out of fMRI, not only an area that's involved in activity. And so here's what we saw, that hexadecanele alone increased activity, white pronounced lean, and an area of the brain known as the left angular gyrus. Now, this is an area involved in what's referred to as social appraisal. So that was kind of cool in that a social order activated the social brain, not the olfactory system, per se, and very pronounced. So on one hand, that was cool, but then what was uncool was that it did the same in men and women.

This was in contrast to behavior, which you don't like seeing, right? I mean, because you would expect brain activity to reflect behavior. It increased activity in the left hand, girl, a gyros, and both men and women. Then she did a follow-up analysis, which was, look at what's referred to as functional connectivity. That is, how does this region of the brain talk with the entire brain as it were, under hexadecanal versus control? And here, the dissociation re-emerged powerfully whereby the connectivity from the angular

gyros was mostly to the classic neural substrates of aggression, so they are mingdala and the temporal pole. And the connectivity went in opposite directions in men and women. So hexadecanele increased functional connectivity in men and decreased it in women. So in a way, this is almost saying that the default brain reaction is aggression, right?

The default is to address. And in menadecanal increases the control that the left angrily tyros is holding over your aggression and keeping you back. And in women it let it roam free and they became more aggressive. But I was still puzzled. So I was convinced this happened twice. The MR data provided not only a pattern but a mechanism, which is unusual. And yet I was telling you, but you know, this makes no sense to me. And then her insight, which of course afterwards is like, duh, is no, there's a place where

this makes perfect sense. And that is if you're a mammalian offspring, because paternal aggression is often directed at you. There is infanticide all over and sadly there is male aggression towards human children as well. And maternal aggression is often protective. So if you are an offspring, if you have a molecule that will make your mother more aggressive and your daddy less aggressive, both of those are good for you. So you're winning. So we remember to recently published paper from a group in Japan that looked at the orders emanating from baby heads.

We now come full circle to circus grandchildren. They used a method known as GCMS, gas chromatography, mass spectrometry, to measure the volatiles from baby heads, because baby head odor is a cultural thing across cultures, even in Japan. And so we quickly went to that paper and to see if one of the molecules that report is hexadecanal and we were very disappointed that it wasn't one of the molecules that report is hexadecanal, and we were very disappointed that it wasn't one of the molecules that reported in the paper. And so we wrote to the authors, who are since then our co-authors, and we said, look, we're studying this molecule

hexadecanal, and we don't see any results. And we were wondering maybe you had some results that you didn't publish or some supplementary adduals or whatever, and this lab, which is a hardcore GC lab, said, no, no, Hex, the decanol is a semi-volatile, which we knew. And our previous paper was not directed to the semi-volatile range, but we can now do use what's called GCX, GCWGC, that is directed at semi-volatiles.

And we can do this again. We just studied 11 babies. And we can see if this is an issue. So I said, yeah, please do. The bottom line of all this is that hexadecannels, the most abundant semi-valothol in baby hits. It's tons of it coming out of baby hits. So babies, again, speaking about if humans do or don't

keep us thinking, well, babies are conducting chemical warfare, right? They're, you know, reducing aggression in their fathers or males around them, and increasing aggression in their mothers or females around them, and both of those things are good for them. Incredible. This is somewhat different than what we're talking about

and yet similar in other ways because it's built off of anecdotal evidence, but it's anecdotal evidence that you hear all the time and yet when you look in the scientific literature, at least by my read, the data are not clear, maybe even contradictory. And that relates to the coordination of menstrual cycles among co-housed women or women who are friends. The many women listening to this, and maybe some men who are aware of this effect will say, oh yeah, absolutely.

When I spend time with my friends or go away camping or even spend a day with them, our menstrual cycles become coordinated. However, my understanding is that the early literature, Barbara McClendon, correct. Discovered this phenomenon, published a paper in science as an undergraduate. 1971 Nature. Amazing, Nature, paper. Again, one of the three apex journals

and as an undergraduate, fantastic. So, discover this, describe this, and probably women all over the world who became aware of this one way or another, probably said, yes, absolutely. This gives validation to what we've observed over and over. And yet, as subsequent papers have been published, this result has been called into question. Is there any final word on whether or not menstrual cycles become coordinated among women

who spend time together? And if so, is there any role of olfaction in this, or chemosensing through the nostrils, or an endormouth to support this idea? So, yeah. So, I'll start off, indeed, to echo the background, is that this study was conducted by Martha McClendock when she was an undergraduate at Wesleyan College, and she noticed that she thought her menstrual cycle

and her co-inhabitants in her dorm room were coordinated in time. And I should say that this comes on the basis of similar or related type effects in rodents. Now, rodents don't have a menstrual cycle like humans do. But there's an effect in ruins which refers to the witton effect, which resembles this type of effect.

And she published indeed that paper is an undergraduate in nature in 1971. And to answer your question, she published a follow-up in 1998, also in nature, with then her graduate student, Chicago Stern. So this is Stern and McClendon, 1998. And here's what they did.

They collected sweat from donor women and deposited it on the upper lip of recipient women. So this would be a fun experiment for you at least weeks since you said you like body orders, but for many others, perhaps it would be daunting. Well, I like certain body orders from certain individuals. Okay. Yeah. I don't think I uniformly like all body orders.

Although I do seem to uniformly not like the smell of perfume, although I, just declare why, because I put this out there and I learned the hard way in the comment section on YouTube. Some of those perfumes I find downright aversive. Yeah. Like it's a, I think the great Marcus Meister who, great norbile just once said there's basically three responses to either young me, or me. So some of our truly young never heard that one. Yeah.

Like that one, right? In terms of the animal behavior, human behavior. We're either a move forward or a stockboard pause. So some are truly a yuck. Some many are met, zero to date, or yum for me. Now body odors, the distribution is shifted. It could be any one of those three yum yuck are met, so just to be clear, but the yum category is definitely included. Thank you for allowing me to do that. Yeah. So she did this study,

so because right in the original McLean Talk study, you might suspect other drivers of the effect. Let's see, you accept the effect, but still there might be other social drivers of the effect that Let's see, you accept the effect, but still there might be other social drivers of the effect. There are no body order, right? There might be some dominant woman who's dominant in some other way, and this might be driving the coordination, right? So here, there was no direct link between these women other than body order, so if the effect re-emerged, it would definitely be an olfactory effect. And what she found is that if she took sweat

from the follicular or the ovulatory phase of the donors, one extended the cycle in recipients and one shortened the cycle in recipients. I don't remember which was which, but basically, definitely denoting a chemosignalling effect with opposing effects on duration based on the time it was collected from, again, published in Nature in 1998. That said, there's a quotation, I think this is from from, I'm not sure about, but you know, that if something is published in nature or science, that doesn't necessarily

mean it's not true. So with that in mind, the findings were since called into question widely. One reason is just statistics of cyclic events are surprisingly complicated. So it's tricky. It's once you have a cyclic event, statistics become tricky. And so Martha took a lot of heat on the statistics of claiming an effect. And I think there was at least one effort of replication that didn't really work out.

If you ask me, I'm on the fence. So I'm, but I may be in a minority in my field, I think a majority in the field is currently negative. I'm not. And I've said in lab that we should do a planned replication. We will. It's just, again, it's a horrible study to run. It's tons of work and you have to run it for really long time. It's tons of work and you have to run it for really long time. So it's just completely non-trivial. But we have graduates who are now in lab interested in these exact things, a road rice growth signage, and she's doing similar stuff,

and I hope we'll do that. I hope we'll try to replicate this. Very interesting result, and I think interesting because of its real world, meaning outside the laboratory, of course, our experiment analog, but also because pheromone affects and all factory effects in humans. Seem unique among neurobiological slash endocrine phenomena because there seems to be so many stories that we all have of the smell of our grandmother's hands

or the recognizing the scent of somebody, or I knew from the moment that I smelled their breath or I just liked their smell kind of thing. These kind of things that inform the deep potential for a real biological phenomenon. As opposed to the kind of thing like, oh, you just throw something out there, oxytocin is bonding and all of a sudden,

the general public, not to no fault of their own, comes to think that every aspect of bonding is oxytocin and every defect in bonding is lack of oxytocin and every defect in bonding is lack of oxytocin. But the general public provides a sort of a rich, it's butter for exploring all these things. And a lot of times they turn out to be true, right? In the context of old action. Yeah, it's a very primal system, you know. So it's linked to the most, you know, limbic primal mechanisms in our brain. And it drives primal behavior. It's an incredible system. I have a question about

a particular study, but I'm just going to queue it up and you'll know immediately what I'm queuing up. And that is, what is the relationship between odors and hormones and in particular crying? As I pointed out previously, the sort of flavor of the month in human and social chemo signaling research is the smell of fear and the media of the month is sweat, right? So the few, maybe tens of labs in the world that study human social chemo signaling all collect sweat and that's the media they look at. Is it always from the armpit? Or is there meaningful differences

in terms of the sweat emitted from different locations on the body? I already know the answer to that as I ask it, but let's just stay above the waistline. Oh, no, no, yeah. Or below the waistline. I mean, we're biologists after all. We just yeah so it's it's funny we we we have we're working on a paper on that right now on the

smell of fear. So we have a nice paradigm for generating fear. We throw people out of airplanes. It's a very effective way to generate fear to come to your lab. We didn't invent that by the way. The first to do that was and I hope I'm pronouncing her name correctly, I think it's Mujika Perudi. But that's our paradigm for generating fear, and we started that on our own, but we've since entered into collaboration with the Israeli Power Trip was brigade, and we now collect body order from every first time jumper. So we went that path because we like everybody else in this field, you know, the holy grail there is finding the molecules, right? I mean, if you'll have the

fear molecules, that's a banana, right? Because I mean, you know, you could think of many reasons why it would be a banana, but for me, you know, if could think of many reasons why it would be a bananza, but for me, you know, if you find the molecules, you can then try and find the receptors. And when you find the cognitive receptors, you can then develop blockers. And you can imagine, you know, what's the turn on looking for switching into Hebrew. It's about midnight now, right? I'm sorry. It's too early. you're doing incredibly well considering

that inversion of the morning. We would never know. No travel in today from Israel. So he's a circadian inverted as we say. Anxiety. Anxiety. So you can imagine developing like a nasal spray against anxiety, right?

Where you would quell those receptors and kill the fear response, right? Which rather than going to the carmpath, which is through neurotransmitters, that then have effect all over the place, you would be getting fear at its source, right? So that would be why I would want that. And we figured out that doing that, you know, collecting fear from like three, four, five people in an experiment, you'll

never be able to do analytical chemistry on that. So we now have a setting we call fear bank, which now has more than 1,000 samples in it. So we're trying to do analytics on that. But in doing that, we've joined the crowd, everybody's doing fear and everybody's doing sweat. And in one of our discussions in the lab, we're saying, well, there's got to be, you know, or their potential definitely could be additional bodily media that are playing to social chemo-signal. Now, many of these, you can't really study, right?

I mean, so, you know, just to throw what most terrestrial mammals communicate social information through urine. But starting doing experiments with humans, with smelling urine, it would be difficult, both in IRB and in agreement. And then we, this is a rare case where we actually hypothesized what we said to do and, you know, and they don't only claim in retrospect that it was hypothesis, is, is tears. We, we started thinking about tears and looking into tears because tears are a bodily liquid emotional tears that, that we emit in emotional situations where, where these are situations where nonverbal

communication is critical and key. And tears are a liquid that is puzzling beyond ocular maintenance. And so the most influential text, I think, to this day in emotion research is Darwin's book, the showing of the emotions in man and animals, I think, is the following of the book. And an entire chapter, chapter six, is devoted to tears. An entire chapter of this book. why? With no conclusion, why? Because the book revolves around describing the functional antecedents of emotional expressions.

So for example, showing of the teeth is a sign of aggression, right? So animals first bit with their teeth and Darwin argued that through evolution, just showing the teeth alone became an aggressive sign because it started from biting. Or what I find is a beautiful example and this is work partly done by Adam Anderson now at Cornell is the emotional expression of disgust. So disgust which comes from land dysguzia, distaste, right, is spinning something out of yourust. So disgust, which comes from one dysguzia, distaste, right, is

spinning something out of your mouth. Now what Adam showed is that the musculature patterns of activation and the temporal sequence of activation, when you experience moral disgust, are the same as when you spit a bitter taste out of your mouth. So again, so there's a functional antecedent spitting something out. And through evolution, the argument was that it became an expression of emotion, and you expressed disgust just as if you're spitting something out of your mouth, even though they're in the case of moral disgust, there's nothing you're spitting out of your mouth. So, so darn systematically,

went through the expressions of emotions, and for each one went to their functional antecedent and explained everything very nicely. And then he got stuck with tears, right? Because tears are an obviously emotional expression and he could not find a functional antecedent. So he ended up saying, this is an epic phenomenon. Basically. Right, I don't know what all scientists do

when they don't have a good explanation. And I'm blaming on basically. Right, I don't know what all scientists do and they don't have a good explanation. And I'm blaming on nature. Right, right. But he bothered to write this entire chapter on the ocular sort of maintenance function of tears and so on and so forth, but nothing emotional. So he thought, well, maybe the function is a chemical signal. And, and, you know, so with that in mind, we harvested emotional tears, which was also an amusing event

on its own, right? Because we posted messages on all sorts of that we're seeking experiment participants who cry with ease. Now this generated an unfortunate gender bias in our study, right? Because we received about 100 women volunteers and about one man. And I think this is not a problem only in Macho, Israel, right? Probably anywhere in the West. This would be, I mean, definitely in America would be the same. I guess is that they're probably men out there

who cry easily, emotional tears. Oh, I'm sure, but they're just gonna show up. Yeah, that's what I'm saying. That it's a cultural thing. It's not, you know, you're not gonna come to a lab and say, you know, I cry all the time. It's just not gonna happen. And then we, what we did is, for each one of these participants,

you know, we would ask them, you know, is there each one of these participants, we would ask them, is there a particular film event of that scene that makes you cry? And interestingly in these effective cryors, there's, oh yes, the scene and so on. So I always cry profusely from that. They have their main example

of one of the more commonly seen. Yeah, with these, the movie The Champ, from that. You know, they have their main example of one of the more commonly seen with these, the movie The Champ. The champ dies. He's a boxer. And he dies. And literally in the hands of his about eight year old son. And his son is standing next to his bed and, you know, saying, champ, champ, and he dies, right? It's a winner, okay? Waterfall. And yeah, yeah.

Got it. So, you know, we're probably the neurobiology lab with most sad movie films on those shelves in the world, right? We have a whole huge collection. There is such a huge deal. There is a huge deal of joy, by the way. So no, no. Well, we're going ahead of ourselves,

but I'd say we try to collect them and failed. Even people who think they shed tears of joy and laughter, their eyes water a bit, but it's not the same thing. In the effective cries, we end up screening. So we collect a full ML of tears, a full ML of tears in about 15 minutes. So, that's pouring, right? And that doesn't happen from laughter. Or we've never seen that. We've never seen that happen from laughter. We tried. So, we have all these sad films. And by the way, one of the amusing things is,

when we ultimately published this paper in science, we were forced in retrospect to go out and actually buy the films. I mean, originally we like downloading them or we're there, but you can't, because you'd be violating copyright laws. Right, so we had to buy, like, purchase all these films that the parts of the plot.

And so we actually have these in live, like DVDs that we actually purchased. But so I- Nice coverage of potential legal fallout, no. No, we did. No, I believe you. I believe you. Yeah, it was that.

So, yeah, and, and, and, no, we did. No, I believe it was that. So, yeah, and, and, and, well, we can touch on that later, but, but up. So, um, we, so most of these, uh, volunteers who, who come saying they can cry with ease, actually don't meet the bill. Um, and so out of the about 100, at least, more women that we screened, we ended up with about six who could really come to lab week after week and port years. There's a name for this in psychiatry, they call it a narrative distancing.

Some people when they watch a film where someone's getting hit, they flinch quite a lot. It's almost as if they're experiencing it, but it works in the opposite direction too. I know someone like this where if they watch a film that someone's experiencing something even mildly positive, their mood elevates. So they can quickly bridge. And it's not always adaptive, as you can imagine. So there's lack of narrative distancing. Right. Yeah. Well, one issue you can bring. So there's lack of narrative distancing. Right, yeah.

What one issue you can bring up with this entire line of studies in our lab is, is I don't know if there's something very unique about the donors, right? I mean, we're assuming these are tears. And this is pretty common. I think the numbers I saw out there about five to eight percent. That's exactly what we got about right. I just think so. Exactly.

So, so we collected tears, and we exposed participants to these tears. And we found a few things. First of all, the tears are completely odorless. You cannot detect them at all, completely odorless. And yet, when you sniff them, you have a pronounced reduction in testosterone within about 20 minutes, half an hour. This is men and women smelling women's tears. Just men smelling women's tears, but not perceiving any odor. Nothing. Just sniffing them.

And you have about 14% drop in free testosterone. Free. So this is testosterone that's already been liberated from the testes free testosterone. We've done a few hormonidates, either bound or unbound, is unbalanced, excuse me, from sex hormone, bonding, glogul, and so on. And it's the active form.

So it's subject to very short time scale changes. Yeah. And this is, you know, people who studied testosterone, which is not me, but they tell me this is a really strong effect. Like it's, it's hard to even pharmacologically get an effect like that, that fast. Yeah. No infarmingology.

Yeah, years ago I spent time studying endocrine effects of this sort and that's a tremendous recised effect. So and so here I'll point out in passing that one of the concerns we had because of the effort to run this study is that nobody would ever try to replicate it and to our joy about two years later, an independent group from South Korea, OIT-AL, who I don't know it all, replicated the testosterone effect to a T, I mean like same numbers. So it lowers testosterone. And we then also looked using MR at the effect on brain activity and saw pronounced effect on activity, dampening a lowering of activity under a rousing state, a lowering of activity under a, under a, an arousing state, a lowering of activity, both in the hypothalamus, and in the fusesiform gyrus for whatever reason I

don't know. They're recognition area amongst other things, yes, and we don't know why, but pronounced. And currently, Shenier-Groen in our lab is replicating this again, and this time with a stronger behavioral component, and I can share with you unpublished data now under review that, as you would expect, given the effect on testosterone, perhaps, sniffing tears lowers aggression in men. Using again, the tap, the same experiment used by Yvine in the hexadecannol experiment. I'm gonna tap the, I'm gonna think of that as the satis, the titration, the satis titration.

Yeah, yeah, the titular aggression paradigm. So not on like the nobleman experiments of the 1950s, which post, this was looking at sort of post holocaust behavior. Right. You know, people basically, in American laboratories, thinking they were torturing other people, simply because they were told to,

and a lot of people did that, even though most people would report that they would never torture something. Yeah, no humans are not a wonderful species. Or as we could say, I think it was the great Carl Jung that said, we have all things inside of us. But the goal is not to experience them all certainly. It's an incredible study and it points again to the power of these chemo sensory systems

and pathways. And obviously, there's so much here. I don't know if you want me to tell about this or not, and I guess you can edit it out. Please don't. But this is just sharing stories about the politics of science. And so whereas the effect on testosterone

was replicated by an independent group, In the original study in science, where we had, it had three components. One was the effect on testosterone, which was robust, the second, which was brain activity, which was robust. And there was a significant, but weaker effect on behavior. And I don't think we studied the right behavior in retrospect. What we looked at then was ratings of a rouse all associated with pictures.

And there was an effect, it was significant, but it was not what carried the story. Now there's a lab in Holland of a guy by the name of... I'm probably mispronouncing this, but I think it's Vinger Hoats. For the non-Dutch names are always a little bit of a challenge, but... And I shouldn't say that. Being in Israel, I shouldn't go too much on that line, but... That lab really didn't like our original tier story. And the reason they didn't like it is because they've built a career on this notion, including

a book with this title that emotional tiers are uniquely human. Now here I should, well, I should share. So one of the things we really liked about the tear result is that partially before we did our work, but more afterwards, and we liked that because usually things, so usually in our chemosigling work, like what I told you before about the Bruce Effect, we look at what happens in ruins and we see if the same things happen in humans.

This was a rare case where after we did this work, more or less identical effects were discovered in ruins. So a paper published in Nature 2 years later found that mouse tears, mouse pup tears, lower aggression in male adult mice towards them in a smell dependent way. Yeah, yeah. And they also actually found the actual component in tears that so the tear farm on that lower is aggression. So you know, this has us thinking of a great tears is you can think of tears is like a chemical

blanket in a way that you're covering yourself up again with, you know, to protect against aggression, right? And so our finding, you know, which to me, I mean, this is consistent with how I think about behavior and general, I don't think, you know, beyond language, there are very few things, definitely sensory things that are uniquely human. I'd be hard pressed. But so our finding when it gets against their story, because here we're saying, tears are this chemosignoling mechanism like all animals.

And by the way, just after this entire debate about six months ago, there was a paper in current biology that dogs emit emotional tears. And it was the dogs emit emotional tears when they reunite with their owners. And you were talking before about about oxytocin. So I think what they showed there is that not only that, but that the view as seeing the tears and the dog influences the oxytocin in the humans. I absolutely hope I'm getting this right. But that's absolutely, believe this.

I mean, from the time I brought Castillo home at eight weeks old, because that was your dog. He was my dog in four years. Yeah. And for the past way, they haven't had a long time. Actually, the only time I can recall crying, listen, I've certainly cried before,

many times in my life, many, many times. The only time I ever recall crying to the point where I wasn't sure that I could keep producing two years, but somehow it is when I had to put him down, right? Is this like, you know, and if I talk about too long now, I'll start trying to, you know, it's one of those things.

And I think it's a healthy emotional state. For sure. But I recall when he was a puppy, thinking this oxytocin thing must be real because I can recall being in faculty meetings, which you know, very fairly state are not always that interesting, but they could be pretty interesting. And someone presenting data at my mind, thinking, I hope Costello is okay. What's he doing down in my office? This is when he was very little. And also not needing to eat, not being able to focus on anything else except my attachment to him

for about the first two or three weeks that I had him. Then it was easy. Then I could focus off on other things. And I think that dogs, perhaps through oxytocin, hijacked the circuitry that's intended for child rear. I really do otherwise why would people be so ridiculously attached to their dogs? I mean, hence all the posts of everyone thinks their dog is the cutest dog. The same way everyone thinks their children are the cutest

children. Yeah. You know, custom of by the way, it was a very handsome bulldog. So, so yeah, so again, so there, so even, you know, to put another nail in that story of tears are uniquely human, so they're not dogs-ched emotional tears. And so, that really didn't like this. And they went ahead and tried to replicate, and through your listeners, I'm showing double quotations on the replicate only the behavioral part the ratings of arousal in women of women and fail to replicate that I see. Now this was you know just sharing on how science works and doesn't work in my in my notion in this case. So and it doesn't work in my notion in this case. So at the time, after they got this accepted in some journal, not a field journal, in the journal of memory of something,

they contacted me for a response. And I wrote to the author, and I said, look, you know, this is very out to me. Why don't you come? You know, why don't we replicate this again together and see if it doesn't work. If it doesn't work, I'll publish it with you that it doesn't work. But, you know, and so I said, why don't you send over a graduate student or the lead author and we'll do it here and we'll show them how it's done because they did it very wrongly in the paper. And so they replied that no, they don't have money to send over a graduate student to

do it. So I replied saying, okay, I'll fund the graduate student coming over and I'll fund the entire study and their stay and so on and so forth. And let's do this together. And they replied, no, they're not willing to do that. Which I don't think is the way things should work. And they published this sort of failed behavioral effect in that paper. So I'm just sharing this, you know, that it's not only there was that successful replication with the effect on testosterone, but there was supposedly this failed replication on the effect in behavior.

And then I published a rebuttal on that, which I don't know if I should have done, but I did. Well, I think it's interesting. I think provided studies are done correctly. I mean, the positive result almost always trumps the negative result. And yet I think replication is key. The problem is you point out is that replication is rarely pure replication of the exact study.

This one is not even real. But I published the detail. So actually, they hid something in their data that did partially rip. So I asked for their data and I reanalyzed it. And that's what I published in the rebuttal. But this is just sharing on how science works. I took advice.

So it's not that friends with him, but at that time I was communicating a bit because we're on some board with Daniel Conman, who's Nobel laureate of Aston's Law. And so I asked him, how should I deal with this? You know, give me some advice here. I was really, you know, it was an emotionally not fun to be in that position and he said, don't, don't never publish a rebuttal. Don't do anything. I was, you know, how can I, you know, I have to do something. He said, no, don't because once you do that, then, you know, people don't go into the details. They won't read the details of your rebuttal, though. They'll be like, well, there's a group that says this and there's a group that says that.

So it's unclear. Well, and, you know, I mean, I appreciate that you're bringing it up today and I do appreciate that you publish the rebuttal and that you offered in a very magnanimous way to do a collaboration. That's what he then said. So comments advised after that was that, well, if you insist, then just publish, right, a response

that you offered them to come and do it together, they refused and there's nothing you can do about that. It's a lot like fight sports, right? People talk a lot of trash. Although in science, you know, I will say this, you know, as long as we're on the sociology of science. Science is very different than podcasting or social media or other fields because in science people

generally are very kind to your face and then they you get it in the neck on grant reviews or anonymous reviews. I was on a grant review panel this morning. I'm a nice reviewer, meaning I judged things objectively but I try to always think from the perspective of the graduate student or author of the proposal. Listen, I think that science is a game of people who most of them are seeking facts. However, the ego is strongly woven into it like anything else. I think it was very magnanimous of you to offer the collaboration. So I'm going to tell this lab whose name I can't pronounce. Please accept the collaboration.

Then we can invite everyone on here for a round table. I appreciate that you shared that story and I know a number of other people will for a number of reasons. I have a couple of more questions and I realize, and thank you, by the way, for your willingness and stamina because it is probably one AM Israel time now,

and you just arrived. But you're doing it terrifically well. for your willingness and stamina, because it is probably 1 a.m. Israel time now, and you just arrived. But you're doing it terrifically well. So if you'll indulge us just a touch further, there are two topics that I want to touch on in. If you want to cover those in shorter thrift, that's fine, although don't feel any obligation to. The first one is, I think most people are familiar

with the scent of food or foods as a signal of the nutrient contents of those foods. You know, an orange that smells great or that smell of something baking, you know, it suggests something about the contents and quality of that food. After all, you and I both separately lived in the same apartment in Berkeley above the cheese board, which the smell of cheese is wafting up through the cheese board is something I will never forget and the breads.

Never forget it. Amazing bread. I mean, I don't know if you've conveyed that clearly enough to listeners or watchers. Now the probability is really just discovered that we lived in the same, we never met, I mean, a fit like this before. Yeah.

And we lived in the same apartment. Are we click friends? What? I had a lingering way, I guess. Absolutely. Through the through the through the floorboards and having great floor of that place. I had a great wooden floor. It was an amazing place. I lived there with my girlfriend for a year and a half. And then it was an amazing place. We won't give it out at the address, for out of respect for the people that live there now.

But do check out the cheese board, if you ever in Berkeley. Their hours are weird, but you have to look online, but it's a unique place with great bread and cheese and some good flavors of pizza. In any case, I'm wondering whether or not smell can signal things about the nutrient contents of foods in a way that's divorced from the smell that we are perceiving. So for instance, I could imagine based on what you've told us about smell today, that I don't know.

I smell a piece of meat cooking and it smells great to me. And I think of it as how that's so savory and my mouth is watering and I love the smell of this. And I'm thinking, okay, this is protein and fat and I love the taste of steak and a little bit of char. But that nature has co-opted that to get inure or I should say increase the likelihood that I will ingest some other thing that's in stake for that has no odor but whose nutrient content is very important to me.

For instance, amino acids. Right. I mean, amino acids are essential to life. And yet, we don't go around sniffing for amino acids. We go around sniffing for savouriness, umami type tastes and things of that sort. So I could imagine a million different examples of this. In the same way, I could imagine that the scent of somebody that we fall in love with or become romantically attached to or sexually attracted to is signalling all sorts of things

about sure the potential for offspring of a particular immune status. That's a long-term game, but also something about pleasure and safety of a potential interaction. So what I'm asking here is about whether or not there are subconscious signals that the olfactory system has learned to seek, but learned to seek through more overt signals, sort of the tip of the iceberg from Lebanon. So I don't have a good answer for you, although I think it's a really good question or a good idea, in fact. So whether there's, you know, order cues on nutrient value is a really good idea.

Moreover, it's probably good to the extent that somebody probably did it and I should know and don't. We haven't done anything on that line. So I don't know. I don't know if the nutrient value of food is systematically encoded in order, if that's not been done and I will check after our meeting today, then it should be. That's a really good idea. I mean, one of the reasons I asked this is because the obesity crisis in the US is a huge

issue and elsewhere. And highly processed foods have a lot of things that are problematic. But one of the things that they don't have often is a direct relationship between the scent, the taste and the nutrient content. And I don't mean macro nutrient sugar fat, I excuse me, carbohydrates, fats and proteins. But the vitamins and micronutrients things that support the microbiome, whereas foods that are not highly processed, for instance, meat or a piece of fruit, contain many micronutrients that are vital to aspects of our biology.

We don't go around sniffing for probiotics. I'll tell you one sort of factoid that may support your hypothesis here. And that is that there appears to be potential or factory perceptual similarity in metabolic products. So something that's metabolized from something else has perceptual similarity something else has perceptual similarity across those two things. So metabolic cascades plane to the coding of olfactory space, and that is consistent with the direction you're implying. But again, I don't know of a direct test of nutritional value in smell. And again, the fact that I don't know doesn't mean, of course, that it doesn't exist. And in this

case, I would suspect that it should exist in scientific press. And if not there, then with the companies that have vested interest in this, which are many. Briefly, an amusing anecdote to share with you is that we've received two independent companies who have turned to our lab recently asking for help to bring older to engineered meat. That's a growing thing and all these meats that are going. You had to bring it up. This audience is going to be very polarized along the lines of engineered meat. You're not promoting it. Oh, no, no, no, no, I'm agnostic.

But we've had two companies turn to us and say, look, no, no, no, I am agnostic, but, but, but we've had two companies turn to us and say, look, you know, we have this great product, but it just doesn't smell like meat. So help us make it smell like meat. Interesting. The reason it's so polarizing is that anything related to nutrition on social media is a total barbed wire topic. We've had experts on nutrition come on here. We'll have more. But I'm just, I'm just, don't worry, you're safe. No, don't worry. No, it's not promoting, as he hasn't even said whether or not he's gonna help them out.

No. We're not actually, not because, yeah, it just didn't happen. No, the whether or not those engineered meats are yum, yuck, are met is a personal issue to people in terms of taste. Whether or not they are better for neutral or worse for you and the planet than given the ingredients that are required, that's a whole world will avoid now.

But I'll take the opportunity to highlight something related maybe because I'm on what we're saying on the scale. You know, there's this, you know, I'll take the opportunity to dispel another misconception about all faction. Right? There's this common notion that our sense of smell is incredibly subjective, right? And that what you might like in a smell, I will not like in a smell, and that we all have our own, you know, totally subjective world of all faction. I think I know this study you're going to tell me.

There are many. The cross-cultural similarly. There are many. That is utterly untrue. Many, not only from my lab, there are many from many labs. Uh, please clarify for those that have all of this literature. So, um, yeah. So, so, humans are incredibly similar to one another and they're all factory perception.

And this is in contrast to what most people think. So why, why is there this misconception? The misconception is there are two reasons. First of all, or for several reasons, but two are stand out. First of all, we're attracted by outliers because I'll tell somebody, look, for example, a factory pleasantness is highly correlated amongst humans.

And let's first put this in numbers, you'll take a bunch of humans and a bunch of odorants and have them rate pleasantness, the correlation across the humans will be about 0.8. That's incredibly hot. Incredibly high. What do you think is pleasant, I think is pleasant. Yeah. Yeah. Now, why is that go against what culturally people think for two reasons? First of all, we're attracted or biased by outliers, but that's particularly that shows, in fact, the result. What do I mean? So you'll tell somebody, look, people are very similar in their pleasant assessments. And the

cell, you know, that can't be, I love cilantro. And you know, my girlfriend hates the smell of cilantro, right? Or in there are a few classic examples, they're gulla, right? You know, is another polarizing order. So there are a few polarizing orders, right? And that's true. Right? So that's true. That half of the population loves the smell of cilantro and half-hates it, half-loves Guillaume, half-hates it. That's microwave popcorn. However, I assure you that you can come to our lab, we have about a thousand odorants in our lab. We won't smell the thousand, right? But I assure you, you know, take a hundred odourants, okay, from our mixtures and labs, right? And we'll smell them, right? And out of the hundred odour's 90, we'll totally agree on, right? And including the universe, I mean,

you know, nobody else say they like the smell of feces or fecal smells. And everybody will say they like the smell of rose and flowery smells. There will be rare rare exceptions. Again, the correlation is about 0.8 across individuals. So on 90 of 100 will be in high agreement. Then five orderings will be in intermediate agreement. And yes, there will be the five orderings that we're in total disagreement on. But I ask you, you know, if we agree on 95 and disagree on five, are we the same or are we different?

We're the same. They're just outliers to this rule. And so one reason is this issue of outliers attract how we think about things, but no, we're actually much more similar than what we think. And the second thing that drives this cultural effect is our poor application of language tool faction.

So in other sensory systems, we develop with anchors. So since you're a little kid, your mother shows you a cow and says, what does a cow do, moo, right? And we all know moo, moo. And what colors this? It's, well, this is kind of an odd black, but it's black, right? Or what color is that? It's red, right? So you have these anchors. But as you all know, you know, the red that I'm seeing is not necessarily the red that you're seeing, we just both know to call

that red. And since you say red, and I say red, I think why we're seeing the same thing, but no, we're not seeing the same thing, right? And in order, we don't have those anchors, right? We don't from childhood, you know, our mom doesn't tell us, so what's this smell and what's that smell, right? And so we don't have these language anchors that make us think that we're perceiving the same thing. Now, how can you quantify that?

The most important term in measuring sensory systems is similarity. That's the measure. What can you, let's say we take 10 odorants, and I have you rate all the pairwise similarities. You end up with 45 numbers. How similar is 1 to 2, 1 to 3, 1 to 4, and then 2, and all the possible pairwise similarities. You rate similarity from 1, which is totally dissimilar to 100 exactly the same.

Right? So now I have a similarity matrix that describes Andrew's perception of smell. Right? I have, you know, based on these 10 orderrants that I selected. Now I can run my similarity matrix, and then I can see if the similarity matrix are correlated. Right? And then we've gotten rid of the issue of names and orders, right? It doesn't matter if I'll call this lemon in this orange,

and you call this sweet potato in this marshmallow, right? It doesn't matter. If I think that these two are highly similar, and you agree, and I think that these two are very different, and you agree, right? We perceive the world in the same way. If our similarity matrices are aligned, right? And what's nice about that is that then you can do that for vision audition and all faction in a common group.

And you can see where we're more alike each other or not. And we've done that for color vision, all faction and tonal audition, okay? And we are most dissimilar in color vision. Okay? We're in color vision, the variance is about 100%. Amazing. That's quite different. Yeah. And there's tons of literature on this, tons of it, tons of it, right? And in

all faction and audition, they're about the same. So we're not different, we're very similar. We're just very poor at appreciating this. And mind you, not that there's not variability, there is variability. And of course, the system is malleable as all sensory systems are. So you can learn to like an order, and that will change you and learn to this like an order.

But just the way you can learn to like a sound or just like a sound. So this doesn't take away from the hard-wired link of a structure to its perception that you can, that they're malleable. And, and, and we're, we're not very variable. We're, we're actually kind of similar. That's a perfect segue to the question I have next, which is if, in general, people perceive certain odors similarly, you could imagine that odors could be manufactured, co-opted, et cetera, in order to elicit richer sensory experiences and drive choice making.

That's obvious at the level of the smell of a hot dog stand or freshly baked bread, et cetera. But what I'm talking about here, and I'd like to ask you about is doing this at scale and scientists geeks like to say in silico, in through computers. So for a long time now, there's been this idea that there will soon be Google smell, not to call out Google is the only search engine, but duck, duck, go smell for those of you that don't hear smell. Chat GPT. Here's a chat GPT.

And on and on. In other words, you know, vision, visual key information is sent through computer interfaces as is auditory information. Not so much haptic somatosensory, although it can, you know, we are lab uses VR. It can be done, but it hasn't really taken hold. However, smell being such a rich source of behavioral and hormonal and other sorts of deep, deep information that can drive people into yum yak or me type decision making seems like an amazing candidate. So what is your experience with generating smells in silico and computers?

And here folks, if for those of you that aren't catching on to this, and I don't expect that everyone would, because what we're really alluding to here is the idea that you'll look at, you'll put into a search engine, blueberry pancakes recipe, and that not only will you get photos of those blueberry pancakes and a recipe, but you will get the hopefully validated odor of those pancakes and that recipe coming at you in real time through the computer. So I'll start off answering from the the name you threw out there, Google. So about probably about five years ago, Google had an Apple Fools booth. All right, and they put out this video of Google smell, okay, and it had all these like classic like sales images of, you know, holding up your phone to a rose and generating

rose and all these things, right? So Google is now trying to do that. And they just, they just published, I mean, I know they've been trying to do it for a while. They visited our lab, but they just sort of went public with this that really just like about a month ago or something, that they have this offshoot startup. I think it's called Osmo or something like that that started off with a ridiculous sum of money for a startup. Like, yeah, I don't know. Tons of money.

A lot. There's a lot of money in that world. Yeah, in Google, yeah, I don't know. Tons of money. There's a lot of money in that world. Yeah, in Google, yeah. To digitize a smell. And there are other companies that are trying to do this as well. And we've been talking now for quite a while about our labs' chemosigling work, but actually half of our lab is devoted to this question of ultimately digitizing smell. And so this is a very, very active field of research, and I'll say

one thing that dovetails with what you were talking about before in many ways COVID is going to be one of the best things that ever happened to a faction research because suddenly all the world is all the world. Lots of people are very cognizant of the importance of smell and the smell is like way up there and people's awareness because of COVID. And this is driving a renaissance of of all-faction research and and awareness to all-faction. There's something that's worth paying attention to. And and our lab has been involved in this way in this effort for a long time where where the initial part of this effort is in fact to develop a set of rules that link order structure to order perception. That is, the going

saying was that until recently, at least there was no scientist or performer for that matter, who could look at the structure of a novel, a molecular mixture, and predict for you how it will smell, or smell something, and tell you what molecular structure could or should be. So in contrast, let's say the trivial like color vision, let's say. So if you know what the wavelength of the light is, you more or less know what perceived color is going to be. Of course, there are exceptions to that and all sorts of issues, but as a rule, you would know, or the other way around, you can generate a wavelength, and you would know what color light it's going to be perceived.

So that's an example of where the rules linking structure, in this case, measured by wavelength and perception, in this case, experienced this color, the rules are well known. In all fact, we didn't have that until recently. But over the past two years a bunch of labs have really pushed this forward. There's a bunch of work out of Leslie Voshaal's lab at Rockefeller and Andreas Keller working with Leslie who've done a lot of work on this front. who've done a lot of work on this front, also work from Joel Mainland's lab at Monel,

and Fair Discovery Joel was a graduate student in our lab. And recently in our lab, we've had, and I hope this doesn't come across as overly arrogant, but we've had a sort of mini breakthrough on this front to call something a mini breakthrough as far from American. And this is a paper led by Arn Raviyah from our lab and Kobe Snitz also, a major contributor there, a paper published in nature about a year and a half ago in the height of

a COVID pandemic. So nobody really, I won't see nobody, but it wasn't noticed in the way otherwise would have been. it was it was published in nature really on like a week where the whole world was like going berserk over COVID. And in this paper, we develop an algorithmic framework where we can predict the perceptual similarity of any two molecular mixtures with very, very high accuracy. So if you give me two molecular mixtures, I can predict how similar you will smell them to be. Now, not only could we predict that, but we could design it. So we can generate mixtures with no similarities. And the result was highlighted and you'll appreciate this coming from vision

is that using our algorithmic solution, we generated olfactory metamirus. So we measured mixtures completely not overlapping in their molecular structure, but they smell exactly the same. Okay? Now, if you would come to a classic perfumer, or most classic perfumers, and tell them that you can generate two mixtures

with zero molecules in common, but smell exactly the same, they would tell you no. And yet, we did, and anybody can recreate them. This is simple, actually. And in the paper and anybody can recreate them. This is simple actually. And in the paper, we do a few things like we generate a metamir for a Chanel number five. So you don't like perfume. So this one, but we take, so we generate a Chanel number five with no component from Chanel number five in it. Okay. And we actually have a publicly available

website. I'll give it to you for your links. If you want that anybody can do this, we built an engine that you can generate these, these metameras. Now, once we did that, in a way, we've generated the infrastructure for digitizing smell, because what, again, what we, what our algorithm predicts are, our framework predicts a similarity. But in a way, that's enough for you. Why is that enough? We have a map of 4,000 molecules. For each one, we know there are perceived smell. Now you can make up any mixture you want for me. I can project it into that map and measure its pairwise distance from all the points in the map.

If it falls on lemon, then what you generated smells like lemon. And if it falls on tomato, then what you generated smells like tomato. So we now solve that problem. We can predict the order of any molecular mixture. We can see how it's going to smell. What we can do is then find a set of components, which we call odor primaries, that can be used to mix any odor that you can perceive.

And that's what we're working on now. And about a month ago, so this is in collaboration with a lab of Jonathan Williams and Max Plank in Munich. Jonathan Williams is an atmospheric chemist, but he's really good at using GCMS, these tools that measure molecules. So Jonathan Williams measured odorance in Germany, transmitted the information to us over IP.

We fed that into our algorithmic framework and recreated it from a device that mixes primaries. And we tried to do four different odorants in our proof of concept test. One of them was rose and we failed at recreating rose. We in fact recreated something that had a precip but most people perceived it as bubble gum. The second one we tried to do was a niece and we failed at recreating a niece and most people said it was cherry, which is not very far, but it failed. The third was gasoline and we were slightly but significantly better than chance at recreating gasoline. And the fourth was violence and 15 of 16 people sent violence.

So the first order ever transmitted over IP as violence and we did that last month. Of course, this is not anything near a practical solution. The device that Jonathan was using to measure is a $1.5 million device bigger than this table. That's right, I remember when VCRs half the audience won't even know what that is. VCRs were like this big. So we're all good. I'm all good with the prediction that I will come down in size and cost.

Yeah, I was saying, you know, don't hold your breath for this to be on your table tomorrow. And, you know, again, even, you know, all we have in hand is this very initial proof of concept. You know, it doesn't, it's not not even close to being a paper we are submitting because there's still lots of work to be done. But we're on the path. We're on the path.

And Google will probably beat us to it. They got a lot more. You seem pretty dogged in there. Yeah, but they have so much more resources that at this stage, and they've already published two papers from that effort that are good. Yeah, you know, they definitely have a lot of dollars

and a lot of people, a lot of good neuroscience and other biology engineering graduate students and post-docs go there, but the real question is, are they getting the best people? Because as you and I both know in science, the oftentimes it's small groups of the very best and most creative people that can outrun and outgun large groups.

And here I don't have anything against Google. Right away. I know. I use it all the time. I'm not a betting man, but I would put my money on Google on this race, but I'll try and give them a run for their money. There you go.

That was, what seems like most of you just want to see the problem solved regardless of who gets there first, what I'll say is you better get going, Google, because no must be in peace humble and he's dogged. So better, better get cracking. There, we just cost the weekends and broke up the relationships and a bunch of signs that I remember when I was a graduate student at Berkeley. I remember hearing there was a guy in our common friend, Irving Zucker's lab that worked 100 hours a week.

So I was like, oh, I'll work 102 hours a week, which was not a good choice, but in any case, it's abundantly clear that you're making progress here. And I go to some of the earlier discussions we had, and I think we're not just talking about transferring recipes and smells of food, gasoline from people watching the F1 race or something, but thinking dating apps, thinking, nowadays everyone knows that when you travel and you wanna see your family, your grandkids or kids,

you better to get on FaceTime and see them or zoom than to just hear their voice. We're all starting about being able to smell them. I'll tell you more than that. I'll tell you more than that. I mean, we're talking now of trying to achieve the olfactory equivalent of circa 1956 black and white TV, okay? Basically, right? I mean, you know, I'm not dreaming,

let's say, of being able to transmit to you the difference between a Cabernet or a Marlou, right? But if I can generate something that's vaguely wine, that will be an amazing success from my perspective, right? But jump ahead in your imagination to 4K order transmission, then medical diagnostics is what you want to be talking about. Because in this is this is over extension, but you can almost say that every disease will have an

order. I mean, every disease is a specific metabolic process. Metabolic process have metabolites, metabolites have a smell, olfaction, once it's digitized and high resolution, which again, in our hands, it's not going to be, I mean, we're talking, you know, in my retirement, maybe I'll read about this one day if I'll still have vision. I mean, this is not close, but when olfaction digitization is brought to the equivalent of 4K vision and audition that you have now, then it will be in medical diagnosis. You'll have, excuse me for the imagery, but you will have an electronic news in your bathroom.

Each one of us will have in the toilet, and it will be doing diagnostics all the time. we'll have in the toilet and it will be doing diagnostics all the time. And that's where it's going to go. But again, not anywhere in the very close future. Well, it's certainly an exciting proposition and I'm delighted that you and other groups who are so strong are working on it. I have really am. No, Mike. I want to say thank you for your time today.

First of all, this was a tremendously interesting conversation. We touched on so many things, hormones, smells, the architecture, the olfactory system. I know that people listening to this are realizing, but I'm gonna say it anyway, what an incredible gift you've given us in, as a expert in this field, giving us this tour of the work that you and others who you credit so generously have

done to elucidate this incredible system that we call olfaction and chemosensation. Also just for the incredibly pioneering work that you've done. You know, I don't have many heroes in science. I have heroes outside of science and a few in science, but I'm gonna purposely embarrass myself a little bit by saying that from the time I was at Berkeley and I then saw that experiment being done of people foraging, appalling scent trails. And then until I was a junior professor,

I used that in my teaching slides in a class that I taught that was sort of the early origins of this podcast in many way. And over and over again, when your laboratory publishes papers, I find like, this is super interesting, super cool and I find myself telling everybody about it and that's really what I do for a living is I learn and then I blab about it to the world.

So thank you so much for the work that you've done in the work that you've done and the spirit that you bring to it. Whatever drives that spirit as the great late Ben Baris used to say, keep going because we are all benefiting tremendously. And I also just want to say that, you know, for people listening to this, the spirit of science is one of, as you mentioned, there's complex politics and all these things, but it's absolutely clear that you delight in the work you do. And so I delight in it. I'm grateful for it. I'm grateful for your time today.

And so on behalf of me and many, many people listening to this, I just want to extend a huge debt of gratitude. Thank you so much. Oh, so I'm blushing. I don't know if this doesn't come across on the radio podcast, but thank you so much for very warm words. I mean, you know, as you know, when you work in your lab, you don't, there's these moments

where you suddenly discover that somebody is like, cares a bit about it, and those are always very rewarding moments because usually you function without that. I mean, I guess that's one of the things you need to be a scientist is to have the, you know, the drive to work without that because it comes only rarely. There's immense gratitude and appreciation for you and what you do from me and now I know from a large segment to the world as well. So my only request is that you come back and tell us about the next results. Sometimes not too long now. Yeah, well, I'm going to catch you

live now, although you have the power to edit this. I guess that's not fair, but first you come visit us in Israel and tell us both about the science and the public science work you're doing and then I'll come again. I had a good bargain and I enjoyed it. Delighted. Thank you so much. Yeah, pleasure. Thank you for joining me for today's discussion about olfaction and chemosensation with

Dr. Nome Sobel. If you'd like to learn more about the work in the Sobel Laboratory, or read some of the papers described during today's episode, as to learn more about the work in the Sobel Laboratory, or read some of the papers described during today's episode, as well as learn about the current and future projects in the Sobel Laboratory, please go to the link provided in the show note caption. If you're learning from and or enjoying this podcast,

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