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

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

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Andrew Huberman, Noam Sobel
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May 1, 2023
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Episode Transcript
0:00
Welcome to the huberman Lab podcast, where we discuss science and science based tools for everyday life. I'm Andrew huberman and I'm a professor of neurobiology and Ophthalmology at Stanford school of medicine. Today, my guest is dr. Gnome Sobel,
0:17
dr. Nam Sobel is a professor of
0:19
neurobiology in the department of brain Sciences at The weizmann Institute of science. His laboratory studies olfaction and chemo. Sensation olfaction is of course, our sense of smell chemo.
0:30
Sensation is our ability to respond to chemicals in our environment. Today, we're 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.
1:00
For 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 stress, they are their hormone levels things that operate at a subconscious level, on your brain and nervous system, and the impact, your emotions, your decision making, and who you choose to relate to or not to relate to you. Also, learn that tears. Yes, the tears of others are impacting your hormone levels in powerful.
1:30
Always, you will also learn that. Every so often actually on a regular schedule, there is an alternation of he's 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
1:52
the list of things that dr. Gnomes sobel's
1:53
laboratory is discovered that relate to everyday life and that are going to make you say, wow, I can't believe that happened.
2:00
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 laboratory through a rather odd.
2:30
Observance, that observance took place when I was a graduate student many years ago at UC Berkeley at the time. Noma, Sobel was a professor at UC Berkeley. As I mentioned before, he has since moved to the Weisman. Well, I was walking through the Berkeley campus and I saw people on their hands and knees but with their head very close to the ground, and their eyes were covered, their hands were covered their mouths were covered and only their nose was exposed. And what I was observing was an experiment being conducted by the Sobel laboratory in which humans were following a
3:00
Trail. That Central was actually buried some depth underneath the Earth and yet, they could follow that scent trail with a high degree of fidelity. It was from that experiment and other experiments done in doctor, sobel's laboratory at Berkeley. And at the weizmann, involving neuroimaging and a number of other tools and techniques that revealed the incredible power of human olfaction and humans ability to follow scent Trails if they need to. And that, of course, led to many other important discoveries, some of which I alluded to a few moments ago, but you are going to learn
3:30
Learn about many, many other important discoveries in the realm of olfaction and chemo Sensation that have been carried out by dr. Silva'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 roles at Stanford. It is however, part of my desire and effort to bring zero cost to Consumer information about science and science related tools to the general public in keeping with that.
4:00
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6:00
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pillows and now for my discussion with dr. Gnome Sobel, dr. Sobel known welcome. Thank you 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.
7:00
The overlap at UC Berkeley some time ago, although we did not meet and
7:05
we lived in the same
7:06
apartment. 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 love for you to share with us all about the amazing landscape of chemo sensation in.
7:30
Allure olfaction or sense of smell and some related perceptual abilities or subconscious abilities, including pheromones Etc to get everybody on the same page. I 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
8:00
That we are sensing through this thing and for those of you listening them and not watching, I'm tapping my nose that we are not aware of, you know, that 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
8:24
play. So, you've asked a lot of questions at once, you know, I'll start with
8:30
A little comment on the way you said, smiling through our nose, which we need do, but we also smell through our mouths. Actually, there's a process referred to as retro nasal olfaction, where odorants come up through our the back of our throat and out of our nose. The reverse way. And we smelled things that way as well. And in fact, a big part of the contribution of olfaction to food and taste comes from that from retro nasal olfaction, but primary olfaction
8:59
Is referred to as Ortho nasal faction that is through our nose. We Sniff and sniffing is a big thing. Well, I have a sense. We might talk about that a lot today, and 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 news distance in the human of about six or seven centimeters to about here where they interact with I will you use the word sheet of
9:30
Receptors. But she is a bit misleading here. It's not a sheet. It's very convoluted. We have about 7 million, such receptors lining, a structure known as the olfactory. Epithelium, this is the sensory surface of the olfactory system though Factory. Be Liam again about probably about six or seven million receptors in the human in the human probably of about 350 different kinds so that's amazing. That means a meaningful percentage.
10:00
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 6 or 7 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 billion receptors in their know.
10:29
Knows which is why they're so amazing. And this number was, you know, it's sort of propagated through the literature and, and our lab has written over the years a few review chapters. And we were repeatedly writing the olfaction chapter for a very large. One of these large textbooks, that gazzaniga Handbook of cognitive Neuroscience. I think it's called, and, and we have that in there as well somewhere. And one time, when we renewing the chapter for a
11:00
New version of the book. I told the graduate student, who's leading that at the time, are I assure you? And 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
11:18
textbook.
11:19
And we found the author of The Textbook and we wrote her and I said, look, there's this thing in the literature of a billion receptors in the Bloodhound. Where did that come from?
11:30
And as far as the, she answered me and you know, I was hoping to get a reference, right? But it wasn't a reference and and this is where it really becomes funny for us. Because she said, I I was once at a lecture of an old-fashioned geneticists, 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 Durham lasted is in the building next to me. Okay. He's in
11:59
Weitzman Institute, genetics. I mean, he used to be, he's retired now and he had meaningful contributions in the history of olfaction. So I picked up the internal phone and I said, hey there on, you know, did you say that there's a billion receptors in the Bloodhound nurse and he said, what's a bloodhound? So this is totally made up, right? It totally made up and it proper you did. I mean, you can you can probably go into Google and type like a billion receptors in the bog down and you'll get a lot of hits.
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But there was absolutely no evidence for
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that. Amazing. And not just amazing in light of what it tells us about olfaction and Bloodhounds are otherwise, but amazing, because it sheds, light on just how much of what is in textbooks. Scientific and medical is absolutely
12:46
wrong things. Things propagate and you know, you set yourself and right so we fix that and that version of rate of the and and so to finish the line. So that so odorants interact with these receptors here in our AP helium. Where the
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Undergo, what is referred to as transduction. That is the odorants our docket, a receptor and turn into a neural signal or 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
13:21
from RBC, Liam, right here, behind the forehead, no it will. Ya here
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through the
13:29
In this part of our skull, an area referred to, as the cribriform plate, which is preffer ated, 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
13:57
structure ahead, hit type trauma. Well,
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well, yes,
14:00
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 contrecoup injury. So as your listeners, probably know, our brain is floating in liquid and CSF and cerebrospinal 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.
14:29
It's sort of crashes, it can crash against the front of the skull, which is why you also have in a contract wintry, you also often have frontal damage but what happens is that this generates a shearing motion on the cribriform plate. And the olfactory nerve is severed and if it's completely severed, it's lost forever because my understanding is
14:50
that the olfactory Sensory neurons can are among the few central nervous system neurons in adult humans that can regenerate. So
14:59
Replenish
15:00
themselves, right? So I'll again, there are a few questions? Yeah, that's okay. We so
15:04
first of all, we will spend any plate
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simultaneously. 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 cell level at the epithelium, they won't manage to find their way back to the bulb. If if you have partial or something left or something, shows up in a short while
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After the injury then you have a good chance of recovery because
15:33
they grow along the trajectory of the other accents or pioneering the way for them
15:37
assuming him. And so basically, and basically the time frame and you know, it's funny, I get a lot of emails on this and 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 and basically the rule of thumb is that if you don't get it back,
15:59
Within a year to a year and a half, you'll never get it
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back. My understanding of the statistics on olfactory loss in covid and and and other viral type infections, is that first of all, I had I experienced that when I got covid,
16:13
including total anosmia
16:15
for one day and not total. It was just, there was a remnant of an ability to to smell your scent 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
16:29
Not pseudoscience because there's a number of papers published about this on PubMed that alpha lipoic acid can accelerate the recovery of of smell. Yeah. And and so that's something that it worked successfully for me. I'm not saying that that's the only
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or I don't know if it worked successfully for your if you would have recovered anyway. I mean, you didn't do a control group that I was not willing to do the control experiment? Exactly. Yeah, let me say two things on this front. First, the dean on the alpha lipoic acid is yeah, it's not
16:57
overwhelming. Yeah, but but losing your son.
16:59
The smell is overwhelming. Yeah you know I know it so and I think people know that super it one
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word about the smelling the lemon and this is a I'll take that opportunity to share more information when we smell things. It's the result of War, sensory, subsystems in the olfactory system long. So you have several chemosensory sensitive nerves in your nose. A primary one beyond the olfactory nerve is the trigeminal nerve, the fifth cranial nerve. So the trigeminal nerve
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As sensory endings in your nose, in your throat, and in your eye, it has three branches. That's why an onion has smell and burns your eyes and burns in your throat. Is that why trigeminal? Yeah, the
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tearing of cutting an onion
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is trigeminal. Exit, trigeminal reflex, amazing. We
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talked about trigeminal in the context of headache, during a headache
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episode. It's a trigeminal reflex. So the lemon you were, smelling may have been a trade, geminal sensation. So smelly, the lemon with
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my eyes is what you're saying? Well, no your nose but with
17:59
Trigeminal receptors and not your olfactory receptors. So in within, you know, olfaction researcher jargon. There's what we refer to as pure all facts, these are orders, that will stimulate your olfactory 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 puerile fact tent, vanilla isn't known, puerile fact, that these things have no trigeminal
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activation.
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But as long as we're on this topic and will weave back and forth, but I'm glad we are on the top of it 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 where whereby if you have a partial or even a complete loss of primary olfaction, right? That one is encouraged to smell of a number of different smells I grew up studying activity-dependent. Why?
18:57
Ring of the nervous system, it makes total sense to me. Why keeping neurons active keeps them alive. This is not fire together, wire together type thing by the way, that's a quote from Carl Schatz. Not Donald had folks or me.
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But this is about keeping
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neurons electrically active this case. Olfactory neurons in order to maintain their connections because otherwise they will
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die.
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Olfaction 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 lipoic acid. And so that's a real thing and 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 or your, you know.
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Makeup cabinet or whatever and smell them, you know, attentional and constantly and sniff them and 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 you can study many things through olfaction and indeed, one of them is is an is neural regeneration because the olfactory neurons are really the only neurons that do that.
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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 Iran. I think somewhere around 2014, where to address this question, I just really like the idea of doing that, what the authors did was
20:48
As look at in post-mortem, they looked at low levels of c14 in adults who are exposed to Atomic Bomb experiments, right? So you have, you can actually look at these at these neurons and and time them based on exposure to radiation. And that paper, suggested that, that there's not as much turnover in the human or factory.
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Bob is, there isn't other mammals other lines of data suggests otherwise. So this is kind of a debated question. Is to what extent an urgent degeneration you have in the human olfactory system as opposed to other mammals. But that was just really cool paper. I think of doing
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that. Fascinating, I
21:40
should I finish that the path just to Lisa. So we said to information, then synapses at the olfactory bulb from from
21:49
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 body.
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And this location is referred to as a glomerulus or an employer glomeruli. And and that may be a slight over simplification, it's in fact to glomeruli there is a mirror, sort of a mirror cut line. And so all the receptors of one subtype will converge to to murmur glomeruli on the olfactory bulb. So you end up having to glomeruli the reflect that one receptor subtype. And so if in this is as far as I'm giving you an out of the textbook view of
22:48
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 view of how things work is that every such receptor subtype is responsive to a small subset of different molecular shapes. What's sometimes referred to as oh, topes the molecular aspects of the odorant. So each receptors is responsive to a different subset of Odo. To Ops, let's say, 10 and each o taupe will activate a different subset of
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actors. So potentially you have this insane comment and torrox of this potentially 350 dimensional space in the human potentially.
23:27
But then because of this convergence you end up having on the bulb in a way a map reflecting receptor identity. So let's say this coffee activates receptors of type 1 3 & 7. So the glomeruli of receptor is 13 and 7 will light up quote-unquote when I smell the coffee and if you can take a snapshot of that theoretically you would have the map of coffee and so on and so forth. This this is sort of the textbook view of how the system works and
23:57
and then information goes from the bulb to several Targets in the brain. I mean, what is it fair to is primarily Factory cortex is perform cortex and into renal 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 information projects widely from there.
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And as far as people understand the map that may exist on the bulb doesn't exist in the rest of the brain. And then understanding of how coding occurs in the rest of the brain is is murky.
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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
24:57
My grandmother's hands or the smell of cookies in her kitchen.
25:01
At a minimum, it points to the fact that smell and memory are closely linked and you just mentioned a direct, you know, multi-station but nonetheless somewhat direct path from the nostrils to the hippocampus, one of the primary encoding centers of two new synapses away. Yeah which is which is a remarkably short pathway considering that for instance just by example because some of our listeners won't be familiar with this but some will that sound waves that you know are transduced into neural signals at the level of the
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Rear 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 to the memory centers. Is there any just-so story or real objective truth to the idea that olfactory memories are formed more easily or maintained longer or more robustly than other sorts of memories?
25:58
So yes but first
26:01
Why should I should say that? I'm not an authority on all Factory memory. It sort of it will have to remember is a huge field research and somehow our lab has never really
26:14
Gone much into that. Although, again, the same student I happened to talk about before they are Irish Rune. Who's again? Now A Faculty at Tel Aviv ran a study of paper with. I think we published in current biology, biology called the privilege representation of early. Olfactory has 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 what you in fact.
26:43
Are. So there's something about the first exposure to a smell in terms of the brain and coding that etches it into our being. And, and this is an effect that has, you know, it has Echoes. Of course in literature. I mean, you know, the the biggest cliche in the system bring up the proust effect, right? So the priest effect is when he ate the Madeline and it immediately the taste and smell immediately reminded him of an event in his childhood were the same Madeline.
27:13
Appeared. But, 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
27:24
authority, but it does sound like there's something special about olfaction and that doesn't mean that there isn't something special about Vision or audition. Each one has its own unique. I'm the last our use it. There's something
27:37
special about the time. My students make fun of me because they say,
27:43
And there's some truth to that that I try to explain everything through the olfactory system. I mean, for me, everything is all Factory. So so
27:50
yes, through the lens of the nose. I'd like to take a quick break and acknowledge one of our sponsors. Athletic greens, athletic greens. Now called a G1 is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs. I've been taking athletic green since 2012 so I'm delighted that they're sponsoring the podcast. The reason I started taking athletic Greens in the reason I still take athletic greens
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It tastes great. If you'd like to try athletic greens, you can go to athletic greens.com huberman and they'll give you five free travel packs. That make it really easy to mix up athletic greens. While you're on the road, in the car, on the plane that cetera and they'll give you a year's supply of vitamin D3 K to again, that's athletic greens.com huberman to get the five free travel packs. And the year supply of vitamin D3 K to when I was at Berkeley, I was walking across campus one day and I saw
29:13
Saw.
29:15
I think students but I saw people on their hands and knees with goggles on gloves on and I think their mouths were covered to was covered was covered and they were walking. Well, they were crawling along the ground 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
29:39
fire, right? One or the other would not be sufficient. Please don't run this experience
29:43
that kind of place.
29:44
Um, yeah, but nonetheless, a paper came out of a few years later, describing the results of what turned out to be your experiment that your laboratory was running, which was having people follow an odor trail with their nose. And and my understanding is that people can improve their ability to track sense, quite robustly, especially if we deprive them of vision and somatosensation that is too.
30:14
And some other Sensations, maybe you could just tell us a little bit about that study. And and for, I think, in our audience, I'm suspecting that many people have a keen sense of smell various. I have a family member who just like detect any - you know, putrid odor in the environment, but also go to 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
30:44
As possible in terms of training up or improving our ability to smell and perhaps in the context of that study, if you
30:50
will, yes, okay, so first before even talking about improving, just
30:55
off the bat
30:57
humans have a remarkable sense of smell and this is something again in our lab. We already said, we know. Yeah, we know this. This is old news, but but to people who come from different worlds, we have to reiterate this sometimes when I give, you know, public lectures to not olfaction audiences, I reiterate this.
31:14
Humans have an utterly remarkable sense of smell to put that a bit into, sort of, you know, things that you could there are tangible. So for example, mercaptans which are added to cooking a so that we smell it because otherwise, it wouldn't have a smell so that the smell of gas is not the smell of gas of propane. It's an additive. We're trapped. Yeah, it's a Captain Alfred. Yeah, so so our detection threshold that is the level at which we can detect it.
31:45
Is zero point two 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 an odorant in our lab called extra Tetra. You know that our participants can detect when we have it mixed at 10 to the negative 12, molar in the liquid phase to give you a real sense of that. We
32:14
Did the math. If you would take to Olympic-sized swimming pools and you would pipe it, 1 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, you know, remarkable really up there on the mammalian World we're not.
32:42
A bad mammal and olfaction
32:46
and and
32:49
beyond that we can 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 cheerful in because I'm your guest from The weizmann Institute of Science in Israel. But before going back to my home in Israel. I was a faculty at UC Berkeley and Helen Wells.
33:12
Neuroscience Institute. And this study was done during that time and we were on a lab picnic and we were having indeed one of these sort of lab discussions arguments on what humans can and can't do with their sense of smell. And and I said that humans can 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 regional picnic video. We have it and a graduate student, by the name of
33:41
Christina's olano, a brilliant graduate student. At that time, who is now she's now a professor at Northwestern and she's really leading the field of olfaction Imaging today, but she was the volunteer and we dragged a chocolate bar across the grass and blindfolded her and checked. If she could track the track, we made with the chocolate, which he did very effectively, right? And as far as
34:06
I saw at the starting point of the line
34:08
or I think we did, I don't exactly remember what we did on that sort of
34:11
Nick try out. 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 is a lab bed and way that, that I said to my students. Okay, we have to make this into an experiment, put in an experimental setting and and and quantify, what's going on. And they all said that, it would be an interesting that was the bad and I told him it would be in nature, which is a bet I want.
34:41
In this case nature of questioning, one of the 83 Apex Journal. So and so he was it was Nature Neuroscience Affair. But but so then we turned it into an experiment and what the experiment was is that we brought in participants naive. Participants not not graduate students from our lab completely deprived them of any other sensory input. So, we block their eyes, we block their ears, we blocked, everything we bought. What they were wearing? Heavy gloves, you know, they can't sense anything.
35:11
And we generated a consistent order path in the grass which is what you saw. We did that by burying twine under the grass and odor, impregnated twine. So that way we could generate a consistent order Trail. Every time was it in at the base of the grass or in the dirt it was buried. It was buried under the grass, really? Yeah.
35:34
Yeah. Wow. And did not know
35:36
that it was buried under the grass and we conducted aerial photography.
35:41
And participants also had this sensor pack that they were wearing where we measured nasal airflow in each nostril in real time. And they also use something called rtk GPS, which is a way to lay our radio frequency grid over the GPS grid so that you have millimeter resolution in space. Basically, it's used by surveyors mostly so that we can track behavior and we found a few things.
36:11
He's doing this one. Is that people could just do this right off the bat? The second thing we found that is when we train 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 send track. Of course you can call as fast as dog can run, but you as fast as you can crawl, you can send track.
36:39
And then to sort of add what made it really interesting from a systems neuroscience perspective is 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
37:09
Team two, separated our nostrils. And we compared 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 your two separate. Totally separate nostrils. By the way, the system I described before of your, if you feeling them in bulb and and connection, the cortex, you have two of those, right? It's completely unilateral. Well, almost
37:38
Completely, you know, I roll system. There are some
37:43
Very small exceptions to that,
37:44
but representation on both sides of the brain much in the same way we have two eyes were not a cyclops we can gain depth perception information. We can perceive motion better as a consequence and a number of a depth especially stereopsis and
37:58
I can locate sound because of the difference between our ears and how head blocks them between. And
38:05
another question about the mechanics and strategies that you observed because I think there's information about the system, the brain,
38:13
As a consequence, were you in a position to measure sniffing frequency? And that specific question. I have is, were people doing something along the lines of a quick sniffing or a like a, you know, a long-range role in. So, inhale, you know, we didn't. So yes, we were measuring sniffing and recording it. And, and we have all the data.
38:38
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 didn't 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,
39:00
but I'm sure if it was a major component of it, whatever
39:03
isn't? It definitely wasn't a major finding the sniffing.
39:07
Behavior in the paper. Although again, we, you know, sniffing behavior is a huge portion of our life and lab and and it's it's taking us to places and it's re-emerging. Now in our work we're doing tons of sniffing work, you know. I can share with you something that I think will interest your your listeners and viewers as well. And we think is is really one of the most
39:37
Overlook things in Neuroscience is do about you. I invite you to do the following experiment. So, occlude 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. You know why? That is? No. And it was the next question
39:54
on my list. They don't
39:55
feel badly about not knowing where that is. Most people don't.
40:00
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
40:14
average in an absolute way. Or is it kind of like a sine wave? Like gradual shift to that one and then gradual shift back, it can
40:20
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.
40:29
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
40:42
And it turns out that this is linked to balance in the autonomic nervous system. So as you and your listeners, know we have an autonomic nervous system that has a sympathetic and parasympathetic component to it and they're in balance or imbalance in many diseases for example, and this interplay between the auto between the sympathetic and parasympathetic nervous system drives the switch from left to right nostril, just to remind people sympathetic nervous.
41:12
Tim 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 it 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
41:39
perfect. So now, imagine right. Imagine imagine you would
41:42
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 have this, I cycle. All right? And that was linked to autonomic arousal. I assure you, you would go to PubMed, they would be five million papers on the I cycle, right? And the I cycle in every disease, you can name and what it denotes and what it tells us, and what we can do with it, you have exactly this marker, you're walking around with a marker on balance in your autonomic nervous system and we do nothing.
42:12
With it. So we're in fact now doing a lot with it. Okay, so we built we built a wearable device that is pasted to your body and measures air flow in each nostril, separately and logs it for 24 hours, and we're collecting these 24-hour recordings. We're calling it the nasal halter. So we measure with the nasal halter, and, and we're finding it as a disease marker. I can, I can give you a nasal halter.
42:42
Aunt is an adult, and I can say this is work by team. Now, Soroka, graduate sooner. I'll have now, I can so 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 on ritalin or not. So I can I can measure your nasal airflow and see if you are or are not with ADHD and if you are not on riddling,
43:07
incredible, I have a couple of questions about this.
43:11
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 maximal on one side versus the other is that simply reflective of an overall balance. He lets maybe. Is it the hinge in the Seesaw, or is it the tilt of the seesaw?
43:42
So I don't have a good answer. I don't have a good answer. I mean, you know, I can give you sort of a, you know, I could say that to some extent, right nostril. More open is more a sympathetic and left nostril. More open is more parasympathetic, but that wouldn't be very correct. I mean, you know, I'm sure that it's, you know, the Yogi's are gonna be all over
44:02
this. Oh wait, I as I get this crike, my lab does do some stuff on on breathing and the Yogi's are always saying okay, you know, because there's this thing I don't do yoga anymore by not for any parent.
44:11
I am, but where they'll have you breathe through one nostril or the other and I've probably been asked this question on social media, ten thousand times.
44:21
Oh yeah, I'm going to become Public Enemy. Number One of the Yogi's right now. Soul, is it really? So we we,
44:27
they'll come at me with yoga mats, which are not very dangerous.
44:30
We really. So since we're so interested in this mechanism, one of the things really like to know how to do is, is to gain control of it somehow and there's this world out there of yoga who claims
44:41
Have control over this. So we said, okay, let's bring like really serious yoga practitioners and see if they can shift their nasal cycle from left to right by Will alone right now by manipulating themselves somehow. And and if yes, you know, we'll learn from them. How they do this and then we might, you know, use this to cure ADHD or whatnot, right? So so we posted like on all the lists of like the yoga teachers and have this parade of yoga, teachers walking into our lab is this
45:11
This was one of the strangest. A lot of Sandalwood odors and bare feet, right white clothing and so on and so we study 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. An awesome. Yeah. But by the power of thought alone and you know how many of 14 succeeded
45:42
Zero including including one, you know, there was Extreme Motors. We have this guy who, you know, and we're recording and we know how to grow this really well. Right. And he's sitting there saying, yeah, I'm switching now and I was it's switching and, you know, you're looking at the Monitor and no, no, it's not switching. And and so no, no yoga teacher that we found could willfully switch between left and right nostril flow.
46:08
And yet, there they are convinced that they are. And I have to imagine there.
46:11
Not trying to, you know, there's no incentive for them to lie,
46:14
right? Yeah. No. I 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 but none of them can do it
46:25
given that the alternating flow through one or the other nostril, is reflective of the autonomic nervous system has this two-and-a-half-hour periodicity.
46:34
If I suddenly enter about of stress, for instance, does it switch? Because that's reflective of the autonomic nervous system. And 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 hazard that unilateral smelling through or unilateral nostril. Smelling periodicity there 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 this
47:02
shift? So you've
47:04
Concisely now worded aim to of a grant 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 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 it there's huge individual differences.
47:33
As we just started this, we built the set up just now and you have a lot of meat to work with there because there's a lot of individual differences. Your it's capped at 3 minutes, so big for safety reasons because you have, you have participants putting their hand in 2, degree celsius water, but they'll be participants will pull it out at like ten seconds, nine seconds and then you'll have you'll have three minutes as well. So there's lots of lots of and, and already. And so now I'm sharing pilot data with you so I don't know too.
48:03
To this might you know when it when this ends up being published in might be the opposite. But so far it seems that the exposure to cold generates a shift in the nasal floor and is on
48:12
balance. So, autonomic arousal can drive the shift potentially earlier, you were describing the architecture of these smelling systems and you mention these glomeruli where the olfactory receptors converge right in the bulb. And then later, you mentioned that the system is unilateral. But with a mere
48:33
Annotation 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 clearly. 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 the alternating nostril air flow.
49:03
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
49:33
Your thoughts on why the information would switch from one side of the brain to the other at all?
49:39
Yeah, I don't think, I don't think that that the nasal cycle isn't all faction story.
49:49
So, so I don't think that that, this was shaped by the olfactory system, nor do, I think this has major impact on olfaction. I think the nasal cycle story is a different story about brain function. So, you know, we have, we have this set of
50:10
Pet Theory. We're calling now the the sniffing brain approach where
50:17
We're basically.
50:20
We think that that nasal inhalation is timing and driving a lot of aspects and patterns of neural activity and cognitive processing. And and this theory is is olfaction inspired and it's beginning. That is I mean if you think of the mammalian brain right? It's
50:40
Which which evolved from olfaction it's sitting there and in all faction because olfaction depends on sniffing. You have this situation where you have a, you have a sniff, you have information and then flat nothing, right? And then you have information and then nothing. So information processing is is 121 linked to nasal inhalation.
51:05
And and we think that that this property evolved to be meaningful and brain processing in general, not only of olfactory information but of any type of information because the brain evolved in this way, in this way that it processes information on inhalation onset. So study led by offer Pearl from our lab 23 years ago. We looked at at something completely not all Factory we looked at visual space.
51:35
Processing. And we compared visuospatial processing on inhalation versus exhalation. And the brain does this completely different on inhalation versus exhalation you you're in that particular task people performed significantly better on inhalation versus exhalation. What was the task was in an olfactory? Do know, it's a visual spatial tasks. So this is passed. We're the the specifics of the tasks were that you see a shape and you
52:05
have to determine if it's a shape that can or cannot exist in the real world. So some of them are these like our shapes like you know, where one facet doesn't reach the other facet. The Impossible figure is that yeah. But-but-but structural shapes, not not and and so a pure visual spatial tasks. We intentionally went for a task that is not considered a ventral. Temporal task and olfactory cortex task in any way.
52:33
And, and people performed much better on inhalation versus exhalation. At doing this
52:39
task, was there a both nostrils? Occluded version where people were forced to mouth? Breathe.
52:44
Yes. And in this particular task, they also did better on mouth inhalation versus mouth exhalation, but the difference wasn't as pronounced as it was with nasal inhalation versus exhalation.
52:58
So bet you I'm a big proponent of nasal not mouth-breathing. Whenever
53:03
Possible. Sure. For many health related Reasons. I'm a big fan of the book. Jaws a hidden epidemic written by colleagues of mine at Stanford familiar with it. Yeah, and this idea that people who mouth breathe experience, more colds, more infections of various kinds, it's not good aesthetically. Or for the dentist Dental chur. I never know the teeth and gums and stuff.
53:24
Yes, sorry my my dentist is going to come after me. I need to go to the dance. Anyway
53:29
the that nose breathing is great for your
53:33
Health relative
53:34
to mouths. It's, I think it's also good for your cognition, not only for your dental health. I think that that news breathing shapes cognition and and there are other labs who are finding the same again, Christina's Delano is doing work on this line sheet. She had major contributions here and and you on linstrom is doing work on this line. There's lots of studies suggesting that nasal
54:03
Inhalation is timing cognitive processing and modulating it.
54:09
Incredible, perhaps not surprising given what you've taught us about the olfactory system, I mean that these two holes in the front of our face, he's nostrils. I mean our Pathway to the brain, right? I love to tell people because I work on the visual system in my lab, that your eyes are two pieces of brain extruded from the cranial vault, which they are there. The retina is any anyhow. And, and then you never look at anyone the same way again. It's kind of but the the olfactory Sensory neurons
54:39
Is are right there at the top. So those Caverns that we call nostrils and they are brain.
54:44
Yeah, definitely. It's the only place where your brain meets the outside world because in your retina they're protected by a lens and here, here you have neurons in contact with with the world. This this actually has been the source for some theories on a potential route for neurodegenerative mechanisms. So as you may
55:09
No 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 lost 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 nonspecific. 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
55:39
You can have many reasons to lose your sense of smell and and so on. But but all Factory 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. Interested, it's not of course mean,
56:09
Three more widely accepted theory of any type, but it just highlights this notion that that the nose is a path to our
56:17
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 retina is often associated with other forms of central degeneration, Alzheimer's, Parkinson's cetera, as it's a little more invasive than what you're describing.
56:39
Typing. I'm beginning to wonder why we don't get have a olfactory task. Every time we go to the doctor that would allow tracking over time because 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.
56:57
The next that's a really bad time. Yeah, that's a
56:59
bad sign. And so what we're talking about something completely non-invasive and could be relatively Pleasant to innocuous depending on the owners use.
57:07
So, yeah. So so
57:09
First, I can answer that right in 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 olfaction has not been effectively digitized, right? So if you need to generate, you know really precise visual information, you can buy a monitor for you know, a hundred bucks. That is that there is a solution of the visual system basically and if you want to generate auditory stimuli really precisely than you can buy an amplifier for
57:39
or, you know, maybe a bit more than a hundred bucks but not that much more and you'll be at the resolution of the auditory system.
57:46
In our lab, we build devices that generate orders, we call them off, hm, which is a misnomer because they don't measure anything, but that's what they've always been called. So we call them off am as well. And we've already built at least one olfactometer, they cost a quarter of a million euro and it's pathetic, right? So it just 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
58:15
The utterly poor control of the stimulus. Mind you to some extent. It has happened in that there are standard clinical tests of olfaction, basically, to that sort of control the world. In this respect, the older one is test called the UPS it which stands for the University of Pennsylvania. Smell identification test. It was developed by Richard Doty in pain and it's a test where you scratched and sniffing, and it's a for alternative forced choice.
58:44
Test with 40 odorant. So you have these 40 pages that you page through and you sniff and smell and, you know, it's been warm done, gazillions of tests. I'm always amused by it because so Richard Doty made a ton of money on the UPS it but he needed it because he has a habit, he has a NASCAR. So this every time we buy UPS it's-- in the lab I said there's another gallon of gas into Richard Doty races, NASCAR it's not
59:14
Like, NASCAR, but like one lower than that, like I didn't know like some sort of formula a or forms a four-door some, he races a car. And so that's where all the ups it's--when. So I always feel good about buying UPS 80s because I know they're going to that good cause but keeping him in in 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 UPS it and Alzheimer's and Parkinson's and in a host of other diseases and there's a European
59:44
Version called sniffing sticks that Thomas who made it 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 and stiff but there's exist but they're not as is convenient, as is delivering stimuli and vision and audition and that's why you don't have what you've just suggested just, you know, another thing, another place where you don't have it, which I think is even more
1:00:14
Worm would have been even more meaningful is is you don't know, fashion is not tested in newborns right where vision and audition is, you know, there's this thing called congenital and ask me outright which is being without the sense of smell from birth supposedly congenital, which is a half a percent of the population. It's not a trivial number. Hmm. Not totally. Yeah, but nobody knows if that really is true because here's an amazing factoid.
1:00:45
Guess the average age at which congenital anosmia is diagnosed and this is, this is a horrible statistic for me for the way, I see the world, but what do you think? The average age of diagnosis is for congenital and osmium, five years, old age, 14,
1:01:01
incredible 14. So most people who are one, half of one percent of the human population. Presumably yeah. Is without the sense of smell and doesn't realize that until they're 14 years
1:01:13
old, I don't know. When
1:01:14
Realized it first, but it's formally diagnosed at 14 on average, which means some of them even later, right? And,
1:01:22
and right, so distribution, what, what do they suffer? Yes. So,
1:01:29
first of all the suffer socially, and there's a host of of deleterious life events associated with congenital anosmia, the die younger
1:01:45
The the so it's a it's this is work out of Ilona cry in Germany and, you know, amongst the various things that are predicted by anosmia is shorter lifespan but things like, you know, reduced social contacts reduced romantic social contacts. It's not a good
1:02:09
thing and do. They lack olfactory bulbs.
1:02:14
I'm presuming, they have noses and nostrils. There is a condition. I'm aware of where, where children are born without noticing this very rare. Yeah, very rare little Turkish on that because it's exceedingly rare,
1:02:25
but they're born with 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 or I should rephrase that have Remnant olfactory bulbs really shriveled olfactory bulbs.
1:02:45
But you know, nobody can say the cause and effect
1:02:47
here before we talk about the role of the the requirement for olfactory bulbs for olfaction, a very interesting topic and its own right? I am curious as to whether or not their endocrine system is altered because as we will 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.
1:03:15
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 to 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 and estrogen production, Etc. So are they hormonal e
1:03:37
normal? So some are and some aren't, and I'll be specific. So there is a condition known as common sense.
1:03:44
Drum, which is hypokinetic development in men. And in Kuhlman syndrome, they're practically all announced make. So, so to answer your question, yes, there's a direct link and and it materializes in comments and rum that said, not all congenitally. And also make individuals have common syndrome and not all, but almost all people have common syndrome are in aspic.
1:04:14
So common syndrome goes with and asked me how I think. So, there's a female equivalent of Commons or I mean, I don't remember its name,
1:04:26
it's not turn. It's not a in the Turner
1:04:29
syndrome family. I'm not sure. Okay. And I think it's also associated with an office Mia, but I'm not confident of that. But Commons is socio-economic Mia. So the answer is is yes. And and, you know, we can maybe
1:04:44
You know, olfaction and reproduction are tightly linked and they're tightly Linked In all. Mammals and we are big terrestrial, mammals and olfaction. Reproduction are linked in humans as well.
1:05:00
We will definitely get into that. I'd like to just take a brief moment and thank one of our
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huberman to get 20% off. I have a story. / question that I'd like to tell you ask you as a segue to that noting, of course the will get back to the, the requirement for olfactory bulbs. Yes. Or no for olfaction and this 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,
1:06:44
Ders, were my sister, my older sisters age as fortunate. So 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 for Stuff.
1:06:56
Get into trouble or what not, and often times, 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 close, like someone left this here. I don't know who it was. We were all more or less the same size and from the as far back as I could remember,
1:07:20
67 years old and onward. I could pick up a shirt or a jacket smell it and say oh well that's Eric eisenhart. Sure friend of mine there. I just gave us a more. Oh that's got Madsen 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 if I had pretend they hadn't if I had, but having never actually done the exercise of going and taking and smelling my friend intentionally right, okay?
1:07:50
I in fact, if anything, I had all the reasons in the world to avoid smelling the other young boy. Yeah, neighborhood. Okay. So yeah, 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 and or some other aspect of their chemistry.
1:08:15
Yeah. So yes
1:08:20
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 why Human Nature has a whore nature or culture or whatnot? Has as push this into the realm of subconscious and something we're unaware of but
1:08:49
We do it all the time and in 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, we look at human behavior, a lot. We try to look at it through our nose and in the way we look at what people are doing. You know we try to think you know, if I was a dog, what would I think of this? And, and
1:09:21
If you look at dogs, right? They've you know when they interact, the visibly sniff each other, it's very obvious. They walk up to each other and they sniff each other and yet humans don't typically walk up to a stranger and carefully snip them, right. I mean it's we're sort of obliged to sniff are our babies. That's considered almost something you're supposed to do and it's not culturally taboo to sniff. Our loved ones. It's sort of doesn't seem like an odd thing to do, but we
1:09:50
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 because we started looking at hand, shaking and shaking is this really odd behavior and it's not only in the west, by the way, is some people thinks it's only Western thing. It's not it's almost everywhere and and
1:10:14
There's really poor understanding of how this Behavior evolved like, where did where did this thing come from? So if you, you know, if you look for the Wikipedia version, right? Then they'll tell you that it's to show that you're not holding a weapon in your hand, but there's really no good evidence for that. It's a bit like the trillion 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 handshaking and, and we noticed or it seemed to us that were noticing
1:10:44
That people will shake hands and then
1:10:47
go like this, and like this. Those of you listening now, Jim know, it was taking his hand and and wiping it on his face yelling at her nose or touching myself side. Yeah, these
1:10:57
things. These things that we do all the time after a handshake. Well, so first of all, we do them all the time. Just period, right? The Baseline here is really high and we'll get to that in a second. But, but, but these behaviors that, you know, you could easily not notice, right? And and so we asked whether that's a real thing.
1:11:16
And this was a study led by you done framing in our lab at the time and what we did first. And if you want, we can link. So so this was published an easy 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 that you lied
1:11:36
in the show notes, captions as a link on YouTube and the other for platform Spotify
1:11:41
Apple. So, so what we did is
1:11:44
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 agreed, uh, 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, for the video. That's now on Eli.
1:12:14
And 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 forehead, or their chain or how many times they're a hand reaches their face. And by the way, that Baseline is not low. Okay? And then three months later, an experiment, you would walk into the room and would share.
1:12:43
Or a consistent text. It would be, you know we're still setting up our equipment in the other room are and so, just wait here, and we'll be right back with you. But in the meantime, just wait here. And the experimental went through this like 22nd fixed text and in half of the cases included a handshake. This was a new experiment or not. The one put them in the room so that it's the first time they met so it'd be a little I'm you know so and so they would put out their hand and shake their hand or not. Okay. And we did all possible interactions in terms of gender. So we match
1:13:14
Male participants with male and female, experimenters and female participants with female and male experimenters. And so, you had handshake and new henchy 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 uh it's unreal. The video is unreal. So interested in the hand goes to
1:13:43
Ooh, the nose. Now, we did a few controls here to verify that this is not a factory Behavior. One is unbeknownst the into participants. We measured nasal airflow, and, and people not only bring their hand to their nose, they sniff it. So in this is perfectly time, they go like this, okay? So they're sniffing their hand and an additional control study. We manipulated it. So, we built this little James Bond thing of a watch. On the experimenters hand, they could emit an odor and the experimenter didn't know what odor they were emitting and they could emit either a pleasant or a no.
1:14:13
Has an odor and we could drive the self sampling afterwards up or down. So, this was an olfactory Behavior, no doubt about it. I mean, we're quite confident that. So
1:14:23
people, in that case, people must have been sensing the odor on their own hand because they check 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
1:14:37
experimenter. Yeah, but I know, I think, I think they were sensing the ambient odor that came in with the hand that
1:14:43
At that joke and then that either drove him to sniff their hand more or less, the odor cloud and the express. Yeah, and there's an interesting thing going on here too because people didn't only smell the hand, the choke. They also smelled the other hand and 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 is on the same line and again to it to link to your childhood story of
1:15:13
On your friends. Bye bye. Smell study. We published just last year, by bhairav rebellion, in our lab. We're in bad 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, you know, is poorly described or is poorly described in the literature is
1:15:43
As as as an entity and yet anybody will tell you they know what you're talking about, right? I mean, if you tell, you know, somebody you click with right away, you become intimate with in five minutes, right? Everybody experienced this in their life, you know, to some extent. And the question is what was their right? What was it? Was it because you look the same could be, was it because you know, you have the same sports team that you liked or is there something deeper here and an invalid theory? Was that
1:16:14
That that a similarity in body odor, May contribute to this. That people who smell, the same will click in some way. And so, to address that she 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 diet. So these are friends men and women.
1:16:43
Whose friendship started is a click, we're 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 that other
1:16:55
person, there's a name for that in neurology that our common friend, the late been bear has taught me, which is there's a phrase that neurologists use okay called sticky. These are people that come up to you and, and start asking questions and then won't leave you alone. There are so called sticky people that it. And if you ask these sticky people,
1:17:13
Sticky in air quotes because they're not physically sticky, maybe what they could be. You know, what do you think of the person this person? They'll say, oh they're great. We're really good friends and so they've made a unilateral click friendship. Yeah, and yes, neurologists are talking about you, if you're
1:17:32
one of these people who ologists are talking about you, there's a and informal diagnostic code sticky. So, so so she recruited
1:17:44
Click friends and then she sampled their body odor and we have a protocol for this, they're given you know, odorless 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 odor. And then she first asked, whether indeed
1:18:14
Click friends are more similar in their body order than you would expect by chance. And she first tested this with them with the device a machine we call an electronic nose. So an electronic nose is sort of a very poor effort to mimic what the my million knows does basically it's a bunch of sensors that respond to Airborne molecules. In this case sensors referred to as mock sirs as a metal oxide covered sensors and so she used an electronic nose to sample, these body. Odors and she found that Clique friends are in danger.
1:18:43
Indeed more similar to each other than you would expect by chance by random diets. And in this was a significant difference and after she found that device could do this, she had other participants do this. So so she had people smelling The Clique friends versus non click friends and, and they judge 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 are all the
1:19:13
I'm whatever live in the same neighborhood, and that's why they, they smell the same. So to address causality, she recruited total strangers, and for smell 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 11 predictions.
1:19:43
In there are panned out, but another didn't the one 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 raided each other.
1:20:13
And 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 nose. So people who smell more similar to each other. Think that the other person is more likely to be their friend, is more likely to be a nice person, etcetera. Etc. So we could actually predict friendship using the electronic news. So this is not a result of friendship. It's it plays into the cause
1:20:43
Elements of building friendship. So this is to relate to your childhood story. There's something going on here. We're constantly smelling ourselves, constantly. This constantly, I mean, if you want to, like, I'm now, the reason I'm smiling. I mean, and your viewers or listeners will understand why I'm smiling. I'll send you a video to link
1:21:05
in the
1:21:06
interior podcast here. We thought of calling the the fact that people constantly sniff themselves, we thought of calling this
1:21:13
The low effect and low as so in America. This moment passed that effectively, but in in the rest of the normal world, you are talking, low is the soccer 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, or 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.
1:21:42
And, and once people will see this video, they'll understand why we thought of calling this. The low effect is very graphic, but people are constantly smelling themselves. They're smiling themselves with their hands. They're smelling them solved explicitly people are constantly smiling themselves. Constantly smelling others.
1:22:03
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
1:22:12
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 well 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.
1:22:42
Different mice.
1:22:44
They will bias their choice toward the mouse. That has the immune composition, the so-called Mac major histocompatibility, complex, which reflects immune diversity the immune system. That is most distant from theirs. And the, The evolutionary argument being that were 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
1:23:13
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 produces a higher rate of mutations. In other words, whereas you describe 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
1:23:43
In romantic partners are sexual partners or both. That you choose the person who's odor and therefore immune composition is most different,
1:23:53
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
1:24:14
Webkinz and a Talon, and the wiccan lab, and also Porter, I'll email these to you later on. That have have done a lot of this work and find exactly as you say, that, that romantic odor, preferences in humans are influenced by Body order and that this is linked to MHC histocompatibility complex makeup of the portion of our genome that that shapes our immune system.
1:24:43
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
1:25:01
Tangent work, we've done and and I'd like to maybe tell you about it, relates to to an effect that that is one of the most remarkable effects in mammalian, social chemo signaling. So and also related to two, so it's not related to Romanticism in any way or but it's related to reproduction in it. And indeed, in our lab, we've not looked at Romanticism. We have looked at or are looking
1:25:31
being a true production. They're not always the same. Certainly again, we can animal Matt million or terrestrial. My million reproductive behavior is dominated by by the sense of smell in mammals. And here, remember, initially, when you start off, I noted that there are several subsystems in our news that transducer utterance and so primarily the main olfactory system the which is cranial nerve number one and the
1:26:01
A geminal nerve which is Criminal. Number five most terrestrial mammals have another subsystem referred to as the the secondary olfactory system that has a separate sense organ in the nose, this organ is known as the vomeronasal 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 can, it connects both.
1:26:30
And so there's this sense organ with its specific receptor subtypes vnr is ver, more nasal receptors and this is linked to a to a sort of separate portion of the olfactory bulb. Not really the main olfactory bulb. Oh, it's referred to as the accessory, olfactory bulb and from there directly to the limbic system to the two portions of the brain that control reproductive Behavior.
1:27:01
And aggressive behavior. And and in most terrestrial, mammals this subsystem processes odorants there are sometimes referred to as pheromones. Although that's in many ways a problematic term. But but odorants that are referred to as pheromones namely odorants. There are emitted by another member of the species to influence that member of the species and alter Behavior, or hormonal State. And and and some of these firms.
1:27:30
No 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,
1:28:00
To the order of what is referred to in technical terms as the non stud male, that is a male who did not father the pregnancy, she will miss carry the pregnancy, she will abort it. Now that that's an insane decision made by the female here, right? Because she's invested quite a lot in this, right? And in biological terms and informing this pregnancy and maintaining it and yet she drops it on the basis of an odor. And this effect is remarkably.
1:28:30
Boxed. And what do I mean by 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. It more than eighty percent. So it's a remarkably be remarkably robust effect this. This dropping of the pregnancy and we know
1:28:51
it's mediated by chemo, sensation through the nose,
1:28:53
sure. And we know in the following way. So first, it's enough to just bring the order of the non stud mail.
1:29:00
You don't have to bring the mail himself, right? So you just can bring bedding from an unsent mail 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 vomeronasal organ. You just burn this tiny structure in the nose and the effect disappears. So the effect is completely dependent on the vomeronasal organ and and I find this out all of your remarkable effect, right? I mean it because again because of the
1:29:30
The extent of cost that the female takes on here based on this information in smell. Now humans
1:29:43
The sort of the going notion in olfaction is that humans don't have a functional vomeronasal 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 the structure or the outlining structure is there, but the pit that we have is considered vestigial and non-functional.
1:30:07
And what about this thing? I've learned about at Berkeley in integrated biology
1:30:12
EG class that we have something called Jacobson's
1:30:16
organ. This is the same organ. So, Jacobson organs is the vomeronasal, 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, in a soldier who was operating on or something like that, the story comes from something like that. But Jacobson organ, is another name for
1:30:43
Manolis the organ. These are one in the same, the sensory organ of the accessory olfactory system. And again the going notion is that the human Jacobson organ are from where his organ is vestigial. It's non-functional. Does that necessarily mean that we don't have these pheromone effects? No, it does not. So, first of all, we know that lots of what are considered for a monel effects, namely social chemo signaling in rodents are mediated by the main olfactory system. We know that for sure, there are several examples for this in mice and rats.
1:31:12
And rabbits and so on and so forth. So so a these can be mediated by the main olfactory system and I'll I'll come back to that in a second. But first to finish the Bruce effect,
1:31:27
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 the decision or the notion that it's non-functional. Relies on about one and a half papers, post-mortem looking for the nerve that connects this thing to the brain. And
1:31:56
Find it using staining and so on and so forth. But standing post-mortem studies in humans are notoriously.
1:32:04
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 and, and study its tissue. So, so based on on really, really a positive studies that failed to find this nerve the notion is that the structure is vestigial and
1:32:33
Humans, I don't have any evidence that it's functional mind you, but 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 ruse effect. So first of all, humans have an enormous number, or ratio of spontaneous
1:33:01
miscarriage, are they?
1:33:04
Occurring more often in the first trimester. Because you mentioned yes that in the Bruce effect, in the mice's, in the first three days or so following pregnancy which in the mouse just station. As I recall is about 21 days in the Mauser talk about one-seventh of total gestation so I'm now I'm not quick enough to nor is it important to translate but this would be first trimester yes which
1:33:21
is indeed really focused when most miscarriage of occurs. Now humans have again a huge number of miscarriages and the numbers I'll soon share them with you. They sound odd and the reason they
1:33:33
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 12, nobody ever knows. Okay. So some papers talk about, 90% of all, human pregnancies end in miscarriage. This is counting a failed. Implantation in day, 1 2 Etc. More conservative studies, talk about 50%. Nobody will argue 30%. Okay, so a huge number. A huge number of
1:34:03
Of human pregnancies end in miscarriage. Now, out of these, there's a portion that are 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 proportion that are unexplained
1:34:24
And and so all I'm saying is that there is 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 approached the group
1:34:40
Of we enlisted a group of. They're not really patients and participants in a study of people who are 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 that is sufficient for the diagnosis of unexplained. Repeated pregnancy loss, however in our cohort of 30, we had
1:35:09
Couples who experience 12 consecutive. Unexplained repeated pregnancy losses. So so the to the to is just the formal, all of our cohort was like twelve five, you know? So this is an emotional difficult place to be.
1:35:25
And 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, you know, genetic incompatibilities and all sorts of issues. Clotting. All the, all the, the new and suspects. For for pregnancy Lawson, the medical establishment remains totally at a loss as to why these pregnancies aren't holding. And so we hypothesized that that perhaps here, there's something I can do to a Bruce type.
1:35:54
Effect. Obviously, it's not going to be the same as in mice, but 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 see, you know, to seek circumstantial evidence, to see if where there's fire, maybe there's smoke. And what we did was we tested
1:36:17
Olfaction and more specifically the response to male body odor in in the couple's experiencing repeated pregnancy loss. And we found a few things. First of all, if you think of the mechanisms behind the Bruce effect
1:36:40
The Bruce effect implies that the female has to have a very clear memory of the fathering meal. Because if she's going to miscarry in response to the non father, she has to know, father and on father. I mean, that means that there is a pronounced olfactory memory at the moment of meeting, okay? And in mice, this has been very well characterized and attributed to the Ontario Factory, nucleus structure in the brain.
1:37:13
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.
1:37:42
And you might be disappointed or, you know, we would all probably a bit disappointed to learn that control. Women are very poor at this. So, so you would think that, that women would be good at identifying the body odor of their spouse. They're not, they're not far from chance.
1:38:03
However, the women who experienced repeated pregnancy loss are more than their their double, their performance level. So, this is not a nuanced affect women, who, who experienced repeated pregnancy loss, can identify their husbands or their spouses by their body,
1:38:26
odor with much greater Acuity than the typical person double
1:38:31
A bit more than double and way above chance.
1:38:34
Yeah, no. I sorry I posed as a question but I meant yes, with much greater Acuity. And double is is a significant Improvement. Are they much better at detecting
1:38:45
any odor? No, they're not. We did the controls and they're not and then we also measured using fmri re-measured their their brain responds to stranger male body odor and there
1:39:00
R. And, and this was quite remarkable because, you know, we approach to 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 the male body odor. And asking de novo, 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 to stranger male body order between the two groups.
1:39:32
So so olfaction is altered in spontaneous repeated spontaneous pregnancy loss. We don't know this is causal, right? But but that was enough for us to approach the Ethics Committee to run a causal experiment and we're at the beginning of that. L
1:39:54
incredible. I can't wait to hear the results of that.
1:39:56
It's going to take it'll probably take years a few because
1:40:00
Because the these are slow experiments to run. Recruitment is complicated but basically we're blocking. We're blocking smell in couples who are trying to maintain a
1:40:18
pregnancy.
1:40:20
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 pheromone effects in humans. Very nicely, as you said, you know, whether or not it's a classic for pheromone effect or whether or not it's olfaction or something else. This is chemosensory signaling between individuals. The reason this is important to me is a few years ago, I did a social media post about pheromone effects and animals and some potential pheromone effects in humans and a couple of the human
1:40:50
Olfaction East has more from the actually who work on animal models really came after me with, you know, intense sniffing saying, you know, there is no evidence for human pheromone. Affects human pheromone organs and I think today, you've beautifully Illustrated how regardless of the answer to that humans are contain and are emitting chemical signals that influence each other's physiology and
1:41:15
behavior for sure, for sure. And the term pheromone is a problematic term.
1:41:20
In any case, I mean the term the term was put forth to described insect Behavior, right? So you know if you were given a hard time by the mouse people you could have given an eat them and equally hard time if you were an insect person, right? Because really the place that term is is, is accurate. Is, you know, so the first firm on that was discovered was bamboo Coral, which is the pheromone that has the male moth. Follow the, the scent Trail of the female moth bamboo. Call is a pheromone
1:41:51
Insect pheromone. People will argue that this stuff that people talk about in mice and rats is not pheromones. I see. And, and it all becomes
1:41:59
semantics. Yes, sort of like nerdy inside ball.
1:42:01
It's all semantics. So, I don't, I 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 talked about chemo signals and humans, definitely emit chemo signals from their body and these chemo signals influence, other humans and influence.
1:42:20
It's their behavior. You know, in
1:42:24
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 for our lab actually. I mean the, the flavor of the month for the past ten 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.
1:42:54
State of fear. This was first discovered in humans by Denise Chen. Out of, I think Brown not true. Think that's right. Yep. Humans emit a particular body odor when they're in a state of fear and this body would or influences other humans in effect increasing their autonomic arousal. They're sympathetic state. So in effect, you could say that fear is contagious a bit. So the smell of fear is contagious by the
1:43:24
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 showing effectively was showing about a year and a half ago and study the dogs and deed can smell human fear and humans can smell human fear. So several Labs starting from Denise, Chen and have, Alan Jones, and and then in our lab and other labs, if you collect body odor from people, in a state of,
1:43:54
Your and collect body odor from the same people, when they're not in state of fear, other people can determine, which is the state of fear or not and this influences, their
1:44:03
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 the, I had a friend who approach here, but well,
1:44:24
phenomenon that has nothing to do with me in particular. I think this is a common phenomenon is
1:44:31
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 scent marking territory is very common in the animal kingdom. It's not uncommon for romantic Partners when one is traveling or a way for the other partner, to smell their article of clothing in order to bring about positive connotations of the other partner, very common Behavior. If you're doing this folks, other people are doing this.
1:45:01
Yeah, it raises questions for instance about whether or not the mourning period part post-breakup whether by decision by death or by some other phenomenon, that's forced The Break-Up whether or not that mourning period has something to do with in olfactory, unlearning of and made such and on, and on, and on
1:45:20
with all these insights, I would offer you to be a postdoc in. Well, I was lying.
1:45:45
But for reasons that are unclear to me. The first one died of suicide. The second one cancer at 50 in the third one pancreatic cancer in his early 60s in the last one before he died was an MD and a common friend of gnomes. And I turned to me and said,
1:46:01
You know Andrew you're the common denominator so you know the joke I prefer joke to my business is you don't want me to work. So nonetheless I would love to do a sabbatical in your life.
1:46:11
So when I was trying to say in that roundabout ways that those are all really Keen observations and good ideas for sure and and and they just highlight again, you know, that that we're incredibly olfactory animals, you know, and and you're even talking about the Nuance, we're very all Factory, even not in the Nuance. I mean
1:46:31
Yeah, I have this when people tell me that, you know, that we don't use our sense of smell and we don't need it and 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. The vision is unimportant right
1:46:41
after visually dependent. 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 bit into blue, I love blueberries and like a drive-by blueberry heater there there. I
1:46:56
just kind of pick them up like a grizzly, bear and cramming in my mouth. So keep them away from me if you don't want the
1:47:00
meeting.
1:47:01
But I can't, I almost can't help myself. I bit into a blueberry or a handful of blueberries and they just, it was the sensation of little bags of water. And I immediately felt a tremendous tremendous
1:47:13
grief. I'll tell you sort of throw a line that I use in this. When I talk with people, you know, I'm at, I mean, you know, take the two most basic behaviors that sustain us. Right. Let's say, I give you a choice between
1:47:30
A beautiful-looking layer cake with with with strawberries and blueberries and and and whipped cream but that smells of sewage versus some gray brown. Mix that smells of cinnamon which do you eat simple. All right you eat the letter right now. Imagine I offer you a mate choose the gender of your liking right? It looks like a Greek. God.
1:48:00
Or goddess, right? But smells of sewage or an ordinary-looking individual that smells of sin itself. Who do you choose?
1:48:10
The ladder, right? So in the two, most basic behaviors, we have we follow our nose, not our eyes, right? Definitely not always in
1:48:20
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
1:48:40
Particular about that and I know within an instant. And so this is a problem for any romantic partner who likes perfume for me. And I know many people like perfumes and colognes and things of that sort. 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 I've unfortunately for me, there's at least one
1:49:05
person on the planet who said,
1:49:08
so the so I completely
1:49:10
Agree with what you're saying. Yeah, I can also say that I imprinted on the smell of my to 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 feel smelled like home, and he was my best animal friends for a long time. So, and on, and on, and on, right? The
1:49:40
Of children, as you said, the backs of, we had a guest on this podcast who I'm sure you're familiar, Charles hooker. Yeah, Professor Colombia has done incredible work and vision and action thirst sensing it. And he, and I talked a little bit about this, that there's something in the breadth of romantic Partners. That's hopefully appetitive not aversive as well. As in children, he was talking about the smell of his grandchild, the bat, the nape of their, under the back of their neck and how he misses that smell because it when he
1:50:10
He thinks about missing his grandchild or children. It's that smell that that's associated with that feeling hexa dick now. Hexa Deca now. Yes. Is that Charles everything? Your grandchildren smell like hexa Deca now? Yes, he's going to be after
1:50:24
me. Now, the and into this, this is a steady ran by Eve Amish War who was a graduate student in our lab and and Eva was interested in aggression.
1:50:40
She was really into aggression and actually when she start and social when she started off, we said okay let's do chemo signaling of aggression she actually was going like MMA clubs and collecting body odors and we had all sorts of ideas going and she worked on that for quite a bit. It never went anywhere. Really. And then at the same time we had a colleague of ours from Germany. I mean my see,
1:51:10
Colleague, primarily a friend or acquaintance. I medic conferences Hines Briere, and he was standing in his lab molecule exit that Canal, that was a chemo signal in mice, we're in mice. It was described as a chemo signal that promotes social buffering, where social buffering is far. As I understand, it's not my field.
1:51:40
Field. But as far as I understand, it's basically a feel-good together thing. So when lots of whites are together, they feel good about being in a group and that's social buffering and it's promoted by hexadecimal, which they emit in their feces mice and in his work on hexa Deca now and and so so rear and his colleagues Sportsman, they discovered the receptor for this and then they went and discovered that the receptor is very highly conserved.
1:52:10
And throughout my million Evolution and therefore they hypothesized that maybe this is a universal mammalian signal now, which is unusual because in chemo. Signaling typically, you tend to think of things as being very species-specific, but here they hypothesized that maybe hexade, a canal, which promotes social buffering in mice. May do something in all mammals we again because this receptor is very highly conserved or 37b, I think.
1:52:40
So they so he approached us and said, look, you got to study the stuff in humans, right? Because he knows us as the human people, right? I mean, we go to these olfaction conferences, where lots of people, studying, mice, and and and zebra fish and whatnot, and where the, the human group. So and eventually he just fedexed us exit that canal and and so we have this thing sitting around and Eva was not going anywhere with her aggression studies.
1:53:09
With sweat, from Human participants. And yet she built the entire Paradigm to study human aggression. So, their standard paradigms, this is a paradigm known as the tap, the Tyler aggression Paradigm, I'll soon describe it. And so, we said, okay, we have this hexa dick and I'll 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 hexadecimal?
1:53:37
What's the tap experiment? So basically what 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, you can do something, like, have another person walking to the other room playing online so to stay 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
1:54:07
Um, on each round there they're provided with the 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 is programmed to be an inside tick terminology a jerk, right? So that you know, like let's say they have to divvy up
1:54:36
100 check 0, which is the Israeli currency. So, so the community the other player would say, okay, you know, I'll keep 96 and you get four right? And then if you can, either accept it or not accept in the neither of you get anything, right? 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, they're really not nice right there. They're shafting. You on every trial or almost
1:55:06
Can you play this game? And it goes to its end and then you put 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 in 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, 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 a no
1:55:36
Our be committee will let you endure on a participant in the experiment, unless you're in Stanford, 70 years ago, or whatever. That was known as referring to the put that classic prisoner expire which took place in the building next door to where I went. So you can blast the other part to spend 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 then allows you to quantify aggression, because the more volume you're blasting. The opponent with the more aggressive you are
1:56:06
Our 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, the tap, either under exposure to exit that Canal or control now exit, the canal doesn't it's incredibly difficult. Even detect text of the canal, but just in case.
1:56:36
It's because it's not very very it's considered a semi-volatile, it doesn't have a strong smell but we buried it both the control and the exit, a canal in control order that hid them in a mask. And and she ran, lots and lots, and lots. And lots of participants men and women and offers, tell you the result with men, which is that hexade that Canal consistently reduced aggression.
1:57:03
People were less aggressive under hexagonal. The effect size was was quite meaningful and later on, we learn because I'm no specialist in the world of aggression, but compared to the effects teen in the aggression World in research really, really strong effects. So unusually strong, so hexa deck and a lowered aggression in men and we were like cool. This is, you know, sort of what we were hoping to see consistent with the hypothesis and consistent with it seems to do in my
1:57:32
Nice.
1:57:34
But then we looked at data from women and hexagonal increased aggression, equally
1:57:40
significantly is this thought to be something related to maternal protectiveness. We're getting there.
1:57:44
So you you got there really fast. It took me a year but and and Eva got to it, really? I'll tell you because remember we're reaching the back of the head of your of whose was it. The grandchildren are all zones, occur just go lie on the show one
1:58:00
of the kingpins of the New York Neuroscience Mafia.
1:58:03
Yes.
1:58:04
So so this was really odd to me at that time so I didn't have the intuition, you just had and I was like about this. There is some bug here. I mean this this it makes no sense to me. You know, why would something increase aggression and women and decrease aggression and Men this is really, really strange.
1:58:24
And and I said, okay, I want to see this happen again before. You know, we go ahead with this so she went and did the entire experiment again and this time she did it with in the fmri magnet so that we can also track brain activity while this was happening and first of all it replicated again. So once again hexa dickon Alum, men made men, less aggressive, and women, more aggressive and and and the extent of more than the effect alone, the dissociation was
1:58:53
Markable this has the it's almost like a chromosomal tests. I mean, you look at the data on the unit, unit slope line and all the men are above below and all the women are above. There's this figure in the paper, then she also looked at the brain date. And this is, you know, Although our lab does a ton of fmri, it's one of the major tools we use to measure brain activity. I'm, I'm quite cognizant of the limitations of fmri. And, and this is, I think,
1:59:24
Lee. 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, and so here's what we saw that hexa deck and I'll elune increased activity, quite pronounced lie in 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.
1:59:53
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 and this was in contrast to behavior which you don't like seeing right. I mean, because you would expect brain activity, reflect behavior and it increased activity in the left, angular gyrus in both both men and women, but then she did a follow-up analysis, which was look at what's referred to as functional.
2:00:24
Activity that is how does this region of the brain talk with the entire brain as it were under hex addiction, Al versus control and here the dissociation re-emerged powerfully whereby the connectivity from the angular gyrus was mostly to the classic neural substrates of aggression so the amygdala and the temporal pole and the connectivity went in opposite directions in men and women. So hexadecimal
2:00:53
Well, 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 aggress. And in men hex the Deccan Al increases the control that the left angular gyrus is holding over your aggression and keeping you back. And in women it, let it roam free and they became more aggressive,
2:01:18
but I was
2:01:19
still puzzled. So the so I was convinced this happened twice the EMR data.
2:01:24
Provided not only a pattern but a mechanism which is unusual and yet I was telling you what I know but you know there's makes no sense to me and then and then her inside which of course, afterwards is like, duh is know there's a place where this makes perfect sense. And that is if you are a million Offspring because paternal aggression is often directed at you, there is infanticide all over and sadly, there's male aggression towards
2:01:54
It's human children as well. And maternal aggression is often protective. So if you're an offspring, if you have a molecule that will make your mother more aggressive in your daddy, a less aggressive, both of those are good for you. So you're winning. So we remembered a recently published paper from a group in Japan.
2:02:14
That looked at the odors emanating from baby heads. We now come full circle to soakers. Grandchildren, they used a method known as gcms gas. Chromatography-mass, spectrometry to measure the volatiles from baby heads because baby had odor is a cultural thing across cultures. Even in Japan
2:02:36
And so we quickly went to that paper and to see if one of the molecules the report is hexa Deccan Al 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 are co-authors. And we said look, you know, we're studying this molecule X Addiction on, we don't see in your results and we were wondering maybe you had some results that you didn't publish or some supplementary materials or whatever. And at this lab, which is a
2:03:05
A hardcore GC lab said no, no hexa. They can all is the semi-volatile. Which we knew in our previous paper was not directed to the semi-volatile range, but we can. Now, do you use? What's called, G CX, g c, GG C. That is directed at semi-volatile house and we can do this again. We just studied 11 babies and we can we can see if this is an issue. So he said, yeah, please do the bottom line of all this is that hexadecimal is the most abundant semi-volatile and baby hits, its tons of it. Coming out
2:03:36
Baby hits so babies. Again speaking about us, humans do or don't chemo. Signal babies are conducting chemical warfare right there. There there, 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
2:03:56
them. Incredible this is somewhat different than what we're talking about and yet similar in other ways because it's
2:04:05
Is 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, and 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,
2:04:35
Camping or even spend a day with him our menstrual cycles become coordinated. However, my understanding is that the early literature Barbara McClintock, correct, discovered this phenomenon published a paper in science as an undergraduate
2:04:49
1971
2:04:50
nature, amazing nature paper again. One of the three Apex journals and as an undergrad. Fantastic. So discover this describe this and probably women all over the world who became aware of this one way or another, probably probably said, yes, absolutely. This gives validation to what we've observed over.
2:05:05
And over again and yet as subsequent papers have been published, this result has been called into question. Is, 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 chemo sensing through the nostrils warm and or mouth to support this
2:05:29
idea. So yeah so I'll start off. Indeed to Echo the back.
2:05:35
Around, is that this study was conducted by Martha, McClintock. 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, ruins don't have a menstrual cycle like humans do but but
2:06:06
There's a defect in Ruins referred to as the witness effect, which resembles this type of effect and she published indeed that paper as 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 students in Chicago Stern. So, this is Stern and McClintock 1998, and here's what they did, they collected.
2:06:35
David 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. You said, you liked body orders. But for many others, perhaps it would be daunting well. I liked certain body, odors from certain individuals. Okay.
2:06:54
I don't, I
2:06:55
don't think I uniformly, like
2:06:57
all yours, although I do not like the smell of perfume, although I should
2:07:02
just to clarify because I put this out there and I learned
2:07:04
the hard way in the comments.
2:07:05
Session on YouTube.
2:07:06
Some of those perfumes. I find downright aversive. Yeah. Like it's a I think the great Marcus Meister, who great neurobiologist one said, there's basically three responses either yum, yuck or met. So
2:07:17
some I are truly, I've never heard that one. Can take that one, right?
2:07:20
Interesting, animal behavior? Yeah.
2:07:30
Some many are met zero to date. Are yum for me, now, body, odors the distribution is shifted. It could be any one of those three younger men. So, just to be clear, but the, the Yum category is definitely included.
2:07:49
Thank you for Aladdin.
2:07:54
So she did this study. So because right in the original, McClintock study, you might suspect other drivers of the effective. Let's see what you accept the effect, but still, there might be other social drivers of the effect. There are not body odor, right? There might be some dominant woman, who's dominant in some other way? In this might be driving the coordination, right? So here, there was no direct link between these women other than body odor. So if the effect re-emerged, it would definitely be an olfactory effect and what she found.
2:08:24
Found is that if she took sweat from the follicular or the ovulatory phase of the donors, one extended the the cycle and recipients and one shorten the cycle in recipient. I don't remember, which was which, but, but basically, definitely denoting a chemo signaling effect with, with opposing effects on duration, based on the time, it was collected from again published in nature in 1998.
2:08:53
That's it. I the there's a quotation. I think this is from from from from I'm not sure but but you know that 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. Um, one reason is just
2:09:23
Statistics of cyclic events, are surprisingly complicated. So so It's Tricky. It's once you have a cyclic event statistics, statistics become tricky and and so she show Martha took a lot of heat on the statistics of claiming an effect.
2:09:47
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 in but I may be in a minority and my field. I think a majority in the field is currently - I'm not. And I've said, we've said in the lab that we should do a planned replication, we will it
2:10:17
Is again, it's a horrible studied run. It's tons of work and you have to run it for a really long time. And so it's just completely non-trivial. But we have graduate student now in lab interested in these exact things, through twice, gross inch and she's doing similar stuff, and I hope we'll do that. I hope all will try to replicate this
2:10:43
very interesting result. And I think interesting because of
2:10:47
It's real world, meaning outside the laboratory of course or experiment analog. But also because
2:10:57
Pheromone effects and olfactory. Effects in humans, seem unique among neurobiological /. 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 you know, or I just liked their smell kind of thing. These kind of things that that inform the the Deep
2:11:26
Potential for a real biological phenomenon as opposed to the kind of thing like, oh you know, you just throw something out there, oxytocin is bonding and all of a sudden, you know, the general public. Not at no, to no fault of their own comes to think that every aspect of bonding is is oxytocin. And every defect in bonding is lack of oxytocin. But the, the general public provides a sort of a rich. It's fodder for, for exploring all these things, and a lot of times, they turn out to be true.
2:11:56
Right? And when in the context of all back.
2:11:58
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.
2:12:09
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 cueing up and that is what is the relationship between odors and hormones and in particular
2:12:26
Crying as I pointed out, previously, the sort of flavor of the month in human social chemo. Signaling researchers, the smell of fear and the, the media of the month is Sweat, Right? So, so the the few maybe tens of labs in the world that study Human, Social chemo, signaling, all collect sweat. And, and that's the media, they look
2:12:50
at, is it always from the armpit or guys? There are there meaningful differences in terms of the sweat emitted from
2:12:56
Locations on the body. I already know the answer to that. Is I ask it. But let's just stay above the waistline and oh no. Yeah, we're below the waistline. Yeah, we're biologist after all.
2:13:06
We just. Yeah, so it's funny. 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 here to come to your lab in the world. We didn't invent that. By the way, the first to do that was
2:13:26
and I hope I'm pronouncing her name correctly. I think it's mooji. Copy, Rudy, 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 paratroopers Brigade, and we now collect body odor 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
2:13:56
If you'll have the fear molecules, that's a bonanza, right? Because I mean you know, you can think of many reasons why would be a bonanza. But for me, you know, if you find the molecules you can then try and find The receptors and when you find the cognate receptors, you can then develop blockers and you can imagine, you know, what's the term I'm looking for?
2:14:21
I'm switching into Hebrew. It's about midnight now, right? I'm sorry. Oh yeah, you're running. You're doing
2:14:25
incredibly well, considering that he never should
2:14:27
have been this morning. Yeah, we would never know
2:14:31
traveled in today from Israel. So he's a circadian
2:14:33
inverted as we say anxiety. So you can imagine developing like a nasal spray against anxiety, right? Where you would quell those receptors and kill the fuhrer response right? Which rather than going the current path which is through neurotransmitters that
2:14:50
Then have affect all over the place, you would be getting fear at its source, right? So that would be why I would want that. And, and, and we figure out the doing that, you know, collecting fear from like three four or five people in an experiment, you'll never be able to do analytical chemistry on that. So, we now have, we 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
2:15:21
but in doing that we've joined, you know, the crowd everybody is doing fear and everybody's doing sweat and in one of our discussions in the lab, you know, 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. Signaling. Now, many of these, you know, you can't really study right? I mean so you know, just to throw it what most terrestrial, mammals communicate social information through urine.
2:15:49
But you know starting doing experiments with humans with smelling urine, it would be difficult, you know, both in IRB and an agreement and you know and and then we know this is a rare case where we actually hypothesize what we set out to do. And it's you know not only claim in retrospect that it was hypothesized is is tears.
2:16:14
We started thinking about tears and looking into tears because tears are a bodily liquid, emotional tears that we emit in emotional situations, where these are situations where nonverbal communication is critical and key and and tears are a liquid that that is puzzling Beyond ocular maintenance, right? And so,
2:16:42
so, so, you know, the most
2:16:45
Influential text, I think till this day in Emotion, research is Darwin's book. The showing of the emotions in man and animals. I think is the full name of the book and an entire chapter chapter 6 is devoted to tears an entire chapter of this book. Why we with no conclusion, why? Because the book revolves around,
2:17:10
Describing the functional anticipate events of emotional Expressions. So for example, showing of the teeth is a sign of aggression, right? So, so animals first bit with their teeth and Darwin, argued the 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 is the
2:17:39
emotional expression of disgust so discussed which comes from Lund is Guzzi a distaste, right is spinning something out of your mouth. Now what what Adam showed is is that the musculature patterns of activation and the temporal sequence of activation when you experience moral discussed are the same as when you spit a bitter taste out of your mouth, right? So again so there's a functional anticipated, ain't spinning something out.
2:18:09
And through Evolution the argument was that it became an expression of emotion and you express disgust just as if you're spinning something out of your mouth even though they're, you know, in the case of moral discussed there's nothing you're spinning out of your mouth. So so darn systematically. Went through the expressions of emotions, and for each one, went to their functional, anticipate and explained everything very nicely. And then he got stuck with tears, right? Because tears aren't obviously emotional expression and he could not find a functional anticipated,
2:18:39
So he ended up saying this is an epic phenomena basically, right? I don't know what all scientists do when they don't have a good explanation, blame it on nature. Great, right? So, so but he bothered to write this entire chapter on the ocular sort of Maintenance, communis function of tears and so on, so forth, but nothing emotional. So we thought well maybe the function is a chemical signal.
2:19:03
And
2:19:05
and, you know, so with that in mind, we harvested emotional tears which was also an amusing event on its own, right? Because we we posted messages on all sorts of boards that are now we're seeking experiment. Participants who cry with ease. Now, this generated an unfortunate gender bias.
2:19:33
Study, right? Because we received about 100 women volunteers and about one man. And, you know, I think this is not a problem only in Macho Israel, right? Probably anywhere in the west. This would mean definitely in America would be the same. My
2:19:45
guess is that they're probably men out there who cry, easily emotional tears. I'm sure they're just going to show up. Yeah, that's
2:19:51
what I'm saying. That's a cultural thing. It's not, you know you're not going to come to lab and see how, you know, I cry all the time and it's just not going to happen.
2:19:59
And then we we did is for each one of these participants. You know, we would ask them, you know, is there a particular film event that you know of that you know a scene that makes you cry and interestingly in these effective choirs there's always oh yes you know the scene in so and so I always cry profusely from that, you know they haven't
2:20:21
give me an example of a one of the more commonly. Yeah.
2:20:23
Yeah with these.
2:20:27
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.
2:20:40
And his son is standing next to his bed and you know saying champ champ and he
2:20:47
dies, right?
2:20:50
It's a winner. Okay, waterfall in the yeah got it. So you know, we're probably the neural biology lab with most sad movie films on those shelf in the world, right? We have a whole huge collection there is ending his Tears of Joy. Anyway so no, no. Well, we're going ahead of ourselves. Let's say we tried.
2:21:09
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 with in the effective criers we end up screening so I can we collect a full mL of Tears, a full amount of Tears in about 15 minutes so that's pouring right? And that doesn't happen from laughter that we are. We've never seen that. We've never seen that happen from what we tried.
2:21:39
So,
2:21:42
So we have, we have all these sad films. And by the way, the one of the amazing things is when we ultimately published this paper in science, we were forced in retrospect to go out and actually by the film's, right? We, I mean, you know, and originally, we like downloaded the rear there, but you can't, because your be violating, you know, copyright laws, right? So we need to buy like purchase all these films that departs and watch them. So it
2:22:11
We actually have these in live like DVDs. You know that we actually purchased but so
2:22:18
as coverage of potential legal
2:22:19
Fallout. No,
2:22:21
no. We did
2:22:29
touch on that later. But up so. So most of these are volunteers who come saying they can cry with. He's actually don't meet the bill.
2:22:42
I'm into 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 portieres.
2:22:55
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 flinched quite a lot. They it's almost as if they're experiencing it, but it works in the opposite direction to. I know someone like this.
2:23:11
Where if they watch a film, that someone's experiencing something even mildly positive that their mood Elevate so they they can quickly Bridge. Yeah. And and it's not always adaptive as you can imagine. So there's a lack of narrative
2:23:24
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 you know very unique about the donors, right? I mean we're assuming these are tears and
2:23:35
this is pretty common. I think that numbers I sought out there about five to eight percent of exactly what we got.
2:23:41
About Ranch,
2:23:42
but six of accurate. So, so, so we collected
2:23:48
Tears.
2:23:49
And and we exposed participants to these tears. And, and we found a few things. First of all, the tears are completely odorless, you cannot detect them at all, completely odorless.
2:24:06
And yet
2:24:07
when you sniff them, you have a pronounced reduction in testosterone within about
2:24:16
20 minutes half an
2:24:18
hour. This is men and women
2:24:19
smelling Management's, tears just men
2:24:21
yelling woman's tears, but not perceiving any
2:24:24
odor. Nothing just sniffing them and you have about 14 percent drop in free testosterone free. Okay. So this is
2:24:34
testosterone that's already been liberated from the testes, free tester that we've done a few homeowner. That's either bound or Unbound, is unbalanced? Yeah, me from sex hormone-binding globulin, cetera, and it's the active.
2:24:46
So it's a it's subject to very short time scale
2:24:51
changes. Yeah. And and this is you know people who who studied testosterone which is not me, but they tell me this is a really strong effect like it's hard to even pharmacologically get an effect like that that fast I'm you know, in Pharmacology. Yeah, years ago, I
2:25:06
spent time studying endocrine effects of this sort and that's a tremendous we sized
2:25:11
effect. So and so here I'll point out in passing that one.
2:25:16
one of the concerns we had, because of the
2:25:20
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. Oh, it out who I don't know, at all replicated, the testosterone effect to a tee. I mean, like same numbers. So it lowers testosterone and, and we, then also looked using Mr. It
2:25:50
At the effect on brain activity and saw pronounced if effect on activity. A dampening, a lowering of activity under under an arousing State, a lowering of activity both in the hypothalamus and in the fusiform gyrus for whatever reason, I don't know recognition area, amongst other things? Yes. And we don't know why but pronounced.
2:26:21
And currently SHINee are grown in our lab is replicating this again. And this time with them, stronger behavioral component and I can share with you unpublished data. Now under review, that's as you would expect. Given the effect on testosterone, perhaps sniffing tears, lowers aggression in men,
2:26:45
Using again, the tap the same experiment used by even in the exid economics
2:26:50
permit the Tapley. I'm gonna think of that. As the, the sated, the tightrope Walker said, that titration, the statist hydration.
2:26:57
Yeah. Tyler aggression Paradigm. So not only the Milgram
2:27:00
experiments of the of the 1950s, which post, this is looking at sort of post-holocaust. Behavior. You know, people, basically in American, Laboratories thinking they were torturing other people. Yeah. Simply
2:27:15
They were told to and a lot of people did that even though most people would report that they would never torture. See
2:27:20
ya, humans are not a wonderful species
2:27:23
or as we think I think it was the great Carl Jung 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 the power of these chemosensory systems and Pathways. And obviously there's so much
2:27:45
Much here.
2:27:46
I don't know if you want me to tell about this or not and I guess you can edit it out at least you don't. But this is just, you know, sharing stories about the politics of Science. And so whereas the effect on testosterone was replicated by by an independent group in the original studying in science where we had, we had it had three components. One was the effect on testosterone which was robust the second which was brain activity which
2:28:15
With 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 readings of arousal associated with pictures
2:28:32
And there was an effect, it was significant, but it was, it was not what? Carried the story. Now, there's a lab in Holland of a guy, by the name of think, I'm probably mispronouncing this but I think it's vinegar
2:28:51
hotz
2:28:53
For the non Dutch. Yeah, Dutch names are always a little bit of a
2:28:57
challenge but and I shouldn't say that it being an Israeli. I shouldn't go too much on that line but that
2:29:04
lab
2:29:06
really didn't like our original tear 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 tears are uniquely human
2:29:24
Now, here I should be. Well, I should share. So, one of the things we really liked about that that tear result is
2:29:34
that partially before we did our work more afterwards and we like that because usually things. So, usually in our chemo signaling work. Like what I told you before, about the Bruce effect, we look at what happens in Ruins and we see if the same thing is happening in humans. This was a rare case where after we did this work.
2:29:53
More or less identical, effects were discovered in rodents. So paper, published in nature, two years later. Found that Mouse tears Mouse puppeteers, lower aggression, in male adult mice towards them
2:30:07
in a, in a smell dependent way. Yeah.
2:30:10
So and and they also actually found the actual component in tears. That so the tear pheromone that lowers aggression, right? So, you know, this has us thinking of a gret is tears. Is
2:30:22
You can think of Tears is like a chemical blanket in a way that that you're covering yourself up again with, you know, to protect against aggression, right? And and so are finding, you know, which to me. I mean, this is consistent with how I think about behavior in general at you. I don't think, you know, beyond language. There are very few things, definitely sensory things that are uniquely human, you know, ii-i'd be hard-pressed, but so, you know, are finding when it gets, you know, against their
2:30:52
Story right? Because you know here we're saying no you know tears are this chemo signaling mechanism like all animals and by the way I you know, just after this entire debate about six months ago, there was a paper in current biology, the dogs emit, emotional tears and and it was the dogs admit emotional tears when they reunite with their owners and you were talking before about about oxytocin. So, I think what they showed their is that not only that but that the
2:31:22
The, the view a seeing the tears in the dog influences, oxytocin, and in the
2:31:28
humans, I hope I'm getting this. Right? But that's absolutely believe this. I mean, I from the, from the time I brought Costello home at eight weeks old guys. Tell us your
2:31:38
dog. He's my dog, unfortunately, that's why they haven't a
2:31:40
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,
2:31:52
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 don't want to know, you know, it's one of those things. Yeah. I think it's a healthy. Yeah, motional say 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, fairly fairly state are not always that interesting, but they can be pretty interesting and someone presenting data. And my mind,
2:32:22
Thinking I hope Costello is. Okay, what's he doing down in? My office 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 I think that dogs perhaps through oxytocin, hijack, the circuitry that's intended for child-rearing. Yeah, I really do otherwise, why would people be so ridiculously attached to their dogs and hence all the the post of everyone thinks their dog.
2:32:52
Is the cutest dog. The same way. Everyone thinks their children are the cutest children you know
2:32:55
custody by the way, was a very so yeah. So so again so they're so even you know, to put another nail in that story of tears are uniquely human. So they're not dogs shed, emotional tears. And and and so that really didn't like this and they went ahead and tried to replicate and to your listeners. I'm
2:33:22
I'm showing double quotations on the replicate only the behavioral part the ratings of arousal, in women of women and, and failed to replicate that I see. Now, this was in, you know, just sharing on how science works and doesn't work in my, in my notion in this case. So, at the time, after they got this accepted in some Journal,
2:33:52
not a field journal and the Journal of memory of something.
2:34:00
They contacted me for a response and I wrote to the office and I said, look, you know, this is very odd to me. Why don't you come? Even 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
2:34:28
plaid that know. They don't have money to send over a graduation to do it. So, I replied saying, okay, I'll fund the graduate student coming over and I'll fund the entire study and they're staying so on and so forth. And let's do this together and they replied, no, they're not willing to do that. Which, you know, I don't think is the way things should work and 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
2:34:58
Was that successful replication with the effect on testosterone but there was supposedly, the spell 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.
2:35:12
Well I think it's interesting. I mean I think provided studies are done correctly. I mean the the positive result almost always Trump's 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 just buddy.
2:35:28
This one is not even
2:35:29
remotely but and I published a detailed so actually they hid something in their data that did partially rope so I asked for their data and Arie analyzed it and that's what I published in the rebuttal but you know this is just sharing on how science works. I took advice. So I'm it's not that that I'm friends with him but at that time I was communicating a bit because we're on some board with with with Daniel Kahneman who's Nobel Laureate fast and slow. Right. And so so I asked him how should I deal?
2:35:58
With
2:35:58
this.
2:36:00
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, don't never publish every bottle, don't do anything. As 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 about, although be like well, there's a group that says this and there's a group that says that so it's unclear. Well
2:36:27
and yeah, I mean, I appreciate that your
2:36:30
Bring it up today and I do appreciate that you publish the rebuttal and that you offered in a very magnanimous way to do a collapse. What he then said that's
2:36:38
its currents advice after that was that. Well, if you insist then just publish Write a response that you offered them to come do together, they refused and there's nothing you can do about that.
2:36:51
It's a lot like fight sports, right? People talk a lot of trash although in science, you know, I will say this to you as long as we're on the the sociology of science.
2:37:00
They took our size 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, you get it in the neck on Grant reviews or Anonymous reviews. I was on a grants review, panel this morning, I'm a nice reviewer. Meaning, I judge things objectively, but I try to always, think from the perspective of the graduate student or author of the of the proposal listen, I think that science is a
2:37:30
Game of people who most of them are seeking facts. However, the the ego is strongly woven into it like any like anything else. So 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 him 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 more questions and I realized and thank you by the way, for your
2:38:00
you for your willingness and stamina because it is probably one am Israel time now and you just arrived I think but you're doing terrifically well. So I if you'll indulge us just a touch further, there are two topics that I want to touch on a few want to cover these 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.
2:38:29
You know, an orange that smells great or the smell of something baking, you know, I didn't it suggests something about the the contents and quality 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 wafting up through the cheese board is something I will never forget and the breads never forget it, amazing
2:38:51
ready. I mean, I don't know if you've conveyed that clearly enough to listeners, or Watchers. Now, the probability really just discovered that we lived in
2:38:59
In the same we never met. I mean your feet like this before. Yeah and we lived in the same exactly
2:39:05
where we click friends. What?
2:39:10
Lingering way. Yes. Absolutely through the floorboards and having read floor that place has a great wooden
2:39:17
floor, has an amazing place. I live there with my girlfriend for a year and a half and then it was an amazing place. We won't give out the address for out of respect for the people that live there now, but do check out the cheese board, if you
2:39:30
Berkeley their hours are weird, but so you have to look online. But that there 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 content 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
2:39:59
that you know I don't know I smell a piece of meat cooking and it smells great to me and I think of it as hot as it'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 ensure or I should say increase the likelihood that I will ingest some other thing that's in steak.
2:40:30
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 savoriness who mommy 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
2:40:59
We attracted to is signaling 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 that whether or not there are subconscious signals that the olfactory system has learned to seek but learn to seek through more overt signal, sort of the tip of the iceberg phenomenon
2:41:30
You know, 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, so whether whether the, there's, you know, older cues on nutrient value is 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.
2:41:59
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. It's a really good idea. I mean, one of the
2:42:18
reasons I ask this is because, you know, the Obesity crisis in the u.s. is a huge issue and elsewhere and highly processed foods. You know, I have a lot of things that are problematic, but one of the things that
2:42:30
I don't have often is a direct relationship between the sent the taste and the neutral and the nutrient content. And I don't mean macronutrient sugar fat, excuse me, carbohydrates, fats and proteins but the 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
2:42:59
probiotics.
2:42:59
otix, I'll tell you one sort of factoid May support your hypothesis here and that, is that
2:43:07
There appears to be potential olfactory, perceptual similarity, in metabolic products. So something that's metabolized from something else because perceptual similarity across those those two things. So so so metabolic Cascades playing to the coding of olfactory space and, and that is consistent with
2:43:38
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. In this case, I would suspect that it should exist in scientific press and if not there than with companies that have vested interest in this which are many briefly shit, just
2:44:07
Just leaves and an amusing, anecdote to share with you is that we've received two independent.
2:44:17
People, you know companies who have turned to our lab recently asking for help to bring odor the engineered meat, right? That's a growing thing and all these you know, meats that are knowing
2:44:30
you had to bring it up. This this audience is going to be very polarized along the along, the lines of engineered meet. You're not from you're not promoting. No, no, no. I
2:44:41
have, I'm agnostic, but but, but we've had got two companies turn to us.
2:44:46
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.
2:44:52
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 accidents on nutrition. Come on here, we'll have more but
2:45:02
I know nothing, don't worry, Tristan, you're safe.
2:45:04
No, don't worry, is not promoting. He hasn't even said whether or not he's going to help them out.
2:45:10
No, we're not actually. Not because yeah, just know it didn't happen
2:45:15
know that the the
2:45:16
Or not, those engineered meets our younger 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
2:45:33
will avoid now I want. But it, you know, I'll take that the opportunity to highlight something related maybe because I mean what were you saying on the on the scale, you know, there's this
2:45:46
You know, I'll take the opportunity to dispel another misconception about olfaction, 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 olfaction. I think I
2:46:08
know the study you're going to tell me. There are many
2:46:10
the cross-cultural similar. There are many that is utterly untrue. Many not only for my life.
2:46:16
Many, for many laps,
2:46:17
please. Clarify for those that. Yes, follow this.
2:46:19
So yeah, so
2:46:24
Humans.
2:46:26
Are incredibly similar to one another in their olfactory perception. And this is in contrast to which most people think. So, why is there this misconception? The misconception, is there two reasons, first of all, or for several reasons but to our stand out,
2:46:44
First of all, we're attracted by outliers because you know what, I'll tell somebody look you know, for example Factory pleasantness is highly correlated among humans. And let's first put this in numbers you'll take a bunch of humans in a bunch of odorants and have them write pleasantness, the correlation across the humans will be about point eight, that's incredibly hot incredibly High. What do you think is Pleasant? I think is yeah, yeah, now why is that go against what?
2:47:14
Actually, people think for two reasons. First of all,
2:47:18
We're we're attracted or biased by outliers, but that's particularly that Joe is, in fact, the result, what do I mean? So you'll tell somebody you look, people are very similar in their pleasantness estimates in 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, a few classic examples, there we Ava, right? You know, is another polarizing order. So there are few polarizing orders, right? And that's true, right? So that's true that, you know, half of the population.
2:47:48
Has the smell of cilantro and half hates it. Half loves guava have hates it.
2:47:52
That's microwave popcorn. However,
2:47:56
I assure you that, you know, you can come to our lab. We have about 1000 or Durance in our lab, okay? We won't smell the Thousand, right? But I assure you, you know, take 100 or Durance okay from our mixtures and Labs, right? And will smell them right and
2:48:13
Are the 100 orders 90 will totally agree on right and including 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 roses and Flowery smells, there will be rare exceptions. Again, the correlation about point eight across individuals. So, on a 90 of 100 will really be in high agreement. Then 50 Durance will be in sort of intermediate agreements. And yes, they'll be the 50 Durance that were
2:48:43
Total disagreement on. But I asked, 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 to this Rule and and 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 the cultural effect is the law is our poor application of language to a faction, right? So so in other sensory,
2:49:13
Systems, we grow up with we're we developed with anchors, right? So since you're a little kid, you know, your mother shows you cow and says, what does the cow do move, right? And we all know muumuu and what color is 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.
2:49:44
Right? And in order, we don't have those anchors, right? We don't from childhood, you know, our mom doesn't tell 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, right? That's the measure, right? So what can you let's say? We take 10 odorants and I have you rate all the pairwise similarities, right?
2:50:13
So you end up with 45 numbers, right? So you know how similar is 122 123 124 and then to it and all the possible pairwise similarities. Let's say you rate similarity from one, which is totally dissimilar to 100 exactly the same, right? So now I have a similarity Matrix that describes Andrews perception of smell, right? I have, you know, based on these 10 odorants that I selected. Now, I can run my similarity Matrix and then I can see if the similarity Matrix are correlated, right?
2:50:43
Then we've gotten rid of the issue of names in order as 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 olfaction in the common group. And you can see where
2:51:13
Are more like each other or not. And we've done that for color vision olfaction. Internal audition. Okay. And we are most dissimilar in color vision. Okay. We're in color vision. The variance is about 100% amazing. It's yeah. And there's tons of literature on this tons of it, tons of it, right? And in olfaction and audition, they're about the same.
2:51:40
So we're not different were very similar. We're just very poor at appreciating this and 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 dislike in order, right? But just the way you can learn to like a sound or just like a sound. So you know, this doesn't take away from the hardwired link of a structure to its perception that you can that they're malleable and and and we're
2:52:10
Very variable, we're actually kind
2:52:12
of similar.
2:52:14
that's a perfect segue to the question I have next, which is if in general, people perceive certain odors similarly,
2:52:24
You could imagine that odors could be manufactured co-opted Etc. In order to elicit richer, sensory experiences and drive choice-making. Yeah, that's obvious at the level of the smell of a hot dog stand or freshly baked bread. Etc. 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 computer. So for a long time,
2:52:53
Now, there's been this idea that there will soon be Google smell not to call out. Google is the only search engine but DuckDuckGo smells for those of you that don't hear. Smell Chad, be tears, your coach at GPT and on and on in other words, you know, Vision visual 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's it can be done, right? But it hasn't really taken hold
2:53:24
However smell being such a rich source of Behavioral and hormonal and other sorts of deep deep information that can drive people in to Yum, Yum, Gourmet type decision-making. Yeah, seems like an amazing candidate. So what is your experience with generating smells in silico in computers and here Folks at for those of you that aren't catching on to this and I don't expect that everyone would because what we're really
2:53:53
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.
2:54:18
So I'll start off answering from, from the, the name you throughout
2:54:23
Are Google. So about probably about five years ago. Google had an April Fool's
2:54:32
spoof, all right? And they put out this
2:54:35
video of Google smell. Okay. And and it had all these like classic like sales images of, you know, holding up your phone to a rose, and it generating Rose and, and, and all these things, right? So, Google is now trying to do that.
2:54:53
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 start-up. Like, yeah, I don't know. Tons of
2:55:22
money, a lot. There's a lot.
2:55:23
Of money in that world.
2:55:24
Yeah. In Google. Yeah to, you know, to digitize smell and and
2:55:34
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 chemo signaling work but actually half of our lab is devoted to this question of ultimately digitizing smell.
2:55:53
And so this is a very very active field of research. And 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 are all the world. Lots of people are are very cognizant of the importance of smell and smells like way up there.
2:56:22
And people's awareness because of covid. And this is driving a Renaissance of olfaction research and in Awareness to olfaction is something that's worth paying attention to. And in our lab has been involved in this way in this effort for a long time 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
2:56:52
The going thing was that that until recently, at least, there was no scientist or perfumer for that matter. Who could look at the structure of a novel molecular mixture and predict for you, how it will smell or a smell something and tell you what it molecular structure could or should be, you know. So in contrast, let's say to trivial like, color vision. Let's say, so, you know, 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
2:57:22
You you would know or, you know, or the other way around, you know, 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 experience, discolor the rules are well, known and olfaction. We didn't have that until recently, but over the past few years, a bunch of labs have really pushed this forward. There's a bunch of
2:57:52
Work
2:57:52
out of Leslie, vauxhall's Lab at Rockefeller and Andreas Keller working with Leslie who've done a lot of work on this front. Also work from Joel mainland's lat Lab at monell and their Discovery Joel was a graduate student in our lab and 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
2:58:20
front to
2:58:22
Something a mini break through as far from
2:58:23
arrogant and and this is a paper led by our camera via from our lab and could be Schnitz. Also a major contributor. There are paper published in nature about a year and a half ago in the height of covid pandemics and nobody really earned. I won't see nobody but it wasn't noticed in the way what otherwise would have been. It was it was published in nature really on like a week where the whole world was like.
2:58:50
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. Hmm. Okay. Now not only could we predict that but we could design it
2:59:20
We can generate mixtures with knowing similarities and the result was highlighted and you'll appreciate this coming from vision. Is that using our algorithmic solution? We generated all Factory metal mirrors so we measured mixtures completely non overlapping in their molecular structure, but the smell exactly the same.
2:59:47
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 know, and yet we did and anybody can recreate them, this is simple actually. And in the paper we do a few things. Like we generate a minimum error for Chanel. Number 5. So you don't like perfume. So this one but but we take
3:00:16
So we generate a Chanel Number 5 with no component from Chanel. Number five in it. Okay. And we actually have a publicly available web site. 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 metal mirrors. Now once we did that,
3:00:35
in way we've generated the the infrastructure for digitizing smell because
3:00:43
What again, what we, what are what our algorithm predicts, our framework predicts is similarity but in a way that's enough for you. Why is that enough? We have a map of four thousand molecules for each one. We know there are perceived smell now you can make up any make sure 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
3:01:13
Falls. You know on tomato. Then what you generated smells like tomato. So we now solve that problem, we can predict the odor 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.
3:01:36
And that's what we're working on now and then about a month ago. So this is in collaboration with the lab of a Jonathan Williams and Max Planck in Munich. Jonathan Williams is an atmospheric chemist but he's really good at it using gcms these tools that measure molecules so Jonathan Williams measured odorants in Germany. Transmitted the information to us over IP.
3:02:06
We fed that into our algorithmic framework and recreated it from a device that makes this primaries and we tried to do for different odorants in our proof-of-concept. Test one of them was Rose and we failed at recreating Rose. We in fact we created something that had a purse it but most people perceived it as Bubblegum the second one we tried to do is I nice and we failed. It recreating a nice
3:02:36
Um, 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 with was violets and 15 of 16, people said violence. So the first odor ever transmitted over IP is violets and we did that last month. Of course.
3:03:05
This is not anything near a practical solution. The device that Jonathan was using to measure is a 1.5 million dollar device bigger than this table.
3:03:18
That's right. I remember when VCRs half the audience, won't even know what that is because yours were like this big. So, we're all good. All right. I'm all good with the, with the prediction that things will come down in size and
3:03:29
cost. Hey, I'm just saying, you know, we don't hold your breath for this to be on your table tomorrow.
3:03:35
And you know, again, even even, you know, although we haven't had this very initial proof of concept, you know, it doesn't, it's not even yet. Close to being a paper. We are submitting because they're so lots of work to be done, but we're on, we're on the path. We're on the path and you know, Google probably beat us to it. They got a
3:03:56
lot of you seem pretty, dog it in there. Yeah, they
3:03:59
have so much more resources than that at this stage, it
3:04:05
And there they were already published two papers from that effort. That are good. Yeah, you know, if they
3:04:12
definitely have a lot of dollars in a lot of people, a lot of good neuroscience and other biology, Engineering, Graduate students and postdocs go there. But, but the real question is, are they getting the best people? Because as you and I both know in science, the often times its small groups of the very best and most creative people that can outrun and outgun large groups and
3:04:35
Here. I don't have anything against Google. Yeah. Yeah. I use it all the time. Huh. I'm not a betting man but I
3:04:41
would put my money on Google on this race, but I'll give I'll try and give them a run for their money. There you go. That was
3:04:49
inside. Moses want to see the problem solved regardless of who gets there. First, what I'll say is, you better get going and Google because no miss being, he's humble, and he's dogging, so better better get cracking there. We just cost the weekends of and
3:05:02
broke up the relationships of a bunch of signs of
3:05:05
When I was a graduate student at Berkeley, I remember hearing there was a guy and in our common friend or Irving's, hookers, lab, that worked 100 hours a week. So, I was like, oh, I'll work on her in two hours a week which is not a good
3:05:15
choice in any case it's
3:05:18
it's abundantly clear that you're making progress here and and I 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 the F1 race or something but thinking
3:05:35
Dating apps. I'm thinking you know nowadays everyone knows that when you travel and you want to see your family your grandkids are kids, you better to get on FaceTime and see them or Zoom then to just hear their voice. We're all talking about being able to smell them. I'll tell you
3:05:50
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
3:06:05
Dreaming, let's say of being able to transmit to you, the difference between a Cabernet or Merlot, 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. 24K order transmission.
3:06:23
Then medical Diagnostics is worth. 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 odor. I mean, every disease is a specific metabolic process. Metabolic process have metabolites metabolites have a smell.
3:06:44
Olfaction once it's digitized and 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 a vision, I mean this is not closed 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 to excuse me for the
3:07:14
The imagery, but you will have an electronic nose in your bathroom. Each one of us will have in the toilet and it will be doing Diagnostics all the time. And that's, that's where it's going to go. But again, not anywhere in the very close
3:07:32
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.
3:07:43
No, my want to say thank you for your time today. First of all, it was a tremendously interesting conversation and we touched on so many things hormones. Smells the architecture of the olfactory system. I know that people listening to this are realizing what I'm going to say it anyway, what an Incredible Gift, you've given us in as a as a expert in this field. Giving us this tour of the work that you and others who you credit. So,
3:08:13
So generously have done to elucidate this incredible system that
3:08:17
we call olfaction chemo sensation.
3:08:19
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 signs, but I'm going to, I'm going to purposely embarrass myself a little bit by saying that from the time I was at Berkeley, and I then install that experiment being done, and people, foraging falling scent trails. And then, when I was a child,
3:08:43
Until I was a junior Professor. I use 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 and that's really what I do for for a living as 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 spirit that you bring to it, whatever drives that Spirit as the great late been beerus used to say,
3:09:13
Keep going because we are all benefiting tremendously and and I also just want to say that, you know, for people listening to this that 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 and many, many people listening to this, I just want to extend it. A huge debt of gratitude. Thank you so much.
3:09:44
So I'm I'm blushing. I don't know if this doesn't come across on the on the radio Podcast but thank you so much for very warm words. I mean, you know we as you know it 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 at you you function without that I mean I guess that's one of the things you need.
3:10:13
Need to be a scientist is to have the you know the drive to work without
3:10:18
that 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 of the world as well. So my only request is that you come back and tell us about the next result. Sometime not too late now.
3:10:35
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
3:10:43
In Israel and and tell us both about the science and the public science were here doing. And then I'll come again, I'd a good bargain and I can I could delighted. Thank you so much. Yeah. Pleasure,
3:10:55
thank you for joining me for today's discussion about olfaction and chemo, sensation with dr. Nam Sobel. If you'd like to learn more about the work in the Sobel laboratory or read some of the papers describe 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 notes.
3:11:13
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