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

welcome to the huberman Lab podcast where we discuss science and science-based tools for everyday life I'm Andrew huberman and I'm a professor of neurobiology and Ophthalmology at Stanford School of Medicine today my guest is Dr Noam Sobel Dr Noam Sobel is a professor of neurobiology in the department of brain Sciences at the Wiseman Institute of science his laboratory studies olfaction and chemosensation olfaction is of course our sense of smell chemo 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 or directly from the surface of their body and you are actually applying it to your own body and you are processing information about that person's chemicals to determine many things about them including how stressed they are their hormone levels things that operate at a subconscious love 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 will also learn that tears yes the tears of others are impacting your hormone levels in powerful ways you will also learn that every so often actually on a regular schedule there is an alternation of ease through which you can breathe through one nostril or the other and that alternation reflects an underlying Dynamic of your nervous system and has a lot to do with how alert or sleepy you happen to be the list of things that Dr Nome sobel's laboratory has discovered that relate to everyday life and that are going to make you say wow I can't believe that happens but then go out into the real world and actually observe that that happens in ways that are incredibly interesting just goes on and on in fact his laboratory discovered that we are always sensing our own odors that's right even though you might not notice your own smell you are always sensing your own odor cloud and throughout the day you periodically smell yourself deliberately even though you might not realize it in order to change your cognition and behavior I first learned of Dr sobel's laboratory through a rather odd observance that observance took place when I was a graduate student many years ago at UC Berkeley at the time Nom Sobo was a professor at UC Berkeley as I mentioned before he has since moved to the Weissman well I was walking through the Berkeley campus and I saw people on their hands and knees but with their head very close to the ground and their eyes were covered their hands were covered their mouths were covered and only their nose was exposed and what I was observing was an experiment being conducted by the Sobel laboratory in which humans were following a scent trail that Central was actually buried some depth underneath the Earth and yet they could follow that Central with a high degree of fidelity it was from that experiment and other experiments done in Dr sobel's laboratory at Berkeley and at the Wiseman involving neuroimaging and a number of other tools and techniques that revealed the incredible power of human old faction and humans ability to follow scent Trails if they need to and that of course led to many other important discoveries some of which I alluded to a few moments ago but you are going to learn about many many other important discoveries in the realm of olfaction in chemosensation that have been carried out by Dr Silver'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 theme I'd like to thank the sponsors of today's podcast our first sponsor is Roca Rococo makes eyeglasses and sunglasses that are of the absolute highest quality I've spent a lifetime working on the biology the visual system and I can tell you that your visual system has to contend with an enormous number of challenges in order for you to be able to see clearly Roca eyeglasses and sunglasses were designed with the biology of the visual system in mind so no matter whether or not you're wearing them for sport whether or not you're wearing them for work or for socializing you can always see with Crystal Clarity their glasses are extremely lightweight so most of the time you don't even realize that you're wearing them I wear Roca readers at night and sometimes when 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that was the dusk dusk mattress which is not too firm and not too soft and I've been sleeping on it for more than two years and it's the best sleep that I've ever had if you'd like to try a helix mattress go to helixsleep.com huberman take that two minute quiz and they'll match you to a customized mattress and you'll get up to 350 off any mattress order and two free pillows again if you're interested you can go to helixsleep.com huberman for up to 350 off and two free pillows and now for my discussion with Dr Noam Sobel Dr Sobel gnome welcome thank you must say I am extremely excited for this come conversation I've been a huge fan of your work for more than a decade or two uh yes kind of frightening yeah but yeah we overlapped at UC Berkeley some time ago although we did not meet and we lived in the same apartment and we just learned that the amazing apartment that you moved out of was the apartment that my girlfriend and I at the time moved into in 2006 I believe so uh we've shared quite a few things um and today I would love for you to share with us um All About The Amazing landscape of chemo sensation in particular olfaction or sense of smell and some related perceptual abilities or subconscious abilities including pheromones Etc to get everybody on the same page I'd like to just start off by asking what are the major components of our ability to smell obviously or I like to think it involves the nose at some level it does to what extent is that mixed in with other senses like taste and perhaps more importantly what about the chemicals that we are sensing through this thing and for those of you listening um 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 um making sense of without our awareness if you could just um give us the top Contour or even deep Contour if you like of the uh the parts list and the various roles they play so you you've asked a lot of questions at once um you know I'll start with a little comment on the way you you said smelling through our nose which we indeed do but we also smell through our mouth actually there's a process referred to as retronasal olfaction where um odorants come up through our the back of our throat and out of our nose the reverse way and we smell things that way as well and in fact a big part of the contribution of olfaction to food and taste comes from that from retro nasal off action but uh uh primary olfaction is referred to as orthonasal faction that is through our news we Sniff and sniffing is a big thing well I have a sense we might talk about that a lot today in all sorts of contexts so we sniff in through our nose and to answer your general question of the organization of the system um so molecules Airborne molecules travel up our nose a distance in the human of about six or seven centimeters to about here where they interact with I will use the word sheet of receptors but she is a bit misleading here it's not a sheet it's very convoluted we have about seven million such receptors uh lining a structure known as the olfactory epithelium this is the sensory surface of the olfactory system the olfactory epithelium again about probably about six or seven million receptors in the human in the human probably of about 350 different kinds so that's amazing that means a meaningful percentage of your genome is devoted just to this just to the kinds of olfactory receptor subtypes you have in your nose by the way I can share an amusing story I would imagine amusing stories are good for podcasts so that number of six or seven million receptors is probably not very well grounded it's hard to count but it's reasonably grounded and there was this thing roaming around in the literature about Bloodhounds having billion receptors in their nose which is why they're so amazing and this number was you know it sort of propagated through the literature and and our lab has written over the years a few review chapters and and we were repeatedly writing the olfaction chapter for a very large one of these large textbooks the gazanaga handbook of cognitive Neuroscience I think it's called um and and we had that in there as well somewhere and and one time when we're renewing the chapter for a new version of the book I told the graduate student who was leading that at the time she's now a professor at Tel Aviv University I told her check that check that reference out where in the world did that come from and we started going back and back and back and it turns out it comes from a textbook an Australian textbook and we found the author of The Textbook and and we wrote her and I said look there's this thing in in the literature of a billion receptors in in the Bloodhound where did that come from and and surprisingly she answered me and you know I was hoping to get a reference right but it was a reference and and this is where it really becomes funny for us because she said I I was once um at a lecture of uh an all-faction geneticists geneticist by the name of Duron 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 Doran lancid is in the building next to me okay he's in Weitzman Institute genetics I mean he used to be he's retired now uh and and he he had meaningful contributions in the history of wolf action um so I picked up the internal phone and and I said hey Duron you know did you say that there's a billion receptors in the Bloodhound knows and he said what's a bloodhound so this is totally made up right it totally made up and it propagated I mean you can you can probably go into Google and type like a billion receptors in the blood town and you'll get a lot of hits but there was absolutely no evidence for that amazing and not just amazing in light of what it it tells us about olfaction and Bloodhounds or otherwise but amazing because it sheds light on just how much of what is in textbooks scientific and medical is absolutely wrong things things propagate and and you know you set yourself in right so we fixed that in that version of right and and so to finish the line so that so odorants interact with these receptors um here in our epithelium where they undergo what is referred to as transduction that is the odorance our Dock of the receptor and turn into a neural signal or enforce the receptor to respond in a neural signal and this neural signal in fact action potential is not gradient potentials of any kind uh propagates uh via the olfactory nerve now this is a nerve that goes from our epithelium right here behind the forehead no it's well yeah yeah here uh through uh the thinnest part of our skull an area referred to as the cribriform plate which is perforated it has a lot of holes the nerve goes through those holes and synapses at the first Target in the brain uh which is the olfactory bulb and humans that forms an interesting uh point of sensitivity um because a lot of people lose their sense of smell due to trauma uh because of that structure yeah a head hit type trauma well yes although uh you denoted hitting on the front of the head which is where all this real estate is but actually uh the more common cause for losing your sense of smell for trauma is the back of the head because of what's referred to as a contra coup injury so as your listener is probably no our brain is floating in liquid in 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 in the skull it sort of crashes it can crash against the front of the skull which is why you also have in a contract Winery you also often have frontal damage but what happens is that this generates a shearing motion on the crib form plate and the olfactory nerve is severed and if it's completely severed it's it's lost forever because my understanding is that the olfactory Sensory neurons can are among the few central nervous system neurons in adult humans that can regenerate so or replenish themselves right so so I'll I'll again there are a few questions yeah that's okay so first of all we will spin many plates simultaneously if it's completely severed completely then yes you're lost forever yeah if it's completely savored because even if you'll have regeneration at the basal cell level at epithelium they won't manage to find their way back uh to the bulb if if you have partial or something left or something shows up in a short while after the injury then you have a good chance of recovery because they grow along the trajectory of the other axons or pioneering the way for them assumingly yeah interesting and so so basically and and basically the time frame and you know it's funny I get a lot of emails on this although I'm not a medical doctor but but I get a lot of emails from people who have lost their sense of smell because it's very distressing and now more people know this because of kovid that it's very distressing and and basically the rule of thumb is that if you don't get it back within a year to a year and a half you'll never uh get it back my understanding of the statistics on olfactory loss in covid and and other viral type infections is that um first of all I had I experienced that when I got covered including total and awesome for one day and not total it was just there was a remnant of an ability to to smell or set or perceive the smell of a lemon and I was huffing as hard as I possibly could I actually uh there's an over-the-counter remedy and this is not uh pseudoscience because there's a number of papers published about this on PubMed the 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 or I don't know if it works successfully for you or if you would have recovered anyway I mean you didn't do a control that I was not willing to do the control experiment uh exactly yeah let me say two things on this front first the date on the alpha lipoic acid is [Music] one word about the smelling the lemon and this is uh I'll take that opportunity to to share more information when we smell things it's the result of more sensory subsystems than the olfactory system alone 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 has sensory endings in your nose and 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 itself trigeminal yeah the tearing of cutting an onion is a trigeminal reflex amazing we talked about trigeminal in the context of headache during a headache episode it's a trigeminal reflex so the lemon you are smelling may have been a trigeminal sensation so smelling the lemon with my eyes is what you're saying well no with your nose but with your trigeminal receptors and not your olfactory receptors um so in within you know all faction researcher jargon uh there's what we refer to as pure olfactants 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 uh the coffee right here is a purolfactant of vanilla is a known plural factant these things have no trigeminal activation um but as long as we're on this topic and we'll weave back and forth but I'm glad we are on this topic because a tremendous number of people wrote to me during the pandemic and continue to about olfactory uh loss um is the I I've heard of this olfactory training where whereby if you have a partial or even a complete loss of of primary olfaction right that um one is encouraged to smell a number of different smells I I grew up studying activity dependent wiring of the nervous system it makes total sense to me why keeping neurons active keeps them alive so this is not fired together wired together type thing by the way that's a quote from Carla Schatz not Donald head folks or me um but this is about keeping neurons electrically active in this case olfactory neurons in order to maintain their connections because otherwise they will die of action 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 of the training programs more than the alpha lipoic acid right and 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 makeup cabinet or whatever and smell them you know attentionally and constantly and sniff them and and that exposure will help you recover uh there's good data on that by now you made that uh point in passing about regeneration in the olfactory system and neither one of one of the cool things so in all faction you can you can study many things through all faction indeed one of them is is an is neuro regeneration uh because the olfactory neurons are really the only neurons that do that systematically in the adult mammalian brain and whether the human olfactory system shows the same level of regeneration as it does in in uh in other mammals is and was somewhat questionable and I'm just bringing that up to share a really cool study that was published in neuron I think somewhere around 2014 um where to address this question I just really like the idea of doing that what they what the authors did um was look at in in postmortem they looked at levels of c14 in in adults were 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 um and that paper suggested that that there's not as much turnover in the human olfactory bulb as there is in other mammals uh other lines of data suggest otherwise so this is kind of a debated question as to what extent degeneration you have in in the human olfactory system as opposed to other uh mammals but but that was just a really cool paper I think of of doing that fascinating no I I should I finish the the path just so we have to so so we said so so information then synapses at the olfactory bulb from from uh uh 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 a thousand two hundred probably so all the receptors of one subtype converge to one location in the bulb and this location is referred to as a glomerulus or an employee and and that may be a slight oversimplification it's in fact two glomeruli there is a mirror sort of a mirror cut line and so all the receptors of one subtype will converge to two mirror glomeruli on the olfactory bulb so you end up having uh two glomeruli that reflect that one receptor subtype and so if and this is as far as I'm giving you now the textbook view of of how the system works but then I can I'll happily share with you things that pose a problem for the textbook view of how things work but the textbook view of how things work is that every such receptor subtype is responsive to a small subset of different molecular shapes what sometimes referred to as autotopes the molecular aspects of deodorant so each receptor is is responsive to a different subset of odotopes let's say 10 and each ototope will activate a different subset of receptors so potentially you have this insane common and torics of this potentially 350 dimensional space in the human potentially but then because of this convergence you end up having on the bulb in a way a map reflecting or receptor identity so so let's say this coffee activates receptors of type 1 3 and 7 so the glomeruli of receptors one three and seven will light up quote unquote when I smell the coffee and if you could take a snapshot of that theoretically you would have the map of of coffee and and so on and so forth this this is sort of the textbook view of how the system works and and then information goes from the bulb to several Targets in the brain I mean what is referred to as primary olfactory cortex is piriform cortex and then the Rhino cortex this is on the ventral surface of the brain the lower portion of our temporal lobe um and information goes there directly but it also goes directly to the amygdala it probably goes directly to the hypothalamus it may go directly to the cerebellum uh it goes all over the brain so so information projects widely from there and as far as people understand the map that may exist on the bulb doesn't exist in the rest of the brain and the understanding of of how coding occurs in the rest of the brain is is murky commonly one here is that the memories that we have of odors are somehow more robust um than the memories of other perceptual events in our life I I don't know if this is true or not but um people will say for instance I can still remember the smell of my grandmother's hands or the smell of cookies in her kitchen at a minimum it points to the fact that smell and memory are closely linked and you just mentioned a direct um you know multi-station but nonetheless somewhat Direct path from the nostrils to the hippocampus one of the primary encoding centers away yeah which is which is a remarkably short pathway considering that for instance uh just by example because some of our listeners won't be familiar with this but some will that sound waves that uh you know are transduced into neural signals at the level of the inner ear go through many stations before they arrive at the location in the brain where we make sense of those sound waves as voices or music Etc whereas olfaction is more of a direct route um to the to the memory centers um is there any uh gesso story or real uh objective truth to the idea that olfactory memories are formed more easily or maintained longer or more robustly than other sorts of memories so so yes but first I I should I should say that I'm not an authority in all Factory memory it's sort of it all have to remember is a huge field of research and somehow our lab has never really um gone much into that although again the same student I happened to talk about before I Sharon who's again now A Faculty at Tel Aviv uh um ran a study a paper we I think we published in current biology biology called the privilege representation of early olfacturers associations basically there's something about the first time you experience a smell that generates a particularly robust representation more than other sensory stimuli and and that's what chain fact compared so there's something about the first exposure to a smell um in terms of the brain encoding that that etches it into our uh being and and this is an effect that has you know it has Echoes of course in literature I mean you know the the biggest cliche in this is to bring up the priest effect right so the priest effect is when he ate the Madeleine and it immediately the taste and smell immediately reminded him uh of of an event in his childhood where where uh where the same Madeleine uh appeared uh um but but so that's something very real there there's a lot of research on it uh not coming from our work so I'm not an authority but it does sound like there's something special about olfaction um and that doesn't mean that there isn't something special about Vision or audition each one has its own uh unique uh I'm the last argue that there's something special about actions my students make fun of me because they saying there's some truth to that that I try to explain everything through the olfactory system I mean for me everything is olfactory so so yes 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 ag1 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 and the reason I still take athletic greens once are usually twice a day is that it gets to be the probiotics that I need for gut health our gut is very important it's populated by gut microbiota that communicate with the brain the immune system and basically all the biological systems of our body to strongly impact our immediate and long-term health and those probiotics and athletic greens are optimal and vital for microbiotic health in addition athletic greens contains a number of adaptogens vitamins and minerals that make sure that all of my foundational nutritional needs are met and it tastes great if you'd like to try athletic greens you can go to athleticgreens.com huberman and they'll give you five free travel packs that make it really easy to mix up athletic greens while you're on the road in the car on the plane Etc and they'll give you a year's supply of vitamin d3k2 again that's athleticgreens.com huberman to get the five free travel packs and the year supply of vitamin D3 K2 when I was at Berkeley I was walking across campus one day and I saw I think students but I saw people on their hands and knees with goggles on gloves on and um I think their mouths were covered too everything was covered was covered and they were walking well they were crawling along the ground um and I thought this was peculiar but then again it's UC Berkeley and the joke is if it to get noticed on the UC Berkeley campus you have to be naked and on fire right one or the other would not be sufficient please don't run this experience that kind of place um yeah but nonetheless a paper came out a few years later describing the results of what turned out to be your experiment that your laboratory was running which was having people follow an odor trail with their nose and um and my understanding is that people can improve their ability to track sense quite robustly especially if we deprive them of vision and somatic Sensation that is touched in some other um Sensations maybe you could just tell us a little bit about that study and um and for I think in our audience I'm suspecting that many people have a Keen Keen sense of smell very I have a family member who just like detect any negative you know putrid odor in the environment but also good odors um exquisitely well and I I have other family members who sense of smell is quite poor um I'd love for all of those people to learn a bit about what is possible in terms of training up or improving our ability to smell and perhaps in the context of that study if you will yeah so so first before even talking about improving just off the bat humans have a remarkable sense of smell and this is something again in our lab we already said we know yeah we know this this is old news but but to people who who come from different worlds we have to reiterate this sometimes when I give you know public lectures to to non-all-faction audiences I reiterate this humans have an utterly remarkable sense of smell to put that a bit into sort of you know things that you could that are tangible so so for example um mercaptans which are added to cooking gas so that we smell it because otherwise it wouldn't have a smell so that the smell of gas is not the smell of gas of propane it's an additive yeah it's more Captain the sulfur like smell so so uh our detection threshold that is the level at which we can detect it is 0.2 parts per billion okay there's no machine that can really do that that effectively no gas chromatograph nothing now to give you another sense of of making this again really tangible we're working with an odorant in our lab called estro tetra enol that our participants can detect when we have it mixed at 10 to the negative 12 molar in the liquid phase to give you a real sense of that we did the math if you would take two olympic size swimming pools and you would pipe it 1ml 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 so that's just in terms of its detection abilities which are are just you know remarkable really up there in the mammalian World we're not a bad mammal at all faction um and and beyond that we can we can improve okay and and the example you're talking about actually started off uh is a lab bet okay we were having a lab picnic so I guess I should hear fill in because I I'm your guest from The Weisman Institute of Science in Israel but before going back to my home in Israel I was a uh um faculty at UC Berkeley and the Helen Wells Neuroscience Institute and this study was done during that time and we were on a lab picnic and we were having indeed one of these sort of lab discussions arguments on what humans can and can't do with their sense of smell and and I said that humans could truly even track odor like a dog and people there said no way and we ran this quick experiment uh which I have video of but I don't think we'll show it here uh but I actually have original the picnic video we have it and uh a graduate student by the name of Christina zellano a brilliant graduate student at that time who's now she's now a professor at Northwestern and she's really leading the field of all faction Imaging today but she was the volunteer and we dragged a chocolate bar across the grass and blindfolded her and checked if she could track the track we made with the chocolate which he did very effectively right and as far as Placer at the starting point of the line or I think we did I don't exactly remember what we did on that sort of picnic uh tryout but you know I assume she never practiced that in her life before right and yet you know she she did it really really well and and then this went on as a lot better in a way that that I I said to my my students okay we we have to make this into an experiment put in an experimental setting and and and quantify what's going on uh and they all said that it would be uninteresting that was the BET and and I told them it would be in nature which is a bit I won in this case nature of course being one of the the three Apex journals so it was it was Nature Neuroscience to prepare but but uh so so then we we turned it into an experiment and and what the experiment was is that we brought in participants naive participants not not graduate students from our lab uh completely deprived them of any other sensory input so we blocked their eyes we block their ears we blocked everything we blocked they were wearing heavy gloves uh you know they they couldn't sense anything and we generated a 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 uh odor Trail every time was it and at the base of the grass or in the dirt it was buried it was buried under the grass really yeah yeah wow and I did not know that it was buried under the grass and we conducted aerial photography and um participants also had this sensor pack that they were wearing where we measured nasal airflow in each nostril in real time and uh they all we also used something called rtk GPS which is a way to lay uh radio frequency grid over the GPS grid so that you have millimeter resolution in space basically it's used by surveyors mostly um so that we could track Behavior and we found a few things doing this one is that people could just do this right off the bat um the second thing we found that is when we train them up then within uh average of four days uh 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't crawl as fast as the dog can run but you as fast as you can crawl you can send track and then to sort of add what made it really interesting from from a systems neuroscience perspective is that we asked where they're having two nostrils uh contributes to this so we built we constructed a nasal prosthesis if you will uh that had two versions one is that it combined both nostrils into one big nostril centered and the other is that it maintained two separated uh nostrils and we compared performance under these two conditions and people perform better uh with two nostrils over one centralized nostril although the flu remain the same so you're taking advantage of the information uh that comes from your two separate totally separate nostrils by the way the system I described before of your epithelium and bulb and and connection to Cortex um you have two of those right it's completely unilateral well almost completely unilateral system there's some very small exceptions to that but but so a representation on both sides of the brain much in the same way we have two eyes we're not a cyclops we can gain depth perception information we can perceive motion better as a consequence and a number of depth especially stereopsis and we can locate sound because of the difference between our ears and how head blocks them between and amazing another question about the the mechanics and strategies that you observed because I think there's information about the system the brain as a consequence um were you in a position to measure sniffing frequency and the specific question I have is were people doing something along the lines of a quick sniffing or a like a you know a long um withdrawal in so inhale you know we didn't so yes we were measuring sniffing and recording it and and we have all the data um there was nothing um 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 it wasn't a major component of our analysis although we did look at it uh 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 um but I'm sure if it was a major component of it it would have risen it definitely wasn't a major finding of the sniffing behavior um in the paper although again we you know sniffing behavior is a huge portion of our our life in lab uh and and it's it's taking us to to places and and it's re-emerging now in our work we're doing tons of sniffing work um you know I can share with you something that that I think will interest your your uh listeners and viewers as well and and and we think is is really uh one of the most overlooked things in in neuroscience I invite you to do the following experiment so occlude one nostal by pressing on it from the side and sniff in and then include the other and sniff in do you sense a difference in flow yes okay do you know why that is no and it was the next question on my list so don't feel badly about not knowing why that is um most people don't uh but that is a reflection of something referred to as the nasal cycle so in fact if you were to do that repeatedly you would find that your high flow nostril and low flow nostril alternate every two and a half hours on average in an absolute way or is it kind of like a sine wave like gradual shift to the one and then gradual shift back it can vary it can vary and we don't yet know the rules uh all the rules but but you have this constant shift from side to side the shift becomes incredibly pronounced in sleep so we can measure the power of the difference and in sleep you have this phase shift of power you have a huge like one closes and one opens totally and it turns out that this is linked to uh balance in the autonomic nervous system so as you and your listeners know we have an autonomics nervous system that has a sympathetic and parasympathetic component to it and and they're in balance or imbalance in many diseases for example and this interplay between the uh Auto between the the sympathetic and parasympathetic nervous system drives the switch from left to right nostril just to remind people um sympathetic nervous system has nothing to do with sympathy um has everything to do with generating patterns of alertness it's sometimes called the fight or flight system but any pattern of arousal positive or negative and then it's balanced in a coordinated way or at least in parallel with the parasympathetic nervous system which is sometimes called the rest and digest system but as a 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 yeah perfect so now imagine right imagine imagine you would walk around living your life right half of the time with one eye closed like this and the other half with one eye closed like this and you have this eye cycle all right and that was linked to autonomic arousal I assure you you would go to PubMed there would be five million papers on the eye cycle right and the eye cycle in every disease you can name and what it denotes and what it tells us and what we can do with it you have exactly this marker you're walking around with a marker on balance in your autonomic nervous system and we do nothing with it so 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 airflow in each and nostrils 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 um I can I can give you a nasal halter measurement as an adult and I can say this is work by team nasaroka graduates in our lab 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 in ritalin or not so I can I can measure your nasal airflow and say if you are or are not with ADHD and if you are or not on Ritalin incredible I have a couple of questions about this is it the case that airflow through one nostril is reflective of a sympathetic nervous system dominance versus parasympathetic um or is it simply the case that this alternating Left Right nostril periodicity um 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 uh maximal on one side versus the other is that simply reflective of an overall balancing let's maybe is it the hinge in the Seesaw or is it the tilt of the Seesaw so I don't have a good answer I don't have a good answer I mean you know I could give you sort of a you know I could say that to some extent uh uh right nostril more open um is more sympathetic and the left nostril more open is more parasympathetic but that that wouldn't be very correct I mean you know I'm sure that it's you know the yogis are going to be all over this so right because I get this my lab does do some stuff on on breathing and the the yogis are always saying okay you know because there's this thing I don't do yoga anymore but not for anybody but um where they'll have you breathe through one nostril or the other and I've I've probably even asked this question on social media I'm gonna become Public Enemy Number One of the yogis right now so listen we so we we they'll come at you with um yoga mats which are not very dangerous we really so since we're so interested in this mechanism one of the things we'd really like to know how to do is is to gain control of it somehow and there's this world out there of yoga who claims to have control over this so we said okay let's bring like really serious yoga practitioners and see if they can shift their nasal cycle from left to right but by Will alone right not 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 to cure ADHD or or whatnot right so so we posted like on all the lists of like the yoga teachers and had this parade of yoga teachers walking into our lab this was one of the strangers a lot of Sandalwood odors and bare feet white white uh clothing and and so on and and so we we study I actually know we studied 14 yoga teachers all 14 uh by you know by the conditions of enlistment for this uh came in saying that they they can control shifting from left to right uh nostril without plugging a nostril yeah by the power of thought come on um and you know how many of 14 succeeded zero including including one you know the most extreme one was we had this guy who who you know and we're recording and we know how to record this really well right and and he's sitting there saying yeah I'm switching now and I'm it's switching and you know you're looking at the Monitor and no it's not switching and and so no no yoga teacher that we found uh could uh willfully switch uh between left and right nostril flow and yet they're they are convinced that they are and I have to imagine they're not trying to you know there's no incentive for them to lie right yeah no I I it 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 um given that the alternating flow through one or the other nostrils reflective of the autonomic nervous system has this two and a half hour periodicity if I suddenly enter a bout of stress for instance does it switch because that's reflective of the autonomous 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 unilateral smelling through or unilateral nostril smelling periodicity they've been we named it something I could think of the wrong thing I'm sure is that driving the shift in the autonomic nervous system or is it merely reflective of the shift so you've you've very concisely now worded aim two of a grant that was probably just rejected but but basically we're trying to answer exactly uh that question and we're currently running experiments on that line so so we have one experiment where uh uh we're looking um so we're exposing participants to pain uh we're using a cold water hand exposure it's a really cool Paradigm because it it there's huge individual differences we just started this we built the setup just now and you have a lot of meat to work with there because there's a lot of individual differences here it's capped in three minutes so be for safety reasons because you have you have participants putting their hand in in two degrees Celsius water but there'll be participants who will pull it out at like 10 seconds 9 seconds and then you'll have you'll have three minutes as well so there's lots of lots of uh and and already in so now I'm sharing pilot data with you so you know to to this might you know when it when this ends up being published it might be the opposite but so far it seems that that uh the exposure to Coal generates a shift in the nasal and nasal balance so autonomic arousal can drive the shift potentially um earlier you were describing the architecture of these um smelling systems and you mentioned these glomeruli where the olfactory receptors converge right in the bulb and then later you mentioned that the system is unilateral but with a mirror representation on both sides of the brain so for those who don't think in terms of neuroanatomy on what no one was describing is the fact that of course there are two nostrils and then a bunch of receptors they converge in these glomerular 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 process so the question I have is whether or not you believe I'm not asking for data first I just want to know what you believe that this alternating nostril airflow phenomenon has anything to do with preferential processing of olfactory information in terms of right brain left brain with the caveat that anytime we hear right brain left brain um we've covered this in a previous episode most of what people hear out there about right brain left brain emotionality logical stuff is completely wrong completely wrong doesn't exist is a total fabrication um and we'd like to abolish that myth but with that aside or set aside rather what are your thoughts on why the information would switch from one side of the brain to the other at all yeah I don't think I don't think that that the nasal cycle is an olfaction story um so so I I don't think that um that this was shaped by the olfactory system nor do I think this has major impact on olfaction I think the nasal cycle story is a different story about brain function um so so you know we have we have this sort of pet Theory where calling now the the sniffing brain approach where where basically we think that that nasal inhalation is timing and driving a lot of aspects and patterns of of neural activity and cognitive processing and and this theory is is all faction inspired in its beginning that is I mean if you think of the mammalian brain right it's which which evolved from all faction it's sitting there and an 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 one-to-one linked to nasal inhalation and and we think that that this property evolved to to be meaningful in brain processing in general not only of olfactory information but of any type of information because the brain evolved in this way in this way that it processes information on inhalation onset so a study led by offer Peril from our our lab uh two three years ago um we looked at something completely not all Factory we looked at visual spatial processing and we compared visual spatial processing on inhalation versus exhalation and the brain does this completely different on inhalation versus exhalation you're in that particular task people performed significantly better on inhalation versus exhalation what was the task was in an olfactory no no it's a visual spatial task so this is a task where uh the the specifics of the tasks were um that you see a shape and you have to determine if it's a shape that can or cannot exist in the real world so some of them were these like Usher shapes like you know where where one facet doesn't reach the other facet The Impossible figures yeah yeah but but but uh structural shapes not not and and so so a pure visual spatial task we intentionally went for a task that is not considered a ventral temporal task in olfactory cortex task in any way and and people performed much better on inhalation versus exhalation and doing this task was there a both nostrils occluded um version where people were forced to mouth breathe yes and in this particular task they also did better on mouth inhalation versus mouth exhalation but the difference wasn't as pronounced as it was with nasal inhalation versus exhalation so I'm a big proponent of nasal not mouth breathing whenever possible for um many health related Reasons I'm a big fan of the book Jaws a hidden epidemic uh written by colleagues of mine at Stanford familiar with it yeah and this idea that uh people who mouth breathe experience more colds more infections of various kinds it's not good aesthetically or for the dentist dentature I never know the teeth the gums and stuff sorry my uh my dentist is going to come after me um need to go to the dentist anyway the um that nose breathing is great for your health relative to mouth so I think it's also good for your cognition not only for your your dental health uh I think that that news breathing shapes cognition and and there other labs who are finding the same uh again uh Christina zellano is doing work on this line she she had major contributions here and and yuan lundstrom is doing work on this line there's lots of studies suggesting that um nasal inhalation is timing cognitive processing and modulating it incredible um 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 these nostrils I mean are a pathway to the brain right I I love to tell people because I work on the visual system in my lab that you know your eyes are two pieces of brain extruded from the cranial Vault right which they are the retina is any anyhow and um and then you never look at anyone the same way again it's okay but the the olfactory Sensory neurons are right there at the tops of those Caverns that we call nostrils and they are brain yeah definitely it's it's the only place where your brain meets the outside world because in your retina they're protected by 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 uh route for for neurodegenerative um mechanisms so as as you may know um loss of the sense of smell is one of the if not the earliest sign of neurodegenerative disease so for example in Parkinson's disease there's uh uh loss in the sense of smell probably 10 years before any other symptom um but people have failed to make this a diagnostic tool because it's non-specific so it's not as if you could come to your doctor and say I'm losing my sense of smell and they'll say oh early sign of Parkinson's because you can have many reasons to lose your sense of smell and and so on um but but olfactory loss again is 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 of a pathogen that enters the brain through the olfactory system um oh interesting it's it's not of course a a mainstream or widely accepted theory of any type but but it just highlights this notion that that the nose is a path to our brain I think these non-invasive um readouts of potential neurodegeneration um such as uh visual tests because of the fact that the retinas are part of the brain and loss of neurons in the retina is often associated with other forms of central generation Alzheimer's Parkinson's Etc as it's a little more invasive than what you're describing I'm beginning to wonder why we don't um get have a 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 percent worse than actually that's a really bad sign yeah that's a bad sign and so what we're talking about something completely non-invasive and could be relatively Pleasant to innocuous depending on the odor's use so yeah so so first I can answer that right and the reason that that's not happened and that might that that may be changing right now but the reason that has not happen 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 100 bucks that is it the resolution of the visual system basically and if you want to generate auditory stimuli really precisely then you can buy an amplifier for you know maybe a bit more than 100 bucks but not that much more and you'll be at the resolution of the auditory system in our lab we build devices that generate orders we call them all factometers which is a misnomer because they don't measure anything but that's what they've always been called so we call them all factometers as well and we've already built at least one all factometer that cost a quarter of a million euro and it's pathetic right so it just it's pathetic it's it's slow it's contaminated it's nowhere near the resolution of your system so one of the reasons that's not happened is just the utterly poor control of the stimulus mind you to some extent it has happened in that there there are a standard clinical tests of olfaction basically two that sort of control uh the world in this respect the older one is is a test called the upsit which stands for the University of Pennsylvania smell identification test it was developed by Richard Dodie and Penn and it's a test where you scratch and sniff and it's a four alternative forced choice test with 40 odorants so you have these 40 pages that you page through and you sniff and smell and and um you know it's been normed on gazillions of tests um I I'm always amused by it because so Richard Dodie made a ton of money uh on the upsit but he needed it because he has a habit he has a NASCAR so this every time we buy upsits and live I said there's another gallon of gas into Richard he races NASCAR it's not not like NASCAR but like one lower than that like I don't know like some some sort of formula a or formula for it or something he races a car and so that's where all the ubsites went so I always feel good about buying either PSATs because I know they're going to that good cause but keeping him in in in the fast lane yeah but but so so that's one test that's out there and indeed you know has been shown as a you know so there's reduced upsit and Alzheimer's and Parkinson's and and then a host of other diseases and there's a European version called sniffing sticks has developed and and it's 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 sniff but but those exist but they're not as as convenient as as uh is delivering stimuli and vision and audition and that's why you don't have what you've just suggested you know another thing another place where you don't have it which which I think is even more would have been even more meaningful is is you don't oh actually it's not tested in in newborns right where vision and audition is you know there's this thing called congenital anosomia right which is being without the sense of smell from birth supposedly in general uh which is a half a percent of the population it's not a trivial number not totally yeah but nobody knows if that really is true because here's an amazing factoid guess the average age at which can General and osmia is diagnosed and this is this is a horrible statistic for me for the way I see the world but what do you think the average age of diagnosis is for congenital anosmia five years of age 14. incredible 14. so most people who are one half of a one percent of the human population presumably yeah is uh without the sense of smell and doesn't realize that until they're 14 years old well I don't know when they realized it first but but it's formally diagnosed at 14 on average which means some of them even later right and um and uh right it's a distribution well what um do they suffer yes so so first of all they they suffer socially um and there's a host of of deleterious life events associated with congenital anosmia um the the die younger um the so it's it's it's uh it's this is work out of uh Ilona Croy in Germany um and you know amongst the various things that are predicted by an osmia is shorter lifespan uh but things like you know reduced uh social contacts uh reduced um romantic social contacts um it's not a good thing um and and do they lack olfactory bulbs I'm presenting they have noses and nostrils there is a condition I'm aware of where where uh children are born without no very rare yeah very rare focus on that because it's exceedingly rare um but they're born with noses and nostables um and here's the thing right we don't know if they're born with olfactory bulbs um most of them although not all of them but most of them don't have olfactory bulbs in adulthood or or I should rephrase that have remnants olfactory bulbs really shriveled olfactory bulbs but you know nobody can say the cause and effect here before we talk about the role of the the uh requirement for olfactory bulbs for olfaction a very interesting topic in its own right I I'm curious as to whether or not their endocrine system is altered because as we'll soon talk about there's a lot of signaling through the nose from between individuals that uh triggers things everything from the onset of puberty to feelings of romantic attraction attachment these sorts of things um is it known whether or not and I should say excuse me for interrupting myself but as long as I'm interrupting you every five minutes I might as well interrupt myself too that um 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 um are they uh hormonally normal so some are and some aren't and I'll I'll be specific so um there's a condition known as common syndrome which is hypogonadic development um in in men and in Kalman syndrome uh they're practically all announcement so so to answer your question yes there's a direct link and and it materializes in common syndrome that said not all congenital anosomic uh individuals have common syndrome and not all but almost all people who have common syndrome are in osmaker so so common syndrome uh goes with uh anosmia I think so there is a female equivalent of Commons or I don't remember its name uh it's not turn it's not a in the Turner syndrome family I'm not sure okay and I think it's also associated with anosmia uh but I'm not confident of that but Commons is is associated with an osmia uh so so the answer is is yes and and you know we can maybe you know of action and reproduction are are tightly linked and and they're tightly Linked In all mammals and we are big terrestrial mammals and all fashion reproduction are linked in humans as well um yeah we will definitely get into that I'd like to just take a brief moment and thank one of our podcast sponsors which is inside tracker inside tracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals I've long been a believer in getting regular blood work done for the simple reason that blood work is the only way that you can monitor the markers such as hormone markers lipids metabolic factors Etc the impact your immediate and long-term Health one major challenge with blood work however is that most of the time it does not come back with any information about what to do in 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uh and um this really so when I was growing up I grew up at the uh end of a street with a lot of boys of my age who just by coincidence had a lot of older sisters were my sister my older sister's age it was fortunate so I had a lot of kids to play with we would hang out at each other's houses bike build jumps and do all those things like kid stuff Fort stuff get into trouble or whatnot and oftentimes we would end up leaving our articles of clothing at each other's houses all the time like t-shirts and jackets and so my mom was constantly coming in and saying there's all there's this close like someone left us here I don't know who it was we were all more or less the same size and from the as far back as I could remember six seven years old and onward I could pick up a shirt or a jacket smell it and say oh well that's Eric eisenhart's shirt a friend of mine there I just gave his name or oh that's Scott Madsen shirt I I could just smell the shirt and in a conscious way know who it belonged to having never I promise not that I would pretend if I had if I had um pretend I hadn't if I had but having never actually done the exercise of going and taking and smelling my friend intentionally right okay in fact if anything I had all the reasons in the world to avoid smelling to other young boys in my neighborhood okay so yeah um that raises the question of whether or not we are consciously and or subconsciously coding identification of people that we interact with frequently or infrequently in terms of their smell and or some other aspect of their um chemistry yeah so yes um 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 uh Human Nature has has uh or nature or culture or whatnot has has pushed this into the realm of of subconscious and something we're unaware of um but we do it all the time and um in our lab has lots of studies on this front um one of them you may be familiar with it that had gained some notoriety because it's amusing um so we we look at human behavior a lot we try to look at it through our news 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 what would I think of this and and you know if you look at dogs right they've you know when they interact they visibly sniff each other it's very obvious they walk up to each other and they sniff each other um and yet humans don't typically walk up to a stranger and carefully sniff them right I mean it's we're sort of obliged to sniff our our babies that's considered almost something you're supposed to do um and it's not culturally taboo to sniff our loved ones it sort of doesn't seem like an odd thing to do but we don't sniff strangers right well or do we so we're finding more and more mechanisms where we do this and the one I'm referring to now for one example is we started looking at handshaking handshaking is this really odd behavior and it's not only in the west by the way some people think it's only a western thing it's not it's almost everywhere and and 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 and they just do and we started looking at people handshaking and and we noticed or it seemed to us that we're noticing that you know people will shake hands and then we'll go like this and like for those of you listening not watching them no um it was taking his hand and and wiping it on his face yeah grabbing his nose or touching myself yeah these 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 you could easily not notice right and and so we we asked whether that's a real thing um and this was a study led by John fruming in our lab at the time um and what we did first and if you want we can link so so this was published in E-Life and one of the nice things about E-Life is that it has a very effective way to embed videos in the publication so if you want we can link this to your system later on even the show note captions as a link on YouTube and the other for uh platforms Spotify Apple so so what we did is is um we we brought in participants to our lab and we sat them in the room uh experiment room and and told them the experiment would start soon and they should wait for us there they didn't know what they were coming from unbeknownst to them they were already being videoed uh of course later on they had the opportunity to to not agree to us saving the video in which case we would delete it immediately or or letting us use it for science or someone letting us use it for more than science for for the video that's now on elife and and we walk into the room and say okay just wait here I will be right back with you uh to set up our experiment and they would sit there for three minutes and during those three minutes we could later quantify how much indeed they just by Baseline how much they touched their nose or their forehead or their chin or how many times their hands uh reaches their face and by the way that Baseline is not low okay um and then three minutes later an experimenter would walk into the room and uh would share a consistent text it would be you know we're still setting up our equipment in the other room uh our and and so just wait here and we'll be right back with you but in the meantime just wait here and the experimenter went through this like 20 second fixed text and in half of the cases it included the handshake this was a new experimenter not the one who put them in the room so that's the first time they met so it would be a little I'm you know so and so they would put out their hand and shake their hand or not okay and we did all possible interactions in terms of gender so we matched male participants with male and female experimenters and female participants with female and male experimenters and so you had handshake and no handshake conditions and then you can quantify that behavior of the hand going to the nose after a handshake and there was a remarkable increase in the hand going to the news 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 on it's unreal the video is unreal so interesting so the hand goes to the nose now we did a few controls here to verify that this is an olfactory Behavior one is unbeknownst into participants we measured nasal airflow and and people not only bring their hand to their nose they sniff it so and this is perfectly time they go like this okay so they're sniffing their hands and in an additional control study we manipulated it so we built this little James Bond thing of a watch on the experimenter's 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 an unpleasant odor and we could drive the self-sampling afterwards up or down so this was an olfactory Behavior no doubt about it I mean we're quite confident so people in that case people must have been sensing the odor on their own hand because they'd Shake shook the hand of the of the experimenter pleasant odor and they're more frequently bringing that hand to their nose versus unpleasant odor that had been introduced to their own hand by the experimenter Yeah but no I think I think they were sensing the the ambient odor that came in with the hand that That Shook and then that either drove them to snip their more or less the odor cloud of the expression yeah and there's an interesting thing going on here too because people didn't only smell The Hand That Shook 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 might reflect that there's on the same line and again to to link to your childhood story of of uh identifying your friends by by smell um study we published just last year by uh in battle Ravi in our lab um where inval came with this uh uh basic interest in this phenomenon that's Loosely referred to as click friendships so people you meet and you click right away right you immediately become close friends and this is a phenomena that you know is poorly described or is poorly ascribed in literature as as an entity and yet anybody will tell you they know what you're talking about right I mean if you tell you know if somebody you click with right away you you become intimate within five minutes right everybody experienced this in their life you know to some extent and the question is what what was there right what was it was it because you looked the same could be was it because you know you had the same sports team that you liked or is there something uh uh deeper here and and in Buzz theory was that that um that a similarity in body order May contribute to this that people who smell the same will click in some way and so to address that she actually recruited uh um click friends from all over Israel she posted all of her social media uh to identify uh pairs of friends so these are our same-sex non-romantic diets so these are friends men and women uh whose friendship started is a click where here this becomes sensitive because it has to be a mutual click right later on we discovered there could be one-sided clicks so if somebody's sure they clicked with somebody else but the other person there's a name for that in neurology that our uh common friend the late Ben Barris taught me which is there's a phrase that neurologists use okay called sticky these are people that come up to you and and start asking you questions and then won't leave you alone they're so-called sticky people that and if you ask these sticky people um sticky in air quotes because they're not physically sticky um maybe what they could be um you know what do you think of the per this person they'll say oh they're great we're really good friends and so they've made a unilateral um click friendship yeah yeah and uh yes neurologists are talking about you if you're if you're one of these people neurologists are talking about you there's a an informal diagnostic code sticky so so so uh she she recruited um um click friends and then she sampled their body odor and and we have a a protocol for this so they're given you know uh odorless shampoo and soap to use for three weeks or something and then they sleep two nights in this t-shirt uh where they have to sleep alone and then we extract the body odor from the t-shirt and so we have a way to extract a method to extract body odor and then she she first asked um whether indeed click friends are more similar in their body order than you would expect by chance and she first tested this with them with a device a machine we call an electronic nose so an electronic nose is sort of a very poor effort to mimic what the mammalian nose does basically it's a bunch of sensors that respond to Airborne molecules in this case sensors referred to as moxers as a metal oxide covered sensors um and so she used an electronic nose to sample these body odors and she found that click friends are indeed more similar to each other than you would expect by chance by random diets and this was a significant difference and after she found that a device could do this she had other participants do this so so she had people smelling the click friends versus non-click friends and and they judge them as being more similar to each other uh than not now again you you might wonder is this causal or not right because maybe click friends go to the same restaurant together or all the time or whatever or live in the same neighborhood and and that's why they they they smell the same so to address causality she recruited total strangers and first 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 one one prediction there panned out uh but another didn't the one that didn't so she predicted that people would smell more uh similar to each other would be better at the mirror game that is they would follow each other better that did not pan out however she then also had the interaction was completely non-verbal they were not allowed to speak with each other and she did an entire round robin so everybody played with everybody else this was an insane experiment to run and and she then at the end of the experiment each person raided each other person as to how much they think they would want to be their friends and also on a bunch of ratings how nice they think they are how affectionate they think a bunch of ratings okay all of this was predicted by the electronic news so people who smell more similar to each other think that the other person is more likely to be their friend is more likely to be a nice person etc 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 causal elements of of building friendship so this is to relate to your childhood story uh there's something going on here we're constantly smelling ourselves constantly this constantly so I mean if you want to like I don't know the reason I'm smiling I mean and your viewers are listeners will understand why I'm smiling I'll send you a video to link uh uh in in the in into your podcast here we thought of calling the the fact that people constantly sniff themselves we thought of calling this the low effect and low so in America this won't pass that effectively but in in the rest of the normal world is the soccer the national soccer coach of the German soccer team so yeah I mean I don't know who would be a very famous coach here but Steve Kerr I mean this is the choice this is a super super famous uh name all around the world where soccer is the primary sport that people watch um and and once people will see this video they'll understand why we thought of calling this the low effect uh it's a very graphic uh but but people are constantly smelling themselves they're smelling themselves with their hands they're smelling themselves explicitly people are constantly smelling themselves constantly smelling others um I find this topic so interesting um and first of all confession I definitely smell myself multiple times per day and everybody does okay good yeah and I I um I would do it anyway um uh I think I like most people I either find my own smell to be neutral to Pleasant right I um occasionally I'll be like well I need to take a shower as long as we're talking about smelling oneself and um friendship kinship and its relationship to smell we have to talk about the relationship between smell and romantic attraction and bond so my understanding is that if for instance a mouse is given the option to mate with any number of other different mice they will bias their choice toward the mouse that has the immune composition the so-called MHC major histocomatibility complex which reflects immune diversity the immune system that is most distant from theirs and the The evolutionary argument being that were they to um produce offspring that the array of immune genes would be much broader than if they were to select an animal very close to them and in addition to that that one of the most strongly selected against behaviors not just culturally but at the level of eliciting a sense of disgust maybe even from the activity of the hypothalamus is mating with very close kin AKA incest because that can potentially we know produces a higher rate of mutations in other words whereas you describe the relationship between smell and choice of friends as you uh choose people who smell more like you my understanding is that in the context of uh choosing romantic Partners or sexual partners or both that you choose the person who's odor and therefore immune composition is most different right so the way you describe the animal literature is correct and there's evidence to similar mechanisms in humans our lab has not worked directly on this issue of of uh of uh romantic selection based on odor um there's a bunch of papers um wedkins Ed Allen and the wedkin lab and also Porter I'll I'll email these to you later on um that have have done a lot of this work and find exactly as you say that that um um romantic order preferences in humans are influenced by Body order and that this is linked to MHC uh uh is the compatibility complex makeup of the the portion of our genome that that shapes our immune system uh to some extent um so so this effect um has been studied and reported on again extensively in mice and also uh in in humans um not work that that we've done um the one sort of 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 in mammalian social chemo signaling so and and also related to to so it's it's not related to Romanticism in any way or or but but it's related to reproduction and and indeed in our lab we've not looked at Romanticism we have looked at or are looking at reproduction they're not always the same um certainly oh they can they can animal mammalian or terrestrial mammalian reproductive behavior is is dominated by by the sense of smell um in in mammals and here remember initially when you started off I I noted that there are several subsystems in our news that transduce utterance and and so primarily the manual factory system which is cranial nerve number one and the trigeminal nerve which is cranial number five um 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 vulnerable nasal organ it's a small pit in the nasal passage of of most terrestrial mammals sometimes it's uh described as a communicating pit because sometimes it connects the nasal passage to the roof of the mouth sometimes it can it connects both and so there's this sense organ with its specific receptor subtypes uh vnr's vermonasal receptors and uh this um um is linked to a to a sort of separate portion of the olfactory bulb not really a manual Factory bubble it's referred to as the accessory olfactory bulb um and from there directly to the limbic system to the to the portions of the brain that control reproductive Behavior Uh and aggressive behavior and and in most um terrestrial mammals this subsystem processes utterance there are sometimes referred to as pheromones although that's in many ways a problematic term but but utterance that are referred to as pheromones namely odorants that are emitted by another member of the species to influence that member of the species and alter Behavior or hormonal state and and and some of these pheromonal effects are are utterly remarkable and in my view the most remarkable of all is an effect known as the Bruce effect uh 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 um I think up to about day three uh if you expose the pregnant Mouse uh to the order of what is referred to in technical terms is the non-stud male that is a male who did not father the pregnancy she will miscarry the pregnancy she will abort it now that that's an insane decision made by the female here right because she's invested quite a lot in this right in in biological terms and in in forming this pregnancy and maintaining it and yet she drops it on the basis of an odor um and this effect is remarkably robust and what do I mean by remarkably robust so this will occur on about 80 percent of exposures now as you know 80 is 100 in biology right I mean there's nothing that happens at more than 80 percent so it's a remarkably remarkably robust effect this this dropping of the pregnancy and we know it's mediated by chemosensation three no for sure and we know in the following way so first it's enough to just bring the order of the non-stead male you don't have to bring the mail himself right so you just can bring bedding from a nonsense male and that will induce uh the Bruce effect but of course uh the most telling set of experiments is that if in the female Mouse you ablate the vulner nasal organ you just burn this tiny structure in the nose and the effect disappears so the effect is completely dependent on the former nasal organ um and and I find this out really a remarkable effect right I mean because again because of the the extent of of cost that the female takes on here uh based on on this information and smell now humans the the sort of the going notion in all faction is that humans don't have a functional vomarinasal 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 uh but the pit that we have is considered vestigial and non-functional and what about this thing I learned about at Berkeley uh in integrative biology class that we have something called Jacobson's organ this is the same organ so so Jacobson Orion is the former nasal organ uh it's also called Jacobson because um I think Jacobson was a military physician in like the 1800s in Holland or something and he found it in in in a soldier who was operating on or something like that the the story comes from something like that but but Jacobson organ is another name for the former known as organ these are one and the same the sensory organ of the accessory olfactory system and again the going notion is that the human Jacobson organ or Romanus 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 pheromonal effects namely social chemo segolian rodents are mediated by the manual factory system we know that for sure um there are several examples for this in mice and rats and rabbits and so on and so forth so so a uh these can be mediated by by the manual factory system and and I'll I'll come back to that in a second but first to finish the the Bruce effect um and and second and and I'm going out on a limb here uh but I'm willing to take that that uh risk I'm I'm for me the jury is still out on human vulner nasal organ um the the decision or the the notion uh that it's non-functional relies on about one and a half papers postmortem uh looking for the nerve that connects this thing to the brain and failing to find it using staining and so on and so forth but sustaining postmortem studies in humans are are notoriously complicated um basically you know for many reasons one of them is that the material is just always has gone through you know it's it's not ideally uh uh set as it is when you sacrifice an animal and and and and study its its tissue um so so based on on really really a positive studies that fail to find uh this nerve the notion is that the structure is vestigial uh in 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 um what we do have a suspicion is that humans may experience something similar to Bruce effect so first of all humans have an enormous um number or ratio of of spontaneous miscarriage are they um occurring more often in the first trimester because you mentioned yes that in the Bruce effect in the mice is in the first three days or so following pregnancy which in the mouse gestation as I recall is about 21 days in the mouse you're talking about one-seventh of total gestation so I'm I'm not quick enough to to nor is it important to translate but this would be first trimester yes which is indeed when most miscarriage occurs now humans have again a huge number of miscarriages and and the numbers I'll soon share them with you they sound odd and the reason they sound odd is because if if you have what's sometimes simply referred to as failed implantation right this can occur you know in days one two nobody ever knows okay so so some papers talk about 90 of all human pregnancies end in miscarriage this is counting a failed implementation in day one two Etc more conservative studies talk about 50 percent nobody will argue 30 okay so a huge number a huge number of of uh 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 by all sorts of genetic factors developmental factors and so on and so forth but there's also a proportion that are unexplained and and and so all I'm saying is that there's there's a statistical backdrop or setting if you will force something like a Remnant Bruce effect in humans now with that in mind we we approach the group um of we we enlisted a group of of they're not really patients and participants in a study of people who or couples who are experiencing what is referred to as as unexplained repeated pregnancy loss so formally if you have uh two consecutive uh unexplained miscarriages then uh that that is sufficient for the diagnosis of unexplained repeated pregnancy loss however in our cohort of 30 we had couples who experienced 12 consecutive unexplained repeated pregnancy losses so so the two the two is just the formal all of our cohort was like twelve five you know so this is an emotional difficult place to be and and these are couples who who are losing uh 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 uh clotting all the all the the known suspects uh for for pregnancy Lawson the 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 akin to to a Bruce type 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 to test this right but what we could do is to see uh you know to seek circumstantial evidence to see if if where there's fire maybe there's smoke and what we did was we tested uh olfaction and more specifically the response to male body odor uh in in the the couples experiencing um uh repeated pregnancy loss and we found a few things first of all if you think of the mechanisms behind the Bruce effect the Bruce effect implies that the female has to have a very clear memory of uh the following meal because if she's gonna miscarry in response to the non-father she has to know father non-father I mean that means that there's a pronounced olfactory memory at the moment of mating okay and in mice this has been very well characterized and and attributed to the Ontario olfactory nucleus a structure in the brain um 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 in your childhood story from before stand out a bit as as skillful is that the first thing we did was just behaviorally test uh whether um these women and control women could identify the smell of their uh spouse [Music] and you might be disappointed or you know it we would all are probably a bit disappointed to learn that control where I'm in uh are very poor at this so so you you would think that that women would be good at identifying the body order of their spouse they're not uh they're not far from chance however um the uh women who experience uh repeated pregnancy loss are more than they're they're double uh at their performance level so this is not a Nuance effect uh women who who who experience repeated uh pregnancy loss can identify uh their husbands or their spouses uh by their body odor with much greater Acuity than the typical person double a bit more than double and way above chance yeah no I I sorry I posed as a question but I meant yes with much greater Acuity uh and double is is a significant um Improvement are they much better at detecting any odor no they're not we did the controls and they're not and then um we also measured using fmri we measured their their brain response to uh stranger male body odor and there and and and this was quite remarkable because you know we approached so this was a full brain analysis so without a region of Interest analysis so it's not as if you're uh tweaking your statistics to look at one part of the brain you're just looking at the entire brain in the response to male body order and asking de novo is there a difference between these two groups of participants and there was one huge difference and it was in the hippothalamus and so there was a difference in response to stranger male body order uh between the two groups um so so olfaction is altered in spontaneous repeated spontaneous uh pregnancy loss we don't know this is causal right uh but but that was enough for us to approach the Ethics Committee um to run a causal experiment um and we're at the beginning of that now incredible I can't wait to hear the the results of that it's gonna take it'll probably take years um a few because because the these are slow experiments to run uh um recruitment is complicated uh but basically we're we're blocking um we're blocking smell in in uh couples who are trying to maintain a pregnancy I want to touch on some other so-called pheromone effects and one thing I heard you say during a talk which I think really captures this whole issue of are there pheromone effects in humans um very nicely as you said you know whether or not it's a classic pheromone effect or whether or not it's olfaction or something else this is chemos sensory signaling between individuals um 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 um human uh olfactionistas um more from the the actually who work on animal models really came after me with um you know intense sniffing saying uh you know there is no evidence for human pheromone effects 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 behavior for sure for sure and and the the term pheromone is a problematic term in any case I mean the term the term was um put forth to describe insect Behavior right so you know if if you were given a hard time by the mouse people you could have given them an equally hard time if you were an insect person right because really the place the term is is uh is accurate is you know so the first pheromone that was discovered was bambicol which is the pheromone that has the male moth follow the the scent Trail of the female moth is a pheromone um 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 semantics yeah sort of like nerdy inside ball 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 talk about chemo signals and humans definitely emit chemo signals from their body and these chemo signals influence other humans and influence their behavior you know in in there are several examples of this one of them I'll point out first which is is sort of the most widely studied and and not mostly from our lab actually I mean the the flavor of the month for the past 10 years in this field is what's referred to as the smell of fear right so um this is probably true of of many mammals and humans uh it's true of um we emit a specific body odor when we're in a state of fear uh this was first discovered in humans by Denise Chen um out of I think Brown I'm not sure think that's right yep humans emit a particular body odor when they're in a state of fear and this body order influences other humans in effect increasing uh their autonomic uh arousal their sympathetic State um so in effect you could say that fear is contagious a bit so the smell of fear is contagious by the way culturally uh we know for ages that dogs can smell if you're in humans but actually that was only really shown about a year and a half ago in a study so it was always said but it wasn't really shown effectively it was shown about a year and a half ago in a study the dogs indeed can smell human fear um and humans can smell human fear so several Labs starting from Denise Chen and Javelin Jones and and then in our lab and in other labs if you collect body odor from people in a state of fear uh and collect body order from the same people when they're not in a state of fear other people can determine which is is the state of fear or and this influences their behavior what about the smell of safety or is that simply the absence of the odor corresponding to fear and the reason I ask this is somewhat woven into our um prior discussion about mate Choice um again I'll ask the question in a form of of brief anecdotes um I'll use the I had a friend who uh approach here but um well one phenomenon that has nothing to do uh with me in particular I think this is a common phenomenon is um romantic Partners leaving articles of clothing at each other's homes now this could have other purposes to Mark territory but um visually marking territory but also um scent marking territory is very common in the animal kingdom um it's not uncommon uh for uh romantic Partners when one is traveling or away for the other partner to smell their article of clothing in order to bring about positive uh connotations of the other partner very common Behavior if you're doing this folks other people are doing this too yeah um it raises questions for instance about whether or not the morning period part post breakup whether by decision by death or by um some other phenomenon that's forced to break up whether or not that morning period has something to do with an olfactory unlearning of uh um and made slash and on and on and on with all these insights I would offer you to be a postdoc well finished so I would love to do it but it's going to kill me yeah exactly you don't want me to work for you we talked about this that's what I'm saying that don't really work uh earlier I was just I was afraid of the fact that I've had three incredible scientific mentors uh undergraduate graduate and postdoc but um for reasons uh that are unclear to me um uh the first one died of suicide the second one cancer at 50 and the third one um pancreatic cancer in his early 60s and the last one before he died was an MD and a common friend of gnomes and I turned to me and said you know Andrew you're the common denominator so um you know that the joke so nonetheless I would love to do a sabbatical in your life so so what I was trying to say in that round about way is that those are all really Keen observations and good ideas um for sure and and and they just highlight again you know that that we're incredibly olfactory animals you know and and and you're you're even talking about the Nuance we're very ol' Factory even not in the Nuance I mean 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 I have to deal with this a lot right I have to deal a lot you study Vision nobody will tell you that vision is unimportant right I have to visually dependent I don't need a dog to take over my olfactory system if I lose old faction but I'll tell you from having lost my sense of smell for one day right I was in intense fear I bit into a blue I love blueberries I'm like a drive-by blueberry either if they're there I just kind of picked them up like a grizzly bear and cram them in my mouth so keep them away from me if you don't want them eaten but I can't I almost can't help myself um 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 like tremendous tremendous grief I'll tell you a sort of a throwy line that I use in this when I talk with people you know I mean you know take the two most basic behaviors that sustain us right let's say I give you a choice between a beautiful looking layer cake with with with strawberries and blueberries and and uh and whipped cream but the smells of sewage versus some gray brown mix that smells of cinnamon which do you eat oh simple right you eat the latter right now imagine I offer you a mate choose the the gender of your liking right it looks like a Greek god or goddess right but smells of sewage or an ordinary looking individual that smells of sin itself who do you choose the latter right so in the two most basic behaviors we have we follow our nose not our eyes right definitely not always in predictable ways because you offered an extreme example which is the best example but I for instance for reasons I don't know I've never liked the smell of perfume ever in fact I find it aversive but I do I confess I do like the smell of certain body odors very much and I'm very um particular about that and I know within an instant um and so uh this is a problem for any romantic partner uh who likes perfume for me but I know many people like perfumes and colognes and things and In fairness I've also been told um that uh by someone that they couldn't spend time with me because they do not like my smell in fact they dislike it and I unfortunately for me there's at least one person on the planet who said yes so the um so I completely agree with what you're saying yeah um I can also say that um I imprinted on the smell of my I had a Bulldog Mastiff um 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 averse to me he he smelled delicious right and it made me it smelled like home and he was my best animal friend for a long time so and on and on and on right the smell of children as you said the backs we had a guest on this podcast who I'm sure you're familiar with Charles Zucker yeah a professor Columbia has done incredible work and vision and old-fashioned yeah they're sensing it and he and I talked a little bit about this that um there's something in the breath of romantic Partners um that's hopefully a pettitive not aversive as well as in children he was talking about the smell of his grandchild's the bat the nape of their the back of their neck and how he misses that smell because when he thinks about missing his grandchild or children it's that smell that that that's associated with that feeling hexadecanal hexadecanal yes is it Charles your grandchildren smell like hexadecanal yes he's gonna come after me now and so this this is a steady uh ran by uh Eva mishore who was a graduate student in our lab um and and Eva was interested in aggression she was really into aggression um and actually when she start and and when she start off we said okay let's do chemo signaling of aggression she actually was going to like MMA clubs and collecting body odors uh and we we had all sorts of ideas going and and she 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 when I say colleague primarily a friend or acquaintance I made it conferences um Heinz Breer um and and um he was studying in his lab a molecule hexadecanal um that was a chemo signal in mice where in mice it was described as a chemo signal that promotes social buffering where social buffering as far as I understand it's not my field but as far as I understand it's basically a feel-good together thing so when lots of whites are together they feel good about being in a group and that's social buffering and it's promoted by hexadecanal which they emit in their feces mice and in his work on hexadecanal um and and so so Brier and his colleague swordsman they discovered the receptor for this and then they went and discovered that the receptor is very highly conserved throughout mammalian Evolution and therefore they hypothesized that maybe um this is a universal mammalian signal now which is unusual because in in chemo signaling typically you tend to think of things as being very species specific but here they're hypothesized that maybe hexadecanal which promotes social buffering in mice may do something in all mammals again because this receptor is very highly conserved or 37b I think um so they so he approached us and said look you got to study this stuff in humans right because he knows us as the human people right I mean we go to these old-fashioned conferences where where lots of people study mice and and zebrafish and whatnot and we're the the human group so and and eventually he just fedexed us hexadecanal and and so we had this thing sitting around and Eva was not going anywhere with her aggression studies with sweat from Human participants and yet she built the entire um 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 hexadecanal stuff here and it promotes social buffering social buffering sounds like it would make you less aggressive why don't you run your TAP experiment using hexadecanal what's the tap experiment so basically what you do is you bring in a participant to lab and you have them um thinking that they're going to be playing against another person in in this game and you can you can do something like have another person walk into the other room playing online so so connected so you can fool them into being quite convinced that this is what's happening and they go into their own room and in the initial game they play um on each round their uh they're provided with a sum of money and this is real money that they'll receive at the end of the experiment and by turn each one of them decides how to divide the money up between the two right so they're playing against another person they think but that's actually a computer algorithm that they're playing against and the computer algorithm is is programmed to be in in scientific terminology a jerk right so that you know like let's say they have to divvy up 100 cheko which is the Israeli currency so so the com you know the other player would say okay you know um I'll keep 96 and you get four right and then if you can either accept it or not accept and then neither of you get anything right so basically you're being shafted by 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 they're they're shafting you on every trial or almost and you play this game and it goes to its end and then you click you play a second game as far as you know against the same participant and the second game is a reaction time game so a Target shows up and the first to press it wins and on every trial where you win if you want you can blast the other parts spent 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 it's a screeching horrible sound it's the most punishment that an IRB committee will let you uh endure on on a participants and experiment unless you're in Stanford 70 years ago or whatever that was I was referring to the classic prisoner experiment which took place in the building next door to where I work so you can blast the other participant with varying levels of sound and you have a selection box from something very low to something very high and what's nice about this is that it then allows you to quantify aggression because the more volume you're blasting the opponent was the more aggressive you are towards your opponent and and so you have a measure of aggression again the Tyler aggression Paradigm obviously invented by Tyler uh very well validated studied all over you know a very standard protocol so we broaden participants and had them play uh the title of the tap uh either under exposure to hexadecanal or control now access that Canal doesn't it's it's incredibly difficult to even detect Texas now but just in case uh because it it it's not very very it's considered a semi-volatile it doesn't have a strong smell um but we buried it both the control and the hexadecan island in a 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 I'll first tell you the result with men which is that hexadecanal consistently reduced aggression people were less aggressive under hexadecanal um the effect size was was uh uh quite meaningful and later on we learned because I'm no specialist in the world of aggression but compared to effects seen in the aggression World in research really really strong effects so unusually strong so hexadecanal lowered aggression in men and we were like well this is you know sort of what we were hoping to see consistent with the hypothesis uh and consistent with it seems to do in mice but then we looked at data from women and hexadecanal increased aggression equally significantly is this thought to be something related to maternal protectiveness we're getting there so you you got there really fast it took me a year but and and ever got to it really I'll I'll tell you because remember we're reaching the back of the head of your of one of the kingpins of the New York Neuroscience Mafia yes so um 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 was some bug here I mean this this it makes no sense to me you know why would something increase aggression in women and decrease aggression in men this is really really strange and 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 within the fmri magnet so that we we can also uh track uh brain activity uh while this was happening and first of all it replicated again so once again uh hexadecan element made men less aggressive and women more aggressive and and the extent of more than the effect alone the dissociation was remarkable this has the it's almost like a chromosomal test I mean you you look at the data on the unit unit slope line and all all the men are below and all the women are above there's this figure in the paper then she also looked at the brain data and this is you know Although our lab does a ton of fmri it's one of the major tools we use to measure uh uh brain activity I'm I'm quite cognizant of the limitations of fmri and and this is I think sadly I think the only study in my career at least where 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 hexadecanal alone increased activity quite pronouncedly 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 the social brain not the olfactory system per se and 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 to 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 connectivity that is how does this region of the brain talk with the entire brain as it were under hexadecanal versus uh 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 hexadecanal 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 hexadecanal increases the control that the left angular virus is holding over your aggression and keeping you back and in women it let it roam free and they became more aggressive but I was still Apostle so so I was convinced this happened twice the mro data provided not only a pattern but a mechanism which is unusual and yet I I was telling Eva you know but you know this makes no sense to me and then and then her Insight which of course afterwards is like duh it is no there's a place where this makes perfect sense and that is if you're a mammalian Offspring because paternal aggression is often directed at you there is infanticide all over and sadly there's male aggression towards 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 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 that looked at the odors emanating from baby heads we now come full circle to sucker's grandchildren they used a method known as gcms gas chromatography Mass spectrometry to measure the volatiles from baby heads because baby head odor is a cultural thing across cultures even in Japan and so we quickly went to that paper and to see if one of the molecules that report is hexadecanal and we were very disappointed that it wasn't one of the molecules they reported in the paper and so we wrote to the authors who are since then our co-authors uh and we said look you know we're studying uh this molecule hexadecanon we don't see in your results and and we were wondering maybe you had some results that you didn't publish or some supplementary materials or whatever and this lab which is a hardcore GC lab said no no hexadecanal is a semi-volatile which we knew uh in our previous paper was not directed to the semi-volatile range but we can now do use what's called gcx GC WGC that is directed at semi volatiles and we can do this again we just uh studied 11 babies and we can we can see if this is an issue so he said yeah please do uh the bottom line of all this is that hexadecanal is the most abundant semi-volatile in baby hits It's tons of it coming out of baby hits so babies again speaking about if humans do or don't chemo single babies are conducting chemical warfare right they're they're they're you know reducing aggression in their fathers or males around them and increasing aggression in their mothers or females around them and both of those things are good for them incredible this is somewhat different than what we're talking about um and yet similar in other ways because it's uh 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 yeah women or women who are friends the you know many women listening to this and maybe some men who are aware of of this effect will say oh yeah absolutely when I spend time with my friends or go away camping or even spend a day with them our menstrual cycles become coordinated however my understanding is that the early literature Barbara McClintock correct um discovered this phenomenon published a paper in science as an undergraduate 1971 nature amazing nature paper again one of the three Apex journals and as an 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 and over again and yet as subsequent papers have been published this result has been called into question is uh is there any uh final word on whether or not menstrual cycles uh become coordinated among women who spend time together and if so is there any role of olfaction in this uh or chemosensing through the nostrils or end or mouth um to support this idea so so yeah so so I'll start off indeed to Echo uh the background is that this study was conducted by by Martha McClintock when she was an undergraduate Wesleyan College uh and she noticed that she thought her menstrual cycle and her co-inhabitants in her dorm room um um were coordinated in time um 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 um but but um there's a an effect in runes referred to as the whiten effect which um resembles uh this type of of effect um 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 uh with then her graduate students Chicago uh Stern so this is Stern and McClintock 1998 and here's what they did they collected um 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 because you said you like body orders but for many others perhaps it would be daunting well I like certain body orders from certain individuals um I don't know I don't think I uniformly like all body orders although I do send a uniformly not like the smell of perfume although I should just to clarify because I put this out there and I learned the hard way in the comment section on YouTube some of those perfumes I find downright aversive yeah like it's a uh I think the great Marcus Meister who a great neurobiologist once said there's basically three responses it's either yum yuck or meh so some are true yeah I've never heard that one yeah that one right in terms of the animal behavior yeah or pause um so some are truly a yuck some many are meh zero to date or yum for me now body odors the distribution is shifted it could be any one of those three yum yuck or meh so just to be clear but the the um yum category is definitely included thank you so uh um so so she did this study so so because right in the original McClintock study you might suspect other uh drivers of the effect let's see if 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 and this might be driving the coordination right so here there was no direct link between these women other than body orders so if the effect re-emerged um it would definitely be an olfactory effect and what she found is that if she took a sweat from the follicular or the ovulatory phase of the donors one extended the cycle in recipients and one shortened the cycle in recipients I don't remember which was which but but basically uh uh definitely denoting uh a chemo signaling effect uh with with the opposing uh effects on duration based on the time it was collected from again published in nature in 1998. that's it I I there's a quotation I think this is from from uh I'm not sure but but you know that that uh uh if something is published in nature or science that doesn't necessarily mean it's not true so uh with that in mind um the findings were since called into question quite widely um one reason is just statistics of cyclic events are surprisingly complicated so so It's Tricky it's once you have a cyclic event statistics become tricky and and so Martha took a lot of heat on the statistics of of claiming an effect and I think there was at least one effort of replication that didn't really work out um if you ask me I'm on the fence so I I'm and but I'm maybe in a minority in my field I think a majority in the field uh is currently negative I'm not um and I've we've said in lab that we should do a planned replication um we will it's just again it's a horrible study to run it's tons of work and you and and you have to run it for a really long time uh and and uh so it's just completely non-trivial um but we have a graduate student now and lab interested in these exact things uh Road wisegross and she's doing similar stuff and and I hope we'll we'll do that I hope we'll try to to replicate this um very interesting result and I think uh interesting because it of its Real World um meaning outside the laboratory of course our experiment analog but also because pheromone effects and olfactory effects in humans seem unique among uh neurobiological slash endocrine phenomena because there seems to be so many stories that we all have of the smell of our grandmother's hands or the recognizing the scent of of somebody or I knew from the moment that um 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 potential for a real biological phenomenon as opposed to the kind of thing like oh uh you know you just throw something out there oxytocin is bonding and all of a sudden you know the the general public not at no to no fault of their own comes to think that every 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 um it's fodder for for exploring all these things and a lot of times they turn out to be true right when in the context of old action yeah no it's it's a very Primal system you know so so uh it's it's linked to the most you know limbic Primal mechanisms in our brain and it drives Primal Behavior it's an incredible system I I have a question about a particular study but I'm just going to cue it up and you'll know immediately what I'm I'm queuing up um and that is what is the relationship between odors and hormones and in particular crying as I pointed out previously the the sort of flavor of the month in in human social chemo signaling research is the smell of fear and the the media of the month is Sweat Right so so um the the few maybe tens of labs in the world that study uh Human Social chemo signaling all collect sweat and and that's the media uh they look at is it always from the armpit org is there are there meaningful differences in terms of the sweat emitted from different locations on the body I already know the answer to that as I ask it but let's just stay above the waistline and um oh no no yes or below the waistline I mean we're biologists after all we we just yeah so it's it's funny we we have we're working on a paper on that right now on the smell of fear uh so so we have a nice Paradigm for uh generating fear we throw people out of airplanes it's a very effective way to generate fear to come to your lab it sounds like the greatest lab in the world we didn't invent that by the way uh the first to do that was uh um and I hope I'm pronouncing her name correctly I think it's mujika perudi um but but um that's our Paradigm for generating fear and we started that on our own but uh We've since entered into collaboration with the Israeli paratroopers Brigade and we now collect body odor from every First Time Jumper so um we we went that path because we like everybody else in this field you know the Holy Grail there is is finding the molecules right I mean if you'll have the fear molecules that's a bonanza right because I mean you know you could think of many reasons why it would be a bonanza but for for me you know if you find the molecules you can then try and find The receptors and when you find the cognitive receptors you can then develop blockers and you can imagine you know uh um uh um what's the term I'm looking for um I'm switching into Hebrew it's about midnight now right I'm sorry you're doing incredibly well considering two in the morning yeah we would never know um no one traveled in today from Israel so he's a circadian inverted as we say uh um anxiety so so uh you can imagine developing like a nasal spray against anxiety right where where you would quell those receptors and kill the fear response right which rather than going the current path which is through neurotransmitters that then have effects all over the place you would be getting fear at its source right so so that would be why I would want that and and we figure out that doing that you know collecting fear from like three four or five people um in an experiment you'll never be able to do analytical chemistry on that so we now have uh we have uh a setting we call fear Bank uh which now has more than a thousand samples in it so we're trying to do uh uh analytics on that but in doing that we've we've joined you know the the crowd everybody's 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 there potentially definitely could be additional bodily media that are are playing into social chemo signaling uh now many of these you know you can't really study right I mean so you know just to throw what most terrestrial mammals communicate social information through urine um but you know starting doing experiments with humans with smelling urine it would be difficult you know both in IRB and in agreement and you know and and then we we you know this is a rare case where we actually hypothesize what we set out to do and you know and then only claim in retrospect that it was hypothesis um is is tears [Music] um we we started thinking about tears and looking into tears because tears are a bodily liquid emotional tears that that we emit in emotional situations where where these are situations where nonverbal communication is is critical and key and and tears are a liquid that that is puzzling Beyond ocular maintenance right and so so you know the the most influential text I think till this day in in Emotion research is is Darwin's book uh uh the showing of the emotions in men and animals I think is the full name of the book and an entire chapter chapter six is devoted to tears an entire chapter of this book why with no conclusion why because the book revolves around describing the functional antecedence of emotional Expressions so for example uh showing of the teeth is a sign of aggression right so so animals first bit with their teeth and and Darwin argued that through Evolution uh just uh showing the teeth alone became an aggressive sign because it started from biting or what I I find is a beautiful example and this is work partly done by by Adam Anderson now at Cornell um is is the uh emotional expression of disgust so disgust which comes from Line This goosia distaste right is spitting 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 disgust are the same as when you spit a bitters taste out of your mouth right so again so there's a functional antecedent spitting something out and through Evolution the argument was that it became an expression of emotion and you express disgust just as if you're spitting something out of your mouth even though they're you know in the case of moral disgust 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 antecedent and explained everything very nicely and then he got stuck with tears right because tears are an obviously emotional expression and he could not find a functional uh antecedent so he ended up saying this is an epic phenomenon basically right I I don't know what all scientists do when they don't have a good explanation you know blame it on nature right right so so and but he bothered to write this entire chapter on on the ocular or sort of Maintenance you know function of tears and so on so forth but but nothing emotional so we thought well maybe the function is is a chemical signal and and you know so so with that in mind we we harvested emotional tears uh which was also an amusing event on its own right because we we uh we uh we we posted um messages on all sorts of boards that that uh we're seeking um experiment participants who cry with ease now this generated an unfortunate gender bias in our study right because we received about 100 women volunteers and about one man and you know I think this is not a problem only in in Macho Israel right probably anywhere in the west this would be I mean definitely in America would be the same I think my guess is that there are probably men out there who cry easily emotional tears because I'm sure that they're just going to show up yeah that's what I'm saying it's a cultural thing it's not you know you're not going to come to a lab and say yeah you know I cry all the time it's just not going to happen oh and then um we we what we did is uh 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 that makes you cry and and interestingly in these effective choirs there's always oh yes you know the scene in in so and so I always cry profusely from that you know they they have to give me an example of one of the more commonly used scenes yeah with these um the movie The Champ the champ dies he's a boxer and he dies and literally in the hands of his about eight-year-old son and his son is standing next to his bed and you know saying chap Chap and and he dies right it's a winner okay waterfall yeah yeah got it so you know we're probably the neurobiology lab with most sad movie films on those shelf in the world right we have a whole huge collection there is the same thing as Tears of Joy by the way so no no well we're going ahead of ourselves but they say we tried to collect them and failed um even people who think they shed tears of joy and laughter their eyes water a bit but it's not the same thing in in in the effective choirs we end up screening so I can write we collect a full mL of Tears a full mL of Tears in about 15 minutes wow so so that's pouring right and that doesn't happen from laughter that we or we've never seen that we've never seen that happen from a lot but we tried um so so um so we have we have all these sad films and by the way one of the amusing things is uh when we ultimately published this paper in in science um we were forced in retrospect to go out and actually buy the films right I mean you know originally we like downloaded the rear there but you can't because you're you'd be violating uh uh you know uh copyright laws right so we had to buy like purchase all these films that the parts and watch them so we we actually have these in lab like DVDs you know that we actually purchased um but so nice coverage of a potential legal Fallout that I've known no we did yeah so uh and yeah and and well we can touch on that later but up so um so most of these uh volunteers who who come saying they can cry with ease actually don't meet the bill um and so out of the about 100 at least more women that we screened we ended up uh with about six who who could really come to lab week after week and and poor tiers there's a name for this in Psychiatry they call it um a narrative distancing some people when they watch a film where someone's getting hit they they they they Flinch quite a lot they it's almost as if they're experiencing it it but it works in the opposite direction too I know someone like this um where if they watch a film that someone's experiencing something even mildly positive that their mood elevates so they they can quickly Bridge yeah um and it's not always adaptive as you can imagine so there's a lack of narrative distancing right yeah what one you know issue you can bring up with this entire line of studies in our lab is is I don't know if there's something very unique about the donors right I mean we're assuming these are tiers and this is pretty common I think that the numbers I saw out there about five to eight percent that's exactly what we got about right so so we collected um um tears and and we exposed uh participants uh to these tiers and and we found a few things first of all the tears are completely odorless you cannot detect them at all completely odorless um And yet when you sniff them you have a pronounced uh reduction in testosterone uh within about 20 minutes half an hour this is men and women smelling in women's tears just men swelling women's tears but not perceiving any odor nothing just sniffing them and you have uh about uh 14 drop in free testosterone free okay so this is testosterone that's already been liberated from the testes free testers we've done a few hormone that's uh either bound or Unbound is Unbound excuse me um from sex hormone and globulin Etc and it's the active form so it's it's uh it's subject to very short time scale changes yeah and and this is you know people who who study testosterone which is not me but they tell me this is a really strong effect like it's it's hard to even pharmacologically get an effect like that that fast I mean no in Pharmacology yeah years ago I spent time studying endocrine effects of this sort um and that's a tremendous resized effect so and so here I'll point out in passing uh that uh one of the concerns we had because of the uh 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 uh uh South Korea uh oh it Al who I don't know at all uh replicated the testosterone effect to a t i mean like same numbers so so um it it lowers testosterone and and we then also looked uh using Mr at the at the uh um effect on brain activity and saw pronounced uh if effect on activity a dampening a lowering of activity uh under under uh an arousing State a lowering of activity um both in the hypothalamus um and in the fusiform gyrus for whatever reason I don't know recognition area amongst other things yes um and we don't know why um but pronounced um and currently um Shania gron in our lab is replicating this again and this time with a stronger behavioral component um and I can share with you uh unpublished uh data now under review um that's as you would expect given the effect on testosterone perhaps uh sniffing tears lowers aggression in men uh using again the tap the same experiment used by evine in the uh hexadecanal experiment that's happening I'm going to think of that as the the say to the title The titration the sadist hydration yeah Tyler aggression Paradigm so not unlike the Milgram experiments of the of the 1950s which post um this is looking at sort of uh post Holocaust Behavior you know people basically in American Laboratories thinking they were torturing other people yeah simply because they were told to and a lot of people did that even though most people would report that they would never torture someone yeah no humans are not a wonderful species I think it was the the great Carl Jung that said um we have all things inside of us but um the goal is not to experience them all certainly um it's an incredible study and it points again to the the power of of um these chemo sensory systems and Pathways and uh obviously there's so much here um I don't know if you want me to to tell about this or not and I guess you can edit it out at least you don't but uh please this is just you know sharing stories about the politics of Science and and so whereas the effect on testosterone was was uh replicated by by an independent group um in the original study in in science where we had we it had three components one was the effect on testosterone which was robust the second which was brain activity which was robust and there was a significant but weaker effect on behavior and I don't think we studied the right behavior in retrospect what we looked at then was uh readings of arousal associated with pictures and there was an effect it was significant but it was it was not what carried the story um now there's a lab in Holland um of a guy by the name of I'm probably mispronouncing this but I think it's vingerhots for the non-dutch yeah Dutch names are always a little bit of a challenge but and I shouldn't say that being an Israeli I shouldn't go too much on that line but but uh that lab really didn't like our original tear story and the reason they didn't like it is because they've they've built a career on this notion um including a book with this title that emotional cheers are uniquely human now here I should well I should share so one of the things we really liked about that the the uh tier result is that partially before we did our work but more afterwards and 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 um more or less identical effects were discovered in rodents so uh a paper published in nature two years later found that Mouse tears uh Mouse pup tears lower aggression in in male adult mice towards them in a in a smell dependent way yeah yeah so and and they also actually found the actual component in tears that so the tier pheromone that lowers aggression right so so you know this has us thinking of regret as tears is as you can think of Tears as 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 our finding you know which to me I mean this is consistent with how I think about behavior in general you know I don't think you know beyond language there are very few things definitely sensory things that are uniquely human you know I I I'd be hard-pressed but so so you know our finding when it gets you know against their their story right because you know here we're saying no you know tears are this schema signaling mechanism like all animals and by the way I you know just after this entire debate about uh um six months ago there was a paper in current biology the dogs emit emotional tears and and it was uh the dogs emit emotional Interiors when they reunite with their owners and you were talking before about about um oxytocin so I think what they showed there is that not only that but that the the the view as seeing the tears and the dog influences oxytocin and in the humans hope I'm getting this right now I absolutely believe this I mean I from the from the time I brought Costello home at eight weeks old guys tell us your dog is my dog unfortunately a long time actually the only time I can recall crying listen I've certainly cried before many times in my life um many many times [Music] um the only time I ever recall crying to the point where I wasn't sure that I could keep producing two years but somehow it is when I had to put him down right it's just like you know and if I talk about too long ago you know it's one of those things yeah I think it's a healthy yeah emotional state for sure but I recall when he was a puppy thinking this oxytocin thing must be real because I can recall being in faculty meetings which you know very fairly stated are not always that interesting but they could be pretty interesting and someone presenting data in my mind thinking I hope Costello's 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 rear yeah I really do otherwise why would people be so ridiculously attached to their dogs I mean hence all the the posts of everyone thinks their dog is the cutest dog the same way everyone thinks their children are the cutest children you know by the way too so so yeah so so again so they're so even you know to put another nail in that story of of uh of tears are uniquely human so they're not dogs shed emotional tears um and and and so that really didn't like this and they went ahead and and tried to replicate and to your listeners I'm showing double uh quotations on the replicate uh only the behavioral part the ratings of arousal um uh in women of women uh and and failed to replicate that I see now this was you know just sharing on how science works and it doesn't work in my in my notion in this case so at the time um after they got this accepted in some Journal [Music] um not a field journal in the Journal of memory of something um they contacted me for a response and I I wrote to the office and I said look you know uh this is very odd to me why don't you come you know why don't we replicate this again together and see if it doesn't work if it doesn't work I'll publish it with you that it doesn't work but you know um 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 they did it very wrongly in the paper um and so they replied that uh no they don't have money to send over uh graduation to do it so I replied saying okay I'll fund the graduate student coming over and I'll fund the entire study in their stay and so on and so forth then let's do this together and they replied no they're not willing to to do that which you know I don't think is the way things should work um and and they published this sort of failed uh uh behavioral effect in in that paper um so I'm just sharing this you know that it's not only there was that successful replication with the effect on testosterone but there was supposedly this fail replication on the effect in in Behavior um and then I published a rebuttal on on that which I don't know if I should have done but I did well I think it's it's interesting I mean I I think um provided studies are done correctly I mean the positive result um almost always trumps the negative result and yet I think replication is key the problem as you point out is that replication is rarely pure replication of these yeah this one's not even remotely but in I I published the detail so actually they hid something in their data that did partially rip so I asked for their data and I re-analyzed it and that's what I published in the rebuttal but you know this is just sharing on how science works I 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 uh with uh Daniel conman who's who's Nobel looking fast and slow right and so so uh I asked him how how should I deal with this you know give me some advice here I was really you know it it was an emotionally not fun to be in that position and he said don't don't never publish a rebuttal don't do anything 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 all they'll be like well there's a group that says this and there's a group that says that so it's unclear well and yeah I mean I I appreciate that you're bringing it up today and I I do appreciate that you published the rebuttal and that you offered in a very magnificent way to do a collection that's what he then said that's so so Common's advice after that was that well if you insist then just publish Write a response that you offered them to to come do it together they refused and there's nothing you can do about that it's a lot like um fight sports right people talk a lot of trash although in science you know I will say this you know as long as we're on the the sociology of science science is very different than podcasting or social media or other fields because in science people generally are very kind to your face and then they you get it in the you get it in the neck on Grant reviews or Anonymous reviews um I was on a grants review panel this morning I'm a nice reviewer meaning I judge things objectively but I I try to always um think from the perspective of the graduate student or author of the of the proposal listen I I think that um science is a is a game of 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 uh very magnanimous of you to offer the collaboration so I'm going to tell this lab whose name I can't pronounce um please accept the collaboration then we can invite everyone on here for a round table um I appreciate that you shared that story and I know a number of other people will um for a number of reasons I have a couple of more questions um and I realize and thank you by the way for your uh for your willingness and stamina because it is probably 1am Israel time now um and you just arrived later I think um but you're doing uh terrifically well so I I um if you'll indulge us just a touch further there are two topics that um I want to touch on and if you want to cover these in shorter Thrift that's fine although don't feel any obligation to um 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 um you know an orange that smells great or the smell of something baking you know it didn't it it suggests something about the the contents and quality of that food after all you and I both separately lived in the same apartment in Berkeley above the cheeseboard which the smell is wafting up through the cheeseboard is something I will never forget and the breads never forget it um amazing uh 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 the same we've never met I mean like this before yep and we lived in the same room exactly where we click friends in a lingering way I guess absolutely through the uh through the floorboards it had a great floor of that place it had a great wooden floor it was an amazing place I lived there with my girlfriend for a year and a half and then uh it was an amazing place um we won't give it out the address for out of respect for the people that live there now um but do check out the cheese board if you ever in Berkeley their hours are weird but so you have to look online but that they're it's a unique Place yeah with great bread and cheese and um some good flavors of pizza um in any case um I'm wondering whether or not smell can signal things about the nutrient contents of foods in a way that's divorced from the smell that we are perceiving so for instance I could imagine based on what you've told us about smell today that um you know I I don't know I I I smell a a piece of meat cooking and it smells great to me and I think of it as oh that's so Savory and my mouth is watering and I love the smell of this and I'm thinking okay this is protein and fat and I love the taste of steak and a little bit of char but that nature has co-opted that to get ensure or I should say increase the likelihood that I will ingest some other thing that's in stake for that has no odor but whose nutrient content is very important to me for instance amino acids right right I mean amino acids are essential to life and yet um we don't go around sniffing for amino acids we go around sniffing for savoriness Umami type uh us tastes and things of that sort so um 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 you know sexually 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 um something about um 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 um olfactory system has learned to seek but learn to seek through more overt signals sort of the tip of the iceberg phenomenon so you know I don't have a good answer for you although I think it's a really good question um or or a good idea in fact so so whether the there's you know order cues on nutrient value is a really good idea moreover it's probably good to the extent that somebody probably did it and I should know and don't um we haven't done anything on that line so I don't know I don't know if if the nutrient value of food is systematically encoded in order um if that's not been done and I will check after our uh meeting today then it should be um it's a really good idea I mean one of the reasons I asked this is because um you know the Obesity crisis in the U.S is a huge issue and elsewhere and highly processed foods um you know I have a lot of things that are problematic but one of the things that they don't have uh often is a direct relationship between the scent The Taste and the new 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 um contain many micronutrients that are vital to aspects of our biology but we don't go around sniffing for probiotics I'll tell you one sort of factoid that may support your hypothesis here and that is that there appears to be potential olfactory perceptual similarity in metabolic products so something that's metabolized from something else has perceptual similarity across those those two things so so so metabolic Cascades play into the coding of olfactory space and and that is consistent with the direction your your implying but again I don't I don't know of a direct test of of nutritional value in smell and and again the fact that I don't know it doesn't mean of course that it doesn't exist and in this case I would suspect that it should exist um in scientific press and and if not there then with the companies that have vested interest in this which are many um uh briefly sure just just an amusing anecdote to share with you is that we've received too independent um um people you know companies who have turned to our lab recently uh asking for help uh to to bring odor to engineered meat right that's a growing thing and all these you know meats that are annoying you had to bring it up this this audience is going to be very polarized along the along the lines of engineered meat um you're not you're not from you're not promoting oh no no no no no no I am I'm agnostic but but uh but we've had two companies turn to us and say look you know we have this great product but it just doesn't smell like meat so help us make it smell like meat interesting uh the reason it's so polarizing is that anything related to nutrition on social media is a total barbed wire topic we've had experts on nutrition come on here we'll have more but I I have nothing you're safe no don't worry no it's not and it's not promoting uh this he hasn't even said whether or not he's going to help them out no um we're not actually no no because yeah I just never it didn't happen no yeah no the the whether or not those um engineered meats are uh yum yuck or met is 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 we'll avoid now I will but you know I'll take that the opportunity to to highlight something related maybe because I'm on what were you saying on the on the scale you know there's this you know I'll take the opportunity to dispel another misconception about olfaction right there's this common notion that our sense of smell um is incredibly subjective right and that what you might like in a smell I will not liken the smell and that we all have our own you know totally subjective world of all faction I think I know the study you're going to tell me there are many the cross-cultural similarities there are many that that is utterly untrue many not only from my lab there are many from many Labs uh please clarify for those that don't follow this list so um yeah so so humans are incredibly similar to one another and they're olfactory perception and this is in contrast to what most people think so why why is there this misconception the misconception is there for two reasons first of all or for several reasons but two are stand out first of all we're attracted by outliers because you know what I'll tell somebody look you know for example a factory pleasantness is highly correlated amongst humans and let's first put this in numbers you'll take a a bunch of humans and a bunch of odorants and have them write pleasantness the correlation across uh the humans will be about 0.8 that's incredibly High incredibly High what do you think is Pleasant I think is yeah yeah now why why is that go against what culturally people think for two reasons first of all where we're attracted or biased by outliers but that's particularly that shows in fact the results what do I mean so you'll tell somebody look people are very similar in their pleasantness estimates and that's all you know that can't be I love cilantro and you know my girlfriend hates the smell of cilantro right or and there are a few classic examples there right you know is another uh uh polarizing order so there are a few polarizing orders right and and that's true right so that's true that you know half of the population loves the smell of cilantro and half hates it half loves guiava half hates it that's microwave popcorn however I assure you that you know you can come to our lab we have about a thousand odorants in our lab okay we won't smell the Thousand right but I assure you you know take a hundred odorants okay from our mixtures and Labs right and we'll we'll smell them right and out of the hundred orders 90 will totally agree on right and including Universe I mean you know nobody will say they like the smell of feces or fecal smells and everybody will say they like the smell of rose and Flowery smells there will be rare rare exceptions again the correlation is about 0.8 across individuals so on 90 of 100 will really be in high agreement then five orderings will be in sort of intermediate agreements and yes they'll be the five orderings that were in total disagreement on but I asked you you know if we agree on 95 and disagree on five are we the same or are we different we're the same they're just outliers to this to this Rule and and and so one reason is this issue of of outliers attract how we think about things but no we're actually much more similar than than what we think and the second thing that that drives this cultural effect is the LA is our poor application of language to olfaction right so so in other sensory systems we grow up with we're we're we develop with anchors right so since you're a little kid you know your mother shows you a cow and says what does a cow do moo right and we all know moo moo 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 thing right and in odor we don't have those anchors right we we don't from childhood you know our mom doesn't tell us so what's this smell and what's that smell right and so we don't have these language anchors that make us think that we're perceiving the same thing now how can you quantify that the most important term in 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 so you'd end up with 45 numbers right so you know how similar is one to two one to three and one to four and then two 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 Andrew's 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 and then we've gotten rid of the issue of names and orders right it doesn't matter if I'll call this lemon in this orange and you call this sweet potato in this marshmallow right it doesn't matter if I think that these two are highly similar and you agree and I think that these two are very different and you agree right we perceive the world in the same way if our similarity matrices are aligned right and what's nice about that is that then you can do that for vision audition and off action in a common group and you can see where we're more alike each other or not and we've done that for color vision all faction internal audition okay and we are most dissimilar in color vision okay where in color vision the variance is about 100 amazing it's quite different and there's tons of literature on this tons of it tons of it right and in all faction and audition they're about the same so we're not different we're very similar we're just very poor at appreciating this and 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 and that will change you and learn to dislike in order right but just the way you can learn to like a sound or dislike 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 we're not very variable we're we're actually kind of similar that's a perfect segue to the question I have next which is if in general people perceive certain odors similarly you could imagine that odors could be um manufactured co-opted uh Etc in order to elicit richer sensory experiences and drive Choice making um 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 uh through computers so for a long time now there's been this idea that there will soon be Google smell not to call out Google is the only search engine but Duck Duck Go smell for those of you that don't want to hear smell chat chat and on and on in other words you know Vision visual key information is sent through uh computer interfaces as is auditory information not so much haptic somatosensory although it can you know we our lab uses VR it's it it can be done right um but it hasn't really taken hold um 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 yuck or meh type decision making yeah uh seems like an amazing candidate so what is your experience with um generating smells in silico in computers and here folks for those of you that aren't catching on to this and and I don't expect that everyone would because what we're really alluding to here um is the idea that you'll look at you'll put into a search engine um uh blueberry pancakes recipe and that not only will you get photos of those blueberry pancakes and a recipe but you will get the hopefully validated odor of those pancakes and that recipe coming at you in real time through the computer so I'll start off answering from uh from the uh the name you threw out there Google so about probably about five years ago uh Google had an April Fool's spoof oh right and they put out this 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 rows and and and all these things right so Google is now trying to do that um and they just they just uh uh published I mean I I know they've been trying to do it for a while they visited our lab uh but they just sort of went public with this that really just like about a month ago or something that that um they have this offshoot startup um I think it's called osmo or something like that that started off with a ridiculous sum of money for a startup like yeah I don't know tons of money a lot there's a lot of money in that world yeah yeah in Google yeah um to to um you know to digitize uh smell and and um and there are other companies that are trying to do this as well um and we've been talking now for quite a while about our our Labs chemo signaling work but actually half of our lab is devoted to this question of of uh ultimately digitizing smell um and and so so this is a very very active field of research and and and I'll say um one thing that that dovetails with what you were talking about before um in many ways covid is going to be one of the best things that ever happened to all faction research because suddenly all the world um is all the world lots of people are are um very cognizant of the importance of smell and smells like way up there in people's awareness because of covet and this is driving a Renaissance of of olfaction research and in Awareness to all faction is something that's worth paying attention to uh and and our lab has been involved in this way in this effort for a long time where where the initial part of this effort is in fact to develop a set of rules that link order structure to odor perception that is 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 smell something and tell you what molecular structure could or should be you know so in contrast let's say the 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 it's going to be of course there are exceptions to that and and all sorts of issues but as a rule 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 uh it's going to be perceived um so so that's an example of where the rules linking structure in this case measured by wavelength and perception in this case experience this color the rules are well known in olfaction we didn't have that until recently um but over the past two years a bunch of labs have really um uh pushed this forward uh there's a bunch of work out of Leslie vosh Hall's Lab at Rockefeller and Andreas Keller working with Leslie um uh who've done a lot of work on this front um also work from Joel mainland's Lab at monell um and fair Discovery Joel was a graduate student in our lab um and and recently in our lab we've had it and I hope this doesn't come across as overly arrogant but we we've had a sort of mini breakthrough on this front to call something a mini breakthrough is far from arrogant and and this is a paper uh led by Aaron ravia uh uh from our lab and Kobe snitz also a major contributor there a paper published in nature uh about a year and a half ago in the height of a coveted pandemic so nobody really or I won't say nobody but it wasn't noticed in the way it would otherwise would have been it was it was published in nature really on like a week where the whole world was like going berserk over covid um and in this paper we develop an algorithmic framework uh 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 you will smell them to be okay now not only could we predict that but we could design it so we can generate um um mixtures with known similarities and the the result was highlighted and you'll appreciate this coming from vision is that using our algorithmic solution we generated olfactory metameres so we measured mixtures completely non-overlapping in their molecular structure but they smell exactly the same okay now if you would come to a classic perfumer or most classic perfumers and tell them that you can generate two mixtures with zero molecules in common but smell exactly the same they would tell you no and yet we did and anybody can recreate them this is simple actually um in in the paper we do a few things like we generate amid a mirror for uh Chanel Number Five so you don't like perfume so this one but but we we take so we generate a Chanel Number Five with no component from Chanel number five in it okay um and we actually have a publicly available website I'll give it to you for your links if you want that anybody can do this we built an engine that you can generate these these metameras now once we did that in a way we've generated the the the infrastructure for digitizing smell because 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 4 000 molecules uh for each one we know there are perceived smell now you can make up any mixture you want from me I can project it into that map and measure its pairwise distance from all the points in the map if it falls on Lemon then what you generated smells like lemon and if it falls you know on tomato then what you generated smells like tomato so we we now solve that problem we can predict the order of any molecular mixture we can see how it's going to smell what we can do is then find a set of components which we call outer primaries that can be used to mix any odor that you can perceive and that's what we're working on now um and in about a month ago so this is in collaboration with a lab of Jonathan Williams and Max Planck in Munich Jonathan Williams is an uh atmospheric chemist uh but he's really good at at using gcms these tools that measure molecules so Jonathan Williams measured odorants in Germany uh transmitted the information to us over IP uh we fed that into our algorithmic framework and recreated it from a device that mixes primaries uh and we tried to do four different odorants uh in our our proof of concept test uh one of them uh was Rose and we failed at recreating rows we in fact recreated something that had a preset but most people perceived it as bubble gum uh the second one we tried to do was a nice and we failed at recreating Anis and most people said it was Cherry which is not very far but it failed the third was gasoline um and we were slightly but significantly better than chance at recreating Gasoline um and the fourth was was violets and 15 of 16 peoples and violets so the first order ever transmitted over IP is violets and we did that last month um of course this is not anything near a practical solution uh the device uh uh that Jonathan was using to measure uh is uh 1.5 million dollar device bigger than this table uh that's right I remember when VCRs half the audience won't even know what that is yours were like this big so we're we're all good okay I'm all good with the uh with the prediction that things will come down in size and cost yeah I'm just saying here you know don't hold your breath for this to be on your table tomorrow um and and you know again even even you know all we have in hand is 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 there's still lots of work to be done uh but we're on we're on the path uh we're on the path and you know Google will probably beat us to it uh they got a lot no you seem pretty dogged in there yeah but they have so much more resources that uh that um at this stage it and they've already published uh two papers from that effort that are good uh yeah you know they definitely have a lot of dollars and a lot of people a lot of good uh neuroscience and other biology Engineering Graduate students and postdocs go there but but um the real question is are they getting the best people because as you and I both know in science the oftentimes it's small groups of of the very best and most creative people that can uh out run and outgun large groups and and here I don't have anything against Google either way yeah um I I use it all the time I'm not a betting man but I would put my my money on Google on this race but I'll give I'll try and give them a a run for their money there you go that was well since I mostly just want to see the problem solved regardless of who gets there first what I'll say is you better get going Google because gnomes being he's humble and he's dogged so I don't know um better better get cracking there we just cost the weekends of and uh and broke up the relationships of a bunch of scientists I remember when I was a graduate student at Berkeley I remember hearing there was a guy in in our common friend uh or uh Irving zucker's lab that worked hundred hours a week so I was like oh I'll work 102 hours a week which was not a good choice but in any case it's it's uh it's abundantly clear that you're making progress here and 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 uh gasoline from people watching the the F1 race or something but um I'm thinking dating apps I'm thinking um you nowadays everyone knows that when you travel and you want to see your family your grandkids or kids you better to get on FaceTime and see them resume um than to just hear their voice we're also talking about being able to smell them I'll tell you more than that I'll tell you more than that I mean we're talking now of trying to achieve uh the olfactory equivalent of Circa 1956 black and white TV okay basically right and you know I'm not dreaming let's say of being able to transmit to you the difference between a Cabernet or Amarillo right but if I can generate something that's legally wine that will be an amazing success from my perspective right but Jump Ahead in your imagination to to 4K order transmission than medical Diagnostics is what you want to be talking about because in this is this is uh uh over uh 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 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 Vision I mean this is not close but when when olfaction digitization is brought to the equivalent of 4K uh of vision and audition that you have now then it will be in medical diagnosis you'll have excuse me for the uh the imagery but you will have an electronic nose in your bathroom uh each one of us will have in the toilet and it will be doing Diagnostics all the time and and that's that's where it's going to go but again not anywhere in the very close future well it's it's certainly an exciting proposition and I'm delighted that you and other groups um who are so strong are working on it I really am no my I want to say thank you for your time today first of all uh this was a tremendously interesting conversation I mean we touched on so many things hormone smells the architecture of the olfactory system I know that people listening to this are realizing but I'm going to say it anyway uh what an Incredible Gift you've given us in um as a expert in this field giving us this tour of of the work that you and others uh who you credit so generously um have done to elucidate this incredible system that we call olfaction chemo sensation also just for the incredibly pioneering work that you've done you know I I don't have many heroes in science I have Heroes outside of Science and a few insights but I'm gonna um I'm gonna uh purposely embarrass myself a little bit by saying that from the time I was at Berkeley and I then and saw that experiment being done and people foraging uh falling Ascent trails and then when I was a until I was a junior Professor I used that in my teaching slides um in a class that I taught that was sort of the early origins of this podcast in many way and over and over again when your laboratory publishes papers I find like this is super interesting super cool and I find myself telling everybody about it and that's really what I do for uh for a living is I I learn and then I blab about it to 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 Ben Barris used to say keep going because we are all benefiting tremendously and um and I also just want to say that you know for people listening to this the 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 um 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 say send a huge debt of gratitude thank you so much so I'm I'm the 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 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 you you function without that I mean I guess that's one of the things you need to be a scientist is to have the you know the drive to work without that because it comes only rarely uh there's immense gratitude and appreciation for you and what you do from me and now I know from uh a large segment of the world as well so uh my only request is that you come back and tell us about the next results sometime not too long now yeah well I'm going to catch you live now although you have the power to edit this so I guess that's not fair but first you come visit us in Israel and and tell us both about the science and the public science work you're doing and then I'll come again a good bargain and again I accept delighted thank you so much yeah pleasure thank you for joining me for today's discussion about olfaction and chemo sensation with Dr Noam Sobel if you'd like to learn more about the work in the Sobel laboratory or read some of the papers described during today's episode as well as learn about the current and future projects in the Sobel laboratory please go to the link provided in the show note caption if you're learning from and or enjoying this podcast please subscribe to our YouTube channel that's a terrific zero cost way to support us in addition please subscribe to the podcast on both Spotify and apple and on both Spotify and apple you can leave us up to a five star review if you have questions for me or comments about the podcast or guests or topics that you'd like me to include in future huberman Lab podcast please put those in the comment comment section on YouTube I do read all the comments please also check out the sponsors mentioned at the beginning and throughout today's episode that's the best way to support this podcast not so much on today's episode but on many previous episodes of The huberman Lab podcast we discuss supplements while supplements aren't necessary for everybody many people derive tremendous benefit from them for things like improving their sleep their focus and hormone support the huberman Lab podcast is proud to have partnered with momentous supplements if you'd like to see the supplements discussed on the huberman Lab podcast please go to live momentous spelled ous so that's livemomentis.com huberman if you're not already following the huberman Lab podcast on social media we are huberman lab on LinkedIn Facebook Twitter and Instagram and on all those accounts I include information some of which overlaps with content of the uberman Lab podcast but often which is distinct from information covered on the huberman Lab podcast so again it's huberman lab on all social media platforms if you haven't already subscribed to our newsletter we have a zero cost monthly newsletter it's called the neural network new newsletter and it includes podcast summaries and toolkits or protocols for things like enhancing sleep for exercise for meditation for dopamine for focus and many other topics to sign up you simply go to hubermanlab.com go to the menu and click on newsletter and provide your email and I want to be clear that not only is the neural network newsletter zero cost we also do not share your email with anybody once again I'd like to thank you for joining me for today's discussion about olfaction and chemo sensation with Dr Noam Sobel and last but certainly not least thank you for your interest in science [Music]

Channel: Andrew Huberman

Views: 1,302,889

Keywords: andrew huberman, huberman lab podcast, huberman podcast, dr. andrew huberman, neuroscience, huberman lab, andrew huberman podcast, the huberman lab podcast, science podcast, noam sobel, Weizmann Institute of Science, smell, olfactory, olfaction

Id: cS7cNaBrkxo

Length: 193min 16sec (11596 seconds)

Published: Mon May 01 2023