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

welcome to the huberman Lab podcast where we discuss science and science-based tools for everyday [Music] life I'm Andrew huberman and I'm a professor of neurobiology and Opthalmology at Stanford school of medicine today my guest is Dr gome soel Dr gome soel is a professor of neurobiology in the department of brain Sciences at The wisman Institute of science his laboratory studies olfaction and chemo sensation olfaction is of course our sense of smell Cho sensation is our ability to respond to chemicals in our environment today you are going to learn some absolutely incredible facts about how you interact with the world and other people around you for instance you will learn that humans can smell things around them as well as dogs can in fact humans are incredibly good at sensing the chemical world around them you also learn for instance that every time you meet somebody you are taking chemicals from that person either from the chemical Cloud that surrounds them or directly from the surface of their body and you are actually applying it to your own body and you are processing information about that person's chemicals to determine many things about them including how stressed they are their hormone levels things that operate at a subconscious level on your brain and nervous system and that impact your emotions your decision-making and who you choose to relate to or not to relate to you 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 Nom sobel's laboratory has discovered that relate to everyday life and that are going to make you say wow I can't believe that happen s 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 soel was a professor at UC Berkeley as I mentioned before you 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 soo laboratory in which humans were following a scent trail that scent Trail was actually buried some depth underneath the Earth and yet they could follow that scent trail with a high degree of fidelity it was from that experiment and other experiments done in Dr sobel's laboratory at Berkeley and at the wisman 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 vaction and chemo Sensation that have been carried out by Dr so'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 with that theme I'd like to thank the sponsors of today's podcast our first sponsor is Roka roko 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 Roa 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 extreme extremely lightweight so most of the time you don't even realize that you're wearing them I wear Roa readers at night 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sleep needs for me that was the dusk Duss 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 Hu 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 gnome soel Dr soble gnome welcome thank you must say I am extremely excited for this conversation I've been a huge fan of your work for more than a decade or two uh yes kind of frightening yeah yeah we overlapped at UC Berkeley some time ago although we did not meet and although 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'd love for you to share with us um All About The Amazing landscape of chemo sensation in particular olfaction our sense of smell and some related perceptual abilities or subconscious abilities including phermones 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 where I like to think it involves the nose at some level it does to what extent is that mixed in with other senses like taste and perhaps more importantly what about the chemicals that we are sensing through this thing and for those of you listening I'm and not watching I'm tapping my nose that we are not aware of you know the the chemicals that are that we're inhaling and um making sense of without our awareness 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 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 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 all faction 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 all faction to food and taste comes from that from retro nasal Alf faction but uh uh primary Al faction is referred to as orthonasal Al faction that is through our nose we Sniff and sniffing is a big thing well I have a sense we might talk about that a lot today 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 cmers to about here where they interact with I will you use the word sheet of receptors but sheet is a bit misleading here it's not a sheet it's very convoluted we have about 7 million such receptors linning a structure known as the olfactory epithelium this is the sensory surface of the olfactory system the alaor 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 uh it's hard to count uh but it's reasonably grounded and there was this thing roaming around in the literature about blood hounds having a billion receptors than their nose which is why they're so amazing and this number was you know it's sort of propagated through the literature and and our lab um has written over the years a few review chapters and and we were repeatedly writing the all faction chapter for a very large one of these large textbooks the gazan handbook of cognitive Neuroscience I think it's called um and and we had that in there as well somewhere and and one time when we were renewing the chapter for a new version of the book I told the graduate soon who was leading that at the time arah sharun she's now a professor at tviv 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 Blood Hound where did that come from and and surprisingly she answered me and you know I was hoping to get a reference right but it wasn't reference and and this is where it really becomes funny for us because she said I I I was once um at a lecture of an allf faction geneticists geneticist by the name of donon Lancet uh 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 Duron laned is in the building next to me okay he's in Whit Institute genetics I mean he used to be he's retired now uh and and he he had meaningful contributions in the history of wol action um so I picked up the internal phone and and I said hey Don you know did you say that there's a billion receptors in The Blood Hound knows and he said what's a blood hound so this was 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 BL hound and and you'll get a of hits but there was absolutely no evidence for that amazing and not just amazing in light of what it it tells us about old faction in blood hounds 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 sight yourself and right so we fix that in in that version of the of the and and so to finish the line so that so so odorant interact with these receptors um here in our epithelium uh where they undergo what is referred to as transduction that is the odorants are dock at a receptor and turn into a neural signal or or in force the receptor to respond in a neural signal and uh this neural signal in fact Action potentials not gradient potentials of any kind uh propagates uh via the olfactory nerve now this is a nerve that goes from our epithelium uh right here behind the forehead no well yeah yeah here uh through uh the thinnest part of our skull an area refer to as the CRI form plate which is preforated 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 AL Factory bulb in humans uh that forms an interesting uh uh point of sensitivity um because a lot of people lose their sense of smell due to trauma uh because of that structure 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 injury so as your listeners probably know our brain is floating in liquid in CSF in cerebral spinal fluid inside our skull and when we get HD 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 contrical injury you also often have frontal damage but what happens is that this generates a shearing motion on the cbor plate and the olfactory nerve is severed and if it's completely severed it's it's lost forever because my my understanding is that the olfactory Sensory neurons can are among the few central nervous system neurons in adult humans that can regenerate so or replenish themselves right so so I'll I'll again there are a few questions in so first of all we will spin many plates simultaneously it's completely severed completely then yes you're lost forever yeah if it's completely severed because even if you'll have regeneration at the basil cell level at the epithelium they won't manage to find their way back uh to the bulb if if you have partial or something left or something shows up in a short while after the injury then you have a good chance of recovery H because they grow along the trajectory of the other Axel so pioneering the way for them assumingly yeah 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 covid that it's very distressing and and basically the rule of thumb is that if you don't get it back within a year a year and a half you'll never uh get it back my my understanding of the statistics on olfactory loss in covid and and and other viral type infections is that um first of all I had I experienced that when I got covid including total anosia for one day and not total it was just there was a remnant of an ability to to smell or or perceive the smell of a lemon and I was huffing as hard as I possibly could I actually there's an over-the-counter remedy and this is not uh pseudoscience because there's a number of papers published about this on PubMed that alpha lpoic acid can accelerate the recovery of of of smell and and so that's something that um it worked successfully for me I'm not saying that that's the only or rout you don't know if it works successfully for your if you would have recovered anyway I mean you didn't do a control true but I was not willing to do the control experimen uh exactly so yeah that let me say two things on this front first the dean on the alphalipoic acid is yeah it's not overwhelming but losing your sense of smell is overwhelming so so I think people feel desperate one word about the smelling the lemon and this is uh I'll take that opportunity to to uh share more information when we smell things it's the result of more uh sensory subsystems in 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 geminal nerve has sensory endings in your nose in your throat and in your eye it has three branches that's why an onion has a smell and burns your eyes and burns in your throat is that trigeminal yeah the tearing of of cutting an onion is Tri 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 were 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 allory receptors um so in within you know all faction researcher jargon uh there's what we refer to as pure olfactants these are odors 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 uh the coffee right here uh is a pure alaant uh vanilla is a known pural faant these things have no trigeminal activation um 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 primar faction 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 makes total sense to me why keeping neurons active keeps them alive so this is not fire together wire together type thing by the way that's a quote from Carla shats not Donal head folks or me um but this is about keeping neurons electrically active in this case Factory neurons in order to maintain their connections because otherwise they will die well all faction is a definite use it or lose it system and so that makes total sense and indeed there's very strong evidence for success of of uh the training programs more than the alphalipoic acid um 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 nether one one of the cool things so so in Al action you can you can study many things through Alf faction and 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 meleon brain and whether the human old factory 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 the what the authors did um was look at in in postmortem they looked at levels of c14 in in adults who 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 all Factory 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 of neurog degeneration you have in in the human factory system as opposed to other uh uh mammals but but that was just a really cool paper I think of of of doing that fascinating no I I should I finish the the path just so we have so so we said so so information then synapses at the olfactory bulb from from uh uh uh the the olfactory epithelium and the pattern of that synapsing follows what's referred to as the most extreme case of convergence in the mamelon uh nervous system more specifically what happens is that all the receptors of a given subtype and remember in humans we said we have about 350 in the mouse we have about 1,200 probably um so all the receptors of one subtype converge to one location in the bulb and uh this location is referred to as a glus or an impl gleri and and that may be a slight oversimplification it's in fact two glomi there's a mirror sort of a mirror a cut line and so all the receptors of one subtype will converge to two miror gleri on the olfactory bulb so you end up having uh two gleri 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 oopes the molecular aspects of the odorant so each receptor is responsive to a different subset of oopes let's say 10 and each otop will activate a different subset of receptors so potentially you have this insane common and Torx of this potentially 350 dimensional space in the human potentially but then because of this convergence you end up having on the bulb in a way a map reflecting o receptor identity so so let's say this coffee uh activates receptors of type 13 and 7 so the gloi of receptors 13 and 7 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 ball bulb to several Targets in the brain I mean what is referred to as primary Factory cortex is perform cortex and and enthorinal 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 amigdala it probably goes directly to the hypothalamus it may go directly to the cerebellum uh it goes all over the brain so so information projects widely from there and as far as people understand the map that may exist on the bulb uh doesn't exist in the rest of the brain and the understanding of of how coding occurs in the rest of the brain is is murky commonly one hears that the memories that we have of odors are somehow more robust um than the memories of other perceptual events in our life I I don't know if this is true or not but um people will 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 multistation but nonetheless somewhat direct path from the nostrils to the hippocampus one of the primary encoding centers of meor 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 uh memory centers um is there any uh just so story or real uh objective truth to the idea that olfactory memories are formed more easily or maintained longer or more robustly than other sorts of memories so so yes uh but first I I should I should say that I'm not an authority on all Factory memory it's sort of it Factory memory is a huge field of research and somehow our lab has never really um gone much into that although uh again the same student I happened to talk about before the Ari sharun who's again now A A Faculty at Tel Aviv uh um ran a study a paper we I think we published in current biology biology called the privileged representation of early Al Factory uh associations basically there's something about the first time you experience a smell that generates a particularly robust representation more than other sensory stimuli and and that's what she in fact compared so there's something about the first exposure to a smell um in terms of the brain encoding that that etches it into our uh being and and this is an effect that has you know it has Echo was of course in literature I mean you know the the the biggest cliche in this is to bring up the pr effect right so the pr effect is when he ate the meline and it immediately the taste and smell immediately reminded him uh of of an event in his childhood where where uh where the same meline U appeared uh um but but so so that's something very real there there's a lot of research on it uh not coming from our works so I'm not an authority but it does sound like there's something special about all faction 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 to argu that there's something special about all faction it's a my my students make fun of me because they say and there's some truth to that that I try to explain everything through the all factory system I mean for me everything is all Factory 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 greens since 2012 so I'm delighted that they're sponsoring the podcast the reason I started taking athletic greens and the reason I still take athletic greens once or usually twice a day is that it gets me the probiotics that I need for gut health our gut is very important it's populated by 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 athletic greens.com huberman and they'll give you five free travel packs that make it really easy to mix up athletic greens while you're on the road in the car on the plane Etc and they'll give you a year supply of vitamin D3 K2 again that's athletic greens.com huberman to get the five free travel packs and the year supply of vitamin D3 K2 when I was at Berkeley um I was walking across campus one day and I saw I think students but I saw people on their hands and knees with goggles on gloves on yeah and um I think their mouths were covered too um 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 uh it's UC Berkeley and the joke is if it to get noticed on the UC Berkeley campus you have to be naked and on fire right one or the other would not be sufficient please don't run this experiment anybody um It's that kind of place um yeah but nonetheless um 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 some am of Sensation that is touch 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 exquisitly well and I I have other family members whose sense of smell is quite poor um I'd love for all of those people to learn a bit about what is possible in terms of training up or improving our ability to smell and um perhaps in the context of that study if you will yes 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 s of you know yeah we know this this is old news but but to people who who come from different worlds we have to reiterate this sometimes when I give uh you know public lectures to to non-all faction audiences I reiterate this humans have an utterly remarkable sense of smell to to put that a bit into sort of you know things that you could that are tangible so so for example um mer capons which are added to cooking gas so that we smell it because otherwise it wouldn't have a smell so that the smell of gas it's not the smell of gas of propane it's an additive Captain yeah it's merap 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 of making this again really tangible we're working with a odorant in our lab called estr Tetra enol that our participants can detect when we have it mixed at 10 to the -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 pipet 1 ml one drop into one pool versus the other you could smell the difference between the pools in 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 Mamon 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 as a lab bet okay we we were having a lab picnic so I guess I should hear fill in because I I'm I'm your guest from The whitesman Institute of Science in Israel but before going back to my home in Israel I was a uh um faculty at UC Berkeley in the Helen Wills Neuroscience Institute and this study was done during that time and we were on a lab picnic and we were having indeed one of these sort of lab discussions arguments on what humans can and can't do with their sense of smell and and I said that humans could truly even track odor like a dog and people there said no way and we ran this quick experiment uh which I have video of but I don't think we'll show it here uh but I actually have original the picnic video we have it and uh a graduate student by the name of Christina Zano 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 of all faction Imaging today but she was the volunteer and we dragged a chocolate bar across the grass and blindfolded her and checked if she could track the track we made with the chocolate which she did very effectively right and as far did you place her 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 uh tryy out 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 labed 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 bet I W in this case nature of course being one of the the a three Apex Journal science it was it was nature neural science to be fair 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 from our lab uh completely deprived them of any other sensory input so we blocked their eyes we blocked their ears we blocked everything we block they were wearing heavy gloves uh you know they they couldn't sense anything and we generated a a a consistent odor path in the grass which is what you saw uh 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 at the base of the grass or in the dirt it was buried it was buried under the grass really yeah yeah wow I did not know that it was buried under the grass and we uh conducted aerial photography and um participants also had the sensor pack that they were wearing where we um measured nasal air flow in each nostril in real time and uh they all we also use 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 um 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 trained them up then within uh average of 4 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 a dog can run but you as fast as you can crawl you can sent track and then to to sort of add what made it really interesting from from a system as neurosin perspective is that we asked whether having two nostrils uh contributes to this so uh we built we constructed a nasal prosthesis if you will uh that had two versions one is that it it combined both nostrils into one big nostril centered and the other is that it it maintained two separated uh nostrils and we compared performance under these two conditions and people performed better uh with two nostrils over one centralized nostril although the flow 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 and a number of AD 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 draw in inh 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 you're asking me about a paper from quite a few years ago so I I may be forgetting parts of it as well um but I'm sure if it was a a major component of it it would have risen to the top it definitely wasn't a major finding 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 uh and and it's it's taking us to to places and and it's reemerging now in our work we're we're doing tons of sniffing work um I you know I can share with you some something that that I think will interest your your uh listeners and viewers as well and and we think is is really uh uh one of the most overlooked things in in Neuroscience uh I'll invite you I'll invite you to do the following experiment so olude one nostril by pressing on it from the side and sniff in and then olude 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 Con Conant shift from side to side the shift becomes incredibly pronounced in sleep so we can measure the power of the difference and and in sleep you have this phase shift of power you have a huge like one closes and one opens totally and it turns out that this is linked to uh balance in the autonomic nervous system so as you and your listeners know we have an autonomic nervous system that has a sympathetic and parasympathetic component to it and and they're in balance or imbalance in many diseases for example and this interplay between the uh Auto 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 ORF flight system but any pattern of arousal positive or negative and then it's balanced in a coordinated way or at least in parallel with the parasympathetic nervous system which is sometimes called the rest and digest system but is associated with all sorts of things the sexual arousal response um 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 had this eye cycle right and that was linked to autonomic arousal I assure you you would go to pbed there would be 5 million papers on the ey cycle right and the eye cycle and 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 uh is pasted to your body and measures air flow in each nostril separately and logs it for 24 hours and 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 worked by team nooka graduate soon our lab now uh I can so we can tell the difference between uh ADHD and non-adhd adults and we can tell just from the record in we can tell if the adults are on riddling or not so I can I can measure your nasal air flow and say if you are or are not with ADHD and if you are or are not on riddlin incredible I have a couple of questions about this is it the case that air flow 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 um periodicity um which you said I think is on the order of about every two hours and two and a half it switches to uh maximal on one side versus the other is that simply reflective of an overall balancing like 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 you know the yogis are going to be all over this cuz 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 any particular but um where they'll have you breathe through one nostril or the other and I've I've probably been asked this question on social media 10,000 times okay wait I'm gonna become Public Enemy Number One of the yogis right now so listen we so we we come at you with yoga mats which are not very dangerous we really so 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 by 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 we might you know use this to to cure ADHD or or whatnot right so so we posted like on all lists of like the yoga teachers and had this parade of yoga teachers walking into our lab it this was one of the strangest Sandalwood odors and bare feet white white clothing and and so on and and so we we studied 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 an nostr Yeah by by the power of thought Alone um and you know how many of 14 succeeded zero including including one you know the most extreme one was we we have 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 I'm it's switching and you know you're looking at the moderator 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 there's no incentive for them to lie right yeah no I even the opposite I mean you know this puts them in an awkward position once yeah I don't know what the deal is but but none of them can do it 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 autonomic nervous system and the reason I'm asking this question is not because I think that's necessarily important as it relates to stress but I'm trying to understand the direction of causality in other words is the the unilateral smelling through or unilateral nostril smelling periodicity there when we named it something I named it the wrong thing I'm sure is that driving the shift in the autonomic nervous system or is it merely reflective of the the shift so you've you've very concisely now worded aim to 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 uh 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 you're it's capped at 3 minutes so for safety reasons because you have you have participants putting their hand in in uh two degre 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 3 minutes as well so there's lots of lots of uh and and already 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 cold generates a shift in the nasal FL in in 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 glami where the 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 neuron Anatomy what Nom was describing is the fact that of course there are two nostrils and then a bunch of receptors they converge in these glar but you have a mirror representation of that on both sides of the brain and that most of that information is kept on one side of the brain or the other there isn't a lot of extensive intermixing at the first order of processing so the question I have is whether or not you believe I'm not asking for data first I just want to know what you believe that this alternating nostril airflow phenomenon has anything to do with preferential processing of olfactory information in terms of right brain left brain with the caveat that anytime we hear right brain left brain um we've covered this in a previous episode most of what people hear out there about right brain left brain emotionality logical stuff is completely wrong completely wrong doesn't exist it's a total fabrication um and we'd like to abolish that myth but with that aside or set aside rather what are your thoughts on why that 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 all faction story um so so I I don't think that um that this was shaped by Thea system nor do I think this has major impact on all faction I think the nasal cycle story is a different story about brain function um so so you know we have we have this sort of pet Theory where are calling now the the sniffing brain approach where where basically we think that that nasal inhalation is timing and driving a 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 if you think of the Maman brain right it's which which evolved from all faction it's sitting there and and in all faction because all faction 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 toone linked to nasal inhalation and and we think that that this property evolved to to be meaningful in brain processing in general not only of of allory 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 off Perl from our our lab uh two 3 years ago um we looked at at something completely nonolfactory we looked at 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 in that particular task people performed significantly better on inhalation versus exhalation what was the task was it an old factory task no no it's a visual spatial task so this is a task where where uh the the specifics of the task were um that you see uh 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 figure yeah but but but but uh structural shapes not not and and so so a pure visual spatial task we we intentionally went for a task that is not considered a vental temporal task an old factory cortex task in any way and and people performed much better on inhalation versus exhalation at doing this task was there a both nostrils uded 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 n inhalation versus exhalation so bet 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 Y and this idea that people who mouth breathe um experience more colds more infections of various kinds it's not good aesthetically or for the dentist denure I never know the teeth the gums it's stuff folks sorry my uh 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 uh news breathing shapes cognition and and there there are other labs uh who who are uh are finding the same uh again uh Christina Zano is doing work on this line she she had major contributions here and and Yan lunstrum is doing work on this line there there's lots of studies suggesting that um nasal inhalation is timing cognitive processing and and modulating it incredible um perhaps not surprising given what you've taught us about the old factory 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 which they are the retinas any anyhow and um and then you never look at anyone the same way again it's but the the olfactory Sensory neurons are right there at the top so those Caverns that we call nostrils and they are brain yeah definitely it's it's the only place where your brain meets the outside world because in your R now 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 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 and so on um but but all Factory loss again is is an early sign of of neurod degeneration and there's at least one Theory particularly about Alzheimer's disease suggesting that that Alzheimer's may be the result of of a a pathogen that enters the brain through the olfactory system um how interesting it's it's not of course a a a mainstream or widely accepted theory of any type but but it's just it just highlights this notion that that the nose is a path to our brain I think these non-invasive um readouts of potential neurod degeneration um such as uh visual tests because of the fact that the retinas are part of the brain and loss of neurons in the retina is often associated with other forms of central degeneration Alzheimer's um Parkinson 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 old factory task every time we go to the doctor um that would allow tracking over time because of course as you mentioned someone can lose their sense of smell does that mean they're getting Alzheimer's not necessarily but if their sense of smell was terrific the year before and it's 50% worse the next year that's a really bad sign yeah that's a bad sign and so what we're talking about something completely non-invasive um and could be relatively Pleasant to innocuous depending on the odors used so yeah so so first I can answer that right and the reason that that's not happened and that might that that may be changing right now but the reason that has not happened is because all faction 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 at the resolution of the visual system basically and if you want to generate auditory stimuli really precisely then you can buy an amplifier for you know maybe a bit more than 100 bucks but not that much more and you'll be at the resolution of the auditory system in our lab we build devices that generate odors uh we call them all feters which is a misnomer because they don't measure anything but that's what they've always been called so we call them all foms as well and we've already built at least one alcometer 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 and that there there are a standard clinical tests of vaction basically to that s out 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 and it's a four alternative Force choice test with 40 odorant so you have these 40 pages that you page through and you sniff and smell and and um you know it's been normed on gazillions of tests um I I'm always amused by it because so so Richard 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 upsit in live I say there's another gallon of gas into Richard he races NASCAR not like NASCAR but like one lower than that like I don't know like some some sort of formula a or Formula Ford or something he races a car and so that's where all the ubit went so I always feel good about buying psit 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 so there's reduced upsit in Alzheimer's and Parkinson's and in a host of other diseases and there's a European version called sniffing sticks uh that Thomas hum has developed and and it's it's basically the same sort of concept of that one isn't scratch and sniff it's 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 uh you don't have what you've just suggested interesting 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 Al action it's not tested in in newborns right where vision and audition is you know there's this thing called congenital anosmia right which is being without the sense of smell from birth supposedly conal uh which is half a percent of the population it's not a trivial number not totally yeah but nobody knows if that really is true because here's an amazing factoid guess the average age at which congenital anosmia is diagnosed and this is 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 1% 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 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 conal anosia um the die younger um the so it's it's it's a it's this is work out of uh Elon 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 uh romantic social contacts um it's not a good thing um and and do they lack ol Factory bulbs I'm presuming they have noses and nostrils there is a condition I'm aware of where where children are born without noses very rare very rare we won't focus on that because it's it's exceedingly rare um they're born with noses and nostal um and here's the thing right we don't know if they're born with all Factory bulbs um most of them although not all of them but most of them don't have all Factory bulbs in adulthood or or I should rephrase that have remnants ol Factory 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 ol faction 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 factory system to some of the hypothalamic systems that regulate the release of ganat tropins 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 calman syndrome which is hypogenetic uh development um in in men and in cman syndrome uh they practically all anosmic so so to answer your question yes there's a direct link and and it materializes in calman syndrome that said not all congenitally anosmic uh individuals have calman syndrome and not all but almost all people who have common syndrome are anosmic so so common syndrome uh goes with uh anosmia I think so so there's a female equivalent of cmans or I don't remember its name uh it's not turn it's not a in the Turner syndrome family is I'm not sure and I think it's also associated with anosmia uh but I'm not confident of that but commmons is is associated with anosmia uh so so the answer is is yes and and you know we can maybe you know all faction and reproduction are are tightly linked and and they're tightly Linked In all mammals and we are big terrestrial mammals and all factions 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 insid tracker insid 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 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tracker's plans again that's insid tracker.com huberman to get 20% off I have a a story slash question that I'd like to um tell you ask you as a segue to that um noting of course that that we'll get back to the requirement for old factory bulbs yes or no for old faction uh and um this relates to when I was growing up I grew up at the uh end of a street with a a lot of boys of my age who just by Winson had a lot of older sisters they 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 these things like kids stuff for Stuff get into trouble or whatnot and oftentimes we would end up leaving our articles of clothing at each other's houses all the time like t-shirts and jackets and so my mom was constantly coming in and saying there's all there's this clothes like someone left 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 eisenh Hart's shirt a friend of mine there I just gave his name or oh that's Scott madson's shirt I I could just smell the shirt and in a conscious way know who it belonged to having never I promise not that I would pretend if I 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 the 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 a or some other aspect of their um chemistry yeah so yes um we're doing that all the time in my view and a a lot of this processing almost all of it uh is subconscious and I don't know why I'll already I'll already put that out there right I have no idea why why uh Human Nature has has uh or or nature or culture or whatnot has has has pushed this into the realm of of subconscious and something we're unaware of um but we do it all the time and and um and our lab has lots of studies on this front um one of them you may be familiar with that that had gained some notoriety because it's amusing um so so we we look at human behavior a lot we try to look at it through our nose 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 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 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 where finding more and more mechanisms where we do this and 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 as 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 if you you know if you look for the Wikipedia version right then they'll tell you that it's to show that you're not holding a weapon in your hand but there's really no good evidence for that it's a bit like the trillion Blood Hound receptor story right I mean we tried to find it you know why do people say that 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 go like this and like this those of you listening not watching gnome um is taking his hand and and wiping it on his face touching these things these things that we do all the time after a handshake well so so first of all we do them all the time just period right the Baseline here is really high and we'll get to that in a second but but but these behaviors that you know you 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 joh frine in our lab at the time um and what we did first and and if you want we can link so so this was published in E and one of the nice things about eif is that it has a very effective way to uh embed videos in the publication so if you want we can link this to your system later on the put it in 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 of course later on they they had the opportunity to to not agree to us saving the video in which case we would delete it immediately or or letting us use it for science or some letting us use it for more than science for for the video that's now on E life and and we would walk into the room and say okay just wait here we'll be right back with you uh to set up our experiment and they would sit there for 3 minutes and during those 3 minutes we could later quantify how much indeed they just by Baseline how much they touch their nose or their forehead or their chin or how many times their hand uh uh reaches their face and by the way that Baseline is not low okay um and then three minutes later an experiment 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 and and so just wait here and we'll be right back with you but in the meantime just wait here and the experiment went through through this like 20 second fix text and in half of the cases it included a handshake this was a new experiment or not the one who put them in the room so it's the first time they met so it would' be hello 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 inactions in terms of gender so we matched male participants with male and female experimenters and female participants with female and male experimenters and so you had handshake and no handshake conditions and then you can quantify that behavior of the hand going to the nose after handshake and there was a remarkable increase in the hand going to the nose after handshake and this is one of the nice cases we the paper includes statistics but you don't need statistics here just look at the video it's un 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 Alla Factory Behavior one is unbeknown thean to participants we measured nasal air flow and and people not only bring their hand to their nose they sniff fit 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 that could emit an odor and the experimentor didn't know what odor they were emitting and they could emit either a pleasant or an unpleasant odor and we could drive the self sampling afterwards up or down so this was an all Factory Behavior no doubt about it I mean we're we're quite confident that so people in that case people must have sensing the odor on their own hand because they 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 would had been introduced to their own hand by the experimentor correct yeah but I 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 sniff their hand more or less the odor cloud of the experiment yeah and and there's an interesting thing going on here too because people didn't only smell the hand that chook 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 this same line and again to to link to your childhood story of of of uh identifying your friends by by smell um study we published just last year by in Bal rebi in in our lab um where in 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 that you know was poorly described or is poorly described in L literature as as as an entity and yet anybody will tell you they know what you're talking about right I mean if you tell you know somebody you click with right away you you become intimate within 5 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 look 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's 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 way and so to address that she she actually recruited uh um click friends from all over Israel she posted all over social media uh to identify uh pairs of friends so these are are same-sex non-romantic diets so these are friends men and women uh whose friendship started as a click where here this becomes sensitive because it has to be a mutual click right later on we discovered there could be one-sided clicks so 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 bars 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 are and if you ask these sticky people um sticky in air quotes because they're not physically sticky um they may be 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 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 an informal diagnostic code uh sticky so so so uh she she recruited um um click friends and then she um sampled their body order and and we have a a protocol for this so they're given you know uh odal shampoo and soap to use for 3 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 order from the t-shirt and so we have a way to extract a method to extract body order 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 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 Mamon nose does basically it's a bunch of sensors that respond to Airborne molecules in this case sensors refer to as moers as metal oxide covered sensors um and so she used an electronic nose to sample these body orders and she found that click friends are indeed more similar to each other uh than you would expect uh by chance by random diads and and this was a significant difference and after she found that a device could do this she had other participants do this so so she had people smelling the click friends versus non- click friends and and they 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 all the time or whatever live in the same neighborhood and and that's why they they they smell the same so to address causality she recruited ttal 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 she then at the end of the experiment each person rated each other person as to how much they think they would want to be their friends and also on a bunch of ratings how nice they think they are how affectionate they think a bunch of ratings okay all of this was predicted by the electronic 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 nose so this is not a result of friendship it's it it plays into the causal elements of of building friendship so this is to relate to your childhood story uh there's something going on here we're we're constantly smelling ourselves constantly this constantly I mean if you want to L the reason I'm smiling I mean and your viewers or listeners will understand why I'm smiling I'll send you a video to link uh uh in in the in into your podcast here uh we thought of calling the fact that people constantly sniff themselves we thought of calling this the low effect and low so so in America this won't pass that effectively but in in in the rest of the normal world uh Yim L is the soccer the national soccer coach of the German soccer team so I mean I don't know who would be a very famous coach here but Steve Kerr I mean this is the you know 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 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 well then 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 whoa 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 hisst compatibility 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 potential 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 whose odor and therefore immune composition is most different right so the way you describe the animal literature is correct and there's evidence to similar mechanisms in humans our lab has not worked directly on this issue of of uh of romantic selection based on odor um there's a bunch of papers um wedin at Allen and the wedin 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 odor preferences in humans are influenced by body odor and that this is linked to uh MHC uh uh uh histo 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 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 mamelon 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 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 but they can they can animal mamelon or or terrestrial mamelon 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 nose that transduce odorant and and so primarily the the manal 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 vulon nasal organ it's a small pit in the nasal passage of of most terrestrial mammals sometimes it's uh described as a communicated pit because sometimes it connects the nasal passage to the roof of the mouth sometimes it it connects both and so there's this sense organ with its specific receptor subtypes uh vnrs vermal receptors and uh this um um is linked to a to a sort of separate portion of the olfactory bulb not really the main olfactory bulb but it's refer to as the accessory olfactory bulb um and from there directly to the lyic 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 odorant that are sometimes referred to as pheromones um although that's in many ways a problematic term but but odorants that are referred to as phermones namely odorant that are emitted by another member of the species to influence uh that member of the species she an alter Behavior or hormonal State and and and some of these hormonal 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 uh scientist and in the Bruce effect when you expose a pregnant Mouse at an early critical stage of the pregnanc 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 and in in biological terms and in in forming this pregnancy and maintaining it and yet she drops it 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% of exposures now as you know 80% is 100% in biology right I mean there's nothing that happens at more than 80% so it's a remarkably remarkably robust effect this this dropping of the pregnancy and we know it's mediated by chemo sensation through the nose for sure and we know in the following way so first it's enough to just bring the odor of the non- stud male you don't have to bring the male himself right so you just can bring bedding from a nons sudden male and then 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 oblate the vul nasal organ you just burn this tiny structure in the nose then the effect disappears so the effect is completely dependent on the former nasal organ um and and and I find the s a remarkable effect right I mean because again because of the the extent of of cost that that the female takes on here uh based on on this information and smell now humans the the the sort of the going notion in all faction is that humans don't have a functional vulon nasal organ so we don't have that uh functional organ in our nose now I'll point out we we actually do have the pit so the 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 integrated biology class that we have something called Jacobson's organ this is the same organ so so Jacobson organs is the vulon 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 he was operating on or something like that the the the story comes from something like that but but the Jacobson organ is another name for the vul noal organ these are one and the same the sensory organ of the accessorial factory system and again the going notion is that the human Jacobson organ or his organ is vestigial it's non-functional does that necessarily mean that we don't have these pheromone effects no it does not so first of all we know that lots of what are considered fonal effects namely social chemos signaling and rodents are mediated by the mol 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 mol factory system and and and I'll I'll come back to that in a second but first to finish the the Bruce effect 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 vulon nasal organ um the the decision or the notion uh that it's nonfunctional 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 staining 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 aity of 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 uh of spontaneous miscarriage are they um occurring more often in the first trimester because you mentioned that in the Bruce effect in the mice is in the first three days or so Fallen pregnancy which in the mouse gestation as I recall is about 21 days in the mouse so you're talking about 17th 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 of hum yes which is indeed when most Carriage occurs now humans have again a huge number of miscarriages and and the numbers I I'll soon share them with you they 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 uh a failed implantation in day one two Etc more conservative studies talk about 50% 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 portion that are explained but all sorts of genetic factors developmental factors and so on and so forth but there's also a proportion that are unexplained and and and so all I'm saying is that there's there's a statistical backdrop or setting if you will for something like a Remnant Bruce effect in humans now with that in mind we we approached the group um of of we we we enlisted a group of of of they're not really patients and participants in a study of people who couples who are experiencing what is referred to as is 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 experienc 12 consecutive unexplained repeated pregnancy losses so so the two the two is just the formal all of our cohort was like 12 five you know so 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 all the all the the known suspects for for pregnancy loss and 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 to seek circumstantial evidence to see if if where there's fire maybe there's smoke and what we did was we tested uh all faction and more specifically the response to 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 fathering male because if she's going to miscarry in response to the non-fa she has to know father non-fa I mean that means that there's a pronounced all Factory memory at the moment of mating okay and in mice this has been very well characterized and and attributed to the anterior Factory nucleus uh 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 a skill 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 [Music] spouse and you might be disappointed or you know we would all are probably a bit disappointed to learn that control women uh are very poor at this so so you would think that that women would be good at identifying the O 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 their performance level so this is not a Nuance effect uh women who who who who experience repeated uh pregnancy loss can identify uh their husbands or their spouses uh by their body order with much greater Acuity than the typical person double a bit more than double and and way above chance yeah no I I sorry I posed it 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 remeasured their their brain response to uh stranger male body order and they 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 denovo is there a difference between these two groups of participants and there was one huge difference and it was in the hppo and so there was a difference in response to stranger male body order between the two groups um so so all faction 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 fewc 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 effect effects and one thing I heard you say during a talk which I think really captures this whole issue of are there pherone effects in humans um very nicely as you said you know whether or not it's a classic for pheromone effect or whether or not it's olfaction or something else this is 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 in animals and some potential pheromone effects in humans and a couple of the um human uh Al factionist as 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 an 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 Fone that was discovered was bambol which is the ferone that has the male moth follow the the scent Trail of the female moth bambol 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 and it all becomes semantics sort of like nerdy inside ball it's all semantic so I don't I in 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 and and there there are several examples of this one of them I I'll point out first which is is thought of the most widely studied and and not mostly from our lab actually I mean the 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 I think that's right yep humans emit a particular body order 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 fear 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 that dogs indeed can smell human fear um and humans can smell human fear so several Labs starting from Denise Chen and havin Jones and and then in our lab and in other labs um if if you collect body order 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 uh other people can determine which is is the state of fear and not and 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 asked 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 AR 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 the breakup um whether or not that morning period has something to do with an old factory unlearning of uh um and made and on and on and on with with all these insights I would offer you to be a postum say listen I have AAL coming up so I would love to do a it's going to kill me exactly you don't want me to work for you we talked about this earlier other reasons exactly there's a story there what n is referring to I'll just tell people because inside jokes on a podcast don't really work earlier I was just I was refering 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 who 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 the joke in my business is you don't want me to work for you so nonetheless I would love to do a sabatical in your La no so so what I was trying to say in that roundabout 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 all Factory animals you know I and and and you're you're even talking about the Nuance we're very old factory even not in the Nuance I mean you know 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 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 visually dependent I don't need a dog to take over my olfactory system if I lose olfaction but I'll tell you from having lost my sense of smell for one day I was in intense fear I into blue I love blueberries I'm like a driveby blueberry eater if they're there I just kind of pick them up like a grizzly bear and cram them in my mouth so keep them away from me if you don't want them eating but I can't I almost can't help myself 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 tremend a tremendous grief I I'll tell you a sort of a a throw line that I use in this when 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 whip cream but that smells of sewage versus some gray brown mix that smells of cinnamon which do you eat oh simple the ladder right you eat the lad right now imagine I I offer you a mate choose the the gender of your liking right that 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 and 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 perfum fumes and colognes and things of that sort and 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 and fortunately for me there's at least one person on the planet who said the opposite 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 he was a Bulldog Mastiff after all his smell was was rather aversive 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 zooker yeah a professor of Columbia has done incredible work and vision and old faction thirst sensing 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 appetitive not aversive as well as in children he was talking about the smell of his grandchild's the back 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 hexanal yes is Charles zuer your grandchildren smell like hex a Dean now he's going to come after me now they do and and so this this is a study uh ran by uh Eva mishor uh 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 and so when she started off we said okay let's do chemo signaling of aggression she actually was going to like MMA clubs and collect ing body oders 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 uh from Germany I mean when I say colleague primarily a friend or acquaintance I met at conferences um Hines Brier um and and um he was studying his lab a molecule hexa Canal 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 Feelgood together thing so when lots of mice are together they feel good about being in a group and that's social buffering and it's promoted by hexanal which they emit in n feces mice and in his work on hexadecanal um and and so so so Brier and his colleague stman they they discovered the receptor for this and then they went and discovered that the receptor is very highly conserved uh throughout Maman Evolution and therefore they hypothesized that maybe um this is a universal meleon signal now which is unusual because in in chemo signal in typically you you tend to think of things as being very species specific but here they hypothesize that maybe hexanal which promotes social buffering in mice may do something in all mammals again because this receptor is very highly conserved o 37b I think um so they so 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 all faction conferences where where lots of people study mice and and and zebra fish and whatnot and we're the the human group so and and eventually he just fedexed us hexad now 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 they're 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 hexad canal 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 hexad Canal 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 they're 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 a 100 checkel which is the Israeli currency so so the 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 it 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 and it goes to its end and then you you play a second game as far as you know against the same participant and the second game is a reaction time game so a Target shows up and the first to press it wins and on every trial where you win if you want you can blast the other participant with a loud noise and 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 participant in an experiment unless you're in Stanford 70 years ago or whatever that was no was referring to the the classic prisoner experiment which took place in the building next door to where I work by the way so you can blast the other participant with verying levels of of sound and you have a selection box from something very low to something very high and what's nice about this is it then allows you to quantify aggression because the more volume you're blasting the opponent with the more aggressive you are towards your opponent and and so you have a a measure of aggression again the Tyler aggression Paradigm obviously invented by Tyler uh very well validated studied all over you know a a very standard protocol so uh we brought in participants and had them play uh the Tyler the tap uh either under exposure to hexadecanal or control now hexanal doesn't it's it's incredibly difficult to even detect hexad Canal but just in case uh uh because it's not very very it's considered a semivolatile it doesn't have a strong smell um but we buried it both the control and the hexad canal in a a control order that hid them in a mask and and she ran lots and lots and lots and lots of parts of men and women and I'll first tell you the result with men which is that hexanal consistently reduced aggression people were less aggressive under hexad Canal um the effect size was was uh uh quite meaningful and later on we learned because I'm I'm no specialist in the world of regression but compared to the effects seen in the aggression world in in research really really strong effects so unusually strong so hexad Canal lowered aggression in men and we were like cool this is you know sort of what we were hoping to to see consistent with the hypothesis uh and consistent what it seems to do in mice but then we looked at the data from women and hexad canile 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 and EV got to it really I'll I'll tell you because remember we reaching the back of the head of your of of U who was it grandchildren Char Grand the charer 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 EV this there is 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 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 hexadin men made men less aggressive and women more aggressive and and and the extent of more than the effect alone the dissociation was remarkable this has the it's 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 at the brain data and 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 a brain activity I'm 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 FM not only an area that's involved in activity and and so here's what we saw that hexad deile Alon 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 all factory 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 angr Ag gyus and 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 reemerged powerfully whereby the connectivity from the angular gyus was mostly to the classic neural substrates of aggression so the amigdala and the temporal pole and the connectivity went in opposite directions in men and women so hexanal 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 hexanal increases the control that the left angulus is holding over your aggression and and keeping you back and in women it let it Ro free and they became more aggressive but I was still puzzled so so so I was convinced this this happened twice the M 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 I is no there's a place where this makes perfect sense and that is if you're a Maman Offspring because paternal aggression is often directed at you there's 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 and 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 sukur's grandchildren they used a method known as gcms gas chromatography Mass spectrometry uh to measure the volatiles from baby heads because baby head odor is a cultural thing across cultures even in Japan and so we quickly went to that paper and to see if one of the molecules that report is hexadecanal and we were very disappointed that it wasn't one of the molecules that 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 exal and 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 uh this lab which is a hardcore GC lab said no no hexad is a semivolatile which we knew uh and our previous paper was not directed to the semivolatile range but we can now do use what's called gcx GC double GC that uh is directed at semi volatiles and we can do this again 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 hexanol 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 chemos signal 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 uh 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 cour coordination of menstrual cycles among co-housed 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 mlin talk 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 proba 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 chemos sensing through the nostrils or Andor 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 mclintoch when she was an undergraduate at Wesleyan College uh and she noticed that she thought her menstrual cycle and 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 rodents don't have a menstrual cycle like humans do uh but but um there's an effect in rins referred to as the Whitten effect which um resembles uh this type of 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 student Chicago uh Stern so this is Stern and mclintoch 1998 and here's what they did they uh 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 ERS from certain individuals um I don't I don't think I uniformly like all body orders although I do seem to uniformly not like the smell of perfume although I just 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 great neurobiologist once said there's basically three responses it's either yum yuck or me so some are truly yuck never heard that one kind like that one right in terms of animal behavior human behavior we're either move forward back or or or pause um so some are truly a yuck some many are meh zero to date are yum for me now body odors the distribution is shifted it could be any one of those three yum yuck or me so just to be clear but the the um yum category is definitely included thank you for for allowing me to do that so so uh um so so she did this study so so because right in the original mlto study you might suspect other uh drivers of the effect let's say you you accept the effect but still there might be other social drivers of the effect that are not body order right there might be some dominant woman who's dominant in some other way and this might be driving the coordination right so here there was no direct link between these women other than body order so if the effect reemerged um it definitely be an olfactory effect and what she found is that if she took sweat from the follicular or the ovulatory uh phase of the donors one extended the 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 chemos signaling effect uh with with opposing uh uh effects on duration based on the time it was collected from uh again published in nature in 1998 that's it I I there there's a a quotation I think this is from from uh 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 sta statistics become tricky and and so show 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'm I'm and but I may may be in a minority in my field I think uh 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 and and you have to run it for a really long time uh and and uh so it's it's just completely non-trivial uh but we have a graduate student now in lab interested in these exact things R WIS gross and and she's doing similar stuff and and I hope we'll we'll do that I hope we 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 laborat of course or experiment analog but also because pheromone effects and olfactory effects in humans seem unique among uh neurobiological endocrine phenomena because there seems to be so many stories that we all have of the smell of our grandmother's hands or the recognizing the scent of 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 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 a rich um it's bodder 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 know it's it's a very Primal system you know so so uh it's it's linked to the most you know lyic Primal mechanisms in our brain and it drives Primal Behavior it's it's an incredible system I I have a question about a particular study but I'm just going to queue it up and you'll know immediately what I'm I'm queuing up um and that is what is the relation ship 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 or 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 yeah or below the waistline I mean we're biologists after all we we just yeah so it's it's funny we we we have we're working on a paper on that right now on the smell of fear 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 have to come to your lab it sounds like the greatest lab in the world we 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 mua perui 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 uh Israeli paratroopers Brigade and we now collect body odor from every firsttime jumper so um we we went that path because we like everybody El 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 cogn 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 it's 2 in the morning you're doing incredibly well considering the in we would never know um no one traveled in today from Israel so he's 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 K 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 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 we have a 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 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 lab you know we were 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 right 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 we you know this is a rare case where we actually hypothesized what we s to do and you know then only claim in retrospect that it was hypothesis um is is tears um we 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 non-verbal 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 in Emotion research is is Darwin's book uh uh the showing of the emotions in man 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 with no conclusion why because the book revolves around describing the functional anticipant 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 is a beautiful example and this is work partly done by by Adam Anderson now at Corell um is is the uh emotional expression of disgust so disgust which comes from the line disgus 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 bitter taste out of your mouth right so again so there's a functional antient spinning 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 there you know in the case of moral disgust there's nothing you're spitting out of your mouth so so Daren systematically went through the expressions of emotions and for each one went to their functional anticipant and explained everything very nicely and then he got stuck with tears right because tears are an obvious emotional expression and he could not find a functional uh anciant 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 blame it on nature right right so so and but he bothered to write this entire chapter on on on the ocular 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 um we we posted um m 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 a 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 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 easily going to show up yeah 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 you know I cry all the time it's just not going to happen uh 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 criers there's always oh yes you know the scene in in so and so I always cry profusely from that you know they have can you give me an example of one of the more commonly named scenes yeah with e um the movie The Champ the champ dies he's a boxer and he dies and it literally in the hands of his about 8-year-old son and his son is standing next to his bed and you know saying champ champ and and he dies right it's a winner okay waterfalls yeah yeah got it so you know we're probably the neurobiology lab with most sad movie films on the Shelf in the world right we have a whole huge collection there is such a thing as Tears of Joy by the way so no no well we're going ahead of ourselves but 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 it in in in the effective criers we end up screening so right 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 laughter 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 them here and there but you can't because you're you'd be violating uh uh you know uh copyright law right so we have to buy like purchase all these films that the participants watch them so so we we actually have these in lab like DVDs you know that we actually purchased um but so so um nice coverage of potential legal Fallout there no no no no we did we did it was that so uh and yeah and and well we can touch on that later but but uh so um we so most of these uh uh volunteers who who come saying they can cry with ease actually don't meet the bill um and so out of the about hundred 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 poor tears there's a name for this in Psychiatry they call it um 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 their mood elevates so they they can quickly Bridge yeah um and and it's not always adaptive as you can imagine so there's lack of narrative distancing right yeah what one you know issue you can bring up with this entire line of studies inab 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% of exactly what we got about right about six so so so we collected um um tiers and and we 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 women's tears men swelling women's tears but not perceiving any odor nothing just sniffing them and you have uh about a 14% drop in free testosterone free okay so this is testosterone that's already been liberated from the testes free test we've done a few hormone aded that's either bound or Unbound is Unbound excuse me um from sex hormon binding 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 know in Pharmacology yeah years ago I spent time studying endocrine effects of this sort um and that's a a tremendously sized 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 o Al who I don't know at all uh replicated the testosterone effect to a te I mean like same numbers so so um it it lowers testosterone and and and we then also looked uh using Mr at the 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 Shenia gron in our lab is replicating this again and this time uh 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 Eva in the uh hexadic experiment I'm going the tap I'm going to think of that as the the satus the the titration the sis titration aggression Paradigm so not on like the mgrm experiments of the of the 1950s which post um this was looking at sort of uh post Holocaust Behavior you know people basically Tor 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 or as we can say I think it was the the great Carl Young that said um we have all things inside of us but um uh the goal is not to experience them all certainly um it's an incredible study and it points again to the 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 out but uh this is just you know sharing stories about the politics of Science and and so whereas the effect on testosterone was was 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 ratings of arousal associated with pictures and there 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 V I'm probably mispronouncing this but I think it's vinger Hotes 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 tier story and the reason they didn't like it is because they've they've built a career uh on this notion um including a book with this title that emotional tears are uniquely human now here I should well I should share so one one of the things we really liked about the 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 the 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 tear uh Mouse pup tiar lower aggression in in U male adult mice towards them in a in a smell dependent way yeah yeah so and and and they also actually found the actual component in tiers that so the tier pheromone that lowers aggression right so so you know this has us thinking of AG as tears is 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 I'd be hard pressed but so so you know our went you know against their their story right because you know here we're saying no you know tears are this chemo singling 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 on K biology that dogs emit emotional tears and and it was uh the dogs emit emotional tears 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 seeing the tears and the dog influences oxytocin in in the humans I hope I'm getting this right I absolutely believe this I mean I from the from the time I brought Costello home at8 weeks old costell is your dog he's my dog unfortunately passed away but having a long time actually the only time I can recall crying I listen I I've certainly cried before uh many times in my life um many many times um the only time I ever recall crying to the point where I wasn't sure that I could keep producing TI years but somehow did is when I had to put him down right is just like you know and if I talk about too long now I'll start crying you know it's one of those things and I think I think it's a healthy emotional state for sure but I recall when he was a puppy thinking this oxytocin thing must be real because I can recall being in faculty meetings which you know fair Fairly stated are not always that interesting but they could be pretty interesting and someone presenting data and my mind thinking I hope Costello is okay what's he doing down in my office this is when he was very little and also not needing to eat not being able to focus on anything else except my attachment to him for about the first two or three weeks that I had him then it was easy then I could focus off on other things and I think I think that dogs perhaps through oxytocin hijack the circuitry that's intended for child rear I really do otherwise why would people be so ridiculously attached to their dogs I me hence all the the post of everyone thinks their dog is the cutest dog the same way everyone thinks their children are the cutest children you know C by the way was a very handome Bulldog so so so yeah so so so again so there 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 group 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 fail to replicate that I see now th this was you know just sharing on how science works and doesn't work in my in in my notion in this case so at the time um after they got this accepted in some Journal um not a field journal in a journal of memory of something um they contacted me for a a response and I I wrote to the authors and I said look you know uh this is very odd to me why don't you come you 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 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 no they don't have money to send over graduate St to do it so I replied saying okay I'll fund the graduate student coming over and I'll fund the entire study and their stay and so on and so forth and let's do this together and they replied no they're not willing to 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 there was that successful replication with the effect on testosterone but there was supposedly this failed 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 the positive result um almost always trumps the the negative result and yet I think replication is key the problem as you pointed out is that replication is rarely pure replication of the exact this this one is not even roly but and I I published the detailed so actually they hid something in their data that did partially R so I I asked for the data and I reanalyzed 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 uh I'm friends with him but that time I was communicating a bit because we were on some board with with uh with uh Daniel conman who's who's Nobel L 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 was an emotionally not fun to be in that position and he said don't don't don't never publish a rebuttal don't do anything and I was you know how can I you know I have to do something he said no don't because once you do that then you know people don't go into the details they won't read the details of your rebuttal 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 magnam way to to do a collaboration that's what he then said that's so 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 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 magnimous 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 1: am Israel time now um and you just arrived later I think um but you're doing 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 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 of cheese wafting up through the cheeseboard is something I will never forget and the breads never forget it um amazing uh red I mean I don't know if you've conveyed that clearly enough to listeners or Watchers the prob really just discovered that we lived in the same we've never met I mean like this before Y and we lived in the same AP are we click friends I had in a lingering way I guess absolutely through the through the the through the uh floorboards it had a great floor that place it had a great wooden floor it was an amazing place I lived there with my girlfriend 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 cheeseboard if you're ever in Berkeley their hours are weird but so you have to look online but that they're it's a unique place with with grap 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 I smell a 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 uh tastes and 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 longterm game but also um something about um uh 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 uh learned to seek but learned to seek through um 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 or a good idea in fact so so whether whether the there's you know order cues on nutrient value is a really good idea more 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 odor um if that's not been done and I will check after our uh uh uh meeting today than 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 US is a huge issue and elsewhere and highly processed foods um you know 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 nut and the nutrient content and I don't mean macronutrient sugar fat excuse me uh carbohydrates fats and proteins but the the vitamins and micronutrients things that support the microbiome whereas foods that are not 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 all Factory perceptual similarity in metabolic products so something that's metabolized ized from something else has perceptual similarity across those those two things so so so metabolic Cascades play into the coding of all Factory space and and that is consistent with the direction you're you're you're implying but again I don't I don't know of a direct test of of uh of nutritional value in smell and and again the fact that I don't know doesn't mean of course that it doesn't exist and in this case I would suspect that it should exist um in scientific press and and if not there then with the companies that have vested interest in this which are many um share just just an an an amusing anecdote to share with you is that we've received two independent um um PE 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 not you had to bring it up this this audience is going to be very polarized along the along the lines of engineered meat um yeah you're not you're not pro you're not promoting oh no no no no I 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 know nothing wor you're you're safe no don't worry no is not is not promoting uh he hasn't even said whether or not he's going to help them out no um we we're not actually not not because yeah it just never it didn't happen yeah no that the the whether or not those um engineered Meats are uh yum yuck or me 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 will avoid now I I will but you know I'll take that the opportunity to to to highlight something related maybe because on 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 all faction right there's this common notion that our sense of smell um is incredibly subjective right and that what you might like in the smell I will not like in 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 crosscultural similarity 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 [Music] so um yeah so so humans are incredibly similar to one another in their all Factory perception and this is in contrast to which 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 send out first of all we're we're attracted by outliers because you know what I'll tell somebody look you know for example Factory pleasantness is highly correlated amongst humans and let's first put this in a num if you'll take a a bunch of humans and a bunch of odorant and have them rate pleasantness the correlation across uh the humans will be about 8 that's incredibly High incredibly High what do you think is Pleasant I think is Pleasant yeah now why why is that go against what culturally people think for two reasons first of all where we're attracted or or biased by outliers but that's particularly that shows in fact the result what do I mean so you'll tell somebody look people are very similar in their pleasantness estimates and they s 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 guava 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 guava half hates it that's true microwave popcorn however I assure you that you know you can come to our lab we have about a thousand odorant in our lab okay we won't smell the Thousand right but I assure you you know take a 100 odorant okay from our mixers and Labs right and we'll we'll smell them right and out of the 100 odors 90 will totally agre on right and including univer 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 about 08 across individuals so on 90 of 100 will really be in high agreement then five ordance will be in sort of intermediate agreement and yes there'll be the five ordance that we're in total disagreement on but I ask you you know if we agree on 95 and disagree on five are we the 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 is our poor application of language to all faction right so so in other sensory systems we grow up with we we 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 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 in odor we don't have those anchors right we we don't from childhood you know our mom doesn't tell us oh 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 do 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 1 to 2 1: 3 1 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 odorant 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 odors right it doesn't matter if I'll call this lemon and this Orange and you call this sweet potato and this marshmallow right it doesn't matter if I think that these two are highly similar and you agree and I think that these two are very different and you agree right we perceive the world in the same way if our similarity matrices are aligned right and what's nice about that is that then you can do that for vision audition and all 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 fact and tonal audition okay and we are most dissimilar in color vision okay we're in color vision the variance is about 100% amazing that's quite different 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 odor and and that will change you and learn to dislike an 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 um there will soon be Google smell not to call out Google is the only search engine but duck ducko smell for those of you that don't want your smell DP chat GPT and on and on in other words you know Vision visual information is sent through uh computer interfaces as his auditory information not so much haptic samata sensory 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 into yum yuck or me type decisionmaking 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 uh 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 H 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 Rose 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 I don't know tons of money 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 dovet tales 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 or all the world lots of people are are um very cognizant of the importance of smell and smell is like way up there in people's awareness because of covid and this is driving a Renaissance of of all faction research and and 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 odor 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 a smell something and tell you what it molecular structure could or should be um you know so in contrast let's say the trivial like color vision let's say so you know if 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 of 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 experienced as color the rules are well known in all faction we didn't have that um until recently um but over the past few years a bunch of labs have really um uh push this forward uh there's a bunch of work uh out of Leslie Vos Hall's Lab at Rockefeller and Andreas Keller working with Leslie um uh who who've done a lot of work on this front um also work from Joel mainlands La lab uh at monell um and fair Discovery Joel was a a graduate student in our lab um and and recently in our lab we've had and 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 as far from arogant and and and this is a paper uh led by Aon ravia uh uh from our lab and Kobe snit also a major contributor there a paper published in nature uh about a year and a half ago in the height of a covid pandemic so nobody really or I won't say nobody but it it wasn't noticed in the way otherwise would have been it was it was publish 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 uh mixtures with no in similarities and the the the result was highlighted and you'll appreciate this coming from Vision um is that using our algorithmic solution we generated all Factory metamer 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 and anybody can recreate them this is simple actually um and and in the paper we do a few things like we generate a metamer for a chenel number five so you don't like perfumes so this one but but we 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 an engine that you can generate these these metamer now once we did that in a way we've generated the the the infrastructure for digitizing smell because what again what we what our what our algorithm predicts our our framework predicts 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 they're are perceived smell now you can make up any mixture you want for me I can project it into that map and measure its pairwise distance from all the points in the map if it falls on Lemon then what you generated smells like lemon and if it falls you know on tomato then what you generated smells like tomato so we we now solve that problem we can predict the odor of any molecular mixture we can say how it's going to smell what we can do is then find a set of components which we call odor primaries that can be used to mix any odor that you can perceive and that's what we're working on now um and about a month ago um so this is in collaboration with a lab of Jonathan Williams at Max plank in Munich um Jonathan Williams is an uh atmospheric chemist uh but he's really good at at using gcms these tools that measure molecules so uh Jonathan Williams measured odorant 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 Rose we in fact recreated something that had a PRP but most people perceived it as bubble gum uh the second one we tried to do was an and we failed at recreating anise um and most people said it was Cherry which is not very far but it failed um 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 people and violets so the first odor 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 a $1.5 million device bigger than this table uh that's right I remember when VCRs half the audience won't even know what that is VCRs were like this big so we're we're all good I'm all good with the uh with the prediction that things will come down in size and cost yeah I was just saying 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 more I know you seem pretty dogged in there yeah but they have so much more resources that uh that um at this Stage IT and and they they've already published uh two papers from that effort that are good uh yeah you know if 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 postt talk 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 outrun and outgun large groups and and here I don't have anything against Google by the way 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 you go 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 cuz gnome being he's humble and he's dogged so um better better get cracking there we just costed 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 IR uh Irving zooker lab that worked 100 hours a week so I was like oh I'll work 102 hours a week which was not a good choice folks in any case it's it's uh it's abundantly clear that you're making progress here and and I and I go to some of the earlier discussions we had and I think we're not just talking about transferring recipes and smells of of of food uh gasoline from the 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 or Zoom um than to just hear their voice we're 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 old factory equivalent of Circa 1956 black and white TV okay basically right I me you know I'm not dreaming let's say of being able to transmit to you the difference between a Cabernet or armor low right but if I can generate something that's vely wine that will be an amazing success from my perspective right but Jump Ahead in your imag ination to to 4K odor transmission then 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 all faction 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 all faction digitization is brought to the equivalent of 4K uh uh 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 news in your bathroom uh each one of us will have in the toilet and it will be doing Diagnostics all the time and and uh 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 Nome I I want to say thank you for your time today first of all uh this was a tremendously interesting conversation I we touched on so many things hormone smells the architecture of the old factory 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 and um as a 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 callaction and 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 in science but I'm gonna um I'm GNA 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 of people foraging uh following scent trails and then when I was a until I was a junior Professor I used that in my teaching slides um 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 you 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 and the spirit that you bring to it whatever drives that Spirit as the great late Ben Baris used to say keep going because we are all benefiting tremendously and 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 mention 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 the many many people listening to this I just want to extend a huge debt of gratitude thank you so much uh so I'm I'm the I'm blushing I don't know if this does come across on the on the radio Podcast but thank you so much for very warm words I mean you know we as you know 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 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 uh the next results sometime not too long from now yeah well I'm I'm GNA 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 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 gome soel if you'd like to learn more about the work in the soel laboratory or read some of the papers described during today's episode as well as learn about the current and future projects in the soo 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 zeroc cost way to support us in addition please subscribe to the podcast on both Spotify and apple and on both 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interest in science [Music]