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

welcome to the huberman Lab podcast

where we discuss science and

science-based tools for everyday life

I'm Andrew huberman and I'm a professor

of neurobiology and Ophthalmology at

Stanford School of Medicine

today my guest is Dr Noam Sobel Dr Noam

Sobel is a professor of neurobiology in

the department of brain Sciences at the

Wiseman Institute of science his

laboratory studies olfaction and

chemosensation olfaction is of course

our sense of smell chemo sensation is

our ability to respond to chemicals in

our environment today we're going to

learn some absolutely incredible facts

about how you interact with the world

and other people around you for instance

you will learn that humans can smell

things around them as well as dogs can

in fact humans are incredibly good at

sensing the chemical world around them

you also learn for instance that every

time you meet somebody you are taking

chemicals from that person either from

the chemical Cloud that surrounds them

or directly from the surface of their

body and you are actually applying it to

your own body and you are processing

information about that person's

chemicals to determine many things about

them including how stressed they are

their hormone levels things that operate

at a subconscious love level on your

brain and nervous system and the impact

your emotions your decision making and

who you choose to relate to or not to

relate to you will also learn that tears

yes the tears of others are impacting

your hormone levels in powerful ways

you will also learn that every so often

actually on a regular schedule there is

an alternation of ease through which you

can breathe through one nostril or the

other and that alternation reflects an

underlying Dynamic of your nervous

system and has a lot to do with how

alert or sleepy you happen to be

the list of things that Dr Nome sobel's

laboratory has discovered that relate to

everyday life and that are going to make

you say wow I can't believe that happens

but then go out into the real world and

actually observe that that happens in

ways that are incredibly interesting

just goes on and on in fact his

laboratory discovered that we are always

sensing our own odors that's right even

though you might not notice your own

smell you are always sensing your own

odor cloud and throughout the day you

periodically smell yourself deliberately

even though you might not realize it in

order to change your cognition and

behavior I first learned of Dr sobel's

laboratory through a rather odd

observance that observance took place

when I was a graduate student many years

ago at UC Berkeley at the time Nom Sobo

was a professor at UC Berkeley as I

mentioned before he has since moved to

the Weissman well I was walking through

the Berkeley campus and I saw people on

their hands and knees but with their

head very close to the ground and their

eyes were covered their hands were

covered their mouths were covered and

only their nose was exposed and what I

was observing was an experiment being

conducted by the Sobel laboratory in

which humans were following a scent

trail that Central was actually buried

some depth underneath the Earth and yet

they could follow that Central with a

high degree of fidelity it was from that

experiment and other experiments done in

Dr sobel's laboratory at Berkeley and at

the Wiseman involving neuroimaging and a

number of other tools and techniques

that revealed the incredible power of

human old faction and humans ability to

follow scent Trails if they need to and

that of course led to many other

important discoveries some of which I

alluded to a few moments ago but you are

going to learn about many many other

important discoveries in the realm of

olfaction in chemosensation that have

been carried out by Dr Silver's

laboratory through the course of today's

episode and by the end of today's

episode I assure you that you will never

look at or smell the world around you

the same way again before we begin I'd

like to emphasize that this podcast is

separate from my teaching and research

roles at Stanford it is however part of

my desire and effort to bring zero cost

to Consumer information about science

and science related tools to the general

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off and two free pillows and now for my

discussion with Dr Noam Sobel Dr Sobel

gnome welcome thank you must say I am

extremely excited for this come

conversation I've been a huge fan of

your work for more than a decade or two

uh yes kind of frightening yeah but yeah

we overlapped at UC Berkeley some time

ago although we did not meet and we

lived in the same apartment and we just

learned that the amazing apartment

that you moved out of was the apartment

that my girlfriend and I at the time

moved into in 2006 I believe so uh

we've shared quite a few things

um and today I would love for you to

share with us

um All About The Amazing landscape of

chemo sensation in particular olfaction

or sense of smell and some related

perceptual abilities or subconscious

abilities including pheromones Etc

to get everybody on the same page I'd

like to just start off by asking

what are the major components of our

ability to smell

obviously or I like to think it involves

the nose at some level it does to what

extent is that mixed in with other

senses like taste and

perhaps more importantly

what about the chemicals that we are

sensing through this thing and for those

of you listening um and not watching I'm

tapping my nose that we are not aware of

you know that the chemicals that are

that we're inhaling and

um making sense of without our awareness

if you could just um give us the top

Contour or even deep Contour if you like

of the uh the parts list and the various

roles they play so you you've asked a

lot of questions at once

um you know I'll start with a little

comment on the way you you said smelling

through our nose which we indeed do but

we also smell through our mouth actually

there's a process referred to as

retronasal olfaction where

um odorants come up through our the back

of our throat and

out of our nose the reverse way and we

smell things that way as well and in

fact a big part of the contribution of

olfaction to food and taste comes from

that from retro nasal off action but uh

uh primary olfaction is referred to as

orthonasal faction that is through our

news we Sniff and sniffing is a big

thing well I have a sense we might talk

about that a lot today in all sorts of

contexts so we sniff in through our nose

and to answer your general question of

the organization of the system

um so molecules Airborne molecules

travel up our nose a distance in the

human of about six or seven centimeters

to about here where they interact with I

will use the word sheet of receptors but

she is a bit misleading here it's not a

sheet it's very convoluted

we have about seven million such

receptors uh lining a structure known as

the olfactory epithelium this is the

sensory surface of the olfactory system

the olfactory epithelium again about

probably about six or seven million

receptors in the human in the human

probably of about

350 different kinds so that's amazing

that means a meaningful percentage of

your genome is devoted just to this just

to the kinds of olfactory receptor

subtypes you have in your nose by the

way I can share an amusing story I would

imagine amusing stories are good for

podcasts

so that number of six or seven million

receptors

is probably not very well grounded it's

hard to count but it's reasonably

grounded and there was this thing

roaming around in the literature about

Bloodhounds having billion receptors in

their nose which is why they're so

amazing and this number was you know it

sort of propagated through the

literature and and our lab has written

over the years a few review chapters and

and we were repeatedly writing the

olfaction chapter for a very large one

of these large textbooks the gazanaga

handbook of cognitive Neuroscience I

think it's called

um

and and we had that in there as well

somewhere and and one time when we're

renewing the chapter for a new version

of the book I told the graduate student

who was leading that at the time she's

now a professor at Tel Aviv University I

told her check that check that reference

out where in the world did that come

from and we started going back and back

and back and it turns out it comes from

a textbook

an Australian textbook

and we found the author of The Textbook

and and we wrote her and I said look

there's this thing in in the literature

of a billion receptors in in the

Bloodhound where did that come from

and and surprisingly she answered me and

you know I was hoping to get a reference

right but it was a reference and and

this is where it really becomes funny

for us because she said I I was once um

at a lecture of uh an all-faction

geneticists geneticist by the name of

Duron Lancet and he said that in the

lecture now this is really funny because

she's in Australia this is all over the

world this number and I'm writing her

from Israel and Doran lancid is in the

building next to me okay he's in

Weitzman Institute genetics I mean he

used to be he's retired now uh and and

he he had meaningful contributions in

the history of wolf action

um so I picked up the internal phone and

and I said hey Duron you know did you

say that there's a billion receptors in

the Bloodhound knows and he said what's

a bloodhound

so this is totally made up right it

totally made up and it propagated I mean

you can you can probably go into Google

and type like a billion receptors in the

blood town and you'll get a lot of hits

but there was absolutely no evidence for

that amazing and not just amazing in

light of what it it tells us about

olfaction and Bloodhounds or otherwise

but amazing because it sheds light on

just how much of what is in textbooks

scientific and medical is absolutely

wrong things things propagate and and

you know you set yourself in right so we

fixed that in that version of right and

and so to finish the line so that so

odorants interact with these receptors

um here in our epithelium where they

undergo what is referred to as

transduction that is the odorance our

Dock of the receptor and turn into a

neural signal or

enforce the receptor to respond in a

neural signal and this neural signal in

fact action potential is not gradient

potentials of any kind uh propagates uh

via the olfactory nerve now this is a

nerve that goes from our epithelium

right here behind the forehead no it's

well yeah yeah here uh through uh the

thinnest part of our skull an area

referred to as the cribriform plate

which is perforated it has a lot of

holes the nerve goes through those holes

and synapses at the first Target in the

brain uh which is the olfactory bulb

and humans

that forms an interesting

uh point of sensitivity

um because a lot of people lose their

sense of smell due to trauma uh because

of that structure yeah a head hit type

trauma well yes although uh you denoted

hitting on the front of the head which

is where all this real estate is but

actually uh the more common cause for

losing your sense of smell for trauma is

the back of the head because of what's

referred to as a contra coup injury so

as your listener is probably no our

brain is floating in liquid in CSF and

cerebrospinal fluid inside our skull and

when we get hit in the back of the head

the brain has this forward and backward

movement in the liquid in in the skull

it sort of crashes it can crash against

the front of the skull which is why you

also have in a contract Winery you also

often have frontal damage but what

happens is that this generates a

shearing motion on the crib form plate

and the olfactory nerve is severed and

if it's completely severed it's it's

lost forever because my understanding is

that the olfactory Sensory neurons can

are among the few central nervous system

neurons in adult humans that can

regenerate so or replenish themselves

right so so I'll I'll again there are a

few questions yeah that's okay so first

of all we will spin many plates

simultaneously if it's completely

severed completely then yes you're lost

forever yeah if it's completely savored

because even if you'll have regeneration

at the basal cell level at epithelium

they won't manage to find their way back

uh to the bulb if if you have partial or

something left or something shows up in

a short while after the injury then you

have a good chance of recovery because

they grow along the trajectory of the

other axons or pioneering the way for

them assumingly yeah interesting and so

so basically and and basically the time

frame and you know it's funny I get a

lot of emails on this although I'm not a

medical doctor but but I get a lot of

emails from people who have lost their

sense of smell because it's very

distressing and now more people know

this because of kovid that it's very

distressing

and and basically the rule of thumb is

that if you don't get it back within a

year to a year and a half you'll never

uh get it back my understanding of the

statistics on olfactory loss in covid

and and other viral type infections is

that

um first of all I had I experienced that

when I got covered including total and

awesome for one day and not total it was

just there was a remnant of an ability

to to smell or set or perceive the smell

of a lemon and I was huffing as hard as

I possibly could I actually uh there's

an over-the-counter remedy and this is

not uh pseudoscience because there's a

number of papers published about this on

PubMed the alpha lipoic acid can

accelerate the recovery of of smell yeah

and and so that's something that it

worked successfully for me I'm not

saying that that's the only or I don't

know if it works successfully for you or

if you would have recovered anyway I

mean you didn't do a control that I was

not willing to do the control experiment

uh exactly yeah let me say two things on

this front first the date on the alpha

lipoic acid is

[Music]

one word about the smelling the lemon

and this is uh I'll take that

opportunity to to share more information

when we smell things

it's the result of more sensory

subsystems than the olfactory system

alone

so you have several chemosensory

sensitive nerves in your nose

a primary one beyond the olfactory nerve

is the trigeminal nerve the fifth

cranial nerve so the trigeminal nerve

has sensory endings in your nose and

your throat and in your eye it has three

branches that's why an onion has smell

and burns your eyes and burns in your

throat itself trigeminal yeah the

tearing of cutting an onion is a

trigeminal reflex amazing we talked

about trigeminal in the context of

headache during a headache episode it's

a trigeminal reflex so the lemon you are

smelling may have been a trigeminal

sensation so smelling the lemon with my

eyes is what you're saying well no with

your nose but with your trigeminal

receptors and not your olfactory

receptors

um so in within you know all faction

researcher jargon uh there's what we

refer to as pure olfactants these are

orders that will stimulate your

olfactory nerve alone they won't

influence your trigeminal nerve at all

and an example just to get a sense of

what that might be would be uh the

coffee right here is a purolfactant of

vanilla is a known plural factant these

things have no trigeminal activation

um but as long as we're on this topic

and we'll weave back and forth but I'm

glad we are on this topic because a

tremendous number of people wrote to me

during the pandemic and continue to

about olfactory uh loss

um

is the I I've heard of this olfactory

training where whereby if you have a

partial or even a complete loss of of

primary olfaction right that um one is

encouraged to smell a number of

different smells I I grew up studying

activity dependent wiring of the nervous

system it makes total sense to me why

keeping neurons active keeps them alive

so this is not fired together wired

together type thing by the way that's a

quote from Carla Schatz not Donald head

folks or me

um but this is about keeping neurons

electrically active in this case

olfactory neurons in order to maintain

their connections because otherwise they

will die

of action is a definite use it or lose

it system and so that makes total sense

and indeed there's very strong evidence

for success of of the training programs

more than the alpha lipoic acid right

and and so that's a real thing and and

what's cool about that is that you don't

need to go out and buy expensive things

although you can of course there are

people who are capitalizing on this

commercially already but you can just

take things from your refrigerator or

your or your you know makeup cabinet or

whatever and smell them

you know attentionally and constantly

and sniff them and and that exposure

will help you recover uh there's good

data on that by now you made that uh

point in passing about regeneration in

the olfactory system and neither one of

one of the cool things so in all faction

you can you can study many things

through all faction indeed one of them

is is an is neuro regeneration uh

because the olfactory neurons are really

the only neurons that do that

systematically in the adult mammalian

brain and whether the human olfactory

system shows the same level of

regeneration as it does in in uh in

other mammals is and was somewhat

questionable and I'm just bringing that

up to share a really cool study that was

published in neuron I think somewhere

around 2014

um where to address this question I just

really like the idea of doing that what

they what the authors did

um

was look at in in postmortem they looked

at levels of c14 in in

adults were exposed to Atomic Bomb

experiments right so you have you can

actually look at these at these neurons

and and time them based on exposure to

radiation

um and that paper suggested that that

there's not as much turnover in the

human olfactory bulb as there is in

other mammals

uh

other lines of data suggest otherwise so

this is kind of a debated question as to

what extent degeneration you have in in

the human olfactory system as opposed to

other uh mammals but but that was just a

really cool paper I think of of doing

that fascinating no I I

should I finish the the path just so we

have to so so we said so so information

then synapses at the olfactory bulb from

from uh uh the olfactory epithelium

and

the pattern of that synapsing follows

what's referred to as the most extreme

case of convergence in the mammalian

nervous system more specifically what

happens is that all the receptors of a

given subtype and remember in humans we

said we have about 350 in the mouse we

have about a thousand two hundred

probably

so all the receptors of one subtype

converge to one location in the bulb and

this location is referred to as a

glomerulus or an employee and and that

may be a slight oversimplification it's

in fact two glomeruli there is a mirror

sort of a mirror cut line and so all the

receptors of one subtype will converge

to two mirror glomeruli on the olfactory

bulb so you end up having uh two

glomeruli that reflect that one receptor

subtype

and so if and this is as far as I'm

giving you now the textbook view of of

how the system works but then I can I'll

happily share with you things that

pose a problem for the textbook view of

how things work but the textbook view of

how things work is that every such

receptor subtype is responsive to a

small subset of different molecular

shapes what sometimes referred to as

autotopes the molecular aspects of

deodorant so each receptor is is

responsive to a different subset of

odotopes let's say 10 and each ototope

will activate a different subset of

receptors so potentially you have this

insane common and torics of this

potentially 350 dimensional space in the

human potentially

but then because of this convergence you

end up having on the bulb in a way a map

reflecting or receptor identity so so

let's say this coffee activates

receptors of type 1 3 and 7 so the

glomeruli of receptors one three and

seven will light up quote unquote when I

smell the coffee and if you could take a

snapshot of that theoretically you would

have the map of of coffee and and so on

and so forth this this is sort of the

textbook view of how the system works

and and then information goes from the

bulb

to several Targets in the brain I mean

what is referred to as primary olfactory

cortex is piriform cortex and then the

Rhino cortex this is on the ventral

surface of the brain the lower portion

of our temporal lobe

um and information goes there directly

but it also goes directly to the

amygdala it probably goes directly to

the hypothalamus it may go directly to

the cerebellum uh it goes all over the

brain so so information projects widely

from there and as far as people

understand

the map that may exist on the bulb

doesn't exist in the rest of the brain

and the understanding of of how coding

occurs in the rest of the brain is is

murky commonly one here is that the

memories that we have of odors are

somehow more robust

um than the memories of other perceptual

events in our life I I don't know if

this is true or not but um people will

say for instance I can still remember

the smell of my grandmother's hands or

the smell of cookies in her kitchen

at a minimum it points to the fact that

smell and memory are closely linked and

you just mentioned a direct

um you know multi-station but

nonetheless somewhat Direct

path from the nostrils to the

hippocampus one of the primary encoding

centers away yeah which is which is a

remarkably short pathway considering

that for instance uh just by example

because some of our listeners won't be

familiar with this but some will that

sound waves that uh you know are

transduced into neural signals at the

level of the inner ear go through many

stations before they arrive at the

location in the brain where we make

sense of those sound waves as voices or

music Etc whereas olfaction is more of a

direct route

um to the to the memory centers

um is there any uh gesso story or real

uh objective truth to the idea that

olfactory memories are formed more

easily or maintained longer or more

robustly than other sorts of memories so

so yes but first I I should I should say

that I'm not

an authority in all Factory memory it's

sort of it all have to remember is a

huge field of research and somehow our

lab has never really

um

gone much into that although again the

same student I happened to talk about

before I Sharon who's again now A

Faculty at Tel Aviv uh

um ran a study a paper we I think we

published in current biology biology

called the privilege representation of

early olfacturers associations basically

there's something about the first time

you experience a smell

that generates a particularly robust

representation

more than other sensory stimuli and and

that's what chain fact compared so

there's something about the first

exposure to a smell

um in terms of the brain encoding that

that etches it into our uh being

and and this is an effect that has you

know it has Echoes of course in

literature I mean you know the the

biggest cliche in this is to bring up

the priest effect right so the priest

effect is when he ate the Madeleine and

it immediately the taste and smell

immediately reminded him uh of of an

event in his childhood where where uh

where the same Madeleine uh appeared uh

um but but so that's something very real

there there's a lot of research on it uh

not coming from our work so I'm not an

authority but it does sound like there's

something special about olfaction

um and that doesn't mean that there

isn't something special about Vision or

audition each one has its own uh unique

uh I'm the last argue that there's

something special about actions my

students make fun of me because

they saying there's some truth to that

that I try to explain everything through

the olfactory system I mean for me

everything is olfactory so so yes

through the lens of the nose I'd like to

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to get the five free travel packs and

the year supply of vitamin D3 K2 when I

was at Berkeley

I was walking across campus one day and

I saw

I think students but I saw people on

their hands and knees with goggles on

gloves on and

um I think their mouths were covered too

everything was covered was covered and

they were walking well they were

crawling along the ground

um and I thought this was peculiar but

then again it's UC Berkeley and the joke

is if it to get noticed on the UC

Berkeley campus you have to be naked and

on fire right one or the other would not

be sufficient please don't run this

experience that kind of place

um yeah but nonetheless a paper came out

a few years later

describing the results of what turned

out to be your experiment that your

laboratory was running which was having

people follow an odor trail with their

nose and

um and my understanding is that people

can improve their ability to track sense

quite robustly especially if

we deprive them of vision and somatic

Sensation that is touched in some other

um Sensations maybe you could just tell

us a little bit about that study and um

and for I think in our audience I'm

suspecting that many people have a Keen

Keen sense of smell very I have a family

member who just like detect any negative

you know putrid odor in the environment

but also good odors

um exquisitely well and I I have other

family members who sense of smell is

quite poor

um

I'd love for

all of those people to learn a bit about

what is possible in terms of training up

or improving our ability to smell and

perhaps in the context of that study if

you will yeah so so first before even

talking about improving just

off the bat humans have a remarkable

sense of smell and this is something

again in our lab we already said we know

yeah we know this this is old news but

but to people who who come from

different worlds we have to reiterate

this sometimes when I give you know

public lectures to to non-all-faction

audiences I reiterate this

humans have an utterly remarkable sense

of smell to put that a bit into sort of

you know things that you could that are

tangible so so for example

um mercaptans which are added to cooking

gas so that we smell it because

otherwise it wouldn't have a smell so

that the smell of gas is not the smell

of gas of propane it's an additive

yeah it's more Captain the sulfur like

smell so so uh our detection threshold

that is the level at which we can detect

it is 0.2 parts per billion

okay there's no machine that can really

do that that effectively no gas

chromatograph nothing now to give you

another sense of of making this again

really tangible we're working with an

odorant in our lab called estro tetra

enol

that our participants can detect when we

have it mixed at 10 to the negative 12

molar in the liquid phase to give you a

real sense of that we did the math if

you would take two olympic size swimming

pools and you would pipe it 1ml one drop

into one pool versus the other you could

smell the difference between the pools

incredible that's the detection

threshold that you have with your nose

people have an utterly amazing nose Okay

so so that's just in terms of its

detection abilities which are are just

you know remarkable really up there in

the mammalian World we're not

a bad mammal at all faction

um

and and

beyond that we can we can improve okay

and and the example you're talking about

actually started off

uh is a lab bet okay we were having a

lab picnic so I guess I should hear fill

in because I I'm your guest from The

Weisman Institute of Science in Israel

but before going back to my home in

Israel I was a uh um faculty at UC

Berkeley and the Helen Wells

Neuroscience Institute and this study

was done during that time and we were on

a lab picnic and we were having indeed

one of these sort of lab discussions

arguments on what humans can and can't

do with their sense of smell and and I

said that humans could truly even track

odor like a dog and people there said no

way and we ran this quick experiment uh

which I have video of but I don't think

we'll show it here uh but I actually

have original the picnic video we have

it

and uh a graduate student by the name of

Christina zellano a brilliant graduate

student at that time who's now she's now

a professor at Northwestern

and she's really leading the field of

all faction Imaging today but she was

the volunteer and we dragged a chocolate

bar across the grass and blindfolded her

and

checked if she could track the track we

made with the chocolate which he did

very effectively right and as far as

Placer at the starting point of the line

or I think we did I don't exactly

remember what we did on that sort of

picnic uh tryout but you know I assume

she never practiced that in her life

before right and yet you know she she

did it really really well and

and then this went on as a lot better in

a way that that I I said to my my

students okay we we have to make this

into an experiment put in an

experimental setting and and and

quantify what's going on

uh

and they all said that it would be

uninteresting that was the BET and and I

told them it would be in nature which is

a bit I won in this case nature of

course being one of the the three Apex

journals so it was it was Nature

Neuroscience to prepare but but uh so so

then we we turned it into an experiment

and and what the experiment was is that

we brought in participants naive

participants not not graduate students

from our lab uh completely deprived them

of any other sensory input so we blocked

their eyes we block their ears we

blocked everything we blocked they were

wearing heavy gloves uh you know they

they couldn't sense anything

and we generated a a consistent order

path in the grass which is what you saw

we did that by burying twine under the

grass and odor impregnated twine so that

way we could generate a consistent uh

odor Trail every time was it and at the

base of the grass or in the dirt it was

buried it was buried under the grass

really yeah

yeah wow and I did not know that it was

buried under the grass

and we conducted aerial photography and

um participants also had this sensor

pack that they were wearing where we

measured nasal airflow in each nostril

in real time

and uh they all we also used something

called rtk GPS which is a way to lay uh

radio frequency grid over the GPS grid

so that you have millimeter resolution

in space basically it's used by

surveyors mostly

um so that we could track Behavior and

we found a few things doing this one is

that people could just do this right off

the bat

um the second thing we found that is

when we train them up

then within uh average of four days uh

the rate limiting factor became the

speed at which they could crawl

so as fast as you could crawl you could

send track of course you can't crawl as

fast as the dog can run but you as fast

as you can crawl you can send track

and then to sort of add what made it

really interesting from from a systems

neuroscience perspective

is

that we asked where they're having two

nostrils uh contributes to this

so we built we constructed a nasal

prosthesis if you will

uh that had two versions one is that it

combined both nostrils into one big

nostril

centered and the other is that it

maintained two separated uh nostrils and

we compared performance under these two

conditions and people perform better uh

with two nostrils over one centralized

nostril although the flu remain the same

so you're taking advantage of the

information uh that comes from your two

separate totally separate nostrils by

the way the system I described before of

your epithelium and bulb and and

connection to Cortex

um you have two of those right it's

completely unilateral well almost

completely unilateral system there's

some

very small exceptions to that but but so

a representation on both sides of the

brain much in the same way we have two

eyes we're not a cyclops we can gain

depth perception information we can

perceive motion better as a consequence

and a number of depth especially

stereopsis and we can locate sound

because of the difference between our

ears and how head blocks them between

and amazing another question about the

the mechanics and strategies that you

observed because I think there's

information about the system the brain

as a consequence

um were you in a position to measure

sniffing frequency and the specific

question I have is were people doing

something along the lines of a

quick sniffing or a like a you know a

long um withdrawal in so inhale you know

we didn't so yes we were measuring

sniffing and recording it and and we

have all the data

um

there was nothing

um very remarkable in that data in that

study although it may reflect that we

didn't analyze it carefully enough as

well I mean it didn't it was it it

wasn't a major component of our analysis

although we did look at it uh to some

extent again you're asking me about a

paper from quite a few years ago so I

may be forgetting parts of it as well

um but I'm sure if it was a major

component of it it would have risen it

definitely wasn't a major finding of the

sniffing behavior

um in the paper although again we you

know sniffing behavior is a huge portion

of our our life in lab uh

and and it's it's taking us to to places

and and it's re-emerging now in our work

we're doing tons of sniffing work

um you know I can share with you

something

that that I think will interest your

your uh listeners and viewers as well

and and and

we think is is really uh one of the most

overlooked things

in in neuroscience

I invite you to do the following

experiment so occlude one nostal by

pressing on it from the side and sniff

in and then include the other and sniff

in do you sense a difference in flow yes

okay do you know why that is no and it

was the next question on my list so

don't feel badly about not knowing why

that is

um most people don't

uh but that is a reflection of something

referred to as the nasal cycle

so in fact if you were to do that

repeatedly you would find that your high

flow nostril and low flow nostril

alternate every two and a half hours on

average in an absolute way or is it kind

of like a sine wave like gradual shift

to the one and then gradual shift back

it can vary it can vary and we don't yet

know the rules uh all the rules but but

you have this constant shift from side

to side the shift becomes incredibly

pronounced in sleep so we can measure

the power of the difference and in sleep

you have this phase shift of power you

have a huge like one closes and one

opens totally

and

it turns out that this is linked to uh

balance in the autonomic nervous system

so as you and your listeners know we

have an autonomics nervous system that

has a sympathetic and parasympathetic

component to it and and they're in

balance or imbalance in many diseases

for example and this interplay between

the uh Auto between the the sympathetic

and parasympathetic nervous system

drives the switch

from left to right nostril just to

remind people um sympathetic nervous

system has nothing to do with sympathy

um has everything to do with generating

patterns of alertness it's sometimes

called the fight or flight system but

any pattern of arousal positive or

negative and then it's balanced in a

coordinated way or at least in parallel

with the parasympathetic nervous system

which is sometimes called the rest and

digest system but as a associated with

all sorts of things the sexual arousal

response and a number of other aspects

of our physiology so think of it like a

seesaw of alertness and calm yeah

perfect so now imagine right imagine

imagine you would walk around living

your life right half of the time with

one eye closed like this and the other

half with one eye closed like this and

you have this eye cycle all right and

that was linked to autonomic arousal I

assure you you would go to PubMed there

would be five million papers on the eye

cycle right and the eye cycle in every

disease you can name and what it denotes

and what it tells us and what we can do

with it

you have exactly this marker you're

walking around with a marker on balance

in your autonomic nervous system and we

do nothing with it so we're in fact now

doing a lot with it okay so we built we

built a wearable device

that is pasted to your body and measures

airflow in each and nostrils separately

and logs it for 24 hours

and we're collecting these 24-hour

recordings we're calling it the nasal

halter

so we measure with the nasal halter

and and we're finding it as a disease

marker

um I can I can give you a nasal halter

measurement as an adult and I can say

this is work by team nasaroka graduates

in our lab now I can so we can tell the

difference between ADHD and non-adhd

adults

and we can tell just from the recording

we can tell if the adults are in ritalin

or not

so I can I can measure your nasal

airflow and say if you are or are not

with ADHD and if you are or not on

Ritalin incredible I have a couple of

questions about this

is it the case that airflow through one

nostril is reflective of a sympathetic

nervous system dominance versus

parasympathetic

um or is it simply the case that this

alternating Left Right nostril

periodicity

um which you said I think is on the

order of about every two hours two and a

half two and a half it switches to uh

maximal on one side versus the other

is that simply reflective of an overall

balancing let's maybe is it the hinge in

the Seesaw or is it the tilt of the

Seesaw so I don't have a good answer I

don't have a good answer I mean you know

I could give you sort of a you know I

could say that to some extent uh uh

right nostril more open

um is more sympathetic and the left

nostril more open is more

parasympathetic but that that wouldn't

be very correct I mean you know I'm sure

that it's you know the yogis are going

to be all over this so right because I

get this my lab does do some stuff on on

breathing and the the yogis are always

saying okay you know because there's

this thing I don't do yoga anymore but

not for anybody but um where they'll

have you breathe through one nostril or

the other and I've I've probably even

asked this question on social media

I'm gonna become Public Enemy Number One

of the yogis right now so listen we so

we we they'll come at you with um yoga

mats which are not very dangerous we

really so since we're so interested in

this mechanism one of the things we'd

really like to know how to do is is to

gain control of it somehow and there's

this world out there of yoga who claims

to have control over this

so we said okay let's bring like really

serious yoga practitioners and see if

they can shift their nasal cycle from

left to right but by Will alone right

not by manipulating themselves somehow

and and if yes you know we'll learn from

them how they do this and then we might

you know use this to to cure ADHD or or

whatnot right so

so we posted like on all the lists of

like the yoga teachers and had this

parade of yoga teachers walking into our

lab this was one of the strangers a lot

of Sandalwood odors and bare feet

white white uh clothing and and so on

and and so we we study I actually know

we studied 14 yoga teachers

all 14 uh by you know by the conditions

of enlistment for this uh came in saying

that they they can control shifting from

left to right uh nostril without

plugging a nostril yeah by the power of

thought come on

um and you know how many of 14 succeeded

zero including including one you know

the most extreme one was we had this guy

who who you know and we're recording and

we know how to record this really well

right and and he's sitting there saying

yeah I'm switching now and I'm it's

switching and you know you're looking at

the Monitor and no it's not switching

and and so no no yoga teacher that we

found uh could uh willfully switch uh

between left and right nostril flow and

yet they're they are convinced that they

are and I have to imagine they're not

trying to you know there's no incentive

for them to lie right yeah no I I it

even the opposite I mean you know this

puts them in an awkward position once

yeah I don't know what the deal is but

but none of them can do it

um given that the alternating flow

through one or the other nostrils

reflective of the autonomic nervous

system has this two and a half hour

periodicity

if I suddenly enter a bout of stress for

instance does it switch because that's

reflective of the autonomous nervous

system and the reason I'm asking this

question is not because I think that's

necessarily important as it relates to

stress but I'm trying to understand the

direction of causality in other words is

the unilateral smelling through or

unilateral nostril smelling periodicity

they've been we named it something I

could think of the wrong thing I'm sure

is that driving the shift in the

autonomic nervous system or is it merely

reflective of the shift so you've you've

very concisely now worded aim two of a

grant that was probably just rejected

but but basically we're trying to answer

exactly uh that question and we're

currently running experiments on that

line so so we have one experiment where

uh uh we're looking

um so we're exposing participants to

pain uh we're using a cold water hand

exposure it's a really cool Paradigm

because it it there's huge individual

differences we just started this we

built the setup just now

and you have a lot of meat to work with

there because there's a lot of

individual differences here it's capped

in three minutes so be for safety

reasons because you have you have

participants putting their hand in in

two degrees Celsius water

but there'll be participants who will

pull it out at like 10 seconds 9 seconds

and then you'll have you'll have three

minutes as well so there's lots of lots

of uh and and already in so now I'm

sharing pilot data with you so you know

to to this might you know when it when

this ends up being published it might be

the opposite but so far it seems that

that uh the exposure to Coal generates a

shift in the nasal and nasal balance so

autonomic arousal can drive the shift

potentially

um earlier you were describing the

architecture of these um smelling

systems and you mentioned these

glomeruli where the olfactory receptors

converge right in the bulb and then

later you mentioned that the system is

unilateral but with a mirror

representation on both sides of the

brain so for those who don't think in

terms of neuroanatomy on what no one was

describing is the fact that of course

there are two nostrils and then a bunch

of receptors they converge in these

glomerular but you have a mirror

representation of that on both sides of

the brain and that most of that

information is kept on one side of the

brain or the other there isn't a lot of

extensive intermixing at the first order

of process so the question I have is

whether or not you believe I'm not

asking for data first I just want to

know what you believe that this

alternating nostril airflow phenomenon

has anything to do with preferential

processing of olfactory information in

terms of right brain left brain with the

caveat that anytime we hear right brain

left brain

um we've covered this in a previous

episode most of what people hear out

there about right brain left brain

emotionality logical stuff is completely

wrong completely wrong doesn't exist is

a total fabrication

um and we'd like to abolish that myth

but with that aside or set aside rather

what are your thoughts on why the

information would switch from one side

of the brain to the other at all yeah I

don't think I don't think

that that the nasal cycle is an

olfaction story

um so so I I don't think that

um

that this was shaped by the olfactory

system nor do I think this has major

impact on olfaction

I think the nasal cycle story is a

different story about brain function

um so so you know we have we have this

sort of

pet Theory where calling now the the

sniffing brain approach

where

where basically

we think that that nasal inhalation

is timing and driving a lot of aspects

and patterns of of neural activity and

cognitive processing and and this theory

is is all faction inspired in its

beginning that is I mean if you think of

the mammalian brain right it's

which which

evolved from all faction it's sitting

there and an in all faction because

olfaction depends on sniffing you have

this situation where you have a you have

a sniff you have information

and then flat nothing right and then you

have information and then nothing so

information processing is is one-to-one

linked to nasal inhalation

and and we think that that

this property evolved

to to be meaningful in brain processing

in general not only of olfactory

information but of any type of

information because the brain evolved in

this way in this way that it processes

information on inhalation onset

so

a study led by offer Peril from our our

lab uh two three years ago

um we looked at something completely not

all Factory we looked at visual spatial

processing and we compared visual

spatial processing on inhalation versus

exhalation

and the brain does this completely

different on inhalation versus

exhalation you're in that particular

task people performed significantly

better on inhalation versus exhalation

what was the task was in an olfactory no

no it's a visual spatial task so this is

a task where uh the the specifics of the

tasks were

um that you see a shape and you have to

determine if it's a shape that can or

cannot exist in the real world so some

of them were these like Usher shapes

like you know where where one facet

doesn't reach the other facet The

Impossible figures yeah yeah but but but

uh structural shapes not not and and so

so a pure visual spatial task we

intentionally went for a task that is

not

considered a ventral temporal task in

olfactory cortex task in any way

and and people performed much better on

inhalation versus exhalation and doing

this task was there a both nostrils

occluded

um version where people were forced to

mouth breathe yes

and in this particular task they also

did better on mouth inhalation versus

mouth exhalation

but the difference wasn't as pronounced

as it was with nasal inhalation versus

exhalation so I'm a big proponent of

nasal not mouth breathing whenever

possible for

um many health related Reasons I'm a big

fan of the book Jaws a hidden epidemic

uh written by colleagues of mine at

Stanford familiar with it yeah and this

idea that uh people who mouth breathe

experience more colds more infections of

various kinds it's not good

aesthetically or for the dentist

dentature I never know the teeth the

gums and stuff sorry my uh my dentist is

going to come after me

um need to go to the dentist anyway the

um that nose breathing is great for your

health relative to mouth so I think it's

also good for your cognition not only

for your your dental health uh I think

that that news breathing shapes

cognition and and there other labs who

are finding the same uh again uh

Christina zellano is doing work on this

line she she had major contributions

here and and yuan lundstrom is doing

work on this line there's lots of

studies suggesting that

um nasal inhalation is timing cognitive

processing and modulating it

incredible um perhaps not surprising

given what you've taught us about the

olfactory system I mean that these two

holes in the front of our face these

nostrils I mean are

a pathway to the brain right I I love to

tell people because I work on the visual

system in my lab that you know your eyes

are two pieces of brain extruded from

the cranial Vault right which they are

the retina is any anyhow and um and then

you never look at anyone the same way

again it's okay but the the olfactory

Sensory neurons are right there at the

tops of those Caverns that we call

nostrils and they are brain yeah

definitely it's it's the only place

where your brain meets the outside world

because in your retina they're protected

by by a lens and here here you have

neurons in contact with with the world

this this actually has been the source

for some

theories on a potential uh route for for

neurodegenerative

um mechanisms so as as you may know

um loss of the sense of smell is one of

the if not the earliest sign of

neurodegenerative disease

so for example in Parkinson's disease

there's uh uh loss in the sense of smell

probably 10 years before any other

symptom

um but people have failed to make this a

diagnostic tool because it's

non-specific

so it's not as if you could come to your

doctor and say I'm losing my sense of

smell and they'll say oh early sign of

Parkinson's because

you can have many reasons to lose your

sense of smell and and so on

um

but but

olfactory loss again is is an early sign

of neurodegeneration and there's at

least one Theory particularly about

Alzheimer's disease

suggesting that that Alzheimer's may be

the result of of a pathogen that enters

the brain through the olfactory system

um oh interesting it's it's not of

course a a mainstream or widely accepted

theory of any type but but it just

highlights this notion that that the

nose is a path to our brain

I think these non-invasive

um readouts of potential

neurodegeneration

um such as uh visual tests because of

the fact that the retinas are part of

the brain and loss of neurons in the

retina is often associated with other

forms of central generation Alzheimer's

Parkinson's Etc as it's a little more

invasive than what you're describing I'm

beginning to wonder why we don't

um get have a olfactory task every time

we go to the doctor

that would allow tracking over time

because of course as you mentioned

someone can lose their sense of smell

does that mean they're getting

Alzheimer's not necessarily but if their

sense of smell was terrific the year

before and it's 50 percent worse than

actually that's a really bad sign yeah

that's a bad sign and so what we're

talking about something completely

non-invasive and could be relatively

Pleasant to innocuous depending on the

odor's use so yeah so so first I can

answer that right and the reason that

that's not happened and that might that

that may be changing right now but the

reason that has not happen

is because olfaction has not been

effectively digitized

right so if you need to generate you

know really precise visual information

you can buy a monitor for you know 100

bucks that is it the resolution of the

visual system basically and if you want

to generate auditory stimuli really

precisely then you can buy an amplifier

for you know maybe a bit more than 100

bucks but not that much more

and you'll be at the resolution of the

auditory system

in our lab we build devices that

generate orders we call them all

factometers which is a misnomer because

they don't measure anything but that's

what they've always been called so we

call them all factometers as well

and we've already built at least one all

factometer that cost a quarter of a

million euro and it's pathetic right so

it just it's pathetic it's it's slow

it's contaminated it's nowhere near the

resolution of your system

so one of the reasons that's not

happened

is just

the utterly poor control of the stimulus

mind you to some extent it has happened

in that there there are a standard

clinical tests of olfaction basically

two that sort of control uh the world in

this respect the older one is is a test

called the upsit which stands for the

University of Pennsylvania smell

identification test

it was developed by Richard Dodie and

Penn and it's a test where you scratch

and sniff and it's a four alternative

forced choice test with 40 odorants so

you have these 40 pages that you page

through and you sniff and smell and and

um you know it's been normed on

gazillions of tests

um

I I'm always amused by it because so

Richard Dodie made a ton of money uh on

the upsit but he needed it because he

has a habit he has a NASCAR so this

every time we buy upsits and live I said

there's another gallon of gas into

Richard he races NASCAR it's not not

like NASCAR but like one lower than that

like I don't know like some some sort of

formula a or formula for it or something

he races a car and so that's where all

the ubsites went so I always feel good

about buying either PSATs because I know

they're going to that good cause but

keeping him in in in the fast lane yeah

but but so so that's one test that's out

there and indeed you know has been shown

as a you know so there's reduced upsit

and Alzheimer's and Parkinson's and and

then a host of other diseases and

there's a European version called

sniffing sticks

has developed and and it's it's

basically the same sort of concept of

that one isn't scratch and sniff it's

like these pens that you open up and and

sniff but but those exist but

they're not as as convenient as as uh

is delivering stimuli and vision and

audition and that's why you don't have

what you've just suggested

you know another thing another place

where you don't have it which which I

think is even more would have been even

more meaningful is

is you don't oh actually it's not tested

in in newborns right where vision and

audition is

you know there's this thing called

congenital anosomia right which is being

without the sense of smell from birth

supposedly in general

uh which is a half a percent of the

population

it's not a trivial number not totally

yeah

but nobody knows if that really is true

because here's an amazing factoid guess

the average age at which can General and

osmia

is diagnosed and this is this is a

horrible statistic for me for the way I

see the world but what do you think the

average age of diagnosis is for

congenital anosmia five years of age 14.

incredible 14. so most people who are

one half of a one percent of the human

population presumably yeah is uh without

the sense of smell and doesn't realize

that until they're 14 years old well I

don't know when they realized it first

but but it's formally diagnosed at 14 on

average which means some of them even

later right and um and uh right it's a

distribution well what um do they suffer

yes so so first of all

they they suffer socially

um and there's a host of of deleterious

life events associated with congenital

anosmia

um the the die younger

um the so it's it's it's uh it's this is

work out of uh Ilona Croy in Germany

um and you know amongst the various

things that are predicted by an osmia is

shorter lifespan uh but things like you

know reduced uh social contacts uh

reduced

um romantic social contacts

um it's not a good thing

um and and do they lack olfactory bulbs

I'm presenting they have noses and

nostrils there is a condition I'm aware

of where where uh children are born

without no very rare yeah very rare

focus on that because it's exceedingly

rare

um but they're born with noses and

nostables um and here's the thing right

we don't know if they're born with

olfactory bulbs

um most of them although not all of them

but most of them don't have olfactory

bulbs in adulthood or or I should

rephrase that have remnants olfactory

bulbs really shriveled olfactory bulbs

but you know nobody can say the cause

and effect here before we talk about the

role of the the uh requirement for

olfactory bulbs for olfaction a very

interesting topic in its own right I I'm

curious as to whether or not their

endocrine system is altered because as

we'll soon talk about there's a lot of

signaling through the nose

from between individuals that uh

triggers things everything from the

onset of puberty to feelings of romantic

attraction attachment these sorts of

things

um is it known whether or not and I

should say excuse me for interrupting

myself but as long as I'm interrupting

you every five minutes I might as well

interrupt myself too that um we are well

aware of the proximity of the olfactory

system to some of the hypothalamic

systems that regulate the release of

gonadotropins which control testosterone

and estrogen production Etc so um are

they uh hormonally normal so some are

and some aren't and I'll I'll be

specific so

um there's a condition known as common

syndrome

which is hypogonadic development

um in in men

and in Kalman syndrome uh they're

practically all announcement

so so to answer your question yes

there's a direct link and and it

materializes in common syndrome that

said not all congenital anosomic uh

individuals have common syndrome

and not all but almost all people who

have common syndrome are in osmaker so

so common syndrome uh goes with uh

anosmia I think so there is a female

equivalent of Commons or I don't

remember its name uh it's not turn it's

not a in the Turner syndrome family I'm

not sure okay and I think it's also

associated with anosmia uh but I'm not

confident of that but Commons is is

associated with an osmia uh so so the

answer is is yes and and you know we can

maybe you know

of action and reproduction are are

tightly linked and and they're tightly

Linked In all mammals and we are big

terrestrial mammals and all fashion

reproduction are linked in humans as

well

um yeah we will definitely get into that

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get 20 off I have a story slash question

that I'd like to

um tell you ask you as a segue to that

noting of course that we'll get back to

the the requirement for olfactory bulbs

yes or no for olfaction uh and um this

really so when I was growing up I grew

up at the uh end of a street with a lot

of boys of my age who just by

coincidence had a lot of older sisters

were my sister my older sister's age it

was fortunate so I had a lot of kids to

play with we would hang out at each

other's houses bike build jumps and do

all those things like kid stuff Fort

stuff

get into trouble or whatnot

and oftentimes we would end up leaving

our articles of clothing at each other's

houses all the time like t-shirts and

jackets and so my mom was constantly

coming in and saying there's all there's

this close like someone left us here I

don't know who it was we were all more

or less the same size and

from the as far back as I could remember

six seven years old and onward I could

pick up a shirt or a jacket smell it and

say oh well that's Eric eisenhart's

shirt a friend of mine there I just gave

his name or oh that's Scott Madsen shirt

I I could just smell the shirt and in a

conscious way know who it belonged to

having never I promise not that I would

pretend if I had if I had

um pretend I hadn't if I had but having

never actually done the exercise of

going and taking and smelling my friend

intentionally right okay in fact if

anything I had all the reasons in the

world to avoid smelling to other young

boys in my neighborhood okay so yeah

um that raises the question of whether

or not we are consciously and or

subconsciously

coding identification of people that we

interact with frequently or infrequently

in terms of their smell

and or some other aspect of their um

chemistry yeah

so yes

um

we're doing that all the time in my view

and a lot of this processing almost all

of it is subconscious and I don't know

why already already put that out there

right I have no idea why why uh Human

Nature has has uh or nature or culture

or whatnot has has pushed this into the

realm of of subconscious and something

we're unaware of

um but we do it all the time and

um

in our lab has lots of studies on this

front

um one of them you may be familiar with

it that had gained some notoriety

because it's amusing

um so we

we look at human behavior a lot we try

to look at it through our news and in

the way we look at what people are doing

you know we try to think you know if I

was a dog

what what would I think of this and and

you know if you look at dogs right

they've you know when they interact they

visibly sniff each other it's very

obvious they walk up to each other and

they sniff each other

um

and yet humans don't typically walk up

to a stranger and carefully sniff them

right I mean it's we're sort of obliged

to sniff our our babies that's

considered almost something you're

supposed to do

um and it's not culturally taboo to

sniff our loved ones it sort of doesn't

seem like an odd thing to do

but we don't sniff strangers right well

or do we so we're finding more and more

mechanisms where we do this and the one

I'm referring to now for one example is

we started looking at handshaking

handshaking is this really odd behavior

and it's not only in the west by the way

some people think it's only a western

thing it's not it's almost everywhere

and and

there's really poor understanding of how

this Behavior evolved like where did

where did this thing come from so if you

you know if you look for the Wikipedia

version right then they'll tell you that

it's to show that you're not holding a

weapon in your hand but there's really

no good evidence for that it's a bit

like the trillion Bloodhound receptor

story right I mean we tried to find it

you know why do people say that and they

just do and we started looking at people

handshaking and and we noticed or it

seemed to us that we're noticing that

you know people will shake hands and

then we'll go like this and like for

those of you listening not watching them

no um it was taking his hand and and

wiping it on his face yeah grabbing his

nose or touching myself yeah these

things these things that we do all the

time after a handshake well so first of

all we do them all the time just period

right the Baseline here is really high

and we'll get to that in a second but

but but these behaviors that you know

you you could easily not notice right

and and so we we asked whether that's a

real thing

um

and this was a study led by John fruming

in our lab at the time

um

and what we did first and if you want we

can link so so this was published in

E-Life and one of the nice things about

E-Life is that it has a very effective

way to embed videos in the publication

so if you want we can link this to your

system later on even the show note

captions as a link on YouTube and the

other for uh platforms Spotify Apple so

so what we did is is

um we we brought in participants to our

lab

and we sat them in the room uh

experiment room

and and told them the experiment would

start soon and they should wait for us

there they didn't know what they were

coming from unbeknownst to them they

were already being videoed uh of course

later on they had the opportunity to to

not agree to us saving the video in

which case we would delete it

immediately or or letting us use it for

science or someone letting us use it for

more than science for for the video

that's now on elife

and and we walk into the room and say

okay just wait here I will be right back

with you uh to set up our experiment and

they would sit there for three minutes

and during those three minutes we could

later quantify how much indeed they just

by Baseline how much they touched their

nose or their forehead or their chin or

how many times their hands uh reaches

their face and by the way that Baseline

is not low okay

um and then three minutes later an

experimenter would walk into the room

and uh would share a consistent text it

would be you know we're still setting up

our equipment in the other room uh our

and and so just wait here and we'll be

right back with you but in the meantime

just wait here

and the experimenter went through this

like 20 second fixed text and in half of

the cases it included the handshake this

was a new experimenter not the one who

put them in the room so that's the first

time they met so it would be a little

I'm you know so and so they would put

out their hand and shake their hand or

not okay and we did all possible

interactions in terms of gender so we

matched male participants with male and

female experimenters and female

participants with female and male

experimenters and so you had handshake

and no handshake conditions and then you

can quantify that behavior of the hand

going to the nose after a handshake

and there was a remarkable increase in

the hand going to the news after

handshake and this is one of the nice

cases we the paper includes statistics

but you don't need statistics here just

look at the video it's on it's unreal

the video is unreal so interesting so

the hand goes to the nose now we did a

few controls here

to verify that this is an olfactory

Behavior one is unbeknownst into

participants we measured nasal airflow

and and people not only bring their hand

to their nose they sniff it so and this

is perfectly time they go like this okay

so they're sniffing their hands and in

an additional control study we

manipulated it so we built this little

James Bond thing of a watch on the

experimenter's hand they could emit an

odor and the experimenter didn't know

what odor they were emitting and they

could emit either a pleasant or an

unpleasant odor and we could drive the

self-sampling afterwards up or down so

this was an olfactory Behavior no doubt

about it I mean we're quite confident so

people in that case people must have

been sensing the odor on their own hand

because they'd Shake shook the hand of

the of the experimenter pleasant odor

and they're more frequently bringing

that hand to their nose versus

unpleasant odor that had been introduced

to their own hand by the experimenter

Yeah but no I think I think they were

sensing the the ambient odor that came

in with the hand that That Shook and

then that either drove them to snip

their more or less the odor cloud of the

expression yeah and there's an

interesting thing going on here too

because people didn't only smell The

Hand That Shook they also smelled the

other hand

and and we think that there's something

going on here comparing self to other

and we think a lot of self-sampling

might might reflect that there's on the

same line and again to to link to your

childhood story of of uh identifying

your friends by by smell

um

study we published just last year by uh

in battle Ravi in our lab

um

where inval came with this uh uh basic

interest in this phenomenon that's

Loosely referred to as click friendships

so people you meet and you click right

away right you immediately become close

friends and this is a phenomena that you

know is poorly described or is poorly

ascribed in literature as as an entity

and yet anybody will tell you they know

what you're talking about right I mean

if you tell you know if somebody you

click with right away you you become

intimate within five minutes right

everybody experienced this in their life

you know to some extent

and the question is what what was there

right what was it was it because you

looked the same could be was it because

you know you had the same sports team

that you liked or is there something uh

uh deeper here and and in Buzz theory

was that that

um

that a similarity in body order May

contribute to this

that people who smell the same will

click in some way and so to address that

she actually recruited uh

um click friends from all over Israel

she posted all of her social media uh to

identify uh

pairs of friends so these are our

same-sex non-romantic diets so these are

friends men and women uh whose

friendship started is a click

where here this becomes sensitive

because it has to be a mutual click

right later on we discovered there could

be one-sided clicks so if somebody's

sure they clicked with somebody else but

the other person there's a name for that

in neurology that our uh common friend

the late Ben Barris taught me which is

there's a phrase that neurologists use

okay called sticky these are people that

come up to you and and start asking you

questions and then won't leave you alone

they're so-called sticky people that and

if you ask these sticky people

um sticky in air quotes because they're

not physically sticky

um maybe what they could be

um you know

what do you think of the per this person

they'll say oh they're great we're

really good friends and so they've made

a unilateral um click friendship yeah

yeah and uh yes neurologists are talking

about you if you're if you're one of

these people neurologists are talking

about you there's a an informal

diagnostic code sticky so so so uh she

she recruited

um

um

click friends

and then she sampled their body odor and

and we have a a protocol for this so

they're given you know uh odorless

shampoo and soap to use for three weeks

or something and then they sleep two

nights in this t-shirt uh where they

have to sleep alone and then we extract

the body odor from the t-shirt and so we

have a way to extract a method to

extract body odor and then she she first

asked

um whether indeed

click friends are more similar in their

body order than you would expect by

chance

and she first tested this with them with

a device a machine we call an electronic

nose so an electronic nose is sort of a

very poor effort to mimic what the

mammalian nose does basically it's a

bunch of sensors that respond to

Airborne molecules in this case sensors

referred to as moxers as a metal oxide

covered sensors

um

and so she used an electronic nose to

sample these body odors and she found

that click friends are indeed more

similar to each other than you would

expect by chance by random diets and

this was a significant difference and

after she found that a device could do

this

she had other participants do this so so

she had people smelling the click

friends versus non-click friends and and

they judge them as being more similar to

each other

uh than not now again you you might

wonder is this causal or not right

because maybe click friends go to the

same restaurant together or all the time

or whatever or live in the same

neighborhood and and that's why they

they they smell the same so to address

causality she recruited total strangers

and first smell them with the electronic

nose and then engage them in a social

interaction something called the mirror

game so in the mirror game one person

moves their hands and the other person

is really close to them like right here

so they can smell each other and has to

move their hands with the other person

and one one prediction there panned out

uh but another didn't the one that

didn't so she predicted that people

would smell more uh similar to each

other would be better at the mirror game

that is they would follow each other

better that did not pan out however

she then also had the interaction was

completely non-verbal they were not

allowed to speak with each other and she

did an entire round robin so everybody

played with everybody else this was an

insane experiment to run

and

and she then at the end of the

experiment each person raided each other

person as to how much they think they

would want to be their friends and also

on a bunch of ratings how nice they

think they are how affectionate they

think a bunch of ratings okay

all of this was predicted by the

electronic news so people who smell more

similar to each other think that the

other person is more likely to be their

friend is more likely to be a nice

person etc etc so we could actually

predict friendship using the electronic

news so this is not a result of

friendship it's it plays into the causal

elements of of building friendship so

this is to relate to your childhood

story uh there's something going on here

we're constantly smelling ourselves

constantly this

constantly so I mean if you want to like

I don't know the reason I'm smiling I

mean and your viewers are listeners will

understand why I'm smiling I'll send you

a video to link uh uh in in the in into

your podcast here we thought of calling

the the fact that people constantly

sniff themselves we thought of calling

this the low effect and low so in

America this won't pass that effectively

but in in the rest of the normal world

is the soccer the national soccer coach

of the German soccer team so

yeah I mean I don't know who would be a

very famous coach here but Steve Kerr I

mean this is the choice this is a super

super famous uh name all around the

world where soccer is the primary sport

that people watch

um

and and once people will see this video

they'll understand why we thought of

calling this the low effect uh it's a

very graphic uh but but people are

constantly smelling themselves they're

smelling themselves with their hands

they're smelling themselves explicitly

people are constantly smelling

themselves constantly smelling others

um I find this topic so interesting um

and first of all confession I definitely

smell myself multiple times per day and

everybody does okay good yeah and I I um

I would do it anyway

um uh I think I like most people I

either find my own smell to be neutral

to Pleasant

right I um occasionally I'll be like

well I need to take a shower as long as

we're talking about smelling oneself and

um friendship kinship and its

relationship to smell we have to talk

about the relationship between smell and

romantic attraction and bond so my

understanding is that if for instance a

mouse is given the option to mate with

any number of other different mice

they will bias their choice toward the

mouse that has the immune composition

the so-called MHC major

histocomatibility complex which reflects

immune diversity the immune system that

is most distant from theirs and the The

evolutionary argument being that were

they to

um produce offspring that the array of

immune genes would be much broader than

if they were to select an animal very

close to them and in addition to that

that one of the most strongly selected

against behaviors not just culturally

but at the level of eliciting a sense of

disgust

maybe even from the activity of the

hypothalamus is mating with very close

kin AKA incest because that can

potentially we know produces a higher

rate of mutations in other words whereas

you describe the relationship between

smell and choice of friends as you uh

choose people who smell more like you my

understanding is that in the context of

uh

choosing romantic Partners or sexual

partners or both that you choose the

person who's odor and therefore immune

composition is most different right so

the way you describe the animal

literature is correct

and there's evidence to similar

mechanisms in humans our lab has not

worked directly on this issue of of uh

of uh romantic selection based on odor

um there's a bunch of papers

um wedkins Ed Allen and the wedkin lab

and also Porter I'll I'll email these to

you later on

um that have have done a lot of this

work and find exactly as you say that

that um um romantic order preferences in

humans are influenced by Body order and

that this is linked to MHC uh uh is the

compatibility complex makeup of the the

portion of our genome that that shapes

our immune system uh to some extent

um so so this effect

um has been studied and reported on

again extensively in mice and also uh in

in humans

um

not work that that we've done

um

the one sort of

tangent work we've done and and

I'd like to maybe tell you about

it relates to to an effect

that that is one of the most remarkable

effects in in mammalian social chemo

signaling so

and and also related to to so it's it's

not related to Romanticism in any way or

or but but it's related to reproduction

and and indeed in our lab we've not

looked at Romanticism we have looked at

or are looking at reproduction

they're not always the same

um certainly

oh they can they can animal mammalian or

terrestrial mammalian reproductive

behavior is is dominated by by the sense

of smell

um in in mammals and here remember

initially when you started off I I noted

that there are several subsystems in our

news that transduce utterance and and so

primarily the manual factory system

which is cranial nerve number one and

the trigeminal nerve which is cranial

number five

um most terrestrial mammals have another

subsystem referred to as the the

secondary olfactory system

that has a separate sense organ in the

nose this organ is known as the

vulnerable nasal organ

it's a small pit in the nasal passage of

of most terrestrial mammals sometimes

it's uh described as a communicating pit

because sometimes it connects the nasal

passage to the roof of the mouth

sometimes it can it connects both

and

so there's this sense organ with its

specific receptor subtypes uh vnr's

vermonasal receptors

and uh this

um

um is linked to a to a sort of separate

portion of the olfactory bulb not really

a manual Factory bubble it's referred to

as the accessory olfactory bulb

um and from there directly to the limbic

system to the to the portions of the

brain that control reproductive Behavior

Uh and aggressive behavior and

and in most

um terrestrial mammals this subsystem

processes utterance there are sometimes

referred to as pheromones although

that's in many ways a problematic term

but but utterance that are referred to

as pheromones namely odorants that are

emitted by another member of the species

to influence that member of the species

and alter Behavior or hormonal state

and

and and some of these pheromonal effects

are are utterly remarkable and in my

view the most remarkable of all is an

effect known as the Bruce effect

uh this was an effect discovered by

Margaret Bruce in 1959 she was a British

scientist

and in the Bruce effect when you expose

a pregnant Mouse

at an early critical stage of the

pregnancy

um I think up to about day three uh if

you expose the pregnant Mouse uh to the

order of what is referred to in

technical terms is the non-stud male

that is a male who did not father the

pregnancy

she will miscarry the pregnancy she will

abort it

now that that's an insane decision made

by the female here right because she's

invested quite a lot in this right in in

biological terms and in in forming this

pregnancy and maintaining it and yet she

drops it on the basis of an odor

um and this effect is remarkably robust

and what do I mean by remarkably robust

so this will occur

on about 80 percent of exposures now as

you know 80 is 100 in biology right I

mean there's nothing that happens at

more than 80 percent

so it's a remarkably remarkably robust

effect this this dropping of the

pregnancy and we know it's mediated by

chemosensation three no for sure and we

know in the following way so first it's

enough to just bring the order of the

non-stead male you don't have to bring

the mail himself right so you just can

bring bedding from a nonsense male and

that will induce uh the Bruce effect but

of course uh the most telling set of

experiments is that if in the female

Mouse you ablate the vulner nasal organ

you just burn this tiny structure in the

nose and the effect disappears so the

effect is completely dependent on the

former nasal organ

um

and and I find this out really a

remarkable effect right I mean because

again because of the the extent of of

cost that the female takes on here uh

based on on this information and smell

now

humans

the the sort of the going notion in all

faction is that humans don't have a

functional vomarinasal organ

so we don't have that functional organ

in our nose now I'll point out we

actually do have

the pit

so the the structure or the outlining

structure is there

uh but the pit that we have is

considered vestigial and non-functional

and what about this thing I learned

about at Berkeley uh in integrative

biology class that we have something

called Jacobson's organ this is the same

organ so so Jacobson Orion is the former

nasal organ uh it's also called Jacobson

because

um I think Jacobson was a military

physician in like the 1800s in Holland

or something and he found it in in

in a soldier who was operating on or

something like that the the story comes

from something like that but but

Jacobson organ is another name for the

former known as organ these are one and

the same the sensory organ of the

accessory olfactory system and again the

going notion is that the human Jacobson

organ or Romanus organ is vestigial it's

non-functional does that necessarily

mean that we don't have these pheromone

effects no it does not so first of all

we know that lots of what are considered

pheromonal effects namely social chemo

segolian rodents are mediated by the

manual factory system we know that for

sure

um there are several examples for this

in mice and rats and rabbits and so on

and so forth so so a uh these can be

mediated by by the manual factory system

and and I'll I'll come back to that in a

second but first to finish the the Bruce

effect

um

and and second and and I'm going out on

a limb here uh but I'm willing to take

that that uh risk I'm I'm for me the

jury is still out on human vulner nasal

organ

um the the decision or the the notion uh

that it's non-functional relies on about

one and a half papers

postmortem uh looking for the nerve that

connects this thing to the brain and

failing to find it using staining and so

on and so forth but sustaining

postmortem studies in humans are are

notoriously

complicated

um basically you know for many reasons

one of them is that the material is just

always has gone through you know it's

it's not ideally uh uh set as it is when

you sacrifice an animal and and

and and study its its tissue

um so so based on on really really a

positive studies that fail to find uh

this nerve the notion is that the

structure is vestigial uh in humans I

don't have any evidence that it's

functional mind you but but I'm just not

sure that it's not but

um what we do have a suspicion

is that humans may experience something

similar to Bruce effect

so

first of all humans have an enormous

um number or ratio of of spontaneous

miscarriage are they

um occurring more often in the first

trimester because you mentioned yes that

in the Bruce effect in the mice is in

the first three days or so following

pregnancy which in the mouse gestation

as I recall is about 21 days in the

mouse you're talking about one-seventh

of total gestation so I'm I'm not quick

enough to to nor is it important to

translate but this would be first

trimester yes which is indeed when most

miscarriage occurs now humans have again

a huge number of miscarriages and and

the numbers I'll soon share them with

you they sound odd and the reason they

sound odd is because if if you have

what's sometimes simply referred to as

failed implantation right this can occur

you know in days one two nobody ever

knows okay so so some papers talk about

90 of all human pregnancies end in

miscarriage this is counting a failed

implementation in day one two Etc more

conservative studies talk about 50

percent nobody will argue 30 okay so a

huge number a huge number of of uh human

pregnancies end in miscarriage

now out of these there's a portion

that are are unexplained right so nobody

knows why I mean there are portions that

are explained by all sorts of genetic

factors developmental factors and so on

and so forth but there's also a

proportion that are unexplained

and and and so all I'm saying is that

there's there's a statistical backdrop

or setting if you will force something

like a Remnant Bruce effect in humans

now with that in mind we we approach the

group

um

of we we enlisted a group of of they're

not really patients and participants in

a study of people who or couples who are

experiencing what is referred to as as

unexplained repeated pregnancy loss

so formally if you have uh two

consecutive uh unexplained miscarriages

then uh that that is sufficient for the

diagnosis of unexplained repeated

pregnancy loss

however in our cohort of 30 we had

couples who experienced 12 consecutive

unexplained repeated pregnancy losses so

so the two the two is just the formal

all of our cohort was like twelve five

you know so this is an emotional

difficult place to be

and and these are couples who who are

losing uh their pregnancy for no

apparent reason so they've gone through

all the tests that you can imagine of

you know genetic incompatibilities and

all sorts of issues uh clotting all the

all the the known suspects uh for for

pregnancy Lawson the the medical

establishment remains totally at a loss

as to why these pregnancies aren't

holding and so we hypothesized that that

perhaps here there's something akin to

to a Bruce type effect obviously it's

not going to be the same as in mice but

but something like a Bruce effect now of

course at that stage we could not do

anything causal to to test this right

but what we could do is to see uh you

know to seek circumstantial evidence to

see if if where there's fire maybe

there's smoke and what we did was we

tested uh

olfaction and more specifically the

response to male body odor uh in in the

the couples experiencing

um

uh repeated pregnancy loss and

we found a few things first of all if

you think of the mechanisms behind the

Bruce effect

the Bruce effect implies that the female

has to have a very clear memory

of uh the following meal because if

she's gonna miscarry in response to the

non-father she has to know father

non-father I mean that means that

there's a pronounced olfactory memory at

the moment of mating okay and in mice

this has been very well characterized

and and attributed to the Ontario

olfactory nucleus a structure in the

brain

um

but you'd have to have this memory in

order to make that decision

now so to address that and here you're

going to see that you in your childhood

story from before stand out a bit as as

skillful

is that the first thing we did was just

behaviorally test uh whether

um

these women and control women

could identify the smell of their uh

spouse

[Music]

and you might be disappointed or you

know it we would all are probably a bit

disappointed to learn that control where

I'm in uh are very poor at this

so so you you would think that that

women would be good at identifying the

body order of their spouse they're not

uh they're not far from chance

however

um the uh women who experience uh

repeated pregnancy loss

are more than they're they're double uh

at their performance level so this is

not a Nuance effect

uh women who who who experience repeated

uh pregnancy loss can identify uh their

husbands or their spouses uh by their

body odor

with much greater Acuity than the

typical person double

a bit more than double and way above

chance yeah no I I sorry I posed as a

question but I meant yes with much

greater Acuity uh and double is is a

significant

um Improvement

are they much better at detecting any

odor no they're not we did the controls

and they're not

and then

um we also measured using fmri we

measured their their brain response to

uh stranger male body odor

and there and and and this was quite

remarkable because you know we

approached so this was a full brain

analysis so without a region of Interest

analysis so it's not as if you're uh

tweaking your statistics to look at one

part of the brain you're just looking at

the entire brain in the response to male

body order and asking de novo is there a

difference between these two groups of

participants and there was one huge

difference and it was in the

hippothalamus and so there was a

difference in response to stranger male

body order uh between the two groups

um

so so

olfaction is altered in spontaneous

repeated spontaneous uh pregnancy loss

we don't know this is causal right uh

but but

that was enough for us to approach the

Ethics Committee

um to run a causal experiment

um and we're at the beginning of that

now

incredible I can't wait to hear the the

results of that it's gonna take it'll

probably take years

um a few because because

the these are slow experiments to run uh

um recruitment is complicated uh but

basically we're we're blocking

um

we're blocking smell in in uh couples

who are trying to maintain a pregnancy