I think even for touch, we still don't fully understand it.
I think robots are, obviously these days,
the robots are become more and more fancier,
but they still are not as good as our human fingers.
So I think part of that is because we don't fully understand
the sense of touch and how we use it,
it's sort of an online feedback manner
to control our fingers.
The human brain is the most complex structure
in the known universe.
And we are in the middle of a scientific revolution
to understand its inner workings.
Join us for a conversation
with world renowned neuroscientists
as they visit Rochester.
I am Dr. John Foxe,
Director of the Del Monte Institute for Neuroscience
at the University of Rochester,
and you are listening to Neuroscience Perspectives.
I'm John Foxe.
I'm the Director of the Del Monte Institute for Neuroscience
at the University of Rochester.
And I'd like to welcome you to another episode
of Neuroscience Perspectives.
Today, we're very, very pleased to have with us
a guest from all the way from Boston here to Rochester,
where it's a frigid day indeed, Professor Fan Wang,
who is a professor of brain and cognitive sciences
at the world famous McGovern Institute for Brain Sciences
at Massachusetts Institute of Technology, MIT.
Fan, it's really wonderful to have you here today.
My pleasure.
The chat with us.
You know, I know you study touch,
sensation of touch,
and have had a specific interest in touch and pain.
Yes.
And more recently, this has evolved into looking towards
more efficacious treatments for drug addiction.
That's quite a span of work there.
Let's hear a little bit about, you know,
how did you get into studying touch?
What about that made,
was of particular interest to you?
As a PhD student, I work with Richard Axel,
and I studied smell.
And it was a really fun time.
I had really a best of time in my life as a graduate student.
And as I finishing up and I was looking for post-docs,
and I was thinking, which area should I get into?
And I remembered in graduate school,
we always talk about this, you know,
there's a factory sensory map.
And then, but then who is reading the map, right?
And then Richard used to say,
there's no ghosts in the machine, right?
So that always made me wonder,
because we always say, I am looking,
I am smelling, I am feeling, right?
So who am I?
And then I was deeply interested
in understanding this question.
What gave us a sense of self?
Who am I?
And I figured I needed to study something
related to the body,
because when we talk about ourselves,
we always point at our body, right?
So that made me wanted to study touch.
So somatosensation, the bodily senses.
So that is sort of the fundamental reason
why I decided to go into the bodily sensations.
It's an amazing connection you've just made
between something so fundamental,
the sense of touch and the maps of touch,
and a deep philosophical question, who am I?
I'm here.
And I love the expression, no ghost in the machine.
Yes.
Help our viewers and listeners understand that.
What do we mean by that, the ghost in the machine?
Yeah, so if you look into the brain,
you can find somatosensory cortex, visual cortex,
auditory cortex, motor cortex,
but it's always like there is an eye there, right?
I feel as if there is someone looking
at your somatosensory cortex telling you
what you're feeling or what you're moving or what you're seeing.
But if you look at it, there's no region in the brain
that is an eye, right?
Me, I, self.
So what is that?
And I don't know, I still don't know what is the question.
That's what scientists mean.
There's no ghost in the machine.
There's no soul in a particular region in the brain,
even though we think neuroactivity is sort of the basis
for the sense of self.
But who is this knower, this reader of the brain activity?
I think, you know, this is sort of standard.
A lot of the paradigms, the models we use boil down
to some little man or woman pulling the levers in there,
switching back and forth.
But of course, that's you yourself
and how that self is represented.
We talk about things like emergent properties
of like the network dynamics of a brain,
but this is still a complete mystery, really.
Still a complete mystery, yes.
I love how you've related something quite fundamental,
really, in the study of touch.
Tell us about then from touch to pain
and why that's important.
If I may be truly honest with you, okay.
So when I was writing touch grant application for R01s
and you always try to relate to human health, right?
Yeah, always.
Okay, so initially I'm really only interested in touch.
But then when you try to write grant,
it seems that touch can become painful
in neuropathic conditions.
So there's a lot more pain opportunity there.
So that was initial, I would just made that conceptual link,
touch can become painful.
But then over the years, it actually really become
a deep interest of mine.
And I really decided the pain is what I also
truly fundamentally and both scientifically
and as a scientist, I feel like it's my society duty
that I'm interested in pain,
because I pain, especially chronic pain,
affecting so many people.
That's now a very big area of research in my lab.
Fantastic, and yeah, I mean, this is such
an extraordinarily unmet need in the community.
So many people suffering from chronic pain
with very little in the line of solutions.
And of course, we've been through a huge opioid epidemic
on the backs of trying to help people
with chronic pain issues.
Can you draw that link for us then between,
really fundamental mapping of your fingers
and your joints in cortex and this transition
into a chronic pain condition?
How do you see that?
Yeah, actually today in my talk,
I will actually talk about it.
What is the role of the sensory cortex,
somatosensory cortex in pain, right?
Because we study touch, touch as a clear map
in the somatosensory cortex.
So Pantheon many years ago stimulated the brain.
And if you stimulate the sensory cortex,
you evoke sensations.
And that's always tactile sensation, touch sensation.
No matter how strongly you stimulate
the somatosensory cortex, you never evoke pain.
Oh, that's very interesting.
Just for our listeners,
Penfield was a great neurologist, neurosurgeon.
And when we were talking with stimulating the brain,
he was literally in true craniotomy,
stimulating directly onto the human brain
while they were having brain surgeries.
Yeah, yet you do know which part of your body
feel pain, right?
So there is a localization.
And then you know what kind of pain you feel.
Like it's pre-clean, or it's just a dull pain,
and all of these things.
So that seems you do require sensory cortex.
However, why is it that stimulating the sensory cortex
never evoke pain, right?
So pain must have another component.
So the only area in cortex that Pantheon stimulated
that evoke pain is part of the insula.
Okay, so when he stimulated the insula cortex,
the patients can, yeah, sometimes,
have a pain sensation.
Interesting.
In fact, pain has two components, right?
One is the sensory component.
The other is this emotional component.
I would argue without this emotional suffering component,
then it's not pain, it's just an intense sensation.
So my interest in pain, from touch perspective,
I feel like touch give you a location.
And also, it's sort of a train your system
have a fine discrimination, right?
So that help you to localize the pain,
and also help discriminate the pain,
and that help you to pay attention
to which part of your body are in pain.
Whereas there's a separate system
that encode emotional aspect.
So my work is trying to link both these aspects together
to derive a full understanding of pain.
And I think in case of chronic pain,
if you do chronic pain patient with functional MRI,
the somatosensory cortex is not so activated.
It's actually sort of seems to be amygdala,
insular or the other sort of emotional regions.
Limbic structure is, yeah.
So it's the persistence of this emotional reactivity
and some kind of an iterative process then
that just deeply encodes this.
And it's so hard then for folks to get out of it.
It's so hard.
And we don't really have effective medications for this.
No, opiates it's the same, right?
Unfortunately, it can cause dependence, addictions.
Can we go back?
You said something very interesting
and I suspect there are many scientists out there.
I know it really resonated with me,
which is you start out studying something very basic
and you do it for the pure knowledge of it.
And you end up through the pragmatics
of the grant system and the funding system.
And it's not unreasonable, the taxpayer pays for our work
for them to say, I want you to be doing something
that has pertinence and relevance to our health system.
That's, this is we, after all, we get our money
from the National Institute of Health.
But, and of course then that took you up
and became a passion too.
And I have to say, that's exactly parallel
to how my own career went.
But I do think it's important, right,
for people to understand that sometimes
you need to just study something
for the pure knowledge of it
without the specter of the funding engine
or the motivation of a disease model.
Because finding out how things work
in and of itself is important.
I completely agree.
That's why I'm, you know, I study the whisker system,
rodent whisker, they use whiskers as tactile sensors.
And I remember every time I publish something,
I tell my mother, she's in China, she's like,
why should I care, right?
But it was like, but I care,
I find it super interesting.
So I just like, I think I did it,
and I'm still doing it for the sake of curiosity.
And I find it a fascinating topic and system to study.
But I do understand scientists has also society duties.
Yeah, absolutely.
But I think, you know, even for touch, right?
You know, we still don't fully understand it, right?
I mean, I think robots are obviously,
these days the robots are become more and more fancier,
but they still are not as good as our human fingers, right?
Yeah, exactly.
Yeah, so I think part of that is
because we don't fully understand the sense of touch
and how we use it,
it's sort of in online feedback manner
to control our fingers.
Yeah, and developmentally too.
I mean, right, touch, correct me if I'm wrong,
I'm no expert in this,
but this is the first and most basic formative sense, right?
This is what an infant coming from the womb is,
you know, this somatic sensation and smell
and really, you know, and attachment to the mother
is very, very connected to touch.
And then our emotional health is very connected
to how touch impacts us across early development.
Absolutely, right?
There was a study in Romania that infants left,
you know, not be hugged, and they don't develop well,
some of them even die, right?
Yes, exactly.
So touch is absolutely essential.
And it also sets the boundary, right,
of yourself versus, you know, the rest of world.
So that's why I, you know, coming back to my interest
in understanding self is really,
it's the touch sensory receptors all over your body, right?
That give you a boundary, you are in this body.
Yeah.
And I think it's also really is the fundamental sense
for who you are and why you are in this body,
you embody this body, right?
Yeah, yeah, yeah.
Fantastic.
You mentioned your mom in China.
So let's talk about you.
You know, you grew up in China
and you studied in China early.
I have it on good authority
that you were very interested in science
very early in life.
Tell us about that.
Why did that passion develop?
Is it something from your family
or was it just curiosity?
I would say it's probably just curiosity.
And also part of that is I'm always a nerdy child.
So socially, I don't feel like I have lots of friends
or I get along with other kids.
But when I read scientific books
or when I'm just studying it, I'm totally in my element.
So honestly, I am always the number one student
from elementary school, middle school, high school,
and college.
So I'm just a sort of a nerd.
I think it's probably genetics.
I'm proud of it.
Yes.
So I know I'm always gonna be a scientist.
You did.
How early, I mean, could you quantify that?
How early are we talking about?
You know, as a...
As early as in middle school.
I just find that reading scientific books,
a lot of things I learn on my own.
So I'm just so interested in learning everything.
I find it more interesting than sort of a go out with friends.
It's very interesting.
So you really draw onto the science components
of schooling.
And then when it came to things like the humanities
and that, were you walking away from them
or did you bring them along with you at the same time?
Like your literature and...
I am good at tests.
In a Chinese system, you have to do well in tests
to rise to the top.
So that, but that's study, right?
I can study, I study humanity,
and all of that I have a really good memory.
I think in the Chinese education system,
if you have a good memory, you can do very well in tests.
So I think I probably just have a very good memory.
I memorize things very well.
I would not say I have a deep interest
in the sort of a literature or history.
I'm just more of a STEM.
Very, very interesting.
That's great.
So tell us then how, so you did your university in...
Yeah, Tsinghua.
Yeah, yeah, in Beijing.
In Beijing.
And then what brought you to the States?
How did that come about?
Or was that always the plan?
No.
So I would honestly say that I didn't think about
going abroad, but I got into Tsinghua in 1988 in the fall.
1989 is Tiananmen Square.
So I was on the ground on Tiananmen Square for two months.
Goodness me.
So that obviously in the end led to the crackdown and all that.
At that moment I felt like I need to leave here.
I felt like I do need a country that you can sort of
express and have some freedom, right?
And all that and democracy.
So the whole thing started as a democratic demonstration
and that turned out obviously, sadly.
And looking back at that time I just felt like
I need to get out of China.
It was too much of a dictatorship and that.
So that motivated me.
Then I studied English and did well in TOEFL and GRE.
And applied.
Applied those good test taking skills.
Yes, yes exactly.
And I'm also very lucky because at that time Columbia
sent a person to China to interview these applicants.
And I interviewed well so I got an offer from Columbia.
So I went to Columbia for my PhD.
And that's where you met Richard Axel
and it takes off from there.
Yeah.
And then your trajectory.
So you did your PhD at Columbia and then you were
a post-doc at Stanford, is that right?
Right, so Mark Tressie-Lavine is my mentor.
He was at UCSF so we started UCSF then moved to Stanford.
So I just simplified it as Stanford.
And a big chunk of your career at Duke University.
Yes, yes.
Somewhat warmer climbs.
17 years in Duke.
So you're quite some time now in the United States.
I really appreciate you getting into how politics
interface with your love of science
and coming to a free country.
I mean I'm an immigrant as well
and there's great attraction to America
especially for anybody interested in the sciences.
We won't go too deep into politics
but we must distress you a little bit
to see the politics of today and worry about
where freedom and the science engine is going.
It does worry me a little bit
but I've now taken more of a Zen approach.
I've decided whatever it is, it is.
We'll just deal with it.
We're back to philosophy.
Excellent, excellent, excellent.
Now there's a drug addiction component.
So how do we go from touch to pain to addiction?
I think we probably know a little bit
but tell us about that.
Yeah, so that again is actually a new project
after I moved to MIT.
And I at that time thought,
okay now I got this new fancy startup.
I want to really do something
even more helping the people and society.
So and as you said, this opioid pandemic,
what is opioid epidemic?
Sorry, my English sometimes is not very good.
No, that's perfectly fine.
So and I felt like it's because I study pain, right?
And then a lot of people become opioid dependent
because of opioid is the prescription drug
for treating chronic pain.
So I felt like it's my duty as a scientist
and to study this.
So it's a new direction
and I'm very fortunate to have recruited a postdoc
and I have two technicians working on it.
It's a difficult question to tackle in a way
when I was talking to donors
because this is not a nice funded.
I haven't had any prior publication in this area
therefore it's impossible to get.
Yeah, so I have to publish first.
So I was trying to talk to the donors
and then what I got is two responses.
First is why do you study this?
People can just stop taking the drugs.
If only that were true.
Yeah, they blame the people themselves.
Yeah, of course.
Okay, very sad.
And the second response is
there is National Institute of Drug Addiction, right?
NIDA has been there for 30 years.
If they haven't come up with anything,
what are you going to do?
That's so different.
Wow.
People have actually said that to you.
Amazing, amazing.
Yeah, it's a hard question.
I mean the first one obviously is easy to address, right?
A lot of times it's now their fault
and it's not as simple as they like of will, right?
It's really truly a disease.
Yes, absolutely.
And it's actually a brain-body disease.
It's not just here.
It's their entire physical physiology
is altered by the drug making it so hard
to overcome the addiction.
Now the second question I have sought very hard.
Yes, what am I going to do, right?
But you can almost ask the same question
for almost every area of research, right?
For pain.
Neuron and NIDA has been funding pain for also years.
So I thought, okay, I need to do something
maybe a little bit more unique, right?
A niche.
So the goal centered in the addiction field
is to develop an animal model
of self-administration of drugs, right?
So we developed this in mice,
which is somewhat harder than rat
because mouse has a very small vein.
You can put a casseter in and then hook up to a pump.
And when the mouse press a lever,
they will get intravenous infusion, right?
So we developed a model for cocaine self-administration
and fentanyl administration,
and then they work very nicely.
So what happens that hasn't been done
in these animal models
are in vivo monitoring of neural activities.
Right, right.
In these tasks.
So that's what I'm doing.
So we're doing a lot of obviously,
the obvious things is dopamine sensor,
fiber photometry in different regions.
But the more sophisticated ones are
multi-electro recordings
from multiple brain regions simultaneously.
It's the reason that it is hard
is the mouse is doing these tasks, right?
With all these hookups.
And if you have an electrode,
the mouse move around,
these two systems can tangle.
Sure, of course.
So the mouse stop doing it.
So you have to solve the technical issue.
So yeah, so but it's finally working.
Working in extraordinarily small spaces.
Yes, exactly.
With critters that don't necessarily
wanna just comply with what you have to do.
Let me ask you a question actually.
So this drug self-administration model
is very well known in the neurosciences.
Does every mouse self-administer
or is it a sub population?
Good question.
It's a spectrum, okay.
Some self-administer more,
some self-administer less.
So we're also trying to figure out.
Which of course goes right back to,
there's some mice who can help themselves
and there's others who can take it or leave it.
And if you're a person who can take it or leave it,
it can be hard to put yourself into the position
of somebody who just can't live without.
Exactly.
And we all need a little bit more compassion.
You started out talking about being a child
that maybe didn't socialize so much
and didn't worry so much about people
because you were concentrated on your science.
But one thing that's coming out loud and clear
is your compassion for the people
who are suffering out there.
And I think that's a really nice aspect
of the work that you're doing.
It's clear that human suffering is at the back end
of what you're trying to do.
Part of that is because as I growing up
and then become more mature
and then being in science field longer and longer,
I realized it's not about me, right?
Whatever I do, it's no fun if it's only about me,
my fame and my success.
I publish another paper.
And whatever I do is there's all these resources
and supports and then taxpayers' money
made me able to do what I want to do.
I felt like it's my turn.
I have to return some of those.
I think that's an absolutely fantastic sentiment.
Thank you for being here in Rochester
on this freezing cold day.
We really appreciate you.
Thank you for having me here.