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Hello everybody.
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I brought with me today a baby diaper.
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You'll see why in a second.
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Baby diapers have interesting properties.
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They can swell enormously
when you add water to them,
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an experiment done
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by millions of kids every day.
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(Laughter)
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But the reason why is that they're
designed in a very clever way.
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They're made out oaf a thing
called a swellable material.
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It's a special kind of material that,
when you add water,
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it will swell up enormously,
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maybe a thousand times in volume.
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And this is a very useful,
industrial kind of polymer.
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But what we're trying to do
in my group at MIT
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is to figure out if we can do
something similar to the brain.
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Can we make it bigger,
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big enough that you can
peer inside and see
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all the tiny building blocks,
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the biomolecules, how they're organized
in three dimensions,
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the structure, the [??]
structure of the brain, if you will?
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If we could get that, maybe
we could have a better understanding
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of how the brain is organized
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to yield thoughts and emotions
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and actions and sensations.
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Maybe we could try to pinpoint
the exact changes in the brain
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that result in diseases,
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diseases like Alzheimer's
and epilepsy and Parkinson's,
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for which there are few treatments,
much less cures,
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and for which very often we don't know
the cause or the origins
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and what's really causing them to occur.
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Now, our group at MIT
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is trying to take sort of
a different point of view
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from the way that neuroscience has
been done over the last hundred years.
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We're designers. We're inventors.
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We're trying to figure out how
to build technologies
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that let us look at and repair the brain.
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And the reason is, the brain
is incredibly, incredibly complicated.
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So what we learned over the first
century of neuroscience is that the brain
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is a very complicated network
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made out of very specialized cells
called neurons
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with very complex geometries,
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and electrical currents will flow
through these complexly shaped neurons.
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Furthermore, neurons
are connected in networks.
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They're connected by little junctions
called synapses that exchange chemicals
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and allow the neurons
to talk to each other.
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Now, the density
of the brain is incredible.
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In a cubic millimeter of your brain,
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there are about 100,000 of these neurons
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and maybe a billion of those connections.
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But it's worse.
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So, if you could zoom into a neuron,
and of course this is just
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our artist's rendition of it,
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what you would see are thousands
and thousands of kinds of biomolecules,
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little nanoscale machines that are
organized in complex, 3D patterns,
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and together they mediate
those electrical pulses,
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those chemical exchanges
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that allow neurons to work together
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to generate things
like thoughts and feelings
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and so forth.
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Now, we don't know how
the neurons in the brain are organized
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to form networks, and we don't know
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how the biomolecules are organized
within neurons to form
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these complex, organized machines.
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If we really want to understand this,
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we're going to need new technologies.
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But if we could get such maps,
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if we could look at the organization
of molecules and neurons
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and neurons and networks,
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maybe we could really understand
how the brain conducts information
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from sensory regions,
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mixes it with emotion and feeling,
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and generates our decisions and actions.
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Maybe we could pinpoint the exact set
of molecular changes that occur
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in a brain disorder,
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and once we know how
those molecules have changed,
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whether they've increased in number
or changed in pattern,
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we could use those as targets
for new drugs,
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for new ways of delivering
energy into the brain
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in order to repair the brain
computations that are afflicted
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in patients who suffer
from brain disorders.
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We've all seen lots of different
technologies over the last century
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to try to confront this.
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I think we've all seen brain scans
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taken using MRI machines.
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These, of course, have the great power
that they are non-invasive,
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they can be used on living human subjects,
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but also they're spatially crude.
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Each of these blobs that you see,
or [??] as they're called,
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can contain millions
and millions of neurons.
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So it's not at the level of resolution
where we can pinpoint
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the molecular changes that occur
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or the changes in the wiring
of these networks
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that contributes to our ability
to be conscious and powerful beings.
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At the other extreme,
you have microscopes.
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So microscopes, of course, we use light
to look at little tiny things,
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and for centuries they've been used
to look at things like bacteria.
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For neuroscience, microscopes are actually
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how neurons were discovered
in the first place,
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about 130 years ago,
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but light is fundamentally limited.
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You can't see individual molecules
with a regular old microscope.
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You can't look at these tiny connections.
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So if we want to make our ability
to see the brain more powerful,
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to get down to that [??] structure,
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we're going to need to have
even better technologies.
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So my group, a couple years ago,
we started thinking,
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why don't we do the opposite?
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If it's so darn complicated
to zoom into the brain,
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why can't we make the brain bigger?
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Initially started with two
graduate students in my group,
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[??],
and now many others in my group
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are helping with this process,
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we decided to try to figure out
if we could take polymers
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like the stuff from the baby diaper
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and install it physically within the brain.
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If we could do it just right,
and you add water,
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you could potentially blow the brain up
to the point where you could actually
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distinguish those tiny biomolecules
from each other.
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You could see those connections
and get maps of the brain.
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This could potentially be quite dramatic,
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and so we brought a little demo here.
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We got some purified baby diaper material.
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It's much easier just to buy it
off the Internet
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than to extract the few grains
that actually occur in these diapers.
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And I'm going to put
just one teaspoon here
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of this purified polymer.
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And here we have some water,
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and what we're going to do is see
if this teaspoon of the baby diaper
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material can increase in size.
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And what you're going to see it's going
to increase in volume
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by about a thousandfold
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before your very eyes.
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So I could go and pour much more
of this in there,
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but I think you've gotten the idea there,
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that this is a very,
very interesting molecule,
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and if can use it in the right way,
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we might be able to really zoom in
on the brain in a way
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that you can't do with past technologies.
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Okay. So a little bit of chemistry now.
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What's going on
in the baby diaper polymer?
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If you could zoom in,
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it might look something like
what you see on the screen.
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Polymers are chains of atoms
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arranged in long, thin lines,
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and the chains are very tiny,
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about the width of a biomolecule,
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and these polymers are really dense.
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They're separated by distances that are
around the size of a biomolecule.
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So this is very good, because
we could potentially move everything
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apart in the brain.
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If we add water, what will happen is,
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this swellable material is going
to absorb the water,
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the polymer chains are going
to move apart from each other,
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and the entire material
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is going to become bigger.
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And because these chains are so tiny,
and spaced by biomolecular distances,
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we could potentially blow up the brain
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and make it big enough to see.
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So here's the mystery though:
how do we actually make
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these polymer chains inside the brain
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so we can move
all the biomolecules apart?
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If we could do that, maybe we could
get these [??] maps of the brain.
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We could look at the wiring.
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We can peer inside
and see the molecules within.
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So to explain this, we made
some animations where we actually
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look at, in these artists renderings,
what biomolecules might look like
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and how we might separate them.
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Step one: what we'd have to do
first of all
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is to attach to every biomolecule
shown in brown here
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a little anchor, a little handle.
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We need to pull the molecules
of the brain apart from each other,
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and to do that we need to have
a little handle that allows
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those polymers to bind to them
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and to exert their force.
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Now, if you just take
baby diaper polymer
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and dump it on the brain,
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obviously it's going to sit there on top,
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so we need to find a way
to make the polymers inside,
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and this is where we're really lucky.
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It turns out, you can actually
get the building blocks,
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monomers, as they're called,
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and if you let them go into the brain
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and then trigger the chemical reactions,
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you can get them to form those long chains
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right there inside the brain tissue.
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They're going to wind their way
around biomolecules,
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and between biomolecules,
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forming those complex webs
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that will allow you, eventually, to pull
apart the molecules from each other.
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And every time that one
of those little handles is around,
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the polymer is going to bind to the handle
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and that's exactly what we need in order
to pull the molecules apart
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from each other.
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All right, the moment of truth.
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We have to treat this specimen
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with a chemical to kind of loosen up
all the molecules from each other,
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and then, when we add water,
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that swellable material is going
to start absorbing the water,
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the polymer chains will move apart,
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but now, the biomolecules
are going to come along for the ride,
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and much like drawing
a picture on a balloon,
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and then you blow up the balloon,
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the image is the same,
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but the ink particles have moved
away from each other.
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And that's what we've been able
to do now, but in three dimensions.
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There's one last trick.
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As you can see here, we've color-coded
all the biomolecules brown.
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That's because they all
kind of look the same.
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Biomolecules are made
out of the same atoms,
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but just in different orders.
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So we need one last thing
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in order to make them visible.
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We have to bring in little tags
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with glowing dyes
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that will distinguish them.
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So one kind of biomolecule
might get a blue color.
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Another kind of biomolecule
might get a red color.
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And so forth.
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And that's the final step.
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Now we can look at something
like a brain,
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and look at the individual molecules,
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because we've moved them
far apart enough from each other
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that we can tell them apart.
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So the hope here is that we
can make the invisible visible.
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We can turn things that might seem
small and obscure
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and blow them up until they're
constellations of information about life.
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And so here's an actual video
of what it might look like.
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We have here a little brain in a dish,
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a little piece of a brain actually,
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and we've infused the polymer in,
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and now we're adding water.
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And what you're going to see
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is that right before your eyes --
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this video is sped up
about sixtyfold --
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this little piece of brain tissue
is going to grow.
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And it can increase by a hundredfold
or even more in volume.
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And the cool part is, because
those polymers are so tiny,
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we're separating biomolecules
evenly from each other.
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It's a smooth expansion.
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We're not losing the configuration
of the information.
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We're just making it easier to see.
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So now we can take actual brain circuitry.
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Here's a piece of the brain
involved with, for example, memory,
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and we can zoom in.
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We can start to actually look at
how circuits are configured.
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Maybe someday we could
read out a memory.
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Maybe we actually look at how
circuits are configured
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to process emotions,
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how the actual wiring
of our brain is organized
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in order to make us who we are.
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And of course, we can pinpoint,
hopefully, the actual problems
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in the brain at a molecular level.
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What if we could actually look into
cells in the brain and figure out, wow,
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here are the 17 molecules
that have altered
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in this brain tissue that has been
undergoing epilepsy
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or changing in Parkinson's disease
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or otherwise being altered.
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If we get that systematic list
of things that are going wrong,
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those become our therapeutic targets.
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We can build drugs to bind those.
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We can maybe aim energy
at different parts of the brain
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in order to help people
with Parkinson's or epilepsy
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or other conditions that affect
over a billion people
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around the world.
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Now, something interesting
has been happening.
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It turns out that throughout biomedicine,
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there are other problems
that expansion might help with.
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This is an actual biopsy
from a human breast cancer patient.
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And it turns out that
if you look at cancers,
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if you look at the immune systems,
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if you look at aging,
if you look at development,
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all these processes
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are involving large scale
biological systems,
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but of course the problems begin
with those little nanoscale molecules,
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the machines that make the cells
and the organs in our body tick.
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So what we're trying to do now
is to figure out
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if we can actually use this technology
to map the building blocks of life
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in a wide variety of diseases.
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Can we actually pinpoint
the molecular changes in a tumor
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so that we can actually go after it
in a smart way
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and deliver drugs that might wipe out
exactly the cells that we want to?
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You know, a lot of medicine
is very high risk.
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Sometimes, it's even guesswork.
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My hope is we can actually turn
what might be, like, a high-risk moonshot
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into something that's more reliable.
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If you think about the original moonshot,
where they actually landed on the moon,
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it was based on really solid science.
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We understood gravity.
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We understood aerodynamics.
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We knew how to build rockets.
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The science risk was under control.
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It was still a great, great
feat of engineering,
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but in medicine, we don't necessarily
have all the laws.
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Do we have all the laws
that are analogous to gravity,
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that are analogous to aerodynamics?
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And I would argue that with technologies
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like the kinds that I'm
talking about today,
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maybe we can actually derive those.
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We can map the patterns
that occur in living systems
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and to figure out how to overcome
the diseases that plague us.
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You know, my wife and I
have two young kids,
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and one of my hopes as a bioengineer
is to make life better for them
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than it currently is for us.
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And my hope is, you know,
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if we can turn biology and medicine
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from these high-risk endeavors
that are governed by chance and by luck,
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and we can make them things
that we win by skill and hard work,
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then that would be a great advance.
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So thank you very much.
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(Applause)