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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
by millions of kids every day.

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(Laughter)

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But the reason why

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is that they're designed
in a very clever way.

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They're made out of 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

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and see all the tiny building blocks,
the biomolecules,

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how they're organized in three dimensions,

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the structure, the ground truth
structure of the brain, if you will?

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If we could get that,

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maybe we could have a better understanding
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
a different point of view

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from the way 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,

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the brain is incredibly,
incredibly complicated.

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So what we've learned
over the first century of neuroscience

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is that the brain 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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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 in to a neuron,

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and, of course, this is just
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
organized in complex, 3D patterns,

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and together they mediate
those electrical pulses,

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those chemical exchanges
that allow neurons to work together

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to generate things like thoughts
and feelings 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,

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and we don't know how
the biomolecules are organized

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within neurons

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to form 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 noninvasive,

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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 voxels, 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

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where it can pinpoint
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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Microscopes, of course, will use light
to look at little tiny things.

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For centuries, they've been used
to look at things like bacteria.

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For neuroscience,

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microscopes are actually 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 the ground truth structure,

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we're going to need to have
even better technologies.

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My group, a couple years ago,
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 in to the brain,

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why can't we make the brain bigger?

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It initially started

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with two grad students in my group,
Fei Chen and Paul Tillberg.

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Now many others in my group
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 in 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 can potentially blow the brain up

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to where you could distinguish
those tiny biomolecules from each other.

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You would see those connections
and get maps of the brain.

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This could potentially be quite dramatic.

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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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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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What we're going to do

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is see if this teaspoon
of the baby diaper material

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can increase in size.

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You're going to see it increase in volume
by about a thousandfold

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before your very eyes.

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I could pour much more of this in there,

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but I think you've got the idea

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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

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in a way that you can't do
with past technologies.

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OK. 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
arranged in long, thin lines.

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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

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that are around the size of a biomolecule.

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This is very good

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because we could potentially
move everything 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 will move
apart from each other,

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and the entire material
is going to become bigger.

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And because these chains are so tiny

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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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Here's the mystery, then:

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How do we actually make
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,

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maybe we could get
ground truth 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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To explain this, we made some animations

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where we actually look
at, in these artist renderings,

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what biomolecules might look
like 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 attach every biomolecule,
shown in brown here,

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to 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

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that allows 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 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
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

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from each other.

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And every time one
of those little handles is around,

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the polymer will bind to the handle,
and that's exactly what we need

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in order to pull the molecules
apart 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
will 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,

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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
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

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until they're like constellations
of information about life.

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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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We've infused the polymer in,

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and now we're adding water.

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What you'll see 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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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 could 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,

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the actual problems in the brain
at a molecular level.

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What if we could actually
look into cells in the brain

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and figure out, wow, 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 that 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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It turns out that if you look at cancers,

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if you look at the immune system,

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if you look at aging,
if you look at development --

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all these processes 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 a high-risk moon shot

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into something that's more reliable.

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If you think about the original moon shot,

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where they actually landed on the moon,

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it was based on 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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I would argue that with technologies

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like the kinds 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 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, if we can
turn biology and medicine

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from these high-risk endeavors
that are governed by chance and luck,

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and 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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Thank you very much.

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(Applause)