Translator: Jaegun Lee Reviewer: Arvind Patil
My beloved grandmother passed away earlier this year on February 28th
after suffering for a very long time from a stroke.
One day, she collapsed.
A few days later she woke up in the hospital
to find herself completely paralyzed on the right side of her body.
It was just a small little vessel that burst inside her head,
but it had a life-altering implication for her
where now she could no longer move her own body.
For the next three-and-a-half years she was hospitalized,
and went through extensive rehabilitation therapy,
at the end of which she could barely walk
on her own with an extensive help of a walker.
Then, she returned home and stayed bed-bound for another eight years
before she passed away this year.
Watching her suffer through this very painful and devastating disease,
the most difficult thing, the most painful thing for me,
was the fact that there was nothing that any of us could do
to give her back what she had lost
when the small blood vessel burst in her head
so that she can have control over her own body again.
When we have a device broken, like a computer or a cellphone,
what do we do?
Do we just put it on a place, comfortable somewhere,
and just press the button repeatedly until maybe it starts working again?
Well, yes, I sometimes do that.
But if we really want it fixed, that's not what we should do.
When we have a device broken, what we do is we directly go in.
If there is a broken software, we reprogram it.
If there is a broken wire, we rewire it.
If there is a worn out or broken part, we replace it.
The question is: Can we do something like this for our own brains?
There are many different forms of brain diseases.
Some of which includes the following.
It includes stroke, where your blood vessel bursts and damages your brain.
There's also a disease called epilepsy,
where you suddenly have uncontrollable activity
that happens inside your brain without any warning,
where you are no longer able to control yourself.
And this seems like a very foreign concept to most of us,
but this is something that can happen to any of you
by simply hitting your head in the wrong place at the wrong time.
Another important brain disease, psychiatric disease,
includes depression, where you feel hopelessness and sadness.
There is also a form called autism,
where children find it difficult to relate to other people.
And there's also a category of neurodegenerative diseases,
which includes Parkinson's and Alzheimer's disease,
where in the Parkinson's disease case
you start to tremor and you can no longer control your body movements,
and in the case of Alzheimer's disease,
you have memory loss, where ultimately you forget even who you are.
While there are these many forms of neurological diseases,
there is one thing that is common to all of these.
Despite the increasing prevalence and cost,
there is one common thing which is that there is absolutely no cure.
You see all of these numbers on the screen?
These are very, very large numbers.
For example, in the Alzheimer's disease case,
we are expected to spend about 1.1 trillion dollars by 2050
on treating Alzheimer's disease
if we go at the current rate where we can't cure anything
and we just keep providing support.
This is over 6% of the US GDP.
This is not a sustainable number.
In addition to the fact that we have the need to treat our loved ones,
we also need to have a solution for this
in order to not get completely bankrupt by our need to treat our patients.
So the question is: Why do we not know how to treat any of these diseases?
The answer to that boils down to this one question:
How does the brain work?
Does anybody have an answer to that?
Unfortunately, none of us do.
And so because we do not know how the brain works,
the task of trying to fix it becomes impossible.
Well, it's too early to give up.
Let's think about what we know and what we can do
to perhaps fix this situation.
First thing that we know about the brain
is the fact that it consists of this unit called the neurons.
This is a very special kind of cell.
It has inputs that come in with a signal through what's called the dendrites.
And these inputs are processed inside the cell,
where it produces an output, an electrical signal in a digital form,
what's called an action potential,
that is sent throughout the axon to send this message to the next neuron.
It's a little device that does this simple processing.
And many of these neurons are put together in our brain
forming a brain circuit.
And this brain circuit does dynamic electrical signaling
to control all of the things that we do, all of our behaviors.
So, then the task is pretty simple now.
What we need to do is to understand
how exactly these neuronal circuits work to elicit our behaviors
and perhaps fix it when it goes wrong.
As easy as that sounds, it's actually quite complicated.
There is a very good reason why we do not have a solution to this.
Let's look at some of these reasons.
Some of these reasons are quite obvious.
One is the fact that our brain is surrounded by a skull.
This is there to protect our brain.
But for those of us who are trying to figure out what's going on inside,
it makes it extremely difficult.
All of our fancy microscopic imaging tools cannot be really used to look inside
because of the fact that it's surrounded by the skull.
Once you go inside the skull you have an even greater problem,
which is that it has extreme complexity.
The number of neurons inside your brain are about a hundred billion.
To give you an idea of what a hundred billion means,
you can think of the world's population.
A hundred billion is an order of magnitude larger than the whole world's population.
We talk about big data, network of all of these different people,
but in fact we have something that's much more complex sitting inside our skull.
On top of that, I told you about a neuron,
but there are also many different kinds of neurons.
They're not all the same. They do different things.
And they are densely intermingled inside your brain,
where you can't really say
this part of your brain has this type of neuron,
and the other part has another kind of neuron.
To make matters worse on top of that,
every one of your neurons,
they don't just talk to neighbors surrounding them,
they have connections going all the way to different sides of the brain,
making very large-scale connections,
which means that if you just go in and look at one part of your brain,
there is no way to understand what this neuron is doing.
And so all of this combined,
it makes the task of understanding how the brain works extremely difficult.
However, given this situation,
we need to start thinking about how we might fix this situation
of understanding this brain.
If you want to understand a complex system,
there are many different approaches.
But let's think of two different ones.
Let's say I gave you a new device that was given to you on your hand.
Let's say this is a cell phone.
One way you can try to figure out what this device is,
is to sit there and passively observe what happens.
Depending on whose cell phone I gave you,
you might sit there for hours and nothing happens,
and conclude that it's actually a clock.
A much better way to try and understand
and get meaningful information out of a system
is to try and play with them.
Press the button, give it input, and see what happens.
Even if this is a cell phone that never receives any calls,
if you press a button and see what happens,
you will know that it makes calls and that it is a cell phone.
So to do something like that for the brain,
what we need to be able to do,
is to provide test inputs to specific parts of the brain circuit
and measure its dynamic activity across this whole intact system.
So, to do this task, what do we need?
We need two components.
One is to be able to stimulate every circuit elements with high specificity.
I just told you earlier that the circuit consists of many different types of cells,
and that they communicate with electrical signal.
If you put an electrode
- that's one strategy that you can use to perturb the system -
and put an input into this brain.
But because there are many different cell types,
it is very difficult to decipher what that means.
For example, if you are trying to figure out
the volume up and down button on your cell phone,
if you press both buttons at the same time, what would you see?
It might not do anything.
It might go up, it might go down.
You'll be very confused as to what this button does.
What you need to be able to do is to press these buttons separately
and see that one button increases volume,
the other one decreases the volume,
which gives you a clear idea of what that does.
And so to have something similar for the brain,
there is a novel technology that allows us to do that called optogenetics.
What this does is genetically engineer the cells inside the brain
so that only a specific cell type, only the volume up button,
responds to light upon stimulation.
That way, now we have a tool
to specifically press a button in our brain
so that we might understand what it does.
To give you an example of what this means,
we'll look at an experiment
where we stimulate two different types of neurons
that are placed in the same location within the brain.
These are called medium spiny neurons.
One is a D1 receptor type, the other is a D2 receptor type,
but these two neurons are placed in the same location,
and have very important implications for things like Parkinson's disease.
And what this does is, upon stimulation,
even though these are neurons in the same location,
when you stimulate one of the neurons on the left side,
you will see that the mouse starts to rotate in the clockwise direction,
and generally increases activity.
And in the other case,
you will see that the mouse starts rotating in the opposite direction,
and it will stay generally still,
where you might even think that the video has stalled but it actually hasn't.
And so these are two different cell types, exactly in the same location,
but because we have this new genetic tool, we could manipulate them separately,
have volume up and down buttons separately
so that we might understand what this does.
That's great!
We have one problem solved
of being able to specifically manipulate important buttons of the brain.
Next, what we need is to be able to read out what is happening inside the circuit.
We want to press this button and see what happens in the overall system.
To do that, we combine this optogenetics stimulation technology
with the functional MRI methods,
where we can now selectively control specific cell types
with temporal precision in a live subject.
You want to monitor this in a live brain
- once you take out the tissue it doesn't do what it was designed to do -
and monitor its brain wave activity responses.
And so here is an example of an experiment
where we can now stimulate -
You see the blue line in the image there?
This is where we specifically target a set of neurons
that are called excitatory neurons of the hippocampus.
This is a very special area of the brain
that is implicated in Alzheimer's disease and epilepsy
and other important neurological disease.
And now by stimulating them specifically and monitoring what happens throughout -
these are brain images from the front to the back of the brain,
all the way throughout.
And you can now see what happens in every part of the brain
as a result of provoking this particular type of neuron.
What this means for us is that now we have tools
to start and investigate, see,
have access to the data of what goes on inside the brain.
What this means is that we now can perhaps open
a new era of neuro- information technology.
We no longer have to wonder about: What is it that the brain does?
Is this a property of the brain? Is that the property?
Instead, we can have direct access to the information there.
Where in the case of diseases,
we might attempt to directly restore what has gone wrong inside the brain.
One of the most promising therapies that are being tested right now,
and some are being used in the clinic for brain disease,
is called neurostimulation therapy.
Because the brain is an electrical circuit,
by putting an electrode inside the brain and disrupting the erroneous signal,
we attempt to get rid of the symptoms,
such as tremoring in the Parkinson's disease,
and restore its normal function.
The keyword here is "disrupt."
We call it disrupt because we really don't know what we're doing.
It was doing something that we didn't like.
We put it there and zapped it,
and somehow it gave us a desirable result - sometimes.
But now that we have access to information directly inside the brain.
What this means is that, instead of disrupting,
we can reprogram what our brain can do.
On top of that,
if the damage was more extensive, where you actually need to replace parts,
which is what stem cell therapy promises us,
despite the fact that we have the powerful stem cell therapy option,
one of the reasons why we could not make progress
in treating brain disease with the stem cell therapy
was the fact that there was no way to know exactly
what it does once it enters the brain.
And by having programmable stem cells
that we can put in and look at with access to all the information,
we might be able to also enter an era where we can replace parts.
And so with all of these technologies
that allows us to get into the realm of neuro-information technology,
we might be able to open a new era
where we no longer need to be frustrated
with our inability to control our own brains.
Beyond being able to fix diseases,
the future of being able to have access to neurological information and data
promises much more than just treating diseases.
This is one of my favorite scenes from the movie "Avatar"
where you have the human brain and the avatar brain that is being synced up.
In this particular scene, the syncing is 40.665% complete.
This is just a fantasy, a movie, for us right now,
but by having the ability to access your neurological information,
the power of what we can do with that is limitless.
It deeply saddens me to think about the fact that
I could not help my grandmother in the time of her desperate need.
However, it is my hope and dream
that she will live on in our memory
as we make bold and brave steps towards this new era of information technology.
Thank you very much.
(Applause)