Transcriber: Carlos Arturo Morales Reviewer: Denise RQ
We start in the future.
The year is 2034.
Alex has just come home.
It's his birthday, he turns 61 years old today.
He comes home and before he puts his keys into the door to open the door,
he remembers something.
He lets his arms dangle to his side for a moment.
No shaking, no resting tremor.
Moves his arms up and down.
No rigidity, no signs of Parkinson's disease.
He remembers when his mom was diagnosed with Parkinson's disease
when she was just 50 years old, much younger than he is today.
And he remembers her frustrations with simple tasks
like putting the keys in the door or even dressing herself.
He also remembers the day
that he found out that he, just like his mom,
carries a genetic mutation
that makes it more likely for him to get the disease.
Now, he shakes it off, opens the door, and goes inside
and a loud noise of "Surprise!" greets him
as his friends and family cheer and celebrate his birthday.
His wife hands him a glass of champagne and everyone raises a toast,
"To Alex!"
He smiles to himself.
Another year gone, and no sign of Parkinson's disease.
The drugs are working.
He secretly raises a toast to the warriors, the champions,
who changed his fate.
Now, let's rewind, ten years.
The year is 2024.
The new Parkinson's disease drug has just received FDA approval
after showing great promise in clinical trials.
Not just in masking the symptoms of the disease, like the previous drugs,
but actually stopping the progressive degeneration.
This drug is nothing short of a miracle taking less than ten years;
usually, the time line of drug development is long, over 15 years,
and even then, a very high failure rate.
This time, it was much faster.
This time, there were tools that predicted interactions and successes
and avoided a sea of failed studies and negative data.
Alex is still asymptomatic, but brain scans show
there's already some degeneration in his brain.
He starts treatment immediately to avoid further damage.
Let's keep rewinding.
The year is 2014.
I stand here in front of you,
and I tell you about two progressive and debilitating brain diseases:
Parkinson's disease and Alzheimer's disease.
I tell you that this is what happens to your brain in Alzheimer's disease.
And I ask you: what would you do to keep your brain from this fate?
How much would you pay
to save your most precious memories,
your cognition, your identity?
What about Parkinson's disease?
What would you pay
to keep enough motor control, to dress yourself, feed yourself,
even go to the bathroom by yourself?
And I tell you that as life expectancy grows,
we will be faced with a dramatically higher number
of both of these diseases with no cure.
But there is hope.
I tell you that we are warriors,
conquerors fighting these inhumane diseases.
I tell you of revolutionary advances in the field of neuroscience
and that we are on the verge of powerful, new tools like neurostimulation.
This tool uses video game technology
to create a model of what happens inside an individual neuron or brain cell.
It allows us to put together the pieces of the puzzle
and make our brains healthier
which I think it's an idea worth spreading.
Alex is here tonight.
He hears this talk and joins the warriors.
He decides to live better, learn more,
and use his skills set to contribute to research.
While we're here already, let's keep rewinding.
The year is 2004.
Scientists have just discovered a mutation in a gene called LRRK2.
This genetic mutation significantly increases
a person's likelihood of getting Parkinson's disease.
Meanwhile, Alex is with his mom at the hospital,
watching as the neurologist performs motor tests
and trying to come to grip with his mom's Parkinson's disease,
helpless.
Neither he nor his mom have any idea
that they both carry this newly discovered genetic mutation.
2004 was also the first year
that I attended the Society for Neuroscience Meeting.
I have just started my research on Parkinson's disease,
and I had my first piece of data in hand.
I was so excited
because I actually found something that no one else knew before.
Not like researching on Google.
Actually finding something that no one knew.
(Laughter)
It was like nature had whispered
a little secret to me that I could tell the world.
It was addictive.
And when I went to this meeting,
I saw 25,000 other neuroscientists and trainees
who were just as giddy and excited about the brain as I was.
Each of them unlocking the 'hows' of the brain and the nervous system.
How this fantastic system allows us to think,
to learn, remember, to feel emotions,
even see, hear, and move our bodies.
If you had gone there, you would have, no doubt, seen a lot of nerds.
And we are quite proudly nerds.
But I knew, standing there, at that moment in time,
that we are warriors, explorers,
we boldly go where no one has gone before.
We are people who develop and utilize new tools and techniques
so that we can explore the unknown,
rethink what we already know,
and reshape the fate of future generations.
Look at the people next to you.
You are one of the six people directly adjacent to you
who'll get Alzheimer's disease.
And while it looks bleak today, there is a bright future waiting us.
But we must be diligent and there's no time to waste.
Every single one of you has the skills set,
a weapon that can be used in this fight.
If you are here,
if you are interested in ideas worth spreading,
If you are curious enough, motivated enough,
and spending your free time listening to TED talks,
I have news for you,
you are already one of us, you are a warrior.
So unsheathe your weapons and stand with us
because every action that we take now,
will transform the fate of future generations.
For people like Alex, for people like you and me.
Now, before I tell you my second story, I want to ask you a question:
raise your hand if you would want to know if you have one of these genetic mutations
that increases your risk for Alzheimer's or Parkinson's diseases.
Oh, that's good!
Keep on mind there's no cure still.
If you raised your hand, it's actually quite inexpensive,
only about a hundred dollars and very quick,
to get tested for this genetic mutations.
If you didn't raise your hand, I guess that's something
that we each have to decide for ourselves,
but I tend to think that knowledge is always good,
that by knowing our genetic risk,
we can change our environments and our lifestyle factors.
We can contribute to organizations like the Michael J. Fox Foundation
for Parkinson's or an Alzheimer's association.
You have the power then, to reshape your own future.
Now, for my second story.
This story is about one tiny little neuron
inside the brain of someone with Alzheimer's or Parkinson's disease.
You can't see it,
it's embedded deep inside the brain and protected by a very thick skull.
And contrary to what you may have seen
in the movies, on TV, or even in this animation,
we don't have any tools to be able to see this type of resolution,
individual neurons in the brain.
Let alone the molecules inside of these neurons.
We can do a couple of things: we can take one of these neurons,
stick it in the petri dish and look at it under microscope on the laboratory.
It's very cool.
We can even tag different types of molecules,
and we can see them move and change.
But we miss everything else, we only see what we tag.
Another thing we can do is we can take these neurons,
and we can look at a whole bunch of different things.
We can look at the concentrations of molecules inside them,
the way they move, where they are located, their interactions.
But we can only see it for one point in time
because once we take that neuron for analysis, it's dead,
we can't use it anymore.
This is a huge limitation because the brain doesn't look like this.
The neurons are no static, they're incredibly dynamic,
moving, changing every millisecond.
Now, I know the neuron can be intimidating.
I'm now going to show you any pictures.
I just want you to imagine with me for a second.
I think neurons are so intimidating because they're so tiny.
Let's imagine that this tiny little neuron that we're talking about today,
the one in the brain of someone with Alzheimer's or Parkinson's disease
is actually really big.
Let's say it's the size of our city.
Neuron is actually a lot like a city.
Just like there are different types of people
in the city that make it function,
there are different types of molecules inside a neuron that make it function.
Some give it energy, others transport things back and forth,
kind of like a metro system or a railroad system.
Others are border patrols controlling what goes in and out of the neuron.
And others are neurotransmitters, they go between the neurons
and that's how your neurons communicate.
Now, that's a normal neuron.
But what happens in this particular neuron?
It's not normal,
it's inside someone's brain with Alzheimer's or Parkinson's disease,
it's being damaged.
You actually all know the story already,
and this is where it gets really interesting.
If we go back to our city analogy, this is a city that's under attack.
Whether it's Independence Day, or World War Z,
what happens when a city is under attack?
"Mayday, mayday, we have a problem, we are under attack, do you copy?"
All you get from the other side is hiss-hiss.
Maybe a couple of broken words here and there.
Because chances are other cities are under attack too.
That's exactly what we see in our neurons.
They stop communicating efficiently with each other.
What else happens in a city under attack? Widespread panic.
People are running and screaming with their arms up in the air.
I know you can picture it. That's exactly what happens in our neuron.
In a normal neuron, molecules are somewhat predictable,
you know where they might be at a given time
or what they might be doing.
But when it gets damaged,
it's like they were not the same old molecules we use to know,
they go places and do things they wouldn't do,
and the damage begets more damage.
Speaking of damage, that's something else you see in a city under attack:
piles of rubble, pieces of broken buildings, cars,
dead bodies clumped together.
And that's what we see in our neuron too:
we see clumps of aggregated, damaged molecules.
In Parkinson's disease, we have Lewy bodies,
in Alzheimer's disease, we have tangles and plaques.
And don't forget that in the midst of all of this crazy chaos,
we are trying to figure out what's actually killing the cell.
In the movies, it's easy,
it's a giant green monster running around - a green villain always seems to be -
but in our neuron, it seems to be different.
There's no Godzilla.
It seems that a variety of different factors contribute.
For example, if you work with toxins like pesticides
that can increase your risk for Parkinson's disease.
Your life style factors:
I guess it shouldn't come as a surprise
that exercise decreases your risk for both diseases.
A Mediterranean diet decreases your risk for Alzheimer's disease.
And, of course, genetic variation, like the one that Alex and his mom have.
And more, and more of these genetic variations
are being discovered every day.
But what we're still missing and what we need is a tool to put together
these genetic and environmental factors,
and explain to us how they affect the neuron.
And we need a tool that is just as dynamic and changeable as the neuron is,
and we need this tool now
because so far, in this story, the story of the neuron in the brain
of someone with Alzheimer's or Parkinson's disease,
there are no survivors.
The neurons stop communicating with each other, retract their processes,
shrivel up and die.
Our cities, wiped out.
I don't know about you, but I hate this story.
I like the stories where the good guys win at the end.
That is why our team is working on computer simulations of neurons,
so that we can actually zoom in
and see the interactions that are happening inside the neuron.
So we can see those interactions, manipulate them,
and then ask what happens?
What happens when we apply a drug to this dying neuron?
Can we then save this neuron from dying?
And yes, it'll still have to be replicated
inside the clinic and in the laboratory first.
But now, we can go in with a lot more knowledge of the interactions,
setting ourselves up for success
and shortening that timeline of drug development.
You know, every time a revolutionary new tool is developed,
it can push us forward faster that we could imagine using old tools.
I would probably still be looking for this building
if I didn't have a GPS in my back pocket.
For those of you who know me, that's sad, but true.
But in all seriousness, if we wiped out Alzheimer's and Parkinson's disease today,
we would save 500,000 lives this year alone.
This year alone.
So, stand with us because we are all in this fight together,
all over the planet.
Because we'll not succumb to the darkness
that robs us of our identity, memory, and control.
We will not weather away with our fight, we will not surrender, not on my watch.
I'm a warrior and you, all of us, we are all in this fight together.
Our time is now and we will prevail.
Thank you.
(Applause)