On June 12, 2014, precisely at 3:33 in a balmy winter afternoon in São Paulo, Brazil, a typical South American winter afternoon, this kid, this young man that you see celebrating here like he had scored a goal, Juliano Pinto, 29 years old, accomplished a magnificent deed.
Despite being paralyzed and not having any sensation from mid-chest to the tip of his toes as the result of a car crash six years ago that killed his brother and produced a complete spinal cord lesion that left Juliano in a wheelchair, Juliano rose to the occasion, and on this day did something that pretty much everybody that saw him in the six years deemed impossible.
Juliano Pinto delivered the opening kick of the 2014 Brazilian World Soccer Cup here just by thinking.
He could not move his body, but he could imagine the movements needed to kick a ball.
He was an athlete before the lesion.
He's a para-athlete right now.
He's going to be in the Paralympic Games, I hope, in a couple years.
But what the spinal cord lesion did not rob from Juliano was his ability to dream.
And dream he did that afternoon, for a stadium of about 75,000 people and an audience of close to a billion watching on TV.
And that kick crowned, basically, 30 years of basic research studying how the brain, how this amazing universe that we have between our ears that is only comparable to universe that we have above our head because it has about 100 billion elements talking to each other through electrical brainstorms, what Juliano accomplished took 30 years to imagine in laboratories and about 15 years to plan.
When John Chapin and I, 15 years ago, proposed in a paper that we would build something that we called a brain-machine interface, meaning connecting a brain to devices so that animals and humans could just move these devices, no matter how far they are from their own bodies, just by imagining what they want to do, our colleagues told us that we actually needed professional help, of the psychiatry variety.
And despite that, a Scot and a Brazilian persevered, because that's how we were raised in our respective countries, and for 12, 15 years, we made demonstration after demonstration suggesting that this was possible.
And a brain-machine interface is not rocket science, it's just brain research.
It's nothing but using sensors to read the electrical brainstorms that a brain is producing to generate the motor commands that have to be downloaded to the spinal cord, so we projected sensors that can read hundreds and now thousands of these brain cells simultaneously, and extract from these electrical signals the motor planning that the brain is generating to actually make us move into space.
And by doing that, we converted these signals into digital commands that any mechanical, electronic, or even a virtual device can understand so that the subject can imagine what he, she or it wants to make move, and the device obeys that brain command.
By sensorizing these devices with lots of different types of sensors, as you are going to see in a moment, we actually sent messages back to the brain to confirm that that voluntary motor will was being enacted, no matter where -- next to the subject, next door, or across the planet.
And as this message gave feedback back to the brain, the brain realized its goal: to make us move.
So this is just one experiment that we published a few years ago, where a monkey, without moving its body, learned to control the movements of an avatar arm, a virtual arm that doesn't exist.
What you're listening to is the sound of the brain of this monkey as it explores three different visually identical spheres in virtual space.
And to get a reward, a drop of orange juice that monkeys love, this animal has to detect, select one of these objects by touching, not by seeing it, by touching it, because every time this virtual hand touches one of the objects, an electrical pulse goes back to the brain of the animal describing the fine texture of the surface of this object, so the animal can judge what is the correct object that he has to grab, and if he does that, he gets a reward without moving a muscle.
The perfect Brazilian lunch: not moving a muscle and getting your orange juice.
So as we saw this happening, we actually came and proposed the idea that we had published 15 years ago.
We reenacted this paper.
We got it out of the drawers, and we proposed that perhaps we could get a human being that is paralyzed to actually use the brain-machine interface to regain mobility.
The idea was that if you suffered -- and that can happen to any one of us.
Let me tell you, it's very sudden.
It's a millisecond of a collision, a car accident that transforms your life completely.
If you have a complete lesion of the spinal cord, you cannot move because your brainstorms cannot reach your muscles.
However, your brainstorms continue to be generated in your head.
Paraplegic, quadriplegic patients dream about moving every night.
They have that inside their head.
The problem is how to get that code out of it and make the movement be created again.
So what we proposed was, let's create a new body.
Let's create a robotic vest.
And that's exactly why Juliano could kick that ball just by thinking, because he was wearing the first brain-controlled robotic vest that can be used by paraplegic, quadriplegic patients to move and to regain feedback.
That was the original idea, 15 years ago.
What I'm going to show you is how 156 people from 25 countries all over the five continents of this beautiful Earth, dropped their lives, dropped their patents, dropped their dogs, wives, kids, school, jobs, and congregated to come to Brazil for 18 months to actually get this done.
Because a couple years after Brazil was awarded the World Cup, we heard that the Brazilian government wanted to do something meaningful in the opening ceremony in the country that reinvented and perfected soccer until we met the Germans, of course.
(Laughter) But that's a different talk, and a different neuroscientist needs to talk about that.
But what Brazil wanted to do is to showcase a completely different country, a country that values science and technology, and can give a gift to millions, 25 million people around the world that cannot move any longer because of a spinal cord injury.
Well, we went to the Brazilian government and to FIFA and proposed, well, let's have the kickoff of the 2014 World Cup be given by a Brazilian paraplegic using a brain-controlled exoskeleton that allows him to kick the ball and to feel the contact of the ball.
They looked at us, thought that we were completely nuts, and said, "Okay, let's try."
We had 18 months to do everything from zero, from scratch.
We had no exoskeleton, we had no patients, we had nothing done.
These people came all together and in 18 months, we got eight patients in a routine of training and basically built from nothing this guy, that we call Bra-Santos Dumont 1.
The first brain-controlled exoskeleton to be built was named after the most famous Brazilian scientist ever, Alberto Santos Dumont, who, on October 19, 1901, created and flew himself the first controlled airship on air in Paris for a million people to see.
Sorry, my American friends, I live in North Carolina, but it was two years before the Wright Brothers flew on the coast of North Carolina.
(Applause) Flight control is Brazilian.
(Laughter) So we went together with these guys and we basically put this exoskeleton together, 15 degrees of freedom, hydraulic machine that can be commanded by brain signals recorded by a non-invasive technology called electroencephalography that can basically allow the patient to imagine the movements and send his commands to the controls, the motors, and get it done.
This exoskeleton was covered with an artificial skin invented by Gordon Cheng, one of my greatest friends, in Munich, to allow sensation from the joints moving and the foot touching the ground to be delivered back to the patient through a vest, a shirt.
It is a smart shirt with micro-vibrating elements that basically delivers the feedback and fools the patient's brain by creating a sensation that it is not a machine that is carrying him, but it is he who is walking again.
So we got this going, and what you'll see here is the first time one of our patients, Bruno, actually walked.
And he takes a few seconds because we are setting everything, and you are going to see a blue light cutting in front of the helmet because Bruno is going to imagine the movement that needs to be performed, the computer is going to analyze it, Bruno is going to certify it, and when it is certified, the device starts moving under the command of Bruno's brain.
And he just got it right, and now he starts walking.
After nine years without being able to move, he is walking by himself.
And more than that -- (Applause) -- more than just walking, he is feeling the ground, and if the speed of the exo goes up, he tells us that he is walking again on the sand of Santos, the beach resort where he used to go before he had the accident.
That's why the brain is creating a new sensation in Bruno's head.
So he walks, and at the end of the walk -- I am running out of time already -- he says, "You know, guys, I need to borrow this thing from you when I get married, because I wanted to walk to the priest and see my bride and actually be there by myself.
Of course, he will have it whenever he wants.
And this is what we wanted to show during the World Cup, and couldn't, because for some mysterious reason, FIFA cut its broadcast in half.
What you are going to see very quickly is Juliano Pinto in the exo doing the kick a few minutes before we went to the pitch and did the real thing in front of the entire crowd, and the lights you are going to see just describe the operation.
Basically, the blue lights pulsating indicate that the exo is ready to go.
It can receive thoughts and it can deliver feedback, and when Juliano makes the decision to kick the ball, you are going to see two streams of green and yellow light coming from the helmet and going to the legs, representing the mental commands that were taken by the exo to actually make that happen.
And in basically 13 seconds, Juliano actually did.
You can see the commands.
He gets ready, the ball is set, and he kicks.
And the most amazing thing is, 10 seconds after he did that, and looked at us on the pitch, he told us, celebrating as you saw, "I felt the ball."
And that's priceless.
(Applause) So where is this going to go?
I have two minutes to tell you that it's going to the limits of your imagination.
Brain-actuating technology is here.
This is the latest: We just published this a year ago, the first brain-to-brain interface that allows two animals to exchange mental messages so that one animal that sees something coming from the environment can send a mental SMS, a torpedo, a neurophysiological torpedo, to the second animal, and the second animal performs the act that he needed to perform without ever knowing what the environment was sending as a message, because the message came from the first animal's brain.
So this is the first demo.
I'm going to be very quick because I want to show you the latest.
But what you see here is the first rat getting informed by a light that is going to show up on the left of the cage that he has to press the left cage to basically get a reward.
He goes there and does it.
And the same time, he is sending a mental message to the second rat that didn't see any light, and the second rat, in 70 percent of the times is going to press the left lever and get a reward without ever experiencing the light in the retina.
Well, we took this to a little higher limit by getting monkeys to collaborate mentally in a brain net, basically to donate their brain activity and combine them to move the virtual arm that I showed you before, and what you see here is the first time the two monkeys combine their brains, synchronize their brains perfectly to get this virtual arm to move.
One monkey is controlling the x dimension, the other monkey is controlling the y dimension.
But it gets a little more interesting when you get three monkeys in there and you ask one monkey to control x and y, the other monkey to control y and z, and the third one to control x and z, and you make them all play the game together, moving the arm in 3D into a target to get the famous Brazilian orange juice.
And they actually do.
The black dot is the average of all these brains working in parallel, in real time.
That is the definition of a biological computer, interacting by brain activity and achieving a motor goal.
Where is this going?
We have no idea.
We're just scientists.
(Laughter) We are paid to be children, to basically go to the edge and discover what is out there.
But one thing I know: One day, in a few decades, when our grandchildren surf the Net just by thinking, or a mother donates her eyesight to an autistic kid who cannot see, or somebody speaks because of a brain-to-brain bypass, some of you will remember that it all started on a winter afternoon in a Brazilian soccer field with an impossible kick.
Thank you.
(Applause) Thank you.
Bruno Giussani: Miguel, thank you for sticking to your time.
I actually would have given you a couple more minutes, because there are a couple of points we want to develop, and, of course, clearly it seems that we need connected brains to figure out where this is going.
So let's connect all this together.
So if I'm understanding correctly, one of the monkeys is actually getting a signal and the other monkey is reacting to that signal just because the first one is receiving it and transmitting the neurological impulse.
Miguel Nicolelis: No, it's a little different.
No monkey knows of the existence of the other two monkeys.
They are getting a visual feedback in 2D, but the task they have to accomplish is 3D.
They have to move an arm in three dimensions.
But each monkey is only getting the two dimensions on the video screen that the monkey controls.
And to get that thing done, you need at least two monkeys to synchronize their brains, but the ideal is three.
So what we found out is that when one monkey starts slacking down, the other two monkeys enhance their performance to get the guy to come back, so this adjusts dynamically, but the global synchrony remains the same.
Now, if you flip without telling the monkey the dimensions that each brain has to control, like this guy is controlling x and y, but he should be controlling now y and z, instantaneously, that animal's brain forgets about the old dimensions and it starts concentrating on the new dimensions.
So what I need to say is that no Turing machine, no computer can predict what a brain net will do.
So we will absorb technology as part of us.
Technology will never absorb us.
It's simply impossible.
BG: How many times have you tested this?
And how many times have you succeeded versus failed?
MN: Oh, tens of times.
With the three monkeys?
Oh, several times.
I wouldn't be able to talk about this here unless I had done it a few times.
And I forgot to mention, because of time, that just three weeks ago, a European group just demonstrated the first man-to-man brain-to-brain connection.
BG: And how does that play?
MN: There was one bit of information -- big ideas start in a humble way -- but basically the brain activity of one subject was transmitted to a second object, all non-invasive technology.
So the first subject got a message, like our rats, a visual message, and transmitted it to the second subject.
The second subject received a magnetic pulse in the visual cortex, or a different pulse, two different pulses.
In one pulse, the subject saw something.
On the other pulse, he saw something different.
And he was able to verbally indicate what was the message the first subject was sending through the Internet across continents.
Moderator: Wow.
Okay, that's where we are going.
That's the next TED Talk at the next conference.
Miguel Nicolelis, thank you.
MN: Thank you, Bruno.
Thank you.
Nine years ago, my sister discovered lumps in her neck and arm and was diagnosed with cancer.
From that day, she started to benefit from the understanding that science has of cancer.
Every time she went to the doctor, they measured specific molecules that gave them information about how she was doing and what to do next.
New medical options became available every few years.
Everyone recognized that she was struggling heroically with a biological illness.
This spring, she received an innovative new medical treatment in a clinical trial.
It dramatically knocked back her cancer.
Guess who I'm going to spend this Thanksgiving with?
My vivacious sister, who gets more exercise than I do, and who, like perhaps many people in this room, increasingly talks about a lethal illness in the past tense.
Science can, in our lifetimes -- even in a decade -- transform what it means to have a specific illness.
But not for all illnesses.
My friend Robert and I were classmates in graduate school.
Robert was smart, but with each passing month, his thinking seemed to become more disorganized.
He dropped out of school, got a job in a store ...
But that, too, became too complicated.
Robert became fearful and withdrawn.
A year and a half later, he started hearing voices and believing that people were following him.
Doctors diagnosed him with schizophrenia, and they gave him the best drug they could.
That drug makes the voices somewhat quieter, but it didn't restore his bright mind or his social connectedness.
Robert struggled to remain connected to the worlds of school and work and friends.
He drifted away, and today I don't know where to find him.
If he watches this, I hope he'll find me.
Why does medicine have so much to offer my sister, and so much less to offer millions of people like Robert?
The need is there.
The World Health Organization estimates that brain illnesses like schizophrenia, bipolar disorder and major depression are the world's largest cause of lost years of life and work.
That's in part because these illnesses often strike early in life, in many ways, in the prime of life, just as people are finishing their educations, starting careers, forming relationships and families.
These illnesses can result in suicide; they often compromise one's ability to work at one's full potential; and they're the cause of so many tragedies harder to measure: lost relationships and connections, missed opportunities to pursue dreams and ideas.
These illnesses limit human possibilities in ways we simply cannot measure.
We live in an era in which there's profound medical progress on so many other fronts.
My sister's cancer story is a great example, and we could say the same of heart disease.
Drugs like statins will prevent millions of heart attacks and strokes.
When you look at these areas of profound medical progress in our lifetimes, they have a narrative in common: scientists discovered molecules that matter to an illness, they developed ways to detect and measure those molecules in the body, and they developed ways to interfere with those molecules using other molecules -- medicines.
It's a strategy that has worked again and again and again.
But when it comes to the brain, that strategy has been limited, because today, we don't know nearly enough, yet, about how the brain works.
We need to learn which of our cells matter to each illness, and which molecules in those cells matter to each illness.
And that's the mission I want to tell you about today.
My lab develops technologies with which we try to turn the brain into a big-data problem.
You see, before I became a biologist, I worked in computers and math, and I learned this lesson: wherever you can collect vast amounts of the right kinds of data about the functioning of a system, you can use computers in powerful new ways to make sense of that system and learn how it works.
Today, big-data approaches are transforming ever-larger sectors of our economy, and they could do the same in biology and medicine, too.
But you have to have the right kinds of data.
You have to have data about the right things.
And that often requires new technologies and ideas.
And that is the mission that animates the scientists in my lab.
Today, I want to tell you two short stories from our work.
One fundamental obstacle we face in trying to turn the brain into a big-data problem is that our brains are composed of and built from billions of cells.
And our cells are not generalists; they're specialists.
Like humans at work, they specialize into thousands of different cellular careers, or cell types.
In fact, each of the cell types in our body could probably give a lively TED Talk about what it webblaura@example.org.
But as scientists, we don't even know today how many cell types there are, and we don't know what the titles of most of those talks would be.
Now, we know many important things about cell types.
They can differ dramatically in size and shape.
One will respond to a molecule that the other doesn't respond to, they'll make different molecules.
But science has largely been reaching these insights in an ad hoc way, one cell type at a time, one molecule at a time.
We wanted to make it possible to learn all of this quickly and systematically.
Now, until recently, it was the case that if you wanted to inventory all of the molecules in a part of the brain or any organ, you had to first grind it up into a kind of cellular smoothie.
But that's a problem.
As soon as you've ground up the cells, you can only study the contents of the average cell -- not the individual cells.
Imagine if you were trying to understand how a big city like New York works, but you could only do so by reviewing some statistics about the average resident of New York.
Of course, you wouldn't learn very much, because everything that's interesting and important and exciting is in all the diversity and the specializations.
And the same thing is true of our cells.
And we wanted to make it possible to study the brain not as a cellular smoothie but as a cellular fruit salad, in which one could generate data about and learn from each individual piece of fruit.
So we developed a technology for doing that.
You're about to see a movie of it.
Here we're packaging tens of thousands of individual cells, each into its own tiny water droplet for its own molecular analysis.
When a cell lands in a droplet, it's greeted by a tiny bead, and that bead delivers millions of DNA bar code molecules.
And each bead delivers a different bar code sequence to a different cell.
We incorporate the DNA bar codes into each cell's RNA molecules.
Those are the molecular transcripts it's making of the specific genes that it's using to do its job.
And then we sequence billions of these combined molecules and use the sequences to tell us which cell and which gene every molecule came from.
We call this approach "Drop-seq," because we use droplets to separate the cells for analysis, and we use DNA sequences to tag and inventory and keep track of everything.
And now, whenever we do an experiment, we analyze tens of thousands of individual cells.
And today in this area of science, the challenge is increasingly how to learn as much as we can as quickly as we can from these vast data sets.
When we were developing Drop-seq, people used to tell us, "Oh, this is going to make you guys the go-to for every major brain project."
That's not how we saw it.
Science is best when everyone is generating lots of exciting data.
So we wrote a 25-page instruction book, with which any scientist could build their own Drop-seq system from scratch.
And that instruction book has been downloaded from our lab website 50,000 times in the past two years.
We wrote software that any scientist could use to analyze the data from Drop-seq experiments, and that software is also free, and it's been downloaded from our website 30,000 times in the past two years.
And hundreds of labs have written us about discoveries that they've made using this approach.
Today, this technology is being used to make a human cell atlas.
It will be an atlas of all of the cell types in the human body and the specific genes that each cell type uses to do its job.
Now I want to tell you about a second challenge that we face in trying to turn the brain into a big data problem.
And that challenge is that we'd like to learn from the brains of hundreds of thousands of living people.
But our brains are not physically accessible while we're living.
But how can we discover molecular factors if we can't hold the molecules?
An answer comes from the fact that the most informative molecules, proteins, are encoded in our DNA, which has the recipes our cells follow to make all of our proteins.
And these recipes vary from person to person to person in ways that cause the proteins to vary from person to person in their precise sequence and in how much each cell type makes of each protein.
It's all encoded in our DNA, and it's all genetics, but it's not the genetics that we learned about in school.
Do you remember big B, little b?
If you inherit big B, you get brown eyes?
It's simple.
Very few traits are that simple.
Even eye color is shaped by much more than a single pigment molecule.
And something as complex as the function of our brains is shaped by the interaction of thousands of genes.
And each of these genes varies meaningfully from person to person to person, and each of us is a unique combination of that variation.
It's a big data opportunity.
And today, it's increasingly possible to make progress on a scale that was never possible before.
People are contributing to genetic studies in record numbers, and scientists around the world are sharing the data with one another to speed progress.
I want to tell you a short story about a discovery we recently made about the genetics of schizophrenia.
It was made possible by 50,000 people from 30 countries, who contributed their DNA to genetic research on schizophrenia.
It had been known for several years that the human genome's largest influence on risk of schizophrenia comes from a part of the genome that encodes many of the molecules in our immune system.
But it wasn't clear which gene was responsible.
A scientist in my lab developed a new way to analyze DNA with computers, and he discovered something very surprising.
He found that a gene called "complement component 4" -- it's called "C4" for short -- comes in dozens of different forms in different people's genomes, and these different forms make different amounts of C4 protein in our brains.
And he found that the more C4 protein our genes make, the greater our risk for schizophrenia.
Now, C4 is still just one risk factor in a complex system.
This isn't big B, but it's an insight about a molecule that matters.
Complement proteins like C4 were known for a long time for their roles in the immune system, where they act as a kind of molecular Post-it note that says, "Eat me."
And that Post-it note gets put on lots of debris and dead cells in our bodies and invites immune cells to eliminate them.
But two colleagues of mine found that the C4 Post-it note also gets put on synapses in the brain and prompts their elimination.
Now, the creation and elimination of synapses is a normal part of human development and learning.
Our brains create and eliminate synapses all the time.
But our genetic results suggest that in schizophrenia, the elimination process may go into overdrive.
Scientists at many drug companies tell me they're excited about this discovery, because they've been working on complement proteins for years in the immune system, and they've learned a lot about how they work.
They've even developed molecules that interfere with complement proteins, and they're starting to test them in the brain as well as the immune system.
It's potentially a path toward a drug that might address a root cause rather than an individual symptom, and we hope very much that this work by many scientists over many years will be successful.
But C4 is just one example of the potential for data-driven scientific approaches to open new fronts on medical problems that are centuries old.
There are hundreds of places in our genomes that shape risk for brain illnesses, and any one of them could lead us to the next molecular insight about a molecule that matters.
And there are hundreds of cell types that use these genes in different combinations.
As we and other scientists work to generate the rest of the data that's needed and to learn all that we can from that data, we hope to open many more new fronts.
Genetics and single-cell analysis are just two ways of trying to turn the brain into a big data problem.
There is so much more we can do.
Scientists in my lab are creating a technology for quickly mapping the synaptic connections in the brain to tell which neurons are talking to which other neurons and how that conversation changes throughout life and during illness.
And we're developing a way to test in a single tube how cells with hundreds of different people's genomes respond differently to the same stimulus.
These projects bring together people with diverse backgrounds and training and interests -- biology, computers, chemistry, math, statistics, engineering.
But the scientific possibilities rally people with diverse interests into working intensely together.
What's the future that we could hope to create?
Consider cancer.
We've moved from an era of ignorance about what causes cancer, in which cancer was commonly ascribed to personal psychological characteristics, to a modern molecular understanding of the true biological causes of cancer.
That understanding today leads to innovative medicine after innovative medicine, and although there's still so much work to do, we're already surrounded by people who have been cured of cancers that were considered untreatable a generation ago.
And millions of cancer survivors like my sister find themselves with years of life that they didn't take for granted and new opportunities for work and joy and human connection.
That is the future that we are determined to create around mental illness -- one of real understanding and empathy and limitless possibility.
Thank you.
(Applause)