A new way to study the brain's invisible secrets | Ed Boyden

Translator: Silvia Fernández Crespo Reviewer: Serv. de Norm. Lingüística U. de Santiago de Compostela

Hello, everybody.

Ola a todos.

I brought with me today a baby diaper.

Hoxe trouxen un cueiro de bebé

You'll see why in a second.

Nun segundo verán por que.

Baby diapers have interesting properties.

Teñen propiedades interesantes,

They can swell enormously when you add water to them,

poden incharse enormemente ó engadirlles auga.

an experiment done by millions of kids every day.

Millóns de cativos realizan este experimento cada día.

(Laughter)

(Risas)

But the reason why

Isto débese

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

a que teñen un deseño moi intelixente.

They're made out of a thing called a swellable material.

Están feitos dun material inchábel.

It's a special kind of material that, when you add water,

É un material especial que, ó engadirlle auga,

it will swell up enormously,

ínchase enormemente,

maybe a thousand times in volume.

quizais mil veces o seu volume.

And this is a very useful, industrial kind of polymer.

É un polímero industrial moi útil.

But what we're trying to do in my group at MIT

No meu grupo do MIT tratamos

is to figure out if we can do something similar to the brain.

de descubrir se podemos facer algo similar co cerebro.

Can we make it bigger,

Podemos expandilo

big enough that you can peer inside

abondo como para ver dentro

and see all the tiny building blocks, the biomolecules,

os diminutos compoñentes esenciais, as biomoléculas,

how they're organized in three dimensions,

a súa organización tridimensional,

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

a estrutura, a verdadeira estrutura do cerebro, por así dicilo?

If we could get that,

Se a puidésemos obter,

maybe we could have a better understanding of how the brain is organized

quizais poderiamos chegar a entender como está organizado o cerebro

to yield thoughts and emotions

para xerar pensamentos, emocións,

and actions and sensations.

accións e sentimentos.

Maybe we could try to pinpoint the exact changes in the brain

Tal vez poderiamos identificar os cambios exactos no cerebro

that result in diseases,

que conducen a enfermidades

diseases like Alzheimer's and epilepsy and Parkinson's,

como alzheimer, epilepsia e párkinson,

for which there are few treatments, much less cures,

para as que hai poucos tratamentos e menos curas,

and for which, very often, we don't know the cause or the origins

e das que, moi a miúdo, descoñecemos a causa ou a orixe

and what's really causing them to occur.

que as produce en realidade.

Now, our group at MIT

Agora, o noso grupo no MIT

is trying to take a different point of view

trata de velo desde un punto de vista diferente

from the way neuroscience has been done over the last hundred years.

ó que estudou a neurociencia nos cen últimos anos.

We're designers. We're inventors.

Somos inventores, deseñadores.

We're trying to figure out how to build technologies

Tentamos descubrir como construír tecnoloxía

that let us look at and repair the brain.

que nos permita analizar e reparar o cerebro.

And the reason is,

A razón é

the brain is incredibly, incredibly complicated.

que o cerebro resulta ser extremadamente complicado.

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

Durante o primeiro século da neurociencia aprendemos

is that the brain is a very complicated network,

que o cerebro é unha rede moi complicada,

made out of very specialized cells called neurons

formada por células moi especializadas, as neuronas,

with very complex geometries,

con xeometrías moi complexas

and electrical currents will flow through these complexly shaped neurons.

e correntes eléctricas que flúen por esas neuronas de estrutura complexa.

Furthermore, neurons are connected in networks.

Ademais, as neuronas están conectadas en redes

They're connected by little junctions called synapses that exchange chemicals

por pequenas unións, as sinapses, que intercambian substancias químicas

and allow the neurons to talk to each other.

que lles permiten falar unhas coas outras.

The density of the brain is incredible.

A densidade do cerebro é sorprendente.

In a cubic millimeter of your brain,

Nun milímetro cúbico de cerebro

there are about 100,000 of these neurons

existen preto de cen mil neuronas

and maybe a billion of those connections.

e mil millóns desas conexións.

But it's worse.

Pero é peor.

So, if you could zoom in to a neuron,

Se puidésemos ampliar unha neurona

and, of course, this is just our artist's rendition of it.

e, por suposto, esta é unha interpretación artística,

What you would see are thousands and thousands of kinds of biomolecules,

poderiamos ver miles e miles de tipos de biomoléculas,

little nanoscale machines organized in complex, 3D patterns,

pequenas máquinas a escala nanométrica organizadas en complexos patróns 3D

and together they mediate those electrical pulses,

e en conxunto conectan estes impulsos eléctricos,

those chemical exchanges that allow neurons to work together

eses intercambios químicos que permiten que as neuronas traballen xuntas

to generate things like thoughts and feelings and so forth.

para xerar pensamentos, sentimentos, etcétera.

Now, we don't know how the neurons in the brain are organized

Pero non sabemos como se organizan as neuronas no cerebro

to form networks,

para formar redes

and we don't know how the biomolecules are organized

e non sabemos como se organizan as biomoléculas

within neurons

dentro das neuronas

to form these complex, organized machines.

para formar esas máquinas organizadas e complexas.

If we really want to understand this,

Se realmente queremos entender iso,

we're going to need new technologies.

imos precisar de novas tecnoloxías.

But if we could get such maps,

Pero se puidésemos obter estes mapas,

if we could look at the organization of molecules and neurons

se puidésemos ver a organización das moléculas e as neuronas,

and neurons and networks,

e as neuronas e as redes,

maybe we could really understand how the brain conducts information

quizais poderiamos entender como o cerebro leva a información

from sensory regions,

das rexións sensoriais,

mixes it with emotion and feeling,

a mestura con emoción e sentimento

and generates our decisions and actions.

e xera as nosas decisións e accións.

Maybe we could pinpoint the exact set of molecular changes that occur

Quizais poderiamos identificar ó detalle tódolos cambios moleculares que ocorren

in a brain disorder.

nun trastorno cerebral,

And once we know how those molecules have changed,

e unha vez soubésemos como cambian estas moléculas,

whether they've increased in number or changed in pattern,

se aumentan o seu número ou cambian de patrón,

we could use those as targets for new drugs,

poderiamos usar isto como obxectivo para novos fármacos,

for new ways of delivering energy into the brain

para novas formas de darlle enerxía ó cerebro,

in order to repair the brain computations that are afflicted

para arranxar os cálculos cerebrais afectados

in patients who suffer from brain disorders.

en pacientes que sofren de trastornos cerebrais.

We've all seen lots of different technologies over the last century

Vimos moitas tecnoloxías diferentes no último século

que intentaban arranxar isto.

to try to confront this.

I think we've all seen brain scans

Creo que todos vimos imaxes do cerebro

taken using MRI machines.

tomadas con equipos de resonancia magnética.

These, of course, have the great power that they are noninvasive,

Esta ten a gran propiedade de non ser invasiva,

they can be used on living human subjects.

pódese empregar en seres humanos vivos,

But also, they're spatially crude.

pero é basta, a nivel espacial

Each of these blobs that you see, or voxels, as they're called,

Cada unha desas burbullas que ven, chamadas voxels,

can contain millions and millions of neurons.

pode conter millóns de neuronas.

So it's not at the level of resolution

Así que non está ó nivel de resolución

where it can pinpoint the molecular changes that occur

para precisar os cambios moleculares que ocorren

or the changes in the wiring of these networks

na cablaxe destas redes

that contributes to our ability to be conscious and powerful beings.

que nos dan a capacidade de ser conscientes e poderosos.

At the other extreme, you have microscopes.

No outro extremo temos os microscopios.

Microscopes, of course, will use light to look at little tiny things.

Os microscopios empregan a luz para mirar cousas diminutas.

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

Durante séculos, usáronse para ollar cousas como bacterias.

For neuroscience,

En neurociencia,

microscopes are actually how neurons were discovered in the first place,

grazas aos microscopios descubríronse as neuronas por primeira vez,

hai uns 130 anos.

about 130 years ago.

But light is fundamentally limited.

Pero a luz ten serias limitacións.

You can't see individual molecules with a regular old microscope.

Non se poden ver moléculas individuais co microscopio antigo.

You can't look at these tiny connections.

Non se poden ver estas pequenas conexións.

So if we want to make our ability to see the brain more powerful,

Polo tanto, se queremos unha mellor visión do cerebro,

to get down to the ground truth structure,

para introducirnos á verdadeira estrutura,

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

imos necesitar ter incluso mellores tecnoloxías.

My group, a couple years ago, started thinking:

O meu grupo, hai dous anos, pensou:

Why don't we do the opposite?

E se facemos o contrario?

If it's so darn complicated to zoom in to the brain,

Se é tan complicado ampliar a vista do cerebro,

why can't we make the brain bigger?

Por qué non ampliar o cerebro?

It initially started

Nun principio comezamos

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

con dous estudantes do meu grupo, Fei Chen e Paul Tillberg.

Now many others in my group are helping with this process.

Agora moitos do meu grupo están axudando neste proceso.

Decidimos descubrir se podiamos tomar polímeros,

We decided to try to figure out if we could take polymers,

like the stuff in the baby diaper,

como os dos cueiros dos bebés,

and install it physically within the brain.

e instalalos fisicamente no cerebro.

If we could do it just right, and you add water,

Se puidésemos facelo ben, e engadiramos auga,

you can potentially blow the brain up

poderiamos expandir o cerebro

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

e poderíase distinguir esas pequenas biomoléculas unhas das outras.

Poderíase ver estas conexións e obter mapas cerebrais.

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

This could potentially be quite dramatic.

Isto podería ser moi drástico.

We brought a little demo here.

Trouxemos unha pequena demostración.

We got some purified baby diaper material.

Conseguimos material purificado dos cueiros dos bebés.

It's much easier just to buy it off the Internet

É moito máis fácil a compra en liña

than to extract the few grains that actually occur in these diapers.

que extraer os poucos grans que realmente teñen eses cueiros.

I'm going to put just one teaspoon here

Aquí vou poñer só unha culler de té

of this purified polymer.

deste polímero purificado

And here we have some water.

e aquí temos un pouco de auga.

What we're going to do

Imos ver

is see if this teaspoon of the baby diaper material

se esta culler de material dos cueiros

can increase in size.

pode aumentar de tamaño.

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

Van ver que aumenta de volume ó redor de mil veces

before your very eyes.

diante dos seus ollos.

I could pour much more of this in there,

Podería verter moito máis aí dentro,

but I think you've got the idea

pero creo que entenden

that this is a very, very interesting molecule,

que esta é unha molécula moi interesante

and if can use it in the right way,

e que usada correctamente

we might be able to really zoom in on the brain

permítenos facer zoom no cerebro,

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

o que non é posible coas tecnoloxías anteriores.

OK. So a little bit of chemistry now.

Ben, agora un pouco de química.

What's going on in the baby diaper polymer?

Que está pasando no polímero do cueiro?

If you could zoom in,

Se puidésemos facer zoom,

it might look something like what you see on the screen.

veriamos algo como o que se ve na pantalla.

Polymers are chains of atoms arranged in long, thin lines.

Os polímeros son cadeas de átomos dispostas en liñas longas e delgadas.

The chains are very tiny,

As cadeas son diminutas,

about the width of a biomolecule,

do ancho dunha biomolécula

and these polymers are really dense.

e estes polímeros son moi densos.

They're separated by distances

Están separados por distancias

that are around the size of a biomolecule.

do tamaño dunha biomolécula.

This is very good

Isto é moi bo

because we could potentially move everything apart in the brain.

porque poderiamos potencialmente mover todo o cerebro.

If we add water, what will happen is,

Se engadimos auga, acontecerá que

this swellable material is going to absorb the water,

este material inchábel vai absorbela,

the polymer chains will move apart from each other,

as cadeas de polímero separaranse entre elas,

and the entire material is going to become bigger.

e todo o material se expandirá.

And because these chains are so tiny

Como estas cadeas son tan pequenas

and spaced by biomolecular distances,

e separadas por distancias biomoleculares,

we could potentially blow up the brain

potencialmente poderiamos inflar o cerebro

and make it big enough to see.

e expandilo ata que sexa visible.

Here's the mystery, then:

Aquí está o misterio:

How do we actually make these polymer chains inside the brain

Cómo construír estas cadeas de polímero no interior do cerebro

so we can move all the biomolecules apart?

para separar as biomoléculas?

If we could do that,

Se puidésemos facelo,

maybe we could get ground truth maps of the brain.

quizais poderiamos mapear realmente o cerebro.

We could look at the wiring.

Poderiamos ver a cablaxe.

Poderiamos ollar para dentro e ver as moléculas que hai.

We can peer inside and see the molecules within.

To explain this, we made some animations

Para explicalo, fixemos unhas animacións

where we actually look at, in these artist renderings,

onde realmente se ve, nestas representacións,

what biomolecules might look like and how we might separate them.

qué aspecto terían as biomoléculas e como poderiamos separalas.

Step one: what we'd have to do, first of all,

Paso 1: en primeiro lugar teriamos

is attach every biomolecule, shown in brown here,

que anexar cada biomolécula, aquí aparecen en marrón,

to a little anchor, a little handle.

a unha pequena áncora, unha pequena asa.

We need to pull the molecules of the brain apart from each other,

Temos que separar as moléculas do cerebro unhas das outras,

and to do that, we need to have a little handle

e para facelo, necesitamos ter unha pequena asa

that allows those polymers to bind to them

que lles permita ós polímeros unirse a eles

and to exert their force.

e exercer a súa forza.

Now, if you just take baby diaper polymer and dump it on the brain,

Pero se poñemos o polímero do cueiro do bebé no cerebro,

obviously, it's going to sit there on top.

loxicamente, situarase na parte superior.

So we need to find a way to make the polymers inside.

Necesitamos topar a forma para poñer o polímero dentro

And this is where we're really lucky.

e aquí é onde temos moita sorte.

It turns out, you can get the building blocks,

Podemos obter os compoñentes esenciais,

monomers, as they're called,

chamados monómeros,

and if you let them go into the brain

e deixalos entrar no cerebro,

and then trigger the chemical reactions,

e logo, desencadear as reaccións químicas,

you can get them to form those long chains,

para chegar a formar esas longas cadeas,

right there inside the brain tissue.

alí, no interior do tecido cerebral.

They're going to wind their way around biomolecules

Abriranse camiño ó redor

and between biomolecules,

e entre as biomoléculas,

forming those complex webs

formando esas redes complexas

that will allow you, eventually, to pull apart the molecules

que permitirán, finalmente, separar as moléculas,

from each other.

unhas das outras.

And every time one of those little handles is around,

E cada vez que unha destas pequenas asas estea ó redor,

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

o polímero poderá unirse a ela e iso é exactamente o que necesitamos

in order to pull the molecules apart from each other.

para tirar das moléculas e separalas unhas das outras.

All right, the moment of truth.

Moi ben, o momento da verdade.

We have to treat this specimen

Temos que tratar este espécime

with a chemical to kind of loosen up all the molecules from each other,

con produtos químicos para soltar as moléculas entre si,

and then, when we add water,

e, a continuación, ó engadir auga,

that swellable material is going to start absorbing the water,

o material inchábel empezará a absorbela,

the polymer chains will move apart,

as cadeas de polímero separaranse,

but now, the biomolecules will come along for the ride.

pero agora, as biomoléculas acompañaranas.

And much like drawing a picture on a balloon,

Igual ca ao debuxar algo nun globo,

and then you blow up the balloon,

e despois, inflalo,

the image is the same,

a imaxe é a mesma,

but the ink particles have moved away from each other.

pero as partículas de tinta separáronse entre si.

And that's what we've been able to do now, but in three dimensions.

Iso é o que fixemos agora, pero en tres dimensións.

There's one last trick.

Hai un último truco.

As you can see here,

Como poden ver,

we've color-coded all the biomolecules brown.

coloreamos as biomoléculas en marrón.

That's because they all kind of look the same.

Isto débese a que todas se ven igual.

Biomolecules are made out of the same atoms,

As biomoléculas teñen os mesmos átomos,

but just in different orders.

pero en distinta orde.

So we need one last thing

Necesitamos unha última cousa

in order to make them visible.

para facelas visibles:

We have to bring in little tags,

pequenas etiquetas

with glowing dyes that will distinguish them.

con colorantes brillantes para distinguilas.

So one kind of biomolecule might get a blue color.

Así, un tipo de biomolécula podería ter unha cor azul,

Another kind of biomolecule might get a red color.

outra unha cor vermella,

And so forth.

etcétera.

And that's the final step.

E ese é o paso final.

Now we can look at something like a brain

Agora podemos analizar un cerebro

and look at the individual molecules,

e mirar moléculas individuais,

because we've moved them far apart enough from each other

porque as separamos o suficiente

that we can tell them apart.

e podemos distinguilas.

So the hope here is that we can make the invisible visible.

Esperamos poder facer visible o invisible.

We can turn things that might seem small and obscure

Podemos cambiar as cousas pequenas e escuras

and blow them up

e inflalas

until they're like constellations of information about life.

ata que sexan constelacións de información sobre a vida.

Here's an actual video of what it might look like.

Este é un vídeo real, do aspecto que poderían ter.

We have here a little brain in a dish --

Aquí temos un cerebro pequeno nunha placa,

a little piece of a brain, actually.

en realidade, un pequeno anaco.

We've infused the polymer in,

Colocamos o polímero,

and now we're adding water.

e agora engadimos auga.

What you'll see is that, right before your eyes --

Verán, xusto diante dos seus ollos

this video is sped up about sixtyfold --

--nun vídeo acelerado sesenta veces--

this little piece of brain tissue is going to grow.

como este anaco de tecido cerebral vai medrar.

It can increase by a hundredfold or even more in volume.

Pódese aumentar cen veces ou incluso máis, en volume.

And the cool part is, because those polymers are so tiny,

O interesante é que, dado que os polímeros son tan pequenos,

we're separating biomolecules evenly from each other.

estamos separando biomoléculas unhas das outras.

It's a smooth expansion.

É unha expansión suave.

We're not losing the configuration of the information.

Non estamos perdendo a configuración da información.

We're just making it easier to see.

Estámola facendo máis doada de ver.

So now we can take actual brain circuitry --

Así tomariamos circuítos reais do cerebro

here's a piece of the brain involved with, for example, memory --

--unha parte del implicada, por exemplo, coa memoria--

and we can zoom in.

e poderiamos facer zoom.

We can start to actually look at how circuits are configured.

Poderiamos empezar a avaliar como se configuran os circuítos.

Maybe someday we could read out a memory.

Quizais así poderíamos ler un recordo.

Maybe we could actually look at how circuits are configured

Quizais poderiamos ver como configurar circuítos

to process emotions,

para procesar emocións,

how the actual wiring of our brain is organized

como está organizada a cablaxe actual do cerebro

in order to make us who we are.

para facer de nós quen somos.

And of course, we can pinpoint, hopefully,

E, por suposto, precisar, con sorte,

the actual problems in the brain at a molecular level.

os problemas moleculares reais do cerebro.

What if we could actually look into cells in the brain

E se en realidade puidésemos ollar dentro do cerebro

and figure out, wow, here are the 17 molecules that have altered

e, uau, descubrir as dezasete moléculas alteradas

in this brain tissue that has been undergoing epilepsy

neste tecido cerebral que tivo epilepsia,

or changing in Parkinson's disease

ou cambios no párkinson

or otherwise being altered?

ou noutras enfermidades?

If we get that systematic list of things that are going wrong,

Se conseguimos a lista sistemática das cousas que van mal,

esas converteranse en obxectivos terapéuticos.

those become our therapeutic targets.

We can build drugs that bind those.

Crear fármacos que se unan a elas.

We can maybe aim energy at different parts of the brain

Poder apuntar a enerxía a diferentes partes do cerebro

in order to help people with Parkinson's or epilepsy

para axudar a persoas con párkinson, epilepsia

or other conditions that affect over a billion people

ou outras patoloxías que afectan a máis de mil millóns de persoas

around the world.

en todo o mundo.

Now, something interesting has been happening.

Agora, ocorreu algo interesante.

It turns out that throughout biomedicine,

Resulta que en biomedicina,

there are other problems that expansion might help with.

a expansión podería axudar noutros problemas.

This is an actual biopsy from a human breast cancer patient.

Esta é a biopsia real dunha paciente con cancro de mama.

It turns out that if you look at cancers,

Resulta que se analizamos os cancros

if you look at the immune system,

e o sistema inmunolóxico,

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

se estudamos o envellecemento e o desenvolvemento

all these processes are involving large-scale biological systems.

--estes procesos involucran sistemas biolóxicos a grande escala.

But of course, the problems begin with those little nanoscale molecules,

Pero por suposto, os problemas comezan con estas pequenas moléculas a nanoescala,

the machines that make the cells and the organs in our body tick.

as máquinas que compoñen as células e órganos do corpo.

So what we're trying to do now is to figure out

Agora imos tentar descubrir

if we can actually use this technology to map the building blocks of life

se podemos utilizar esta tecnoloxía para mapear os compoñentes esenciais da vida

in a wide variety of diseases.

nunha ampla gama de enfermidades.

Can we actually pinpoint the molecular changes in a tumor

Podemos sinalar os cambios moleculares nun tumor,

so that we can actually go after it in a smart way

ir tras el de forma intelixente

and deliver drugs that might wipe out exactly the cells that we want to?

e subministrar fármacos que poderían acabar só coas células que queiramos?

You know, a lot of medicine is very high risk.

Gran parte da medicina é de moi alto risco.

Sometimes, it's even guesswork.

Ás veces, empregamos conxecturas.

My hope is we can actually turn what might be a high-risk moon shot

Espero poder transformar o que podería ser un gran soño de alto risco

into something that's more reliable.

en algo máis fiable.

If you think about the original moon shot,

Se pensan no soño lunar orixinal,

where they actually landed on the moon,

o que nos levou á Lúa,

baseouse en fundamentos sólidos.

it was based on solid science.

We understood gravity;

Entendiamos a gravidade,

we understood aerodynamics.

a aerodinámica

We knew how to build rockets.

e sabiamos construír foguetes.

The science risk was under control.

O risco da ciencia estaba baixo control.

It was still a great, great feat of engineering.

Aínda era unha grande obra de enxeñería.

But in medicine, we don't necessarily have all the laws.

Pero na medicina, non seguimos todas as leis.

Do we have all the laws that are analogous to gravity,

Cumprimos todas as leis da gravidade

that are analogous to aerodynamics?

e da aerodinámica?

I would argue that with technologies

Diría que coas tecnoloxías

like the kinds I'm talking about today,

das que estou falando hoxe,

maybe we can actually derive those.

quizais poidamos derivalas.

We can map the patterns that occur in living systems,

Poderiamos trazar os patróns existentes nos sistemas vivos

and figure out how to overcome the diseases that plague us.

e atopar a maneira de superar enfermidades que nos aflixen.

You know, my wife and I have two young kids,

A miña muller e eu temos dous nenos,

and one of my hopes as a bioengineer is to make life better for them

e unha das miñas esperanzas como bioenxeñeiro é facerlles a vida mellor

than it currently is for us.

do que hoxe é para nós.

And my hope is, if we can turn biology and medicine

Espero que poidamos converter a bioloxía e a medicina

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

de alto risco, que se rexe polo azar e a sorte

and make them things that we win by skill and hard work,

en algo que gañemos con capacidade e traballo duro.

then that would be a great advance.

Iso sería un grande avance.

Thank you very much.

Moitas grazas.

(Applause)

(Aplausos).