Francis Collins: We need better drugs -- now

Translator: Joseph Geni Reviewer: Morton Bast

Translator: Serv. de Norm. Lingüística U. de Santiago de Compostela Reviewer: Xusto Rodriguez

So let me ask for a show of hands.

Levanten as mans, por favor.

How many people here are over the age of 48?

Cantos dos que están aquí teñen máis de 48 anos?

Well, there do seem to be a few.

Ben, parece que hai uns cantos.

Well, congratulations,

Parabéns,

because if you look at this particular slide of U.S. life expectancy,

porque se miran este gráfico da esperanza de vida nos EE.UU.

you are now in excess of the average life span

verán que superan xa a esperanza de vida media

of somebody who was born in 1900.

de alguén que nacera en 1900.

But look what happened in the course of that century.

Pero vexan o que pasou no correr dese século.

If you follow that curve,

Se seguen esta curva,

you'll see that it starts way down there.

verán que comeza aí abaixo.

There's that dip there for the 1918 flu.

Velaquí a baixada por causa da gripe do 1918.

And here we are at 2010,

E velaquí 2010,

average life expectancy of a child born today, age 79,

a esperanza de vida dun neno ou dunha nena que naza hoxe é de 79 anos,

and we are not done yet.

e isto aínda non rematou.

Now, that's the good news.

Estas son as boas novas.

But there's still a lot of work to do.

Pero aínda queda moito por facer.

So, for instance, if you ask,

Se nos preguntamos, por exemplo,

how many diseases do we now know

a cantas enfermidades lle coñecemos

the exact molecular basis?

a base molecular exacta?

Turns out it's about 4,000, which is pretty amazing,

Son sobre 4000, o cal é incrible,

because most of those molecular discoveries

porque a maioría destes descubrimentos

have just happened in the last little while.

ocorreron hai pouco.

It's exciting to see that in terms of what we've learned,

É emocionante ver o que aprendemos,

but how many of those 4,000 diseases

pero destas 4000 enfermidades,

now have treatments available?

cantas teñen tratamento dispoñible?

Only about 250.

Só unhas 250.

So we have this huge challenge, this huge gap.

Temos este gran desafío, este gran baleiro.

You would think this wouldn't be too hard,

Podería pensarse que non debería ser moi complicado

that we would simply have the ability

se temos a capacidade

to take this fundamental information that we're learning

de coller esa información esencial que estamos adquirindo

about how it is that basic biology teaches us

sobre o que nos ensina a bioloxía básica

about the causes of disease

arredor das causas das enfermidades

and build a bridge across this yawning gap

e construír unha ponte sobre este enorme baleiro

between what we've learned about basic science

entre o que aprendemos de ciencia básica

and its application,

e a súa aplicación,

a bridge that would look maybe something like this,

unha ponte que se puidese parecer a esta,

where you'd have to put together a nice shiny way

onde tes que percorrer un brillante camiño

to get from one side to the other.

para chegar dun lado a outro.

Well, wouldn't it be nice if it was that easy?

Non sería xenial se fose así de sinxelo?

Unfortunately, it's not.

Por desgraza, non o é.

In reality, trying to go from fundamental knowledge

Na realidade, tentar ir dende o coñecemento fundamental

to its application is more like this.

á súa aplicación, é máis ben así.

There are no shiny bridges.

Non hai pontes brillantes.

You sort of place your bets.

En certa medida, fanse apostas.

Maybe you've got a swimmer and a rowboat

Pode que teñan un nadador, un bote,

and a sailboat and a tugboat

un veleiro e unha lancha

and you set them off on their way,

e inician a viaxe,

and the rains come and the lightning flashes,

comeza a chover e a tronar,

and oh my gosh, there are sharks in the water

mi madriña! hai tiburóns na auga,

and the swimmer gets into trouble,

o nadador comeza a ter problemas,

and, uh oh, the swimmer drowned

oh, o nadador afogou,

and the sailboat capsized,

o veleiro envorcou,

and that tugboat, well, it hit the rocks,

e a lancha bateu nas rochas,

and maybe if you're lucky, somebody gets across.

e con sorte, alguén conseguiu cruzar.

Well, what does this really look like?

Ben, como é isto en realidade?

Well, what is it to make a therapeutic, anyway?

Que é facer unha terapia, á fin e ó cabo?

What's a drug? A drug is made up

Que é un fármaco? Un fármaco está formado

of a small molecule of hydrogen, carbon,

por unha pequena molécula de hidróxeno, carbono,

oxygen, nitrogen, and a few other atoms

osíxeno, nitróxeno e outros átomos

all cobbled together in a shape,

todos conectados dunha certa forma,

and it's those shapes that determine whether, in fact,

e estas formas son as que determinan

that particular drug is going to hit its target.

que este fármaco en concreto alcance o seu albo.

Is it going to land where it's supposed to?

Estase indo cara a onde se pretende?

So look at this picture here -- a lot of shapes dancing around for you.

Se miramos esta imaxe vemos unha morea de formas bailando.

Now what you need to do, if you're trying to develop

O que hai que facer, se se quere desenvolver

a new treatment for autism

un tratamento para o autismo,

or Alzheimer's disease or cancer

para o alzhéimer ou para o cancro,

is to find the right shape in that mix

é atopar nesa morea a forma axeitada

that will ultimately provide benefit and will be safe.

que nos provoque o beneficio desexado e que sexa segura.

And when you look at what happens to that pipeline,

Se vemos o que acontece neste funil,

you start out maybe with thousands,

comezamos con milleiros,

tens of thousands of compounds.

decenas de milleiros de compostos.

You weed down through various steps

Descartaranse algúns con varios filtros

that cause many of these to fail.

que amosan que moitos fallan.

Ultimately, maybe you can run a clinical trial with four or five of these,

Finalmente, pode que con catro ou cinco se realice un ensaio clínico,

and if all goes well, 14 years after you started,

e se todo vai ben, 14 anos despois,

you will get one approval.

consegue aprobarse un.

And it will cost you upwards of a billion dollars

E isto custará millóns de dólares

for that one success.

para un único éxito.

So we have to look at this pipeline the way an engineer would,

Debemos mirar este funil como o faría un enxeñeiro,

and say, "How can we do better?"

e dicir: "Como podemos mellorar"?

And that's the main theme of what I want to say to you this morning.

Disto é do que vos quero falar esta mañá.

How can we make this go faster?

Como o podemos facer máis rápido?

How can we make it more successful?

Como podemos ter máis éxito?

Well, let me tell you about a few examples

Vou falarvos duns exemplos

where this has actually worked.

onde isto funcionou.

One that has just happened in the last few months

Un aconteceu hai tan só uns meses

is the successful approval of a drug for cystic fibrosis.

e foi a aprobación dun fármaco para a fibrose quística.

But it's taken a long time to get there.

Pero levou moito tempo.

Cystic fibrosis had its molecular cause discovered in 1989

A base molecular da fibrose quística descubriuna en 1989

o meu grupo en colaboración con outro de Toronto,

by my group working with another group in Toronto,

discovering what the mutation was in a particular gene

e descubrimos que a mutación estaba nun xene

on chromosome 7.

no cromosoma 7.

That picture you see there?

Vedes esta foto?

Here it is. That's the same kid.

Velaquí o está. É o mesmo neno.

That's Danny Bessette, 23 years later,

Danny Bessette, 23 anos despois,

because this is the year,

porque este é o ano,

and it's also the year where Danny got married,

e tamén é o ano en que Danny casou,

where we have, for the first time, the approval by the FDA

en que, por primeira vez, a FDA (Food and Drug Administration)

of a drug that precisely targets the defect in cystic fibrosis

aproba un fármaco que ataca con precisión o defecto da fibrose quística

based upon all this molecular understanding.

baseándose no coñecemento molecular.

That's the good news.

Estas son as boas novas.

The bad news is, this drug doesn't actually treat all cases of cystic fibrosis,

As malas son que o fármaco non trata todos os casos de fibrose quísitica,

and it won't work for Danny, and we're still waiting

e non funcionará para Danny. Estamos á espera

for that next generation to help him.

da seguinte xeración para axudalo.

But it took 23 years to get this far. That's too long.

Levou 23 anos conseguir isto. É demasiado.

How do we go faster?

Como imos máis rápido?

Well, one way to go faster is to take advantage of technology,

Unha opción é aproveitar o avance da tecnoloxía,

and a very important technology that we depend on

e unha tecnoloxía moi importante da que dependemos

for all of this is the human genome,

é o xenoma humano,

the ability to be able to look at a chromosome,

a capacidade de ver un cromosoma,

to unzip it, to pull out all the DNA,

desenrolalo, extraer o ADN,

and to be able to then read out the letters in that DNA code,

e ser capaces de ler as letras neste código do ADN,

the A's, C's, G's and T's

os A, os C, os G e os T

that are our instruction book and the instruction book for all living things,

que son o libro de instrucións que nós, e todos os seres vivos, temos,

and the cost of doing this,

e o custo de facer isto,

which used to be in the hundreds of millions of dollars,

que era de centos de millóns de dólares,

has in the course of the last 10 years

diminuíu nestes últimos 10 anos

fallen faster than Moore's Law, down to the point

máis rápido que a lei de Moore

where it is less than 10,000 dollars today to have your genome sequenced, or mine,

ata o punto de que hoxe custa menos de 10.000 dólares ter un xenoma secuenciado

and we're headed for the $1,000 genome fairly soon.

e axuña custará sobre os 1.000.

Well, that's exciting.

Isto é emocionante.

How does that play out in terms of application to a disease?

Que significa isto en termos de aplicación ás enfermidades?

I want to tell you about another disorder.

Quero falarlles doutra enfermidade.

This one is a disorder which is quite rare.

Esta é unha enfermidade rara.

It's called Hutchinson-Gilford progeria,

Chámase a proxeria de Hutchinson-Gilford,

and it is the most dramatic form of premature aging.

e é a forma máis drástica de envellecemento prematuro.

Only about one in every four million kids has this disease,

Só a ten un de cada catro millóns de nenos

and in a simple way, what happens is,

e dunha forma sinxela, o que acontece é que,

because of a mutation in a particular gene,

a causa dunha mutación nun xene,

a protein is made that's toxic to the cell

créase unha proteína tóxica para a célula

and it causes these individuals to age

o que provoca que estes suxeitos envellezan

at about seven times the normal rate.

sete veces máis rápido do normal.

Let me show you a video of what that does to the cell.

Déixenme amosarlles un vídeo sobre o que provoca na célula.

The normal cell, if you looked at it under the microscope,

A célula normal, vista co microscopio,

would have a nucleus sitting in the middle of the cell,

terá un núcleo situado no seu centro

which is nice and round and smooth in its boundaries

que é bonito, redondo e liso nos seus bordos

and it looks kind of like that.

e aseméllase a isto.

A progeria cell, on the other hand,

Por outro lado, a célula da proxeria

because of this toxic protein called progerin,

a causa da proteína, chamada proxerina,

has these lumps and bumps in it.

ten estes vultos e protuberancias.

So what we would like to do after discovering this

O que queríamos facer despois de descubrir isto,

back in 2003

alá no 2003,

is to come up with a way to try to correct that.

era atopar unha maneira de corrixilo.

Well again, by knowing something about the molecular pathways,

De novo, coñecendo algo das vías moleculares,

it was possible to pick

era posible coller

one of those many, many compounds that might have been useful

un destes compostos que podían ser útiles

and try it out.

e probalo.

In an experiment done in cell culture

Nun experimento "in vitro"

and shown here in a cartoon,

mostrado nesta animación,

if you take that particular compound

se se escolle ese composto particular

and you add it to that cell that has progeria,

e se lle engade á célula que ten proxeria,

and you watch to see what happened,

observen o que acontece,

in just 72 hours, that cell becomes,

en só 72 horas, a célula transfórmase,

for all purposes that we can determine,

para todos os efectos que podemos determinar,

almost like a normal cell.

nunha célula normal.

Well that was exciting, but would it actually work in a real human being?

Funcionará nunha célula humana real?

This has led, in the space of only four years

Isto levou, en tan só catro anos

from the time the gene was discovered to the start of a clinical trial,

dende que se descubriu o xene ata que empezou o ensaio clínico,

to a test of that very compound.

a probar ese composto.

And the kids that you see here

Todos os nenos que ven aquí

all volunteered to be part of this,

participaron voluntariamente no proceso,

28 of them,

28 nenos,

and you can see as soon as the picture comes up

pódese ver, como mostra a foto,

that they are in fact a remarkable group of young people

que son un grupo de xente nova

all afflicted by this disease,

afectado pola enfermidade,

all looking quite similar to each other.

que se parecen bastante entre eles.

And instead of telling you more about it,

Antes de falarlles máis disto,

I'm going to invite one of them, Sam Berns from Boston,

vou invitar a un deles, Sam Berns de Boston,

who's here this morning, to come up on the stage

que está aquí esta mañá, a subir ao escenario

and tell us about his experience

para que nos conte a súa experiencia

as a child affected with progeria.

como un neno afectado de proxeria.

Sam is 15 years old. His parents, Scott Berns and Leslie Gordon,

Sam ten 15 anos. Seus pais, Scott Berns e Leslie Gordon,

both physicians, are here with us this morning as well.

médicos os dous, tamén están aquí esta mañá.

Sam, please have a seat.

Sam, senta por favor

(Applause)

(Aplausos)

So Sam, why don't you tell these folks

Sam, por que non lle dis a esta xente

what it's like being affected with this condition called progeria?

como é estar afectado de proxeria?

Sam Burns: Well, progeria limits me in some ways.

Sam Burns: A proxeria limítame nalgúns aspectos.

I cannot play sports or do physical activities,

Non podo facer deporte ou actividades físicas,

but I have been able to take interest in things

pero fun capaz de facer cousas interesantes

that progeria, luckily, does not limit.

que por sorte a proxeria non me limita.

But when there is something that I really do want to do

Pero cando hai algo que realmente quero facer

that progeria gets in the way of, like marching band

e a proxeria se interpón no meu camiño,

como tocar nunha banda, ou arbitrar,

or umpiring, we always find a way to do it,

sempre atopamos a maneira de facelo,

and that just shows that progeria isn't in control of my life.

e isto demostra que a proxeria non controla a miña vida.

(Applause)

(Aplausos)

Francis Collins: So what would you like to say to researchers

FC: Que lles dirías aos investigadores

here in the auditorium and others listening to this?

que están aquí e a outros que te escoiten?

What would you say to them both about research on progeria

Qué lles dirías sobre a investigación da proxeria

and maybe about other conditions as well?

e tamén doutras doenzas?

SB: Well, research on progeria has come so far

SB: A investigación en proxeria avanzou moito

in less than 15 years,

en menos de 15 anos,

and that just shows the drive that researchers can have

e isto amosa a determinación que os investigadores deben ter

to get this far, and it really means a lot

para avanzar tanto, o cal significa moito

to myself and other kids with progeria,

para min e para outros nenos con proxeria,

and it shows that if that drive exists,

e isto ensínanos que se esa determinación existe

anybody can cure any disease,

calquera pode curar calquera tipo de enfermidade,

and hopefully progeria can be cured in the near future,

e espero que a proxeria poida curarse nun futuro próximo

and so we can eliminate those 4,000 diseases

e que poidamos eliminar esas 4000 enfermidades

that Francis was talking about.

das que Francis falaba.

FC: Excellent. So Sam took the day off from school today

FC: Xenial. Sam faltou hoxe ao instituto

to be here, and he is — (Applause) --

para estar aquí --(Aplausos)--

He is, by the way, a straight-A+ student in the ninth grade

Aínda así, é un estudante de sobresaliente de noveno grado

in his school in Boston.

no seu instituto de Boston.

Please join me in thanking and welcoming Sam.

Deámoslle as grazas a Sam.

SB: Thank you very much. FC: Well done. Well done, buddy.

SB: Moitas grazas. FC: Ben feito, rapaz.

(Applause)

(Aplausos)

So I just want to say a couple more things

Quero dicir un par de cousas máis

about that particular story, and then try to generalize

sobre esta historia e tentar xeneralizar

how could we have stories of success

sobre como podemos ter historias de éxito

all over the place for these diseases, as Sam says,

para todas estas enfermidades, como dixo Sam,

these 4,000 that are waiting for answers.

estas 4000 enfermidades que agardan respostas.

You might have noticed that the drug

Debedes saber que o fármaco

that is now in clinical trial for progeria

que se está probando para a proxeria

is not a drug that was designed for that.

non é un fármaco deseñado para ela.

It's such a rare disease, it would be hard for a company

É unha enfermidade tan rara que unha empresa tería moi difícil

to justify spending hundreds of millions of dollars to generate a drug.

xustificar o gasto de centos de millóns de dólares para producir o fármaco.

This is a drug that was developed for cancer.

Este fármaco desenvolveuse para o cancro.

Turned out, it didn't work very well for cancer,

Non funcionou moi ben contra el,

but it has exactly the right properties, the right shape,

pero ten as propiedades exactas, a forma precisa,

to work for progeria, and that's what's happened.

para tratar a proxeria, e isto foi o que pasou.

Wouldn't it be great if we could do that more systematically?

Non sería fantástico facermos isto máis sistematicamente?

Could we, in fact, encourage all the companies that are out there

Poderiamos animar ás compañías

that have drugs in their freezers

que teñen fármacos nos conxeladores

that are known to be safe in humans

que sabemos que son seguros en humanos

but have never actually succeeded in terms

pero que nunca se demostraron efectivos

of being effective for the treatments they were tried for?

nos tratamentos para os que se deseñaron?

Now we're learning about all these new molecular pathways --

Agora estamos aprendendo sobre estas novas vías moleculares

some of those could be repositioned or repurposed,

algunhas das cales poderían ser reorientadas ou reutilizadas,

or whatever word you want to use, for new applications,

ou como lle queiramos chamar, para novas aplicacións,

basically teaching old drugs new tricks.

ensinándolles novos trucos a vellos fármacos.

That could be a phenomenal, valuable activity.

Podería ser unha actividade extraordinaria e valiosa.

We have many discussions now between NIH and companies

Temos moitos debates entre o Instituto Nacional da Saúde e empresas

about doing this that are looking very promising.

sobre facer isto que tan prometedor parece.

And you could expect quite a lot to come from this.

E temos bastantes esperanzas de que resulte.

There are quite a number of success stories one can point to

Hai abondas historias exitosas que podemos destacar

about how this has led to major advances.

sobre como isto comportou avances relevantes.

The first drug for HIV/AIDS

O primeiro fármaco contra o VIH

was not developed for HIV/AIDS.

non se desenvolveu para o VIH.

It was developed for cancer. It was AZT.

Foino para o cancro. Trátase do AZT.

It didn't work very well for cancer, but became

Non funcionou contra o cancro, pero foi

the first successful antiretroviral,

o primeiro antirretroviral exitoso,

and you can see from the table there are others as well.

e como se ve na táboa, hai outros tamén.

So how do we actually make that a more generalizable effort?

Como facemos este esforzo máis xeneralizable?

Well, we have to come up with a partnership

Temos que chegar a acordos

between academia, government, the private sector,

entre o mundo académico, o goberno, o sector privado,

and patient organizations to make that so.

e organizacións de pacientes para facelo.

No Instituto Nacional da Saúde, creamos un novo

At NIH, we have started this new

National Center for Advancing Translational Sciences.

Centro Nacional de Ciencias Translacionais Avanzadas.

It just started last December, and this is one of its goals.

Comezou en decembro pasado, e este é un dos seus obxectivos.

Let me tell you another thing we could do.

Déixenme dicirlles outra cousa que poderiamos facer

Wouldn't it be nice to be able to a test a drug

Non sería xenial se puidésemos probar un fármaco

to see if it's effective and safe

para ver se é efectivo e seguro

without having to put patients at risk,

sen poñer en risco pacientes,

because that first time you're never quite sure?

porque as primeiras veces non se está seguro?

How do we know, for instance, whether drugs are safe

Como sabemos que un fármaco é seguro

before we give them to people? We test them on animals.

antes de darllo a persoas? Probámolo en animais.

And it's not all that reliable, and it's costly,

E iso non é demasiado fiable, e ademais é custoso,

and it's time-consuming.

e consome tempo.

Suppose we could do this instead on human cells.

Imaxinen que podemos facelo en células humanas.

You probably know, if you've been paying attention

Se lle prestan atención á literatura científica

to some of the science literature

probablemente saberán que

that you can now take a skin cell

pode collerse unha célula da pel

and encourage it to become a liver cell

e estimulala para convertela en hepática

or a heart cell or a kidney cell or a brain cell for any of us.

ou cardíaca, ou renal ou derebral de calquera de nós.

So what if you used those cells as your test

E se utilizamos estas células para probar

for whether a drug is going to work and whether it's going to be safe?

se un fármaco vai ser efectivo e seguro?

Here you see a picture of a lung on a chip.

Velaquí unha imaxe dun pulmón nun chip.

This is something created by the Wyss Institute in Boston,

É unha creación do Wyss Institute en Boston,

and what they have done here, if we can run the little video,

e o que fixeron, se poñemos en marcha o vídeo,

is to take cells from an individual,

foi coller células dun individuo,

turn them into the kinds of cells that are present in the lung,

transformalas en células que hai nos pulmóns,

and determine what would happen

e ver que acontece

if you added to this various drug compounds

se se engaden varios compostos

to see if they are toxic or safe.

para ver se son seguros ou tóxicos.

You can see this chip even breathes.

Poden ver que este chip incluso respira.

It has an air channel. It has a blood channel.

Ten unha canle de aire e outra de sangue.

And it has cells in between

E ten células no medio

that allow you to see what happens when you add a compound.

que permiten ver o que acontece ao engadir un composto.

Are those cells happy or not?

Están contentas as células ou non?

You can do this same kind of chip technology

Pódese usar esta mesma tecnoloxía

for kidneys, for hearts, for muscles,

para riles, corazóns, músculos,

all the places where you want to see whether a drug

calquera órgano onde se queira ver se o fármaco

is going to be a problem, for the liver.

vai ser un problema, para o fígado.

And ultimately, because you can do this for the individual,

E finalmente, porque isto pode facerse para cada persoa,

we could even see this moving to the point

podemos ver que se encamiña ata o punto

where the ability to develop and test medicines

en que a capacidade para desenvolver e testar fármacos

will be you on a chip, what we're trying to say here is

irá con vostedes nun chip, o que implica

the individualizing of the process of developing drugs

a individualización do proceso para desenvolver fármacos

and testing their safety.

e probar a súa seguridade.

So let me sum up.

Resumindo.

We are in a remarkable moment here.

Estamos nun momento extraordinario.

For me, at NIH now for almost 20 years,

Para min, con case 20 anos no Instituto Nacional da Saúde,

there has never been a time where there was more excitement

nunca houbo unha época de maior entusiasmo

about the potential that lies in front of us.

sobre o potencial do que temos diante.

We have made all these discoveries

Fixemos todos estes descubrimentos

pouring out of laboratories across the world.

en laboratorios espallados polo mundo.

What do we need to capitalize on this? First of all, we need resources.

Que fai falla para sacar proveito deles? Primeiro, recursos.

This is research that's high-risk, sometimes high-cost.

Esta é investigación de alto risco, e ás veces de alto custo.

The payoff is enormous, both in terms of health

A recompensa é enorme, en termos de saúde

and in terms of economic growth. We need to support that.

e de crecemento económico. Hai que apoiala.

Second, we need new kinds of partnerships

Segundo, precisamos novos tipos de relacións

between academia and government and the private sector

entre o mundo académico, o goberno, o sector privado

and patient organizations, just like the one I've been describing here,

e as organizacións de pacientes, como xa contei aquí,

in terms of the way in which we could go after repurposing new compounds.

sobre que camiño adoptar despois da reutilización de compostos.

And third, and maybe most important, we need talent.

E terceiro, e pode que máis importante, precisamos talento.

We need the best and the brightest

Precisamos os mellores e máis brillantes

from many different disciplines to come and join this effort --

de diferentes disciplinas para vir e axudar,

all ages, all different groups --

de calquera idade, de calquera grupo,

because this is the time, folks.

porque este é o momento, amigos.

This is the 21st-century biology that you've been waiting for,

Esta é a bioloxía do s. XXI que estabamos a agardar,

and we have the chance to take that

e temos a oportunidade de collela

and turn it into something which will, in fact,

e convertela en algo

knock out disease. That's my goal.

acabe coas enfermidades. Ese é o meu obxectivo.

I hope that's your goal.

Agardo que tamén sexa o seu.

I think it'll be the goal of the poets and the muppets

Penso que será o obxectivo dos poetas, marionetas,

and the surfers and the bankers

surfeiros e banqueiros

and all the other people who join this stage

e de todas as persoas que se unan a esta causa

and think about what we're trying to do here

e pensen no que tentamos facer

and why it matters.

e por qué é importante.

It matters for now. It matters as soon as possible.

É importante para agora, para o antes posible.

If you don't believe me, just ask Sam.

Se non me cren, pregúntenlle a Sam.

Thank you all very much.

Moitas grazas a todos.

(Applause)

(Aplausos)