How CRISPR lets us edit our DNA | Jennifer Doudna

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

A few years ago,

Hai uns anos,

with my colleague, Emmanuelle Charpentier,

canda a miña colega Emmanuelle Charpentier

I invented a new technology for editing genomes.

inventei una nova tecnoloxía para editar xenomas.

It's called CRISPR-Cas9.

Chámase CRISPR-Cas 9.

The CRISPR technology allows scientists to make changes

A tecnoloxía CRISPR permítelles aos científicos facer cambios

to the DNA in cells

no ADN celular, o que podería

that could allow us to cure genetic disease.

permitir curar enfermidades xenéticas.

You might be interested to know

É interesante que saibades que a tecnoloxía CRISPR

that the CRISPR technology came about through a basic research project

xorde dun proxecto de investigación básica

that was aimed at discovering how bacteria fight viral infections.

que buscaba estudar como as bacterias

loitan contra infeccións virais.

Bacteria have to deal with viruses in their environment,

As bacterias teñen que enfrontarse con virus na súa contorna,

and we can think about a viral infection like a ticking time bomb --

podemos pensar nunha infección vírica

coma unha bomba de reloxaría.

a bacterium has only a few minutes to defuse the bomb

A bacteria ten só uns minutos para destruír a bomba

before it gets destroyed.

antes de que a destrúa a ela.

So, many bacteria have in their cells an adaptive immune system called CRISPR,

Así que moitas bacterias teñen nas súas células

un sistema inmune adaptativo chamado CRISPR

that allows them to detect viral DNA and destroy it.

que lles permite detectar ADN vírico e destruílo.

Parte do sistema CRISPR é una proteína que se chama Cas9

Part of the CRISPR system is a protein called Cas9,

que pode buscar, cortar e degradar o ADN viral

that's able to seek out, cut and eventually degrade viral DNA

in a specific way.

dunha forma específica.

And it was through our research

E foi na nosa investigación para

to understand the activity of this protein, Cas9,

entender o funcionamento de Cas9,

cando vimos que podíamos modificar a súa función

that we realized that we could harness its function

as a genetic engineering technology --

coma una tecnoloxía de enxeñería xenética

a way for scientists to delete or insert specific bits of DNA into cells

un xeito de que os científicos

poidan borrar ou inserir

fragmentos específicos de ADN

with incredible precision --

en células cunha precisión incrible

that would offer opportunities

Isto ofrecería oportunidades para facer cousas

to do things that really haven't been possible in the past.

que nunca serían posibles no pasado.

A tecnoloxía CRISPR xa se usou para cambiar o ADN

The CRISPR technology has already been used

to change the DNA in the cells of mice and monkeys,

nas células de ratos e monos,

other organisms as well.

e tamén noutros organismos.

Chinese scientists showed recently

Científicos chineses probaron hai pouco que poden usar

that they could even use the CRISPR technology

a tecnoloxía CRISPR para cambiar xenes en embrións humanos.

to change genes in human embryos.

E científicos en Filadelfia probaron que podían usar CRISPR

And scientists in Philadelphia showed they could use CRISPR

to remove the DNA of an integrated HIV virus

para retirar o ADN dun virus VIH

from infected human cells.

integrado en células infectadas humanas.

The opportunity to do this kind of genome editing

A oportunidade de realizar este tipo de edición xenética

also raises various ethical issues that we have to consider,

tamén implica cuestións éticas

que temos que considerar

because this technology can be employed not only in adult cells,

porque esta tecnoloxía non só se pode usar en células adultas

but also in the embryos of organisms,

senón tamén en embrións de organismos,

including our own species.

incluíndo os da nosa especie.

And so, together with my colleagues,

Así que, xunto cos meus colegas,

I've called for a global conversation about the technology that I co-invented,

convoquei unha conversa global sobre a tecnoloxía que coinventei,

so that we can consider all of the ethical and societal implications

para considerar todas as implicacións éticas e sociais

of a technology like this.

dunha tecnoloxía coma esta.

What I want to do now is tell you what the CRISPR technology is,

Agora quero contarvos

que é a tecnoloxía CRISPR,

o que pode facer,

what it can do,

where we are today

onde nos atopamos actualmente,

and why I think we need to take a prudent path forward

e por que penso que temos

que avanzar con prudencia á hora de empregala.

in the way that we employ this technology.

Cando os virus infectan unha célula,

When viruses infect a cell, they inject their DNA.

inxéctanlle o seu ADN.

And in a bacterium,

Nunha bacteria, o sistema CRISPR

the CRISPR system allows that DNA to be plucked out of the virus,

permite arrincar o ADN do virus

and inserted in little bits into the chromosome --

e inserilo en anacos no ADN bacteriano.

the DNA of the bacterium.

And these integrated bits of viral DNA get inserted at a site called CRISPR.

Estes anacos de ADN vírico

son inseridos na zona CRISPR.

CRISPR stands for clustered regularly interspaced short palindromic repeats.

CRISPR é en inglés "repeticións palindrómicas cortas

agrupadas e regularmente interespazadas".

(Laughter)

Unha palabra moi longa, xa entendedes

A big mouthful -- you can see why we use the acronym CRISPR.

porqué usamos o acrónimo CRISPR.

It's a mechanism that allows cells to record, over time,

É un mecanismo que permite ás células

gravar ao longo do tempo

the viruses they have been exposed to.

os virus aos que estiveron expostas.

And importantly, those bits of DNA are passed on to the cells' progeny,

E de xeito moi importante,

eses anacos de ADN

pásanselle á proxenie celular.

so cells are protected from viruses not only in one generation,

Polo tanto, as células están

protexidas fronte a virus

non só nunha xeración,

but over many generations of cells.

senón en varias.

This allows the cells to keep a record of infection,

Isto permite que as células teñan un rexistro de infeccións.

and as my colleague, Blake Wiedenheft, likes to say,

Como di a miña colega Blake Wiedenheft,

the CRISPR locus is effectively a genetic vaccination card in cells.

o locus CRISPR é un rexistro de vacinas

moi efectivo para as células.

Once those bits of DNA have been inserted into the bacterial chromosome,

Cando eses anacos de ADN

se insiren no cromosoma bacteriano

the cell then makes a little copy of a molecule called RNA,

a célula fai una pequena copia

dunha molécula, o ARN,

which is orange in this picture,

en laranxa na foto.

that is an exact replicate of the viral DNA.

Que é una copia exacta do ARN vírico.

RNA is a chemical cousin of DNA,

O ARN é un curmán químico do ADN.

and it allows interaction with DNA molecules

Permite a interacción con moléculas de ADN

that have a matching sequence.

que teñan una secuencia 'correspondente'.

So those little bits of RNA from the CRISPR locus

Eses anacos de ARN do locus CRISPR

associate -- they bind -- to protein called Cas9,

únense á proteína Cas 9,

which is white in the picture,

en branco na imaxe,

and form a complex that functions like a sentinel in the cell.

e forman un complexo

que funciona como sentinela na célula.

It searches through all of the DNA in the cell,

Busca en todo o ADN

to find sites that match the sequences in the bound RNAs.

para atopar secuencias que corresponden

coas dos ARN unidos.

And when those sites are found --

E cando eses sitios son atopados,

as you can see here, the blue molecule is DNA --

como podedes ver aquí

--a molécula de ADN é azul--

this complex associates with that DNA

o complexo asóciase con ese ADN,

and allows the Cas9 cleaver to cut up the viral DNA.

e Cas9 pode cortar o ADN vírico.

It makes a very precise break.

Fai un corte moi exacto.

Podemos pensar neste complexo sentinela-Cas9-ARN,

So we can think of the Cas9 RNA sentinel complex

like a pair of scissors that can cut DNA --

como un par de tesoiras

que poden cortar ADN,

it makes a double-stranded break in the DNA helix.

facendo un corte na dobre cadea.

And importantly, this complex is programmable,

Este complexo é programable,

so it can be programmed to recognize particular DNA sequences,

pode ser programado para recoñecer

secuencias específicas de ADN

and make a break in the DNA at that site.

e facer un corte no ADN nese lugar.

As I'm going to tell you now,

Démonos conta

we recognized that that activity could be harnessed for genome engineering,

de que esa actividade

podía ser usada para edición xenómica,

para permitirlles ás células facer

to allow cells to make a very precise change to the DNA

un cambio moi preciso no seu ADN

at the site where this break was introduced.

no lugar onde se produce a rotura.

That's sort of analogous

É parecido a usar un procesador de textos

to the way that we use a word-processing program

to fix a typo in a document.

para corrixir un erro nun documento.

The reason we envisioned using the CRISPR system for genome engineering

A razón pola que concibimos usar o sistema CRISPR

para edición xenómica é por que

is because cells have the ability to detect broken DNA

as células teñen a habilidade de detectar ADN roto e reparalo.

and repair it.

So when a plant or an animal cell detects a double-stranded break in its DNA,

Cando una célula animal ou vexetal

detecta una dobre rotura de hélice

no seu ADN, pode reparala,

it can fix that break,

either by pasting together the ends of the broken DNA

xa sexa por copia e pega

dos extremos do ADN roto

with a little, tiny change in the sequence of that position,

cun pequeno cambio na secuencia desa posición,

ou pode reparar a rotura

or it can repair the break by integrating a new piece of DNA at the site of the cut.

integrando un novo anaco de ADN

no lugar do corte.

Así que, se temos un xeito

So if we have a way to introduce double-stranded breaks into DNA

de introducir cortes na dobre cadea de ADN

en determinados lugares,

at precise places,

we can trigger cells to repair those breaks,

podemos inducir as células

a reparar esas roturas por perda

by either the disruption or incorporation of new genetic information.

ou incorporación

de nova información xenética.

So if we were able to program the CRISPR technology

Así que, se fósemos capaces

de programar a tecnoloxía CRISPR

to make a break in DNA

para facer un corte cerca

at the position at or near a mutation causing cystic fibrosis, for example,

ou na posición dunha mutación causante

da fibrose quística, por exemplo,

we could trigger cells to repair that mutation.

poderiamos inducir as células a reparar esa mutación.

Genome engineering is actually not new, it's been in development since the 1970s.

A enxeñería xenómica non é algo recente,

comezou nos anos 70.

We've had technologies for sequencing DNA,

Tiñamos tecnoloxías para secuenciar ADN,

for copying DNA,

copiar ADN,

and even for manipulating DNA.

e incluso para manipular ADN.

And these technologies were very promising,

E estas tecnoloxías eran moi prometedoras,

but the problem was that they were either inefficient,

pero tiñan como problema

a súa ineficiencia

or they were difficult enough to use

ou dificultade de uso,

that most scientists had not adopted them for use in their own laboratories,

polo que moitos científicos non

as usaron nos seus laboratorios

or certainly for many clinical applications.

ou en ningunha aplicación clínica.

So, the opportunity to take a technology like CRISPR and utilize it has appeal,

A oportunidade de usar unha nova

tecnoloxía como é CRISPR

ten certo atractivo

because of its relative simplicity.

debido á súa simplicidade.

Podemos pensar en técnicas de enxeñería xenómica máis vellas,

We can think of older genome engineering technologies

as similar to having to rewire your computer

e comparalas con

ter que recablear un ordenador

each time you want to run a new piece of software,

cada vez que queiras probar un novo software.

whereas the CRISPR technology is like software for the genome,

Pola contra, a tecnoloxía CRISPR

é como software para o xenoma,

we can program it easily, using these little bits of RNA.

xa que pode ser programado doadamente

usando estes anacos de ARN.

So once a double-stranded break is made in DNA,

Así que, cando causamos unha rotura de cadea dobre

we can induce repair,

podemos inducir a reparación

and thereby potentially achieve astounding things,

e obter resultados potencialmente asombrosos.

like being able to correct mutations that cause sickle cell anemia

Como poder corrixir mutacións

que causan anemias falciformes

or cause Huntington's Disease.

ou a enfermidade de Huntington.

I actually think that the first applications of the CRISPR technology

Creo que as primeiras aplicacións da técnica CRISPR

are going to happen in the blood,

terán lugar no sangue,

where it's relatively easier to deliver this tool into cells,

xa que é máis doado introducir

esta ferramenta nas células,

compared to solid tissues.

en comparación con tecidos sólidos.

Right now, a lot of the work that's going on

Hoxe, moitas das investigacións en que se traballa

applies to animal models of human disease, such as mice.

aplícanse sobre modelos animais de enfermidades humanas,

coma os ratos.

The technology is being used to make very precise changes

Esta tecnoloxía úsase para facer cambios precisos no ADN celular,

that allow us to study the way that these changes in the cell's DNA

que permiten estudar o xeito en que estes

cambios no ADN celular

affect either a tissue or, in this case, an entire organism.

poden afectar un tecido,

ou neste caso, un organismo.

Now in this example,

No seguinte exemplo,

the CRISPR technology was used to disrupt a gene

a técnica CRISPR usouse para interromper un xene

by making a tiny change in the DNA

facendo un pequeno cambio

no ADN nun xene responsable

in a gene that is responsible for the black coat color of these mice.

da cor negra destes ratos.

Imagine that these white mice differ from their pigmented litter-mates

Pensade que a diferencia entre os ratos

brancos e os seus compañeiros

de camada negros

é debida soamente a un pequeno cambio

by just a tiny change at one gene in the entire genome,

nun único xene no xenoma enteiro.

and they're otherwise completely normal.

E senón fora por iso serían normais.

And when we sequence the DNA from these animals,

Cando secuenciamos o ADN destes animais

we find that the change in the DNA

comprobamos que o cambio no ADN

has occurred at exactly the place where we induced it,

prodúcese exactamente no sitio onde foi inducido

using the CRISPR technology.

mediante o uso de CRISPR.

Additional experiments are going on in other animals

Estanse facendo experimentos con outros animais

that are useful for creating models for human disease,

que son útiles para crear modelos

de enfermidades humanas,

such as monkeys.

como os monos.

And here we find that we can use these systems

E nestes vemos que podemos usar estes sistemas

to test the application of this technology in particular tissues,

para probar a aplicación

desta técnica en tecidos específicos,

for example, figuring out how to deliver the CRISPR tool into cells.

por exemplo, estudar como introducir

o complexo CRISPR nas células.

We also want to understand better

Tamén queremos entender mellor

how to control the way that DNA is repaired after it's cut,

como controlar a reparación do ADN logo de cortado

and also to figure out how to control and limit any kind of off-target,

e aprender a controlar e limitar calquera

acción fóra dos lugares diana

or unintended effects of using the technology.

ou efectos non desexados

derivados do uso desta tecnoloxía.

I think that we will see clinical application of this technology,

Penso que veremos aplicacións clínicas desta tecnoloxía,

certainly in adults,

probablemente en adultos,

within the next 10 years.

nos próximos 10 anos.

I think that it's likely that we will see clinical trials

Penso que é moi posible que vexamos ensaios clínicos

and possibly even approved therapies within that time,

e posiblemente terapias aprobadas

nesa franxa temporal,

which is a very exciting thing to think about.

o que é moi emocionante.

And because of the excitement around this technology,

E debido á expectación arredor desta tecnoloxía,

there's a lot of interest in start-up companies

hai moitos intereses en empresas emerxentes

that have been founded to commercialize the CRISPR technology,

que foron creadas para vender a tecnoloxía CRISPR,

and lots of venture capitalists

e moitos capitalistas de risco

that have been investing in these companies.

que invisten nestas compañías.

But we have to also consider

Pero tamén temos que ter en conta

that the CRISPR technology can be used for things like enhancement.

que CRISPR pode ser usada en mellora xenética.

Imagine that we could try to engineer humans

Imaxinade que poderiamos intentar

facer enxeñería en humanos,

that have enhanced properties, such as stronger bones,

que teñen propiedades melloradas,

como ósos máis fortes,

or less susceptibility to cardiovascular disease

ou menor susceptibilidade a enfermidades cardiovasculares

ou quizais teñan propiedades

or even to have properties

that we would consider maybe to be desirable,

que consideremos desexables,

como diferente cor de ollos

like a different eye color or to be taller, things like that.

ou ser máis altos.

"Designer humans," if you will.

Humanos á carta, poderíase dicir.

Right now, the genetic information

Neste momento,

a información xenética

to understand what types of genes would give rise to these traits

necesaria para entender

que tipo de xenes producen

este tipo de características

is mostly not known.

é na súa maior parte descoñecida.

But it's important to know

Pero é importante saber

that the CRISPR technology gives us a tool to make such changes,

que coa tecnoloxía CRISPR

podemos facer eses cambios,

unha vez que saibamos esta información.

once that knowledge becomes available.

This raises a number of ethical questions that we have to carefully consider,

Isto pon enriba da mesa cuestión éticas

que temos que considerar con coidado,

and this is why I and my colleagues have called for a global pause

e por iso eu e os meus colegas chamamos a una pausa mundial

na aplicación clínica de CRISPR

in any clinical application of the CRISPR technology in human embryos,

en embrións humanos,

to give us time

para deixarnos tempo para considerar

to really consider all of the various implications of doing so.

todas as implicacións deste tipo de experimentación.

And actually, there is an important precedent for such a pause

E curiosamente, hai un precedente importante

dunha pausa semellante

from the 1970s,

nos anos 70,

when scientists got together

cando científicos se xuntaron

to call for a moratorium on the use of molecular cloning,

para pedir unha moratoria no uso da clonación molecular,

until the safety of that technology could be tested carefully and validated.

ata que a seguridade desa tecnoloxía

puidese ser probada coidadosamente

e validada.

So, genome-engineered humans are not with us yet,

Aínda non temos humanos modificados

xeneticamente entre nós,

but this is no longer science fiction.

pero isto xa non é ciencia ficción.

Genome-engineered animals and plants are happening right now.

Animais e plantas con xenomas deseñados

xa existen actualmente.

And this puts in front of all of us a huge responsibility,

E isto suponnos unha gran responsabilidade,

to consider carefully both the unintended consequences

considerar coidadosamente

as consecuencias non previstas

as well as the intended impacts of a scientific breakthrough.

e os impactos que queremos nun descubrimento científico.

Grazas.

Thank you.

(Applause)

(Aplauso)

(Applause ends)

(O aplauso remata)

Bruno Giussani: Jennifer, this is a technology with huge consequences,

Bruno Giussiani: Jennifer, esta é unha tecnoloxía

cunhas consecuencias importantes,

as you pointed out.

como resaltaches.

Your attitude about asking for a pause or a moratorium or a quarantine

A túa decisión de pedir unha pausa, moratoria ou corentena,

is incredibly responsible.

é incriblemente responsable.

There are, of course, the therapeutic results of this,

Temos por suposto, os resultados terapéuticos,

but then there are the un-therapeutic ones

pero tamén existen os non terapéuticos,

and they seem to be the ones gaining traction,

e estes últimos parecen ser

os que gañan máis atención mediática.

particularly in the media.

This is one of the latest issues of The Economist -- "Editing humanity."

Esta é unha das últimas

publicacións de The Economist:

''Editando a humanidade''.

It's all about genetic enhancement, it's not about therapeutics.

Só fala de mellora xenética,

non da parte terapéutica.

What kind of reactions did you get back in March

Que tipo de reacción recibiches en marzo

from your colleagues in the science world,

por parte dos teus colegas científicos

when you asked or suggested

cando suxeriches ou pediches

that we should actually pause this for a moment and think about it?

que deberiamos tomar un descanso

e pensar no que isto comporta?

Jennifer Doudna: Os meus colegas,

Jennifer Doudna: My colleagues were actually, I think, delighted

penso, estaban realmente contentos de ter a ocasión

to have the opportunity to discuss this openly.

discutir isto abertamente.

It's interesting that as I talk to people,

É interesante que ao falar coa xente,

my scientific colleagues as well as others,

xa sexan, colegas científicos ou outros,

hai moita variedade de puntos de vista.

there's a wide variety of viewpoints about this.

So clearly it's a topic that needs careful consideration and discussion.

Así que, claramente precisamos

un exame detido e debate neste tema.

BG: There's a big meeting happening in December

BG: Planeades unha gran reunión en decembro,

that you and your colleagues are calling,

convocada polos teus colegas,

coa Academia Nacional de Ciencias e outros.

together with the National Academy of Sciences and others,

Que pensas que sairá da reunión a nivel práctico?

what do you hope will come out of the meeting, practically?

JD: Well, I hope that we can air the views

JD: Ben, agardo que poidamos expresar

of many different individuals and stakeholders

os puntos de vista de diferentes individuos

e partes interesadas

who want to think about how to use this technology responsibly.

que queiran pensar como usar esta tecnoloxía de xeito responsable.

It may not be possible to come up with a consensus point of view,

Tal vez non sexa posible chegar

a un punto de vista consensuado,

pero polo menos poderemos entender

but I think we should at least understand

a que problemas nos enfrontaremos

what all the issues are as we go forward.

con este avance.

BG: Outros colegas teus,

BG: Now, colleagues of yours,

like George Church, for example, at Harvard,

como George Church, por exemplo, de Harvard,

they say, "Yeah, ethical issues basically are just a question of safety.

din que “os problemas éticos

son basicamente cuestión de seguridade.

Probamos múltiples veces

We test and test and test again, in animals and in labs,

en animais e en laboratorios,

and then once we feel it's safe enough, we move on to humans."

e cando vemos que é o seguro abondo,

pasamos a humanos".

So that's kind of the other school of thought,

Así que esa é a outra liña de pensamento,

that we should actually use this opportunity and really go for it.

que deberíamos coller esta oportunidade e aproveitala.

Is there a possible split happening in the science community about this?

E posible que a comunidade científica se divida por isto?

I mean, are we going to see some people holding back

Imos ver xente botarse atrás,

because they have ethical concerns,

porque teñen preocupacións éticas,

and some others just going forward

e outros simplemente avanzando

because some countries under-regulate or don't regulate at all?

porque algúns países lexislan pouco ou nada.

JD: Ben, penso que como en calquera nova tecnoloxía,

JD: Well, I think with any new technology, especially something like this,

especialmente algo deste tipo

there are going to be a variety of viewpoints,

vai haber puntos de vista moi distintos,

and I think that's perfectly understandable.

e creo que iso é comprensible.

I think that in the end,

Penso que nun tempo usaremos

this technology will be used for human genome engineering,

esta tecnoloxía para

enxeñería xenómica en humanos,

pero facer iso sen analizar e debater

but I think to do that without careful consideration and discussion

of the risks and potential complications

os riscos potenciais

non sería responsable.

would not be responsible.

BG: There are a lot of technologies and other fields of science

BG: Hai moitas outras tecnoloxías e campos da ciencia

que, como a túa, están crecendo exponencialmente.

that are developing exponentially, pretty much like yours.

I'm thinking about artificial intelligence, autonomous robots and so on.

Estou a pensar en intelixencia artificial,

robots autónomos, etcétera.

Parece que ninguén,

No one seems --

á parte do asunto dos robots autónomos de guerra,

aside from autonomous warfare robots --

nobody seems to have launched a similar discussion in those fields,

ninguén parece ter comezado un debate así,

neses campos, pedindo unha moratoria.

in calling for a moratorium.

Cres que o teu debate poder servir

Do you think that your discussion may serve as a blueprint for other fields?

de precedente para outros campos?

JD: Well, I think it's hard for scientists to get out of the laboratory.

JD: Ben, penso que é difícil para os científicos saír do laboratorio.

Speaking for myself,

Incluso para min,

it's a little bit uncomfortable to do that.

é algo incómodo facer iso.

But I do think that being involved in the genesis of this

Pero realmente penso que

ser parte da xénese disto

really puts me and my colleagues in a position of responsibility.

ponnos, a min e aos meus colegas,

nunha posición de responsabilidade.

And I would say that I certainly hope that other technologies

E certamente,

espero que outras tecnoloxías

will be considered in the same way,

sexan consideradas do mesmo modo,

just as we would want to consider something that could have implications

do mesmo xeito que considerariamos

algo con implicacións

in other fields besides biology.

noutros campos fóra da bioloxía.

BG: Jennifer, thanks for coming to TED.

BG: Jennifer, grazas por vir ás charlas TED.

JD: Thank you.

(Applause)

JD: Grazas.

(Aplausos)