Gene editing can now change an entire species -- forever | Jennifer Kahn

Translator: Daniel Freire Vaamonde Reviewer: traduceTED USC

Nesta charla falaremos da deriva xenética,

pero, para comezar, vou contarvos unha breve historia.

Hai 20 anos, un biólogo chamado Anthony James

So this is a talk about gene drives,

obsesionouse coa idea de crear mosquitos

but I'm going to start by telling you a brief story.

que non transmitisen a malaria.

20 years ago, a biologist named Anthony James

Foi unha grande idea,

got obsessed with the idea of making mosquitos

e, basicamente, un fracaso absoluto.

that didn't transmit malaria.

Por unha parte, resultou ser realmente complicado

crear mosquitos resistentes á malaria.

It was a great idea, and pretty much a complete failure.

James conseguiuno, por fin, hai pouco tempo,

For one thing, it turned out to be really hard

engadindo uns xenes que facían imposíbel

to make a malaria-resistant mosquito.

que o parasito da malaria sobrevivise no interior do mosquito.

James managed it, finally, just a few years ago,

Pero iso creou outro problema.

by adding some genes that make it impossible

Agora que tes un mosquito resistente á malaria,

for the malaria parasite to survive inside the mosquito.

como fas que substitúa todos os mosquitos portadores da malaria?

But that just created another problem.

Hai múltiples opcións,

Now that you've got a malaria-resistant mosquito,

pero o plan A consistía en criar

how do you get it to replace all the malaria-carrying mosquitos?

unha chea dos novos mosquitos modificados xeneticamente,

liberalos na natureza

e esperar que transmitisen os seus xenes.

There are a couple options,

but plan A was basically to breed up

A cuestión é que, literalmente, hai que liberar

a bunch of the new genetically-engineered mosquitos

10 veces a cantidade de mosquitos nativos para que funcione.

release them into the wild

and hope that they pass on their genes.

Deste xeito, nunha aldea

The problem was that you'd have to release

con dez mil mosquitos, liberas cen mil máis.

literally 10 times the number of native mosquitos to work.

Como podedes supoñer,

non foi unha estratexia moi popular entre os aldeáns.

So in a village with 10,000 mosquitos,

(Gargalladas)

you release an extra 100,000.

Entón, o pasado xaneiro, Anthony James recibiu

As you might guess,

this was not a very popular strategy with the villagers.

un correo electrónico dun biólogo chamado Ethan Bier.

(Laughter)

Bier comentou que el e o seu estudante Valentino Gantz

Then, last January, Anthony James got an email

se toparan cunha ferramenta que non só garantiría

from a biologist named Ethan Bier.

que se herdase unha característica xenética particular,

Bier said that he and his grad student Valentino Gantz

senón que, ademais, se espallaría moi rápido.

had stumbled on a tool that could not only guarantee

Se estivesen no correcto, isto resolvería o problema

no que el e James traballaron 20 anos.

that a particular genetic trait would be inherited,

but that it would spread incredibly quickly.

Como proba, modificaron dous mosquitos que levaban o xene antimalaria

If they were right, it would basically solve the problem

e esta nova ferramenta,

that he and James had been working on for 20 years.

un impulso xénico, que explicarei nun minuto.

As a test, they engineered two mosquitos to carry the anti-malaria gene

Finalmente, planeárono de tal xeito

que os mosquitos co xene antimalaria

and also this new tool, a gene drive,

non terían os típicos ollos brancos, senón que terían ollos vermellos.

which I'll explain in a minute.

Finally, they set it up so that any mosquitos

Isto era só por conveniencia,

that had inherited the anti-malaria gene

para identificalos dunha ollada.

wouldn't have the usual white eyes, but would instead have red eyes.

Así, meteron nunha caixa os dous mosquitos antimalaria

That was pretty much just for convenience

de ollos vermellos con 30 normais de ollos brancos

so they could tell just at a glance which was which.

e deixáronos cruzarse.

En dúas xeracións, produciron 3800 netos.

So they took their two anti-malarial, red-eyed mosquitos

and put them in a box with 30 ordinary white-eyed ones,

Iso non é o sorprendente.

and let them breed.

Isto é o sorprendente:

In two generations, those had produced 3,800 grandchildren.

ao comezar con só dous mosquitos de ollos vermellos

e 30 de ollos brancos,

That is not the surprising part.

esperarías unha maioría de descendentes de ollos brancos.

This is the surprising part:

given that you started with just two red-eyed mosquitos

Porén, cando James abriu a caixa,

and 30 white-eyed ones,

todos os 3800 mosquitos tiñan ollos vermellos.

you expect mostly white-eyed descendants.

Cando lle preguntei a Ethan Bier

Instead, when James opened the box,

por este momento, emocionouse tanto que se puxo a gritar polo teléfono.

all 3,800 mosquitos had red eyes.

Obter só mosquitos de ollos vermellos

When I asked Ethan Bier about this moment,

viola a norma que é a pedra angular absoluta da bioloxía:

he became so excited that he was literally shouting into the phone.

a xenética mendeliana.

Serei breve: a xenética mendeliana di que, ao cruzar un macho e unha femia,

That's because getting only red-eyed mosquitos

violates a rule that is the absolute cornerstone of biology,

o fillo herda a metade do ADN de cada un dos pais,

Mendelian genetics.

así que, se o mosquito orixinal era aa e o novo mosquito é aB,

I'll keep this quick,

but Mendelian genetics says when a male and a female mate,

onde B é o xene antimalaria,

their baby inherits half of its DNA from each parent.

os fillos deberían aparecer en catro permutacións:

So if our original mosquito was aa and our new mosquito is aB,

aa, aB, aa, Ba.

En vez diso, co novo impulso xénico,

where B is the anti-malarial gene,

todos son aB.

the babies should come out in four permutations:

aa, aB, aa, Ba.

Bioloxicamente, isto non debería ser posible.

Instead, with the new gene drive,

Entón, que pasou?

O primeiro que ocorreu

they all came out aB.

foi a chegada da ferramenta de modificación xénica CRISPR en 2012.

Biologically, that shouldn't even be possible.

So what happened?

Pode que oísedes falar de CRISPR,

The first thing that happened

así que só direi que CRISPR

permite aos investigadores editar xenes

was the arrival of a gene-editing tool known as CRISPR in 2012.

de xeito moi rápido, simple e preciso.

Many of you have probably heard about CRISPR,

Faino aproveitando un mecanismo que xa existía en bacterias.

so I'll just say briefly that CRISPR is a tool that allows researchers

Hai unha proteína que actúa como unhas tesoiras e corta o ADN,

to edit genes very precisely, easily and quickly.

e hai unha molécula de ARN que dirixe as tesoiras

It does this by harnessing a mechanism that already existed in bacteria.

a calquera punto do xenoma.

O resultado é un procesador de texto para xenes.

Basically, there's a protein that acts like a scissors

and cuts the DNA,

Podes sacar un xene completo, introducir outro,

and there's an RNA molecule that directs the scissors

ou mesmo editar unha única letra dun xene.

to any point on the genome you want.

The result is basically a word processor for genes.

E pódese facer en case calquera especie.

You can take an entire gene out, put one in,

Recordades que dixen que os impulsos xénicos tiñan dous problemas?

or even edit just a single letter within a gene.

And you can do it in nearly any species.

O primeiro era a dificultade de modificar un mosquito

para ser resistente á malaria.

OK, remember how I said that gene drives originally had two problems?

Iso está solucionado grazas a CRISPR.

Pero o outro era loxístico.

The first was that it was hard to engineer a mosquito

Como facemos que a característica se espalle?

to be malaria-resistant.

Aquí ponse interesante.

That's basically gone now, thanks to CRISPR.

Hai un par de anos, un biólogo de Harvard chamado Kevin Esvelt

But the other problem was logistical.

How do you get your trait to spread?

pensou que pasaría

se fixésemos que CRISPR non só inserise o novo xene,

This is where it gets clever.

A couple years ago, a biologist at Harvard named Kevin Esvelt

senón tamén a maquinaria que corta e pega.

wondered what would happen

En outras palabras, que pasaría se CRISPR se copiase e pegase el mesmo?

if you made it so that CRISPR inserted not only your new gene

but also the machinery that does the cutting and pasting.

Acabariamos cunha máquina de movemento perpetuo para a edición xénica.

In other words, what if CRISPR also copied and pasted itself.

E iso foi exactamente o que pasou.

Este impulso xénico con CRISPR que creou Esvelt

You'd end up with a perpetual motion machine for gene editing.

non só garante que a característica se herde;

And that's exactly what happened.

ademais, se se usa nas células xerminais,

This CRISPR gene drive that Esvelt created

copiarase e pegarase o novo xene automaticamente

not only guarantees that a trait will get passed on,

en ambos os cromosomas de cada individuo.

but if it's used in the germline cells,

É coma un buscar e substituír global

ou, en termos científicos, torna un trazo heterocigoto en homocigoto.

it will automatically copy and paste your new gene

into both chromosomes of every single individual.

Entón, que significa isto?

It's like a global search and replace,

Significa que temos unha ferramenta moi poderosa á vez que alarmante.

or in science terms, it makes a heterozygous trait homozygous.

So, what does this mean?

Ata agora, que os impulsos xénicos

For one thing, it means we have a very powerful,

non funcionasen moi ben era, de feito, un alivio.

but also somewhat alarming new tool.

Normalmente, cando manipulamos os xenes dun organismo,

facémolo menos competente evolutivamente.

Up until now, the fact that gene drives didn't work very well

Así, os biólogos poden crear

was actually kind of a relief.

as moscas mutantes que queiran sen preocuparse.

Normally when we mess around with an organism's genes,

Se algunha escapa, a selección natural encárgase dela.

we make that thing less evolutionarily fit.

So biologists can make all the mutant fruit flies they want

O extraordinario, poderoso e aterrador dos impulsos xénicos

without worrying about it.

é que isto xa non é certo.

If some escape, natural selection just takes care of them.

Asumindo que a característica non ten unha gran desvantaxe evolutiva,

What's remarkable and powerful and frightening about gene drives

como que un mosquito non poida voar

is that that will no longer be true.

o impulso xénico baseado en CRISPR ciscará o cambio incansablemente

Assuming that your trait does not have a big evolutionary handicap,

ata que estea en cada individuo da poboación.

like a mosquito that can't fly,

the CRISPR-based gene drive will spread the change relentlessly

Agora, é difícil crear un impulso xénico que funcione ben,

pero James e Esvelt pensan que poden.

until it is in every single individual in the population.

As boas novas son que isto abre a porta a cousas extraordinarias.

Now, it isn't easy to make a gene drive that works that well,

Se pos un impulso xénico antimalaria

but James and Esvelt think that we can.

en só o 1 % de mosquitos Anopheles,

a especie que transmite a malaria,

The good news is that this opens the door to some remarkable things.

os científicos estiman que se espallaría á poboación enteira nun ano.

If you put an anti-malarial gene drive

in just 1 percent of Anopheles mosquitoes,

Nun ano, poderíase practicamente eliminar a malaria.

the species that transmits malaria,

Na práctica, aínda quedan uns anos para ser capaces diso,

researchers estimate that it would spread to the entire population in a year.

pero mentres, mil nenos morren a diario de malaria.

So in a year, you could virtually eliminate malaria.

Nun ano, o número podería ser case 0.

In practice, we're still a few years out from being able to do that,

O mesmo ocorre co dengue, a chikungunya e a febre amarela.

but still, a 1,000 children a day die of malaria.

E a cousa ponse aínda mellor.

In a year, that number could be almost zero.

Imaxinade que queremos acabar cunha especie invasora,

The same goes for dengue fever, chikungunya, yellow fever.

como a carpa asiática nos Grandes Lagos.

Habería que liberar un impulso xénico

And it gets better.

que faga que os peixes só teñan descendencia masculina.

Say you want to get rid of an invasive species,

En poucas xeracións, non haberá máis femias nin máis carpas.

like get Asian carp out of the Great Lakes.

All you have to do is release a gene drive

En teoría, poderiamos restituír centos de especies nativas

that makes the fish produce only male offspring.

case extintas.

In a few generations, there'll be no females left, no more carp.

Esas son as boas novas,

In theory, this means we could restore hundreds of native species

e estas, as malas.

that have been pushed to the brink.

Os impulsos xénicos son tan efectivos

que mesmo unha liberación accidental podería cambiar unha especie enteira,

OK, that's the good news,

this is the bad news.

a miúdo moi rápido.

Anthony James tomou precaucións.

Gene drives are so effective

Cruzou os mosquitos nun laboratorio de contención

that even an accidental release could change an entire species,

e empregou especies non nativas dos EUA para que,

and often very quickly.

mesmo se algún escapaba,

Anthony James took good precautions.

morrese e non tivese nada co que cruzarse.

He bred his mosquitos in a bio-containment lab

Tamén é certo que se unha ducia de carpas asiáticas co impulso xénico de soamente

and he also used a species that's not native to the US

so that even if some did escape,

descendencia masculina se levasen accidentalmente de volta a Asia,

they'd just die off, there'd be nothing for them to mate with.

But it's also true that if a dozen Asian carp with the all-male gene drive

poderían potencialmente aniquilar a poboación de carpa asiática nativa.

accidentally got carried from the Great Lakes back to Asia,

Non é tan improbable polo conectado que está o noso mundo.

they could potentially wipe out the native Asian carp population.

De feito, ese é o motivo polo que temos especies invasoras.

Isto aplica aos peixes.

Outros animais, como mosquitos e moscas,

And that's not so unlikely, given how connected our world is.

non hai forma de contelos.

In fact, it's why we have an invasive species problem.

Cruzan fronteiras e océanos constantemente.

And that's fish.

Things like mosquitos and fruit flies,

A outra mala nova

é que o impulso xénico pode non quedar confinado

there's literally no way to contain them.

no que chamamos especies diana.

They cross borders and oceans all the time.

Isto é polo fluxo xénico,

OK, the other piece of bad news

unha forma sofisticada de dicir que especies veciñas

is that a gene drive might not stay confined

se cruzan entre elas.

Se iso ocorre, é posíbel que un impulso xénico se transmita.

to what we call the target species.

That's because of gene flow,

Unha carpa asiática podería infectar outra carpa.

which is a fancy way of saying that neighboring species

Iso non é tan malo se o impulso só promove un trazo, coma a cor de ollos.

sometimes interbreed.

If that happens, it's possible a gene drive could cross over,

De feito, é posible que vexamos

unha ondada de moscas moi estrañas nun futuro próximo.

like Asian carp could infect some other kind of carp.

That's not so bad if your drive just promotes a trait, like eye color.

Pero podería ser un desastre

se o impulso elimina a especie por completo.

In fact, there's a decent chance that we'll see

a wave of very weird fruit flies in the near future.

O último punto preocupante é que a tecnoloxía para facer isto,

But it could be a disaster

para modificar xeneticamente un organismo e incluír un impulso xénico,

if your drive is deigned to eliminate the species entirely.

é algo que basicamente calquera laboratorio do mundo pode facer.

The last worrisome thing is that the technology to do this,

Un universitario podería facelo.

to genetically engineer an organism and include a gene drive,

Un estudante de bacharelato con talento e equipamento podería facelo.

is something that basically any lab in the world can do.

An undergraduate can do it.

Agora, creo que iso soa aterrador.

(Risa)

A talented high schooler with some equipment can do it.

Curiosamente, practicamente calquera científico co que falo

Now, I'm guessing that this sounds terrifying.

pensa que os impulsos xénicos non son tan aterradores ou perigosos.

(Laughter)

En parte porque cren que os científicos os usarán con coidado e responsabilidade.

Interestingly though, nearly every scientist I talk to

seemed to think that gene drives were not actually that frightening or dangerous.

(Gargalladas)

Ata agora, é certo.

Pero os impulsos xénicos tamén teñen limitacións.

Partly because they believe that scientists will be

Por unha parte, só funcionan en especies con reprodución sexual,

very cautious and responsible about using them.

(Laughter)

So far, that's been true.

así que non poden usarse para modificar virus ou bacterias.

But gene drives also have some actual limitations.

Ademais, a característica transmítese só á seguinte xeración,

So for one thing, they work only in sexually reproducing species.

así que cambiar ou eliminar unha

So thank goodness, they can't be used to engineer viruses or bacteria.

é práctico só se a especie ten un ciclo reprodutivo rápido,

Also, the trait spreads only with each successive generation.

como insectos ou pequenos vertebrados: ratos, peixes…

So changing or eliminating a population

En elefantes ou persoas, levaría séculos

is practical only if that species has a fast reproductive cycle,

que unha característica se espallase tan amplamente.

like insects or maybe small vertebrates like mice or fish.

Ademais, incluso con CRISPR, non é tan sinxelo

In elephants or people, it would take centuries

deseñar unha característica realmente devastadora.

for a trait to spread widely enough to matter.

Imaxinade: queremos unha mosca

que se alimenta de froita fresca no canto de podre,

Also, even with CRISPR, it's not that easy to engineer a truly devastating trait.

para sabotar a agricultura americana.

Primeiro, hai que descubrir

Say you wanted to make a fruit fly

que xenes controlan o que a mosca quere comer,

that feeds on ordinary fruit instead of rotting fruit,

o cal xa é un proxecto longo e complexo.

with the aim of sabotaging American agriculture.

Logo hai que alterar eses xenes para cambiar o comportamento da mosca

First, you'd have to figure out

which genes control what the fly wants to eat,

ao que queremos que sexa,

un proxecto aínda máis longo e complexo.

which is already a very long and complicated project.

E pode fallar, pois os xenes que controlan a conduta son complexos.

Then you'd have to alter those genes to change the fly's behavior

to whatever you'd want it to be,

Se fósemos terroristas e debésemos elixir entre comezar un programa de investigación

which is an even longer and more complicated project.

And it might not even work,

que requirise anos de traballo que pode non saír

because the genes that control behavior are complex.

ou estoupar cousas,

So if you're a terrorist and have to choose

probablemente escolleriamos o último.

between starting a grueling basic research program

É certo sobre todo porque, polo menos en teoría,

that will require years of meticulous lab work and still might not pan out,

debería ser fácil construír o chamado impulso inverso.

or just blowing stuff up?

Este reescribe os cambios feitos polo primeiro impulso xénico,

You'll probably choose the later.

This is especially true because at least in theory,

así que, se non nos gustan os efectos dun cambio,

it should be pretty easy to build what's called a reversal drive.

podemos liberar un segundo impulso que o reverta,

That's one that basically overwrites the change made by the first gene drive.

polo menos en teoría.

So if you don't like the effects of a change,

Onde nos deixa isto?

you can just release a second drive that will cancel it out,

Agora temos a capacidade de cambiar unha especie a vontade.

at least in theory.

Deberiamos?

OK, so where does this leave us?

Somos deuses agora?

We now have the ability to change entire species at will.

Non estou moi segura,

pero direi o seguinte.

Should we?

Primeiro: hai persoas moi intelixentes

Are we gods now?

que están discutindo como regular os impulsos xénicos.

I'm not sure I'd say that.

Ao mesmo tempo, outra xente moi intelixente

But I would say this:

está traballando para crear salvagardas,

first, some very smart people

como impulsos que se autorregulan ou se extinguen despois dunhas xeracións.

are even now debating how to regulate gene drives.

At the same time, some other very smart people

Iso está xenial.

Pero esta tecnoloxía aínda precisa unha conversa.

are working hard to create safeguards,

like gene drives that self-regulate or peter out after a few generations.

E, dada a natureza destes impulsos,

esa conversa ten que ser global.

That's great.

Que pasaría se Kenya quixese usar un impulso e Tanzania non?

But this technology still requires a conversation.

Quen decide se se libera un impulso xénico que poida voar?

And given the nature of gene drives,

that conversation has to be global.

What if Kenya wants to use a drive but Tanzania doesn't?

Eu non teño a resposta.

Who decides whether to release a gene drive that can fly?

Todo o que podemos facer de aquí en diante,

creo, é falar honestamente sobre os riscos e os beneficios

e tomar responsabilidade polas nosas decisións.

I don't have the answer to that question.

All we can do going forward, I think,

Con isto refírome, non só á decisión de usar un impulso xénico,

is talk honestly about the risks and benefits

senón tamén á decisión de non usalo.

and take responsibility for our choices.

Os humanos tendemos a asumir que a opción máis segura

By that I mean, not just the choice to use a gene drive,

é preservar o statu quo.

but also the choice not to use one.

Pero non é sempre o caso.

Humans have a tendency to assume that the safest option

Os impulsos xénicos teñen riscos e deben discutirse,

is to preserve the status quo.

pero a malaria existe agora e mata mil persoas cada día.

But that's not always the case.

Para combatela, espallamos pesticidas que son daniños para outras especies,

Gene drives have risks, and those need to be discussed,

incluíndo anfibios e paxaros.

but malaria exists now and kills 1,000 people a day.

Cando oiades falar dos impulsos xénicos nos próximos meses,

To combat it, we spray pesticides that do grave damage to other species,

e crédeme, escoitaredes falar deles,

including amphibians and birds.

recordádeo.

Pode ser aterrador actuar,

So when you hear about gene drives in the coming months,

pero, ás veces, non actuar é peor.

and trust me, you will be hearing about them,

remember that.

(Aplausos)

It can be frightening to act,

but sometimes, not acting is worse.

(Applause)