A few years ago, with my colleague, Emmanuelle Charpentier, I invented a new technology for editing genomes. It's called CRISPR-Cas9. The CRISPR technology allows scientists to make changes to the DNA in cells that could allow us to cure genetic disease.
Hai uns anos, canda a miña colega Emmanuelle Charpentier inventei una nova tecnoloxía para editar xenomas. Chámase CRISPR-Cas 9. A tecnoloxía CRISPR permítelles aos científicos facer cambios no ADN celular, o que podería permitir curar enfermidades xenéticas.
You might be interested to know that the CRISPR technology came about through a basic research project that was aimed at discovering how bacteria fight viral infections. Bacteria have to deal with viruses in their environment, and we can think about a viral infection like a ticking time bomb -- a bacterium has only a few minutes to defuse the bomb before it gets destroyed. So, many bacteria have in their cells an adaptive immune system called CRISPR, that allows them to detect viral DNA and destroy it.
É interesante que saibades que a tecnoloxía CRISPR xorde dun proxecto de investigación básica que buscaba estudar como as bacterias loitan contra infeccións virais. As bacterias teñen que enfrontarse con virus na súa contorna, podemos pensar nunha infección vírica coma unha bomba de reloxaría. A bacteria ten só uns minutos para destruír a bomba antes de que a destrúa a ela. Así que moitas bacterias teñen nas súas células un sistema inmune adaptativo chamado CRISPR que lles permite detectar ADN vírico e destruílo.
Part of the CRISPR system is a protein called Cas9, that's able to seek out, cut and eventually degrade viral DNA in a specific way. And it was through our research to understand the activity of this protein, Cas9, that we realized that we could harness its function as a genetic engineering technology -- a way for scientists to delete or insert specific bits of DNA into cells with incredible precision -- that would offer opportunities to do things that really haven't been possible in the past.
Parte do sistema CRISPR é una proteína que se chama Cas9 que pode buscar, cortar e degradar o ADN viral dunha forma específica. E foi na nosa investigación para entender o funcionamento de Cas9, cando vimos que podíamos modificar a súa función coma una tecnoloxía de enxeñería xenética un xeito de que os científicos poidan borrar ou inserir fragmentos específicos de ADN en células cunha precisión incrible Isto ofrecería oportunidades para facer cousas que nunca serían posibles no pasado.
The CRISPR technology has already been used to change the DNA in the cells of mice and monkeys, other organisms as well. Chinese scientists showed recently that they could even use the CRISPR technology to change genes in human embryos. And scientists in Philadelphia showed they could use CRISPR to remove the DNA of an integrated HIV virus from infected human cells.
A tecnoloxía CRISPR xa se usou para cambiar o ADN nas células de ratos e monos, e tamén noutros organismos. Científicos chineses probaron hai pouco que poden usar a tecnoloxía CRISPR para cambiar xenes en embrións humanos. E científicos en Filadelfia probaron que podían usar CRISPR para retirar o ADN dun virus VIH integrado en células infectadas humanas.
The opportunity to do this kind of genome editing also raises various ethical issues that we have to consider, because this technology can be employed not only in adult cells, but also in the embryos of organisms, including our own species. And so, together with my colleagues, I've called for a global conversation about the technology that I co-invented, so that we can consider all of the ethical and societal implications of a technology like this.
A oportunidade de realizar este tipo de edición xenética tamén implica cuestións éticas que temos que considerar porque esta tecnoloxía non só se pode usar en células adultas senón tamén en embrións de organismos, incluíndo os da nosa especie. Así que, xunto cos meus colegas, convoquei unha conversa global sobre a tecnoloxía que coinventei, para considerar todas as implicacións éticas e sociais dunha tecnoloxía coma esta.
What I want to do now is tell you what the CRISPR technology is, what it can do, where we are today and why I think we need to take a prudent path forward in the way that we employ this technology.
Agora quero contarvos que é a tecnoloxía CRISPR, o que pode facer, onde nos atopamos actualmente, e por que penso que temos que avanzar con prudencia á hora de empregala.
When viruses infect a cell, they inject their DNA. And in a bacterium, the CRISPR system allows that DNA to be plucked out of the virus, and inserted in little bits into the chromosome -- the DNA of the bacterium. And these integrated bits of viral DNA get inserted at a site called CRISPR. CRISPR stands for clustered regularly interspaced short palindromic repeats. (Laughter)
Cando os virus infectan unha célula, inxéctanlle o seu ADN. Nunha bacteria, o sistema CRISPR permite arrincar o ADN do virus e inserilo en anacos no ADN bacteriano. Estes anacos de ADN vírico son inseridos na zona CRISPR. CRISPR é en inglés "repeticións palindrómicas cortas agrupadas e regularmente interespazadas".
A big mouthful -- you can see why we use the acronym CRISPR. It's a mechanism that allows cells to record, over time, the viruses they have been exposed to. And importantly, those bits of DNA are passed on to the cells' progeny, so cells are protected from viruses not only in one generation, but over many generations of cells. This allows the cells to keep a record of infection, and as my colleague, Blake Wiedenheft, likes to say, the CRISPR locus is effectively a genetic vaccination card in cells. Once those bits of DNA have been inserted into the bacterial chromosome, the cell then makes a little copy of a molecule called RNA, which is orange in this picture, that is an exact replicate of the viral DNA. RNA is a chemical cousin of DNA, and it allows interaction with DNA molecules that have a matching sequence.
Unha palabra moi longa, xa entendedes porqué usamos o acrónimo CRISPR. É un mecanismo que permite ás células gravar ao longo do tempo os virus aos que estiveron expostas. E de xeito moi importante, eses anacos de ADN pásanselle á proxenie celular. Polo tanto, as células están protexidas fronte a virus non só nunha xeración, senón en varias. Isto permite que as células teñan un rexistro de infeccións. Como di a miña colega Blake Wiedenheft, o locus CRISPR é un rexistro de vacinas moi efectivo para as células. Cando eses anacos de ADN se insiren no cromosoma bacteriano a célula fai una pequena copia dunha molécula, o ARN, en laranxa na foto. Que é una copia exacta do ARN vírico. O ARN é un curmán químico do ADN. Permite a interacción con moléculas de ADN que teñan una secuencia 'correspondente'.
So those little bits of RNA from the CRISPR locus associate -- they bind -- to protein called Cas9, which is white in the picture, and form a complex that functions like a sentinel in the cell. It searches through all of the DNA in the cell, to find sites that match the sequences in the bound RNAs. And when those sites are found -- as you can see here, the blue molecule is DNA -- this complex associates with that DNA and allows the Cas9 cleaver to cut up the viral DNA. It makes a very precise break. So we can think of the Cas9 RNA sentinel complex like a pair of scissors that can cut DNA -- it makes a double-stranded break in the DNA helix. And importantly, this complex is programmable, so it can be programmed to recognize particular DNA sequences, and make a break in the DNA at that site.
Eses anacos de ARN do locus CRISPR únense á proteína Cas 9, en branco na imaxe, e forman un complexo que funciona como sentinela na célula. Busca en todo o ADN para atopar secuencias que corresponden coas dos ARN unidos. E cando eses sitios son atopados, como podedes ver aquí --a molécula de ADN é azul-- o complexo asóciase con ese ADN, e Cas9 pode cortar o ADN vírico. Fai un corte moi exacto. Podemos pensar neste complexo sentinela-Cas9-ARN, como un par de tesoiras que poden cortar ADN, facendo un corte na dobre cadea. Este complexo é programable, pode ser programado para recoñecer secuencias específicas de ADN e facer un corte no ADN nese lugar.
As I'm going to tell you now, we recognized that that activity could be harnessed for genome engineering, to allow cells to make a very precise change to the DNA at the site where this break was introduced. That's sort of analogous to the way that we use a word-processing program to fix a typo in a document.
Démonos conta de que esa actividade podía ser usada para edición xenómica, para permitirlles ás células facer un cambio moi preciso no seu ADN no lugar onde se produce a rotura. É parecido a usar un procesador de textos para corrixir un erro nun documento.
The reason we envisioned using the CRISPR system for genome engineering is because cells have the ability to detect broken DNA and repair it. So when a plant or an animal cell detects a double-stranded break in its DNA, it can fix that break, either by pasting together the ends of the broken DNA with a little, tiny change in the sequence of that position, or it can repair the break by integrating a new piece of DNA at the site of the cut. So if we have a way to introduce double-stranded breaks into DNA at precise places, we can trigger cells to repair those breaks, by either the disruption or incorporation of new genetic information. So if we were able to program the CRISPR technology to make a break in DNA at the position at or near a mutation causing cystic fibrosis, for example, we could trigger cells to repair that mutation.
A razón pola que concibimos usar o sistema CRISPR para edición xenómica é por que as células teñen a habilidade de detectar ADN roto e reparalo. Cando una célula animal ou vexetal detecta una dobre rotura de hélice no seu ADN, pode reparala, xa sexa por copia e pega dos extremos do ADN roto cun pequeno cambio na secuencia desa posición, ou pode reparar a rotura integrando un novo anaco de ADN no lugar do corte. Así que, se temos un xeito de introducir cortes na dobre cadea de ADN en determinados lugares, podemos inducir as células a reparar esas roturas por perda ou incorporación de nova información xenética. Así que, se fósemos capaces de programar a tecnoloxía CRISPR para facer un corte cerca ou na posición dunha mutación causante da fibrose quística, por exemplo, poderiamos inducir as células a reparar esa mutación.
Genome engineering is actually not new, it's been in development since the 1970s. We've had technologies for sequencing DNA, for copying DNA, and even for manipulating DNA. And these technologies were very promising, but the problem was that they were either inefficient, or they were difficult enough to use that most scientists had not adopted them for use in their own laboratories, or certainly for many clinical applications. So, the opportunity to take a technology like CRISPR and utilize it has appeal, because of its relative simplicity. We can think of older genome engineering technologies as similar to having to rewire your computer each time you want to run a new piece of software, whereas the CRISPR technology is like software for the genome, we can program it easily, using these little bits of RNA.
A enxeñería xenómica non é algo recente, comezou nos anos 70. Tiñamos tecnoloxías para secuenciar ADN, copiar ADN, e incluso para manipular ADN. E estas tecnoloxías eran moi prometedoras, pero tiñan como problema a súa ineficiencia ou dificultade de uso, polo que moitos científicos non as usaron nos seus laboratorios ou en ningunha aplicación clínica. A oportunidade de usar unha nova tecnoloxía como é CRISPR ten certo atractivo debido á súa simplicidade. Podemos pensar en técnicas de enxeñería xenómica máis vellas, e comparalas con ter que recablear un ordenador cada vez que queiras probar un novo software. Pola contra, a tecnoloxía CRISPR é como software para o xenoma, xa que pode ser programado doadamente usando estes anacos de ARN.
So once a double-stranded break is made in DNA, we can induce repair, and thereby potentially achieve astounding things, like being able to correct mutations that cause sickle cell anemia or cause Huntington's Disease. I actually think that the first applications of the CRISPR technology are going to happen in the blood, where it's relatively easier to deliver this tool into cells, compared to solid tissues.
Así que, cando causamos unha rotura de cadea dobre podemos inducir a reparación e obter resultados potencialmente asombrosos. Como poder corrixir mutacións que causan anemias falciformes ou a enfermidade de Huntington. Creo que as primeiras aplicacións da técnica CRISPR terán lugar no sangue, xa que é máis doado introducir esta ferramenta nas células, en comparación con tecidos sólidos.
Right now, a lot of the work that's going on applies to animal models of human disease, such as mice. The technology is being used to make very precise changes that allow us to study the way that these changes in the cell's DNA affect either a tissue or, in this case, an entire organism.
Hoxe, moitas das investigacións en que se traballa aplícanse sobre modelos animais de enfermidades humanas, coma os ratos. Esta tecnoloxía úsase para facer cambios precisos no ADN celular, que permiten estudar o xeito en que estes cambios no ADN celular poden afectar un tecido, ou neste caso, un organismo.
Now in this example, the CRISPR technology was used to disrupt a gene by making a tiny change in the DNA in a gene that is responsible for the black coat color of these mice. Imagine that these white mice differ from their pigmented litter-mates by just a tiny change at one gene in the entire genome, and they're otherwise completely normal. And when we sequence the DNA from these animals, we find that the change in the DNA has occurred at exactly the place where we induced it, using the CRISPR technology.
No seguinte exemplo, a técnica CRISPR usouse para interromper un xene facendo un pequeno cambio no ADN nun xene responsable da cor negra destes ratos. Pensade que a diferencia entre os ratos brancos e os seus compañeiros de camada negros é debida soamente a un pequeno cambio nun único xene no xenoma enteiro. E senón fora por iso serían normais. Cando secuenciamos o ADN destes animais comprobamos que o cambio no ADN prodúcese exactamente no sitio onde foi inducido mediante o uso de CRISPR.
Additional experiments are going on in other animals that are useful for creating models for human disease, such as monkeys. And here we find that we can use these systems to test the application of this technology in particular tissues, for example, figuring out how to deliver the CRISPR tool into cells. We also want to understand better how to control the way that DNA is repaired after it's cut, and also to figure out how to control and limit any kind of off-target, or unintended effects of using the technology.
Estanse facendo experimentos con outros animais que son útiles para crear modelos de enfermidades humanas, como os monos. E nestes vemos que podemos usar estes sistemas para probar a aplicación desta técnica en tecidos específicos, por exemplo, estudar como introducir o complexo CRISPR nas células. Tamén queremos entender mellor como controlar a reparación do ADN logo de cortado e aprender a controlar e limitar calquera acción fóra dos lugares diana ou efectos non desexados
I think that we will see clinical application of this technology, certainly in adults, within the next 10 years. I think that it's likely that we will see clinical trials and possibly even approved therapies within that time, which is a very exciting thing to think about. And because of the excitement around this technology, there's a lot of interest in start-up companies that have been founded to commercialize the CRISPR technology, and lots of venture capitalists that have been investing in these companies.
derivados do uso desta tecnoloxía. Penso que veremos aplicacións clínicas desta tecnoloxía, probablemente en adultos, nos próximos 10 anos. Penso que é moi posible que vexamos ensaios clínicos e posiblemente terapias aprobadas nesa franxa temporal, o que é moi emocionante. E debido á expectación arredor desta tecnoloxía, hai moitos intereses en empresas emerxentes que foron creadas para vender a tecnoloxía CRISPR, e moitos capitalistas de risco que invisten nestas compañías.
But we have to also consider that the CRISPR technology can be used for things like enhancement. Imagine that we could try to engineer humans that have enhanced properties, such as stronger bones, or less susceptibility to cardiovascular disease or even to have properties that we would consider maybe to be desirable, like a different eye color or to be taller, things like that. "Designer humans," if you will. Right now, the genetic information to understand what types of genes would give rise to these traits is mostly not known. But it's important to know that the CRISPR technology gives us a tool to make such changes, once that knowledge becomes available.
Pero tamén temos que ter en conta que CRISPR pode ser usada en mellora xenética. Imaxinade que poderiamos intentar facer enxeñería en humanos, que teñen propiedades melloradas, como ósos máis fortes, ou menor susceptibilidade a enfermidades cardiovasculares ou quizais teñan propiedades que consideremos desexables, como diferente cor de ollos ou ser máis altos. Humanos á carta, poderíase dicir. Neste momento, a información xenética necesaria para entender que tipo de xenes producen este tipo de características é na súa maior parte descoñecida. Pero é importante saber que coa tecnoloxía CRISPR podemos facer eses cambios, unha vez que saibamos esta información.
This raises a number of ethical questions that we have to carefully consider, and this is why I and my colleagues have called for a global pause in any clinical application of the CRISPR technology in human embryos, to give us time to really consider all of the various implications of doing so. And actually, there is an important precedent for such a pause from the 1970s, when scientists got together to call for a moratorium on the use of molecular cloning, until the safety of that technology could be tested carefully and validated.
Isto pon enriba da mesa cuestión éticas que temos que considerar con coidado, e por iso eu e os meus colegas chamamos a una pausa mundial na aplicación clínica de CRISPR en embrións humanos, para deixarnos tempo para considerar todas as implicacións deste tipo de experimentación. E curiosamente, hai un precedente importante dunha pausa semellante nos anos 70, cando científicos se xuntaron para pedir unha moratoria no uso da clonación molecular, ata que a seguridade desa tecnoloxía puidese ser probada coidadosamente
So, genome-engineered humans are not with us yet, but this is no longer science fiction. Genome-engineered animals and plants are happening right now. And this puts in front of all of us a huge responsibility, to consider carefully both the unintended consequences as well as the intended impacts of a scientific breakthrough.
e validada. Aínda non temos humanos modificados xeneticamente entre nós, pero isto xa non é ciencia ficción. Animais e plantas con xenomas deseñados xa existen actualmente. E isto suponnos unha gran responsabilidade, considerar coidadosamente as consecuencias non previstas e os impactos que queremos nun descubrimento científico.
Thank you.
Grazas.
(Applause)
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(O aplauso remata)
Bruno Giussani: Jennifer, this is a technology with huge consequences, as you pointed out. Your attitude about asking for a pause or a moratorium or a quarantine is incredibly responsible. There are, of course, the therapeutic results of this, but then there are the un-therapeutic ones and they seem to be the ones gaining traction, particularly in the media. This is one of the latest issues of The Economist -- "Editing humanity." It's all about genetic enhancement, it's not about therapeutics. What kind of reactions did you get back in March from your colleagues in the science world, when you asked or suggested that we should actually pause this for a moment and think about it?
Bruno Giussiani: Jennifer, esta é unha tecnoloxía cunhas consecuencias importantes, como resaltaches. A túa decisión de pedir unha pausa, moratoria ou corentena, é incriblemente responsable. Temos por suposto, os resultados terapéuticos, pero tamén existen os non terapéuticos, e estes últimos parecen ser os que gañan máis atención mediática. Esta é unha das últimas publicacións de <i>The Economist</i>: ''Editando a humanidade''. Só fala de mellora xenética, non da parte terapéutica. Que tipo de reacción recibiches en marzo por parte dos teus colegas científicos cando suxeriches ou pediches que deberiamos tomar un descanso e pensar no que isto comporta?
Jennifer Doudna: My colleagues were actually, I think, delighted to have the opportunity to discuss this openly. It's interesting that as I talk to people, my scientific colleagues as well as others, there's a wide variety of viewpoints about this. So clearly it's a topic that needs careful consideration and discussion.
Jennifer Doudna: Os meus colegas, penso, estaban realmente contentos de ter a ocasión discutir isto abertamente. É interesante que ao falar coa xente, xa sexan, colegas científicos ou outros, hai moita variedade de puntos de vista. Así que, claramente precisamos
BG: There's a big meeting happening in December that you and your colleagues are calling, together with the National Academy of Sciences and others, what do you hope will come out of the meeting, practically?
un exame detido e debate neste tema. BG: Planeades unha gran reunión en decembro, convocada polos teus colegas, coa Academia Nacional de Ciencias e outros. Que pensas que sairá da reunión a nivel práctico?
JD: Well, I hope that we can air the views of many different individuals and stakeholders who want to think about how to use this technology responsibly. It may not be possible to come up with a consensus point of view, but I think we should at least understand what all the issues are as we go forward.
JD: Ben, agardo que poidamos expresar os puntos de vista de diferentes individuos e partes interesadas que queiran pensar como usar esta tecnoloxía de xeito responsable. Tal vez non sexa posible chegar a un punto de vista consensuado, pero polo menos poderemos entender a que problemas nos enfrontaremos con este avance.
BG: Now, colleagues of yours, like George Church, for example, at Harvard, they say, "Yeah, ethical issues basically are just a question of safety. We test and test and test again, in animals and in labs, and then once we feel it's safe enough, we move on to humans." So that's kind of the other school of thought, that we should actually use this opportunity and really go for it. Is there a possible split happening in the science community about this? I mean, are we going to see some people holding back because they have ethical concerns, and some others just going forward because some countries under-regulate or don't regulate at all?
BG: Outros colegas teus, como George Church, por exemplo, de Harvard, din que “os problemas éticos son basicamente cuestión de seguridade. Probamos múltiples veces en animais e en laboratorios, e cando vemos que é o seguro abondo, pasamos a humanos". Así que esa é a outra liña de pensamento, que deberíamos coller esta oportunidade e aproveitala. E posible que a comunidade científica se divida por isto? Imos ver xente botarse atrás, porque teñen preocupacións éticas, e outros simplemente avanzando porque algúns países lexislan pouco ou nada.
JD: Well, I think with any new technology, especially something like this, there are going to be a variety of viewpoints, and I think that's perfectly understandable. I think that in the end, this technology will be used for human genome engineering, but I think to do that without careful consideration and discussion of the risks and potential complications would not be responsible.
JD: Ben, penso que como en calquera nova tecnoloxía, especialmente algo deste tipo vai haber puntos de vista moi distintos, e creo que iso é comprensible. Penso que nun tempo usaremos esta tecnoloxía para enxeñería xenómica en humanos, pero facer iso sen analizar e debater os riscos potenciais non sería responsable.
BG: There are a lot of technologies and other fields of science that are developing exponentially, pretty much like yours. I'm thinking about artificial intelligence, autonomous robots and so on. No one seems -- aside from autonomous warfare robots -- nobody seems to have launched a similar discussion in those fields, in calling for a moratorium. Do you think that your discussion may serve as a blueprint for other fields?
BG: Hai moitas outras tecnoloxías e campos da ciencia que, como a túa, están crecendo exponencialmente. Estou a pensar en intelixencia artificial, robots autónomos, etcétera. Parece que ninguén, á parte do asunto dos robots autónomos de guerra, ninguén parece ter comezado un debate así, neses campos, pedindo unha moratoria. Cres que o teu debate poder servir de precedente para outros campos?
JD: Well, I think it's hard for scientists to get out of the laboratory. Speaking for myself, it's a little bit uncomfortable to do that. But I do think that being involved in the genesis of this really puts me and my colleagues in a position of responsibility. And I would say that I certainly hope that other technologies will be considered in the same way, just as we would want to consider something that could have implications in other fields besides biology.
JD: Ben, penso que é difícil para os científicos saír do laboratorio. Incluso para min, é algo incómodo facer iso. Pero realmente penso que ser parte da xénese disto ponnos, a min e aos meus colegas, nunha posición de responsabilidade. E certamente, espero que outras tecnoloxías sexan consideradas do mesmo modo, do mesmo xeito que considerariamos algo con implicacións 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.