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TED, Jennifer Doudna: We can now edit our DNA. But let's do it wisely (1)

Jennifer Doudna: We can now edit our DNA. But let's do it wisely (1)

0:12A 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.

00:32You 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.

01:04Part 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.

01:42The 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.

02:09The 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.

02:39What 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.

02:54When 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)

03:24A 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.

04:24So 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

05:26As 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.

05:48The 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.

06:51Genome 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.

07:53So 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.

08:22Right 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.

08:42Now 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.

09:18Additional 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.

09:55I 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.

10:30But 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.

11:17This 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.

11:54So, 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.

12:21Thank you.

12:22(Applause)

12:30(Applause ends)

12:32Bruno 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?

13:12Jennifer 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.

13:28BG: 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?

13:38JD: 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.

13:56BG: 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?

14:28JD: 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

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Jennifer Doudna: We can now edit our DNA. But let's do it wisely (1) Jennifer Doudna: Wir können jetzt unsere DNA bearbeiten. Aber lassen Sie uns das mit Bedacht tun (1) Jennifer Doudna: Ya podemos editar nuestro ADN. Pero hagámoslo con prudencia (1) Jennifer Doudna : Nous pouvons désormais modifier notre ADN. Mais faisons-le avec sagesse (1) Jennifer Doudna: Ora possiamo modificare il nostro DNA. Ma facciamolo con saggezza (1) Jennifer Doudna: Możemy teraz edytować nasze DNA. Ale róbmy to mądrze (1) Jennifer Doudna: Agora podemos editar o nosso ADN. Mas façamo-lo com sabedoria (1) Дженнифер Дудна: Теперь мы можем редактировать свою ДНК. Но давайте делать это с умом (1) Jennifer Doudna: Artık DNA'mızı düzenleyebiliyoruz. Ama bunu akıllıca yapalım (1) Jennifer Doudna:我们现在可以编辑我们的 DNA。但我们要明智地去做(1) Jennifer Doudna:我們現在可以編輯我們的 DNA。但我們要明智地去做(1)

0:12A 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.

00:32You 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. 00: 32 Quizás le interese saber que la tecnología CRISPR surgió a través de un proyecto de investigación básica que tenía como objetivo descubrir cómo las bacterias combaten las infecciones virales. 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. Las bacterias tienen que lidiar con los virus en su entorno, y podemos pensar en una infección viral como una bomba de tiempo, una bacteria tiene solo unos minutos para desactivar la bomba antes de que se destruya. Les bactéries doivent faire face à des virus dans leur environnement et nous pouvons penser à une infection virale comme une bombe à retardement - une bactérie n'a que quelques minutes pour désamorcer la bombe avant qu'elle ne soit détruite. So, many bacteria have in their cells an adaptive immune system called CRISPR, that allows them to detect viral DNA and destroy it.

01:04Part 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. 01: 04 La parte del sistema CRISPR es una proteína llamada Cas9, que puede buscar, cortar y eventualmente degradar el ADN viral de una manera específica. 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. Y fue a través de nuestra investigación para comprender la actividad de esta proteína, Cas9, que nos dimos cuenta de que podríamos aprovechar su función como una tecnología de ingeniería genética, una forma en que los científicos pueden eliminar o insertar fragmentos específicos de ADN en células con una precisión increíble. - Eso ofrecería oportunidades para hacer cosas que realmente no han sido posibles en el pasado. И именно благодаря нашим исследованиям, направленным на изучение активности этого белка, Cas9, мы поняли, что можем использовать его функцию в качестве технологии генной инженерии - способа, позволяющего ученым удалять или вставлять определенные участки ДНК в клетки с невероятной точностью, - которая открывает возможности для выполнения задач, действительно невозможных в прошлом.

01:42The CRISPR technology has already been used to change the DNA in the cells of mice and monkeys, other organisms as well. 01: 42 La tecnología CRISPR ya se ha utilizado para cambiar el ADN de las células de ratones y monos, y también de otros organismos. 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. Los científicos chinos demostraron recientemente que incluso podrían usar la tecnología CRISPR para cambiar los genes en embriones humanos Y los científicos en Filadelfia demostraron que podrían usar CRISPR para eliminar el ADN de un virus VIH integrado de las células humanas infectadas.

02:09The 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. 02: 09La oportunidad de hacer este tipo de edición del genoma también plantea varios problemas éticos que debemos tener en cuenta, ya que esta tecnología puede emplearse no solo en células adultas, sino también en embriones de organismos, incluida nuestra propia especie. 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. Y así, junto con mis colegas, he pedido una conversación global sobre la tecnología que inventé, para que podamos considerar todas las implicaciones éticas y sociales de una tecnología como esta.

02:39What 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. 02: 39 Lo que quiero hacer ahora es decirle qué es la tecnología CRISPR, qué puede hacer, dónde estamos hoy y por qué creo que debemos tomar un camino prudente hacia adelante en la forma en que empleamos esta tecnología.

02:54When viruses infect a cell, they inject their DNA. 02: 54Cuando los virus infectan una célula, inyectan su ADN. 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. Y en una bacteria, el sistema CRISPR permite que el ADN se extraiga del virus y se inserte en pequeños bits en el cromosoma, el ADN de la bacteria. Y estos fragmentos integrados de ADN viral se insertan en un sitio llamado CRISPR. А в бактерии система CRISPR позволяет вырвать эту ДНК из вируса и вставить ее маленькими кусочками в хромосому - ДНК бактерии. Эти интегрированные кусочки вирусной ДНК вставляются в место, называемое CRISPR. CRISPR stands for clustered regularly interspaced short palindromic repeats. CRISPR es sinónimo de repeticiones palindrómicas cortas, interpuestas y agrupadas regularmente. CRISPR est synonyme de courtes répétitions palindromiques régulièrement espacées. CRISPR означает сгруппированные короткие палиндромные повторы с регулярными промежутками. (Laughter)

03:24A big mouthful -- you can see why we use the acronym CRISPR. 03: 24Una gran bocanada: puedes ver por qué usamos el acrónimo CRISPR. 03:24Вы можете понять, почему мы используем аббревиатуру 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. Es un mecanismo que permite a las células registrar, con el tiempo, los virus a los que han estado expuestos. Y, lo que es más importante, esos fragmentos de ADN se transmiten a la progenie de las células, por lo que las células están protegidas de los virus no solo en una generación, sino en muchas Generaciones de células. Это механизм, который позволяет клеткам со временем записывать вирусы, которым они подверглись. И, что важно, эти фрагменты ДНК передаются потомству клеток, поэтому клетки защищены от вирусов не только в одном поколении, но и в течение многих поколений. поколения клеток. 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. Esto permite a las células mantener un registro de la infección, y como le gusta decir a mi colega, Blake Wiedenheft, el locus CRISPR es efectivamente una tarjeta de vacunación genética en las células. Cela permet aux cellules de garder une trace de l'infection, et comme mon collègue Blake Wiedenheft aime à le dire, le locus CRISPR est en fait une carte de vaccination génétique dans les cellules. 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. ||||||||||||||||||||||||||||||||||exact copy|||| RNA is a chemical cousin of DNA, and it allows interaction with DNA molecules that have a matching sequence. El ARN es un primo químico del ADN y permite la interacción con moléculas de ADN que tienen una secuencia coincidente.

04:24So 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. 04: 24Así que esos pequeños fragmentos de ARN del locus CRISPR se asocian, se unen, a una proteína llamada Cas9, que es blanca en la imagen, y forman un complejo que funciona como un centinela en la célula. It searches through all of the DNA in the cell, to find sites that match the sequences in the bound RNAs. Busca en todo el ADN de la célula, para encontrar sitios que coincidan con las secuencias en los ARN unidos. Он просматривает всю ДНК в клетке, чтобы найти участки, соответствующие последовательностям связанных РНК. 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. Y cuando se encuentran esos sitios, como se puede ver aquí, la molécula azul es el ADN, este complejo se asocia con ese ADN y permite que la cuchilla Cas9 corte el ADN viral. Et lorsque ces sites sont trouvés - comme vous pouvez le voir ici, la molécule bleue est l'ADN - ce complexe s'associe à cet ADN et permet au couperet Cas9 de couper l'ADN viral. It makes a very precise break. Hace un corte muy preciso. Это делает очень точный разрыв. 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. |||||||||||||||which||||||||double-helix||||| Así que podemos pensar en el complejo centinela de ARN Cas9 como un par de tijeras que pueden cortar el ADN: hace una rotura de doble cadena en la hélice del ADN. 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 Y, lo que es más importante, este complejo es programable, por lo que puede programarse para reconocer secuencias de ADN particulares y romper el ADN en ese sitio

05:26As 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. ||||||||||||||utilized for control||||||||||||||||||||||| 05: 26 Como les diré ahora, reconocimos que esa actividad podría aprovecharse para la ingeniería del genoma, para permitir que las células realicen un cambio muy preciso en el ADN en el sitio donde se introdujo esta ruptura. That's sort of analogous to the way that we use a word-processing program to fix a typo in a document. |||similar to||||||||||||||||| Eso es algo similar a la forma en que usamos un programa de procesamiento de textos para corregir un error tipográfico en un documento.

05:48The reason we envisioned using the CRISPR system for genome engineering is because cells have the ability to detect broken DNA and repair it. |||imagined using|||||||||||||||||||| 05: 48 La razón por la que imaginamos usar el sistema CRISPR para la ingeniería del genoma es porque las células tienen la capacidad de detectar el ADN roto y repararlo. 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. Entonces, cuando una planta o una célula animal detecta una ruptura de doble cadena en su ADN, puede corregir esa ruptura, ya sea pegando los extremos del ADN roto con un pequeño y diminuto cambio en la secuencia de esa posición, o puede repare la rotura integrando una nueva pieza de ADN en el sitio del corte. 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. Entonces, si tenemos una manera de introducir rupturas de doble cadena en el ADN en lugares precisos, podemos provocar que las células reparen esas roturas, ya sea mediante la interrupción o la incorporación de nueva información genética. Таким образом, если у нас есть способ вводить двухцепочечные разрывы в ДНК в определенных местах, мы можем заставить клетки восстанавливать эти разрывы путем разрушения или включения новой генетической информации. 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. Entonces, si pudiéramos programar la tecnología CRISPR para hacer una ruptura en el ADN en la posición en o cerca de una mutación que causa fibrosis quística, por ejemplo, podríamos provocar que las células reparen esa mutación.

06:51Genome 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. ||||||||||||altering| 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. |||||||||||||is attractive||||||||||||||||||||||||||||||||||||||||||||||||||||| Entonces, la oportunidad de tomar una tecnología como CRISPR y utilizarla es atractiva, debido a su relativa simplicidad. Podemos pensar que las tecnologías de ingeniería del genoma más antiguas son similares a tener que volver a cablear su computadora cada vez que quiera ejecutar una nueva pieza de software, mientras que La tecnología CRISPR es como un software para el genoma, podemos programarlo fácilmente, usando estos pequeños fragmentos de ARN. Таким образом, возможность использовать такую технологию, как CRISPR, привлекательна из-за ее относительной простоты. Мы можем думать о старых технологиях инженерии генома как о необходимости переподключать свой компьютер каждый раз, когда вы хотите запустить новую часть программного обеспечения, тогда как технология CRISPR подобна программному обеспечению для генома, мы можем легко запрограммировать его, используя эти маленькие кусочки РНК.

07:53So 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. ||||||||||||trigger|fix the damage||||accomplish remarkable outcomes||||||||genetic alterations|||sickle cell anemia|||||| 07: 53Así que una vez que se hace una rotura de doble cadena en el ADN, podemos inducir la reparación y, por lo tanto, lograr cosas sorprendentes, como poder corregir mutaciones que causan anemia de células falciformes o la enfermedad de Huntington. 07: 53Ainsi, une fois qu'une rupture double brin est faite dans l'ADN, nous pouvons induire une réparation, et donc potentiellement réaliser des choses étonnantes, comme être capable de corriger des mutations qui causent la drépanocytose ou la maladie de Huntington. 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.

08:22Right 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. 08: 22 Ahora mismo, gran parte del trabajo que se realiza se aplica a modelos animales de enfermedades humanas, como los ratones. La tecnología se utiliza para realizar cambios muy precisos que nos permiten estudiar la forma en que estos cambios en el ADN de la célula afectan ya sea un tejido o, en este caso, un organismo completo. 08:22На данный момент большая часть работы проводится на животных моделях человеческих заболеваний, таких как мыши. Технология используется для внесения очень точных изменений, которые позволяют нам изучать, как эти изменения в ДНК клетки влияют либо на ткань, либо, в данном случае, на весь организм.

08:42Now 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. 08: 42Ahora en este ejemplo, la tecnología CRISPR se usó para interrumpir un gen al hacer un pequeño cambio en el ADN en un gen que es responsable del color del pelaje negro de estos ratones. 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. Imagina que estos ratones blancos se diferencian de sus compañeros de camada pigmentados por solo un pequeño cambio en un gen en todo el genoma, y por lo demás son completamente normales. Imaginez que ces souris blanches diffèrent de leurs compagnons de portée pigmentés par juste un petit changement au niveau d'un gène dans tout le génome, et qu'elles sont par ailleurs tout à fait normales. 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.

09:18Additional 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. ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||unplanned||||| Y aquí encontramos que podemos usar estos sistemas para probar la aplicación de esta tecnología en tejidos particulares, por ejemplo, descubrir cómo entregar la herramienta CRISPR a las células. También queremos entender mejor cómo controlar la forma en que se repara el ADN después de está cortado, y también para descubrir cómo controlar y limitar cualquier tipo de efectos fuera de destino o no deseados del uso de la tecnología.

09:55I think that we will see clinical application of this technology, certainly in adults, within the next 10 years. 09: 55 Creo que veremos la aplicación clínica de esta tecnología, ciertamente en adultos, dentro de los próximos 10 años. 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. Creo que es probable que veamos ensayos clínicos y posiblemente incluso terapias aprobadas dentro de ese tiempo, lo cual es algo muy emocionante en que pensar. 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. Y debido a la emoción en torno a esta tecnología, existe un gran interés en las empresas de nueva creación que se han fundado para comercializar la tecnología CRISPR y en muchos inversores de capital de riesgo que han estado invirtiendo en estas empresas.

10:30But 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. 10: 30Pero también debemos considerar que la tecnología CRISPR se puede usar para mejorar la imagen. Imagínese que podríamos intentar diseñar seres humanos que tengan propiedades mejoradas, como huesos más fuertes o menos susceptibilidad a las enfermedades cardiovasculares o incluso propiedades que Consideraríamos quizás ser deseable, como un color de ojos diferente o ser más alto, cosas así. "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.

11:17This 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. 11:17This 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.

11:54So, 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.

12:21Thank you.

12:22(Applause)

12:30(Applause ends)

12:32Bruno 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. Su actitud respecto a pedir una pausa o una moratoria o una cuarentena es increíblemente responsable. 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. Hay, por supuesto, los resultados terapéuticos de esto, pero luego están los que no son terapéuticos y parecen ser los que están ganando terreno, particularmente en los medios de comunicación. 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? Todo se trata de mejora genética, no de terapéutica. ¿Qué tipo de reacciones recibió en marzo de parte de sus colegas en el mundo de la ciencia, cuando preguntó o sugirió que deberíamos detener esto por un momento y pensar en ello?

13:12Jennifer Doudna: My colleagues were actually, I think, delighted to have the opportunity to discuss this openly. 13: 12Jennifer Doudna: Creo que mis colegas estaban encantados de tener la oportunidad de discutir esto abiertamente. 13:12Дженнифер Дудна: Мои коллеги, я думаю, были рады возможности обсудить это открыто. 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.

13:28BG: 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?

13:38JD: 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. ||||||||||general agreement|||||||||||||||||||| Может оказаться невозможным выработать единую точку зрения, но я думаю, что мы должны, по крайней мере, понять, каковы все вопросы, когда мы продвигаемся вперед.

13:56BG: 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? Quiero decir, ¿vamos a ver a algunas personas contenerse porque tienen inquietudes éticas y otras simplemente están avanzando porque algunos países no regulan o no regulan en absoluto?

14:28JD: 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 |||||||||||||genetic blueprint||||||||||||||||||||||