CRISPR发明者演讲：当我们开始“定制婴儿”，世界会陷入怎样的疯狂？

首例人类基因编辑婴儿诞生事件一经出现在网络，便引发争议，其原因并不是这项技术的突破性，而是在人类毫无准备的情况下，为“人类物种”打开了一个面临巨大进化和道德风险的疯狂世界入口。

遗传学专家詹妮弗·道娜（Jennifer Doudna）与同事共同发明了突破性的新技术“基因编辑技术”，被称为CRISPR-Cas9。该工具允许科学家们对DNA进行精确的编辑，这可能对遗传性疾病的治疗有帮助...但也可能会被用来创造所谓的“订制婴儿”。道娜展示了CRISPR-Cas9的作用原理——并要求科学界暂缓脚步，来讨论这个新工具背后的伦理问题。

一起来看看她有关这一问题的演讲：

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.

几年前， 我跟同事Emmanuelle Charpentier发明了一个可以编辑基因组的新技术。 它叫做"CRISPR-Cas9"。CRISPR技术让科学家可以改变细胞里的DNA， 从而让我们能够治愈基因疾病。

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.

你可能有兴趣想知道，CRISPR技术其实来自于一个基础的科学研究， 它的主要目的是了解细菌如何与病毒感染进行对抗。 细菌必须在它们的环境里对付病毒。 我们可以这么想， 病毒感染像是个定时炸弹， 细菌在被消灭前， 只有几分钟时间可以拆除炸弹。 很多细菌在它们的细胞里有一种适应力免疫系统叫做"CRISPR"， 它可以使细菌侦测到病毒DNA并消灭它。

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.

CRISPR系统中，有一部分是一种叫Cas9的蛋白质， 它能够以特殊的方式寻找出、剪断， 最后削弱病毒DNA。 我们的研究主要是想了解Cas9蛋白质的活动， 我们意识到可以驾驭它的功能， 把它当做一种基因工程技术—— 一种可以让科学家用难以置信的精准度来消除或插入特定DNA片段到细胞中—— 这项技术提供了一个前所未有的机会， 让我们可以做到在过去根本无法完成的事情。

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.

CRISPR技术已经被应用于改变老鼠和猴子细胞里的DNA， 还包括其他有机体。中国科学家最近发现，他们甚至可以利用CRISPR技术改变人类胚胎里的基因。费城的科学家证实， 他们可以利用CRISPR技术从一个感染的人类细胞中移除HIV病毒(人类免疫缺陷病毒)。

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.

这个充满契机的基因组编辑技术， 也引发了各种我们必须认真思考的道德争议。 因为这种技术不仅可以运用在成人细胞上， 也可以用在有机体的胚胎上， 包含我们人类自己。 所以，我和同事们呼吁， 要针对这项技术展开一次全球对话， 思考应该赋予这种技术的道德与社会责任。

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.

那么现在，我要告诉你们CRISPR技术是什么、 它可以做什么、 目前的发展状况、 以及我为什么认为我们需要一个缜密的思路来运用这项技术。

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.

当病毒感染一个细胞， 它们会插入自身的DNA。 在一个细菌中，CRISPR系统可以把病毒的DNA拔掉， 并且将其中一小段插入到染色体内—— 也就是细菌的DNA。 而这些成簇的病毒DNA会被插入到一个名为CRISPR的位点。CRISPR意思是"规律成簇的间隔短回文重复"。

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.

很绕口——这回你们就知道为什么我们要使用CRISPR的缩写了。CRISPR是一种机制—— 它允许细胞随时记录被感染到的病毒。 而且重要的是，这些片段DNA会遗传到细胞的后代， 所以细胞不只有一代会一直被保护不受病毒感染， 好几代的细胞都会如此。 这允许细胞持有受感染的记录， 就像我同事Blake Wiedenheft喜欢说的，CRISPR的基因座其实上就是细胞的一张基因疫苗接种卡。 一旦这些片段DNA被插入到细菌染色体内， 细胞就会复制出一小段叫RNA的分子， 就是照片上的橘色的部分， 它就是病毒DNA的复制品。RNA相当于DNA的化学表亲， 能够与DNA上相同序列的分子产生反应。

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.

所以这些从CRISPR基因座转录的RNA片段， 会与一种叫Cas9的蛋白质相结合， 也就是照片上白色的部分， 这个蛋白质综合体像是细胞的卫兵。 它会搜寻细胞里所有的DNA， 找到符合所结合的RNA序列的位点。 当这些位置被找到后—— 就是你们看到的蓝色DNA分子， 这个综合体会与DNA结合， 并允许Cas9蛋白质像刀一样切断病毒DNA。 这是一次非常精确的截断。 所以我们可以把Cas9 RNA标记复合体想像成是一把DNA剪刀—— 它在DNA螺旋结构中， 制造了一种"双股螺旋断裂"。 最重要的是， 这种复合体是可程式化的， 在程式化后可以用来辨认特定的DNA序列， 并且在DNA的特定位置制造一个断裂。

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.

我现在想要告诉大家， 我们已经意识到这个技术， 可以被利用于基因工程中， 就在我提到过的断裂处使细胞内的DNA产生一个非常精准的变化。 这个方式有点类似于我们使用文字处理软件在一个文档中修改错字一样。

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.

我们意识到CRISPR系统可以被用于基因组工程的原因是， 细胞具有检测损坏的DNA， 并修复它的能力。 所以当一个植物或动物细胞在它的DNA中检测到双股螺旋断裂时， 它可以修复这种断裂， 把破裂的DNA尾端接合在一起， 只在那个位置的序列产生微小的变化， 或者，也可以借由在该位置处聚集新的DNA片段来修复断裂。 所以如果我们有一种方式可以引导"双股螺旋断裂"精准地进入DNA， 我们就可以刺激细胞来修复这些断裂， 通过破坏或合并新的遗传信息。 所以如果我们可以程式化CRISPR技术在DNA里制造断裂， 例如，在囊性纤维化发生突变的位置处或附近制造断裂， 我们就可以刺激细胞去修复那个突变。

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.

基因工程并不是什么新技术， 它在1970年代就发展起来了。 我们已经拥有DNA测序技术，DNA复制技术， 甚至DNA修改技术。 这些技术前程无量， 但问题是它们要么效率不高， 要么操作太复杂， 所以大部分科学家们并不在实验室采用这项技术， 或是应用于临床。 而CRISPR的技术相对简单， 所以使用它的机会已展露曙光。 我们可以想像一下旧的基因工程技术就好比每次你要安装新的软件， 就要把电脑升级一次一样。 而CRISPR技术就像基因组的软件， 利用这些RNA小片段， 我们可以简单地编辑它。

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.

那么一旦双股螺旋断裂在DNA中发生， 我们就可以诱导修复， 由此有可能达到惊人的效果， 比如,能够修正引起镰刀细胞贫血症， 或引起亨廷顿氏病的突变。 我认为CRISPR技术的第一项应用会在血液里发生， 相对于坚硬组织而言,更能简单地在细胞内导入这项技术。

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.

目前,很多工作已经运用在人类疾病的动物模型中，例如，老鼠。 这技术已经被用来实现非常精准的改变， 使我们能够研究细胞DNA里的变化， 不论是对一个组织或像这个案例中的，整个有机体。

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.

在这个案例中， 借由在DNA里的小改变，CRISPR技术被用来扰乱关联这些老鼠黑色皮肤的基因。 想像一下，这些白色的老鼠与它们有色小同伴不同的原因， 仅是由于在整个基因组中的一个小改变， 除此之外，它们几乎一模一样。 当我们对这些动物的基因做测序， 我们发现了在基因里的变化就精准地发生在我们使用CRISPR技术的地方。

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.

更多的实验也正在其它动物身上进行中， 被当做人类疾病的的试验模型，像是猴子。 我们在此发现，我们可以使用这系统在特定组织中运用这项技术， 例如，如何传送CRISPR工具到细胞中。 我们也想进一步了解如何控制DNA在切断后的修复方式， 也更想知道如何控制并限制任何一种偏离目标的状况， 或者使用这技术时的副作用。

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.

我想我们会在十年内就看到它在临床上的应用， 特别是在成人身上。 我认为在这段期间， 我们很可能会看到临床试验， 甚至也有可能是获得批准的治疗方式， 想想的确是件令人兴奋的事。 另外，因为这项技术的兴起， 也涌现了很多初创公司， 致力于CRISPR技术的商业化， 也有很多风险投资家开始为这些公司投资。

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.

但我们也必须要思考一件事， 就是CRISPR技术能被用在强化性能上。 想像一下我们可以尝试设计制造人类， 像是拥有更强壮的骨骼， 或降低心血管疾病的诱发机率， 甚至拥有我们期待已久的特征， 像是不同的眼睛颜色，或长得更高。"订制人"，你们也可以这么理解。 目前为止，关于哪些类型的基因会有这些特征，相关的基因信息大部分仍是未知的。 但了解CRISPR技术提供了我们一个可以改变现状的工具是很重要的， 尤其是当我们获得了这些基因信息之后。

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.

这会引发一系列我们必须仔细考量的道德问题， 这也是为什么我跟我的同事们想要呼吁全世界暂缓任何临床上有关CRISPR在人类胚胎上的应用， 给我们一些时间， 让我们认真思考各种不同的CRISPR应用。 实际上，在1970年代， 有一个类似这样暂缓的重要例子， 当时科学家们聚集在一起， 呼吁暂缓使用"分子克隆"， 直到那个技术可以安全地被小心测试并验证。

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.

虽然经过基因工程改造的人类还尚未出现， 但这已经不仅仅是科幻小说了。 动物及植物的基因改造正在进行中。 这也使我们每一个人都面临一项重大责任， 来认真思考这个科技突破可能会带来的未知后果和可预见的冲击。

Thank you.

谢谢各位!

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 Giussani (BG)：詹妮弗 ， 这是个具有很大影响力的技术， 你刚才说过了。 你要求暂停、延期或隔离的态度是非常负责任的。 当然有一些应用会有疗效， 但也有一些非治疗性的， 而它们似乎特别受媒体的关注。 这是《经济学人》杂志最新的议题——"定制人类"。 关注点几乎都在基因学性能的提升， 而非治疗。 今年三月你跟你在科学界的同事， 对此技术提出要求并建议——"我们必须立刻停止并思考"后， 你们得到了什么样的回应呢?

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.

詹妮弗 道娜(JD)：我想， 我的同事们实际上很高兴有这个机会可以公开讨论这件事。 向大众介绍这项技术是个很有趣的经历， 和同事或者其他人说起也是这样， 关于这件事大家都有不同的见解。 所以很明显， 这件事需要人们进行深入思考和讨论。

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?

BG：今年12月还有一次大型会议， 你跟你同事都有被邀请， 与国家科学院及其他机构的专家一起开会， 你希望会议中能达成什么共识呢?

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：我希望我们可以与很多不同的私人机构及投资人针对如何负责任地使用此项技术做一次线上会议沟通。 也许不太可能会达成共识， 但我认为我们至少要了解当我们继续前进时会面临哪些问题。

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：你的同事，比方说哈佛大学的George Church， 他们会说"对啊，有关道德上的考量， 基本上只是安全性问题， 我们会不断地在实验室里做动物实验， 一旦我们感觉它够安全， 才会在人体中做测试啊!"所以这有点像其他一类想法，"我们应该利用此机会并大胆尝试。"这有没有可能在科学界产生分歧呢?我的意思是，有些人忍住了， 因为他们有道德方面的顾虑， 有些人则没有，依然我行我素， 因为有些国家有管制， 而有些则完全没有？

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：我想对很多新科技， 尤其类似这样的技术， 大家都会有不同的观点， 这完全可以理解。 我想到最后， 这项技术会被用在人类基因工程上， 但我认为如果没有深思熟虑并讨论其中的风险和可能的并发症， 那是不负责任的表现。

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：我想有很多技术和其他领域的科学跟你的很像，正在急速地发展着。 比如说人工智能、自主性机器人等等...似乎没有人 —— 除了自主作战机器人—— 在这些领域中， 似乎没有人发表相同的言论， 要来呼吁暂缓之类的。 你是否认为你的讨论也许可以成为其他领域的参考蓝图？

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： 我认为，要让科学家不做实验是不太可能的。 就我自己而言， 这样做有点不太舒服。 但我的确认为我们涉及到这件事的源头， 使我跟同事们必须站出来为这件事负责。 我要说我肯定希望其他的科学技术也能用同样的方式来思考， 正如我们考量到某些事也有可能会牵连到除开生物学之外的其他领域。

BG: Jennifer, thanks for coming to TED.

BG：詹妮弗，感谢你来TED演讲。

JD: Thank you.

JD：谢谢。

（来源：口译网/英语演讲视频精选  编辑：yaning）