So, has everybody heard of CRISPR? I would be shocked if you hadn't.
有人听说过 CRISPR 吗 大家应该都知道
This is a technology -- it's for genome editing -- and it's so versatile and so controversial that it's sparking all sorts of really interesting conversations. Should we bring back the woolly mammoth? Should we edit a human embryo? And my personal favorite: How can we justify wiping out an entire species that we consider harmful to humans off the face of the Earth, using this technology?
这是一种人为改变染色体的技术 这种技术如此全能却又十分引人争议 以至于各种有趣的争论应运而生 我们要猛犸象复活吗? 我们应该改造人类胚胎吗? 我最喜欢的一个问题是 我们能够接受 用这种技术 将一个人类认为有害的物种 从地球上完全消灭吗?
This type of science is moving much faster than the regulatory mechanisms that govern it. And so, for the past six years, I've made it my personal mission to make sure that as many people as possible understand these types of technologies and their implications.
这种科技比控制它本身的 常规技术 发展的还要快 在过去六年里 我致力于 让更多人了解这种技术 以及它的意义何在
Now, CRISPR has been the subject of a huge media hype, and the words that are used most often are "easy" and "cheap." So what I want to do is drill down a little bit deeper and look into some of the myths and the realities around CRISPR.
现在,CRISPR已经成了媒体炒作的焦点 最普遍的用于描述它的词 是“容易” 和“廉价” 我想将这个话题深入下去 并探讨与之有关的谜团 以及现实状况
If you're trying to CRISPR a genome, the first thing that you have to do is damage the DNA. The damage comes in the form of a double-strand break through the double helix. And then the cellular repair processes kick in, and then we convince those repair processes to make the edit that we want, and not a natural edit. That's how it works. It's a two-part system. You've got a Cas9 protein and something called a guide RNA. I like to think of it as a guided missile. So the Cas9 -- I love to anthropomorphize -- so the Cas9 is kind of this Pac-Man thing that wants to chew DNA, and the guide RNA is the leash that's keeping it out of the genome until it finds the exact spot where it matches. And the combination of those two is called CRISPR. It's a system that we stole from an ancient, ancient bacterial immune system.
如果 你想在一条染色体 上做CRISPR 你得首先破环DNA分子 这种破坏需要从双螺旋结构上 斩断双链结构 随后细胞的修复机制开始插手 这是我们就可以让这些修复系统 来改造我们想要的基因了 这不是自然的改造 这就是这种技术的原理 这是一个两步走的技术 首先要有一个Cas9蛋白质 还有一种向导RNA 可以将其比作定向导弹 于是Cas9蛋白质 -我喜欢将其拟人化 Cas9 就像是吃豆人中的小圆脸 迫不及待地想要吃掉 DNA 向导 RNA 就像是 控制住它不进入染色体的皮带 直到它找到了符合的位置 这两种分子的结合体就叫做 CRISPR 这是一种我们从 古老的细菌结构中 发现的方法
The part that's amazing about it is that the guide RNA, only 20 letters of it, are what target the system. This is really easy to design, and it's really cheap to buy. So that's the part that is modular in the system; everything else stays the same. This makes it a remarkably easy and powerful system to use.
最令人惊奇的部分是 RNA 虽只有20个有效信息 但却是整个结构的定位部分 CRISPR 设计起来非常容易 并且价格低廉 这种手法已经被模块化 并且一成不变 因此这种技术用起来十分便捷 并且有效
The guide RNA and the Cas9 protein complex together go bouncing along the genome, and when they find a spot where the guide RNA matches, then it inserts between the two strands of the double helix, it rips them apart, that triggers the Cas9 protein to cut, and all of a sudden, you've got a cell that's in total panic because now it's got a piece of DNA that's broken.
向导 RNA 和 Cas9 蛋白质 组成一个整体 在染色体上来回穿梭 当它们发现一个与 向导 RNA 吻合的部位时 就会嵌入双螺旋结构 将其撕裂 导致 Cas9 蛋白质开始切割工作 于是突然之间 你就让一个细胞处在了极大的恐慌之中 因为它的一条 DNA 收到了破坏
What does it do? It calls its first responders. There are two major repair pathways. The first just takes the DNA and shoves the two pieces back together. This isn't a very efficient system, because what happens is sometimes a base drops out or a base is added. It's an OK way to maybe, like, knock out a gene, but it's not the way that we really want to do genome editing.
这时它该怎么办呢- 呼叫现场急救员 细胞有着两种主要的修复机制 第一种是直接将断掉的 DNA 接上 这种方法不是最有效的 由于有时会多一个链环 有时又会少一个 这种方法只能... 算撞出一个基因来 但不是我们通常想要的 基因改造方式
The second repair pathway is a lot more interesting. In this repair pathway, it takes a homologous piece of DNA. And now mind you, in a diploid organism like people, we've got one copy of our genome from our mom and one from our dad, so if one gets damaged, it can use the other chromosome to repair it. So that's where this comes from. The repair is made, and now the genome is safe again.
第二种修复机制更为有趣 在这种机制中 细胞会寻找一条相同的 DNA 在有着双染色体的生物- 比如说人类 我们得到了我们父母 各自的一组染色体 如果一条 DNA 受损 细胞可以 用另外一条来修复它 这就是这种技术的原理 修复成功之后 染色体又重获安全
The way that we can hijack this is we can feed it a false piece of DNA, a piece that has homology on both ends but is different in the middle. So now, you can put whatever you want in the center and the cell gets fooled. So you can change a letter, you can take letters out, but most importantly, you can stuff new DNA in, kind of like a Trojan horse.
我们将其调包的方法 是用一条新的 DNA-- 在两端上与原来相同 中间却不同 --来修复它 于是你可以随心所欲地 将你想要的中间部分安装上去 细胞本身却毫无察觉 你可以改变基因中的一条信息 也可以删除它 但最为重要的是 你可以像特洛伊木马一样 将一条全新的 DNA 嵌入
CRISPR is going to be amazing, in terms of the number of different scientific advances that it's going to catalyze. The thing that's special about it is this modular targeting system. I mean, we've been shoving DNA into organisms for years, right? But because of the modular targeting system, we can actually put it exactly where we want it.
CRISPR 的作用出人预料 它能推动许多 不同领域的科技发展 它的特殊之处在于这个 攻击系统模块 我们多年来一直尝试着 将 DNA 嵌入生物体中 但由于这种模块攻击系统 我们能将它放在我们想要的地方
The thing is that there's a lot of talk about it being cheap and it being easy. And I run a community lab. I'm starting to get emails from people that say stuff like,
问题是现在有很多关于 它的廉价性 和便捷性的话题 我有着一所社区实验室 并且开始收到人们的来信--
"Hey, can I come to your open night and, like, maybe use CRISPR and engineer my genome?"
“我能在开放夜来你那吗? 借我用用 CRISPR 编辑 一下自己的基因行吗?”
(Laugher)
(笑声)
Like, seriously.
讲真的
I'm, "No, you can't."
我说:“不,你不行“
(Laughter)
(笑声)
"But I've heard it's cheap. I've heard it's easy."
“但我听说那很便宜,很简单啊”
We're going to explore that a little bit. So, how cheap is it? Yeah, it is cheap in comparison. It's going to take the cost of the average materials for an experiment from thousands of dollars to hundreds of dollars, and it cuts the time a lot, too. It can cut it from weeks to days. That's great. You still need a professional lab to do the work in; you're not going to do anything meaningful outside of a professional lab. I mean, don't listen to anyone who says you can do this sort of stuff on your kitchen table. It's really not easy to do this kind of work. Not to mention, there's a patent battle going on, so even if you do invent something, the Broad Institute and UC Berkeley are in this incredible patent battle. It's really fascinating to watch it happen, because they're accusing each other of fraudulent claims and then they've got people saying, "Oh, well, I signed my notebook here or there." This isn't going to be settled for years. And when it is, you can bet you're going to pay someone a really hefty licensing fee in order to use this stuff. So, is it really cheap? Well, it's cheap if you're doing basic research and you've got a lab.
我们谈谈这个吧 究竟有多便宜? 相对来说确实便宜 它能将一个实验所需材料 通常的价格 从几千美元降至几百美元 还能节约时间 几周的工作几天就能完成 这很好 但你仍需要专业的实验室来做 没有实验室 是不可能完成这项技术的 别相信那些说 你可以在自家厨房里做实验的人 这项技术真的不简单 更别说有一场如火如荼的 专利战打的正酣 即使发明者创造出了 这样的奇思妙想 布罗德研究所和 UC 伯克利也 在为专利权而争斗不休 隔岸观火很有趣 因为他们都在不断控诉对方, 称其发布诬告性言论 他们中的有人常常说 “我在我的笔记本上到处都记了笔记” 这件事好几年都没完 即使真的解决了 到那时你就得为使用这项技术 支付高昂的费用 所以它真的便宜吗? 如果你有自己的实验室,并且 在做基础学科实验的话——是的
How about easy? Let's look at that claim. The devil is always in the details. We don't really know that much about cells. They're still kind of black boxes. For example, we don't know why some guide RNAs work really well and some guide RNAs don't. We don't know why some cells want to do one repair pathway and some cells would rather do the other.
容易吗? 现在我们来谈谈这个 魔鬼总藏在深处 我们仍然不十分了解细胞 他们就像是一个黑匣子 比如说,我们不知道为什么有一些RNA 十分有效 有一些却不是这样 我们也不知道为什么 一些细胞采用一种修复机制 另一些采用另外一种
And besides that, there's the whole problem of getting the system into the cell in the first place. In a petri dish, that's not that hard, but if you're trying to do it on a whole organism, it gets really tricky. It's OK if you use something like blood or bone marrow -- those are the targets of a lot of research now.
除了这些以外 在一开始 将这个系统植入细胞时 同样面临着问题 在培养皿中,这不是很难 可是如果是整个生物体 那就很麻烦了 采用血液或是骨髓是可行的 它们也是现在的研究重点
There was a great story of some little girl who they saved from leukemia by taking the blood out, editing it, and putting it back with a precursor of CRISPR. And this is a line of research that people are going to do. But right now, if you want to get into the whole body, you're probably going to have to use a virus. So you take the virus, you put the CRISPR into it, you let the virus infect the cell. But now you've got this virus in there, and we don't know what the long-term effects of that are. Plus, CRISPR has some off-target effects, a very small percentage, but they're still there. What's going to happen over time with that?
有一个关于一位女孩 奇迹的故事 她患了白血病 最后通过将血取出,人为将其改造后 放回人体 最终痊愈——用的是CRISPR的前期技术 这是一种人们希望从事的研究 但是如果你想针对整个人体 可能就要用到病毒了 采集病毒以后, 将 CRISPR 放进去 你需要让病毒感染细胞 但只要你将病毒注入细胞内部 就可能出现长期的副作用 而且 CRISPR 还有一些 伤及无辜的攻击行为 只占很小一部分—— 但总之存在 一段时间过后又会发生什么呢?
These are not trivial questions, and there are scientists that are trying to solve them, and they will eventually, hopefully, be solved. But it ain't plug-and-play, not by a long shot. So: Is it really easy? Well, if you spend a few years working it out in your particular system, yes, it is.
这不是小事 有科学家一直想要解决这些问题 而且它们有可能被解决 但研究需要时间 这种方法真的容易吗? 在经过几年的深入研究之后 它才真正变得容易
Now the other thing is, we don't really know that much about how to make a particular thing happen by changing particular spots in the genome. We're a long way away from figuring out how to give a pig wings, for example. Or even an extra leg -- I'd settle for an extra leg. That would be kind of cool, right? But what is happening is that CRISPR is being used by thousands and thousands of scientists to do really, really important work, like making better models of diseases in animals, for example, or for taking pathways that produce valuable chemicals and getting them into industrial production in fermentation vats, or even doing really basic research on what genes do.
还有一个问题是 我们不知道怎样通过改变染色体中的 某个部位 来到达我们想要的目的 我们现在还无法获知 怎样使一只猪长出翅膀 或是多长一条腿 那会十分有趣,不是吗 但确切的是 CRISPR 正被成千上万的科学家利用 去做十分重要的工作 例如建造更好的动物疾病模型 或是找到经济的化学物质 生产方法 用它们进行工业生产和发酵 甚至是有关基因功能的基本研究
This is the story of CRISPR we should be telling, and I don't like it that the flashier aspects of it are drowning all of this out. Lots of scientists did a lot of work to make CRISPR happen, and what's interesting to me is that these scientists are being supported by our society.
这才是 CRISPR 真正的用处 我不赞同让它的瑕疵 掩盖了它真正的光芒 不计其数的科学家 呕心沥血造就了 CRISPR 我认为十分明智的是 这些科学家受到了社会的广泛支持
Think about it. We've got an infrastructure that allows a certain percentage of people to spend all their time doing research. That makes us all the inventors of CRISPR, and I would say that makes us all the shepherds of CRISPR. We all have a responsibility.
想一想 我们有着能够让一小部分人 在里面倾其一生 从事科学研究的机构 这让我们所有人 成为了 CRISPR 的创造者 让我们成为 CRISPR 的掌控者 我们需要负起责任来
So I would urge you to really learn about these types of technologies, because, really, only in that way are we going to be able to guide the development of these technologies, the use of these technologies and make sure that, in the end, it's a positive outcome -- for both the planet and for us.
所以我们需要 重视这方面的技术 因为,只有这样 我们才能掌控这些技术的发展 和它们的应用 然后确保到最后 我们能得到正面的结果 不管是对这颗星球 还是我们自己
Thanks.
谢谢
(Applause)
(掌声)