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So, has everybody heard of CRISPR?
有人听说过 CRISPR吗
I would be shocked if you hadn't.
你没听过我也不感觉很吃惊
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.
它是一种基因编辑技术手段 由于其功能多样 备受争议的特点引起了各种各样非常有趣的争议
Should we bring back the woolly mammoth? Should we edit a human embryo?
我们应该将灭绝的长毛象复活吗 我们应该编辑人类胚胎吗
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?
我最喜欢的一个问题是 我们如何将人类使用这项技术使那些我们认为对自己有害的全部物种清除出地球这种做法变得有理可据
This type of science is moving much faster than the regulatory mechanisms that govern it.
这种科技比控制它本身的常规技术发展的还要快
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.
在过去的六年中 我都将使更多的人了解这种技术和它们的涵义作为自己的使命
Now, CRISPR has been the subject of a huge media hype,
现在 CRISPR已经成了媒体炒作的焦点
and the words that are used most often are "easy" and "cheap."
并且被大众媒体贴上了 简单 容易的标签
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.
我想将这个话题深入下去 探究CRISPR的奥秘以及现实状况
If you're trying to CRISPR a genome, the first thing that you have to do is damage the DNA.
如果 你想编辑一个染色体 你得首先破环DNA分子
The damage comes in the form of a double-strand break through the double helix.
这种破坏需要从双螺旋结构上斩断双链结构
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.
随后细胞的修复机制开始插手这时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
That's how it works. It's a two-part system.
这就是这种技术的原理 这是一个两步走的技术
You've got a Cas9 protein and something called a guide RNA.
首先要有一个Cas9蛋白质 还有一种向导RNA
I like to think of it as a guided missile.
可以将其比作定向引导导弹
So the Cas9 -- I love to anthropomorphize so the Cas9 is kind of this Pac-Man thing that wants to chew DNA,
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
and the guide RNA is the leash that's keeping it out of the genome until it finds the exact spot where it matches.
向导RNA相当于拉住它 使它远离染色体的牵引绳（类似遛狗）直到它找到特定的位点
And the combination of those two is called CRISPR.
这两种分子的结合体就叫做 CRISPR
It's a system that we stole from an ancient, ancient bacterial immune system.
它是在效仿一种极其古老的细菌免疫系统
The part that's amazing about it is that the guide RNA, only 20 letters of it, are what target the system.
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
This is really easy to design, and it's really cheap to buy.
CRISPR 设计起来非常容易并且价格低廉
So that's the part that is modular in the system; everything else stays the same.
这种手法已经被模块化 并且一成不变
This makes it a remarkably easy and powerful system to use.
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,
向导 RNA 和 Cas9 蛋白质组成一个整体在染色体上来回穿梭
and when they find a spot where the guide RNA matches,
当它们发现一个与向导 RNA 吻合的部位时
then it inserts between the two strands of the double helix, it rips them apart,
就会嵌入双螺旋结构 将其撕裂
that triggers the Cas9 protein to cut, and all of a sudden,
导致 Cas9 蛋白质开始切割工作 于是突然之间
you've got a cell that's in total panic because now it's got a piece of DNA that's broken.
你就让一个细胞处在了极大的恐慌之中因为它的一条 DNA 被破坏
What does it do It calls its first responders.
这时它该怎么办呢 呼叫现场急救员
There are two major repair pathways.
细胞有着两种主要的修复机制
The first just takes the DNA and shoves the two pieces back together.
第一种是直接将断掉的 DNA 接上
This isn't a very efficient system, because what happens is sometimes a base drops out or a base is added.
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
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.
第二种修复机制更为有趣
In this repair pathway, it takes a homologous piece of DNA.
在这种机制中 细胞会寻找一条相同的 DNA
And now mind you, in a diploid organism like people,
在有着双染色体的生物 比如说人类
we've got one copy of our genome from our mom and one from our dad,
我们得到了我们父母 各自的一组染色体
so if one gets damaged, it can use the other chromosome to repair it.
如果一条 DNA 受损 细胞可以用另外一条来修复它
So that's where this comes from.
这就是这种技术的原理
The repair is made, and now the genome is safe again.
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.
我们将其调包的方法是用一条新的DNA替换中间段两端与原来相同的新DNA来修复它
So now, you can put whatever you want in the center and the cell gets fooled.
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
So you can change a letter, you can take letters out,
你可以改变基因中的一条信息 也可以删除它
but most importantly, you can stuff new DNA in, kind of like a Trojan horse.
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.
CRISPR 的作用出人预料 它能推动许多不同领域的科技发展
The thing that's special about it is this modular targeting system.
它的特殊之处在于这个攻击系统模块
I mean, we've been shoving DNA into organisms for years, right?
我们多年来一直尝试着将 DNA 嵌入生物体中
But because of the modular targeting system, we can actually put it exactly where we want it.
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.
问题是现在有很多关于 它的廉价性和便捷性的话题
And I run a community lab.
我有一所社区实验室
I'm starting to get emails from people that say stuff like,
并且开始收到人们的来信
"Hey, can I come to your open night
我能在开放夜来你那吗？
and, like, maybe use CRISPR and engineer my genome?"
我能用 CRISPR 编辑一下自己的基因吗？
Like, seriously. I'm, "No, you can't." "But I've heard it's cheap. I've heard it's easy."
讲真的 我说 不能 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.
我们谈谈这个吧 究竟有多便宜 相对来说确实便宜
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.
实验所需材料花费从几千美元降至几百美元 还能节约很多时间
It can cut it from weeks to days. That's great.
几周的工作几天就能完成 这很好
You still need a professional lab to do the work in; you're not going to do anything meaningful outside of a professional lab.
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
I mean, don't listen to anyone who says you can do this sort of stuff on your kitchen table.
我是说 别相信那些类似你能在你家厨房做这个实验这种说法
It's really not easy to do this kind of work.
做这个工程真的不那么容易
Not to mention, there's a patent battle going on, so even if you do invent something,
更不用说 一场专利之争正在进行 所以即使你有某些重大发现
the Broad Institute and UC Berkeley are in this incredible patent battle.
布罗德研究所和 UC 伯克利也在为专利权而争斗不休
It's really fascinating to watch it happen,
隔岸观火很有趣
because they're accusing each other of fraudulent claims
因为他们都在不断控诉对方 称其发布诬告性言论
and then they've got people saying, "Oh, well, I signed my notebook here or there."
他们中的有人常常说 我在我的笔记本上到处都记了笔记
This isn't going to be settled for years.
这件事好几年都没完
And when it is, you can bet you're going to pay someone a really hefty licensing fee in order to use this stuff.
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
So, is it really cheap? Well, it's cheap if you're doing basic research and you've got a lab.
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 确实很便宜
How about easy? Let's look at that claim. The devil is always in the details.
容易吗 现在我们来谈谈这个 魔鬼总藏在深处
We don't really know that much about cells. They're still kind of black boxes.
我们仍然不十分了解细胞 他们就像是一个黑匣子
For example, we don't know why some guide RNAs work really well and some guide RNAs don't.
比如说 我们不知道为什么有一些RNA十分好用有一些却不好使
We don't know why some cells want to do one repair pathway and some cells would rather do the other.
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.
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
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.
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
It's OK if you use something like blood or bone marrow those are the targets of a lot of research now.
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
有个关于一位女孩的奇迹 她患了白血病
by taking the blood out, editing it, and putting it back with a precursor of CRISPR.
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
And this is a line of research that people are going to do.
这是一种人们希望从事的研究
But right now, if you want to get into the whole body, you're probably going to have to use a virus.
但是如果你想针对整个人体可能就要用到病毒了
So you take the virus, you put the CRISPR into it, you let the virus infect the cell.
采集病毒以后 将 CRISPR 放进去你需要让病毒感染细胞
But now you've got this virus in there, and we don't know what the long-term effects of that are.
但只要你将病毒注入细胞内部就可能出现长期的副作用
Plus, CRISPR has some off-target effects, a very small percentage, but they're still there.
而且 CRISPR 还有一些伤及无辜的攻击行为只占很小一部分—— 但总是存在的
What's going to happen over time with that?
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.
这不是小事 有科学家一直想要解决这些问题 而且它们最终会被解决 很有这种可能
But it ain't plug-and-play, not by a long shot. So: Is it really easy?
但研究需要时间 这种方法真的容易吗
Well, if you spend a few years working it out in your particular system, yes, it is.
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.
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达到我们想要的目的
We're a long way away from figuring out how to give a pig wings, for example.
我们现在还无法获知怎样使一只猪长出翅膀
Or even an extra leg -- I'd settle for an extra leg.
或是多长一条腿 就拿这个举例
That would be kind of cool, right?
那会十分有趣 不是吗
But what is happening is that CRISPR is being used by thousands and thousands of scientists to do really, really important work,
但是现在成千上万名科学家正在将CRISPR这项技术应用于很重要的工程中
like making better models of diseases in animals, for example, or for taking pathways that produce valuable chemicals
构建更好的动物疾病模型 或是找到可用的化学物质生产方法
and getting them into industrial production in fermentation vats, or even doing really basic research on what genes do.
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.
这就是 CRISPR 的故事 我不想让它浮华的那一面将它真正的光芒掩盖了
Lots of scientists did a lot of work to make CRISPR happen,
很多科学家都为制造CRISPR做出了很多贡献
and what's interesting to me is that these scientists are being supported by our society. Think about it.
让我感到欣慰的是 这些科学家得到了社会的广泛支持 想一想
We've got an infrastructure that allows a certain percentage of people to spend all their time doing research.
我们有着能够让一小部分人愿意倾其一生从事科学研究的机构
That makes us all the inventors of CRISPR, and I would say that makes us all the shepherds of CRISPR.
这使得我们都成为CRISPR技术的发明者 而我想强调的是那也使我们成为这项技术的引领者
We all have a responsibility.
我们都需要有很强的责任感
So I would urge you to really learn about these types of technologies,
所以我迫切地希望你们能够真正地了解这项技术
because, really, only in that way are we going to be able to guide the development of these technologies,
因为只有这样我们才能掌控这些技术的发展
the use of these technologies and make sure that, in the end, it's a positive outcome for both the planet and for us. Thanks.
引导这些技术的应用方向 确保这项技术最终能够给地球和人类都带来好的结果 谢谢大家
