What you need to know about CRISPR | Ellen Jorgensen

翻译人员: Elvis Liu 校对人员: Tom Liu

So, has everybody heard of CRISPR?

有人听说过 CRISPR 吗

I would be shocked if you hadn't.

大家应该都知道

This is a technology -- it's for genome editing --

这是一种人为改变染色体的技术

and it's so versatile and so controversial

这种技术如此全能却又十分引人争议

that it's sparking all sorts of really interesting conversations.

以至于各种有趣的争论应运而生

Should we bring back the woolly mammoth?

我们要猛犸象复活吗？

Should we edit a human embryo?

我们应该改造人类胚胎吗？

And my personal favorite:

我最喜欢的一个问题是

How can we justify wiping out an entire species

我们能够接受

that we consider harmful to humans

用这种技术

off the face of the Earth,

将一个人类认为有害的物种

using this technology?

从地球上完全消灭吗？

This type of science is moving much faster

这种科技比控制它本身的 常规技术

than the regulatory mechanisms that govern it.

发展的还要快

And so, for the past six years,

在过去六年里

I've made it my personal mission

我致力于

to make sure that as many people as possible understand

让更多人了解这种技术

these types of technologies and their implications.

以及它的意义何在

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."

最普遍的用于描述它的词 是“容易” 和“廉价”

So what I want to do is drill down a little bit deeper

我想将这个话题深入下去

and look into some of the myths and the realities around CRISPR.

并探讨与之有关的谜团 以及现实状况

If you're trying to CRISPR a genome,

如果 你想在一条染色体 上做CRISPR

the first thing that you have to do is damage the DNA.

你得首先破环DNA分子

The damage comes in the form of a double-strand break

这种破坏需要从双螺旋结构上

through the double helix.

斩断双链结构

And then the cellular repair processes kick in,

随后细胞的修复机制开始插手

and then we convince those repair processes

这是我们就可以让这些修复系统

to make the edit that we want,

来改造我们想要的基因了

and not a natural edit.

这不是自然的改造

That's how it works.

这就是这种技术的原理

It's a two-part system.

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.

可以将其比作定向导弹

So the Cas9 -- I love to anthropomorphize --

于是Cas9蛋白质 -我喜欢将其拟人化

so the Cas9 is kind of this Pac-Man thing

Cas9 就像是吃豆人中的小圆脸

that wants to chew DNA,

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

向导 RNA 就像是 控制住它不进入染色体的皮带

until it finds the exact spot where it matches.

直到它找到了符合的位置

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

这是一种我们从

from an ancient, ancient bacterial immune system.

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,

最令人惊奇的部分是 RNA

only 20 letters of it,

虽只有20个有效信息

are what target the system.

但却是整个结构的定位部分

This is really easy to design,

CRISPR 设计起来非常容易

and it's really cheap to buy.

并且价格低廉

So that's the part that is modular in the system;

这种手法已经被模块化

everything else stays the same.

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

向导 RNA 和 Cas9 蛋白质 组成一个整体

go bouncing along the genome,

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,

就会嵌入双螺旋结构

it rips them apart,

将其撕裂

that triggers the Cas9 protein to cut,

导致 Cas9 蛋白质开始切割工作

and all of a sudden,

于是突然之间

you've got a cell that's in total panic

你就让一个细胞处在了极大的恐慌之中

because now it's got a piece of DNA that's broken.

因为它的一条 DNA 收到了破坏

What does it do?

这时它该怎么办呢-

It calls its first responders.

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,

这种方法不是最有效的

because what happens is sometimes a base drops out

由于有时会多一个链环

or a base is added.

有时又会少一个

It's an OK way to maybe, like, knock out a gene,

这种方法只能... 算撞出一个基因来

but it's not the way that we really want to do genome editing.

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,

在这种机制中

it takes a homologous piece of DNA.

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,

如果一条 DNA 受损

it can use the other chromosome to repair it.

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,

修复成功之后

and now the genome is safe again.

染色体又重获安全

The way that we can hijack this

我们将其调包的方法

is we can feed it a false piece of DNA,

是用一条新的 DNA--

a piece that has homology on both ends

在两端上与原来相同

but is different in the middle.

中间却不同 --来修复它

So now, you can put whatever you want in the center

于是你可以随心所欲地 将你想要的中间部分安装上去

and the cell gets fooled.

细胞本身却毫无察觉

So you can change a letter,

你可以改变基因中的一条信息

you can take letters out,

也可以删除它

but most importantly, you can stuff new DNA in,

但最为重要的是 你可以像特洛伊木马一样

kind of like a Trojan horse.

将一条全新的 DNA 嵌入

CRISPR is going to be amazing,

CRISPR 的作用出人预料

in terms of the number of different scientific advances

它能推动许多

that it's going to catalyze.

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,

但由于这种模块攻击系统

we can actually put it exactly where we want it.

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

问题是现在有很多关于 它的廉价性

and it being easy.

和便捷性的话题

And I run a community lab.

我有着一所社区实验室

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?"

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.

我们谈谈这个吧

So, how cheap is it?

究竟有多便宜？

Yeah, it is cheap in comparison.

相对来说确实便宜

It's going to take the cost of the average materials for an experiment

它能将一个实验所需材料 通常的价格

from thousands of dollars to hundreds of dollars,

从几千美元降至几百美元

and it cuts the time a lot, too.

还能节约时间

It can cut it from weeks to days.

几周的工作几天就能完成

That's great.

这很好

You still need a professional lab to do the work in;

但你仍需要专业的实验室来做

you're not going to do anything meaningful outside of a professional lab.

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

别相信那些说

you can do this sort of stuff on your kitchen table.

你可以在自家厨房里做实验的人

It's really not easy to do this kind of work.

这项技术真的不简单

Not to mention, there's a patent battle going on,

更别说有一场如火如荼的 专利战打的正酣

so even if you do invent something,

即使发明者创造出了 这样的奇思妙想

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,

他们中的有人常常说

"Oh, well, I signed my notebook here or there."

“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,

即使真的解决了

you can bet you're going to pay someone a really hefty licensing fee

到那时你就得为使用这项技术

in order to use this stuff.

支付高昂的费用

So, is it really cheap?

所以它真的便宜吗？

Well, it's cheap if you're doing basic research and you've got a lab.

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.

容易吗？ 现在我们来谈谈这个

The devil is always in the details.

魔鬼总藏在深处

We don't really know that much about cells.

我们仍然不十分了解细胞

They're still kind of black boxes.

他们就像是一个黑匣子

For example, we don't know why some guide RNAs work really well

比如说，我们不知道为什么有一些RNA 十分有效

and some guide RNAs don't.

有一些却不是这样

We don't know why some cells want to do one repair pathway

我们也不知道为什么 一些细胞采用一种修复机制

and some cells would rather do the other.

另一些采用另外一种

And besides that,

除了这些以外

there's the whole problem of getting the system into the cell

在一开始

in the first place.

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,

在培养皿中，这不是很难

but if you're trying to do it on a whole organism,

可是如果是整个生物体

it gets really tricky.

那就很麻烦了

It's OK if you use something like blood or bone marrow --

采用血液或是骨髓是可行的

those are the targets of a lot of research now.

它们也是现在的研究重点

There was a great story of some little girl

有一个关于一位女孩 奇迹的故事

who they saved from leukemia

她患了白血病

by taking the blood out, editing it, and putting it back

最后通过将血取出，人为将其改造后 放回人体

with a precursor of CRISPR.

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,

但是如果你想针对整个人体

you're probably going to have to use a virus.

可能就要用到病毒了

So you take the virus, you put the CRISPR into it,

采集病毒以后， 将 CRISPR 放进去

you let the virus infect the cell.

你需要让病毒感染细胞

But now you've got this virus in there,

但只要你将病毒注入细胞内部

and we don't know what the long-term effects of that are.

就可能出现长期的副作用

Plus, CRISPR has some off-target effects,

而且 CRISPR 还有一些 伤及无辜的攻击行为

a very small percentage, but they're still there.

只占很小一部分—— 但总之存在

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,

这不是小事

and there are scientists that are trying to solve them,

有科学家一直想要解决这些问题

and they will eventually, hopefully, be solved.

而且它们有可能被解决

But it ain't plug-and-play, not by a long shot.

但研究需要时间

So: Is it really easy?

这种方法真的容易吗？

Well, if you spend a few years working it out in your particular system,

在经过几年的深入研究之后

yes, it is.

它才真正变得容易

Now the other thing is,

还有一个问题是

we don't really know that much about how to make a particular thing happen

我们不知道怎样通过改变染色体中的 某个部位

by changing particular spots in the genome.

来到达我们想要的目的

We're a long way away from figuring out

我们现在还无法获知

how to give a pig wings, for example.

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

That would be kind of cool, right?

那会十分有趣，不是吗

But what is happening

但确切的是

is that CRISPR is being used by thousands and thousands of scientists

CRISPR 正被成千上万的科学家利用

to do really, really important work,

去做十分重要的工作

like making better models of diseases in animals, for example,

例如建造更好的动物疾病模型

or for taking pathways that produce valuable chemicals

或是找到经济的化学物质 生产方法

and getting them into industrial production in fermentation vats,

用它们进行工业生产和发酵

or even doing really basic research on what genes do.

甚至是有关基因功能的基本研究

This is the story of CRISPR we should be telling,

这才是 CRISPR 真正的用处

and I don't like it that the flashier aspects of it

我不赞同让它的瑕疵

are drowning all of this out.

掩盖了它真正的光芒

Lots of scientists did a lot of work to make CRISPR happen,

不计其数的科学家 呕心沥血造就了 CRISPR

and what's interesting to me

我认为十分明智的是

is that these scientists are being supported by our society.

这些科学家受到了社会的广泛支持

Think about it.

想一想

We've got an infrastructure that allows a certain percentage of people

我们有着能够让一小部分人 在里面倾其一生

to spend all their time doing research.

从事科学研究的机构

That makes us all the inventors of CRISPR,

这让我们所有人 成为了 CRISPR 的创造者

and I would say that makes us all the shepherds of CRISPR.

让我们成为 CRISPR 的掌控者

We all have a responsibility.

我们需要负起责任来

So I would urge you to really learn about these types of technologies,

所以我们需要 重视这方面的技术

because, really, only in that way

因为，只有这样

are we going to be able to guide the development of these technologies,

我们才能掌控这些技术的发展

the use of these technologies

和它们的应用

and make sure that, in the end, it's a positive outcome --

然后确保到最后 我们能得到正面的结果

for both the planet and for us.

不管是对这颗星球 还是我们自己

Thanks.

谢谢

(Applause)

（掌声）

Translated by: Elvis Liu