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基因剪辑现在可以永远改变整个种群 – 译学馆
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基因剪辑现在可以永远改变整个种群

Gene editing can now change an entire species -- forever | Jennifer Kahn

这是一个有关于基因驱动的演讲
So this is a talk about gene drives,
但我要先讲一个小故事
but I’m going to start by telling you a brief story.
20年前 一位名为安东尼·詹姆斯的
20 years ago, a biologist named Anthony James
生物学家正致力于培育不会传播
got obsessed with the idea of making mosquitos
疟疾的蚊子
that didn’t transmit malaria.
这是一个很好的想法 但是结果失败的
It was a great idea, and pretty much a complete failure.
要想让蚊子不携带疟疾
For one thing, it turned out to be really hard
是非常困难的
to make a malaria-resistant mosquito.
最终 詹姆斯在几年前
James managed it, finally, just a few years ago,
利用添加基因的方式才使
by adding some genes that make it impossible
幸存下来的蚊子上不带有疟疾
for the malaria parasite to survive inside the mosquito.
但是接下来还有一个问题
But that just created another problem.
我们有了抵抗疟疾的蚊子
Now that you’ve got a malaria-resistant mosquito,
要如何替换那些携带疟疾的蚊子呢?
how do you get it to replace all the malaria-carrying mosquitos?
有很多方案
There are a couple options,
方案一主要依靠培育的办法
but plan A was basically to breed up
向大自然中释放一群新型的
a bunch of the new genetically-engineered mosquitos
经过基因改造的蚊子
release them into the wild
寄希望于它们大量繁殖 稀释原来的基因
and hope that they pass on their genes.
但是问题在于你不得不释放的数目是
The problem was that you’d have to release
本地区蚊子数目的十倍才能起作用
literally 10 times the number of native mosquitos to work.
如果一个小镇上有一万只蚊子
So in a village with 10,000 mosquitos,
就要释放十万只转基因蚊子
you release an extra 100,000.
可以想象
As you might guess,
对于当地村民来说这个方法不是很好
this was not a very popular strategy with the villagers.
[笑声]
[Laughter]
今年一月的时候 安东尼詹姆斯收到一封来自于
Then, last January, Anthony James got an email
伊森比尔的生物学家的邮件
from a biologist named Ethan Bier.
比尔说他和他的研究生瓦伦蒂诺·甘茨
Bier said that he and his grad student Valentino Gantz
无意中发现了一种工具
had stumbled on a tool that could not only guarantee
不仅可以保证特定的基因会被遗传
that a particular genetic trait would be inherited,
而且基因传播的速度难以置信的快
but that it would spread incredibly quickly.
如果他们是对的 就从基本上解决了这个
If they were right, it would basically solve the problem
詹姆斯潜心研究20年的问题
that he and James had been working on for 20 years.
实验中需要两只携带抗疟疾基因的蚊子
As a test, they engineered two mosquitos to carry the anti-malaria gene
以及新的工具 即基因剪辑装置
and also this new tool, a gene drive,
一会儿我会详细介绍
which I’ll explain in a minute.
实验的工具是任何携带
Finally, they set it up so that any mosquitos
抗疟疾基因的蚊子
that had inherited the anti-malaria gene
它们将拥有红色的眼睛 而不是常见的白色眼睛
wouldn’t have the usual white eyes, but would instead have red eyes.
这也只是为了更好的通过肉眼观察
That was pretty much just for convenience
以至于他们可以瞥一眼就发现哪个是哪个
so they could tell just at a glance which was which.
研究者把两只抗疟疾红眼蚊子
So they took their two anti-malarial, red-eyed mosquitos
和三十个普通白眼蚊子放在一个盒子里
and put them in a box with 30 ordinary white-eyed ones,
让它们自由繁殖
and let them breed.
两代繁殖之后 培养了3800个子二代
In two generations, those had produced 3,800 grandchildren.
这并不是让人惊讶的部分
That is not the surprising part.
下面才是惊人的部分:
This is the surprising part:
如果一开始只有两只红眼蚊子
given that you started with just two red-eyed mosquitos
三十只白眼蚊子
and 30 white-eyed ones,
它们自由繁殖的后代大多数应该是白眼
you expect mostly white-eyed descendants.
然而当詹姆斯打开盒子
Instead, when James opened the box,
3800只蚊子全部都是红眼
all 3,800 mosquitos had red eyes.
当我问伊森比尔这一时刻的感受时
When I asked Ethan Bier about this moment,
他太兴奋了 在电话里一直叫喊着
he became so excited that he was literally shouting into the phone.
因为只得到了红色眼睛的蚊子
That’s because getting only red-eyed mosquitos
打破了生物学的绝对基本定律
violates a rule that is the absolute cornerstone of biology,
孟德尔遗传定律
Mendelian genetics.
这部分我大概讲一下
I’ll keep this quick,
孟德尔遗传定律的观点是当一个雌性和雄性
but Mendelian genetics says when a male and a female mate,
她们的后代的DNA由父母各自提供一半
their baby inherits half of its DNA from each parent.
所以如果本来蚊子的基因是aa 转基因蚊子的基因是aB
So if our original mosquito was aa and our new mosquito is aB,
B是抗疟疾基因
where B is the anti-malarial gene,
后代应该呈现下面四种基因组合:
the babies should come out in four permutations:
aa、aB、aa、Ba染色体
aa, aB, aa, Ba.
然而使用了新的基因驱动之后
Instead, with the new gene drive,
它们全变成了aB型
they all came out aB.
从生物学的角度说 这应该是不可能的
Biologically, that shouldn’t even be possible.
到底发生了什么呢?
So what happened?
首先
The first thing that happened
要追溯到2012年 一种叫做“CRISPR”的基因编辑工具的出现
was the arrival of a gene-editing tool known as CRISPR in 2012.
很多人可能听说过CRISPR(基因编辑技术)
Many of you have probably heard about CRISPR,
所以我只需简略说明 CRISPR是一种工具
so I’ll just say briefly that CRISPR is a tool that allows researchers
它使研究人员能够精确、简单、迅速地编辑基因
to edit genes very precisely, easily and quickly.
它通过利用细菌体内本有的一种机制来完成
It does this by harnessing a mechanism that already existed in bacteria.
简单说 就是有一种能像剪子一样
Basically, there’s a protein that acts like a scissors
剪切DNA的蛋白质
and cuts the DNA,
另外还有一个RNA分子 可以引导这把“剪子”
and there’s an RNA molecule that directs the scissors
在你需要的基因组的任意位置上剪辑
to any point on the genome you want.
其结果说白了就类似于是适用于基因的“文字处理器”
The result is basically a word processor for genes.
你可以取出整段基因 再加入一个进行替换
You can take an entire gene out, put one in,
甚至可以编辑基因中的单个碱基
or even edit just a single letter within a gene.
这个工具几乎适用于所有物种
And you can do it in nearly any species.
前面我提过基因驱动有两大难题
OK, remember how I said that gene drives originally had two problems?
首先是如何培育一只
The first was that it was hard to engineer a mosquito
抗疟疾的蚊子
to be malaria-resistant.
多亏了CRISPR 我们解决了这个难题
That’s basically gone now, thanks to CRISPR.
但是第二个问题随之而来
But the other problem was logistical.
如何让这个性状得以传播?
How do you get your trait to spread?
这就是这个装置精巧的地方
This is where it gets clever.
几年前 一名哈佛大学的生物学家凯文·恩斯福尔特
A couple years ago, a biologist at Harvard named Kevin Esvelt
想知道如果
wondered what would happen
如果不仅在新基因中使用CRISPR
if you made it so that CRISPR inserted not only your new gene
而且在剪切复制机制中也使用CRISPR 那将会发生什么
but also the machinery that does the cutting and pasting.
换言之 如果CRISPR自己也进行复制粘贴会如何
In other words, what if CRISPR also copied and pasted itself.
我们就得到了永动的基因修改工具
You’d end up with a perpetual motion machine for gene editing.
事实果真如此
And that’s exactly what happened.
恩斯福尔特创造的CRISPR基因驱动装置
This CRISPR gene drive that Esvelt created
不仅保证了性状的传播
not only guarantees that a trait will get passed on,
而且当它作用于生殖细胞的时候
but if it’s used in the germline cells,
它会在每个个体的两条染色体上
it will automatically copy and paste your new gene
自动复制粘贴新的基因
into both chromosomes of every single individual.
就像是全面检索并替换的功能
It’s like a global search and replace,
用学术术语来说 就是杂合子性状纯合化
or in science terms, it makes a heterozygous trait homozygous.
那么这意味着什么呢?
So, what does this mean?
首先 我们拥有了一个很强大
For one thing, it means we have a very powerful,
但同时也令人担忧的新工具
but also somewhat alarming new tool.
目前为止 基因驱动还并不是很有效
Up until now, the fact that gene drives didn’t work very well
这反而让我们感到欣慰
was actually kind of a relief.
通常 当我们对有机体的基因进行研究时
Normally when we mess around with an organism’s genes,
我们会使这些基因的演变变得少点
we make that thing less evolutionarily fit.
生物学家可以随心所欲培育变异果蝇
So biologists can make all the mutant fruit flies they want
没有任何的后患之忧
without worrying about it.
如果一些飞走逃跑了 自然选择会好好照顾它们
If some escape, natural selection just takes care of them.
基因驱动的强大和可怕之处在于
What’s remarkable and powerful and frightening about gene drives
这种情况不再是理所当然的了
is that that will no longer be true.
想象新的性状并没有一个 像蚊子不会飞那样的
Assuming that your trait does not have a big evolutionary handicap,
一个很大的进化缺陷
like a mosquito that can’t fly,
基于CRISPR的基因驱动将很快地
the CRISPR-based gene drive will spread the change relentlessly
让每一个个体拥有这种性状
until it is in every single individual in the population.
目前为止基因驱动技术还并不完善
Now, it isn’t easy to make a gene drive that works that well,
但是詹姆斯和恩斯福尔特相信 最终我们可以做到
but James and Esvelt think that we can.
好消息是它拥有美好的前景
The good news is that this opens the door to some remarkable things.
如果你把疟疾基因打入
If you put an anti-malarial gene drive
仅仅1%的蚊子里
in just 1 percent of Anopheles mosquitoes,
疟蚊就是传播疟疾的蚊子
the species that transmits malaria,
研究者预测一年之内 所有疟蚊都会获得新的基因
researchers estimate that it would spread to the entire population in a year.
所以一年之内就可以根除疟疾
So in a year, you could virtually eliminate malaria.
在实际生活中 我们离实现这种状态还有几年时间
In practice, we’re still a few years out from being able to do that,
现在仍然每天有1000名孩子死于疟疾
but still, a 1,000 children a day die of malaria.
一年之内这个数字几乎可能下降为0
In a year, that number could be almost zero.
同样的方法也可以用于登革热、基孔肯亚病、黄热病
The same goes for dengue fever, chikungunya, yellow fever.
然后它就会变得更好
And it gets better.
如果你想根除入侵物种
Say you want to get rid of an invasive species,
比如 把亚洲鲤鱼逐出五大湖
like get Asian carp out of the Great Lakes.
只要使用基因驱动
All you have to do is release a gene drive
使鱼只繁衍雄性后代
that makes the fish produce only male offspring.
几代之后没有了雌性鲤鱼 鲤鱼种群就会随之消失
In a few generations, there’ll be no females left, no more carp.
理论上我们可以通过这个方式保护
In theory, this means we could restore hundreds of native species
濒临灭绝的自然物种
that have been pushed to the brink.
上面都是好的部分
OK, that’s the good news,
下面说说负面影响
this is the bad news.
基因驱动的效率太高
Gene drives are so effective
以至于不经意释放的样本都可能 在短时间内引起整个种群的
that even an accidental release could change an entire species,
巨大改变
and often very quickly.
詹姆斯做好了预防措施
Anthony James took good precautions.
他在一个生物控制实验室繁殖蚊子
He bred his mosquitos in a bio-containment lab
并且蚊子也并不是美国本土的种类
and he also used a species that’s not native to the US
所以就算蚊子逃跑了
so that even if some did escape,
也会因为没有办法交配而灭绝
they’d just die off, there’d be nothing for them to mate with.
但是如果一些携带繁殖雄性后代基因驱动的亚洲鲤鱼
But it’s also true that if a dozen Asian carp with the all-male gene drive
偶然从五大湖被带回了亚洲
accidentally got carried from the Great Lakes back to Asia,
这可能会让整个亚洲鲤鱼种群灭绝
they could potentially wipe out the native Asian carp population.
鉴于现在世界联系的紧密程度 这是很有可能的
And that’s not so unlikely, given how connected our world is.
这也是为什么会出现物种入侵
In fact, it’s why we have an invasive species problem.
这是鱼类的情况
And that’s fish.
而像蚊子和果蝇一类的生物
Things like mosquitos and fruit flies,
我们是没有办法去遏制它们的
there’s literally no way to contain them.
它们经常漂洋过海
They cross borders and oceans all the time.
另外一个坏消息就是
OK, the other piece of bad news
基因驱动不一定被限制在
is that a gene drive might not stay confined
我们所谓的靶物种上
to what we call the target species.
这是源于基因流动
That’s because of gene flow,
基因流动意思是相似的物种
which is a fancy way of saying that neighboring species
或者异种
sometimes interbreed.
如果发生了杂交 有可能基因驱动会穿过物种的限制
If that happens, it’s possible a gene drive could cross over,
就好像亚洲鲤鱼 会传染给其他物种的鲤鱼
like Asian carp could infect some other kind of carp.
如果基因驱动只是改变了一个性状 比如眼睛颜色 可能还好
That’s not so bad if your drive just promotes a trait, like eye color.
而实际上 近期很可能将会有
In fact, there’s a decent chance that we’ll see
大量奇怪的果蝇被培育出来
a wave of very weird fruit flies in the near future.
但是这可能是一个灾难
But it could be a disaster
即使你可以利用基因驱动技术使这些物种全部消失
if your drive is deigned to eliminate the species entirely.
更为可怕的是基因驱动的技术
The last worrisome thing is that the technology to do this,
这种能够培育含有基因驱动的有机体的技术
to genetically engineer an organism and include a gene drive,
基本上在世界上任何一个实验室都可以做到
is something that basically any lab in the world can do.
本科生就可以做到
An undergraduate can do it.
一个优秀的高中生 只要他拥有一些设备也可以做到
A talented high schooler with some equipment can do it.
这就很可怕了
Now, I’m guessing that this sounds terrifying.
[笑声]
[Laughter]
有趣的是 几乎每一个和我探讨基因驱动的科学家
Interestingly though, nearly every scientist I talk to
都不认为基因驱动实际上那么可怕和危险
seemed to think that gene drives were not actually that frightening or dangerous.
部分人认为科学家会
Partly because they believe that scientists will be
谨慎而且负责任地使用这项技术
very cautious and responsible about using them.
[笑声]
[Laughter]
当然 这不可置否
So far, that’s been true.
不过基因驱动也有一些实际的限制
But gene drives also have some actual limitations.
首先它只能应用于有性生殖的物种
So for one thing, they work only in sexually reproducing species.
所以谢天谢地 它们并不能用在细菌和病毒的培育上
So thank goodness, they can’t be used to engineer viruses or bacteria.
其次 性状只有在不停繁衍下才会传播
Also, the trait spreads only with each successive generation.
所以只有在繁殖周期很短的物种中
So changing or eliminating a population
改变或者灭绝种群才是可能的
is practical only if that species has a fast reproductive cycle,
比如昆虫或者类似于鼠类 或者鱼类的小型脊椎动物
like insects or maybe small vertebrates like mice or fish.
对于大象或者人类 可能需要几百年
In elephants or people, it would take centuries
改变的性状才可能传播的足够广
for a trait to spread widely enough to matter.
另外就算有CRISPR 想要制造一个真正 可以引发灭绝的性状也不是简单的事
Also, even with CRISPR, it’s not that easy to engineer a truly devastating trait.
比如你想制造一种果蝇
Say you wanted to make a fruit fly
用普通的水果代替腐坏的水果
that feeds on ordinary fruit instead of rotting fruit,
带到破坏美国农业的目的
with the aim of sabotaging American agriculture.
首先你要搞清楚
First, you’d have to figure out
哪一种基因会控制果蝇吃什么
which genes control what the fly wants to eat,
这已经是很复杂的项目了
which is already a very long and complicated project.
接下来你要根据你的想法通过改变基因
Then you’d have to alter those genes to change the fly’s behavior
去改变果蝇的习性
to whatever you’d want it to be,
这将是更加复杂的项目
which is an even longer and more complicated project.
甚至可能压根儿没什么效果
And it might not even work,
因为通过基因来控制行为的改变是非常复杂的
because the genes that control behavior are complex.
所以如果你是一个恐怖分子
So if you’re a terrorist and have to choose
不得不进行艰苦的基础研究计划
between starting a grueling basic research program
这个计划需要多年待在实验室进行细致地研究 但是可能会失败
that will require years of meticulous lab work and still might not pan out,
或者仅仅把材料全部烧掉
or just blowing stuff up?
你们可能多半会选后者
You’ll probably choose the later.
而且至少在理论上
This is especially true because at least in theory,
这应该更容易去建立一个名叫反向驱动的装置
it should be pretty easy to build what’s called a reversal drive.
这样就可以覆盖第一个基因驱动进行的改变
That’s one that basically overwrites the change made by the first gene drive.
所以如果你对于改变的结果不满意
So if you don’t like the effects of a change,
启动第二个装置取消改变
you can just release a second drive that will cancel it out,
至少理论上是可行的
at least in theory.
那么这一切到底告诉了我们什么呢?
OK, so where does this leave us?
我们现在可以随意改变整个种群
We now have the ability to change entire species at will.
是这样么?
Should we?
我们扮演上帝的角色了么?
Are we gods now?
我不这么认为
I’m not sure I’d say that.
我想说的是:
But I would say this:
首先 很多睿智的人
first, some very smart people
现在已经开始讨论如何规范基因驱动
are even now debating how to regulate gene drives.
与此同时另外一些聪明的人
At the same time, some other very smart people
开始制定安全保护措施
are working hard to create safeguards,
比如让基因驱动自我调控 或者在经过几代之后逐渐消失
like gene drives that self-regulate or peter out after a few generations.
这是很好的
That’s great.
但是这项技术仍然需要更多讨论
But this technology still requires a conversation.
而且鉴于基因驱动的本质
And given the nature of gene drives,
这些讨论必须会面向全球的
that conversation has to be global.
如果肯尼亚想使用一个基因驱动 但坦桑尼亚不想怎么办?
What if Kenya wants to use a drive but Tanzania doesn’t?
谁来决定可以广泛传播的基因驱动 什么时候释放?
Who decides whether to release a gene drive that can fly?
我不知道答案
I don’t have the answer to that question.
接下来我们能做的
All we can do going forward, I think,
是实事求是的讨论利弊
is talk honestly about the risks and benefits
并且对我们做出的选择负责
and take responsibility for our choices.
我的意思是 不仅仅是选择使用基因驱动
By that I mean, not just the choice to use a gene drive,
也可以选择禁用它
but also the choice not to use one.
人类倾向的最安全的方案
Humans have a tendency to assume that the safest option
就是维持现状
is to preserve the status quo.
但是事实往往不一定如此
But that’s not always the case.
基因驱动确实有风险 也需要认真讨论
Gene drives have risks, and those need to be discussed,
但是疟疾现在每天都夺去1000个人的生命
but malaria exists now and kills 1,000 people a day.
为了对抗疟疾 我们喷洒大量农药 这就伤害了其他物种
To combat it, we spray pesticides that do grave damage to other species,
包括两栖动物和鸟类
including amphibians and birds.
当你们在接下来的几个月听到基因驱动时
So when you hear about gene drives in the coming months,
相信我 你们一定会听到的
and trust me, you will be hearing about them,
请记住我说的话
remember that.
行动意味着风险
It can be frightening to act,
但有时无动于衷更加致命
but sometimes, not acting is worse.
[掌声]
[Applause]

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CRISPR基因驱动装置允许科学家改变DNA序列,并确保编辑后性状可以遗传,开辟永远改变整个物种的可能性。更重要的是,该技术引发了新的问题:这项强大的新技术将如何影响人类?我们要使用它来改变什么?我们要扮演上帝的角色吗?聆听记者珍妮弗·卡恩在演讲中对这些问题的思考,同时与我们分享了基因驱动装置潜在的强大应用:打造能够根除疟疾和寨卡病毒的抗病蚊子。

听录译者

收集自网络

翻译译者

B11101001

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自动通过审核

视频来源

https://www.youtube.com/watch?v=OI_OhvOumT0

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