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

譯者: 易帆 余 審譯者: lin quan

So this is a talk about gene drives,

這次的演講是有關於 「基因驅動技術」，

but I'm going to start by telling you a brief story.

但我要從一個小故事開始說起。

20 years ago, a biologist named Anthony James

20年前，有一位叫安東尼．詹姆斯 的生物學家，

got obsessed with the idea of making mosquitos

他迷上了一個

that didn't transmit malaria.

製造出不會傳染 瘧疾的蚊子的想法，

It was a great idea, and pretty much a complete failure.

想法很棒，但幾乎差點失敗。

For one thing, it turned out to be really hard

首先，要做出抗瘧疾的蚊子，

to make a malaria-resistant mosquito.

真的相當困難。

James managed it, finally, just a few years ago,

但詹姆士在幾年前， 終於做到了，

by adding some genes that make it impossible

他是藉由增加基因的方式，

for the malaria parasite to survive inside the mosquito.

讓瘧疾的寄生蟲無法在 蚊子身上生存。

But that just created another problem.

但這會衍生出另外一個問題。

Now that you've got a malaria-resistant mosquito,

現在，你有一隻抗瘧疾的蚊子，

how do you get it to replace all the malaria-carrying mosquitos?

但你要如何讓牠取代掉所有 有攜帶瘧疾病原的蚊子？

There are a couple options,

有幾個選項可以選，

but plan A was basically to breed up

A 計畫基本上就是，

a bunch of the new genetically-engineered mosquitos

培育出一大堆新的 基因改造過的蚊子，

release them into the wild

然後放生牠們，

and hope that they pass on their genes.

並祈禱牠們的基因 可以被遺傳下去。

The problem was that you'd have to release

但問題是，你得釋放出

literally 10 times the number of native mosquitos to work.

將近十倍當地蚊子的數量， 才會有效果。

So in a village with 10,000 mosquitos,

所以，一個有 1 萬隻蚊子的村落，

you release an extra 100,000.

你得釋放出 10 萬隻才能搞定。

As you might guess,

你應該猜的到，

this was not a very popular strategy with the villagers.

對居民來說，這不是一個 很受歡迎的策略。

(Laughter)

（笑聲）

Then, last January, Anthony James got an email

之後，去年一月， 詹姆士收到一封

from a biologist named Ethan Bier.

來自一位叫做伊桑．畢爾 生物學家的 E-mail。

Bier said that he and his grad student Valentino Gantz

畢爾說，他和他的一位名叫 范倫鐵諾．岡茲的研究生

had stumbled on a tool that could not only guarantee

意外發現了一個工具， 它不僅可以保證

that a particular genetic trait would be inherited,

特定的基因特徵 可以被遺傳到下一代，

but that it would spread incredibly quickly.

還可以讓它快速地繁殖擴散。

If they were right, it would basically solve the problem

如果他們是對的， 基本上就可以解決掉

that he and James had been working on for 20 years.

他和詹姆上這 20 年來 一直想要解決的問題。

As a test, they engineered two mosquitos to carry the anti-malaria gene

在實測中，他們做出了兩隻 帶有抗瘧疾基因的蚊子，

and also this new tool, a gene drive,

以及這項新工具， 「基因驅動技術」，

which I'll explain in a minute.

我晚點會在做解釋。

Finally, they set it up so that any mosquitos

最後，他們設置出了一種機制，

that had inherited the anti-malaria gene

他們讓帶有抗瘧疾 基因的蚊子

wouldn't have the usual white eyes, but would instead have red eyes.

不再有正常的白色眼睛， 取而代之的是紅色的眼睛。

That was pretty much just for convenience

這是一個相當方便的辨認方式，

so they could tell just at a glance which was which.

因為他們只要看一眼， 就能分辨出蚊子的種類。

So they took their two anti-malarial, red-eyed mosquitos

所以，他們把兩隻 抗瘧疾、紅眼的蚊子，

and put them in a box with 30 ordinary white-eyed ones,

放進一個裝有30隻 正常白眼蚊子的箱子中，

and let them breed.

然後讓牠們繁殖。

In two generations, those had produced 3,800 grandchildren.

在經過兩個世代後，這些蚊子 繁殖出 3800 隻的後代。

That is not the surprising part.

這一段不最驚人的部分。

This is the surprising part:

接下來這一段才是：

given that you started with just two red-eyed mosquitos

假定，你從只有兩隻紅眼蚊子

and 30 white-eyed ones,

加上30隻白眼蚊子開始繁殖，

you expect mostly white-eyed descendants.

你會以為牠們的後代 應該都是白眼的，

Instead, when James opened the box,

但在詹姆士打開箱子後， 他發現，

all 3,800 mosquitos had red eyes.

全部的 3800 隻蚊子都是紅眼的。

When I asked Ethan Bier about this moment,

當我問伊桑．畢爾這件事時，

he became so excited that he was literally shouting into the phone.

他在電話那頭簡直興奮地不得了。

That's because getting only red-eyed mosquitos

那是因為，你如果 只剩下紅眼蚊子

violates a rule that is the absolute cornerstone of biology,

那就是違反了 生物學的基礎法則，

Mendelian genetics.

孟德爾的遺傳定律。

I'll keep this quick,

我簡單說明一下，

but Mendelian genetics says when a male and a female mate,

孟德爾的遺傳定律說明， 當一公一母交配時，

their baby inherits half of its DNA from each parent.

他們的後代會遺傳到 來自上一代各半的 DNA。

So if our original mosquito was aa and our new mosquito is aB,

所以如果原生種蚊子是 aa， 新的蚊子是 aB，

where B is the anti-malarial gene,

B 代表抗瘧疾的基因，

the babies should come out in four permutations:

那他們的後代， 會有四種排列組合：

aa, aB, aa, Ba.

aa, aB, aa, Ba。

Instead, with the new gene drive,

但，如果你使用了 新的基因驅動技術，

they all came out aB.

他們會全部變成aB。

Biologically, that shouldn't even be possible.

在生物學上，根本 不會有這種情況發生。

So what happened?

但發生了甚麼事？

The first thing that happened

第一件發生的事情就是

was the arrival of a gene-editing tool known as CRISPR in 2012.

2012 年基因編輯技術 CRISPER 的誕生。

Many of you have probably heard about CRISPR,

你們當中很多人可能都 聽過 CRISPER 這項技術了 ，

so I'll just say briefly that CRISPR is a tool that allows researchers

所以我簡單說明一下， CRISPER 是一種工具，

to edit genes very precisely, easily and quickly.

它可以讓研究人員以非常精準、 簡單、快速的方式來編輯 DNA 。

It does this by harnessing a mechanism that already existed in bacteria.

它是藉由控制一個現存在 細菌裡面的一個機制。

Basically, there's a protein that acts like a scissors

基本上，會有一個像 剪刀一樣功能的蛋白質，

and cuts the DNA,

它會切斷 DNA，

and there's an RNA molecule that directs the scissors

然後會有一個 RNA 分子導引剪刀

to any point on the genome you want.

往你希望它剪掉的地方去。

The result is basically a word processor for genes.

它所形成的結果，基本上 就是一個基因造字的過程。

You can take an entire gene out, put one in,

你可以抽出整段基因， 然後換另一段進去，

or even edit just a single letter within a gene.

甚至僅是編輯 基因裡的其中一個字母。

And you can do it in nearly any species.

而且你可以在任何 物種上做這件事。

OK, remember how I said that gene drives originally had two problems?

好的，還記得我剛提的， 基因驅動技術原本的兩個問題嗎？

The first was that it was hard to engineer a mosquito

第一個就是，要做出一隻

to be malaria-resistant.

有抗瘧疾的蚊子是相當困難的。

That's basically gone now, thanks to CRISPR.

而現在有了 CRISPR ， 這一難題迎刃而解。

But the other problem was logistical.

但另一個是後續支援的問題。

How do you get your trait to spread?

你要如何把你的 生物特性散播出去？

This is where it gets clever.

這裡有一個聰明的方法。

A couple years ago, a biologist at Harvard named Kevin Esvelt

幾年前，哈佛大學的一位生物學家， 凱文．伊斯維特

wondered what would happen

他想如果 CRISPER 不僅只有插入新基因的功能，

if you made it so that CRISPR inserted not only your new gene

如果也含有剪下，貼上

but also the machinery that does the cutting and pasting.

的功能，那會怎樣？

In other words, what if CRISPR also copied and pasted itself.

換句話說，要是 CRISPER 本身也有複製及貼上的功能。

You'd end up with a perpetual motion machine for gene editing.

那你就會得到一個 永續性的基因編輯機制。

And that's exactly what happened.

而事情就真的發生了。

This CRISPR gene drive that Esvelt created

伊斯維特創造的 CRISPER 基因驅動技術，

not only guarantees that a trait will get passed on,

不僅可以保證基因特徵可以被遺傳，

but if it's used in the germline cells,

也可以保證能用在生殖細胞上，

it will automatically copy and paste your new gene

它會自動地複製、 貼上你的新基因

into both chromosomes of every single individual.

到每個個體的染色體上。

It's like a global search and replace,

它就像是全球檢索 並取代的功能。

or in science terms, it makes a heterozygous trait homozygous.

或者以科學的術語來說，它造成了 一個「雜合子特徵純合化」現象

So, what does this mean?

所以，這意味著什麼？

For one thing, it means we have a very powerful,

首先，意味著， 我們有了一個非常強大

but also somewhat alarming new tool.

但也有點令人害怕的新工具。

Up until now, the fact that gene drives didn't work very well

到目前為止，基因驅動技術 運作地還不是很順暢的事實

was actually kind of a relief.

的確還算有點令人欣慰。

Normally when we mess around with an organism's genes,

按理說，當我們搞亂掉 一個生物的基因，

we make that thing less evolutionarily fit.

我們只要降低這個東西的 進化適應力即可。

So biologists can make all the mutant fruit flies they want

所以，生物學家們 可以無後顧之憂地

without worrying about it.

製造出任何他們想要的 果蠅突變體。

If some escape, natural selection just takes care of them.

如果有一些逃走了，大自然選擇 （物競天擇）就可以處理這件事。

What's remarkable and powerful and frightening about gene drives

但基因驅動技術最顯著有力、 令人害怕的地方就是

is that that will no longer be true.

這樣的狀況 可能將永遠不存在。

Assuming that your trait does not have a big evolutionary handicap,

假設你的遺傳特徵如果沒有一個 很大的演化肢障產生，

like a mosquito that can't fly,

好比蚊子沒有辦法飛，

the CRISPR-based gene drive will spread the change relentlessly

以 CRISPER 為基礎的基因驅動， 將把這個改變給持續散播出去，

until it is in every single individual in the population.

直到它深入到族群中 的每個個體身上。

Now, it isn't easy to make a gene drive that works that well,

現在，要讓基因驅動技術 量好運行，並非易事，

but James and Esvelt think that we can.

但詹姆士及伊斯維特 認為我們做的到。

The good news is that this opens the door to some remarkable things.

好消息是，這項技術為一些 不可思議的事情打開了一扇門。

If you put an anti-malarial gene drive

你只要在 1% 的

in just 1 percent of Anopheles mosquitoes,

攜帶瘧疾的蚊子身上使用

the species that transmits malaria,

抗瘧疾基因驅動技術，

researchers estimate that it would spread to the entire population in a year.

研究人員預估，一年內這一基因 就可以散播到整個種群中。

So in a year, you could virtually eliminate malaria.

所以，只要一年的時間， 你就可以完全消滅掉瘧疾。

In practice, we're still a few years out from being able to do that,

實際上， 我們仍需好幾年才能做到，

but still, a 1,000 children a day die of malaria.

但每天仍然有 1000 名 兒童死於瘧疾。

In a year, that number could be almost zero.

只要一年的時間，就幾乎 可以把數字降到零。

The same goes for dengue fever, chikungunya, yellow fever.

同樣的，它還可以運用在登革熱、 基孔肯雅熱，黃熱病上。

And it gets better.

更好的是，

Say you want to get rid of an invasive species,

假設你想根除掉一個 外來入侵的物種，

like get Asian carp out of the Great Lakes.

像是把亞洲鯉魚趕出五大湖。

All you have to do is release a gene drive

你所要做的就是，釋放一種

that makes the fish produce only male offspring.

只能繁衍出雄性後代 的基因驅動，

In a few generations, there'll be no females left, no more carp.

幾代之後，没有了雌性鯉魚， 該物種就隨之消失了。

In theory, this means we could restore hundreds of native species

理論上，這意味著， 我們可以透過這種方式，

that have been pushed to the brink.

復育上百種瀕臨絕種的生物。

OK, that's the good news,

好的，這是好消息的部分，

this is the bad news.

接下來，是壞消息的部分。

Gene drives are so effective

基因驅動技術因為很有效率，

that even an accidental release could change an entire species,

以至於不經意釋放的樣本， 通常都可能在短時間內

and often very quickly.

引起整個種群的巨大改變。

Anthony James took good precautions.

詹姆士做了很好的預防措施。

He bred his mosquitos in a bio-containment lab

他都是在生物控制實驗室裡 培養他的蚊子，

and he also used a species that's not native to the US

而且他用的都是 非美國本土的物種，

so that even if some did escape,

所以，即使有一些跑走了，

they'd just die off, there'd be nothing for them to mate with.

也會因為沒有辦法交配而死。

But it's also true that if a dozen Asian carp with the all-male gene drive

但另一個事實就是，如果有一些帶有 全雄性基因驅動的亞洲鯉魚，

accidentally got carried from the Great Lakes back to Asia,

不小心從五大湖被帶回到亞洲，

they could potentially wipe out the native Asian carp population.

牠們也很有可能會毀滅掉 整個當地的亞洲鯉魚物種。

And that's not so unlikely, given how connected our world is.

現在世界聯繫的緊密程度 這是很有可能會發生的。

In fact, it's why we have an invasive species problem.

事實上，這也是為什麼我們 有外來物種入侵的問題。

And that's fish.

這是魚類的情況。

Things like mosquitos and fruit flies,

對蚊子和果蠅這一類 會飛的物種而言，

there's literally no way to contain them.

基本上是沒有辦法限制牠們的。

They cross borders and oceans all the time.

牠們可以隨時 穿越國界或飄揚過海。

OK, the other piece of bad news

好的，還有另外一個壞消息，

is that a gene drive might not stay confined

就是，基因驅動的表現 不一定只被限制在

to what we call the target species.

我們所謂的標靶物種上。

That's because of gene flow,

那是因為有基因轉移（流動）

which is a fancy way of saying that neighboring species

基因轉移就是， 相鄰的物種之間

sometimes interbreed.

偶爾彼此會有雜交的情形。

If that happens, it's possible a gene drive could cross over,

如果發生了雜交，基因驅動 就很有可能會穿過物種的限制，

like Asian carp could infect some other kind of carp.

比如亞洲鯉魚可能會 影響其它種類的鯉魚。

That's not so bad if your drive just promotes a trait, like eye color.

如果你的驅動只是改變眼睛的顏色， 可能還不會那麼糟糕。

In fact, there's a decent chance that we'll see

事實上，不久的未來很有可能

a wave of very weird fruit flies in the near future.

有非常大量奇怪的 果蠅被培養出來。

But it could be a disaster

但如果你的驅動裝置是惡意地

if your drive is deigned to eliminate the species entirely.

被用來消滅一個物種的話， 這也有可能會導致災難。

The last worrisome thing is that the technology to do this,

最後一件令人擔心的事，就是，

to genetically engineer an organism and include a gene drive,

對有機體做基因工程包括基因驅動， 這一技術，

is something that basically any lab in the world can do.

基本上世界上 任何一個實驗室都能做。

An undergraduate can do it.

一個大學本科生就可以做。

A talented high schooler with some equipment can do it.

一個天資聰穎的高中生， 給他一些儀器，他也會做。

Now, I'm guessing that this sounds terrifying.

我猜，你們一定覺得， 這聽起相當恐怖。

(Laughter)

（笑聲）

Interestingly though, nearly every scientist I talk to

有趣的是，因乎每一個 和我討論的科學家都認為，

seemed to think that gene drives were not actually that frightening or dangerous.

基因驅動技術沒有想像中 那麼的恐怖或危險，

Partly because they believe that scientists will be

有部分原因是， 他們相信科學家們

very cautious and responsible about using them.

會非常小心並 負責任地使用這些工具。

(Laughter)

（笑聲）

So far, that's been true.

目前為止，也確實是如此。

But gene drives also have some actual limitations.

不過基因驅動技術 也有一些實質上的限制。

So for one thing, they work only in sexually reproducing species.

首先，它只能應用於 有性生殖的物種。

So thank goodness, they can't be used to engineer viruses or bacteria.

所以感謝上帝，它們不能 用在細菌和病毒的培育上。

Also, the trait spreads only with each successive generation.

其次，遺傳特徵只有在 成功的後代繁衍下才能傳播。

So changing or eliminating a population

所以只有在繁殖周期很短的物種中

is practical only if that species has a fast reproductive cycle,

改變或者滅絕該物種才有可能發生。

like insects or maybe small vertebrates like mice or fish.

比如昆蟲或者類似於鼠類 或者魚類的小型脊椎動物。

In elephants or people, it would take centuries

大象或者人類可能需要幾百年，

for a trait to spread widely enough to matter.

才能把遺傳特徵散播地夠廣。

Also, even with CRISPR, it's not that easy to engineer a truly devastating trait.

而且，就算有 CRISPR ， 也無法輕易做出真正毀滅性的遺傳特徵。

Say you wanted to make a fruit fly

比如說，你想製造一種

that feeds on ordinary fruit instead of rotting fruit,

以普通水果而不是以 腐爛水果為食的果蠅，

with the aim of sabotaging American agriculture.

藉此來摧毀美國的農業。

First, you'd have to figure out

首先，你得搞清楚，

which genes control what the fly wants to eat,

哪些基因控制了 果蠅的食慾，

which is already a very long and complicated project.

這已經算是很長 很複雜的專案了。

Then you'd have to alter those genes to change the fly's behavior

接下來你要根據你的想法， 透過更換基因

to whatever you'd want it to be,

來改變果蠅的習性，

which is an even longer and more complicated project.

這將是更長更複雜的專案。

And it might not even work,

甚至會以失敗告終，

because the genes that control behavior are complex.

因為基因對於行為的 控制是非常複雜的。

So if you're a terrorist and have to choose

所以，如果你是一個恐怖分子，

between starting a grueling basic research program

你會選擇一個需要 耗時多年、細心做實驗

that will require years of meticulous lab work and still might not pan out,

甚至可能會失敗的研究計畫，

or just blowing stuff up?

還是直接放炸彈？

You'll probably choose the later.

你大概會選擇後者。

This is especially true because at least in theory,

這真的是實話，因為至少在理論上，

it should be pretty easy to build what's called a reversal drive.

要製造一個叫做「逆轉驅動」 的東西也相當容易。

That's one that basically overwrites the change made by the first gene drive.

它基本上就可以覆蓋掉 第一個基因驅動所造成的改變。

So if you don't like the effects of a change,

所以，如果你不喜歡改變後的結果，

you can just release a second drive that will cancel it out,

你只要再釋放第二個驅動 就可以把它消滅掉了，

at least in theory.

至少理論上是這樣的。

OK, so where does this leave us?

好的，這告訴了我們甚麼？

We now have the ability to change entire species at will.

我們現在已經有能力， 能隨意改變整個物種。

Should we?

我們應該這樣做嗎？

Are we gods now?

我們現在是上帝了嗎？

I'm not sure I'd say that.

我不太確定 我能否這樣說。

But I would say this:

但我想說的是：

first, some very smart people

首先，有很多頂尖聰明的人，

are even now debating how to regulate gene drives.

現在已經開始討論如何監管 基因驅動技術。

At the same time, some other very smart people

同時，另一批頂尖聰明的人，

are working hard to create safeguards,

也已經開始努力地制定 安全保護措施，

like gene drives that self-regulate or peter out after a few generations.

比如，讓基因自我規範 或幾代之後逐漸消失。

That's great.

太棒了。

But this technology still requires a conversation.

但這項技術仍需要展開一次對話。

And given the nature of gene drives,

而且鑒於基因驅動技術的本質，

that conversation has to be global.

對話必須是全球性的。

What if Kenya wants to use a drive but Tanzania doesn't?

要是肯亞想使用一個驅動， 但坦薩尼亞不要呢？

Who decides whether to release a gene drive that can fly?

誰可以決定是否要釋放一個 會飛的基因驅動呢？

I don't have the answer to that question.

我目前仍沒有答案。

All we can do going forward, I think,

接下來我們能做的， 我認為，

is talk honestly about the risks and benefits

就是針對這項技術的利弊， 大家坦誠對話，

and take responsibility for our choices.

並對我們的選擇負責。

By that I mean, not just the choice to use a gene drive,

但我的意思是，不僅要對 選擇使用基因驅動負責，

but also the choice not to use one.

也要對不使用它的後果負責。

Humans have a tendency to assume that the safest option

人類傾向於認為，

is to preserve the status quo.

維持現狀就是最安全的選項。

But that's not always the case.

但事實往往不一定如此。

Gene drives have risks, and those need to be discussed,

基因驅動確實有風險， 也需要被討論，

but malaria exists now and kills 1,000 people a day.

但現存的瘧疾， 每天在持續奪走 1000 條人命。

To combat it, we spray pesticides that do grave damage to other species,

為了對抗它，我們噴灑的農藥 也會對其它物種造成嚴重的傷害，

including amphibians and birds.

包括兩棲類及鳥類。

So when you hear about gene drives in the coming months,

所以，當各位幾個月後 聽到基因驅動，

and trust me, you will be hearing about them,

相信我，你將會聽到這些事，

remember that.

請記住，

It can be frightening to act,

採取行動或許令人恐懼，

but sometimes, not acting is worse.

但有時候，無動於衷會更糟糕。

(Applause)

（掌聲）