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  • So this is a talk about gene drives,

    譯者: 易帆 余 審譯者: lin quan

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

    這次的演講是有關於 「基因驅動技術」,

  • 20 years ago, a biologist named Anthony James

    但我要從一個小故事開始說起。

  • got obsessed with the idea of making mosquitos

    20年前,有一位叫安東尼.詹姆斯 的生物學家,

  • that didn't transmit malaria.

    他迷上了一個

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

    製造出不會傳染 瘧疾的蚊子的想法,

  • For one thing, it turned out to be really hard

    想法很棒,但幾乎差點失敗。

  • to make a malaria-resistant mosquito.

    首先,要做出抗瘧疾的蚊子,

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

    真的相當困難。

  • by adding some genes that make it impossible

    但詹姆士在幾年前, 終於做到了,

  • for the malaria parasite to survive inside the mosquito.

    他是藉由增加基因的方式,

  • But that just created another problem.

    讓瘧疾的寄生蟲無法在 蚊子身上生存。

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

    但這會衍生出另外一個問題。

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

    現在,你有一隻抗瘧疾的蚊子,

  • There are a couple options,

    但你要如何讓牠取代掉所有 有攜帶瘧疾病原的蚊子?

  • but plan A was basically to breed up

    有幾個選項可以選,

  • a bunch of the new genetically-engineered mosquitos

    A 計畫基本上就是,

  • release them into the wild

    培育出一大堆新的 基因改造過的蚊子,

  • and hope that they pass on their genes.

    然後放生牠們,

  • The problem was that you'd have to release

    並祈禱牠們的基因 可以被遺傳下去。

  • literally 10 times the number of native mosquitos to work.

    但問題是,你得釋放出

  • So in a village with 10,000 mosquitos,

    將近十倍當地蚊子的數量, 才會有效果。

  • you release an extra 100,000.

    所以,一個有 1 萬隻蚊子的村落,

  • As you might guess,

    你得釋放出 10 萬隻才能搞定。

  • this was not a very popular strategy with the villagers.

    你應該猜的到,

  • (Laughter)

    對居民來說,這不是一個 很受歡迎的策略。

  • Then, last January, Anthony James got an email

    (笑聲)

  • from a biologist named Ethan Bier.

    之後,去年一月, 詹姆士收到一封

  • Bier said that he and his grad student Valentino Gantz

    來自一位叫做伊桑.畢爾 生物學家的 E-mail。

  • had stumbled on a tool that could not only guarantee

    畢爾說,他和他的一位名叫 范倫鐵諾.岡茲的研究生

  • that a particular genetic trait would be inherited,

    意外發現了一個工具, 它不僅可以保證

  • but that it would spread incredibly quickly.

    特定的基因特徵 可以被遺傳到下一代,

  • If they were right, it would basically solve the problem

    還可以讓它快速地繁殖擴散。

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

    如果他們是對的, 基本上就可以解決掉

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

    他和詹姆上這 20 年來 一直想要解決的問題。

  • and also this new tool, a gene drive,

    在實測中,他們做出了兩隻 帶有抗瘧疾基因的蚊子,

  • which I'll explain in a minute.

    以及這項新工具, 「基因驅動技術」,

  • Finally, they set it up so that any mosquitos

    我晚點會在做解釋。

  • that had inherited the anti-malaria gene

    最後,他們設置出了一種機制,

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

    他們讓帶有抗瘧疾 基因的蚊子

  • That was pretty much just for convenience

    不再有正常的白色眼睛, 取而代之的是紅色的眼睛。

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

    這是一個相當方便的辨認方式,

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

    因為他們只要看一眼, 就能分辨出蚊子的種類。

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

    所以,他們把兩隻 抗瘧疾、紅眼的蚊子,

  • and let them breed.

    放進一個裝有30隻 正常白眼蚊子的箱子中,

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

    然後讓牠們繁殖。

  • That is not the surprising part.

    在經過兩個世代後,這些蚊子 繁殖出 3800 隻的後代。

  • This is the surprising part:

    這一段不最驚人的部分。

  • given that you started with just two red-eyed mosquitos

    接下來這一段才是:

  • and 30 white-eyed ones,

    假定,你從只有兩隻紅眼蚊子

  • you expect mostly white-eyed descendants.

    加上30隻白眼蚊子開始繁殖,

  • Instead, when James opened the box,

    你會以為牠們的後代 應該都是白眼的,

  • all 3,800 mosquitos had red eyes.

    但在詹姆士打開箱子後, 他發現,

  • When I asked Ethan Bier about this moment,

    全部的 3800 隻蚊子都是紅眼的。

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

    當我問伊桑.畢爾這件事時,

  • That's because getting only red-eyed mosquitos

    他在電話那頭簡直興奮地不得了。

  • violates a rule that is the absolute cornerstone of biology,

    那是因為,你如果 只剩下紅眼蚊子

  • Mendelian genetics.

    那就是違反了 生物學的基礎法則,

  • I'll keep this quick,

    孟德爾的遺傳定律。

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

    我簡單說明一下,

  • their baby inherits half of its DNA from each parent.

    孟德爾的遺傳定律說明, 當一公一母交配時,

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

    他們的後代會遺傳到 來自上一代各半的 DNA。

  • where B is the anti-malarial gene,

    所以如果原生種蚊子是 aa, 新的蚊子是 aB,

  • the babies should come out in four permutations:

    B 代表抗瘧疾的基因,

  • aa, aB, aa, Ba.

    那他們的後代, 會有四種排列組合:

  • Instead, with the new gene drive,

    aa, aB, aa, Ba。

  • they all came out aB.

    但,如果你使用了 新的基因驅動技術,

  • Biologically, that shouldn't even be possible.

    他們會全部變成aB。

  • So what happened?

    在生物學上,根本 不會有這種情況發生。

  • The first thing that happened

    但發生了甚麼事?

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

    第一件發生的事情就是

  • Many of you have probably heard about CRISPR,

    2012 年基因編輯技術 CRISPER 的誕生。

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

    你們當中很多人可能都 聽過 CRISPER 這項技術了 ,

  • to edit genes very precisely, easily and quickly.

    所以我簡單說明一下, CRISPER 是一種工具,

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

    它可以讓研究人員以非常精準、 簡單、快速的方式來編輯 DNA 。

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

    它是藉由控制一個現存在 細菌裡面的一個機制。

  • and cuts the DNA,

    基本上,會有一個像 剪刀一樣功能的蛋白質,

  • and there's an RNA molecule that directs the scissors

    它會切斷 DNA,

  • to any point on the genome you want.

    然後會有一個 RNA 分子導引剪刀

  • The result is basically a word processor for genes.

    往你希望它剪掉的地方去。

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

    它所形成的結果,基本上 就是一個基因造字的過程。

  • or even edit just a single letter within a gene.

    你可以抽出整段基因, 然後換另一段進去,

  • And you can do it in nearly any species.

    甚至僅是編輯 基因裡的其中一個字母。

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

    而且你可以在任何 物種上做這件事。

  • The first was that it was hard to engineer a mosquito

    好的,還記得我剛提的, 基因驅動技術原本的兩個問題嗎?

  • to be malaria-resistant.

    第一個就是,要做出一隻

  • That's basically gone now, thanks to CRISPR.

    有抗瘧疾的蚊子是相當困難的。

  • But the other problem was logistical.

    而現在有了 CRISPR , 這一難題迎刃而解。

  • How do you get your trait to spread?

    但另一個是後續支援的問題。

  • This is where it gets clever.

    你要如何把你的 生物特性散播出去?

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

    這裡有一個聰明的方法。

  • wondered what would happen

    幾年前,哈佛大學的一位生物學家, 凱文.伊斯維特

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

    他想如果 CRISPER 不僅只有插入新基因的功能,

  • but also the machinery that does the cutting and pasting.

    如果也含有剪下,貼上

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

    的功能,那會怎樣?

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

    換句話說,要是 CRISPER 本身也有複製及貼上的功能。

  • And that's exactly what happened.

    那你就會得到一個 永續性的基因編輯機制。

  • This CRISPR gene drive that Esvelt created

    而事情就真的發生了。

  • not only guarantees that a trait will get passed on,

    伊斯維特創造的 CRISPER 基因驅動技術,

  • but if it's used in the germline cells,

    不僅可以保證基因特徵可以被遺傳,

  • it will automatically copy and paste your new gene

    也可以保證能用在生殖細胞上,

  • into both chromosomes of every single individual.

    它會自動地複製、 貼上你的新基因

  • It's like a global search and replace,

    到每個個體的染色體上。

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

    它就像是全球檢索 並取代的功能。

  • So, what does this mean?

    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

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

    所以,這意味著什麼?

  • but also somewhat alarming new tool.

    首先,意味著, 我們有了一個非常強大

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

    但也有點令人害怕的新工具。

  • was actually kind of a relief.

    到目前為止,基因驅動技術 運作地還不是很順暢的事實

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

    的確還算有點令人欣慰。

  • we make that thing less evolutionarily fit.

    按理說,當我們搞亂掉 一個生物的基因,

  • So biologists can make all the mutant fruit flies they want

    我們只要降低這個東西的 進化適應力即可。

  • without worrying about it.

    所以,生物學家們 可以無後顧之憂地

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

    製造出任何他們想要的 果蠅突變體。

  • What's remarkable and powerful and frightening about gene drives

    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。

  • is that that will no longer be true.

    但基因驅動技術最顯著有力、 令人害怕的地方就是

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

    這樣的狀況 可能將永遠不存在。

  • like a mosquito that can't fly,

    假設你的遺傳特徵如果沒有一個 很大的演化肢障產生,

  • the CRISPR-based gene drive will spread the change relentlessly

    好比蚊子沒有辦法飛,

  • until it is in every single individual in the population.

    以 CRISPER 為基礎的基因驅動, 將把這個改變給持續散播出去,

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

    直到它深入到族群中 的每個個體身上。

  • but James and Esvelt think that we can.

    現在,要讓基因驅動技術 量好運行,並非易事,

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

    但詹姆士及伊斯維特 認為我們做的到。

  • If you put an anti-malarial gene drive

    好消息是,這項技術為一些 不可思議的事情打開了一扇門。

  • in just 1 percent of Anopheles mosquitoes,

    你只要在 1% 的

  • the species that transmits malaria,

    攜帶瘧疾的蚊子身上使用

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

    抗瘧疾基因驅動技術,

  • So in a year, you could virtually eliminate malaria.

    研究人員預估,一年內這一基因 就可以散播到整個種群中。

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

    所以,只要一年的時間, 你就可以完全消滅掉瘧疾。

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

    實際上, 我們仍需好幾年才能做到,

  • In a year, that number could be almost zero.

    但每天仍然有 1000 名 兒童死於瘧疾。

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

    只要一年的時間,就幾乎 可以把數字降到零。

  • And it gets better.

    同樣的,它還可以運用在登革熱、 基孔肯雅熱,黃熱病上。

  • Say you want to get rid of an invasive species,

    更好的是,

  • like get Asian carp out of the Great Lakes.

    假設你想根除掉一個 外來入侵的物種,

  • All you have to do is release a gene drive

    像是把亞洲鯉魚趕出五大湖。

  • that makes the fish produce only male offspring.

    你所要做的就是,釋放一種

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

    只能繁衍出雄性後代 的基因驅動,

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

    幾代之後,没有了雌性鯉魚, 該物種就隨之消失了。

  • that have been pushed to the brink.

    理論上,這意味著, 我們可以透過這種方式,

  • OK, that's the good news,

    復育上百種瀕臨絕種的生物。

  • this is the bad news.

    好的,這是好消息的部分,

  • Gene drives are so effective

    接下來,是壞消息的部分。

  • that even an accidental release could change an entire species,

    基因驅動技術因為很有效率,

  • and often very quickly.

    以至於不經意釋放的樣本, 通常都可能在短時間內

  • Anthony James took good precautions.

    引起整個種群的巨大改變。

  • He bred his mosquitos in a bio-containment lab

    詹姆士做了很好的預防措施。

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

    他都是在生物控制實驗室裡 培養他的蚊子,

  • so that even if some did escape,

    而且他用的都是 非美國本土的物種,

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

    所以,即使有一些跑走了,

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

    也會因為沒有辦法交配而死。

  • accidentally got carried from the Great Lakes back to Asia,

    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,

  • they could potentially wipe out the native Asian carp population.

    不小心從五大湖被帶回到亞洲,

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

    牠們也很有可能會毀滅掉 整個當地的亞洲鯉魚物種。

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

    現在世界聯繫的緊密程度 這是很有可能會發生的。

  • And that's fish.

    事實上,這也是為什麼我們 有外來物種入侵的問題。

  • Things like mosquitos and fruit flies,

    這是魚類的情況。

  • there's literally no way to contain them.

    對蚊子和果蠅這一類 會飛的物種而言,

  • They cross borders and oceans all the time.

    基本上是沒有辦法限制牠們的。

  • OK, the other piece of bad news

    牠們可以隨時 穿越國界或飄揚過海。

  • is that a gene drive might not stay confined

    好的,還有另外一個壞消息,

  • to what we call the target species.

    就是,基因驅動的表現 不一定只被限制在

  • That's because of gene flow,

    我們所謂的標靶物種上。

  • which is a fancy way of saying that neighboring species

    那是因為有基因轉移(流動)

  • sometimes interbreed.

    基因轉移就是, 相鄰的物種之間

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

    偶爾彼此會有雜交的情形。

  • like Asian carp could infect some other kind of carp.

    如果發生了雜交,基因驅動 就很有可能會穿過物種的限制,

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

    比如亞洲鯉魚可能會 影響其它種類的鯉魚。

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

    如果你的驅動只是改變眼睛的顏色, 可能還不會那麼糟糕。

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

    事實上,不久的未來很有可能

  • But it could be a disaster

    有非常大量奇怪的 果蠅被培養出來。

  • if your drive is deigned to eliminate the species entirely.

    但如果你的驅動裝置是惡意地

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

    被用來消滅一個物種的話, 這也有可能會導致災難。

  • to genetically engineer an organism and include a gene drive,

    最後一件令人擔心的事,就是,

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

    對有機體做基因工程包括基因驅動, 這一技術,

  • An undergraduate can do it.

    基本上世界上 任何一個實驗室都能做。

  • A talented high schooler with some equipment can do it.

    一個大學本科生就可以做。

  • Now, I'm guessing that this sounds terrifying.

    一個天資聰穎的高中生, 給他一些儀器,他也會做。

  • (Laughter)

    我猜,你們一定覺得, 這聽起相當恐怖。

  • Interestingly though, nearly every scientist I talk to

    (笑聲)

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

    有趣的是,因乎每一個 和我討論的科學家都認為,

  • Partly because they believe that scientists will be

    基因驅動技術沒有想像中 那麼的恐怖或危險,

  • very cautious and responsible about using them.

    有部分原因是, 他們相信科學家們

  • (Laughter)

    會非常小心並 負責任地使用這些工具。

  • So far, that's been true.

    (笑聲)

  • But gene drives also have some actual limitations.

    目前為止,也確實是如此。

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

    不過基因驅動技術 也有一些實質上的限制。

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

    首先,它只能應用於 有性生殖的物種。

  • Also, the trait spreads only with each successive generation.

    所以感謝上帝,它們不能 用在細菌和病毒的培育上。

  • So changing or eliminating a population

    其次,遺傳特徵只有在 成功的後代繁衍下才能傳播。

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

    所以只有在繁殖周期很短的物種中

  • like insects or maybe small vertebrates like mice or fish.

    改變或者滅絕該物種才有可能發生。

  • In elephants or people, it would take centuries

    比如昆蟲或者類似於鼠類 或者魚類的小型脊椎動物。

  • for a trait to spread widely enough to matter.

    大象或者人類可能需要幾百年,

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

    才能把遺傳特徵散播地夠廣。

  • Say you wanted to make a fruit fly

    而且,就算有 CRISPR , 也無法輕易做出真正毀滅性的遺傳特徵。

  • that feeds on ordinary fruit instead of rotting fruit,

    比如說,你想製造一種

  • with the aim of sabotaging American agriculture.

    以普通水果而不是以 腐爛水果為食的果蠅,

  • First, you'd have to figure out

    藉此來摧毀美國的農業。

  • which genes control what the fly wants to eat,

    首先,你得搞清楚,

  • which is already a very long and complicated project.

    哪些基因控制了 果蠅的食慾,

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

    這已經算是很長 很複雜的專案了。

  • to whatever you'd want it to be,

    接下來你要根據你的想法, 透過更換基因

  • which is an even longer and more complicated project.

    來改變果蠅的習性,

  • And it might not even work,

    這將是更長更複雜的專案。

  • because the genes that control behavior are complex.

    甚至會以失敗告終,

  • So if you're a terrorist and have to choose

    因為基因對於行為的 控制是非常複雜的。

  • between starting a grueling basic research program

    所以,如果你是一個恐怖分子,

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

    你會選擇一個需要 耗時多年、細心做實驗

  • or just blowing stuff up?

    甚至可能會失敗的研究計畫,

  • You'll probably choose the later.

    還是直接放炸彈?

  • This is especially true because at least in theory,

    你大概會選擇後者。

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

    這真的是實話,因為至少在理論上,

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

    要製造一個叫做「逆轉驅動」 的東西也相當容易。

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

    它基本上就可以覆蓋掉 第一個基因驅動所造成的改變。

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

    所以,如果你不喜歡改變後的結果,

  • at least in theory.

    你只要再釋放第二個驅動 就可以把它消滅掉了,

  • OK, so where does this leave us?

    至少理論上是這樣的。

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

    好的,這告訴了我們甚麼?

  • Should we?

    我們現在已經有能力, 能隨意改變整個物種。

  • Are we gods now?

    我們應該這樣做嗎?

  • I'm not sure I'd say that.

    我們現在是上帝了嗎?

  • But I would say this:

    我不太確定 我能否這樣說。

  • first, some very smart people

    但我想說的是:

  • are even now debating how to regulate gene drives.

    首先,有很多頂尖聰明的人,

  • At the same time, some other very smart people

    現在已經開始討論如何監管 基因驅動技術。

  • are working hard to create safeguards,

    同時,另一批頂尖聰明的人,

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

    也已經開始努力地制定 安全保護措施,

  • That's great.

    比如,讓基因自我規範 或幾代之後逐漸消失。

  • But this technology still requires a conversation.

    太棒了。

  • And given the nature of gene drives,

    但這項技術仍需要展開一次對話。

  • that conversation has to be global.

    而且鑒於基因驅動技術的本質,

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

    對話必須是全球性的。

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

    要是肯亞想使用一個驅動, 但坦薩尼亞不要呢?

  • I don't have the answer to that question.

    誰可以決定是否要釋放一個 會飛的基因驅動呢?

  • All we can do going forward, I think,

    我目前仍沒有答案。

  • is talk honestly about the risks and benefits

    接下來我們能做的, 我認為,

  • and take responsibility for our choices.

    就是針對這項技術的利弊, 大家坦誠對話,

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

    並對我們的選擇負責。

  • but also the choice not to use one.

    但我的意思是,不僅要對 選擇使用基因驅動負責,

  • Humans have a tendency to assume that the safest option

    也要對不使用它的後果負責。

  • is to preserve the status quo.

    人類傾向於認為,

  • But that's not always the case.

    維持現狀就是最安全的選項。

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

    但事實往往不一定如此。

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

    基因驅動確實有風險, 也需要被討論,

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

    但現存的瘧疾, 每天在持續奪走 1000 條人命。

  • including amphibians and birds.

    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,

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

    包括兩棲類及鳥類。

  • and trust me, you will be hearing about them,

    所以,當各位幾個月後 聽到基因驅動,

  • remember that.

    相信我,你將會聽到這些事,

  • It can be frightening to act,

    請記住,

  • but sometimes, not acting is worse.

    採取行動或許令人恐懼,

  • (Applause)

    但有時候,無動於衷會更糟糕。

So this is a talk about gene drives,

譯者: 易帆 余 審譯者: lin quan

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B1 US TED 基因 蚊子 驅動 瘧疾 物種

【TED】詹妮弗-卡恩:基因編輯現在可以改變整個物種--永遠(基因編輯現在可以改變整個物種--永遠|詹妮弗-卡恩)。 (【TED】Jennifer Kahn: Gene editing can now change an entire species -- forever (Gene editing can now change an entire species -- forever | Jennifer Kahn))

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    Zenn posted on 2021/01/14
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