So this is a talk about gene drives, but I'm going to start by telling you a brief story. 20 years ago, a biologist named Anthony James got obsessed with the idea of making mosquitos that didn't transmit malaria.
這次的演講是有關於 「基因驅動技術」, 但我要從一個小故事開始說起。 20年前,有一位叫安東尼.詹姆斯 的生物學家, 他迷上了一個 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. For one thing, it turned out to be really hard to make a malaria-resistant mosquito. James managed it, finally, just a few years ago, by adding some genes that make it impossible for the malaria parasite to survive inside the mosquito.
想法很棒,但幾乎差點失敗。 首先,要做出抗瘧疾的蚊子, 真的相當困難。 但詹姆士在幾年前, 終於做到了, 他是藉由增加基因的方式, 讓瘧疾的寄生蟲無法在 蚊子身上生存。
But that just created another problem. Now that you've got a malaria-resistant mosquito, how do you get it to replace all the malaria-carrying mosquitos? There are a couple options, but plan A was basically to breed up a bunch of the new genetically-engineered mosquitos release them into the wild and hope that they pass on their genes. The problem was that you'd have to release literally 10 times the number of native mosquitos to work. So in a village with 10,000 mosquitos, you release an extra 100,000. As you might guess, this was not a very popular strategy with the villagers.
但這會衍生出另外一個問題。 現在,你有一隻抗瘧疾的蚊子, 但你要如何讓牠取代掉所有 有攜帶瘧疾病原的蚊子? 有幾個選項可以選, A 計畫基本上就是, 培育出一大堆新的 基因改造過的蚊子, 然後放生牠們, 並祈禱牠們的基因 可以被遺傳下去。 但問題是,你得釋放出 將近十倍當地蚊子的數量, 才會有效果。 所以,一個有 1 萬隻蚊子的村落, 你得釋放出 10 萬隻才能搞定。 你應該猜的到, 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 from a biologist named Ethan Bier. Bier said that he and his grad student Valentino Gantz had stumbled on a tool that could not only guarantee that a particular genetic trait would be inherited, but that it would spread incredibly quickly. If they were right, it would basically solve the problem that he and James had been working on for 20 years.
之後,去年一月, 詹姆士收到一封 來自一位叫做伊桑.畢爾 生物學家的 E-mail。 畢爾說,他和他的一位名叫 范倫鐵諾.岡茲的研究生 意外發現了一個工具, 它不僅可以保證 特定的基因特徵 可以被遺傳到下一代, 還可以讓它快速地繁殖擴散。 如果他們是對的, 基本上就可以解決掉 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 and also this new tool, a gene drive, which I'll explain in a minute. Finally, they set it up so that any mosquitos that had inherited the anti-malaria gene wouldn't have the usual white eyes, but would instead have red eyes. That was pretty much just for convenience so they could tell just at a glance which was which.
在實測中,他們做出了兩隻 帶有抗瘧疾基因的蚊子, 以及這項新工具, 「基因驅動技術」, 我晚點會在做解釋。 最後,他們設置出了一種機制, 他們讓帶有抗瘧疾 基因的蚊子 不再有正常的白色眼睛, 取而代之的是紅色的眼睛。 這是一個相當方便的辨認方式, 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 and put them in a box with 30 ordinary white-eyed ones, and let them breed. In two generations, those had produced 3,800 grandchildren. That is not the surprising part. This is the surprising part: given that you started with just two red-eyed mosquitos and 30 white-eyed ones, you expect mostly white-eyed descendants. Instead, when James opened the box, all 3,800 mosquitos had red eyes.
所以,他們把兩隻 抗瘧疾、紅眼的蚊子, 放進一個裝有30隻 正常白眼蚊子的箱子中, 然後讓牠們繁殖。 在經過兩個世代後,這些蚊子 繁殖出 3800 隻的後代。 這一段不最驚人的部分。 接下來這一段才是: 假定,你從只有兩隻紅眼蚊子 加上30隻白眼蚊子開始繁殖, 你會以為牠們的後代 應該都是白眼的, 但在詹姆士打開箱子後, 他發現, 全部的 3800 隻蚊子都是紅眼的。
When I asked Ethan Bier about this moment, he became so excited that he was literally shouting into the phone. That's because getting only red-eyed mosquitos violates a rule that is the absolute cornerstone of biology, Mendelian genetics. I'll keep this quick, but Mendelian genetics says when a male and a female mate, their baby inherits half of its DNA from each parent. So if our original mosquito was aa and our new mosquito is aB, where B is the anti-malarial gene, the babies should come out in four permutations: aa, aB, aa, Ba. Instead, with the new gene drive, they all came out aB. Biologically, that shouldn't even be possible.
當我問伊桑.畢爾這件事時, 他在電話那頭簡直興奮地不得了。 那是因為,你如果 只剩下紅眼蚊子 那就是違反了 生物學的基礎法則, 孟德爾的遺傳定律。 我簡單說明一下, 孟德爾的遺傳定律說明, 當一公一母交配時, 他們的後代會遺傳到 來自上一代各半的 DNA。 所以如果原生種蚊子是 aa, 新的蚊子是 aB, B 代表抗瘧疾的基因, 那他們的後代, 會有四種排列組合: aa, aB, aa, Ba。 但,如果你使用了 新的基因驅動技術, 他們會全部變成aB。 在生物學上,根本 不會有這種情況發生。
So what happened? The first thing that happened was the arrival of a gene-editing tool known as CRISPR in 2012. Many of you have probably heard about CRISPR, so I'll just say briefly that CRISPR is a tool that allows researchers to edit genes very precisely, easily and quickly. It does this by harnessing a mechanism that already existed in bacteria. Basically, there's a protein that acts like a scissors and cuts the DNA, and there's an RNA molecule that directs the scissors to any point on the genome you want. The result is basically a word processor for genes. You can take an entire gene out, put one in, or even edit just a single letter within a gene. And you can do it in nearly any species.
但發生了甚麼事? 第一件發生的事情就是 2012 年基因編輯技術 CRISPER 的誕生。 你們當中很多人可能都 聽過 CRISPER 這項技術了 , 所以我簡單說明一下, CRISPER 是一種工具, 它可以讓研究人員以非常精準、 簡單、快速的方式來編輯 DNA 。 它是藉由控制一個現存在 細菌裡面的一個機制。 基本上,會有一個像 剪刀一樣功能的蛋白質, 它會切斷 DNA, 然後會有一個 RNA 分子導引剪刀 往你希望它剪掉的地方去。 它所形成的結果,基本上 就是一個基因造字的過程。 你可以抽出整段基因, 然後換另一段進去, 甚至僅是編輯 基因裡的其中一個字母。 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? The first was that it was hard to engineer a mosquito to be malaria-resistant. That's basically gone now, thanks to CRISPR. But the other problem was logistical. How do you get your trait to spread? This is where it gets clever.
好的,還記得我剛提的, 基因驅動技術原本的兩個問題嗎? 第一個就是,要做出一隻 有抗瘧疾的蚊子是相當困難的。 而現在有了 CRISPR , 這一難題迎刃而解。 但另一個是後續支援的問題。 你要如何把你的 生物特性散播出去? 這裡有一個聰明的方法。
A couple years ago, a biologist at Harvard named Kevin Esvelt wondered what would happen if you made it so that CRISPR inserted not only your new gene but also the machinery that does the cutting and pasting. In other words, what if CRISPR also copied and pasted itself. You'd end up with a perpetual motion machine for gene editing. And that's exactly what happened. This CRISPR gene drive that Esvelt created not only guarantees that a trait will get passed on, but if it's used in the germline cells, it will automatically copy and paste your new gene into both chromosomes of every single individual. It's like a global search and replace, or in science terms, it makes a heterozygous trait homozygous.
幾年前,哈佛大學的一位生物學家, 凱文.伊斯維特 他想如果 CRISPER 不僅只有插入新基因的功能, 如果也含有剪下,貼上 的功能,那會怎樣? 換句話說,要是 CRISPER 本身也有複製及貼上的功能。 那你就會得到一個 永續性的基因編輯機制。 而事情就真的發生了。 伊斯維特創造的 CRISPER 基因驅動技術, 不僅可以保證基因特徵可以被遺傳, 也可以保證能用在生殖細胞上, 它會自動地複製、 貼上你的新基因 到每個個體的染色體上。 它就像是全球檢索 並取代的功能。 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? For one thing, it means we have a very powerful, but also somewhat alarming new tool. Up until now, the fact that gene drives didn't work very well was actually kind of a relief. Normally when we mess around with an organism's genes, we make that thing less evolutionarily fit. So biologists can make all the mutant fruit flies they want without worrying about it. If some escape, natural selection just takes care of them.
所以,這意味著什麼? 首先,意味著, 我們有了一個非常強大 但也有點令人害怕的新工具。 到目前為止,基因驅動技術 運作地還不是很順暢的事實 的確還算有點令人欣慰。 按理說,當我們搞亂掉 一個生物的基因, 我們只要降低這個東西的 進化適應力即可。 所以,生物學家們 可以無後顧之憂地 製造出任何他們想要的 果蠅突變體。 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 is that that will no longer be true. Assuming that your trait does not have a big evolutionary handicap, like a mosquito that can't fly, the CRISPR-based gene drive will spread the change relentlessly until it is in every single individual in the population. Now, it isn't easy to make a gene drive that works that well, but James and Esvelt think that we can.
但基因驅動技術最顯著有力、 令人害怕的地方就是 這樣的狀況 可能將永遠不存在。 假設你的遺傳特徵如果沒有一個 很大的演化肢障產生, 好比蚊子沒有辦法飛, 以 CRISPER 為基礎的基因驅動, 將把這個改變給持續散播出去, 直到它深入到族群中 的每個個體身上。 現在,要讓基因驅動技術 量好運行,並非易事, 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. If you put an anti-malarial gene drive in just 1 percent of Anopheles mosquitoes, the species that transmits malaria, researchers estimate that it would spread to the entire population in a year. So in a year, you could virtually eliminate malaria. In practice, we're still a few years out from being able to do that, but still, a 1,000 children a day die of malaria. In a year, that number could be almost zero. The same goes for dengue fever, chikungunya, yellow fever.
好消息是,這項技術為一些 不可思議的事情打開了一扇門。 你只要在 1% 的 攜帶瘧疾的蚊子身上使用 抗瘧疾基因驅動技術, 研究人員預估,一年內這一基因 就可以散播到整個種群中。 所以,只要一年的時間, 你就可以完全消滅掉瘧疾。 實際上, 我們仍需好幾年才能做到, 但每天仍然有 1000 名 兒童死於瘧疾。 只要一年的時間,就幾乎 可以把數字降到零。 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. Say you want to get rid of an invasive species, like get Asian carp out of the Great Lakes. All you have to do is release a gene drive that makes the fish produce only male offspring. In a few generations, there'll be no females left, no more carp. In theory, this means we could restore hundreds of native species that have been pushed to the brink.
更好的是, 假設你想根除掉一個 外來入侵的物種, 像是把亞洲鯉魚趕出五大湖。 你所要做的就是,釋放一種 只能繁衍出雄性後代 的基因驅動, 幾代之後,没有了雌性鯉魚, 該物種就隨之消失了。 理論上,這意味著, 我們可以透過這種方式, 復育上百種瀕臨絕種的生物。
OK, that's the good news, this is the bad news. Gene drives are so effective that even an accidental release could change an entire species, and often very quickly. Anthony James took good precautions. He bred his mosquitos in a bio-containment lab and he also used a species that's not native to the US so that even if some did escape, they'd just die off, there'd be nothing for them to mate with. But it's also true that if a dozen Asian carp with the all-male gene drive accidentally got carried from the Great Lakes back to Asia, they could potentially wipe out the native Asian carp population. And that's not so unlikely, given how connected our world is. In fact, it's why we have an invasive species problem. And that's fish. Things like mosquitos and fruit flies, there's literally no way to contain them. They cross borders and oceans all the time.
好的,這是好消息的部分, 接下來,是壞消息的部分。 基因驅動技術因為很有效率, 以至於不經意釋放的樣本, 通常都可能在短時間內 引起整個種群的巨大改變。 詹姆士做了很好的預防措施。 他都是在生物控制實驗室裡 培養他的蚊子, 而且他用的都是 非美國本土的物種, 所以,即使有一些跑走了, 也會因為沒有辦法交配而死。 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, 不小心從五大湖被帶回到亞洲, 牠們也很有可能會毀滅掉 整個當地的亞洲鯉魚物種。 現在世界聯繫的緊密程度 這是很有可能會發生的。 事實上,這也是為什麼我們 有外來物種入侵的問題。 這是魚類的情況。 對蚊子和果蠅這一類 會飛的物種而言, 基本上是沒有辦法限制牠們的。 牠們可以隨時 穿越國界或飄揚過海。
OK, the other piece of bad news is that a gene drive might not stay confined to what we call the target species. That's because of gene flow, which is a fancy way of saying that neighboring species sometimes interbreed. If that happens, it's possible a gene drive could cross over, like Asian carp could infect some other kind of carp. That's not so bad if your drive just promotes a trait, like eye color. In fact, there's a decent chance that we'll see a wave of very weird fruit flies in the near future. But it could be a disaster if your drive is deigned to eliminate the species entirely.
好的,還有另外一個壞消息, 就是,基因驅動的表現 不一定只被限制在 我們所謂的標靶物種上。 那是因為有基因轉移(流動) 基因轉移就是, 相鄰的物種之間 偶爾彼此會有雜交的情形。 如果發生了雜交,基因驅動 就很有可能會穿過物種的限制, 比如亞洲鯉魚可能會 影響其它種類的鯉魚。 如果你的驅動只是改變眼睛的顏色, 可能還不會那麼糟糕。 事實上,不久的未來很有可能 有非常大量奇怪的 果蠅被培養出來。 但如果你的驅動裝置是惡意地 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, to genetically engineer an organism and include a gene drive, is something that basically any lab in the world can do. An undergraduate can do it. A talented high schooler with some equipment can do it.
最後一件令人擔心的事,就是, 對有機體做基因工程包括基因驅動, 這一技術, 基本上世界上 任何一個實驗室都能做。 一個大學本科生就可以做。 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 seemed to think that gene drives were not actually that frightening or dangerous. Partly because they believe that scientists will be very cautious and responsible about using them.
有趣的是,因乎每一個 和我討論的科學家都認為, 基因驅動技術沒有想像中 那麼的恐怖或危險, 有部分原因是, 他們相信科學家們 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. But gene drives also have some actual limitations. So for one thing, they work only in sexually reproducing species. So thank goodness, they can't be used to engineer viruses or bacteria. Also, the trait spreads only with each successive generation. So changing or eliminating a population is practical only if that species has a fast reproductive cycle, like insects or maybe small vertebrates like mice or fish. In elephants or people, it would take centuries for a trait to spread widely enough to matter.
目前為止,也確實是如此。 不過基因驅動技術 也有一些實質上的限制。 首先,它只能應用於 有性生殖的物種。 所以感謝上帝,它們不能 用在細菌和病毒的培育上。 其次,遺傳特徵只有在 成功的後代繁衍下才能傳播。 所以只有在繁殖周期很短的物種中 改變或者滅絕該物種才有可能發生。 比如昆蟲或者類似於鼠類 或者魚類的小型脊椎動物。 大象或者人類可能需要幾百年, 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. Say you wanted to make a fruit fly that feeds on ordinary fruit instead of rotting fruit, with the aim of sabotaging American agriculture. First, you'd have to figure out which genes control what the fly wants to eat, which is already a very long and complicated project. Then you'd have to alter those genes to change the fly's behavior to whatever you'd want it to be, which is an even longer and more complicated project. And it might not even work, because the genes that control behavior are complex. So if you're a terrorist and have to choose between starting a grueling basic research program that will require years of meticulous lab work and still might not pan out, or just blowing stuff up? You'll probably choose the later.
而且,就算有 CRISPR , 也無法輕易做出真正毀滅性的遺傳特徵。 比如說,你想製造一種 以普通水果而不是以 腐爛水果為食的果蠅, 藉此來摧毀美國的農業。 首先,你得搞清楚, 哪些基因控制了 果蠅的食慾, 這已經算是很長 很複雜的專案了。 接下來你要根據你的想法, 透過更換基因 來改變果蠅的習性, 這將是更長更複雜的專案。 甚至會以失敗告終, 因為基因對於行為的 控制是非常複雜的。 所以,如果你是一個恐怖分子, 你會選擇一個需要 耗時多年、細心做實驗 甚至可能會失敗的研究計畫, 還是直接放炸彈? 你大概會選擇後者。
This is especially true because at least in theory, it should be pretty easy to build what's called a reversal drive. That's one that basically overwrites the change made by the first gene drive. So if you don't like the effects of a change, you can just release a second drive that will cancel it out, at least in theory.
這真的是實話,因為至少在理論上, 要製造一個叫做「逆轉驅動」 的東西也相當容易。 它基本上就可以覆蓋掉 第一個基因驅動所造成的改變。 所以,如果你不喜歡改變後的結果, 你只要再釋放第二個驅動 就可以把它消滅掉了, 至少理論上是這樣的。
OK, so where does this leave us? We now have the ability to change entire species at will. Should we? Are we gods now? I'm not sure I'd say that. But I would say this: first, some very smart people are even now debating how to regulate gene drives. At the same time, some other very smart people are working hard to create safeguards, like gene drives that self-regulate or peter out after a few generations. That's great. But this technology still requires a conversation. And given the nature of gene drives, that conversation has to be global. What if Kenya wants to use a drive but Tanzania doesn't? Who decides whether to release a gene drive that can fly?
好的,這告訴了我們甚麼? 我們現在已經有能力, 能隨意改變整個物種。 我們應該這樣做嗎? 我們現在是上帝了嗎? 我不太確定 我能否這樣說。 但我想說的是: 首先,有很多頂尖聰明的人, 現在已經開始討論如何監管 基因驅動技術。 同時,另一批頂尖聰明的人, 也已經開始努力地制定 安全保護措施, 比如,讓基因自我規範 或幾代之後逐漸消失。 太棒了。 但這項技術仍需要展開一次對話。 而且鑒於基因驅動技術的本質, 對話必須是全球性的。 要是肯亞想使用一個驅動, 但坦薩尼亞不要呢? 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. All we can do going forward, I think, is talk honestly about the risks and benefits and take responsibility for our choices. By that I mean, not just the choice to use a gene drive, but also the choice not to use one. Humans have a tendency to assume that the safest option is to preserve the status quo. But that's not always the case. Gene drives have risks, and those need to be discussed, but malaria exists now and kills 1,000 people a day. To combat it, we spray pesticides that do grave damage to other species, including amphibians and birds.
我目前仍沒有答案。 接下來我們能做的, 我認為, 就是針對這項技術的利弊, 大家坦誠對話, 並對我們的選擇負責。 但我的意思是,不僅要對 選擇使用基因驅動負責, 也要對不使用它的後果負責。 人類傾向於認為, 維持現狀就是最安全的選項。 但事實往往不一定如此。 基因驅動確實有風險, 也需要被討論, 但現存的瘧疾, 每天在持續奪走 1000 條人命。 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, 包括兩棲類及鳥類。
So when you hear about gene drives in the coming months, and trust me, you will be hearing about them, remember that. It can be frightening to act, but sometimes, not acting is worse.
所以,當各位幾個月後 聽到基因驅動, 相信我,你將會聽到這些事, 請記住, 採取行動或許令人恐懼, 但有時候,無動於衷會更糟糕。
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