CRISPR發(fā)明者演講：當我們開始“定制嬰兒”，世界會陷入怎樣的瘋狂？

首例人類基因編輯嬰兒誕生事件一經(jīng)出現(xiàn)在網(wǎng)絡，便引發(fā)爭議，其原因并不是這項技術的突破性，而是在人類毫無準備的情況下，為“人類物種”打開了一個面臨巨大進化和道德風險的瘋狂世界入口。

遺傳學專家詹妮弗·道娜(Jennifer Doudna)與同事共同發(fā)明了突破性的新技術“基因編輯技術”，被稱為CRISPR-Cas9。該工具允許科學家們對DNA進行精確的編輯，這可能對遺傳性疾病的治療有幫助...但也可能會被用來創(chuàng)造所謂的“訂制嬰兒”。道娜展示了CRISPR-Cas9的作用原理——并要求科學界暫緩腳步，來討論這個新工具背后的倫理問題。

一起來看看她有關這一問題的演講：

A few years ago, with my colleague, Emmanuelle Charpentier, I invented a new technology for editing genomes. It's called CRISPR-Cas9. The CRISPR technology allows scientists to make changes to the DNA in cells that could allow us to cure genetic disease.

幾年前， 我跟同事Emmanuelle Charpentier發(fā)明了一個可以編輯基因組的新技術。 它叫做"CRISPR-Cas9"。CRISPR技術讓科學家可以改變細胞里的DNA， 從而讓我們能夠治愈基因疾病。

You might be interested to know that the CRISPR technology came about through a basic research project that was aimed at discovering how bacteria fight viral infections. Bacteria have to deal with viruses in their environment, and we can think about a viral infection like a ticking time bomb -- a bacterium has only a few minutes to defuse the bomb before it gets destroyed. So, many bacteria have in their cells an adaptive immune system called CRISPR, that allows them to detect viral DNA and destroy it.

你可能有興趣想知道，CRISPR技術其實來自于一個基礎的科學研究， 它的主要目的是了解細菌如何與病毒感染進行對抗。 細菌必須在它們的環(huán)境里對付病毒。 我們可以這么想， 病毒感染像是個定時炸彈， 細菌在被消滅前， 只有幾分鐘時間可以拆除炸彈。 很多細菌在它們的細胞里有一種適應力免疫系統(tǒng)叫做"CRISPR"， 它可以使細菌偵測到病毒DNA并消滅它。

Part of the CRISPR system is a protein called Cas9, that's able to seek out, cut and eventually degrade viral DNA in a specific way. And it was through our research to understand the activity of this protein, Cas9, that we realized that we could harness its function as a genetic engineering technology -- a way for scientists to delete or insert specific bits of DNA into cells with incredible precision -- that would offer opportunities to do things that really haven't been possible in the past.

CRISPR系統(tǒng)中，有一部分是一種叫Cas9的蛋白質(zhì)， 它能夠以特殊的方式尋找出、剪斷， 最后削弱病毒DNA。 我們的研究主要是想了解Cas9蛋白質(zhì)的活動， 我們意識到可以駕馭它的功能， 把它當做一種基因工程技術—— 一種可以讓科學家用難以置信的精準度來消除或插入特定DNA片段到細胞中—— 這項技術提供了一個前所未有的機會， 讓我們可以做到在過去根本無法完成的事情。

The CRISPR technology has already been used to change the DNA in the cells of mice and monkeys, other organisms as well. Chinese scientists showed recently that they could even use the CRISPR technology to change genes in human embryos. And scientists in Philadelphia showed they could use CRISPR to remove the DNA of an integrated HIV virus from infected human cells.

CRISPR技術已經(jīng)被應用于改變老鼠和猴子細胞里的DNA， 還包括其他有機體。中國科學家最近發(fā)現(xiàn)，他們甚至可以利用CRISPR技術改變?nèi)祟惻咛ダ锏幕?。費城的科學家證實， 他們可以利用CRISPR技術從一個感染的人類細胞中移除HIV病毒(人類免疫缺陷病毒)。

The opportunity to do this kind of genome editing also raises various ethical issues that we have to consider, because this technology can be employed not only in adult cells, but also in the embryos of organisms, including our own species. And so, together with my colleagues, I've called for a global conversation about the technology that I co-invented, so that we can consider all of the ethical and societal implications of a technology like this.

這個充滿契機的基因組編輯技術， 也引發(fā)了各種我們必須認真思考的道德爭議。 因為這種技術不僅可以運用在成人細胞上， 也可以用在有機體的胚胎上， 包含我們?nèi)祟愖约骸?所以，我和同事們呼吁， 要針對這項技術展開一次全球對話， 思考應該賦予這種技術的道德與社會責任。

What I want to do now is tell you what the CRISPR technology is, what it can do, where we are today and why I think we need to take a prudent path forward in the way that we employ this technology.

那么現(xiàn)在，我要告訴你們CRISPR技術是什么、 它可以做什么、 目前的發(fā)展狀況、 以及我為什么認為我們需要一個縝密的思路來運用這項技術。

When viruses infect a cell, they inject their DNA. And in a bacterium, the CRISPR system allows that DNA to be plucked out of the virus, and inserted in little bits into the chromosome -- the DNA of the bacterium. And these integrated bits of viral DNA get inserted at a site called CRISPR. CRISPR stands for clustered regularly interspaced short palindromic repeats.

當病毒感染一個細胞， 它們會插入自身的DNA。 在一個細菌中，CRISPR系統(tǒng)可以把病毒的DNA拔掉， 并且將其中一小段插入到染色體內(nèi)—— 也就是細菌的DNA。 而這些成簇的病毒DNA會被插入到一個名為CRISPR的位點。CRISPR意思是"規(guī)律成簇的間隔短回文重復"。

A big mouthful -- you can see why we use the acronym CRISPR. It's a mechanism that allows cells to record, over time, the viruses they have been exposed to. And importantly, those bits of DNA are passed on to the cells' progeny, so cells are protected from viruses not only in one generation, but over many generations of cells. This allows the cells to keep a record of infection, and as my colleague, Blake Wiedenheft, likes to say, the CRISPR locus is effectively a genetic vaccination card in cells. Once those bits of DNA have been inserted into the bacterial chromosome, the cell then makes a little copy of a molecule called RNA, which is orange in this picture, that is an exact replicate of the viral DNA. RNA is a chemical cousin of DNA, and it allows interaction with DNA molecules that have a matching sequence.

很繞口——這回你們就知道為什么我們要使用CRISPR的縮寫了。CRISPR是一種機制—— 它允許細胞隨時記錄被感染到的病毒。 而且重要的是，這些片段DNA會遺傳到細胞的后代， 所以細胞不只有一代會一直被保護不受病毒感染， 好幾代的細胞都會如此。 這允許細胞持有受感染的記錄， 就像我同事Blake Wiedenheft喜歡說的，CRISPR的基因座其實上就是細胞的一張基因疫苗接種卡。 一旦這些片段DNA被插入到細菌染色體內(nèi)， 細胞就會復制出一小段叫RNA的分子， 就是照片上的橘色的部分， 它就是病毒DNA的復制品。RNA相當于DNA的化學表親， 能夠與DNA上相同序列的分子產(chǎn)生反應。

So those little bits of RNA from the CRISPR locus associate -- they bind -- to protein called Cas9, which is white in the picture, and form a complex that functions like a sentinel in the cell. It searches through all of the DNA in the cell, to find sites that match the sequences in the bound RNAs. And when those sites are found -- as you can see here, the blue molecule is DNA -- this complex associates with that DNA and allows the Cas9 cleaver to cut up the viral DNA. It makes a very precise break. So we can think of the Cas9 RNA sentinel complex like a pair of scissors that can cut DNA -- it makes a double-stranded break in the DNA helix. And importantly, this complex is programmable, so it can be programmed to recognize particular DNA sequences, and make a break in the DNA at that site.

所以這些從CRISPR基因座轉錄的RNA片段， 會與一種叫Cas9的蛋白質(zhì)相結合， 也就是照片上白色的部分， 這個蛋白質(zhì)綜合體像是細胞的衛(wèi)兵。 它會搜尋細胞里所有的DNA， 找到符合所結合的RNA序列的位點。 當這些位置被找到后—— 就是你們看到的藍色DNA分子， 這個綜合體會與DNA結合， 并允許Cas9蛋白質(zhì)像刀一樣切斷病毒DNA。 這是一次非常精確的截斷。 所以我們可以把Cas9 RNA標記復合體想像成是一把DNA剪刀—— 它在DNA螺旋結構中， 制造了一種"雙股螺旋斷裂"。 最重要的是， 這種復合體是可程式化的， 在程式化后可以用來辨認特定的DNA序列， 并且在DNA的特定位置制造一個斷裂。

As I'm going to tell you now, we recognized that that activity could be harnessed for genome engineering, to allow cells to make a very precise change to the DNA at the site where this break was introduced. That's sort of analogous to the way that we use a word-processing program to fix a typo in a document.

我現(xiàn)在想要告訴大家， 我們已經(jīng)意識到這個技術， 可以被利用于基因工程中， 就在我提到過的斷裂處使細胞內(nèi)的DNA產(chǎn)生一個非常精準的變化。 這個方式有點類似于我們使用文字處理軟件在一個文檔中修改錯字一樣。

The reason we envisioned using the CRISPR system for genome engineering is because cells have the ability to detect broken DNA and repair it. So when a plant or an animal cell detects a double-stranded break in its DNA, it can fix that break, either by pasting together the ends of the broken DNA with a little, tiny change in the sequence of that position, or it can repair the break by integrating a new piece of DNA at the site of the cut. So if we have a way to introduce double-stranded breaks into DNA at precise places, we can trigger cells to repair those breaks, by either the disruption or incorporation of new genetic information. So if we were able to program the CRISPR technology to make a break in DNA at the position at or near a mutation causing cystic fibrosis, for example, we could trigger cells to repair that mutation.

我們意識到CRISPR系統(tǒng)可以被用于基因組工程的原因是， 細胞具有檢測損壞的DNA， 并修復它的能力。 所以當一個植物或動物細胞在它的DNA中檢測到雙股螺旋斷裂時， 它可以修復這種斷裂， 把破裂的DNA尾端接合在一起， 只在那個位置的序列產(chǎn)生微小的變化， 或者，也可以借由在該位置處聚集新的DNA片段來修復斷裂。 所以如果我們有一種方式可以引導"雙股螺旋斷裂"精準地進入DNA， 我們就可以刺激細胞來修復這些斷裂， 通過破壞或合并新的遺傳信息。 所以如果我們可以程式化CRISPR技術在DNA里制造斷裂， 例如，在囊性纖維化發(fā)生突變的位置處或附近制造斷裂， 我們就可以刺激細胞去修復那個突變。

Genome engineering is actually not new, it's been in development since the 1970s. We've had technologies for sequencing DNA, for copying DNA, and even for manipulating DNA. And these technologies were very promising, but the problem was that they were either inefficient, or they were difficult enough to use that most scientists had not adopted them for use in their own laboratories, or certainly for many clinical applications. So, the opportunity to take a technology like CRISPR and utilize it has appeal, because of its relative simplicity. We can think of older genome engineering technologies as similar to having to rewire your computer each time you want to run a new piece of software, whereas the CRISPR technology is like software for the genome, we can program it easily, using these little bits of RNA.

基因工程并不是什么新技術， 它在1970年代就發(fā)展起來了。 我們已經(jīng)擁有DNA測序技術，DNA復制技術， 甚至DNA修改技術。 這些技術前程無量， 但問題是它們要么效率不高， 要么操作太復雜， 所以大部分科學家們并不在實驗室采用這項技術， 或是應用于臨床。 而CRISPR的技術相對簡單， 所以使用它的機會已展露曙光。 我們可以想像一下舊的基因工程技術就好比每次你要安裝新的軟件， 就要把電腦升級一次一樣。 而CRISPR技術就像基因組的軟件， 利用這些RNA小片段， 我們可以簡單地編輯它。

So once a double-stranded break is made in DNA, we can induce repair, and thereby potentially achieve astounding things, like being able to correct mutations that cause sickle cell anemia or cause Huntington's Disease. I actually think that the first applications of the CRISPR technology are going to happen in the blood, where it's relatively easier to deliver this tool into cells, compared to solid tissues.

那么一旦雙股螺旋斷裂在DNA中發(fā)生， 我們就可以誘導修復， 由此有可能達到驚人的效果， 比如,能夠修正引起鐮刀細胞貧血癥， 或引起亨廷頓氏病的突變。 我認為CRISPR技術的第一項應用會在血液里發(fā)生， 相對于堅硬組織而言,更能簡單地在細胞內(nèi)導入這項技術。

Right now, a lot of the work that's going on applies to animal models of human disease, such as mice. The technology is being used to make very precise changes that allow us to study the way that these changes in the cell's DNA affect either a tissue or, in this case, an entire organism.

目前,很多工作已經(jīng)運用在人類疾病的動物模型中，例如，老鼠。 這技術已經(jīng)被用來實現(xiàn)非常精準的改變， 使我們能夠研究細胞DNA里的變化， 不論是對一個組織或像這個案例中的，整個有機體。

Now in this example, the CRISPR technology was used to disrupt a gene by making a tiny change in the DNA in a gene that is responsible for the black coat color of these mice. Imagine that these white mice differ from their pigmented litter-mates by just a tiny change at one gene in the entire genome, and they're otherwise completely normal. And when we sequence the DNA from these animals, we find that the change in the DNA has occurred at exactly the place where we induced it, using the CRISPR technology.

在這個案例中， 借由在DNA里的小改變，CRISPR技術被用來擾亂關聯(lián)這些老鼠黑色皮膚的基因。 想像一下，這些白色的老鼠與它們有色小同伴不同的原因， 僅是由于在整個基因組中的一個小改變， 除此之外，它們幾乎一模一樣。 當我們對這些動物的基因做測序， 我們發(fā)現(xiàn)了在基因里的變化就精準地發(fā)生在我們使用CRISPR技術的地方。

Additional experiments are going on in other animals that are useful for creating models for human disease, such as monkeys. And here we find that we can use these systems to test the application of this technology in particular tissues, for example, figuring out how to deliver the CRISPR tool into cells. We also want to understand better how to control the way that DNA is repaired after it's cut, and also to figure out how to control and limit any kind of off-target, or unintended effects of using the technology.

更多的實驗也正在其它動物身上進行中， 被當做人類疾病的的試驗模型，像是猴子。 我們在此發(fā)現(xiàn)，我們可以使用這系統(tǒng)在特定組織中運用這項技術， 例如，如何傳送CRISPR工具到細胞中。 我們也想進一步了解如何控制DNA在切斷后的修復方式， 也更想知道如何控制并限制任何一種偏離目標的狀況， 或者使用這技術時的副作用。

I think that we will see clinical application of this technology, certainly in adults, within the next 10 years. I think that it's likely that we will see clinical trials and possibly even approved therapies within that time, which is a very exciting thing to think about. And because of the excitement around this technology, there's a lot of interest in start-up companies that have been founded to commercialize the CRISPR technology, and lots of venture capitalists that have been investing in these companies.

我想我們會在十年內(nèi)就看到它在臨床上的應用， 特別是在成人身上。 我認為在這段期間， 我們很可能會看到臨床試驗， 甚至也有可能是獲得批準的治療方式， 想想的確是件令人興奮的事。 另外，因為這項技術的興起， 也涌現(xiàn)了很多初創(chuàng)公司， 致力于CRISPR技術的商業(yè)化， 也有很多風險投資家開始為這些公司投資。

But we have to also consider that the CRISPR technology can be used for things like enhancement. Imagine that we could try to engineer humans that have enhanced properties, such as stronger bones, or less susceptibility to cardiovascular disease or even to have properties that we would consider maybe to be desirable, like a different eye color or to be taller, things like that. "Designer humans," if you will. Right now, the genetic information to understand what types of genes would give rise to these traits is mostly not known. But it's important to know that the CRISPR technology gives us a tool to make such changes, once that knowledge becomes available.

但我們也必須要思考一件事， 就是CRISPR技術能被用在強化性能上。 想像一下我們可以嘗試設計制造人類， 像是擁有更強壯的骨骼， 或降低心血管疾病的誘發(fā)機率， 甚至擁有我們期待已久的特征， 像是不同的眼睛顏色，或長得更高。"訂制人"，你們也可以這么理解。 目前為止，關于哪些類型的基因會有這些特征，相關的基因信息大部分仍是未知的。 但了解CRISPR技術提供了我們一個可以改變現(xiàn)狀的工具是很重要的， 尤其是當我們獲得了這些基因信息之后。

This raises a number of ethical questions that we have to carefully consider, and this is why I and my colleagues have called for a global pause in any clinical application of the CRISPR technology in human embryos, to give us time to really consider all of the various implications of doing so. And actually, there is an important precedent for such a pause from the 1970s, when scientists got together to call for a moratorium on the use of molecular cloning, until the safety of that technology could be tested carefully and validated.

這會引發(fā)一系列我們必須仔細考量的道德問題， 這也是為什么我跟我的同事們想要呼吁全世界暫緩任何臨床上有關CRISPR在人類胚胎上的應用， 給我們一些時間， 讓我們認真思考各種不同的CRISPR應用。 實際上，在1970年代， 有一個類似這樣暫緩的重要例子， 當時科學家們聚集在一起， 呼吁暫緩使用"分子克隆"， 直到那個技術可以安全地被小心測試并驗證。

So, genome-engineered humans are not with us yet, but this is no longer science fiction. Genome-engineered animals and plants are happening right now. And this puts in front of all of us a huge responsibility, to consider carefully both the unintended consequences as well as the intended impacts of a scientific breakthrough.

雖然經(jīng)過基因工程改造的人類還尚未出現(xiàn)， 但這已經(jīng)不僅僅是科幻小說了。 動物及植物的基因改造正在進行中。 這也使我們每一個人都面臨一項重大責任， 來認真思考這個科技突破可能會帶來的未知后果和可預見的沖擊。

Thank you.

謝謝各位!

Bruno Giussani: Jennifer, this is a technology with huge consequences, as you pointed out. Your attitude about asking for a pause or a moratorium or a quarantine is incredibly responsible. There are, of course, the therapeutic results of this, but then there are the un-therapeutic ones and they seem to be the ones gaining traction, particularly in the media. This is one of the latest issues of The Economist -- "Editing humanity." It's all about genetic enhancement, it's not about therapeutics. What kind of reactions did you get back in March from your colleagues in the science world, when you asked or suggested that we should actually pause this for a moment and think about it?

Bruno Giussani (BG)：詹妮弗 ， 這是個具有很大影響力的技術， 你剛才說過了。 你要求暫停、延期或隔離的態(tài)度是非常負責任的。 當然有一些應用會有療效， 但也有一些非治療性的， 而它們似乎特別受媒體的關注。 這是《經(jīng)濟學人》雜志最新的議題——"定制人類"。 關注點幾乎都在基因學性能的提升， 而非治療。 今年三月你跟你在科學界的同事， 對此技術提出要求并建議——"我們必須立刻停止并思考"后， 你們得到了什么樣的回應呢?

Jennifer Doudna: My colleagues were actually, I think, delighted to have the opportunity to discuss this openly. It's interesting that as I talk to people, my scientific colleagues as well as others, there's a wide variety of viewpoints about this. So clearly it's a topic that needs careful consideration and discussion.

詹妮弗 道娜(JD)：我想， 我的同事們實際上很高興有這個機會可以公開討論這件事。 向大眾介紹這項技術是個很有趣的經(jīng)歷， 和同事或者其他人說起也是這樣， 關于這件事大家都有不同的見解。 所以很明顯， 這件事需要人們進行深入思考和討論。

BG: There's a big meeting happening in December that you and your colleagues are calling, together with the National Academy of Sciences and others, what do you hope will come out of the meeting, practically?

BG：今年12月還有一次大型會議， 你跟你同事都有被邀請， 與國家科學院及其他機構的專家一起開會， 你希望會議中能達成什么共識呢?

JD: Well, I hope that we can air the views of many different individuals and stakeholders who want to think about how to use this technology responsibly. It may not be possible to come up with a consensus point of view, but I think we should at least understand what all the issues are as we go forward.

JD：我希望我們可以與很多不同的私人機構及投資人針對如何負責任地使用此項技術做一次線上會議溝通。 也許不太可能會達成共識， 但我認為我們至少要了解當我們繼續(xù)前進時會面臨哪些問題。

BG: Now, colleagues of yours, like George Church, for example, at Harvard, they say, "Yeah, ethical issues basically are just a question of safety. We test and test and test again, in animals and in labs, and then once we feel it's safe enough, we move on to humans." So that's kind of the other school of thought, that we should actually use this opportunity and really go for it. Is there a possible split happening in the science community about this? I mean, are we going to see some people holding back because they have ethical concerns, and some others just going forward because some countries under-regulate or don't regulate at all?

BG：你的同事，比方說哈佛大學的George Church， 他們會說"對啊，有關道德上的考量， 基本上只是安全性問題， 我們會不斷地在實驗室里做動物實驗， 一旦我們感覺它夠安全， 才會在人體中做測試啊!"所以這有點像其他一類想法，"我們應該利用此機會并大膽嘗試。"這有沒有可能在科學界產(chǎn)生分歧呢?我的意思是，有些人忍住了， 因為他們有道德方面的顧慮， 有些人則沒有，依然我行我素， 因為有些國家有管制， 而有些則完全沒有?

JD: Well, I think with any new technology, especially something like this, there are going to be a variety of viewpoints, and I think that's perfectly understandable. I think that in the end, this technology will be used for human genome engineering, but I think to do that without careful consideration and discussion of the risks and potential complications would not be responsible.

JD：我想對很多新科技， 尤其類似這樣的技術， 大家都會有不同的觀點， 這完全可以理解。 我想到最后， 這項技術會被用在人類基因工程上， 但我認為如果沒有深思熟慮并討論其中的風險和可能的并發(fā)癥， 那是不負責任的表現(xiàn)。

BG: There are a lot of technologies and other fields of science that are developing exponentially, pretty much like yours. I'm thinking about artificial intelligence, autonomous robots and so on. No one seems -- aside from autonomous warfare robots -- nobody seems to have launched a similar discussion in those fields, in calling for a moratorium. Do you think that your discussion may serve as a blueprint for other fields?

BG：我想有很多技術和其他領域的科學跟你的很像，正在急速地發(fā)展著。 比如說人工智能、自主性機器人等等...似乎沒有人 —— 除了自主作戰(zhàn)機器人—— 在這些領域中， 似乎沒有人發(fā)表相同的言論， 要來呼吁暫緩之類的。 你是否認為你的討論也許可以成為其他領域的參考藍圖?

JD: Well, I think it's hard for scientists to get out of the laboratory. Speaking for myself, it's a little bit uncomfortable to do that. But I do think that being involved in the genesis of this really puts me and my colleagues in a position of responsibility. And I would say that I certainly hope that other technologies will be considered in the same way, just as we would want to consider something that could have implications in other fields besides biology.

JD： 我認為，要讓科學家不做實驗是不太可能的。 就我自己而言， 這樣做有點不太舒服。 但我的確認為我們涉及到這件事的源頭， 使我跟同事們必須站出來為這件事負責。 我要說我肯定希望其他的科學技術也能用同樣的方式來思考， 正如我們考量到某些事也有可能會牽連到除開生物學之外的其他領域。

BG: Jennifer, thanks for coming to TED.

BG：詹妮弗，感謝你來TED演講。

JD: Thank you.

JD：謝謝。