返回首页

EllenJorgensen_2016T-_关于crispr你必须知道的东西_

So, has everybody heard of CRISPR? 有人听说过 CRISPR 吗
I would be shocked if you hadn't. 大家应该都知道
This is a technology -- it's for genome editing -- and it's so versatile and so controversial that it's sparking all sorts of really interesting conversations. 这是一种人为改变染色体的技术 这种技术如此全能却又十分引人争议 以至于各种有趣的争论应运而生
technology:n.技术;工艺;术语; genome:n.基因组;染色体组; editing:v.编辑,校订(文章、书籍等);编选;(edit的现在分词) versatile:adj.多才多艺的;通用的,万能的;多面手的; controversial:adj.有争议的;有争论的; sparking:n.发火花;点火;v.导致(spark的现在分词);发出火星;使大感兴趣;
Should we bring back the woolly mammoth ? 我们要猛犸象复活吗?
woolly:adj.羊毛的;模糊的;似羊毛的;n.羊;毛织衣服; mammoth:n.长毛象;猛犸象;庞然大物;adj.巨大的,庞大的;猛犸似的;
Should we edit a human embryo ? 我们应该改造人类胚胎吗?
embryo:n.[胚]胚胎;胚芽;初期;adj.胚胎的;初期的;
And my personal favorite: 我最喜欢的一个问题是
personal:adj.个人的;身体的;亲自的;n.人事消息栏;人称代名词;
How can we justify wiping out an entire species that we consider harmful to humans off the face of the Earth, using this technology? 我们能够接受 用这种技术 将一个人类认为有害的物种 从地球上完全消灭吗?
justify:v.证明合法;整理版面;替…辩护; species:n.[生物]物种;种类;
This type of science is moving much faster than the regulatory mechanisms that govern it. 这种科技比控制它本身的常规技术 发展的还要快
regulatory:adj.管理的;控制的;调整的; mechanisms:n.机制;[机]机构(mechanism的复数);机械;[机]机构学;
And so, for the past six years, 在过去六年里
I've made it my personal mission to make sure that as many people as possible understand these types of technologies and their implications . 我致力于 让更多人了解这种技术 以及它的意义何在
mission:n.使命,任务;代表团;布道;v.派遣;向…传教; technologies:n.技术;科技(technology的复数); implications:n.蕴涵式;暗指,暗示;含蓄,含意;卷入(implication的复数);
Now, CRISPR has been the subject of a huge media hype , and the words that are used most often are "easy" and "cheap." 现在,CRISPR已经成了媒体炒作的焦点 最普遍的用于描述它的词是“容易” 和“廉价”
media:n.媒体;媒质(medium的复数);血管中层;浊塞音;中脉; hype:n.大肆宣传;皮下注射;vt.大肆宣传;使…兴奋;
So what I want to do is drill down a little bit deeper and look into some of the myths and the realities around CRISPR. 我想将这个话题深入下去 并探讨与之有关的谜团以及现实状况
myths:神话;谬见;
If you're trying to CRISPR a genome, the first thing that you have to do is damage the DNA. 如果 你想在一条染色体上做CRISPR 你得首先破环DNA分子
The damage comes in the form of a double-strand break through the double helix . 这种破坏需要从双螺旋结构上 斩断双链结构
break through:突破;突围;有重要创见; double helix:双螺旋;
And then the cellular repair processes kick in, and then we convince those repair processes to make the edit that we want, and not a natural edit. 随后细胞的修复机制开始插手 这是我们就可以让这些修复系统 来改造我们想要的基因了 这不是自然的改造
cellular:adj.细胞的;多孔的;由细胞组成的;n.移动电话;单元; repair:v.修理;修补;修缮;补救;n.修理;修补;修缮; processes:n.过程; v.处理(process的第三人称单数形式); convince:v.使确信;使相信;说服,劝说;
That's how it works. 这就是这种技术的原理
It's a two-part system. 这是一个两步走的技术
two-part:n.三分之二;
You've got a Cas9 protein and something called a guide RNA. 首先要有一个Cas9蛋白质还有一种向导RNA
protein:n.蛋白质;
I like to think of it as a guided missile . 可以将其比作定向导弹
guided missile:n.导弹;
So the Cas9 -- I love to anthropomorphize -- so the Cas9 is kind of this Pac-Man thing that wants to chew DNA, and the guide RNA is the leash that's keeping it out of the genome until it finds the exact spot where it matches. 于是Cas9蛋白质-我喜欢将其拟人化 Cas9 就像是吃豆人中的小圆脸 迫不及待地想要吃掉 DNA 向导 RNA 就像是控制住它不进入染色体的皮带 直到它找到了符合的位置
anthropomorphize:vt.赋与人性,人格化; Pac-Man:n.吃豆人(游戏名); leash:n.皮带;束缚;v.束缚;用皮带绑住;
And the combination of those two is called CRISPR. 这两种分子的结合体就叫做 CRISPR
combination:n.结合;组合;联合;[化学]化合;
It's a system that we stole from an ancient, ancient bacterial immune system . 这是一种我们从 古老的细菌结构中发现的方法
bacterial:adj.[微]细菌的; immune system:n.免疫系统;
The part that's amazing about it is that the guide RNA, only 20 letters of it, are what target the system. 最令人惊奇的部分是 RNA 虽只有20个有效信息 但却是整个结构的定位部分
This is really easy to design, and it's really cheap to buy. CRISPR 设计起来非常容易 并且价格低廉
So that's the part that is modular in the system; everything else stays the same. 这种手法已经被模块化 并且一成不变
modular:adj.模块化的;模数的;有标准组件的;
This makes it a remarkably easy and powerful system to use. 因此这种技术用起来十分便捷并且有效
remarkably:adv.非常;极为;格外;出乎意料地
The guide RNA and the Cas9 protein complex together go bouncing along the genome, and when they find a spot where the guide RNA matches, then it inserts between the two strands of the double helix, it rips them apart, that triggers the Cas9 protein to cut, and all of a sudden , you've got a cell that's in total panic because now it's got a piece of DNA that's broken. 向导 RNA 和 Cas9 蛋白质组成一个整体 在染色体上来回穿梭 当它们发现一个与向导 RNA 吻合的部位时 就会嵌入双螺旋结构 将其撕裂 导致 Cas9 蛋白质开始切割工作 于是突然之间 你就让一个细胞处在了极大的恐慌之中 因为它的一条 DNA 收到了破坏
complex:adj.复杂的;合成的;n.复合体;综合设施; strands:n.线; v.搁浅; rips:v.撕破;突然拉开;割开;(rip的第三人称单数) triggers:n.[电子]触发器;触发物(trigger的复数);v.引起(trigger的单三形式);引爆; all of a sudden:突然地,出乎意料地; panic:adj.恐慌的;n.惊恐;恐慌;惶恐不安;v.惊慌失措;
What does it do? 这时它该怎么办呢-
It calls its first responders . 呼叫现场急救员
responders:n.响应器;回答者;(responder的复数)
There are two major repair pathways . 细胞有着两种主要的修复机制
pathways:n.小路;小径(pathway的复数);
The first just takes the DNA and shoves the two pieces back together. 第一种是直接将断掉的 DNA 接上
shoves:vt.挤;强使;撞;猛推;n.推;挤;
This isn't a very efficient system, because what happens is sometimes a base drops out or a base is added. 这种方法不是最有效的 由于有时会多一个链环 有时又会少一个
efficient:adj.有效率的;有能力的;生效的;
It's an OK way to maybe, like, knock out a gene , but it's not the way that we really want to do genome editing. 这种方法只能...算撞出一个基因来 但不是我们通常想要的基因改造方式
knock out:n.淘汰赛;引人注目的人或物;将对方击倒而获胜的一击; gene:n.基因;遗传基因;遗传因子;
The second repair pathway is a lot more interesting. 第二种修复机制更为有趣
In this repair pathway, it takes a homologous piece of DNA. 在这种机制中 细胞会寻找一条相同的 DNA
homologous:adj.相应的;[生物]同源的;类似的;一致的;
And now mind you, in a diploid organism like people, we've got one copy of our genome from our mom and one from our dad, so if one gets damaged, it can use the other chromosome to repair it. 在有着双染色体的生物-比如说人类 我们得到了我们父母各自的一组染色体 如果一条 DNA 受损 细胞可以用另外一条来修复它
diploid:adj.双倍的;倍数的;双重的;n.[遗]二倍体;倍数染色体; organism:n.生物;有机体;有机组织;(尤指)微生物; chromosome:n.[遗][细胞][染料]染色体(形容词chromosomal,副词chromosomally);
So that's where this comes from. 这就是这种技术的原理
The repair is made, and now the genome is safe again. 修复成功之后 染色体又重获安全
The way that we can hijack this is we can feed it a false piece of DNA, a piece that has homology on both ends but is different in the middle. 我们将其调包的方法 是用一条新的 DNA-- 在两端上与原来相同 中间却不同--来修复它
hijack:v.抢劫;揩油;拦路抢劫;n.劫持;威逼;敲诈; homology:n.同源;相同;异体同形;同族关系;
So now, you can put whatever you want in the center and the cell gets fooled. 于是你可以随心所欲地将你想要的中间部分安装上去 细胞本身却毫无察觉
So you can change a letter, you can take letters out, but most importantly, you can stuff new DNA in, kind of like a Trojan horse . 你可以改变基因中的一条信息 也可以删除它 但最为重要的是你可以像特洛伊木马一样 将一条全新的 DNA 嵌入
stuff:n.东西:物品:基本特征:v.填满:装满:标本: Trojan horse:n.特洛伊木马;(来自外部的)颠覆分子(或活动);
CRISPR is going to be amazing, in terms of the number of different scientific advances that it's going to catalyze . CRISPR 的作用出人预料 它能推动许多 不同领域的科技发展
scientific:adj.科学的,系统的; catalyze:vt.催化;刺激,促进;
The thing that's special about it is this modular targeting system. 它的特殊之处在于这个攻击系统模块
I mean, we've been shoving DNA into organisms for years, right? 我们多年来一直尝试着将 DNA 嵌入生物体中
shoving:v.推开,挤浆(shove的现在分词); organisms:n.[生物]生物体(organism的复数);[生物]有机体;
But because of the modular targeting system, we can actually put it exactly where we want it. 但由于这种模块攻击系统 我们能将它放在我们想要的地方
The thing is that there's a lot of talk about it being cheap and it being easy. 问题是现在有很多关于它的廉价性 和便捷性的话题
And I run a community lab. 我有着一所社区实验室
community:n.社区;[生态]群落;共同体;团体;
I'm starting to get emails from people that say stuff like, "Hey, can I come to your open night and, like, maybe use CRISPR and engineer my genome?" 并且开始收到人们的来信-- “我能在开放夜来你那吗? 借我用用 CRISPR 编辑一下自己的基因行吗?”
(Laugher) (笑声)
Like, seriously. 讲真的
I'm, "No, you can't." 我说:“不,你不行“
(Laughter) (笑声)
'"But I've heard it's cheap. I've heard it's easy." “但我听说那很便宜,很简单啊”
We're going to explore that a little bit. 我们谈谈这个吧
explore:v.探索:探测:探险:
So, how cheap is it? 究竟有多便宜?
Yeah, it is cheap in comparison . 相对来说确实便宜
comparison:n.比较;对比;相比;
It's going to take the cost of the average materials for an experiment from thousands of dollars to hundreds of dollars, and it cuts the time a lot, too. 它能将一个实验所需材料通常的价格 从几千美元降至几百美元 还能节约时间
It can cut it from weeks to days. 几周的工作几天就能完成
That's great. 这很好
You still need a professional lab to do the work in; you're not going to do anything meaningful outside of a professional lab. 但你仍需要专业的实验室来做 没有实验室是不可能完成这项技术的
professional:adj.专业的;职业的;职业性的;n.专业人员;职业运动员; meaningful:adj.严肃的;重要的;重大的;意味深长的;
I mean, don't listen to anyone who says you can do this sort of stuff on your kitchen table. 别相信那些说 你可以在自家厨房里做实验的人
It's really not easy to do this kind of work. 这项技术真的不简单
Not to mention , there's a patent battle going on, so even if you do invent something, the Broad Institute and UC Berkeley are in this incredible patent battle. 更别说有一场如火如荼的专利战打的正酣 即使发明者创造出了这样的奇思妙想 布罗德研究所和 UC 伯克利也在为专利权而争斗不休
Not to mention:更不必说;不必提及; patent:vt.授予专利; adj.专利的; n.专利权; Institute:v.开始(调查);制定;创立;提起(诉讼);n.学会,协会;学院; incredible:adj.难以置信的,惊人的;
It's really fascinating to watch it happen, because they're accusing each other of fraudulent claims and then they've got people saying, "Oh, well, I signed my notebook here or there." 隔岸观火很有趣 因为他们都在不断控诉对方,称其发布诬告性言论 他们中的有人常常说 “我在我的笔记本上到处都记了笔记”
fascinating:adj.极有吸引力的;迷人的;v.深深吸引;迷住;(fascinate的现在分词) accusing:adj.谴责的;指责的;v.控告;控诉;谴责;(accuse的现在分词) fraudulent:adj.欺骗性的;不正的; claims:v.宣称; n.声明; (claim的第三人称单数和复数)
This isn't going to be settled for years. 这件事好几年都没完
settled:adj.稳定的; v.结束; (settle的过去分词和过去式)
And when it is, you can bet you're going to pay someone a really hefty licensing fee in order to use this stuff. 即使真的解决了 到那时你就得为使用这项技术 支付高昂的费用
bet:n.打赌;赌注;预计;估计;v.下赌注(于);用…打赌;敢说;八成儿; hefty:adj.重的;肌肉发达的;异常大的;adv.强有力地;非常;n.体格健壮的人; licensing:v.批准;许可;(license的现在分词)
So, is it really cheap? 所以它真的便宜吗?
Well, it's cheap if you're doing basic research and you've got a lab. 如果你有自己的实验室,并且在做基础学科实验的话——是的
How about easy? Let's look at that claim. 容易吗?现在我们来谈谈这个
The devil is always in the details. 魔鬼总藏在深处
devil:n.魔鬼;撒旦;家伙;恶棍;淘气鬼;冒失鬼;v.虐待,折磨;扯碎;做助手;
We don't really know that much about cells. 我们仍然不十分了解细胞
They're still kind of black boxes. 他们就像是一个黑匣子
For example, we don't know why some guide RNAs work really well and some guide RNAs don't. 比如说,我们不知道为什么有一些RNA十分有效 有一些却不是这样
We don't know why some cells want to do one repair pathway and some cells would rather do the other. 我们也不知道为什么一些细胞采用一种修复机制 另一些采用另外一种
would rather:宁愿,宁可;
And besides that, there's the whole problem of getting the system into the cell in the first place . 除了这些以外 在一开始 将这个系统植入细胞时同样面临着问题
besides:adv.此外;而且;prep.除…之外; in the first place:首先;起初;
In a petri dish , that's not that hard, but if you're trying to do it on a whole organism, it gets really tricky . 在培养皿中,这不是很难 可是如果是整个生物体 那就很麻烦了
petri dish:n.培养皿(作细菌培养等用的有盖玻璃碟); tricky:adj.难办的;难对付的;狡猾的;诡计多端的;
It's OK if you use something like blood or bone marrow -- those are the targets of a lot of research now. 采用血液或是骨髓是可行的 它们也是现在的研究重点
bone marrow:n.骨髓;
There was a great story of some little girl who they saved from leukemia by taking the blood out, editing it, and putting it back with a precursor of CRISPR. 有一个关于一位女孩奇迹的故事 她患了白血病 最后通过将血取出,人为将其改造后放回人体 最终痊愈——用的是CRISPR的前期技术
leukemia:n.[内科][肿瘤]白血病; precursor:n.先驱,前导;
And this is a line of research that people are going to do. 这是一种人们希望从事的研究
But right now, if you want to get into the whole body, you're probably going to have to use a virus. 但是如果你想针对整个人体 可能就要用到病毒了
So you take the virus, you put the CRISPR into it, you let the virus infect the cell. 采集病毒以后,将 CRISPR 放进去 你需要让病毒感染细胞
infect:v.传染;使携带病菌;使感染(计算机病毒);
But now you've got this virus in there, and we don't know what the long-term effects of that are. 但只要你将病毒注入细胞内部 就可能出现长期的副作用
long-term:adj.长期的;从长远来看;
Plus, CRISPR has some off-target effects, a very small percentage , but they're still there. 而且 CRISPR 还有一些伤及无辜的攻击行为 只占很小一部分——但总之存在
off-target:脱靶;偏离目标; percentage:n.百分比;百分率;利润的分成;提成;
What's going to happen over time with that? 一段时间过后又会发生什么呢?
These are not trivial questions, and there are scientists that are trying to solve them, and they will eventually , hopefully, be solved. 这不是小事 有科学家一直想要解决这些问题 而且它们有可能被解决
trivial:adj.不重要的,琐碎的;琐细的; eventually:adv.最后,终于;
But it ain't plug-and-play , not by a long shot . 但研究需要时间
plug-and-play:n.一种不必经由用户复杂安装即可使用的软件,即插即用; long shot:n.远景镜头;远射;长球;adj.渺茫的;甚小的;
So: Is it really easy? 这种方法真的容易吗?
Well, if you spend a few years working it out in your particular system, yes, it is. 在经过几年的深入研究之后 它才真正变得容易
Now the other thing is, we don't really know that much about how to make a particular thing happen by changing particular spots in the genome. 还有一个问题是 我们不知道怎样通过改变染色体中的某个部位 来到达我们想要的目的
We're a long way away from figuring out how to give a pig wings, for example. 我们现在还无法获知 怎样使一只猪长出翅膀
Or even an extra leg -- I'd settle for an extra leg. 或是多长一条腿
extra:adj.额外的:n.额外的事物:adv.额外:另外: settle for:满足于;
That would be kind of cool, right? 那会十分有趣,不是吗
But what is happening is that CRISPR is being used by thousands and thousands of scientists to do really, really important work, like making better models of diseases in animals, for example, 但确切的是 CRISPR 正被成千上万的科学家利用 去做十分重要的工作 例如建造更好的动物疾病模型
diseases:n.[医]病(disease的复数);[医]疾病;[植保]病害;疾病种类;
or for taking pathways that produce valuable chemicals and getting them into industrial production in fermentation vats , or even doing really basic research on what genes do. 或是找到经济的化学物质生产方法 用它们进行工业生产和发酵 甚至是有关基因功能的基本研究
valuable:adj.有价值的;贵重的;可估价的;n.贵重物品; chemicals:n.化学制品;化学品;(chemical的复数) industrial:adj.工业的,产业的; n.工业股票; fermentation:n.发酵; vats:abbr.电视辅助胸腔镜手术(Video-assistedThoracoscopicSurgery); genes:n.基因;(gene的复数)
This is the story of CRISPR we should be telling, and I don't like it that the flashier aspects of it are drowning all of this out. 这才是 CRISPR 真正的用处 我不赞同让它的瑕疵 掩盖了它真正的光芒
flashier:闪光的,俗丽的,浮华的,虚饰的(flashy的比较级); aspects:n.方面;相位;面貌(aspect的复数); drowning:v.溺水;淹没;淹死,溺死;浸泡;(drown的现在分词)
Lots of scientists did a lot of work to make CRISPR happen, and what's interesting to me is that these scientists are being supported by our society. 不计其数的科学家呕心沥血造就了 CRISPR 我认为十分明智的是 这些科学家受到了社会的广泛支持
Think about it. 想一想
We've got an infrastructure that allows a certain percentage of people to spend all their time doing research. 我们有着能够让一小部分人在里面倾其一生 从事科学研究的机构
infrastructure:n.基础设施;公共建设;下部构造;
That makes us all the inventors of CRISPR, and I would say that makes us all the shepherds of CRISPR. 这让我们所有人成为了 CRISPR 的创造者 让我们成为 CRISPR的掌控者
shepherds:n.牧羊人; v.带领(shepherd的三单形式);
We all have a responsibility. 我们需要负起责任来
So I would urge you to really learn about these types of technologies, because, really, only in that way are we going to be able to guide the development of these technologies, the use of these technologies 所以我们需要重视这方面的技术 因为,只有这样 我们才能掌控这些技术的发展 和它们的应用
and make sure that, in the end, it's a positive outcome -- for both the planet and for us. 然后确保到最后我们能得到正面的结果 不管是对这颗星球还是我们自己
positive:adj.积极的;[数]正的,[医][化学]阳性的;确定的;n.正数;[摄]正片; outcome:n.结果,结局;成果;
Thanks. 谢谢
(Applause) (掌声)