PaulRothemund_详细讲述 DNA 折叠【中英文对照】

1.So, people argue vigorously about the definition of life.
人们总在激烈的争执生命的定义
2.They ask if it should have reproduction in it, or metabolism, or evolution.
它是否应该具有生殖,新陈代谢或者进化这些特征
3.And I don’t know the answer to that, so I’m not going to tell you.
我也不知道这个问题的答案,所以我不会和你们说这些
4.I will say that life involves computation.
我要说的是生命中有计算的过程
5.So this is a computer program.
这是一个计算机程序
6.Booted up in a cell, the program would execute and it could result in this person or with a small change, it could result in this person —
包含在细胞里,这个程序将来会执行 执行的结果就是诞生了这样一个人 或者有些小的变动,它就会造出这样的一个人
7.or another small change — this person, or with a larger change, this dog or this tree or this whale.
又或者有一些其它的变动,就会是这个人 或者是个大一点的变化,也许会变成这只狗 或者是这棵树,或是这条鲸鱼
8.So now, if you take this metaphor as genome as program seriously, you have to consider that Chris Anderson is a computer-fabricated artifact, as is Jim Watson,
如果你来认真看待 把基因组比成一个程序这样的比喻 你得把Chris Anderson (TED的创始人) 想成是一样电脑合成的制品,就像Jim Watson(DNA结构的发现者之一)
9.Craig Venter, as are all of us.
Craig Venter(最早开始研究人类基因组序列的科学家之一) 以及我们每一个人一样.
10.And in convincing yourself that this metaphor is true, there are lots of similarities between genetic programs and computer programs that could help to convince you.
为了说服你自己这个比喻是真的 如果注意到基因组程序和电脑程序 的许多共同点, 那这可以帮助你相信这个比喻
11.But one to me that is most compelling is the peculiar sensitivity to small changes that can make large changes in biological development the output.
但最吸引我的一点 是对微小变化的特殊敏感性 造就了生物进化中的大的改变
12.A small mutation can take a two-wing fly and make it a four-wing fly.
一个很小的变异可以把一个双翅的苍蝇 变成一个四支翅膀的苍蝇
13.Or it could take a fly and put legs where its antennae should be.
或者也可以把这个苍蝇的腿长在它本该长触角的地方
14.Or if you’re familiar with “The Princess Bride,”
或者,如果你对”公主新娘”这个电影很熟悉的话
15.it could create a six-fingered man.
小的变异也可能造就一个有六个指头的人
16.Now, a hallmark of computer programs is just this kind of sensitivity to small changes.
现在, 电脑程序的一个重要特点 就是可以有像(生物世界里)这样的对微小变化的敏感性
17.If your bank account’s one dollar and you flip a single bit, you could end up with a thousand dollars.
如果你的银行帐户里有一美元, 你只需要把这一位上的数换一下 你就能有一千美元
18.So these small changes are things that I think that — they indicate to us that a complicated computation in development is underlying these amplified large changes.
所以就是这些小的变化让我想到 它们暗示着一个复杂计算过程 总是暗藏在这些被放大的变化背后
19.So now, all of this indicates that there are molecular programs underlying biology, and it shows the power of molecular programs, biology does.
所以,所有这些都在暗示着在生物中隐含着分子程序 而且生物本身也体现了这些分子程序的强大力量
20.And what I want to do is write molecular programs, potentially to build technology.
我想做的是写一些有潜力 发展为技术的分子程序
21.And there are a lot of people doing this, a lot of synthetic biologists doing this like Craig Venter and they concentrate on using cells.
而且有很多人也致力于这一方向 有很多合成生物学家在做这些,比如 Craig Venter 他们集中精力在利用细胞上
22.They’re cell-oriented.
是细胞指向的
23.So my friends, molecular programmers and I, have a sort of bio-molecule centric approach.
我的朋友,分子程序师们以及我自己 有一套以生物-分子为中心的研究方法
24.We’re interested in using DNA, RNA and protein and building new languages for building things from the bottom up, using bio-molecules,
我们想要利用DNA, RNA 以及蛋白质 为从头开始构建全新的事物创造一种语言 利用生物分子
25.potentially having nothing to do with biology.
我们希望将来能把这些用在生物学以外的其它领域中.
26.So, these are all the machines in a cell.
细胞中有所有这些”机器”
27.There’s a camera.
这是一部照相机
28.There’s the solar panels of the cell, some switches that turn your genes on and off, the girders of the cell, motors that move your muscles.
这是细胞中的太阳能电池板 这是些调控基因的开关 这是细胞的大梁, 和驱动肌肉的马达.
29.My little group of molecular programmers are trying to refashion all of these parts from DNA.
我的分子程序研究小组 正在试图从DNA开始重新设计所有这些部件
30.We’re not DNA zealots, but DNA is the cheapest, easiest to understand and easy to program material to do this.
我们并不是DNA的狂热爱好者,但DNA是最便宜的 最容易理解的, 而且也适合于对其编程从而实现目的的.
31.And as other things become easier to use — maybe protein — we’ll work with those.
如果其它的分子变得成容易去利用 例如蛋白质,我们也将会利用的.
32.If we succeed, what will molecular programming look like?
如果我们成功了,分子编程会是什么样子的呢?
33.You’re going to sit in front of your computer.
你将坐在你的电脑面前
34.You’re going to design something like a cell phone, and in a high-level language, you’ll describe that cell phone.
你将能设计一些东西,比如手机 而且如果你用一种高级语言,你将能描绘这部手机
35.Then you’re going to have a compiler that’s going to take that description and it’s going to turn it into actual molecules that can be sent to a synthesizer
之后你得有一部编译器 这部编译器将会接收这些指令 然后把它变成真正的分子 这些分子能被送到合成器
36.and that synthesizer will pack those molecules into a seed.
合成器又能把这些分子组装在一起变成一个种子
37.And what happens if you water and feed that seed appropriately, is it will do a developmental computation, a molecular computation, and it’ll build an electronic computer.
如果你接着给它浇水而且好好栽培它呢? 它会进化成一个计算过程吗? 一个分子计算过程,而且建立起一个电子计算机.
38.And if I haven’t revealed my prejudices already, I think that life has been about molecular computers building electrochemical computers
如果我还没透露我的观点的话 我认为生命的过程是从分子计算机开始 建造电子化学的计算机
39.building electronic computers which together with electrochemical computers, will build new molecular computers which will build new electronic computers and so forth.
再接着建电子计算机 而这些电子计算机和电子化学的计算机 将会创造出新的分子计算机 这些新计算机又将会建造新的电子计算机,如此继续下去
40.And if you buy all of this, and you think life is all about computation, as I do, then you look at big questions through the eyes of a computer scientist.
如果你相信所有这些的话 而且如果你像我一样相信生命全是关于计算的话 那你就是在用一个计算机科学家的眼光来看一个重要问题
41.So one big question is, how does baby know when to stop growing?
一个重要的问题是,婴儿是怎么知道什么时候停止生长的呢?
42.And for a molecular programmer, the question is how does your cell phone know when to stop growing?
作为一个分子程序员 这个问题就相当于,你的手机如果知道什么时候停止生长
43.(Laughter) Or how does a computer program know when to stop running?
(笑声) 或者说一个电脑程序如何知道什么时候停止运行
44.Or more to the point, how do you know if a program will ever stop?
或者更具体点, 你怎么知道一个程序将有可能会停下来
45.There are other questions like this, too.
当然还有其它类似的问题
46.One of them is Craig Venter’s question.
其中一个就是Cragi Venter的问题
47.Turns out I think he’s actually a computer scientist.
其实我认为他实际上是一个计算机科学家
48.He asked how big is the minimal genome that will give me a functioning micro-organism?
他问,能发展成一个微型生物体 的最小基因组需要有多大
49.How few genes can I use?
我能少用几个基因?
50.This is exactly analogous to the question, what’s the smallest program I can write that will act exactly like Microsoft Word?
这个问题其实和,我能写的 能实现像微软的Word一样功能的最小的程序有多小 是很类似的
51.(Laughter) And just as he’s writing, you know, bacteria that will be smaller, he’s writing genomes that will work, we could write smaller programs
(笑声) 而且在他研究基因组的时候,你知道,细菌将会变小 他在研究的基因组能发挥功能 我们也能写更小的程序
52.that would do what Microsoft Word does.
而且让它完成像微软的”Word”的一样的功能
53.But for molecular programming, our question is, how many molecules do we need to put in that seed to get a cell phone?
但对于分子程序来说,我们的问题是 我们需要放多少分子到种子里而能让它”长”成一部手机
54.What’s the smallest number we can get away with?
我们需要的最小数量是多少
55.Now, these are big questions in computer science.
现在,计算科学领域有一个重大的问题
56.These are all complexity questions and computer science tells us that these are very hard questions.
这些都是复杂的问题 而且计算科学家告诉我们这些都是相当困难的问题
57.Almost — many of them are impossible.
几乎,或者说大部分都是不可能回答的
58.But for some tasks, we can start to answer them.
但对于其中的一些,我们可以开始尝试回答
59.So, I’m going to start asking those questions for the DNA structures I’m going to talk about next.
所以, 我现在要开始问这些 关于DNA结构的问题了,这也是我下面要讨论的
60.So, this is normal DNA, what you think of as normal DNA.
在一个正常的DNA里,那种你认为是正常的DNA
61.It’s double-stranded, it’s a double helix, has the As, Ts, Cs and Gs that pair to hold the strands together.
它有两股,是双螺旋 因为有A,T,C,G这些碱基才能把两股维系在一起
62.And I’m going to draw it like this sometimes, just so I don’t scare you.
我下面会用这种方式代表DNA结构 希望不会吓到你们
63.We want to look at individual strands and not think about the double helix.
我们只看这两股中的一股,不把它想成是双螺旋
64.When we synthesize it, it comes single-stranded, so we can take the blue strand in one tube and make an orange strand in the other tube
当我们合成的时候,我们先合成单股的 这样我们可以在一个试管里合成这股蓝色的 而在另一个试管里合成这条橙色的
65.and they’re floppy when they’re single-stranded.
它们在单股的时候是松软的
66.You mix them together and they make a rigid double helix.
但当你把它们混合在一起的时候,他们就形成了稳固的双螺旋
67.Now for the last 25 years, Ned Seeman and a bunch of his descendants have worked very hard and made beautiful three-dimensional structures
在过去的二十五年里 Ned Seeman(纽约大学化学系的一名教授,致力于DNA结构相关的纳米技术的研究)和几个他的学生 一直在辛苦研究,并利用这类DNA单股合在一起的反应
68.using this kind of reaction of DNA strands coming together.
做出了漂亮的三维结构
69.But a lot of their approaches, though elegant, take a long time.
他们多数的方法虽然很精致,但需要很长的时间
70.They can take a couple of years or it can be difficult to design.
也许会需要两三年的时间,或者会特别难以设计
71.So I came up with a new method a couple of years ago I call DNA origami that’s so easy you could do it at home in your kitchen and design the stuff on a laptop.
所以我几年前想出了这样一个新方法 我叫它DNA”折纸” 这是项很简单的技术,你甚至可以在自家的厨房里完成 并用笔记本电脑设计这些东西
72.But to do it, you need a long single strand of DNA, which is technically very difficult to get.
不过,为了做这些,你需要一个长的单股DNA 而从技术角度讲,这种DNA又很难得到
73.So, you can go to a natural source.
所以,你可以找一个自然的来源
74.You can look in this computer-fabricated artifact and he’s got a double-stranded genome that’s no good.
现在来看这个电脑合成的加工品 他有一个并不太好的双股的基因组
75.You look in his intestines. There are billions of bacteria.
来看他的肠子, 有几十亿的细菌
76.They’re no good either.
这也不太妙
77.Double strand again, but inside them, they’re infected with a virus that has a nice, long, single-stranded genome that we can fold like a piece of paper,
这确实也是双股的,但在内部,它被病毒感染了 其内部有一个很好的长长的单股基因组 我们可以折叠这个基因组,就像折叠一张纸
78.and here’s how we do it.
以下是我们如何做的
79.This is part of that genome.
这是基因组的一部分
80.We add a bunch of short synthetic DNAs that I call staples.
我们加入一些短小的合成的DNA结构, 我把这些短链叫作 “订书针”
81.Each one has a left half that binds the long strand in one place, and a right half that binds it in a different place and brings the long strand together like this.
每一个都有一小段可以和长链在某一个地方结全起来 而另一小段可以结合在长链的另一个地方 这样就可以把整个长链改变成这样的结构
82.The net action of many of these on that long strand is to fold it into something like a rectangle.
许多这些小DNA和长链结合的总结果就是 把长链折叠成一个类似于长方形的形状
83.Now, we can’t actually take a movie of this process, but Shawn Douglas at Harvard has made a nice visualization for us that begins with a long strand and has some short strands in it.
目前为止,我们还不能把这一过程拍成电影 但是哈佛大学的Shawn Douglas 为我们做了一个很棒的视觉展示 起初的时候有一条长长的链和一些短小的链
84.And what happens is that we mix these strands together.
然后我们把它们混合在一起
85.We heat them up, we add a little bit of salt, we heat them up to almost boiling and cool them down, and as we cool them down, the short strands bind the long strands
之后加热,并加一点盐 把它们加热到几乎到沸腾了,再冷却下来 在冷却的过程中 那些短小的链会和长链
86.and start to form structure and you can see a little bit of double helix forming there.
开始形成结构 你能在这看到有一点双螺旋形成了
87.When you look at DNA origami, you can see that what it really is, even though you think it’s complicated, is a bunch of double helices that are parallel to each other
当你看DNA”折纸”的时候 你能看到它实际上到底是什么 即使你认为它是个很复杂的东西 其实只是一些双螺旋平行排列在一起
88.and they’re held together by places where short strands go along one helix and then jump to another one.
它们之所以能组合在一起 是因为有那些短小链一端和一个螺旋结合 同时另一端再和另一处结合
89.So there’s a strand that goes like this, goes along one helix and binds — it jumps to another helix and comes back, that holds the long strand like this.
所以会有这样的一些链,和一个螺旋并行结合 同时又跳到另一条螺旋上再回来 这样能把长链组装成这个样子
90.Now, to show that we could make any shape or pattern that we wanted, I tried to make this shape.
为了展示我们能做成各种我们想要的形状和样式 我想做这样一个形状
91.I wanted to fold DNA into something that goes up over the eye, down the nose, up the nose, around the forehead, back down and end in a little loop like this.
我想让DNA这样向上越过眼睛 到鼻子下面,再回到鼻子上面,绕过额头 再回到下面,像这样完全一个圈
92.And so, I thought if this could work, anything could work.
然后我想如果能做成这个形状,那任何其它形状都可以
93.So I had the computer program design the short staples to do this.
之后我用电脑程序来设计小的”订书针”来实现这个目标
94.I ordered them, they came by FedEx.
我订购了这些,联邦快运送来的
95.I mixed them up, heated them, cooled them down, and I got 50 billion little smiley faces floating around in a single drop of water.
把它们混合起来,加热再冷却下来 得到了每滴水中有五百亿个微小 的”笑脸”瓢游着.
96.And each one of these is just one-thousandth the width of a human hair, OK?
而且每一个都只有 人类头发的一千之分一那么细.
97.So, they’re all floating around in solution, and to look at them, you have to get them on a surface where they stick.
它们在水里飘浮着,为了能看清楚 你需要能找到一个表面能让这些”笑脸”粘在上面
98.So, you pour them out onto a surface and they start to stick to that surface, and we take a picture using an atomic-force microscope.
所以,你把它们倒入一个表面上 它们开始粘在这个表面上 我们再用原子显微镜来照张相
99.It’s got a needle, like a record needle, that goes back and forth, over the surface, bumps up and down and feels the height of the first surface.
原子显微镜有一个针,像是个记录针 在表面上往返运动 一会上一会下来感觉表面的高低
100.It feels the DNA origami.
它能感觉到DNA”折纸”
101.There’s the atomic-force microscope working and you can see that the landing’s a little rough.
这里有一个原子显微镜在工作 你能看到表面有一点起伏不平
102.When you zoom in, they’ve got, you know, weak jaws that flip over their heads and some of their noses get punched out, but it’s pretty good.
当你放大来看,这些”笑脸” 有些下巴与额头重叠在一起 有些”笑脸”的鼻子被打了,但总体来说是不错的
103.You can zoom in and even see the extra little loop, this little nano-goatee.
你能继续放大,看到更小的多出来的小圈 这些小小的纳米级的山羊胡子
104.Now, what’s great about this is anybody can do this.
现在,这项技术的好处在于任何人都能做到
105.And so I got this in the mail about a year after I did this, unsolicited.
我一年前在邮件里收到了别人自发寄来的这样东西
106.Anyone know what this is? What is it?
有人知道这是什么吗?
107.It’s China, right?
是中国的版图
108.So, what happened is, a graduate student in China, Lulu Qian, did a great job.
事情是这样的,一个中国的研究生 钱露露(音译),做了一个很棒的工作
109.She wrote all her own software to design and built this DNA origami, a beautiful rendition of China, which even has Taiwan, and you can see that’s sort of on the world’s shortest leash, right?
她自己写了程序 来设计并构建这些DNA 折纸 一份十分漂亮的中国版图,还包括台湾 而且你能看到可能是世界上最短的一条绳子了,是吧?
110.(Laughter) So, this works really well and you can make patterns as well as shapes, OK?
(笑声) 所以这个方法确实很好用 而且除了形状外你还能设计不同的样式
111.And you can make a map of the Americas and spell DNA with DNA.
你可以做一张美国的地图,并用DNA来拼写”DNA”这个单词
112.And what’s really neat about it — well, actually this all looks like nano-artwork, but it turns out that nano-artwork is just what you need to make nano-circuits.
最精彩的是 这些看上去都像是纳米级的艺术品 但实际上纳米级的艺术品 其实就是建造纳米级的电路板所需要的东西
113.So, you can put circuit components on the staples, like a light bulb and a light switch.
所以,你可以把电路板的组件安在这些”订书针”上 就像一个电灯泡和一个灯的开关
114.Let the thing assemble, and you’ll get some kind of a circuit.
让这些东西组装起来,你就能得到一个电路板
115.And then you can maybe wash the DNA away and have the circuit left over.
之后可以把DNA洗掉,而就只剩下电路板
116.So, this is what some colleagues of mine at Caltech did.
这是我在加州理工大学的一些同事们做的工作
117.They took a DNA origami, organized some carbon nano-tubes, made a little switch, you see here, wired it up, tested it and showed that it is indeed a switch.
他们把DNA”折纸”,和用有机分子修饰过的碳纳米管 来组装成小的开关,看这里,把它绕起来 测试后发现它真的是一个开关
118.Now, this is just a single switch and you need half a billion for a computer, so we have a long way to go.
现在它只是单个开关 你需要五亿个这样的单元来组装电脑,所以我们还有很长的路要走
119.But this is very promising because the origami can organize parts just one-tenth the size of those in a normal computer.
但这却是很有前景的 因为这些”折纸”能组装只有普通电脑组件十分之一 那么大的组件
120.So it’s very promising for making small computers.
所以这项技术是很有前景能组装出小计算机的
121.Now, I want to get back to that compiler.
现在,我想再回去编译器的话题上
122.The DNA origami is a proof that that compiler actually works.
DNA”折纸”能证明编译器是真的能工作的
123.So, you start with something in the computer.
所以,你在电脑里开始了某一项工作
124.You get a high-level description of the computer program, a high-level description of the origami.
你有一个高级的关于电脑程序的说明 一个高级的关于”折纸”的说明
125.You can compile it to molecules, send it to a synthesizer and it actually works.
你能把这些编译成分子,把它发给组装的人 而且它还确实可以工作
126.And it turns out that a company has made a nice program that’s much better than my code, which was kind of ugly, and will allow us to do this in a nice,
事实上有个公司发明了一个很好的程序 一个比我的丑陋程序要好得多的程序 这个程序能让我们更好的实现设计过程
127.visual computer-aided design way.
用一种电脑辅助的视觉设计方法
128.So, now you can say, all right, why isn’t DNA origami the end of the story?
现在,你就能明白 为什么DNA “折纸”不是一个终结
129.You have your molecular compiler, you can do whatever you want.
你有分子的编译器,你能用它实现任何你想做的事
130.The fact is that it does not scale.
问题是它不能大规模生产
131.So if you want to build a human from DNA origami, the problem is, you need a long strand that’s 10 trillion trillion bases long.
所以如果你想从DNA”折纸”起发展成一个人 问题是,你需要很长的一股DNA 大概需要有十万亿万亿碱基的DNA链
132.That’s three light years worth of DNA, so we’re not going to do this.
相当于三光年长的DNA 所以我们不能这么做
133.We’re going to turn to another technology called algorithmic self-assembly of tiles.
我们得用别的技术 一种叫作模块的算术自行组装的方法
134.It was started by Erik Winfree, and what it does, it has tiles that are a hundredth the size of a DNA origami.
这项技术是由Erik Winfree 发明的 这项技术是 它有一些大约是DNA”折纸”百分之一长度的模块